Clinical risk factors of colorectal cancer in patients with serrated polyposis syndrome: a multicentre cohort analysis.

OBJECTIVE: Serrated polyposis syndrome (SPS) is accompanied by an increased risk of colorectal cancer (CRC). Patients fulfilling the clinical criteria, as defined by the WHO, have a wide variation in CRC risk. We aimed to assess risk factors for CRC in a large cohort of patients with SPS and to evaluate the risk of CRC during surveillance. DESIGN: In this retrospective cohort analysis, all patients with SPS from seven centres in the Netherlands and two in the UK were enrolled. WHO criteria were used to diagnose SPS. Patients who only fulfilled WHO criterion-2, with IBD and/or a known hereditary CRC syndrome were excluded. RESULTS: In total, 434 patients with SPS were included for analysis; 127 (29.3%) were diagnosed with CRC. In a per-patient analysis ≥1 serrated polyp (SP) with dysplasia (OR 2.07; 95% CI 1.28 to 3.33), ≥1 advanced adenoma (OR 2.30; 95% CI 1.47 to 3.67) and the fulfilment of both WHO criteria 1 and 3 (OR 1.60; 95% CI 1.04 to 2.51) were associated with CRC, while a history of smoking was inversely associated with CRC (OR 0.36; 95% CI 0.23 to 0.56). Overall, 260 patients underwent surveillance after clearing of all relevant lesions, during which two patients were diagnosed with CRC, corresponding to 1.9 events/1000 person-years surveillance (95% CI 0.3 to 6.4). CONCLUSION: The presence of SPs containing dysplasia, advanced adenomas and/or combined WHO criteria 1 and 3 phenotype is associated with CRC in patients with SPS. Patients with a history of smoking show a lower risk of CRC, possibly due to a different pathogenesis of disease. The risk of developing CRC during surveillance is lower than previously reported in literature, which may reflect a more mature multicentre cohort with less selection bias.

Impact of the consideration of serrated polyps to the interval of colonoscopic surveillance in the NHS Bowel Cancer Screening Programme.

AIM: Most international post polypectomy surveillance guidelines do not recommend surveillance for serrated polyps. In the present study the additional impact of serrated polyps on surveillance intervals from international adenoma surveillance guidelines was investigated. METHOD: Endoscopic and pathology records were audited of participants in the NHS Bowel Cancer Screening Programme (guaiac faecal occult blood test, gFOBT) in 2011. Surveillance intervals were calculated for current guidelines and also for serrated polyps based on previously described aggressive and conservative strategies. RESULTS: In total, 389 patients were included of whom 141 (36.2%) were high risk (advanced adenoma: adenoma ≥ 10 mm, villous elements, high grade dysplasia, or adenoma ≥ 3 in number) needing surveillance at ≤ 3 years. Thirty-three (8.5%) had significant serrated polyps, of whom 18 (4.6% of the total) had significant serrated lesions and simultaneous advanced adenoma or ≥ 3 adenomas. Adopting an aggressive surveillance strategy, the mean overall absolute additional proportion of all such patients in the surveillance group at 3 years or less was 4.0% (3.9% - 4.1%; 4.2% women; 3.8% men). These proportions varied according to endoscopist from 2.3% to 4.7%. For more conservative strategies the increase was only 1%. CONCLUSION: The impact of including serrated polyps in current guidelines would result in a small increase in surveillance intervals for FOBT based bowel cancer screening. About half of those who might need surveillance for serrated polyps would already receive surveillance for being in a high risk adenoma group.

A randomized, controlled trial of narrow-band imaging vs high-definition white light for adenoma detection in patients at high risk of adenomas.

AIM: The study aimed to investigate whether narrow-band imaging (NBI) can enhance adenoma detection in patients at high risk for adenomas compared with high-definition white-light endoscopy (WLE). High risk was defined as three or more adenomas at last colonoscopy, history of colorectal cancer and positive faecal occult blood test. METHOD: Two hundred and fourteen patients were randomized 1:1 to examination with NBI or WLE. The primary outcome measure was the proportion of patients with at least one adenoma detected. Secondary outcomes included total adenomas and polyps, flat adenomas, nonadenomatous polyps, advanced adenomas and patients with three or five or more adenomas. A post hoc analysis to examine the effect of endoscopist and bowel preparation was performed. RESULTS: There was no significant difference in the proportion of patients with at least one adenoma: NBI 73%vs WLE 66%, odds ratio 1.40 (95% CI 0.78-2.52), P = 0.26. There was no significant difference for any secondary outcome measure except for the number of flat adenomas which was significantly greater with NBI [comparison ratio 2.66 (95% CI 1.52-4.63), P = 0.001]. Post hoc analysis indicated that one of three endoscopists performed significantly better for adenoma detection with NBI than WLE [comparison ratio 1.92 (95% CI 1.07-3.44), P = 0.03]. Good bowel preparation was associated with significantly improved adenoma detection with NBI [comparison ratio 1.55 (95% CI 1.01-2.22), P = 0.04] but not with fair preparation. CONCLUSION: Overall NBI did not improve detection compared with WLE in a group of patients at high risk for colorectal adenomas, but specific subgroups might benefit.

Achieving high quality colonoscopy: using graphical representation to measure performance and reset standards.

AIM: Completeness and thoroughness of colonoscopy are measured by the caecal intubation rate (CIR) and the adenoma detection rate (ADR). National standards are ≥ 90% and ≥ 10% respectively. Variability in CIR and ADR have been demonstrated but comparison between individuals and units is difficult. We aimed to assess the performance of colonoscopy in endoscopy units in the northeast of England. METHOD: Data on colonoscopy performance and sedation use were collected over 3 months from 12 units. Colonoscopies performed by screening colonoscopists were included for the CIR only. Funnel plots with upper and lower 95% confidence limits for CIR and ADR were created. RESULTS: CIR was 92.5% (n = 5720) and ADR 15.9% (n = 4748). All units and 128 (99.2%) colonoscopists were above the lower limit for CIR. All units achieved the ADR standard with 10 above the upper limit. Ninety-nine (76.7%) colonoscopists were above 10%, 16 (12.4%) above the upper limit and 7 (5.4%) below the lower limit. Median medication doses were 2.2 mg midazolam, 29.4 mg pethidine and 83.3 µg fentanyl. In all, 15.1% of colonoscopies were unsedated. Complications were bleeding (0.10%) and perforation (0.02%). There was one death possibly related to bowel preparation. CONCLUSION: Results indicate that colonoscopies are performed safely and to a high standard. Funnel plots can highlight variability and areas for improvement. Analyses of ADR presented graphically around the global mean suggest that the national standard should be reset at 15%.

What is the most reliable imaging modality for small colonic polyp characterization? Study of white-light, autofluorescence, and narrow-band imaging.

BACKGROUND AND STUDY AIMS: In vivo optical diagnosis of small colorectal polyps has potential clinical and cost advantages, but requires accuracy and high interobserver agreement for clinically acceptability. We aimed to assess interobserver variability and diagnostic performance of endoscopic imaging modalities in characterizing small colonic polyps. METHODS: High quality still images of 80 polyps < 1 cm were recorded using white-light endoscopy (WLE), autofluorescence imaging (AFI) and narrow-band imaging with and without magnification (NBI and NBImag). All images were assessed for quality, prediction of polyp histology, and vascular pattern intensity (with NBI) by nine experienced colonoscopists (four experts in advanced imaging) from five UK centers. Interobserver agreement (kappa statistic), sensitivity, specificity, and accuracy were calculated compared with histopathological findings. RESULTS: Interobserver agreement for predicting polyp histology using NBImag was significantly better for experts (κ = 0.63, substantial) compared with nonexperts (κ = 0.30, fair; P < 0.001), and was moderate for all colonoscopists with WLE, AFI and NBI. Interobserver agreement for vascular pattern intensity using NBI was 0.69 (substantial) for experts and 0.57 (good) for nonexperts. NBImag had higher sensitivity than WLE (experts, 0.93 vs. 0.68, P < 0.001; nonexperts, 0.90 vs. 0.52, P < 0.001) and higher overall accuracy (experts, 0.76 vs. 0.64, P = 0.003; nonexperts 0.61 vs. 0.40, P < 0.001). AFI had worse accuracy than WLE for both expert colonoscopists (0.53 vs. 0.64, P = 0.02) and nonexperts (0.32 vs. 0.40, P = 0.04). CONCLUSIONS: Of the imaging modalities tested, NBImag appeared to have the best overall accuracy and interobserver agreement, although not adequate for in vivo diagnosis. NBI and AFI did not have better sensitivity, specificity, or accuracy compared with WLE.

Faecal immunochemical testing (FIT): sources of result variation based on three years of routine testing of symptomatic patients in English primary care.

Introduction: We aimed to determine the analytical capabilities of a commonly used faecal immunochemical test (FIT) to detect faecal haemoglobin (Hb) in symptomatic people attending primary care in the context of the English NICE DG30 guidance.Materials and Methods: Data obtained from independent verification studies and clinical testing of the HM-JACKarc FIT method in routine primary care practice were analysed to derive performance characteristics.Results: Detection capabilities for the FIT method were 0.5 µg/g (limit of blank), 1.3 µg/g (limit of detection) and 3.0 µg/g (limit of quantitation). Of 33 non-homogenized specimens, 31 (93.9%) analysed in triplicate were consistently categorized relative to 10 µg/g, compared to all 33 (100%) homogenized specimens. Imprecision was higher (median 27.8%, (range 20.5% to 48.6%)) in non-homogenized specimens than in homogenized specimens (10.2%, (7.0 to 13.5%)). Considerable variation was observed in sequential clinical specimens from individual patients but no positive or negative trend in specimen degradation was observed over time (p = 0.26).Discussion: The FIT immunoassay evaluated is capable of detecting faecal Hb at concentrations well below the DG30 threshold of 10 µg/g and is suitable for application in this context. The greatest practical challenge to FIT performance is reproducible sampling, the pre-analytical step associated with most variability. Further research should focus on reducing sampling variability, particularly as post-COVID-19 guidance recommends greater FIT utilization.

Retrospective study of technical aspects and complications of endoscopic submucosal dissection for laterally spreading tumors of the colorectum.

BACKGROUND AND STUDY AIMS: Laterally spreading tumors - non granular type (LST-NG) are more often considered candidates for endoscopic submucosal dissection (ESD) than laterally spreading tumors - granular type (LST-G), because of their higher potential for submucosal invasion. However, ESD for LST-NG can be technically difficult. The aim of our study was to compare our ESD results for LST-NG and for LST-G. PATIENTS AND METHODS: Ninety-nine LST-NG and 169 LST-G measuring 20 mm in size or more were removed by ESD. We retrospectively evaluated the clinicopathological features of the tumors and treatment results (en bloc resection rate, procedure time and speed, rate of use of ancillary devices, and complication and recurrence rates). RESULTS: Histopathology revealed that there were more submucosally invasive lesions in the LST-NG than in the LST-G group (28 % vs. 9 %; P < 0.0001). The en bloc resection rate, en bloc R0 resection rate, and en bloc curative resection rate of LST-NG were similar to those of LST-G (LST-NG: 99 %, 98 %, and 88 %; LST-G: 99 %, 98 %, and 91 %). In LST-NG, the median procedure time tended to be longer (LST-NG: 69 min; LST-G: 60 min) and the median procedure speed was slower (LST-NG: 0.15 cm (2)/min; LST-G: 0.25 cm (2)/min; P < 0.0001). Use of ancillary devices was higher for LST-NG (38 % vs. 15 % for LST-G; P < 0.0001), as was the perforation rate (5.1 % vs. 0.6 % for LST-G; P = 0.027). No recurrence was seen in either group. CONCLUSIONS: ESD was an effective treatment method for both LST-NG and LST-G. However, the degree of technical difficulty appears higher for LST-NG than for LST-G lesions, as shown by the lower dissection speed and higher perforation rate. ESD for LST-NG should probably be performed by those with significant experience of colorectal ESD.

Flat colon polyps: what should radiologists know?

With the recent publication of international computed tomography (CT) colonography standards, which aim to improve quality of examinations, this review informs radiologists about the significance of flat polyps (adenomas and hyperplastic polyps) in colorectal cancer pathways. We describe flat polyp classification systems and propose how flat polyps should be reported to ensure patient management strategies are based on polyp morphology as well as size. Indeed, consistency when describing flat polyps is of increasing importance given the strengthening links between CT colonography and endoscopy.

Narrow band imaging for colonoscopic surveillance in hereditary non-polyposis colorectal cancer.

BACKGROUND: Colonoscopic surveillance for hereditary non-polyposis colorectal cancer (HNPCC) reduces death rates, but early interval cancers still occur, probably due to missed small, aggressive adenomas. Narrow band imaging (NBI), a novel endoscopic technology, highlights superficial mucosal capillaries and improves contrast for adenomas. This study examined whether a second pass with NBI in the proximal colon helped detect additional adenomas in patients with HNPCC. METHODS: 62 patients from HNPCC families (Amsterdam II or genetic criteria) attending for colonoscopic surveillance were examined twice from caecum to sigmoid-descending junction, first with high definition white light and then a second pass with NBI in a back-to-back fashion. All polyps detected were removed for histopathological analysis. RESULTS: At least one adenoma in the proximal colon was detected during the initial white light pass in 17/62 (27%). NBI detected additional adenomas in 17/62 (27%). 26/62 (42%) patients had at least one adenoma detected after both white light and NBI; absolute difference 15% (95% CI 4-25%), p = 0.004 versus white light alone. The total number of adenomas increased from 25 before NBI to 46 after NBI examination, p<0.001. The proportion of flat adenomas detected in the NBI pass, 9/21 (45%), was higher than in the white light pass, 3/25 (12%), p = 0.03. Including white light examination of the sigmoid and rectum, overall 28/62 (45%) patients had at least one adenoma detected. CONCLUSIONS: Use of NBI in the proximal colon for patients undergoing HNPCC surveillance appears to improve adenoma detection, particularly those with a flat morphology. NBI could help reduce interval cancer rates.

A comparative study of standard vs. high definition colonoscopy for adenoma and hyperplastic polyp detection with optimized withdrawal technique.

BACKGROUND: Colonoscopy has a known miss rate for polyps and adenomas. High definition (HD) colonoscopes may allow detection of subtle mucosal change, potentially aiding detection of adenomas and hyperplastic polyps. AIM: To compare detection rates between HD and standard definition (SD) colonoscopy. METHODS: Prospective, cohort study with optimized withdrawal technique (withdrawal time >6 min, antispasmodic, position changes, re-examining flexures and folds). One hundred and thirty patients attending for routine colonoscopy were examined with either SD (n = 72) or HD (n = 58) colonoscopes. RESULTS: Groups were well matched. Sixty per cent of patients had at least one adenoma detected with SD vs. 71% with HD, P = 0.20, relative risk (benefit) 1.32 (95% CI 0.85-2.04). Eighty-eight adenomas (mean +/- standard deviation 1.2 +/- 1.4) were detected using SD vs. 93 (1.6 +/- 1.5) with HD, P = 0.12; however more nonflat, diminutive (<6 mm) adenomas were detected with HD, P = 0.03. Twenty-three proximal hyperplastic polyps (0.32 +/- 0.58) were detected with SD vs. 31 (0.53 +/- 0.86) with HD, P = 0.35. Overall prevalence of proximal large (>9 mm) hyperplastic polyps was 7% (0.09 +/- 0.36). CONCLUSIONS: High definition did not lead to a significant increase in adenoma or hyperplastic polyp detection, but may help where comprehensive lesion detection is paramount. High detection rates appear possible with either SD or HD, when using an optimized withdrawal technique.

Narrow band imaging with magnification for the characterization of small and diminutive colonic polyps: pit pattern and vascular pattern intensity.

BACKGROUND AND STUDY AIMS: Narrow band imaging (NBI) can accurately characterize colonic polyps using microvascular appearances. We aimed to assess whether the Kudo pit pattern classification is accurate when used with NBI (without dye-spray), and if microvascular appearances or NBI pit patterns maintain accuracy for polyp characterization at sizes < 10 mm. PATIENTS AND METHODS: 116 polyps < 10 mm in size were detected in 62 patients undergoing surveillance colonoscopy. The polyps were prospectively assessed using NBI and magnification for Kudo pit pattern (III-V neoplastic, I-II non-neoplastic) and vascular pattern intensity (VPI), a measure of microvascular density (strong VPI, neoplastic; normal or weak VPI, non-neoplastic). Sensitivity, specificity, and accuracy were calculated and compared with results from histopathology. RESULTS: The mean polyp size was 3.4 mm (range 1 - 9 mm). Overall, NBI pit pattern sensitivity, specificity, and accuracy were 0.88, 0.91, and 89.6 %, respectively. Equivalent values for VPI were 0.94, 0.89, and 91.4 %. Results were similar when polyps were subdivided into diminutive polyps (size

Endoscopic haemostasis of staple-line haemorrhage following colorectal resection.

OBJECTIVE: Bleeding from stapled colonic stapled anastomoses is rare, but occasionally may be severe enough to require re-operation, with associated morbidity. Endoscopic therapy is a potential alternative. METHOD: We examined a large 15-year prospective series of patients who had undergone colorectal resection with stapled anastomosis. We reviewed the management of cases where severe postoperative rectal bleeding had occurred. RESULTS: In six of 777 (0.8%) patients, bleeding occurred that was severe enough to require intervention. In the first three cases, conventional re-operation was performed. In the latter three cases, endoscopic therapy (adrenaline injection, diathermy or endoscopic clipping) was used to control the bleeding. No complications occurred as a result of endoscopic therapy, either patient or anastomosis related. CONCLUSION: Endoscopic management using standard endoscopic techniques appears safe and effective for haemostasis in colorectal stapled anastomotic bleeding. Endoscopic therapy should probably be attempted before re-operation is considered.

Narrow band imaging with magnification for dysplasia detection and pit pattern assessment in ulcerative colitis surveillance: a case with multiple dysplasia associated lesions or masses.

A 62 year old man with longstanding ulcerative colitis and previous endoscopic excision of two dysplasia associated lesions or masses (DALMs) was admitted to our endoscopy unit for evaluation and resection of other possible DALMs. He had previously been offered and refused colectomy because of comorbidity from Parkinson's disease. He had multiple polypoid and sessile lesions which were assessed using a third generation prototype narrow band imaging (NBI) colonoscope with magnification. Selected lesions were either biopsied or resected with a combination of endoscopic submucosal dissection and endoscopic mucosal resection techniques. We correlated the pit pattern and vascular pattern intensity seen with magnification NBI with histology of both inflammatory and dysplastic lesions. Dysplastic areas showed Kudo pit patterns II, IIIL, and IV and high vascular pattern intensity. Non-dysplastic and dysplastic areas of recurrence immediately adjacent to the scar from a previous endoscopic mucosal resection site were also assessed. This is the first case report where NBI has been shown to help in DALM detection and to distinguish dysplastic from non-dysplastic mucosa in ulcerative colitis.

New applications of nanotechnology for neuroimaging.

SUMMARY: Advances in nanotechnology have the potential to dramatically enhance the detection of neurologic diseases with targeted contrast agents and to facilitate the delivery of focused therapies to the central nervous system. We present the physicochemical rationale for their use, applications in animal models, and ongoing clinical trials using these approaches. We highlight advances in the use of nanoparticles applied to brain tumor imaging, tumor angiogenesis, neurodegeneration, grafted stem cells, and neuroprogenitor cells.

Meta-analysis: narrow band imaging for lesion characterization in the colon, oesophagus, duodenal ampulla and lung.

BACKGROUND: Narrow band imaging is a new endoscopic technology that highlights mucosal surface structures and microcapillaries, which may be indicative of neoplastic change. AIM: To assess the diagnostic precision of narrow band imaging for the diagnosis of epithelial neoplasia compared to conventional histology both overall and in specific organs. METHODS: We performed a meta-analysis of studies which compared narow band imaging-based diagnosis of neoplasia with histopathology as the gold standard. Search terms: 'endoscopy' and 'narrow band imaging'. RESULTS: Five hundred and eighty-two patients and 1108 lesions in 11 studies were included. Overall, sensitivity was 0.94 (95% confidence interval 0.92-0.95), specificity 0.83 (0.80-0.86); weighted area under the curve was 0.96 (standard error 0.02), diagnostic odds ratio (DOR) 72.74 (34.11-155.15). DORs were 66.65 (25.84-171.90), 61.19 (7.09-527.97), 69.74 (8.04-605.24) for colon, oesophagus and lung respectively. Studies with more than 50 patients had higher diagnostic precision, relative DOR 4.96 (1.28-19.27), P = 0.022. There was no difference in accuracy between microvessel and mucosal (pit) pattern based measures, relative DOR 1.29 (0.05-35.16), P = 0.87. There was significant heterogeneity overall between studies, Q = 31.2, P = 0.003. CONCLUSION: Narrow band imaging is accurate with high diagnostic precision for in vivo diagnosis of neoplasia across a range of organs, using simple microvessel-based measures.

Gentamicin induced ototoxicity during treatment of enterococcal endocarditis: resolution with substitution by netilmicin.

Enterococcal endocarditis can be very difficult to eradicate, requiring prolonged treatment with a combination of a penicillin and an aminoglycoside. In this patient with a pacemaker associated enterococcal endocarditis, ototoxicity occurred due to total gentamicin dose despite plasma concentrations consistently within the treatment range. Substitution with netilmicin, without a break in aminoglycoside treatment, resulted in a rapid improvement in hearing and allowed the required course of aminoglycoside to be completed. The risk factors for ototoxicity with gentamicin are reviewed, in particular the dangers of increasing age and of multiple and prolonged courses. Close treatment monitoring does not totally avoid this risk, especially when prolonged aminoglycoside treatment is required. This case emphasises the need for prompt investigation and adequate, definitive treatment of enterococcal endocarditis to avoid the increased risk consequent on repeated courses of antibiotics. The resolution of the ototoxicity with netilmicin is consistent with other reports of lower cochleotoxicity than with other aminoglycosides.