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D S Sanders

Publications and source records attributed to D S Sanders.

At least 37 records · Page 2Linked to original sources

High-magnification chromoscopic pouchoscopy: a novel in vivo technique for surveillance of the anal transition zone and columnar cuff following ileal pouch-anal anastomosis.

BACKGROUND: Persistence of underlying disease in the residual rectal mucosa and anal transition zone (ATZ) following ileal pouch-anal anastomosis (IPAA) for ulcerative colitis and familial adenomatous polyposis provides a site for potential malignancy. For this reason endoscopic surveillance is performed, although conventional assessment may be unreliable. We hypothesized that the novel technique of high-magnification chromoscopic pouchoscopy (HMCP) may permit accurate anatomical localization of this high risk zone in vivo and permit improved biopsy accuracy. PATIENTS AND METHODS: We studied 132 patients with IPAA using HMCP. Three distinct zones were defined using magnification endoscopy: ATZ, appearing as a linear cellular marix; columnar cuff, identifiable by a type I crypt pattern; and ileal pouch body, appearing as villous projections. Quadrantic biopsies of these zones were taken in addition to biopsies of any other lesions noted. RESULTS: A total of 1586 biopsies were taken from zones 1-3 (median, 12; range, 5-16 per patient). Overall biopsy-targeting accuracies using magnification guidance as compared with histopathology were 82%, 73% and 91% for the ATZ, cuff and pouch body, respectively. No dysplasia was identified in the quadrantic surveillance biopsies. Histologically confirmed columnar metaplasia was visualized in vivo using magnification chromoscopy. Patients with IPAA >3 years' duration were more likely to have pouch reservoir columnar metaplasia as compared to those <3 years (p<0.01). Pouch reservoir metaplasia was associated with a pre-morbid diagnosis of high-grade dysplasia or carcinoma within the premorbid colectomy specimen (p<0.001). CONCLUSIONS: This is the first study to evaluate this novel application of high magnification chromoscopy. Magnification pouchoscopy is a valid predictor of ATZ and cuff anatomy, permitting accurate biopsy targeting. Further randomized studies validating this technique with an emphasis on dysplasia detection in larger cohorts are required.

Adult↗

Does surgical removal of mucosal associated lymphoid tissue protect against adult coeliac disease? A case controlled study.

BACKGROUND AND AIMS: Surgical resection of mucosa associated lymphoid tissue has been suggested as a protective mechanism against the development of inflammatory bowel disease. Mucosal T-cell activity plays a pivotal role in coeliac disease pathogenesis. We aimed to determine if the development of adult coeliac disease is influenced by appendectomy or tonsillectomy. METHODOLOGY: Three hundred patients over 16 years of age with biopsy proven coeliac disease were identified from two hospital databases in South Yorkshire. From these databases, appendectomy and tonsillectomy status was determined and compared with 1033 coeliac disease antibody-negative controls (volunteers recruited from general practice). Logistic regression was performed to correct for the age differences between the two groups; cross-table analysis was performed. RESULTS: Thirteen percent of coeliac disease patients and 12.2% of controls had previous appendectomy (P = 0.71; odds ratio 1.08; 95% confidence interval 0.72-1.62). 20.7% of coeliac disease patients and 24.5% of the controls had previous tonsillectomy (P = 0.17; odds ratio 0.80; 95% confidence interval 0.59-1.10). CONCLUSIONS: No significance was demonstrated in either the appendectomy or tonsillectomy group. Surgical removal of mucosal associated lymphoid tissue does not appear to prevent the development of adult onset coeliac disease.

Adolescent↗

An evaluation of colorectal endoscopic mucosal resection using high-magnification chromoscopic colonoscopy: a prospective study of 1000 colonoscopies.

BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection provides an alternative to surgery for resection of sessile and flat colorectal lesions. High-magnification chromoscopic colonoscopy may allow early detection and anticipate histological diagnosis by identifying colonic crypt patterns. The aim of the present study was to assess the efficacy and safety of en-bloc endoscopic mucosal resection with high-magnification chromoendoscopy in the management of sessile and flat colorectal lesions </= 20 mm. PATIENTS AND METHODS: A single endoscopist using high-magnification chromoendoscopy prospectively examined 1000 patients attending for routine colonoscopy. Patients were selected for inclusion in the study if they were considered to be at high risk for underlying colorectal neoplasia or polyps. Within the study period, 1000 patients (29 %) qualified for entry from a total of 3480 colonoscopies conducted in our institution. Endoscopic mucosal resection was carried out in appropriate flat and sessile lesions. RESULTS: Endoscopic mucosal resection was carried out in 599 lesions. Complete histological resection was confirmed in 576 (96 %). Perforation occurred in one patient (0.2 %) and bleeding in 12 (2 %). A total of 254 lesions (40 %; excluding hyperplasia/metaplasia) were flat or depressed, and 374 (60 %) were sessile. Fifty-eight flat lesions (23 %) contained high-grade dysplasia or beyond, compared to 33 sessile lesions (9.0 %; P = 0.001). After resection, 21 lesions were upgraded histologically, with 17 being defined as adenoma with high-grade dysplasia or beyond. CONCLUSIONS: This study confirms that flat adenomas and carcinomas occur in the West and demonstrates the malignant potential of such lesions, which can be managed successfully using endoscopic techniques. Endoscopic mucosal resection with high-magnification chromoscopy is a safe and effective form of treatment for sessile or flat colorectal lesions. Complete resection can improve the accuracy of histopathological diagnosis. However, colonoscopists require training in these procedures in order to improve the rate of colorectal cancer detection.

Adenoma↗

Endoscopic morphological anticipation of submucosal invasion in flat and depressed colorectal lesions: clinical implications and subtype analysis of the kudo type V pit pattern using high-magnification-chromoscopic colonoscopy.

OBJECTIVE: Focal submucosal invasive colorectal cancers (submucosa-sm1) can be managed by endoscopic mucosal resection (EMR) as local lymph node metastasis (LNM) are rare. Lesions are usually flat, depressed or mixed. In deeper vertical submucosal invasion (sm2-3) LNM rates exceed 10-15%. EMR within this group can be complicated by perforation, noncurative resection and may leave LNM untreated. It is therefore essential to differentiate accurately focal sm1 disease from submucosal sm2/3 disease. The aim of this study was to evaluate the relationship between the invasive type V pit pattern using high-magnification-chromoscopic-colonoscopy (HMCC) and submucosal invasive depth for flat and depressed colorectal lesions. METHODS: Total colonoscopy was performed by a highly selected single endoscopist using the Olympus C240Z on 850 patients between January 2001 and July 2003. Kudo type V pits were identified using 0.05% crystal violet (CV) applied directly to the lesion using a steel tipped catheter. Type V pits were graded into class V(n)A-C as described by Nagata. Morphology was documented using the Japanese Research Society classification (JRSC). Histological sections, with reference to mucosal invasive characteristics, acquired using EMR or surgical excision were then compared with the pit pattern. RESULTS: Fifty-one lesions showed a type V pit pattern. The kappa coefficient of agreement between pit the type V pit pattern and histologically confirmed submucosal invasion was 0.51 (95% CI). Following resection, 97% of lesions were correctly anticipated to have sm2 + invasion using pit type Vn(B) and Vn(C) as clinical indicators of invasive disease. Specificity was low at 50% with an accuracy of 78%. CONCLUSIONS: The type V pit pattern is useful for the in vivo staging of submucosal invasive depth in flat and depressed colorectal lesions and is as sensitive as conventional 7.5 MHz EUS. There was a tendency to over-stage lesions and hence the technique is limited by its low overall specificity.

Biopsy, Needle↗

Gluten sensitivity masquerading as systemic lupus erythematosus.

CASE REPORTS: Three patients are described whose original presentation and immunological profile led to the erroneous diagnosis of systemic lupus erythematosus. The correct diagnosis of gluten sensitivity was made after years of treatment with steroids and other immunosuppressive drugs. CONCLUSIONS: The immunological profile of IgA deficiency and/or raised double stranded DNA in the absence of antinuclear factor together with raised inflammatory markers and symptoms suggestive of an immune diathesis should alert the physician to the possibility of gluten sensitivity. The presence of an enteropathy is no longer a prerequisite for the diagnosis of gluten sensitivity, which can solely present with extraintestinal symptoms and signs. Knowledge of the diverse manifestations of gluten sensitivity is essential in avoiding such misdiagnosis.

Autoantibodies↗

Efficacy of high magnification chromoscopic colonoscopy for the diagnosis of neoplasia in flat and depressed lesions of the colorectum: a prospective analysis.

BACKGROUND: High magnification chromoscopic colonoscopy (HMCC) permits the in vivo examination of the colorectal pit pattern, which has a high correlation with stereomicroscopic appearances of resected specimens. This new technology may provide an "optical biopsy" which can be used to aid diagnostic precision and guide therapeutic strategies. Conflicting data exist concerning the accuracy of this technique when discriminating neoplastic from non-neoplastic lesions, particularly when flat and depressed. AIM: To prospectively examine the efficacy of HMCC for the diagnosis of neoplasia in flat and depressed colorectal lesions using standardised morphological, pit pattern, and histopathological criteria. Clinical recommendations for the use of HMCC are made. METHODS: Total colonoscopy was performed on 1850 patients by a single endoscopist from January 2001 to July 2003 using the C240Z magnifying colonoscope. Identified lesions were classed according to the Japanese Research Society guidelines, and pit pattern according to Kudos modified criteria. Pit pattern appearances were then compared with histopathology. RESULTS: A total of 1008 flat lesions were identified. The sensitivity and specificity of HMCC in distinguishing non-neoplastic from neoplastic lesions were 98% and 92%, respectively. However, when using HMCC to differentiate neoplastic/non-invasive from neoplastic/invasive lesions, sensitivity was poor (50%) with a specificity of 98%. Diagnostic accuracy was not influenced by size or morphological classification of lesions. CONCLUSION: HMCC has a high overall accuracy at discriminating neoplastic from non-neoplastic lesions but is not 100% accurate. HMCC is a useful diagnostic tool in vivo but presently is not a replacement for histology. Requirements for further education and training in these techniques need to be addressed.

Adolescent↗

Detecting diminutive colorectal lesions at colonoscopy: a randomised controlled trial of pan-colonic versus targeted chromoscopy.

BACKGROUND: Diminutive and flat colorectal lesions can be difficult to detect using conventional colonoscopic techniques. Previous data have suggested that pan-chromoscopy may improve detection rates. No randomised control trial has been performed examining detection rates of such lesions while controlling for extubation time and lavage effect. AIM: We conducted a randomised controlled trial of pan-colonic chromoscopic colonoscopy for the detection of diminutive and flat colorectal lesions while controlling for extubation time and lavage effect. METHODS: Consecutive patients attending for routine colonoscopy were randomised to either pan-chromoscopy using 0.5% indigo carmine (IC) or targeted chromoscopy (control group). A minimum diagnostic extubation time was set at eight minutes with controls undergoing a matched volume of saline wash. RESULTS: A total of 260 patients were randomised; 132 controls and 128 to pan-colonic chromoscopy. Extubation times did not differ significantly between the control (median 15 minutes (range 8-41)) and chromoscopy (median 17 minutes (range 8-39)) groups. The volume of IC used in the pan-chromoscopy group (median 68 ml (range 65-90)) and normal saline used in the control group (69 ml (range 60-93)) did not differ significantly. There was a statistically significant difference between the groups regarding the total number of adenomas detected (p<0.05) with significantly more diminutive (<4 mm) adenomas detected in the pan-chromoscopy group (p = 0.03). Pan-chromoscopy diagnosed more diminutive and flat lesions in the right colon compared with controls (p<0.05), with more patients with multiple adenomas (>3) detected using pan-chromoscopy (p<0.01). Hyperplastic lesions were more commonly detected in the pan-chromoscopy group compared with controls (p<0.001). More hyperplastic polyps were detected in the left colon (86% rectosigmoid) using chromoscopy compared with controls. CONCLUSION: Chromoscopy improves the total number of adenomas detected and enhances the detection of diminutive and flat lesions. Importantly, eight diminutive lesions had foci of high grade dysplasia. Chromoscopy may benefit patients, assuming a high risk of colorectal cancer, and help in risk stratification and planning follow up colonoscopy intervals.

Adenoma↗

Clinical significance of azathioprine active metabolite concentrations in inflammatory bowel disease.

BACKGROUND AND AIMS: There are conflicting reports on the role of azathioprine (AZA) thioguanine nucleotide (TGN) metabolites in optimising therapy for inflammatory bowel disease (IBD). The aim of this study was to investigate TGN intrapatient variation, and the relationship between TGN concentrations and disease activity in IBD patients taking long term constant dose AZA. METHODS: TGN and methylmercaptopurine nucleotide (MeMPN) concentrations were measured at intervals over a two year period. Disease activity was assessed at each clinic visit using the Crohn's disease activity index or Walmsley simple index for ulcerative colitis. RESULTS: Serial TGNs were measured in 159 patients (3-14 TGN assays, median 6). Intrapatient variation in TGN concentrations was 1-5-fold (median 1.6); the incidence of non-compliance was 13%. At the end of two years, 131 patients were evaluable at TGN steady state. Of this group, patients who remained in remission had significantly higher mean TGN concentrations than those patients who developed active disease (median TGNs 236 v 175, respectively; median difference 44 pmol (95% confidence interval 1-92); p = 0.04). MeMPN concentrations were not related to AZA efficacy or toxicity. CONCLUSIONS: This study has shown that lower TGN concentrations were linked to the development of active disease, and that TGNs may act as useful markers of compliance. However, it is clear that repeat TGN measurements are required for an unambiguous index of active metabolite exposure. In view of the high intrapatient variability in TGN production over time, TGN measurements may not be currently advocated for routine clinical use.

Adolescent↗

Colonoscopic resection of lateral spreading tumours: a prospective analysis of endoscopic mucosal resection.

BACKGROUND: Lateral spreading tumours are superficial spreading neoplasms now increasingly diagnosed using chromoscopic colonoscopy. The clinicopathological features and safety of endoscopic mucosal resection for lateral spreading tumours (G-type "aggregate" and F-type "flat") has yet to be clarified in Western cohorts. METHODS: Eighty two patients underwent magnification chromoscopic colonoscopy using the Olympus CF240Z by a single endoscopist. All patients had received a previous colonoscopy where an endoscopic diagnosis of lateral spreading tumour was made. All lesions were examined initially using indigo carmine chromoscopy to delineate contour followed by crystal violet for magnification crypt pattern analysis. A 20 MHz "mini probe" ultrasound was used if T2 disease was suspected. Following endoscopic mucosal resection, patients were followed up at 3, 6, 12, and 24 months using total colonoscopy. RESULTS: Eighty two lateral spreading tumours were diagnosed in 80 patients (32% (26/82) F-type and 68% (56/82) G-type). G-type lesions were larger than F-type (G-type mean 42 (SD 14) mm v F-type 24 (6.4) mm; p<0.01). F-type lesions were more common in the right colon (F-type 77% (20/26) compared with G-type 39% (22/56); p<0.01) and more often associated with invasive disease (stage T2) (66% (10/15) v 33% (5/15); p<0.001). Fifty eight lesions underwent endoscopic mucosal resection (G-type 64% (37/58)/F-type 36% (21/58)). Local recurrent disease was detected in 17% of patients (10/58), all within six months of the index resection. Piecemeal resection and G-type morphology were significantly associated with recurrent disease (p<0.1). Overall "cure" rates for lateral spreading tumours using endoscopic mucosal resection at two years of follow-up was 96% (56/58). CONCLUSIONS: Endoscopic mucosal resection for lateral spreading tumours, staged as T1, is a safe and effective treatment despite their large size. Endoscopic mucosal resection may be an alternative to surgery in selected patients.

Adult↗

Dietary treatment of gluten ataxia.

BACKGROUND: Gluten ataxia is an immune mediated disease, part of the spectrum of gluten sensitivity, and accounts for up to 40% of cases of idiopathic sporadic ataxia. No systematic study of the effect of gluten-free diet on gluten ataxia has ever been undertaken. OBJECTIVE: To study the effect of gluten-free diet on patients presenting with ataxia caused by gluten sensitivity. METHODS: 43 patients with gluten ataxia were studied. All were offered a gluten-free diet and monitored every six months. All patients underwent a battery of tests to assess their ataxia at baseline and after one year on diet. Twenty six patients (treatment group) adhered to the gluten-free diet and had evidence of elimination of antigliadin antibodies by one year. Fourteen patients refused the diet (control group). Three patients had persistently raised antigliadin antibodies despite adherence to the diet and were therefore excluded from the analysis. RESULTS: After one year there was improvement in ataxia reflected in all of the ataxia tests in the treatment group. This was significant when compared with the control group. The diet associated improvement was apparent irrespective of the presence of an enteropathy. CONCLUSIONS: Gluten ataxia responds to a strict gluten-free diet even in the absence of an enteropathy. The diagnosis of gluten ataxia is vital as it is one of the very few treatable causes of sporadic ataxia.

Adult↗

Surgical presentation of ischaemic hepatitis.

Intestinal ischaemia typically presents with signs suggestive of an acute surgical abdomen. A raised serum lactate may substantiate the diagnosis. The first case of ischaemic hepatitis mimicking intestinal ischaemia is reported. The recognition of markedly deranged transaminases allows the clinician to differentiate the two diagnoses and potentially avoid the risks incurred with laparotomy.

Abdominal Pain↗

The humoral response in the pathogenesis of gluten ataxia.

OBJECTIVE: To characterize humoral response to cerebellum in patients with gluten ataxia. BACKGROUND: Gluten ataxia is a common neurologic manifestation of gluten sensitivity. METHODS: The authors assessed the reactivity of sera from patients with gluten ataxia (13), newly diagnosed patients with celiac disease without neurologic dysfunction (24), patients with other causes of cerebellar degeneration (11), and healthy control subjects (17) using indirect immunocytochemistry on human cerebellar and rat CNS tissue. Cross-reactivity of a commercial IgG antigliadin antibody with human cerebellar tissue also was studied. RESULTS: Sera from 12 of 13 patients with gluten ataxia stained Purkinje cells strongly. Less intense staining was seen in some but not all sera from patients with newly diagnosed celiac disease without neurologic dysfunction. At high dilutions (1:800) staining was seen only with sera from patients with gluten ataxia but not in control subjects. Sera from patients with gluten ataxia also stained some brainstem and cortical neurons in rat CNS tissue. Commercial anti-gliadin antibody stained human Purkinje cells in a similar manner. Adsorption of the antigliadin antibodies using crude gliadin abolished the staining in patients with celiac disease without neurologic dysfunction, but not in those with gluten ataxia. CONCLUSIONS: Patients with gluten ataxia have antibodies against Purkinje cells. Antigliadin antibodies cross-react with epitopes on Purkinje cells.

Aged↗