Pre-existing Thyroid Autoimmunity and Risk of Papillary Thyroid Cancer: A Nested Case-Control Study of US Active-Duty Personnel.

PURPOSE: Thyroid autoimmunity has been associated with differentiated thyroid cancer although multiple potential biases might have influenced the results of previous studies. METHODS: We conducted a case-control study nested within the cohort of US active-duty personnel 1996-2014 to assess the association between thyroid autoimmunity, defined by serology, and thyroid cancer diagnosis. The primary exposure was thyroid peroxidase (TPO) antibody status 7-10 years before the thyroid cancer index date. We also assessed whether diagnosis of thyroid autoimmunity mediated any associations identified and if thyroid cancer features differed by autoimmunity status. RESULTS: Among 451 incident cases of papillary thyroid cancer and matched controls (median age 36 years, 61.4% men), TPO antibody positivity (v negative) 7-10 years prediagnosis was associated with thyroid cancer (odds ratio [OR] 1.90 [95% CI, 1.33 to 2.70]). Exploratory analyses suggested an increasing risk of thyroid cancer with higher TPO antibody titer (TPO antibody 550-1,399 IU/mL: OR 2.95 [95% CI, 1.37 to 6.36]; and ≥ 1,400 IU/mL: OR 3.91 [95% CI, 1.66 to 9.24]). Positive TPO antibody status remained associated with thyroid cancer after those with diagnosed autoimmunity were excluded, and the association was not mediated by diagnosis of thyroid autoimmunity. Among the cases with diagnosed autoimmunity, 58% thyroid cancers were ≤ 10 mm diameter. CONCLUSION: Longstanding prior thyroid autoimmunity up to 10 years before thyroid cancer diagnosis was associated with papillary thyroid cancer risk. The results could not be fully explained by diagnosis of thyroid autoimmunity although when autoimmunity had been identified, thyroid cancers were diagnosed at a very early stage.

Levels of Vitamin D Are Low After Crohn's Disease Is Established But Not Before.

BACKGROUND & AIMS: Low serum levels of vitamin D have been associated with Crohn's disease (CD). However, it is unclear whether low vitamin D levels cause CD or CD reduces serum vitamin D. METHODS: United States military personnel with CD (n = 240) and randomly selected individuals without CD (controls, n = 240) were matched by age, sex, race, military branch, and geography. We measured 25-hydroxyvitamin D in sera 8-3 years (pre-2) and 3 years to 3 months before diagnosis (pre-1) and 3 months before through 21 months after diagnosis (pre-0). We genotyped VDR and GC vitamin D related polymorphisms. We used conditional logistic regression, including adjustments for smoking, season, enlistment status, and deployment, to estimate relative odds of CD according to vitamin D levels and interactions between genetic factors and levels of vitamin D. RESULTS: Levels of vitamin D before diagnosis were not associated with CD in pre-2 (P trend = .65) or pre-1 samples (P trend = .84). However, we found an inverse correlation between CD and highest tertile of vitamin D level in post-diagnosis samples (P trend = .01; odds ratio, 0.51; 95% CI, 0.30-0.86). Interactions were not detected between vitamin D levels and VDR or GC polymorphisms. We observed an association between VDR Taq1 polymorphism and CD (independent of vitamin D) (P = .02). CONCLUSIONS: In serum samples from military personnel with CD and matched controls, we found no evidence for an association between CD and vitamin D levels up to 8 years before diagnosis. However, we observed an inverse-association between post-diagnosis vitamin D levels and CD. These findings suggest that low vitamin D does not contribute to development of CD-instead, CD leads to low vitamin D.

Same-Day vs Different-Day Elective Upper and Lower Endoscopic Procedures by Setting.

Importance: Performing elective upper and lower endoscopic procedures on the same day is a patient-centered and less costly approach than a 2-stage approach performed on different days, when clinically appropriate. Whether this practice pattern varies based on practice setting has not been studied. Objectives: To estimate the rate of different-day upper and lower endoscopic procedures in 3 types of outpatient settings and investigate the factors associated with the performance of these procedures on different days. Design, Setting, and Participants: A retrospective analysis was conducted of Medicare claims between January 1, 2011, and June 30, 2018, for Medicare beneficiaries who underwent a pair of upper and lower endoscopic procedures performed within 90 days of each other at hospital outpatient departments (HOPDs), freestanding ambulatory surgery centers (ASCs), and physician offices. Main Outcomes and Measures: Undergoing an upper and a lower endoscopic procedure on different days, adjusted for patient characteristics (age, sex, race/ethnicity, residence location and region, comorbidity, and procedure indication) and physician characteristics (sex, years in practice, procedure volume, and primary specialty). Adjusted odds ratios (aORs) and 95% CIs were calculated. Results: A total of 4 028 587 procedure pairs were identified, of which 52.5% were performed in HOPDs, 43.3% in ASCs, and 4.2% in physician offices. The rate of different-day procedures was 13.6% in HOPDs, 22.2% in ASCs, and 47.7% in physician offices. For the 7564 physicians who practiced at both HOPDs and ASCs, their different-day procedure rate changed from 14.1% at HOPDs to 19.4% at ASCs. For the 993 physicians who practiced at both HOPDs and physician offices, their different-day procedure rate changed from 15.8% at HOPDs to 37.4% at physician offices. Patients were more likely to undergo different-day procedures at physician offices and ASCs compared with HOPDs, even after adjusting for patient and physician characteristics (physician office vs HOPD: aOR, 2.02; 95% CI, 1.85-2.20; ASC vs HOPD: aOR, 1.27; 95% CI, 1.23-1.32). Older age (85-94 years vs 65-74 years: aOR, 1.10; 95% CI, 1.08-1.11; 95 years or older vs 65-74 years: aOR, 1.14; 95% CI, 1.03-1.26), black and Hispanic race/ethnicity (black: aOR, 1.15; 95% CI, 1.12-1.17; Hispanic: aOR, 1.12; 95% CI, 1.10-1.14), and residing in the Northeast region (adjusted OR, 1.32; 95% CI, 1.28-1.36) were risk factors for undergoing different-day procedures. Micropolitan location (aOR, 0.94; 95% CI, 0.92-0.96) and rural location (aOR, 0.91; 95% CI, 0.89-0.93), more comorbidities (≥5: aOR, 0.75; 95% CI, 0.74-0.76), physician's fewer years in practice (aOR, 0.84; 95% CI, 0.81-0.87), physician's higher procedure volume (aOR, 0.65; 95% CI, 0.62-0.68), and physician's specialty of general surgery (aOR, 0.86; 95% CI, 0.80-0.91) were protective factors. Conclusions and Relevance: Physician offices and ASCs had much higher different-day procedure rates compared with HOPDs. This disparity may represent an opportunity for quality improvement and financial savings for common endoscopic procedures.

Smoking and Inflammatory Bowel Disease: A Comparison of China, India, and the USA.

BACKGROUND: Cigarette smoking is thought to increase the risk of Crohn's disease (CD) and exacerbate the disease course, with opposite roles in ulcerative colitis (UC). However, these findings are from Western populations, and the association between smoking and inflammatory bowel disease (IBD) has not been well studied in Asia. AIMS: We aimed to compare the prevalence of smoking at diagnosis between IBD cases and controls recruited in China, India, and the USA, and to investigate the impact of smoking on disease outcomes. METHODS: We recruited IBD cases and controls between 2014 and 2018. All participants completed a questionnaire about demographic characteristics, environmental risk factors and IBD history. RESULTS: We recruited 337 participants from China, 194 from India, and 645 from the USA. In China, CD cases were less likely than controls to be current smokers (adjusted odds ratio [95% CI] 0.4 [0.2-0.9]). There was no association between current or former smoking and CD in the USA. In China and the USA, UC cases were more likely to be former smokers than controls (China 14.6 [3.3-64.8]; USA 1.8 [1.0-3.3]). In India, both CD and UC had similar current smoking status to controls at diagnosis. Current smoking at diagnosis was significantly associated with greater use of immunosuppressants (4.4 [1.1-18.1]) in CD cases in China. CONCLUSIONS: We found heterogeneity in the associations of smoking and IBD risk and outcomes between China, India, and the USA. Further study with more adequate sample size and more uniform definition of smoking status is warranted.

Surgeon-Level Variation in Postoperative Complications.

BACKGROUND: Variation in surgical outcomes is often attributed to patient comorbidities and the severity of underlying disease, but little is known about the extent of variation in outcomes by surgeon and the surgeon factors that are associated with quality. METHODS: Using the Maryland Health Services Cost Review Commission database, we evaluated risk-adjusted postoperative events by surgeon. Operations studied were elective laparoscopic and open colectomy procedures for colon cancer performed over a 2-year period (July 2012-September 2014). Postoperative events were defined using the Agency for Healthcare Research and Quality Patient Safety Indicators. Surgeons performing fewer than ten procedures during the study period were excluded. Logistic regression and post-estimation were used to calculate an observed-to-expected (O/E) ratio of postoperative complications for each surgeon, adjusting for patient and surgeon characteristics. RESULTS: A total of 2525 patients underwent an elective colectomy during the study period by 276 surgeons at 44 hospitals. Postoperative complications varied more by surgeon (range 0 to 30.0 %) than by hospital (range 0 to 18.2 %). Surgeon-level use of laparoscopic surgery to perform colectomy ranged from 0 to 100 %. After risk adjustment with patient factors, surgeon experience, surgeon medical school, surgeon gender, and annual surgeon colectomy volume were not associated with postoperative complications. Surgeon use of laparoscopy was the strongest predictor of lower complications (vs fourth quartile of surgeons, first quartile OR = 0.47 (0.26-0.85); second quartile OR = 0.41 (0.22-0.73); and third quartile OR = 0.84 (0.52-1.36). CONCLUSIONS: Quality metrics in health care have been measured at the hospital level, but a greater quality improvement potential exists at the surgeon level. Awareness of this variation could better inform patients undergoing elective surgery and their referring physicians.

A comparative evaluation of outcomes of endoscopic versus percutaneous drainage for symptomatic pancreatic pseudocysts.

BACKGROUND: Endoscopic drainage (ED) and percutaneous drainage (PD) have largely replaced surgical drainage as the initial approach for symptomatic pseudocysts. However, there are few studies comparing ED and PD. OBJECTIVE: To compare the outcomes of ED and PD for symptomatic pseudocysts. DESIGN: Retrospective cohort study. SETTING: Academic center. PATIENTS: Adult patients with symptomatic pseudocysts within ≤ 1 cm of the gastric or duodenal wall who underwent ED or PD between 1993 and 2011. Patients with walled-off pancreatic necrosis were excluded. INTERVENTION: ED or PD. MAIN OUTCOME MEASUREMENTS: Rates of technical success, procedural adverse events, clinical success, reinterventions, and failure. Other outcomes included the length of hospital stay and number of follow-up abdominal imaging studies. RESULTS: There were 81 patients, 41 who underwent ED and 40 who underwent PD, with no differences in age, sex, and comorbidity between the 2 groups. There were no differences in the rates of technical success (90.2% vs 97.5%; P = .36), adverse events (14.6% vs 15%; P = .96), and clinical success (70.7% vs 72.5%; P = .86) between ED and PD, respectively. Patients who underwent PD had higher rates of reintervention (42.5% vs 9.8%; P = .001), longer length of hospital stay (14.8 ± 14.4 vs 6.5 ± 6.7 days; P = .001), and median number [quartiles] of follow-up abdominal imaging studies (6 [3.25, 10] vs 4 [2.5, 6]; P = .02) compared with patients who underwent ED. LIMITATIONS: Single center, retrospective study. CONCLUSION: ED and PD have similar clinical success rates for symptomatic pseudocysts. However, PD is associated with significantly higher rates of reintervention, longer length of hospital stay, and increased number of follow-up abdominal imaging studies.

Comparative effectiveness of strategies to prevent weight gain among women with and at risk for breast cancer: a systematic review.

BACKGROUND: Obesity affects cancer risk and treatment outcomes. Preventing weight gain may prevent some cancers, improve cancer outcomes, reduce cancer recurrence and increase cancer-related survival. We performed a systematic review to identify strategies to prevent weight gain in individuals with or at risk for breast cancer. FINDINGS: We included 2 studies from 27,879 citations. In premenopausal women at risk for breast cancer, a low fat diet prevented weight gain at 12 months. Among women with breast cancer, effective strategies to prevent weight gain included low-fat dietary counseling with self-management techniques. One trial reported on cancer outcomes, mortality and adverse events. Low-fat dietary counseling wilth self-management techniques lowers the risk breast cancer relapse by 24% compared with less intensive counseling with maintenance of nutritional status goal. There was no difference in overall mortality and no adverse events were observed. CONCLUSION: Limited evidence suggests that women with or at risk for breast cancer may successfully employ dietary and exercise strategies to prevent weight gain for at least one year. Low fat dietary counseling may improve cancer outcomes in women with breast cancer. Future studies should confirm these findings and evaluate the impact of weight gain prevention on cancer incidence, recurrence and survival.

Comparative genomic analysis of esophageal adenocarcinoma and squamous cell carcinoma.

Esophageal cancer ranks sixth in cancer death. To explore its genetic origins, we conducted exomic sequencing on 11 esophageal adenocarcinomas (EAC) and 12 esophageal squamous cell carcinomas (ESCC) from the United States. Interestingly, inactivating mutations of NOTCH1 were identified in 21% of ESCCs but not in EACs. There was a substantial disparity in the spectrum of mutations, with more indels in ESCCs, A:T>C:G transversions in EACs, and C:G>G:C transversions in ESCCs (P < 0.0001). Notably, NOTCH1 mutations were more frequent in North American ESCCs (11 of 53 cases) than in ESCCs from China (1 of 48 cases). A parallel analysis found that most mutations in EACs were already present in matched Barrett esophagus. These discoveries highlight key genetic differences between EACs and ESCCs and between American and Chinese ESCCs, and suggest that NOTCH1 is a tumor suppressor gene in the esophagus. Finally, we provide a genetic basis for the evolution of EACs from Barrett esophagus.

Timing of myelosuppression during thiopurine therapy for inflammatory bowel disease: implications for monitoring recommendations.

BACKGROUND & AIMS: Thiopurines (azathioprine and 6-mercaptopurine) can induce life-threatening myelosuppression. This study determined the frequency, timing, and outcomes of mild and severe myelosuppression after initiation of thiopurine therapy. METHODS: This retrospective cohort study included patients with inflammatory bowel disease who were new users of thiopurines; those tested for thiopurine methyltransferase levels before therapy were excluded. Patients were followed from their first thiopurine prescription until the earliest of severe leukopenia (white blood cell count, <1.0 x 10(9)/L), severe thrombocytopenia (platelet level, <20 x 10(9)/L), the end of therapy, the first gap in therapy, disenrollment, or December 31, 2006. RESULTS: Among 1997 new users, the incidence of severe leukopenia per 100 person-months was 0.16 (95% confidence interval [CI], 0.03-0.29; n = 6) in weeks 0 to 8, 0.00 in weeks 9 to 24, and 0.01 (95% CI, 0-0.03; n = 3) after week 26 of therapy. The incidence of severe neutropenia and severe thrombocytopenia per 100 person-months during the first 8 weeks of therapy was 0.51 (95% CI, 0.31-0.80; n = 19) and 0.08 (95% CI, 0.02-0.23; n = 3), respectively. During the first 8 weeks, the median duration from a normal white blood cell count to severe leukopenia was 13 days (range, 8-26 d) and to severe neutropenia was 14 days (range, 7-23 d). CONCLUSIONS: The high incidence of severe myelosuppression justifies frequent monitoring during the first 8 weeks of therapy. Subsequently, the rate of severe myelosuppression and the proportion of patients who progress from mild to severe myelosuppression decrease, justifying less-frequent monitoring.

Mortality by medication use among patients with inflammatory bowel disease, 1996-2003.

BACKGROUND & AIMS: Most previous population-based studies of mortality in inflammatory bowel disease (IBD) did not account for medication use. We evaluated mortality by IBD medication use among members of the Kaiser Permanente Northern California IBD Registry. METHODS: The retrospective, population-based cohort study included 9032 persons who received at least one inpatient or 2 outpatient diagnoses of IBD during 1996-2002. Age and sex standardized mortality ratios measured the associations between IBD and all-cause and cause-specific mortality. Age, sex, and smoking adjusted odds ratios measured the association of mortality by IBD medication use. RESULTS: Compared with health plan members without IBD, mortality was increased in patients with Crohn's disease (CD) (1.4; 95% confidence interval, 1.2-1.6) but not ulcerative colitis (UC) (1.0; 95% CI, 0.9-1.2). CD was associated with increased mortality from infectious and parasitic diseases (4.1; 95% CI, 1.7-8.5), septicemia (6.8; 95% CI, 2.2-15.8), small intestinal cancer (48.1; 95% CI, 5.8-17.4), respiratory diseases (1.9; 95% CI, 1.3-2.7), digestive diseases other than IBD (2.4; 95% CI, 1.0-4.8), and liver diseases (2.6; 95% CI, 1.0-5.3). UC was associated with increased mortality from digestive diseases other than IBD (3.9; 95% CI, 2.4-6.0). The relationship with CD mortality was 0.7 for aminosalicylates (95% CI, 0.5-1.1), 1.3 (95% CI, 0.9-1.9) for immunomodulators, and 1.0 (95% CI, 0.7-1.4) for corticosteroids. Among patients with UC, these odds ratios were 0.8 (95% CI, 0.5-1.1) for aminosalicylates, 0.5 (95% CI, 0.3-0.9) for immunomodulators, and 0.8 (95% CI, 0.6-1.1) for corticosteroids. CONCLUSIONS: Mortality is increased in CD. Infections, respiratory diseases, and digestive diseases are important specific causes of death. IBD medication use has varying associations with mortality.