Dirk R. Larson

Review of 1027 Patients With Newly Diagnosed Multiple Myeloma

OBJECTIVE To determine the clinical and laboratory features of newly diagnosed multiple myeloma. PATIENTS AND METHODS Records of all patients in whom multiple myeloma was initially diagnosed at the Mayo Clinic in Rochester, Minn, from January 1, 1985, to December 31, 1998, were reviewed. RESULTS Of the 1027 study patients, 2% were younger than 40 years, and 38% were 70 years or older. The median age was 66 years. Anemia was present initially in 73% of patients, hypercalcemia (calcium level > or = 11 mg/dL) in 13%, and a serum creatinine level of 2 mg/dL or more in 19%. The beta2-microglobulin level was increased in 75%. Serum protein electrophoresis revealed a localized band in 82% of patients, and immunoelectrophoresis or immunofixation showed a monoclonal protein in 93%. A monoclonal light chain was found in the urine in 78%. Nonsecretory myeloma was recognized in 3% of patients, whereas light-chain myeloma was present in 20%. Conventional radiographs showed an abnormality in 79%. The plasma cell labeling index was 1% or more in 34% of patients. Multivariate analysis revealed that age, plasma cell labeling index, low platelet count, serum albumin value, and the log of the creatinine value were the most important prognostic factors. CONCLUSION The median duration of survival was 33 months and did not improve from 1985 through 1998.

Risk of lymph node metastasis in T1 carcinoma of the colon and rectum.

AbstractPURPOSE: Several recent reports of high local recurrence and lymph node metastasis in T1 carcinoma of the rectum prompted us to study the risk factors for lymph node metastasis in these lesions. METHODS: We reviewed the clinical records of 7,543 patients who underwent operative treatment for carcinoma of the colon and rectum from 1979 to 1995. Only patients with sessile T1 lesions who underwent colorectal resection were included in the study, yielding an analysis cohort of 353 patients. The following carcinoma-related variables were assessed: size, mucinous subtype, carcinomatous component, grade, site in colon and rectum, lymphovascular invasion, and depth of submucosal invasion. For the depth, the submucosa was divided into upper third (sm1), middle third (sm2), and lower third (sm3). Chi-squared tests and logistic regression were used to evaluate the variables as potential risk factors for lymph node metastasis. RESULTS: The incidence of T1 lesions was 8.6 percent. In the analysis cohort, the lymph node metastasis rate was 13 percent. Significant predictors of lymph node metastasis both univariately and multivariately were sm3 (P = 0.001), lymphovascular invasion (P = 0.005), and lesions in the lower third of the rectum (P = 0.007). Poorly differentiated carcinoma was significant univariately (P = 0.001) but not in the multivariate model. No other parameter was associated with a significant risk. CONCLUSIONS: T1 colorectal carcinomas with lymphovascular invasion, sm3 depth of invasion, and location in the lower third of the rectum have a high risk of lymph node metastasis. These lesions should have an oncologic resection. In a case of the lesion in the lower third of the rectum, local excision plus adjuvant chemoradiation may be an alternative.

Dual-Chamber Pacing for Hypertrophic Cardiomyopathy: A Randomized, Double-Blind, Crossover Trial

OBJECTIVES In a double-blind, randomized, crossover trial we sought to evaluate the effect of dual-chamber pacing in patients with severe symptoms of hypertrophic obstructive cardiomyopathy. BACKGROUND Recently, several cohort trials showed that implantation of a dual-chamber pacemaker in patients with severely symptomatic hypertrophic obstructive cardiomyopathy can relieve symptoms and decrease the severity of the left ventricular outflow tract gradient. However, the outcome of dual-chamber pacing has not been compared with that of standard therapy in a randomized, double-blind trial. METHODS Twenty-one patients with severely symptomatic hypertrophic obstructive cardiomyopathy were entered into this trial after baseline studies consisting of Minnesota quality-of-life assessment, two-dimensional and Doppler echocardiography and cardiopulmonary exercise tests. Nineteen patients completed the protocol and underwent double-blind randomization to either DDD pacing for 3 months followed by backup AAI pacing for 3 months, or the same study arms in reverse order. RESULTS Left ventricular outflow tract gradient decreased significantly to 55 +/- 38 mm Hg after DDD pacing compared with the baseline gradient of 76 +/- 61 mm Hg (p < 0.05) and the gradient of 83 +/- 59 mm Hg after AAI pacing (p < 0.05). Quality-of-life score and exercise duration were significantly improved from the baseline state after the DDD arm but were not significantly different between the DDD arm and the backup AAI arm. Peak oxygen consumption did not significantly differ among the three periods. Overall, 63% of patients had symptomatic improvement during the DDD arm, but 42% also had symptomatic improvement during the AAI backup arm. In addition, 31% had no change and 5% had deterioration of symptoms during the DDD pacing arm. CONCLUSIONS Dual-chamber pacing may relieve symptoms and decrease gradient in patients with hypertrophic obstructive cardiomyopathy. In some patients, however, symptoms do not change or even become worse with dual-chamber pacing. Subjective symptomatic improvement can also occur from implantation of the pacemaker without its hemodynamic benefit, suggesting the role of a placebo effect. Long-term follow-up of a large number of patients in randomized trials is necessary before dual-chamber pacing can be recommended for all patients with severely symptomatic hypertrophic obstructive cardiomyopathy.

Meckel Diverticulum: The Mayo Clinic Experience With 1476 Patients (1950–2002)

Objective:Through a comprehensive review of the Mayo Clinic experience with patients who had Meckel diverticulum, we sought to determine which diverticula should be removed when discovered incidentally during abdominal surgery. Summary Background Data:Meckel diverticula occur so infrequently that most articles have reported either small series or isolated cases. From these limited series, various conclusions have been reported without clearly indicating which incidental diverticula should be removed. Methods:Medical records were reviewed of 1476 patients found to have a Meckel diverticulum during surgery from 1950 to 2002. Preoperative diagnosis; age; sex; date of surgery; and intraoperative, macroscopic, and microscopic findings from operative and pathology reports were recorded. Logistic regression analysis was used to determine which clinical or histologic features were associated with symptomatic Meckel diverticulum. The features analyzed were age; sex; length, base width, and ratio of length to base width of the diverticulum; and the presence of ectopic tissue or abnormal tissue (inflammation or enteroliths). Results:Among the 1476 patients, 16% of the Meckel diverticula were symptomatic. The most common clinical presentation in adults was bleeding; in children, obstruction. Among patients with a symptomatic Meckel diverticulum, the male-female ratio was approximately 3:1. Clinical or histologic features most commonly associated with symptomatic Meckel diverticula were patient age younger than 50 years (odds ratio [OR], 3.5; 95% confidence interval [CI], 2.6–4.8; P < 0.001), male sex (OR, 1.8; 95% CI, 1.3–2.4; P < 0.001); diverticulum length greater than 2 cm (OR, 2.2; 95% CI, 1.1–4.4; P = 0.02), and the presence of histologically abnormal tissue (OR, 13.9; 95% CI, 9.9–19.6; P < 0.001). Conclusions:After analyzing our data, we neither support nor reject the recommendation that all Meckel diverticula found incidentally should be removed, although the procedure today has little risk. If a selective approach is taken, we recommend removing all incidental Meckel diverticula that have any of the 4 features most commonly associated with symptomatic Meckel diverticulum.

Results at up to 20 years after ileal pouch–anal anastomosis for chronic ulcerative colitis†

Ileal pouch–anal anastomosis (IPAA) is performed routinely for chronic ulcerative colitis.

Essential Thrombocythemia Beyond the First Decade: Life Expectancy, Long-term Complication Rates, and Prognostic Factors

OBJECTIVE To describe the long-term natural history of essential thrombocythemia (ET) in terms of life expectancy, risk of disease transformation Into a more aggressive myeloid disorder, and prognostic factors for both survival and disease complications. PATIENTS AND METHODS The study population consisted of a consecutive cohort of patients seen at the Mayo Clinic In Rochester, Minn, in whom a diagnosis of ET was established before 1992, thus allowing a minimum of 10 years of potential follow-up. The conventional criteria-based diagnosis was confirmed by bone marrow biopsy in all Instances. RESULTS A total of 322 patients were studied (median age, 54 years; median follow-up, 13.6 years). With a median survival time of 18.9 years, survival in the first decade of disease was similar to that of the control population (risk ratio, 0.72; 95% confidence interval, 0.50-0.99) but became significantly worse thereafter (risk ratio, 2.21; 95% confidence Interval, 1.74-2.76). Multivariable analysis identified age at diagnosis of 60 years or older, leukocytosis, tobacco use, and diabetes mellitus as Independent predictors of poor survival. A 2-variable model based on an age cutoff of 60 years and leukocyte count of 15 x 10(9)/L resulted in 3 risk groups with significant difference in survival. In addition, age at diagnosis of 60 years or older, leukocytosis, and history of thrombosis were independent predictors of major thrombotic events. The risk of leukemic or any myeloid disease transformation was low in the first 10 years (1.4% and 9.1%, respectively) but increased substantially in the second (8.1% and 28.3%, respectively) and third (24.0% and 58.5%, respectively) decades of the disease. CONCLUSION Life expectancy in patients with ET is significantly worse than that of the control population. Leukocytosis is identified as a novel independent risk factor for both inferior survival and thrombotic events.

Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study

Under the auspices of an International Working Group, seven centers submitted diagnostic and follow-up information on 1545 patients with World Health Organization-defined polycythemia vera (PV). At diagnosis, median age was 61 years (51% females); thrombocytosis and venous thrombosis were more frequent in women and arterial thrombosis and abnormal karyotype in men. Considering patients from the center with the most mature follow-up information (n=337 with 44% of patients followed to death), median survival (14.1 years) was significantly worse than that of the age- and sex-matched US population (P<0.001). In multivariable analysis, survival for the entire study cohort (n=1545) was adversely affected by older age, leukocytosis, venous thrombosis and abnormal karyotype; a prognostic model that included the first three parameters delineated risk groups with median survivals of 10.9–27.8 years (hazard ratio (HR), 10.7; 95% confidence interval (CI): 7.7–15.0). Pruritus was identified as a favorable risk factor for survival. Cumulative hazard of leukemic transformation, with death as a competing risk, was 2.3% at 10 years and 5.5% at 15 years; risk factors included older age, abnormal karyotype and leukocytes ⩾15 × 109/l. Leukemic transformation was associated with treatment exposure to pipobroman or P32/chlorambucil. We found no association between leukemic transformation and hydroxyurea or busulfan use.

Clinical Course of Patients With Relapsed Multiple Myeloma

OBJECTIVE To study the clinical course of patients with multiple myeloma (MM) that relapses after initial therapy. PATIENTS AND METHODS Patients with MM, seen at the Mayo Clinic in Rochester, Minn, between January 1, 1985, and December 31, 1998, were identified from a prospectively maintained database. Our study population consisted of 578 patients with newly diagnosed MM who were followed up and monitored throughout their clinical course at our institution. RESULTS The median age of the 578 patients with MM was 65 years (range, 26-92 years); 228 patients (39%) were women. The median follow-up of 71 surviving patients was 55 months (range, 0-202 months). The overall survival (OS) for the 578 patients at 1, 2, and 5 years was 72%, 55%, and 22%, respectively; the median OS from initial therapy was 28.4 months. The median OS of 355 patients who experienced relapse after initial treatment was 17.1 months from initiation of the second therapy, and 84% died within 5 years. The duration of response decreased consistently with each successive regimen. Patients with a high plasma cell labeling index (> or = 1.0%), low platelet count (< 150 x 10(9)/L), high creatinine level (> or = 2.0 mg/dL), and low albumin level (< 3.0 g/dL) had a poorer prognosis. CONCLUSIONS Our study revealed decreasing response duration with increasing number of salvage regimens, probably reflecting acquired drug resistance and an increasing proliferative rate of the myeloma cells. Patients who experienced relapse after initial treatment and received salvage therapy had a median survival of nearly 1.5 years. This must be remembered when making treatment decisions for these patients and must be factored in when assessing the efficacy of new therapies.

Functional Outcomes After Ileal Pouch-Anal Anastomosis for Chronic Ulcerative Colitis

OBJECTIVE To assess long-term outcomes after ileal pouch-anal anastomosis (IPAA) for chronic ulcerative colitis (CUC) with specific emphasis on patient sex, childbirth, and age. SUMMARY BACKGROUND DATA Childbirth and the process of aging affect pelvic floor and anal sphincter function independently. Early function after IPAA is good for most patients. Nonetheless, there are concerns about the impact of the aging process as well as pregnancy on long-term functional outcomes after IPAA. METHODS Functional outcomes using a standardized questionnaire were prospectively assessed for each patient on an annual basis. RESULTS Of the 1,454 patients who underwent IPAA for CUC between 1981 and 1994, 1,386 were part of this study. Median age was 32 years. Median length of follow-up was 8 years. Pelvic sepsis was the primary cause of pouch failure irrespective of sex or age. Functional outcomes were comparable between men and women. Eighty-five women who became pregnant after IPAA had pouch function, which was comparable with women who did not have a child. Daytime and nocturnal incontinence affected older patients more frequently than younger ones. Incontinence became more common the longer the follow-up in older patients, but this was not found in younger patients. Poor anal function led to pouch excision in only 3 of 204 older patients. CONCLUSIONS Incontinence rates were significantly higher in older patients after IPAA for CUC compared with younger patients. However, this did not contribute to a greater risk of pouch failure in these older patients. Patient sex and uncomplicated childbirth did not affect long-term functional outcomes.

Prevalence of Total Hip and Knee Replacement in the United States

BACKGROUND Descriptive epidemiology of total joint replacement procedures is limited to annual procedure volumes (incidence). The prevalence of the growing number of individuals living with a total hip or total knee replacement is currently unknown. Our objective was to estimate the prevalence of total hip and total knee replacement in the United States. METHODS Prevalence was estimated using the counting method by combining historical incidence data from the National Hospital Discharge Survey and the Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases from 1969 to 2010 with general population census and mortality counts. We accounted for relative differences in mortality rates between those who have had total hip or knee replacement and the general population. RESULTS The 2010 prevalence of total hip and total knee replacement in the total U.S. population was 0.83% and 1.52%, respectively. Prevalence was higher among women than among men and increased with age, reaching 5.26% for total hip replacement and 10.38% for total knee replacement at eighty years. These estimates corresponded to 2.5 million individuals (1.4 million women and 1.1 million men) with total hip replacement and 4.7 million individuals (3.0 million women and 1.7 million men) with total knee replacement in 2010. Secular trends indicated a substantial rise in prevalence over time and a shift to younger ages. CONCLUSIONS Around 7 million Americans are living with a hip or knee replacement, and consequently, in most cases, are mobile, despite advanced arthritis. These numbers underscore the substantial public health impact of total hip and knee arthroplasties.