Inability of Radioiodine Remnant Ablation to Improve Postoperative Outcome in Adult Patients with Low-Risk Papillary Thyroid Carcinoma.

OBJECTIVE: To determine whether radioiodine remnant ablation (RRA) reduces cause-specific mortality (CSM) or tumor recurrence (TR) rate after bilateral lobar resection (BLR). PATIENTS AND METHODS: There were 2952 low-risk adult papillary thyroid cancer (LRAPTC) patients (with MACIS scores <6) who underwent potentially curative BLR during 1955-2014. During 1955-1974, 1975-1994, and 1995-2014, RRA was administered in 3%, 49%, and 28%. Statistical analyses were performed using SAS software. RESULTS: During 1955-1974, the 20-year CSM and TR rates after BLR alone were 1.0% and 6.8%; rates after BLR+RRA were 0% (P=.63) and 5.9% (P=.82). During 1975-1994, post-BLR 20-year rates for CSM and TR were 0.3% and 7.5%; after BLR+RRA, rates were higher at 0.9% (P=.31) and 12.8% (P=.01). When TR rates were examined separately for 448 node-negative and 317 node-positive patients, differences were nonsignificant. In 1995-2014, post-BLR 20-year CSM and TR rates were 0% and 9.2%; rates after BLR+RRA were higher at 1.4% (P=.19) and 21.0% (P<.001). In 890 pN0 cases, 15-year locoregional recurrence rates were 3.4% after BLR and 3.7% after BLR+RRA (P=.99). In 740 pN1 patients, 15-year locoregional recurrence rates were 10% higher after BLR+RRA compared with BLR alone (P=.01). However, this difference became nonsignificant when stratified by numbers of metastatic nodes. CONCLUSION: RRA administered to LRAPTC patients during 1955-2014 did not reduce either the CSM or TR rate. We would therefore not recommend RRA in LRAPTC patients undergoing BLR with curative intent.

Papillary Thyroid Carcinoma (PTC) in Children and Adults: Comparison of Initial Presentation and Long-Term Postoperative Outcome in 4432 Patients Consecutively Treated at the Mayo Clinic During Eight Decades (1936-2015).

BACKGROUND: Contemporary guidelines for managing PTC advise an approach wherein primary tumor and regional metastases (RM) are completely resected at first surgery and radioiodine remnant ablation (RRA) is restricted to high-risk patients, policies our group has long endorsed. To assess our therapeutic efficacy, we studied 190 children and 4242 adults consecutively treated during 1936-2015. SUBJECTS AND METHODS: Mean follow-up durations for children and adults were 26.9 and 15.2 years, respectively. Bilateral lobar resection was performed in 86% of children and 88% of adults, followed by RRA in 30% of children and 29% of adults; neck nodes were excised in 86% of children and 66% of adults. Tumor recurrence (TR) and cause-specific mortality (CSM) details were taken from a computerized database. RESULTS: Children, when compared to adults, had larger primary tumors which more often were grossly invasive and incompletely resected. At presentation, children, as compared to adults, had more RM and distant metastases (DM). Thirty-year TR rates were no different in children than adults at any site. Thirty-year CSM rates were lower in children than adults (1.1 vs. 4.9%; p = 0.01). Comparing 1936-1975 (THEN) with 1976-2015 (NOW), 30-year CSM rates were similar in MACIS <6 children (p = 0.67) and adults (p = 0.08). However, MACIS <6 children and adults in 1976-2015 had significantly higher recurrence at local and regional, but not at distant, sites. MACIS 6+ adults, NOW, compared to THEN, had lower 30-year CSM rates (30 vs. 47%; p < 0.001), unassociated with decreased TR at any site. CONCLUSIONS: Children, despite presenting with more extensive PTC when compared to adults, have postoperative recurrences at similar frequency, typically coexist with DM and die of PTC less often. Since 1976, both children and adults with MACIS <6 PTC have a <1% chance at 30 years of CSM; adults with higher MACIS scores (6 or more) have a 30-year CSM rate of 30%.

Developing a standardized healthcare cost data warehouse.

BACKGROUND: Research addressing value in healthcare requires a measure of cost. While there are many sources and types of cost data, each has strengths and weaknesses. Many researchers appear to create study-specific cost datasets, but the explanations of their costing methodologies are not always clear, causing their results to be difficult to interpret. Our solution, described in this paper, was to use widely accepted costing methodologies to create a service-level, standardized healthcare cost data warehouse from an institutional perspective that includes all professional and hospital-billed services for our patients. METHODS: The warehouse is based on a National Institutes of Research-funded research infrastructure containing the linked health records and medical care administrative data of two healthcare providers and their affiliated hospitals. Since all patients are identified in the data warehouse, their costs can be linked to other systems and databases, such as electronic health records, tumor registries, and disease or treatment registries. RESULTS: We describe the two institutions' administrative source data; the reference files, which include Medicare fee schedules and cost reports; the process of creating standardized costs; and the warehouse structure. The costing algorithm can create inflation-adjusted standardized costs at the service line level for defined study cohorts on request. CONCLUSION: The resulting standardized costs contained in the data warehouse can be used to create detailed, bottom-up analyses of professional and facility costs of procedures, medical conditions, and patient care cycles without revealing business-sensitive information. After its creation, a standardized cost data warehouse is relatively easy to maintain and can be expanded to include data from other providers. Individual investigators who may not have sufficient knowledge about administrative data do not have to try to create their own standardized costs on a project-by-project basis because our data warehouse generates standardized costs for defined cohorts upon request.

Minimal extrathyroid extension in papillary thyroid carcinoma does not result in increased rates of either cause-specific mortality or postoperative tumor recurrence.

BACKGROUND: This study assessed the influence of extrathyroid extension (EE) on cause-specific mortality (CSM) and tumor recurrence (TR) in patients treated for papillary thyroid carcinoma (PTC). METHODS: We studied outcome in 3,524 patients with PTC without distant metastases at diagnosis. CSM and TR were investigated in 422 patients with gross EE (GEE) or microscopic EE (MEE). RESULTS: The 30-year CSM rate for GEE of 25% was 12-fold greater (P < .001) than 2% seen with surgically intra-thyroid tumors (SIT); no patient who underwent MEE died of PTC. No difference (P = .36) existed in CSM rates between 127 MEE and 3,102 microscopically intra-thyroid tumors (MITs). The 20-year TR rate for GEE was 43% versus 12% with SIT (P < .001). Analyzing only 2,067 pN0 tumors, we found that GEE patients had greater TR rates (all sites), compared with SIT or MEE (P < .001). When 44 MEE were compared with 1,941 MIT cases, TR (all sites) rates were not different (P = .74). In patients aged >45 with tumors <41 mm, 20-year TR rates for MIT (stages I/II) and MEE (stage III) were not different at 4.7% and 3.8% (P = .71). CONCLUSION: MEE without concomitant GEE did not increase rates of either CSM or TR in PTC. Accordingly, these results raise concerns regarding current AJCC staging recommendations.

Determinants of direct medical costs in primary and revision total knee arthroplasty.

BACKGROUND: TKA procedures are increasing rapidly, with substantial cost implications. Determining cost drivers in TKA is essential for care improvement and informing future payment models. QUESTIONS/PURPOSES: We determined the components of hospitalization and 90-day costs in primary and revision TKA and the role of demographics, operative indications, comorbidities, and complications as potential determinants of costs. METHODS: We studied 6475 primary and 1654 revision TKA procedures performed between January 1, 2000, and September 31, 2008, at a single center. Direct medical costs were measured by using standardized, inflation-adjusted costs for services and procedures billed during the 90-day period. We used linear regression models to determine the cost impact associated with individual patient characteristics. RESULTS: The largest proportion of costs in both primary and revision TKA, respectively, were for room and board (28% and 23%), operating room (22% and 17%), and prostheses (13% and 24%). Prosthesis costs were almost threefold higher in revision TKA than in primary TKA. Revision TKA procedures for infections and bone and/or prosthesis fractures were approximately 25% more costly than revisions for instability and loosening. Several common comorbidities were associated with higher costs. Patients with vascular and infectious complications had longer hospital stays and at least 80% higher 90-day costs as compared to patients without complications. CONCLUSIONS: High prosthesis costs in revision TKA represent a factor potentially amenable to cost containment efforts. Increased costs associated with demographic factors and comorbidities may put providers at financial risk and may jeopardize healthcare access for those patients in greatest need.

Age at diagnosis and the utility of prognostic testing in patients with chronic lymphocytic leukemia.

BACKGROUND: A study was undertaken to analyze the survival of chronic lymphocytic leukemia (CLL) patients relative to age-matched individuals in the general population and determine the age-stratified utility of prognostic testing. METHODS: All 2487 patients diagnosed with CLL between January 1995 and June 2008 and cared for in the Mayo Clinic Division of Hematology were categorized by age at diagnosis and evaluated for differences in clinical characteristics, time to first treatment, and overall survival (OS). RESULTS: Among Rai stage 0 patients, survival was shorter than the age-matched general population for patients aged <55 years (P < .001), 55 to 64 years (P < .001), and 65 to 74 years (P < .001), but not those aged ≥75 years at diagnosis (P = not significant). CD38, IGHV mutation, and ZAP-70 each predicted time to first treatment independent of stage for all age groups (all P < .04), but had less value for predicting OS, particularly as age increased. IGHV and fluorescent in situ hybridization (FISH) predicted OS independent of stage for patients aged <55 years (P ≤ .001), 55 to 64 years (P ≤ .004), and 65 to 74 years (P ≤ .001), but not those aged ≥75 years. CD38 and ZAP-70 each predicted OS independent of stage for only 2 of 4 age categories. Among Rai 0 patients aged <75 years, survival was shorter than the age-matched population only for IGHV unmutated (P < .001) patients or those with unfavorable FISH (P < .001). CONCLUSIONS: Survival of CLL patients aged <75 years is shorter than the age-matched general population regardless of disease stage. Among patients aged <75 years, the simple combinations of stage and IGHV or stage and FISH identifies those with excess risk of death relative to the age-matched population. Although useful for predicting time to first treatment independent of stage for patients of all ages, prognostic testing had little utility for predicting OS independent of stage among patients aged ≥75 years.

Treatment of autoimmune cytopenia complicating progressive chronic lymphocytic leukemia/small lymphocytic lymphoma with rituximab, cyclophosphamide, vincristine, and prednisone.

Treatment of autoimmune cytopenia complicating progressive chronic lymphocytic leukemia (CLL) is constrained by intolerance of myelosuppression and the risk of exacerbation of autoimmune cytopenia by purine analogs particularly when used as single agents. We report on 20 such patients treated with rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP). Autoimmune cytopenia responded in 19 patients (14 complete remissions (CR), five partial remissions (PR)) with a median time to next treatment (TTT) for autoimmune cytopenia of 21.7 months. Progressive CLL responded in 17 patients (nine CR/complete clinical response, eight PR) with a median TTT of 27.7 months. Five patients have not required any re-treatment at 15-30 months. Grade 3-4 toxicities were infections (n = 3) and drug-induced pneumonitis (n = 1). No patient required blood cell transfusions after cycle 1 of therapy. We conclude that R-CVP is effective and tolerable therapy for autoimmune cytopenia complicating progressive CLL, but the duration of response is suboptimal.

Long-term outcome in 215 children and adolescents with papillary thyroid cancer treated during 1940 through 2008.

BACKGROUND: Controversy exists regarding the aggressiveness of initial therapy in childhood papillary thyroid cancer (PTC). Few studies with long-term outcome exist and second primary malignancies have rarely been analyzed. METHODS: We studied 215 PTC patients younger than 21 years old managed during 1940 through 2008. The patients were aged 3-20 year old (median age = 16 years); the median follow-up was 29 years. Recurrence and mortality details were taken from a computerized database. RESULTS: Median primary tumor size was 2.2 cm. Six percent had distant metastases at presentation, 5% had incomplete tumor resection, 86% had nodes removed at initial surgery, and 78% had nodal metastases. After complete surgical resection, PTC recurred in 32% by 40 years. At 20 years, the recurrence rates at local, regional, and distant sites were 7, 21, and 5%, respectively. During 1940-1969, local and regional recurrence rates after unilateral lobectomy (UL) were significantly (P < 0.001) higher than after bilateral lobar resection (BLR). During 1950-2008 radioiodine remnant ablation (RRA) was administered within 18 months to 32%; it did not diminish the 25-year regional recurrence rate of 16% seen after BLR alone (P = 0.86). Only two fatal events from PTC occurred at 28 and 30 years, for a cause-specific mortality at 40 years of only 2%. All-causes mortality rates did not exceed expectation through 20 years, but from 30 through 50 years, the number of deaths was significantly (P < 0.001) higher than predicted. Fifteen of 22 deaths (68%) resulted from nonthyroid malignancy. CONCLUSION: Survival from childhood PTC should be expected, but later death from nonthyroid malignancy is disconcerting. Seventy-three percent of those who died from nonthyroid malignancy had received postoperative therapeutic irradiation.

Autoimmune cytopenia in chronic lymphocytic leukemia/small lymphocytic lymphoma: changes in clinical presentation and prognosis.

Improved medical care could have altered the clinical presentation and survival of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) complicated by autoimmune disease cytopenia (AID cytopenia). We reviewed the clinical characteristics, treatment, and outcome of AID cytopenia that was diagnosed in 75 (4.3%) of 1750 patients with CLL seen at a single institution over 10 years. When compared with the historical reported data, our study shows a lower rate of autoimmune hemolytic anemia (2.3%), and similar rates of immune thrombocytopenia (2.0%), and pure red blood cell aplasia (0.5%). AID cytopenia occurred at all stages of CLL, responded well to treatment, did not alter overall survival, and contributed to death in only 6 (12%) patients. We propose that more sensitive and accurate diagnostic methods for CLL have decreased the perceived prevalence of AID cytopenia and that improvements in management could have increased the survival of these patients.

Incidence and risk factors of prosthetic joint infection after total hip or knee replacement in patients with rheumatoid arthritis.

OBJECTIVE: Prosthetic joint infection is one of the most dreaded complications after total joint arthroplasty, a common procedure in patients with rheumatoid arthritis (RA). We conducted a study to evaluate potential risk factors of prosthetic joint infection and to clarify if RA is an independent predictor of this complication. METHODS: This study included all patients with RA who underwent total hip or knee replacement at the Mayo Clinic Rochester between January 1996 and June 2004. The association of potential risk factors with prosthetic joint infection was examined using Cox models. A matched cohort of patients with osteoarthritis (OA) was assembled to determine whether RA is an independent risk factor for prosthetic joint infection. RESULTS: We identified 462 patients with RA who underwent a total of 657 hip or knee replacements. Overall, 23 (3.7%) joint arthroplasties were complicated by an infection during a mean +/- SD followup of 4.3 +/- 2.4 years. Revision arthroplasty (hazard ratio [HR] 2.99, 95% confidence interval [95% CI] 1.02-8.75) and a previous prosthetic joint infection of the replaced joint (HR 5.49, 95% CI 1.87-16.14) were significant predictors of postoperative prosthetic joint infection. Comparison of RA patients with a matched cohort of OA patients identified an increased risk of prosthetic joint infections (HR 4.08, 95% CI 1.35-12.33) in patients with RA. CONCLUSION: Patients with RA who undergo total hip or knee replacement are at increased risk of prosthetic joint infection, which is further increased in the setting of revision arthroplasty and a previous prosthetic joint infection. These findings highlight the importance of perioperative prophylactic measures and vigilance during the postoperative period.

The prognostic significance of cytopenia in chronic lymphocytic leukaemia/small lymphocytic lymphoma.

The development of cytopenia in chronic lymphocytic leukaemia (CLL) patients can predict poor prognosis. All CLL patients seen in the Division of Hematology at Mayo Clinic Rochester from 1 January 1995 to 31 December 2004 (n = 1750) were evaluated for cytopenia, aetiology of cytopenia and clinical outcome. Cytopenia occurred in 423 (24.2%) patients and was attributable to CLL in 303 (17.3%) cases, with 228 (75%) of these having bone marrow (BM) failure and 75 (25%) having autoimmune disease (AID). Survival from onset of cytopenia was significantly better for patients with AID (median 9.1 years) compared to patients with BM failure (median 4.4 years, P < 0.001). Patients with AID diagnosed within 1 year of the diagnosis of CLL (n = 35) had similar survival from diagnosis compared to patients without CLL-related cytopenia (median 9.3 vs. 9.7 years, P = 0.881). Although cytopenia caused by BM failure predicted a poorer prognosis in CLL, cytopenia caused by AID was not an adverse prognostic factor. These findings suggest that patients with cytopenia due to AID cannot be meaningfully classified by the current clinical staging systems. Revisions of the National Cancer Institute Working Group 96 criteria should consider the aetiology of cytopenia in staging CLL patients.

Preventive medical services among patients with rheumatoid arthritis.

OBJECTIVE: To assess the degree to which patients with rheumatoid arthritis (RA) receive health maintenance and preventive care procedures recommended by the United States Preventive Services Task Force (USPSTF), a government appointed independent expert panel whose recommendations are based on a systematic review of the evidence of effectiveness of clinical preventive services. METHODS: Clinical data from 1987 to 1995 were abstracted from the complete (inpatient and outpatient) medical records of a population based sample of patients with RA (defined using the 1987 American College of Rheumatology diagnostic criteria). We assessed probability of receiving 6 preventive medical services: blood pressure testing (once every 2 years), lipids profile (once every 5 years), flu vaccination (once a year for persons over 65), pneumococcal vaccination (one time for persons over 65), as well as mammograms (biennially for ages 40-49 and annually for those 50 and over) and cervical cancer screening (once every 3 years). These probabilities were summarized using the Kaplan-Meier method. Cox proportional hazards models were used to assess the association of a number of clinical variables with time to performance of each preventive service. RESULTS: A total of 67 men and 197 women, with a mean age of 64.4 years and median length of followup time of 5.4 years, were identified. In this cohort, the probability of lipids screening by 5 years was 88% and blood pressure screening by 2 years was 95%. Among the 169 patients aged > or = 65 years, the probability of a one-time pneumococcal vaccination was 38% by 5 years of followup and the probability of a yearly flu vaccination was 32%. Among 185 women without a history of breast cancer, mammograms were performed for 68% of women by the end of 2 years from ages 40 to 49 years and for 33% of women by one year beginning at age 50 years. Of the 133 women without a history of hysterectomy, the probability of Papanicolaou smears within 3 years was 77%. No consistent statistically significant association of age, sex, calendar year, total or rheumatologist visits, Charlson comorbidity index, or RA disease characteristics with performance of these preventive services was detected. CONCLUSION: Patients with RA do not receive optimal health maintenance and preventive care services. Efforts should be made, on the part of all physicians who care for RA patients, to ensure that these effective preventive services are provided.