Julia E. Weiss

Serrated and adenomatous polyp detection increases with longer withdrawal time: results from the New Hampshire Colonoscopy Registry.

OBJECTIVES:Detection and removal of adenomas and clinically significant serrated polyps (CSSPs) is critical to the effectiveness of colonoscopy in preventing colorectal cancer. Although longer withdrawal time has been found to increase polyp detection, this association and the use of withdrawal time as a quality indicator remains controversial. Few studies have reported on withdrawal time and serrated polyp detection. Using data from the New Hampshire Colonoscopy Registry, we examined how an endoscopists withdrawal time in normal colonoscopies affects adenoma and serrated polyp detection.METHODS:We analyzed 7,996 colonoscopies performed in 7,972 patients between 2009 and 2011 by 42 endoscopists at 14 hospitals, ambulatory surgery centers, and community practices. CSSPs were defined as sessile serrated polyps and hyperplastic polyps proximal to the sigmoid. Adenoma and CSSP detection rates were calculated based on median endoscopist withdrawal time in normal exams. Regression models were used to estimate the association of increased normal withdrawal time and polyp, adenoma, and CSSP detection.RESULTS:Polyp and adenoma detection rates were highest among endoscopists with 9 min median normal withdrawal time, and detection of CSSPs reached its highest levels at 8–9 min. Incident rate ratios for adenoma and CSSP detection increased with each minute of normal withdrawal time above 6 min, with maximum benefit at 9 min for adenomas (1.50, 95% confidence interval (CI) (1.21, 1.85)) and CSSPs (1.77, 95% CI (1.15, 2.72)). When modeling was used to set the minimum withdrawal time at 9 min, we predicted that adenomas and CSSPs would be detected in 302 (3.8%) and 191 (2.4%) more patients. The increase in detection was most striking for the CSSPs, with nearly a 30% relative increase.CONCLUSIONS:A withdrawal time of 9 min resulted in a statistically significant increase in adenoma and serrated polyp detection. Colonoscopy quality may improve with a median normal withdrawal time benchmark of 9 min.

Dendritic Cell Infiltration in Colon Cancer

We quantitatively evaluated dendritic cell (DC) infiltration in primary colorectal cancers from 44 patients and metastatic colorectal tumors from 13 patients using immunohistochemistry for the DC marker CD83, HLA-DR, and the DC activation molecules CD40 and CD86. Nearly all CD83+ cells were also HLA-DR+, CD40+, and CD86+, indicating that the DCs that infiltrate colon cancer in vivo express the activation and costimulatory molecules associated with a mature DC phenotype. The density of DCs in colorectal cancer primaries was three times lower than that seen in normal colonic mucosa (0.29 versus 0.84 CD83+ cells/ high-power field (hpf), p < 0.001). Dendritic cells were rarely observed in metastatic tumors: DC density in metastases was sixfold lower than in colorectal primary tumors (0.05 versus 0.29 CD83+ cells/hpf, p < 0.001). Because cytokines have been shown, in vitro, to exert potent effects on DCs, we also evaluated the relationship between intratumor DC density and the expression of cytokines by tumor-infiltrating lymphocytes (TILs) and tumor cells. Expression of interleukin-10 and transforming growth factor &bgr; by either TIL or tumor cells was not associated with decreased DC density or decreased expression of CD40 or CD86 on DCs. Tumor expression of vascular endothelial growth factor was associated with a more than twofold increase in DC density (p = 0.01). Patients who had a high proportion of TILs expressing tumor necrosis factor (TNF) had a greater intratumor mature DC density than patients with a low proportion of TNF + TIL (0.54 versus 0.21 CD83+ cells/hpf, p < 0.01).

Safety and Tolerability of Transoral Bravo Capsule Placement After Transnasal Manometry Using a Validated Conversion Factor

OBJECTIVES:To prospectively calculate and validate a conversion factor in healthy volunteers that allows accurate nonsedated, transoral (TO) Bravo capsule placement after transnasal (TN) manometry, and to evaluate the ease and safety of nonendoscopic Bravo placement compared with endoscopic placement.METHODS:Part 1. Twenty-five healthy volunteers underwent sequential TN and TO esophageal manometry to measure the distance to the lower esophageal sphincter (LES). A TN to TO conversion factor was calculated from these measurements. Part 2. Twenty volunteers underwent TN manometry followed by unsedated TO Bravo capsule placement using the conversion factor calculated in part 1. TN endoscopy then measured the location of the Bravo capsule in relationship to the squamocolumnar junction (SCJ). Part 3. During an 18-month period, 370 consecutive patients referred for a Bravo procedure underwent nonendoscopic, unsedated TO placement (308 patients) or standard endoscopically assisted placement (62 patients).RESULTS:Part 1. All 25 volunteers completed TN and TO manometry; a conversion factor of 4 cm was calculated. Part 2. Using the calculated conversion factor of 4 cm, a Bravo capsule was deployed TO 5 cm above the proximal border of the LES. The mean ± standard deviation (SD) TN endoscopic distance to the capsule was 6.0 cm (±0.3 cm) above the SCJ. Part 3. A total of 333 patients completed the entire study (90%). Analysis of 48-h pH measurements did not reveal any significant differences between the two groups.CONCLUSIONS:A reliable and valid conversion factor of 4 cm following TN manometry permits accurate TO placement of the Bravo capsule without endoscopy. TO, unsedated Bravo placement is safe, well tolerated, and may minimize costs and potential risks associated with endoscopy.

Effects of anesthetic technique on myocardial wall motion abnormalities during abdominal aortic surgery

OBJECTIVE To assess the impact of regional supplemented general anesthesia (RSGEN) on regional myocardial function during abdominal aortic surgery (AAS). DESIGN Prospective randomized study. SETTING Single academic medical center. PARTICIPANTS Seventy-three patients scheduled for infrarenal aortic aneursymectomy. INTERVENTIONS Patients received standardized intraoperative anesthetic management consisting of either general anesthesia (GA; n = 37) or general anesthesia supplemented by epidural anesthesia (RSGEN; n = 36). MEASUREMENTS AND MAIN RESULTS Hemodynamic measurements and transesophageal echocardiograms (TEE) were obtained at eight intraoperative times. The electrocardiogram (ECG) was continuously recorded using Holter monitoring. Of the 56 patients with interpretable TEE recordings, 8 of 30 (27%) GA patients and 7 of 26 (27%) RSGEN patients developed new segmental wall motion abnormalities (SWMAs). There was no treatment effect on either the incidence (p = 0.23) or the intensity (p = 0.34) of SWMAs. Cross-clamping of the aorta was associated with the onset of new SWMAs (odds ratio, 8.2; 95% CI, 1.1 to 64; p = 0.04). Among the 63 patients with interpretable Holter recordings, 9 of 34 (26%) GA patients and 9 of 29 (31%) RSGEN patients exhibited intraoperative ischemia. There was no treatment effect on the incidence (p = 0.22) or intensity (p = 0.67) of ECG ischemia. CONCLUSION Despite providing modest hemodynamic depression, RSGEN did not reduce the incidence or intensity of either regional myocardial dysfunction or ECG ischemia. New SWMAs were temporally associated with cross-clamping of the aorta and tended to resolve with unclamping.

Influence of Movie Smoking Exposure and Team Sports Participation on Established Smoking

OBJECTIVE To examine the joint effects of movie smoking exposure and team sports participation on established smoking. DESIGN Longitudinal study. SETTING School- and telephone-based surveys in New Hampshire and Vermont between September 1999 through November 1999 and February 2006 through February 2007. PARTICIPANTS A total of 2048 youths aged 16 to 21 years at follow-up. Main Exposures Baseline movie smoking exposure categorized in quartiles assessed when respondents were aged 9 to 14 years and team sports participation assessed when respondents were aged 16 to 21 years. Main Outcome Measure Established smoking (having smoked > or =100 cigarettes in ones lifetime) at follow-up. RESULTS At follow-up, 353 respondents (17.2%) were established smokers. Exposure to the highest quartile of movie smoking compared with the lowest increased the likelihood of established smoking (odds ratio = 1.63; 95% confidence interval, 1.03-2.57), and team sports nonparticipants compared with participants were twice as likely to be established smokers (odds ratio = 2.01; 95% confidence interval, 1.47-2.74). The joint effects of movie smoking exposure and team sports participation revealed that at each quartile of movie smoking exposure, the odds of established smoking were greater for team sports nonparticipants than for participants. We saw a dose-response relationship of movie smoking exposure for established smoking only among team sports participants. CONCLUSIONS Team sports participation clearly plays a protective role against established smoking, even in the face of exposure to movie smoking. However, movie smoking exposure increases the risk of established smoking among both team sports participants and nonparticipants. Parents, teachers, coaches, and clinicians should be aware that encouraging team sports participation in tandem with minimizing early exposure to movie smoking may offer the greatest likelihood of preventing youth smoking.

A comparison of clomiphene citrate and human menopausal gonadotropin for use in conjunction with intrauterine insemination

OBJECTIVE To compare the outcome of superovulation using clomiphene citrate (CC) versus hMG in conjunction with IUI. DESIGN Sequentially assigned, observational study. Couples initially were assigned to receive either CC or hMG for three cycles. SETTING The Clinical Outpatient Department of the Dartmouth-Hitchcock Medical Center. PATIENT(S) Eighty-three infertile couples. INTERVENTION(S) IUI with hMG use. MAIN OUTCOME MEASURE(S) Conception rate, term pregnancy rate (PR), and pregnancy complications, such as spontaneous miscarriage and multiple gestation. RESULT(S) Of 83 couples who underwent at least one treatment cycle, 29 (35%) conceived during the study period. The relative rate of conception for hMG versus CC was 2.08 (95% confidence interval [CI], 0.93 to 4.68). The relative term PR was 2.10 (95% CI, 0.77 to 5.73) for hMG versus CC. There was no difference in the miscarriage rate for hMG versus CC. CONCLUSION(S) Both the conception rate and the term PR were higher using hMG, compared with CC, in combination with IUI, and showed a trend toward statistical significance.

Effects of intraoperative irradiation and intraoperative hyperthermia on canine sciatic nerve: Neurologic and electrophysiologic study

PURPOSE Late radiation injury to peripheral nerve may be the limiting factor in the clinical application of intraoperative radiation therapy (IORT). The combination of IORT with intraoperative hyperthermia (IOHT) raises specific concerns regarding the effects on certain normal tissues such as peripheral nerve, which might be included in the treatment field. The objective of this study was to compare the effect of IORT alone to the effect of IORT combined with IOHT on peripheral nerve in normal beagle dogs. METHODS AND MATERIALS Young adult beagle dogs were randomized into five groups of three to five dogs each to receive IORT doses of 16, 20, 24, 28, or 32 Gy to 5 cm of surgically exposed right sciatic nerve using 6 MeV electrons and six groups of four to five dogs each received IORT doses of 0, 12,16, 20, 24, or 28 Gy simultaneously with 44 degrees C of IOHT for 60 min. IOHT was performed using a water circulating hyperthermia device with a multichannel thermometry system on the surgically exposed sciatic nerve. Neurologic and electrophysiologic examinations were done before and monthly after treatment for 24 months. Electrophysiologic studies included electromyographic (EMG) examinations of motor function, as well as motor nerve conduction velocities studies. RESULTS Two years after treatment, the effective dose for 50% complication (ED50) for limb paresis in dogs exposed to IORT only was 22 Gy. The ED50 for paresis in dogs exposed to IORT combined with IOHT was 15 Gy. The thermal enhancement ratio (TER) was 1.5. Electrophysiologic studies showed more prominent changes such as EMG abnormalities, decrease in conduction velocity and amplitude of the action potential, and complete conduction block in dogs that received the combination of IORT and IOHT. The latency to development of peripheral neuropathies was shorter for dogs exposed to the combined treatment. CONCLUSION The probability of developing peripheral neuropathies in a large animal model was higher for IORT combined with IOHT, than for IORT alone. The dose required to produce the same level of late radiation injury to the sciatic nerve was reduced by a factor of 1.5 (TER) if IORT was combined with 44 degrees C of IOHT for 60 min.

The Clinical Utility of Esophageal Manometry

Background and Aims Esophageal manometry (EM) is performed to evaluate symptoms of chest pain and dysphagia, although its clinical utility is not known. The aim of this study was to evaluate the clinical utility of EM by determining whether EM provides new information, changes diagnoses, or alters patient management. Methods Before performing EM, referring providers noted indications for the test, symptoms, previous tests performed, and medication use. After EM was completed, a follow-up questionnaire ascertained whether EM provided new information or changed the patients diagnosis or management plan. Patients provided demographic information. Results During a 12-month period, 569 EMs were performed and 444 were available for inclusion; 286 fully completed questionnaires were returned (64%) and are the basis for this analysis. The mean age (±SD) at the time of manometry was 52 (±15) years; 58% were women; 98% were white. EM was requested to assist placement of a pH measuring device (34%), and to evaluate symptoms of dysphagia (29%), chest pain (12%), or acid reflux (11%). Overall, 64% of EM were abnormal; 81% in gastroesophageal reflux disease patients, 74% in dysphagia, and 59% in chest pain. New information was obtained in 87% of patients, whereas a change in diagnosis occurred in 30% of patients, and management changed in 44% of patients. Conclusions EM is a clinically useful test because it frequently provides new information and often changes patient diagnosis and management. The clinical utility of EM is greatest in patients with dysphagia.

Discovery of breast cancers within 1 year of a normal screening mammogram: how are they found?

PURPOSE We sought to determine how breast cancers that occur within 1 year after a normal mammogram are discovered. METHODS Using population-based mammography registry data from 2000–2002, we identified 143 women with interval breast cancers and 481 women with screen-detected breast cancers. We surveyed women’s primary care clinicians to assess how the interval breast cancers were found and factors associated with their discovery. RESULTS Women with interval cancers were twice as likely to have a personal history of breast cancer (30.1%) as women with screen-detected cancers (13.6%). Among women with interval cancers, one half of the invasive tumors (49.5%) were discovered when women initiated a health care visit because of a breast concern, and 16.8% were discovered when a clinician found an area of concern while conducting a routine clinical breast examination. Having a lump and both a personal and a family history of breast cancer was the most common reason why women initiated a health care visit (44%) (P <.01). CONCLUSIONS Women with interval cancers are most likely to initiate a visit to a primary care clinician when they have 2 or more breast concerns. These concerns are most likely to include having a lump and a personal and/or family history of breast cancer. Women at highest risk for breast cancer may need closer surveillance by their primary care clinicians and may benefit from a strong educational message to come for a visit as soon as they find a lump.

Tolerability and clinical utility of the Bravo pH capsule in children.

Goals To prospectively evaluate the tolerability and clinical utility of the Bravo pH capsule in children. Background Acid reflux is common in children, and pH testing can be used to correlate acid exposure with symptom expression. The tolerability and clinical utility of the Bravo capsule in children has not been prospectively evaluated. Methods This was a prospective, open-label trial conducted at an academic medical center. Patient demographics, symptoms, and medication use were recorded in an outpatient setting. After Bravo capsule placement, patients were followed to determine whether the results of the Bravo capsule study changed clinical management. Results Fifty children (mean±SD=13±3 y; 52% female) were studied; no complications occurred. Reflux symptoms (40%), abdominal pain (18%), and nausea/vomiting (14%) were the 3 most common symptoms leading to Bravo capsule placement. Nearly all studies (96%) were performed off acid-suppressing medications. Results of the Bravo pH study changed clinical care in 88% of children; management changed more frequently in children with an abnormal study (94%) versus those with a normal study (78%; P<0.0001). Conclusions The Bravo pH capsule is a safe, well-tolerated test to evaluate acid reflux symptoms in children, and the data obtained frequently changes patient management.