Tanya L. Hoskin

High‐dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis

Previous controlled trials are inconclusive regarding the efficacy of ursodeoxycholic acid (UDCA) for treating primary sclerosing cholangitis (PSC). One hundred fifty adult patients with PSC were enrolled in a long‐term, randomized, double‐blind controlled trial of high‐dose UDCA (28‐30 mg/kg/day) versus placebo. Liver biopsy and cholangiography were performed before randomization and after 5 years. The primary outcome measures were development of cirrhosis, varices, cholangiocarcinoma, liver transplantation, or death. The study was terminated after 6 years due to futility. At enrollment, the UDCA (n = 76) and placebo (n = 74) groups were similar with respect to sex, age, duration of disease, serum aspartate aminotransferase and alkaline phosphatase levels, liver histology, and Mayo risk score. During therapy, aspartate aminotransferase and alkaline phosphatase levels decreased more in the UDCA group than the placebo group (P < 0.01), but improvements in liver tests were not associated with decreased endpoints. By the end of the study, 30 patients in the UDCA group (39%) versus 19 patients in the placebo group (26%) had reached one of the pre‐established clinical endpoints. After adjustment for baseline stratification characteristics, the risk of a primary endpoint was 2.3 times greater for patients on UDCA than for those on placebo (P < 0.01) and 2.1 times greater for death, transplantation, or minimal listing criteria (P = 0.038). Serious adverse events were more common in the UDCA group than the placebo group (63% versus 37% [P < 0.01]). Conclusion: Long‐term, high‐dose UDCA therapy is associated with improvement in serum liver tests in PSC but does not improve survival and was associated with higher rates of serious adverse events. (HEPATOLOGY 2009.)

Trends in Mastectomy Rates at the Mayo Clinic Rochester: Effect of Surgical Year and Preoperative Magnetic Resonance Imaging

PURPOSE Recent changes have occurred in the presurgical planning for breast cancer, including the introduction of preoperative breast magnetic resonance imaging (MRI). We sought to analyze the trends in mastectomy rates and the relationship to preoperative MRI and surgical year at Mayo Clinic, Rochester, MN. PATIENTS AND METHODS We identified 5,405 patients who underwent surgery between 1997 and 2006. Patients undergoing MRI were identified from a prospective database. Trends in mastectomy rate and the association of MRI with surgery type were analyzed. Multiple logistic regression was used to assess the effect of surgery year and MRI on surgery type, while adjusting for potential confounding variables. RESULTS Mastectomy rates differed significantly across time (P < .0001), and decreased from 45% in 1997% to 31% in 2003, followed by increasing rates for 2004 to 2006. The use of MRI increased from 10% in 2003% to 23% in 2006 (P < .0001). Patients with MRI were more likely to undergo mastectomy than those without MRI (54% v 36%; P < .0001). However, mastectomy rates increased from 2004 to 2006 predominantly among patients without MRI (29% in 2003% to 41% in 2006; P < .0001). In a multivariable model, both MRI (odds ratio [OR], 1.7; P < .0001) and surgical year (compared to 2003 OR: 1.4 for 2004, 1.8 for 2005, and 1.7 for 2006; P < .0001) were independent predictors of mastectomy. CONCLUSION After a steady decline, mastectomy rates have increased in recent years with both surgery year and MRI as significant predictors for type of surgery. Further studies are needed to evaluate the role of MRI and other factors influencing surgical planning.

A Meta-analysis of Patellar Tendon Autograft Versus Patellar Tendon Allograft in Anterior Cruciate Ligament Reconstruction

PURPOSE Studies have suggested good long-term success rates with bone-patellar tendon-bone (BPTB) autograft and BPTB allograft in anterior cruciate ligament (ACL) reconstruction, but the numbers reported in available prospective studies may be underpowered to elucidate significant differences between the two groups. Here, we present a meta-analysis to compare the results of BPTB autograft and BPTB allograft in primary ACL reconstruction. METHODS A systematic review of prospective trials using BPTB autograft and BPTB allograft tissue for ACL reconstruction with a minimum 2-year follow-up was performed. Summary odds ratios (ORs), confidence intervals, and P values were calculated. RESULTS Of 548 studies, 6 fulfilled our inclusion criteria, with 256 patients in the autograft and 278 patients in the allograft group. Allograft patients were more likely to rupture their graft than autograft patients (OR, 5.03; P = .01) and more likely to have a hop test less than 90% of the nonoperative side (OR, 5.66; P < .01). When irradiated and chemically processed grafts were excluded from analysis, no significant differences were found between allograft and autograft patients with respect to graft rupture, rate of reoperation, normal/near normal IKDC scores, Lachman exam, pivot shift exam, patellar crepitus, hop test, or return to sport. CONCLUSIONS In this meta-analysis, ACL reconstruction with BPTB autograft was favored over BPTB allograft for graft rupture and hop test parameters. However, when irradiated and chemically processed grafts were excluded, results were not significantly different between the two graft types. LEVEL OF EVIDENCE Level III, systematic review of prospective nonrandomized cohort studies.

Common iliac artery aneurysm: expansion rate and results of open surgical and endovascular repair.

OBJECTIVES To assess expansion rate of common iliac artery aneurysms (CIAAs) and define outcomes after open repair (OR) and endovascular repair (EVAR). METHODS Clinical data of 438 patients with 715 CIAAs treated between 1986 and 2005 were retrospectively reviewed. Size, presentations, treatments, and outcomes were recorded. Kaplan-Meier method with log-rank tests and chi2 test were used for analysis. RESULTS Interventions for 715 CIAAs (median, 4 cm; range, 2-13 cm) were done in 512 men (94%) and 26 women (6%); 152 (35%) had unilateral and 286 (65%) had bilateral CIAAs. Group 1 comprised 377 patients (633 CIAAs) with current or previously repaired abdominal aortic aneurysm (AAA). Group 2 comprised 15 patients (24 CIAAs) with associated internal iliac artery aneurysm (IIAA). Group 3 comprised 46 patients (58 isolated CIAAs). Median expansion rate of 104 CIAAs with at least two imaging studies was 0.29 cm/y; hypertension predicted faster expansion (0.32 vs 0.14 cm/y, P = .01). A total of 175 patients (29%) were symptomatic. The CIAA ruptured in 22 patients (5%, median, 6 cm; range, 3.8-8.5 cm), and the associated AAA ruptured in 20 (4%). Six (27%) ilioiliac or iliocaval fistulas developed. Repairs were elective in 396 patients (90%) and emergencies in 42 (10%). OR was performed in 394 patients (90%) and EVAR in 44 (10%). The groups had similar 30-day mortality: 1% for elective, 27% for emergency repairs (P < .001); 4% after OR (elective, 1%; emergency, 26%), and 0% after EVAR. No deaths occurred after OR of arteriovenous fistula. Complications were more frequent and hospitalization was longer after OR than EVAR (P < .05). Mean follow-up was 3.7 years (range, 1 month-17.5 years). The groups had similar 5-year primary (95%) and secondary patency rates (99.6%). At 3 years, secondary patency was 99.6% for OR and 100% for EVAR (P = .66); freedom from reintervention was similar after OR and EVAR (83% vs 69%, P = .17), as were survival rates (76% vs 77%, P = .70). CONCLUSIONS The expansion rate of CIAAs is 0.29 cm/y, and hypertension predicts faster expansion. Because no rupture of a CIAA <3.8 cm was observed, elective repair of asymptomatic patients with CIAA >or=3.5 cm seems justified. Although buttock claudication after EVAR remains a concern, results at 3 years support EVAR as a first-line treatment for most anatomically suitable patients who require CIAA repair. Patients with compressive symptoms or those with AVF should preferentially be treated with OR.

The Impact of Valve Surgery on 6-Month Mortality in Left-Sided Infective Endocarditis

Background— The role of valve surgery in left-sided infective endocarditis has not been evaluated in randomized controlled trials. We examined the association between valve surgery and all-cause 6-month mortality among patients with left-sided infective endocarditis. Methods and Results— A total of 546 consecutive patients with left-sided infective endocarditis were included. To minimize selection bias, propensity score to undergo valve surgery was used to match patients in the surgical and nonsurgical groups. To adjust for survivor bias, we matched the follow-up time so that each patient in the nonsurgical group survived at least as long as the time to surgery in the respective surgically-treated patient. We also used valve surgery as a time-dependent covariate in different Cox models. A total of 129 (23.6%) patients underwent surgery within 30 days of diagnosis. Death occurred in 99 of the 417 patients (23.7%) in the nonsurgical group versus 35 deaths among the 129 patients (27.1%) in the surgical group. Eighteen of 35 (51%) patients in the surgical group died within 7 days of valve surgery. In the subset of 186 cases (93 pairs of surgical versus nonsurgical cases) matched on the logit of their propensity score, diagnosis decade, and follow-up time, no significant association existed between surgery and mortality (adjusted hazard ratio, 1.3; 95% confidence interval, 0.5 to 3.1). With a Cox model that incorporated surgery as a time-dependent covariate, valve surgery was associated with an increase in the 6-month mortality with an adjusted hazard ratio of 1.9 (95% confidence interval, 1.1 to 3.2). Because the proportionality hazard assumption was violated in the time-dependent analysis, we performed a partitioning analysis. After adjustment for early (operative) mortality, surgery was not associated with a survival benefit (adjusted hazard ratio, 0.92; 95% confidence interval, 0.48 to 1.76). Conclusions— The results of our study suggest that valve surgery in left-sided infective endocarditis is not associated with a survival benefit and could be associated with increased 6-month mortality, even after adjustment for selection and survivor biases as well as confounders. Given the disparity between the results of our study and those of other observational studies, well-designed prospective studies are needed to further evaluate the role of valve surgery in endocarditis management.

Dysphagia in inflammatory myopathy: clinical characteristics, treatment strategies, and outcome in 62 patients.

OBJECTIVE To assess the clinical characteristics, treatment, and outcome of patients with inflammatory myopathy-associated dysphagia. PATIENTS AND METHODS We retrospectively reviewed the medical records of all patients with inflammatory myopathy-associated dysphagia seen at the Mayo Clinic in Rochester, Minn, between January 1, 1997, and December 31, 2001. RESULTS A total of 783 patients were diagnosed as having inflammatory myopathy during the 5-year study period. Of these, 62 patients (41 women and 21 men; mean age, 68.6 years) had inflammatory myopathy-associated dysphagia: 26 with inclusion body myositis (IBM), 18 with dermatomyositis, 9 with polymyositis, and 9 with overlap syndrome. Dysphagia was a presenting symptom in 13 patients (21%), with the highest incidence in the IBM group. Videofluoroscopic examinations revealed pharyngeal pooling and impaired oropharyngeal and cricopharyngeal function. The benefits of swallowing compensation techniques and exercises were difficult to establish. Interventional procedures were performed in 24 patients (39%) and most frequently (62%) in patients with IBM, with cricopharyngeal myotomy being most beneficial. Patients with IBM had the least symptomatic improvement. Overall, 11 patients died during the median follow-up of 38 months, with respiratory failure due to aspiration pneumonia as the most common cause. Mortality was high in patients who required percutaneous endoscopic gastrostomy (7/11, 64%), and 1- year mortality was highest (31%) in those with dermatomyositis. CONCLUSION Dysphagia is a serious and at times presenting problem in patients with inflammatory myopathy. It occurs most frequently and appears to be most refractory in patients with IBM. The mortality rate was high in patients who required percutaneous endoscopic gastrostomy, and the 1-year mortality rate was the highest in patients with dermatomyositis.

Wound complications after open Achilles tendon repair: an analysis of risk factors.

Operative treatment of Achilles tendon ruptures has the risk of wound complications. The purpose of this study is to determine the risk ratio for specific risk factors associated with wound related complications in patients with operatively treated Achilles tendon ruptures. Between 1978 and 2001, 167 open Achilles tendon repairs were done at our institution. Clinical data were retrospectively reviewed. Tobacco use, diabetes, age, gender, timing of surgery, body mass index and steroid use were evaluated as potential risk factors for wound healing complications. One patient was lost to follow-up and two patients had nonsimultaneous ruptures and only the first repair was included; the remaining patients were followed up until complete wound healing. There were 17 wound complications in 164 patients (10.4%). Significant risk factors for development of wound complications included tobacco use (p < 0.0001), steroid use (p = 0.0005), and female sex (p = 0.0400). For those patients who had one or more of the following risk factors: diabetes, tobacco use, or steroid use; eight of 19 (42.1%) had a complication, compared with nine of 145 (6.2%) for those without risk factors present (p < 0.0001). Surgeons doing open Achilles tendon repairs should be cognizant of the specific risk factors identified in this study, because they might impact decision making with regard to operative versus nonoperative treatment.

CYP2D6 Metabolism and Patient Outcome in the Austrian Breast and Colorectal Cancer Study Group Trial (ABCSG) 8

Purpose: Controversy exists about CYP2D6 genotype and tamoxifen efficacy. Experimental Design: A matched case–control study was conducted using the Austrian Breast and Colorectal Cancer Study Group Trial 8 (ABCSG8) that randomized postmenopausal women with estrogen receptor (ER)-positive breast cancer to tamoxifen for 5 years (arm A) or tamoxifen for 2 years followed by anastrozole for 3 years (arm B). Cases had disease recurrence, contralateral breast cancer, second non–breast cancer, or died. For each case, controls were identified from the same treatment arm of similar age, surgery/radiation, and tumor–node—metastasis (TNM) stage. Genotyping was conducted for alleles associated with no (PM; *3, *4, *6), reduced (IM; *10, and *41), and extensive (EM: absence of these alleles) CYP2D6 metabolism. Results: The common CYP2D6*4 allele was in Hardy–Weinberg equilibrium. In arm A during the first 5 years of therapy, women with two poor alleles [PM/PM: OR, 2.45; 95% confidence interval (CI), 1.05–5.73, P = 0.04] and women with one poor allele (PM/IM or PM/EM: OR, 1.67; 95% CI, 0.95–2.93; P = 0.07) had a higher likelihood of an event than women with two extensive alleles (EM/EM). In years 3 to 5 when patients remained on tamoxifen (arm A) or switched to anastrozole (arm B), PM/PM tended toward a higher likelihood of a disease event relative to EM/EM (OR, 2.40; 95% CI, 0.86–6.66; P = 0.09) among women on arm A but not among women on arm B (OR, 0.28; 95% CI, 0.03–2.30). Conclusion: In ABCSG8, the negative effects of reduced CYP2D6 metabolism were observed only during the period of tamoxifen administration and not after switching to anastrozole. Clin Cancer Res; 19(2); 500–7. ©2012 AACR.

In Vivo Quantitation of Intratumoral Radioisotope Uptake Using Micro-Single Photon Emission Computed Tomography/Computed Tomography

PurposeThis study was undertaken to determine the ability of micro-single photon emission computed tomography (micro-SPECT)/computed tomography (CT) to accurately quantitate intratumoral radioisotope uptake in vivo and to compare these measurements with planar imaging and micro-SPECT imaging alone.ProceduresHuman pancreatic cancer xenografts were established in 10 mice. Intratumoral radioisotope uptake was achieved via intratumoral injection of an attenuated measles virus vector expressing the NIS gene (MV-NIS). On various days after MV-NIS injection, 123I planar and micro-SPECT/CT imaging was performed. Tumor activity was determined by dose calibrator measurements and region-of-interest (ROI) image analysis. Agreement and reproducibility of tumor activity measurements were assessed by Bland–Altman plots and Lin’s concordance correlation coefficient (CCC).ResultsIntratumoral radioisotope uptake was detected in all mice. Scatterplots demonstrate strong agreement (CCC = 0.93) between micro-SPECT/CT ROI image analysis and dose calibrator tumor activity measurements. The differences between dose calibrator activity measurements and those obtained with ROI image analysis of micro-SPECT alone and planar imaging are less accurate and more variable (CCC = 0.84 and 0.78, respectively).ConclusionsMicro-SPECT/CT can be used to accurately quantify intratumoral radioisotope uptake in vivo and is more reliable than planar or micro-SPECT imaging alone.

Safety and technical success of methylene blue dye for lymphatic mapping in breast cancer.

BACKGROUND We aimed to evaluate the safety and efficacy of methylene blue dye (MBD) for sentinel lymph node (SLN) mapping in breast cancer. METHODS A total of 398 patients undergoing 401 SLN biopsy procedures with MBD were retrospectively reviewed and divided into 3 groups based on dye concentration and location of dye injection. Technical success and complication rates were compared. RESULTS Overall technical success of SLN biopsy was 99.7%. Technical success of SLN mapping with MBD was lowest in the group receiving full strength dye in a peritumoral location (74%) and highest in the group that received very dilute MBD (1.25 mg/mL) in the subareolar location (92%, P = .004). The complication rate was highest in the first group (21%) and lowest in the latter (2%, P = .0003). CONCLUSIONS Dilute MBD (1.25 mg/mL) successfully maps SLNs with very few complications.