Targeted multicolor in vivo imaging over 1,000 nm enabled by nonamethine cyanines.

Recent progress has shown that using wavelengths between 1,000 and 2,000 nm, referred to as the shortwave-infrared or near-infrared (NIR)-II range, can enable high-resolution in vivo imaging at depths not possible with conventional optical wavelengths. However, few bioconjugatable probes of the type that have proven invaluable for multiplexed imaging in the visible and NIR range are available for imaging these wavelengths. Using rational design, we have generated persulfonated indocyanine dyes with absorbance maxima at 872 and 1,072 nm through catechol-ring and aryl-ring fusion, respectively, onto the nonamethine scaffold. Multiplexed two-color and three-color in vivo imaging using monoclonal antibody and dextran conjugates in several tumor models illustrate the benefits of concurrent labeling of the tumor and healthy surrounding tissue and lymphatics. These efforts are enabled by complementary advances in a custom-built NIR/shortwave-infrared imaging setup and software package for multicolor real-time imaging.

Prevalence of neoplasia at colonoscopy among testicular cancer survivors treated with platinum-based chemotherapy.

Testicular cancer survivors (TCS) treated with platinum-based chemotherapy have an increased risk of colorectal cancer (CRC). We determined the yield of colonoscopy in TCS to assess its potential in reducing CRC incidence and mortality. We conducted a colonoscopy screening study among TCS in four Dutch hospitals to assess the yield of colorectal neoplasia. Neoplasia was defined as adenomas, serrated polyps (SPs), advanced adenomas (AAs: ≥10 mm diameter, high-grade dysplasia or ≥25% villous component), advanced serrated polyps (ASPs: ≥10 mm diameter or dysplasia) or CRC. Advanced neoplasia (AN) was defined as AA, ASP or CRC. Colonoscopy yield was compared to average-risk American males who underwent screening colonoscopy (n = 24,193) using a propensity score matched analysis, adjusted for age, smoking status, alcohol consumption and body mass index. A total of 137 TCS underwent colonoscopy. Median age was 50 years among TCS (IQR 43-57) vs 55 years (IQR 51-62) among American controls. A total of 126 TCS were matched to 602 controls. The prevalence of AN was higher in TCS than in controls (8.7% vs 1.7%; P = .0002). Nonadvanced adenomas and SPs were detected in 45.2% of TCS vs 5.5% of controls (P < .0001). No lesions were detected in 46.0% of TCS vs 92.9% of controls (P < .0001). TCS treated with platinum-based chemotherapy have a higher prevalence of neoplasia and AN than matched controls. These results support our hypothesis that platinum-based chemotherapy increases the risk of colorectal neoplasia in TCS. Cost-effectiveness studies are warranted to ascertain the threshold of AN prevalence that justifies the recommendation of colonoscopy for TCS.

Association of Endoscopist Colonoscopy Quality Measures With Follow-Up Colonoscopy Outcomes After Positive Stool Tests (Multitarget Stool DNA or Fecal Immunochemical Test): Retrospective Cross-Sectional Analysis of Data From the New Hampshire Colonoscopy Registry.

INTRODUCTION: Negative colonoscopies following positive stool tests could result from stool test characteristics or from the quality of endoscopist performance. We used New Hampshire Colonoscopy Registry data to examine the association between endoscopist detection rates and polyp yield in colonoscopies performed for positive fecal immunochemical test (FIT) or multitarget stool DNA (mt-sDNA) test to evaluate the degree to which positive stool tests followed by negative colonoscopy ("false positives") vary with endoscopist quality. In addition, we investigated the frequency of significant polyps in the subgroup of highest quality colonoscopies following positive stool tests. METHODS: We compared the frequencies of negative colonoscopies and of specific polyps following positive stool tests across quartiles of endoscopist adenoma detection rate (ADR) and clinically significant serrated polyp detection rate (CSSDR). RESULTS: Our sample included 864 mt-sDNA+ and 497 FIT+ patients. We found a significantly lower frequency of negative colonoscopies following positive stool tests among endoscopists with higher ADR and CSSDR, particularly in the 2 highest quartiles. In addition, detection of any adenoma after a positive stool test for endoscopists in the fourth ADR quartile was 63.3% (FIT+) and 62.8% (mt-sDNA+). Among endoscopists in the fourth CSSDR quartile, sessile serrated lesions were found in 29.2% of examinations following a positive mt-sDNA and in 13.5% following FIT+ examinations. DISCUSSION: The frequency of negative colonoscopies after positive stool tests was significantly higher in examinations performed by endoscopists with low ADR and CSSDR. Our results also suggest a benchmark target of at least 40% for ADR in patients with mt-sDNA+ or FIT+ tests and 20% for sessile serrated lesions in mt-sDNA+ patients.

Association between Colonoscopy Sedation Type and Polyp Detection: A Registry-based Cohort Study.

BACKGROUND: Colorectal cancer is a leading cause of cancer-related death. Adenomas and serrated polyps are precursors of colorectal cancer, with serrated polyps being more difficult to detect during colonoscopy. The relationship between propofol use and polyp detection remains unclear. The authors investigated the association of propofol-based versus mild-moderate sedation on adenoma and serrated polyp detection during colonoscopy. METHODS: This retrospective cohort study used observational data from the New Hampshire Colonoscopy Registry. Patients aged greater than 50 yr with screening or surveillance colonoscopies between January 1, 2015, and February 28, 2020, were included. Exclusions were diagnostic examinations, no sedation, missing pathology data, and poor bowel preparation. Multivariate logistic regression was used to evaluate differences in polyp detection between propofol and moderate sedation in the full sample while adjusting for covariates. Propensity score adjustment and clustering at the endoscopist level were used in a restricted sample analysis that included endoscopists and facilities with between 5% and 95% propofol sedation use. RESULTS: A total of 54,063 colonoscopies were analyzed in the full sample and 18,998 in the restricted sample. Serrated polyp prevalence was significantly higher using propofol (9,957 of 29,312; 34.0% [95% CI, 33.4 to 34.5%]) versus moderate sedation (6,066 of 24,751; 24.5% [95% CI, 24.0 to 25.1%]) in the full sample and restricted samples (1,410 of 4,661; 30.3% [95% CI, 28.9 to 31.6%] vs. 3,690 of 14,337; 25.7% [95% CI, 25.0 to 26.5%]). In the full sample multivariate logistic regression, propofol was associated with higher neoplasm (adjusted odds ratio, 1.25 [95% CI, 1.21 to 1.29]), adenoma (odds ratio, 1.07 [95% CI, 1.03 to 1.11]), and serrated polyp detection (odds ratio, 1.51 [95% CI, 1.46 to 1.57]). In the restricted sample using inverse probability of treatment weighted propensity score adjustment and clustering at the endoscopist level, an attenuated but statistically significant effect size was observed for serrated polyps (odds ratio, 1.13 [95% CI, 1.07 to 1.19]), but not for adenomas (odds ratio, 1.00 [95% CI, 0.95 to 1.05]) or any neoplastic lesion (odds ratio, 1.03 [95% CI, 0.98 to 1.08]). CONCLUSIONS: Propofol sedation during colonoscopy may be associated with improved detection of serrated polyps, but not adenomas.

Higher Serrated Polyp Detection Rates Are Associated With Lower Risk of Postcolonoscopy Colorectal Cancer: Data From the New Hampshire Colonoscopy Registry.

INTRODUCTION: We used New Hampshire Colonoscopy Registry data to examine the association between postcolonoscopy colorectal cancer (PCCRC) and sessile serrated detection rates (SSLDRs). METHODS: We included patients with either a colonoscopy or a CRC diagnosis in the NH State Cancer Registry. PCCRC was any CRC diagnosed ≥ 6 months after index examination. RESULTS: Of 26,901 patients, 162 were diagnosed with PCCRC. The hazard ratio for PCCRC was lowest for patients whose endoscopists had the highest SSLDR quintile (≥6%) (hazard ratio 0.29; 95% confidence interval 0.16-0.50). DISCUSSION: Endoscopists with higher SSLDRs had lower risks of PCCRC. These data validate SSLDR as a clinically relevant quality measure.

Endoscopist adenomas-per-colonoscopy detection rates and risk for postcolonoscopy colorectal cancer: Data from the New Hampshire Colonoscopy Registry.

BACKGROUND AND AIMS: Adenomas per colonoscopy (APC) may be a better measure of colonoscopy quality than adenoma detection rate (ADR) because it credits endoscopists for each detected adenoma. There are few data examining the association between APC and postcolonoscopy colorectal cancer (PCCRC) incidence. We used data from the New Hampshire Colonoscopy Registry to examine APC and PCCRC risk. METHODS: We included New Hampshire Colonoscopy Registry patients with an index examination and at least 1 follow-up event, either a colonoscopy or a colorectal cancer (CRC) diagnosis. Our outcome was PCCRC defined as any CRC diagnosed ≥6 months after an index examination. The exposure variable was endoscopist-specific APC quintiles of .25, .40, .50, and .70. Cox regression was used to model the hazard of PCCRC on APC, controlled for age, sex, year of index examination, index findings, bowel preparation, and having more than 1 surveillance examination. RESULTS: In 32,535 patients, a lower hazard for PCCRC (n = 178) was observed for higher APCs as compared to APCs of <.25 (reference): .25 to <.40: hazard ratio (HR), .35; 95% confidence interval (CI), .22-.56; .40 to <.50: HR, .31; 95% CI, .20-.49; .50 to <.70: HR, .20; 95% CI, .11-.36; and ≥.70: HR, .19; 95% CI, .09-.37. When examining endoscopists with an ADR of at least 25%, an APC of <.50 was associated with a significantly higher hazard than an APC of ≥.50 (HR, 1.65; 95% CI, 1.06-2.56). A large proportion of endoscopists-one-fifth (32 of 152; 21.1%)-had an ADR of ≥25% but an APC of <.50. CONCLUSIONS: Our novel data demonstrating lower PCCRC risk in examinations performed by endoscopists with higher APCs suggest that APC could be a useful quality measure. Quality improvement programs may identify important deficiencies in endoscopist detection performance by measuring APC for endoscopists with an ADR of ≥25%.

Using New Hampshire Colonoscopy Registry data to assess United States and European post-polypectomy surveillance guidelines.

BACKGROUND: Our goal was to compare the updated European Society of Gastrointestinal Endoscopy (ESGE) and United States Multi-Society Task Force on Colorectal Cancer (USMSTF) high risk groups in predicting metachronous advanced neoplasia on first follow-up colonoscopy and long-term colorectal cancer (CRC). METHODS: We compared advanced metachronous neoplasia risk (serrated polyps ≥ 1 cm or with dysplasia, advanced adenomas [≥ 1 cm, villous, high grade dysplasia], CRC) on first surveillance colonoscopy in patients with high risk findings according to ESGE versus USMSTF guidelines. We also compared the positive and negative predictive values (PPV, NPV) of both guidelines for metachronous neoplasia. RESULTS: The risk for metachronous neoplasia in our sample (n = 20 458) was higher in the high risk USMSTF (3 year) (13.6 %; 95 %CI 12.3-14.9) and ESGE groups (13.6 %; 95 %CI 12.3-15.0) compared with the lowest risk USMSTF (5.1 %; 95 %CI 4.7-5.5; P < 0.001) and ESGE categories (6.3 %; 95 %CI 6.0-6.7; P < 0.001), respectively. Adding other groups such as USMSTF 5-10-year and 3-5-year groups to the 3-year category resulted in minimal change in the PPV and NPV for metachronous advanced neoplasia. High risk ESGE (hazard ratio [HR] 3.03, 95 %CI 1.97-4.65) and USMSTF (HR 3.07, 95 %CI 2.03-4.66) designations were associated with similar long-term CRC risk (CRC per 100 000 person-years: USMSTF 3-year group 3.54, 95 %CI 2.68-4.68; ESGE high risk group: 3.43, 95 %CI 2.57-4.59). CONCLUSION: Performance characteristics for the ESGE and USMSTF recommendations are similar in predicting metachronous advanced neoplasia and long-term CRC. The addition of risk groups, such as the USMSTF 5-10-year and 3-5-year groups to the USMSTF 3-year category did not alter the PPV or NPV significantly.

Clinically significant serrated polyp detection rates and risk for postcolonoscopy colorectal cancer: data from the New Hampshire Colonoscopy Registry.

BACKGROUND AND AIMS: Higher adenoma detection rates reduce the risk of postcolonoscopy colorectal cancer (PCCRC). Clinically significant serrated polyps (CSSPs; defined as any sessile serrated polyp, traditional serrated adenoma, large [≥1 cm] or proximal hyperplastic polyp >5 mm) also lead to PCCRC, but there are no data on associated CSSP detection rates (CSSDRs). We used data from the New Hampshire Colonoscopy Registry (NHCR) to investigate the association between PCCRC risk and endoscopist CSSDR. METHODS: We included NHCR patients with 1 or more follow-up events: either a colonoscopy or a colorectal cancer (CRC) diagnosis identified through linkage with the New Hampshire State Cancer Registry. We defined our outcome, PCCRC, in 3 time periods: CRC diagnosed 6 to 36 months, 6 to 60 months, or all examinations (6 months or longer) after an index examination. We excluded patients with CRC diagnosed at or within 6 months of the index examination, with incomplete examinations, or with inflammatory bowel disease. The exposure variable was endoscopist CSSDR at the index colonoscopy. Cox regression was used to model the hazard of PCCRC on CSSDR controlling for age, sex, index findings, year of examination, personal history of colorectal neoplasia, and having more than 1 surveillance examination. RESULTS: One hundred twenty-eight patients with CRC diagnosed at least 6 months after their index examination were included. Our cohort included 142 endoscopists (92 gastroenterologists). We observed that the risk for PCCRC 6 months or longer after the index examination was significantly lower for examinations performed by endoscopists with CSSDRs of 3% to <9% (hazard ratio [HR], .57; 95% confidence interval [CI], .39-.83) or 9% or higher (HR, .39; 95% CI, .20-.78) relative to those with CSSDRs under 3%. CONCLUSIONS: Our study is the first to demonstrate a lower PCCRC risk after examinations performed by endoscopists with higher CSSDRs. Both CSSDRs of 9% and 3% to <9% had statistically lower risk of PCCRC than CSSDRs of <3%. These data validate CSSDR as a clinically relevant quality measure for endoscopists.

Colorectal Neoplasia Detection in Individuals With Positive Multitarget Stool DNA Tests: Data From the New Hampshire Colonoscopy Registry.

BACKGROUND: The US Preventive Services Task Force (USPSTF) includes multitarget stool DNA (mt-sDNA) testing as a colorectal cancer (CRC) screening option in average-risk individuals, but data on colonoscopy outcomes after positive mt-sDNA tests in community settings are needed. AIM: The aim of this study was to investigate colonoscopy outcomes and quality following positive mt-sDNA in the population-based New Hampshire Colonoscopy Registry. METHODS: We compared colonoscopy outcomes and quality between age-matched, sex-matched, and risk-matched patients from 30 endoscopy practices with and without a preceding positive mt-sDNA test. Main outcomes were colonoscopy findings of CRC, advanced noncancerous neoplasia, nonadvanced neoplasia, or normal examination. Quality measures included withdrawal time, bowel preparation quality, examination completion, and percentage of average-risk individuals with normal colonoscopies receiving a USPSTF-recommended 10 year rescreening interval. RESULTS: Individuals with positive mt-sDNA tests (N=306, average age 67.0 y; 61.8% female) were significantly more likely than colonoscopy-only patients (N=918, 66.2 y; 61.8% female) to have CRC (1.3% vs. 0.4%) or advanced noncancerous neoplasia (27.1% vs. 8.2%) (P<0.0001). Neoplasia was found in 68.0% of patients having colonoscopy after a positive mt-sDNA test, (positive predictive value, was 68.0%), versus 42.3% of patients with colonoscopy only (P<0.0001). No significant differences in colonoscopy quality measures were observed between cohorts. CONCLUSIONS: Colonoscopy after a positive mt-sDNA test was more frequently associated with CRC and colorectal neoplasia than colonoscopy alone. Positive mt-sDNA tests can enrich the proportion of colonoscopies with clinically relevant findings. Follow-up recommendations suggest that endoscopists do not inappropriately shorten rescreening intervals in mt-sDNA-positive patients with normal colonoscopy. These findings support the clinical utility of mt-sDNA for CRC screening in community practice.

Colonoscopy Outcomes in Average-Risk Screening Equivalent Young Adults: Data From the New Hampshire Colonoscopy Registry.

INTRODUCTION: Data are needed to further inform the American Cancer Society recommendation to begin colorectal cancer (CRC) screening at age 45. We used the New Hampshire Colonoscopy Registry to compare the prevalence of advanced neoplasia (AN) in an "average-risk screening equivalent" group aged 45-49 years with patients aged 50-54 years and older receiving screening colonoscopy. METHODS: Colonoscopies in adults older than 50 years of age usually have diagnostic indications of varying clinical significance. We combined patients older than 50 years with diagnostic indications (abdominal pain and constipation) expected to yield AN prevalence similar to screening low AN risk and those with a screening indication to form an "average-risk screening equivalent" group. We excluded high-risk indications (e.g., bleeding and anemia), surveillance examinations, and patients with a first-degree family history of CRC, incomplete examinations, and poor bowel preparation. We calculated prevalence/adjusted risks for AN (≥1 cm, villous, high-grade dysplasia, and CRC) and clinically significant serrated polyps (large [≥1 cm] hyperplastic polyps, sessile serrated polyp, traditional serrated adenomas, and proximal hyperplastic polyp ≥ 5 mm). RESULTS: In our sample (n = 40,812), AN prevalence was as follows: <40 years (1.1%), 40-44 years (3.0%), 45-49 years (3.7%), 50-54 years (3.6%), 55-59 years (5.1%), and 60+ years (6.7%) (P < 0.0001 across all groups). The prevalence of both AN and clinically significant serrated polyp was similar in the 45-49 and 50-54 years' age groups. Furthermore, the prevalence of AN increased significantly in the 40-44 group as compared to that in the <40 years group. Adjusted analyses confirmed these results. The diagnostic indications considered to have low risk were not predictive of AN. DISCUSSION: New Hampshire Colonoscopy Registry data, demonstrating an increase in AN risk starting at age 40 and a similar prevalence for individuals aged 45-49 and those ages 50-54, provide clinically useful evidence for optimization of prevention and the age to start screening. However, this is a complex issue involving additional considerations that will need to be addressed.

Young adults and metachronous neoplasia: risks for future advanced adenomas and large serrated polyps compared with older adults.

BACKGROUND AND AIMS: Recent increases in colorectal cancer (CRC) incidence in adults younger than 50 years of age have led to more colonoscopies in this age group. As a result, there may be an increasing number of adults <50 years old with polyps detected. There is concern that younger adults may require closer follow-up. Our goal was to use data from the New Hampshire Colonoscopy Registry (NHCR) to examine the risk for metachronous advanced adenomas (AAs) and large (>1 cm) serrated polyps in younger versus older adults who return for a follow-up colonoscopy. METHODS: Our cohort consisted of NHCR participants with at least 1 polyp on index examination and a follow-up colonoscopy at least 1 year after the index examination. Outcomes were the risks for metachronous AAs (adenomas ≥1 cm, with villous elements or high-grade dysplasia, or CRC) and large (≥1 cm) serrated polyps. We present absolute risk and adjusted risks from a logistic regression model stratified by age at index colonoscopy (<40, 40-49, 50-59, and 60+ [reference]). Covariates included index findings, endoscopist adenoma detection rates, sex, smoking, body mass index, follow-up time (months), bowel preparation quality, and family history of CRC. RESULTS: In our sample of 12,380 adults, absolute risk for metachronous AA was lower for younger patients than for patients aged ≥60. After adjusting for covariates, when comparing with the 60+ group (reference), the lowest risk was observed in those younger than 40 years (odds ratio, .19; 95% confidence interval, .05-.80). Of note, similar risks were observed in the 40 to 49 age group (odds ratio, .61; 95% confidence interval, .41-.92) and 50 to 59 age group (odds ratio, .71; 95% confidence interval, .58-.86). The risk for large metachronous serrated polyps was not associated with age. CONCLUSIONS: Younger adults aged <40 with index adenomas had a lower risk for metachronous AAs than those aged ≥60. The 40- to 49-year age group was found to have metachronous risk similar to the 50- to 59-year age group, with both less than the ≥60 age group. These data suggest that current surveillance interval guidelines for patients aged ≥50 years may appropriately be used with younger adults.

Increased risk of metachronous large serrated polyps in individuals with 5- to 9-mm proximal hyperplastic polyps: data from the New Hampshire Colonoscopy Registry.

BACKGROUND AND AIMS: Because data on metachronous risk for patients with index proximal 5- to 9-mm hyperplastic polyps (HPs) are limited, the clinical significance of these polyps is unclear. Conversely, published data suggest that sessile serrated polyps (SSPs), traditional serrated adenomas (TSAs), and large (≥1 cm) HPs are high-risk lesions requiring close surveillance. We used data from the New Hampshire Colonoscopy Registry (NHCR) to examine the risk of metachronous large SPs and advanced neoplasias (ANs) in patients with 5- to 9-mm proximal HPs. METHODS: We included adults with at least 1 polyp resected at index colonoscopy and a surveillance examination 12 months or more after index. Outcomes were risk for metachronous large (≥1 cm) SPs and ANs (≥1 cm, villous elements, high-grade dysplasia, or colorectal cancer [CRC]). Individuals were hierarchically stratified by the most significant index SP. The risks for adults with proximal 5- to 9-mm HPs at index examination were compared with individuals with index findings of large (≥1 cm) HPs or any SSPs or TSAs, nonsignificant HPs (<1 cm in rectosigmoid or <5 mm anywhere in colon), high-risk adenomas (AAs or ≥3 adenomas, no SPs), and low-risk adenomas (no SPs). We present absolute and adjusted risks of metachronous polyps from a regression model that included age, sex, body mass index, smoking, previous polyp history, family history of CRC, year of diagnosis, endoscopist SP detection rates, and months to surveillance examination. RESULTS: A total of 8560 NHCR participants were included (44.8% women; average age, 59.0 years; standard deviation, 9.1). Similar to those with large HPs or any SSPs/TSAs at index examination (odds ratio, 7.63; 95% confidence interval, 4.78-12.20), individuals with proximal 5- to 9-mm HPs had an elevated risk for metachronous large SPs (odds ratio, 4.77; 95% confidence interval, 2.54-8.94) as compared with adults with low-risk conventional adenomas. CONCLUSIONS: NHCR data suggest that similar to adults with large HPs or any SSPs or TSAs at index examination, individuals with index 5- to 9-mm HPs proximal to the sigmoid are at an increased risk for metachronous large SPs. These novel data suggest that close surveillance intervals may be appropriate for patients with 5- to 9-mm proximal HPs.

Impact of Colonoscopy Bowel Preparation Quality on Follow-up Interval Recommendations for Average-risk Patients With Normal Screening Colonoscopies: Data From the New Hampshire Colonoscopy Registry.

BACKGROUND AND AIMS: National guidelines for colonoscopy screening and surveillance assume adequate bowel preparation. We used New Hampshire Colonoscopy Registry (NHCR) data to investigate the influence of bowel preparation quality on endoscopist recommendations for follow-up intervals in average-risk patients following normal screening colonoscopies. METHODS: The analysis included 9170 normal screening colonoscopies performed on average risk individuals aged 50 and above between February 2005 and September 2013. The NHCR Procedure Form instructs endoscopists to score based on the worst prepped segment after clearing all colon segments, using the following categories: excellent (essentially 100% visualization), good (very unlikely to impair visualization), fair (possibly impairing visualization), and poor (definitely impairing visualization). We categorized examinations into 3 preparation groups: optimal (excellent/good) (n=8453), fair (n=598), and poor (n=119). Recommendations other than 10 years for examinations with optimal preparation, and >1 year for examinations with poor preparation, were considered nonadherent. RESULTS: Of all examinations, 6.2% overall received nonadherent recommendations, including 5% of examinations with optimal preparation and 89.9% of examinations with poor preparation. Of normal examinations with fair preparation, 20.7% of recommendations were for an interval <10 years. Among those examinations with fair preparation, shorter-interval recommendations were associated with female sex, former/nonsmokers, and endoscopists with adenoma detection rate ≥20%. CONCLUSIONS: In 8453 colonoscopies with optimal preparations, most recommendations (95%) were guideline-adherent. No guideline recommendation currently exists for fair preparation, but in this investigation into community practice, the majority of the fair preparation group received 10-year follow-up recommendations. A strikingly high proportion of examinations with poor preparation received a follow-up recommendation greater than the 1-year guideline recommendation. Provider education is needed to ensure that patients with poor bowel preparation are followed appropriately to reduce the risk of missing important lesions.

Risk of Metachronous High-Risk Adenomas and Large Serrated Polyps in Individuals With Serrated Polyps on Index Colonoscopy: Data From the New Hampshire Colonoscopy Registry.

BACKGROUND & AIMS: Surveillance guidelines for serrated polyps (SPs) are based on limited data on longitudinal outcomes of patients. We used the New Hampshire Colonoscopy Registry to evaluate risk of clinically important metachronous lesions associated with SPs detected during index colonoscopies. METHODS: We collected data from a population-based colonoscopy registry that has been collecting and analyzing data on colonoscopies across the state of New Hampshire since 2004, including rates of adenoma and SP detection. Patients completed a questionnaire to determine demographic characteristics, health history, and risk factors for colorectal cancer, and were followed from index colonoscopy through all subsequent surveillance colonoscopies. Our analyses included 5433 participants (median age, 61 years; 49.7% male) with 2 colonoscopies (median time to surveillance, 4.9 years). We used multivariable logistic regression models to assess effects of index SPs (n = 1016), high-risk adenomas (HRA, n = 817), low-risk adenomas (n = 1418), and no adenomas (n = 3198) on subsequent HRA or large SPs (>1 cm) on surveillance colonoscopy (metachronous lesions). Synchronous SPs, within each index risk group, were assessed for size and by histology. SPs comprise hyperplastic polyps, sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas. In this study, SSA/Ps and traditional serrated adenomas are referred to collectively as STSAs. RESULTS: HRA and synchronous large SP (odds ratio [OR], 5.61; 95% confidence interval [CI], 1.72-18.28), HRA with synchronous STSA (OR, 16.04; 95% CI, 6.95-37.00), and HRA alone (OR, 3.86; 95% CI, 2.77-5.39) at index colonoscopy significantly increased the risk of metachronous HRA compared to the reference group (no index adenomas or SPs). Large index SPs alone (OR, 14.34; 95% CI, 5.03-40.86) or index STSA alone (OR, 9.70; 95% CI, 3.63-25.92) significantly increased the risk of a large metachronous SP. CONCLUSIONS: In an analysis of data from a population-based colonoscopy registry, we found index large SP or index STSA with no index HRA increased risk of metachronous large SPs but not metachronous HRA. HRA and synchronous SPs at index colonoscopy significantly increased risk of metachronous HRA. Individuals with HRA and synchronous large SP or any STSA could therefore benefit from close surveillance.

Assessing data availability and quality within an electronic health record system through external validation against an external clinical data source.

BACKGROUND: Approximately 20% of deaths in the US each year are attributable to smoking, yet current practices in the recording of this health risk in electronic health records (EHRs) have not led to discernable changes in health outcomes. Several groups have developed algorithms for extracting smoking behaviors from clinical notes, but none of these approaches were assessed with external data to report on anticipated clinical performance. METHODS: Previously, we developed an informatics pipeline that extracts smoking status, pack year history, and cessation date from clinical notes. Here we report on the clinical implementation performance of our pipeline using 1,504 clinical notes matched to an external questionnaire. RESULTS: We found that 73% of available notes contained no smoking behavior information. The weighted Cohen's kappa between the external questionnaire and EHR smoking status was 0.62 (95% CI 0.56-0.69) for the clinical notes we were able to extract information from. The correlation between pack years reported by our pipeline and the external questionnaire was 0.39 on the 81 notes for which this information was present in both. We also assessed for lung cancer screening eligibility using notes from individuals identified as never smokers or smokers with pack year history extracted by our pipeline (n = 196). We found a positive predictive value of 85.4%, a negative predictive value of 83.8%, sensitivity of 63.1%, and specificity of 94.7%. CONCLUSIONS: We have demonstrated that our pipeline can extract smoking behaviors from unannotated EHR notes when the information is present. This information is reliable enough to identify patients most likely to be eligible for smoking related services. Ensuring capture of smoking information during clinical encounters should continue to be a high priority.

Endoscopist Specialty Predicts the Likelihood of Recommending Cessation of Colorectal Cancer Screening in Older Adults.

OBJECTIVES: Although the 2008 US Preventive Services Task Force guidelines recommend against routine colorectal cancer (CRC) screening for adults aged 76-85, it is unclear what endoscopists recommend in practice. Our goal was to examine current practice around cessation of CRC screening in older adults. METHODS: We included normal screening colonoscopy exams in adults ≥ 50 years old within the New Hampshire Colonoscopy Registry between 2009 and 2014. The primary outcome was endoscopists' recommendation against further screening. The main exposure variables included patient age, family history of CRC, and endoscopist characteristics. Descriptive statistics and univariate and multivariable logistic regression models were used. RESULTS: Of 13,364 normal screening colonoscopy exams, 2914 (21.8%) were in adults aged ≥ 65 and were performed by 74 endoscopists. Nearly 100% of adults aged 65-69 undergoing screening colonoscopy were given the recommendation to return for screening colonoscopy in the future. Only 15% of average-risk patients aged 70-74 were told to stop receiving screening, while 85% were told to return at a future interval, most frequently in 10 years when they would be 80-84. In the multivariable model, advancing patient age and the absence of family history of CRC were significantly associated with a recommendation to stop colonoscopy. Gastroenterologists were more likely to recommend stopping colonoscopy in accordance with guidelines than other non-gastroenterology endoscopists (adjusted OR (95% CI) 2.3 (1.6-3.4)). CONCLUSIONS: In a large statewide colonoscopy registry, the majority of older adults are told to return for future screening colonoscopy. Having a family history of CRC or a non-gastroenterology endoscopist increases the likelihood of being told to return for screening at advanced ages.

Smoking and Other Risk Factors in Individuals With Synchronous Conventional High-Risk Adenomas and Clinically Significant Serrated Polyps.

BACKGROUND AND AIMS: Serrated polyps (SPs) and conventional high-risk adenomas (HRAs) derive from two distinct biological pathways but can also occur synchronously. Adults with synchronous SPs and adenomas have been shown to be a high-risk group and may have a unique risk factor profile that differs from adults with conventional HRAs alone. We used the population-based New Hampshire Colonoscopy Registry (NHCR) to examine the risk profile of individuals with synchronous conventional HRAs and SPs. METHODS: Our study population included 20,281 first time screening colonoscopies from asymptomatic NHCR participants 40 years or older between 2004-15. Exams were categorized by findings: (1) normal, (2) HRA only (adenomas ≥ 1 cm, villous, high grade dysplasia, multiple adenomas ( > 2) and adenocarcinoma), (3) clinically significant SP (CSSP) only (any hyperplastic polyp ≥ 1 cm, sessile serrated adenomas/polyps or traditional serrated adenomas), and (4) synchronous HRA + CSSP. Risk factors examined included exposure of interest, smoking (never, past, and current/pack years), as well as age, sex, alcohol, education, and family history of colorectal cancer (CRC). Multivariable unconditional logistic regression tested the relation of risk factors with having synchronous HRA + CSSP versus having a normal exam or HRA alone. RESULTS: Among NHCR participants with 18,354 screening colonoscopies (with complete smoking, sex, bowel preparation data, and adequate preparation) there were 16,495 normal; 1309 HRA alone; 461 CSSP alone, and 89 synchronous HRA + CSSP. Current smoking was associated with an almost threefold increased risk for HRA or CSSP, and an eightfold risk for synchronous HRA + CSSP (aOR = 8.66; 95% CI: 4.73-15.86) compared to normal exams. Adults with synchronous HRA + CSSP were threefold more likely to be current smokers than those with HRA alone (aOR = 3.27; 95% CI:1.74-6.16). CONCLUSIONS: Our data suggest that current smokers may be at a higher risk for synchronous CSSP + HRA even when compared to having HRA alone.

"Tissue Papers" from Organ-Specific Decellularized Extracellular Matrices.

Using an innovative, tissue-independent approach to decellularized tissue processing and biomaterial fabrication, the development of a series of "tissue papers" derived from native porcine tissues/organs (heart, kidney, liver, muscle), native bovine tissue/organ (ovary and uterus), and purified bovine Achilles tendon collagen as a control from decellularized extracellular matrix particle ink suspensions cast into molds is described. Each tissue paper type has distinct microstructural characteristics as well as physical and mechanical properties, is capable of absorbing up to 300% of its own weight in liquid, and remains mechanically robust (E = 1-18 MPa) when hydrated; permitting it to be cut, rolled, folded, and sutured, as needed. In vitro characterization with human mesenchymal stem cells reveals that all tissue paper types support cell adhesion, viability, and proliferation over four weeks. Ovarian tissue papers support mouse ovarian follicle adhesion, viability, and health in vitro, as well as support, and maintain the viability and hormonal function of nonhuman primate and human follicle-containing, live ovarian cortical tissues ex vivo for eight weeks postmortem. "Tissue papers" can be further augmented with additional synthetic and natural biomaterials, as well as integrated with recently developed, advanced 3D-printable biomaterials, providing a versatile platform for future multi-biomaterial construct manufacturing.

Providing data for serrated polyp detection rate benchmarks: an analysis of the New Hampshire Colonoscopy Registry.

BACKGROUND AND AIMS: Similar to achieving adenoma detection rate (ADR) benchmarks to prevent colorectal cancer (CRC), achieving adequate serrated polyp detection rates (SDRs) may be essential to the prevention of CRC associated with the serrated pathway. Previous studies have been based on data from high-volume endoscopists at single academic centers. Based on a hypothesis that ADR is correlated with SDR, we stratified a large, diverse group of endoscopists (n = 77 practicing at 28 centers) into high performers and low performers, based on ADR, to provide data for corresponding target SDR benchmarks. METHODS: By using colonoscopies in adults aged ≥50 years (4/09-12/14), we stratified endoscopists by high and low ADRs (<15%, 15%-<25%, 25%-<35%, ≥35%) to determine corresponding SDRs by using 2 SDR measures, for screening and surveillance colonoscopies separately: (1) Clinically significant SDR (CSSDR), meaning colonoscopies with any sessile serrated adenoma/polyp (SSA/P), traditional serrated adenoma (TSA), or hyperplastic polyp (HP) >1 cm anywhere in the colon or HP >5 mm in the proximal colon only divided by the total number of screening and surveillance colonoscopies, respectively. (2) Proximal SDR (PSDR) meaning colonoscopies with any serrated polyp (SSA/P, HP, TSA) of any size proximal to the sigmoid colon divided by the total number of screening and surveillance colonoscopies, respectively. RESULTS: A total of 45,996 (29,960 screening) colonoscopies by 77 endoscopists (28 facilities) were included. Moderately strong positive correlation coefficients were observed for screening ADR/CSSDR (P = .69) and ADR/PSDR (P = .79) and a strong positive correlation (P = .82) for CSSDR/PSDR (P < .0001 for all) was observed. For ADR ≥25%, endoscopists' median (interquartile range) screening CSSDR was 6.8% (4.3%-8.6%) and PSDR was 10.8% (8.6%-16.1%). CONCLUSIONS: Derived from ADR, the primary colonoscopy quality indicator, our results suggest potential SDR benchmarks (CSSDR = 7% and PSDR = 11%) that may guide adequate serrated polyp detection. Because CSSDR and PSDR are strongly correlated, endoscopists could use the simpler PSDR calculation to assess quality.