Multivariate Analysis of Risk Factors for Postoperative Complications in Benign Goiter Surgery: Prospective Multicenter Study in Germany

Risk factors for postoperative complications of benign goiter surgery have not been investigated systematically. To this end, a prospective multicenter study (January 1 through December 31, 1998) was conducted involving 7266 patients with surgery for benign goiter from 45 East German hospitals. High-volume providers (>150 operations per year) performed 69% (5042/7266), intermediate-volume providers 27% (50–150), and low-volume providers 4% (258/7266) of operations. Among the hospital groups, the pattern of thyroid disease did not vary significantly, but there was a trend that small-volume providers tended to perform more operations for uninodular goiter and high-volume providers treated more patients with Graves' disease and recurrent goiter. Extent of resection (p < 0.0001) and remnant size (multinodular goiter and recurrent goiter, p < 0.001), differed significantly, with total thyroidectomy being performed more often in hospitals with more than 150 operations compared to hospitals with an operative volume of less than 150 procedures per year. Despite the larger extent of resection and smaller remnant size, rates of recurrent laryngeal nerve (RLN) palsy or hypoparathyroidism were not increased. When the logistic regression analyses were fitted to evaluate the impact of risk factors on transient and permanent RLN palsy and hypoparathyroidism, larger extent of resection [relative risk (RR) 1.5–2.1] and recurrent goiter (RR 1.8–3.4) consistently evolved as independent risk factors. With hypoparathyroidism, additional significant factors included patient gender (RR 2.1–2.4), hospital operative volume (RR 0.8–1.5), and Graves' disease (RR 2.8). Unlike parathyroid gland identification during hypoparathyroidism, RLN identification (RR 1.6) significantly (p= 0.01) reduced permanent RLN palsy rates. The multivariate analyses clearly confirmed the pivotal role of routine RLN identification, independent of the extent of the thyroid resection. These findings might help hospitals with lower operative volumes to identify patients at increased risk whom they might consider for specialist care.     

Left ventricular hypertrophy in hypertensive patients with autosomal dominant polycystic kidney disease: influence of blood pressure and humoral and neurohormonal factors

Left ventricular hypertrophy (LVH) is a common finding in hypertensive autosomal dominant polycystic kidney disease (ADPKD) patients. There are few studies on the influence of blood pressure (BP) and nonhemodynamic factors on LVH in these patients. The aim of this study was to evaluate the relationship between BP, humoral and neurohormonal factors and left ventricular mass (LVM) in hypertensive ADPKD patients. In 20 hypertensive ADPKD patients, ambulatory BP was monitored for 24 h, left ventricular dimensions were estimated by echocardiography, and plasma renin activity (PRA), plasma noradrenaline (NA), angiotensin II (Ang II), aldosterone, atrial natriuretic peptide (ANP) and insulin-like growth factor I (IGF-I) were also determined. Twenty age- and sex-matched essential hypertensive subjects served as controls. Ambulatory BP and LVM index were similar in the two groups, although male ADPKD patients had higher LVM indices than their matched controls. Eight ADPKD patients (40%) and 6 essential hypertensives (30%) showed LVH. PRA, Ang II, aldosterone, ANP and IGF-I levels were similar in the two groups, but plasma NA levels were higher in ADPKD patients than in controls (281 +/- 158 vs. 160 +/- 62 pg/ml, p = 0.004). ADPKD patients with LVH did not differ from those without LVH with regard to humoral and neurohormonal parameters, but had higher ambulatory BP levels. In ADPKD patients, correlation analysis revealed a significant association between LVM index and 24-hour systolic and diastolic BP, but not with any of the hormonal factors evaluated. On multiple regression analysis, 24-hour diastolic BP was the only independent variable linked to LVM index. In conclusion, ambulatory BP is one of the most important determinants of LVM in hypertensive ADPKD patients. Further studies are warranted to elucidate the role of nonhemodynamic factors in the pathogenesis of LVH in this population.     

3D conformal HDR brachytherapy and external beam irradiation combined with temporary androgen deprivation in the treatment of localized prostate cancer.

PURPOSE: To evaluate treatment outcome of 3D conformal high dose rate (HDR) brachytherapy and external beam irradiation (EBRT) combined with temporary androgen deprivation for patients with localized prostate cancer. PATIENTS AND METHODS: Between January 1997 and September 1999 we treated 102 patients with stage T1-3 N0 M0 prostate cancer. Stage T1-2 was found in 71, T3 in 31 patients. Median pretreatment PSA level was 15.3 ng/ml. After ultrasound-guided transrectal implantation of four afterloading needles, CT based 3D brachytherapy planning was performed. All patients received four HDR implants using a reference dose per implant of 5 or 7Gy. Time between each implant was 14 days. After brachytherapy EBRT followed up to 39.6 or 45.0 Gy. All patients received temporary androgen deprivation, starting 2-19 months before brachytherapy, ending 3 months after EBRT. RESULTS: Median follow-up was 2.6 years (range 2.0-4.1 years). Actuarial biochemical control rate was 87% at 2 years and 82% at 3 years. In 14 patients we noted biochemical failure, in five patients clinical failure. Overall survival was 90%, disease specific survival 98.0% at 3 years. Acute grade 3 toxicity occurred in 4%, late grade 3 toxicity in 5%. One patient developed a prostatourethral-rectal fistula as late grade 4 toxicity. The conformal quality of 300 HDR implants was analyzed using dose volume histograms. CONCLUSIONS: 3D conformal HDR brachytherapy and EBRT combined with temporary androgen deprivation is an effective treatment modality for prostate cancer with minimal associated toxicity and encouraging biochemical control rates after a median follow-up of 2.6 years.     

Phase I study of the humanized antiepidermal growth factor receptor monoclonal antibody EMD72000 in patients with advanced solid tumors that express the epidermal growth factor receptor.

PURPOSE: To investigate the safety and tolerability and to explore the pharmacokinetic and pharmacodynamic profile of the humanized antiepidermal growth factor receptor monoclonal antibody EMD72000 in patients with solid tumors that express epidermal growth factor receptor (EGFR). PATIENTS AND METHODS: This was a phase I dose-escalation trial of EMD72000 in patients with advanced, EGFR-positive, solid malignancies that were not amenable to any established chemotherapy or radiotherapy treatment. EMD72000 was administered weekly without routine premedication until disease progression or unacceptable toxicity. RESULTS: Twenty-two patients were treated with EMD72000 at five different dose levels (400 to 2,000 mg/wk). National Cancer Institute common toxicity criteria grade 3 headache and fever occurring after the first infusion were dose limiting at 2,000 mg/wk; thus, the maximum-tolerated dose was 1,600 mg/wk. No other severe side effects, especially no allergic reactions or diarrhea, were observed. Acneiform skin reaction was the most common toxicity, but it was mild, with grade 1 in 11 patients (50%) and grade 2 in three patients (14%). Pharmacokinetic analyses demonstrated a predictable pharmacokinetic profile for EMD72000. Pharmacodynamic studies on serial skin biopsies revealed that EMD72000 effectively abrogated EGFR-mediated cell signaling (eg, reduced phosphorylation of EGFR and mitogen-activated protein kinase), with no alteration in total EGFR protein. Objective responses (23%; 95% CI, 8% to 45%) and disease stabilization (27%; 95% CI, 11% to 50%) were achieved at all dose levels, and responding patients received treatment for up to 18 months without cumulative toxicity. CONCLUSION: Treatment with EMD72000 was well tolerated and showed evidence of activity in heavily pretreated patients with EGFR-expressing tumors. EMD72000 at the investigated doses significantly inhibited downstream EGFR-dependent processes.     

Loss of beta-catenin expression in metastatic gastric cancer.

PURPOSE: Beta-catenin (beta-catenin) participates in intercellular adhesion and is an integral part of the Wnt signaling pathway. The role of beta-catenin in the pathogenesis of gastric cancer and its metastasis is largely unknown. PATIENTS AND METHODS: Immunohistochemistry and Western blot analysis were used to analyze the expression of beta-catenin in 87 human gastric cancers, in metastasis and cancer cell lines. The beta-catenin and the adenomatous polyposis coli (APC) genes were analyzed for gene mutations. Furthermore, methylation of the beta-catenin promoter in cell lines was assessed by treatment with 5'-azadeoxycytidine and sodium bisulfite genomic sequencing. RESULTS: beta-Catenin expression was present at either the cell membrane or the cytoplasm in 34 of 75 primary gastric cancers. Expression of beta-catenin was significantly more frequent in intestinal-type (P =.0049) and well-differentiated gastric cancers (P <.001). There were no quantitative differences between gastric cancers and the nonmalignant gastric tissues, as determined by Western blot analysis. One of 18 metastatic cancer lesions and four of five gastric cancer cell lines expressed beta-catenin protein. N87 cells, derived from the liver metastasis of a gastric cancer, did not express beta-catenin. Treatment with 5'-azadeoxycytidine restored beta-catenin protein levels in this cell line, which exhibited significantly more 5-methylcytosines in the beta-catenin promoter compared with the other cell lines. CONCLUSION: beta-Catenin expression is lost in a subgroup of primary gastric cancers, is frequently absent in metastases, and exhibits nuclear localization in cancers with either beta-catenin or APC gene mutations. Interestingly, the loss of beta-catenin expression in metastatic gastric cancers may result from hypermethylation of the beta-catenin promoter.     

Health status and quality of life in patients with early-stage Hodgkin's disease treated on Southwest Oncology Group Study 9133.

PURPOSE: We describe the short and intermediate-term quality-of-life (QOL) outcomes in patients treated on a randomized clinical trial in early-stage Hodgkin's disease (Southwest Oncology Group [SWOG] 9133) comparing subtotal lymphoid irradiation (STLI) with combined-modality treatment (CMT). PATIENTS AND METHODS: Two hundred forty-seven patients participated in the QOL study (SWOG 9208), completing several standardized instruments (Symptom Distress Scale; Cancer Rehabilitation Evaluation System - Short Form; Medical Outcomes Study 36-Item Short-Form Health Survey Vitality Scale; and a health perception item), as well as questions about work, marital status, and concerns about having children. This article reports on results from baseline before random assignment, at 6 months, and at 1 and 2 years after random assignment. RESULTS: Patients receiving CMT experienced significantly greater symptom distress (P <.0001), fatigue (P =.001), and poorer QOL (P =.015) at 6 months than the STLI patients, reflecting a shorter time since completion of therapy in the CMT arm. Importantly, patients in the two groups did not differ on any outcomes at the 1-and 2-year assessments. Both patient groups reported significantly more fatigue before treatment than healthy reference populations, and fatigue did not improve in either group after treatment. CONCLUSION: This study demonstrated that patients with early-stage Hodgkin's disease experience a short-term decrease in QOL and an increase in symptoms and fatigue with treatment, which is more severe with CMT; by 1 year, however, CMT and STLI patients report similar outcomes. Fatigue scores for both arms were lower at baseline than scores for the general population and did not return to normal levels 2 years after random assignment. The mechanisms responsible for this lingering problem warrant further investigation.     

Unusual Longevity Without Surgical Intervention in Complete Transposition of the Great Arteries

A case of unusual longevity to the age of 58 years is reported for a female patient with complete transposition of the great arteries. The association with a wide atrial septal defect with intact interventricular septum may have contributed to the long survival without surgery. Factors determining intercirculatory mixing and systemic oxygen saturation may be the high pulmonary flow, the location of the anatomic communication, sufficient hemoglobin concentration to allow an adequate level of systemic resistance and recirculated systemic flow, and the belated development of pulmonary vascular disease.     

Researching health inequities among African Americans: the imperative to understand social class.

Racial and ethnic inequities in health abound in many disease categories. African-American communities suffer from an increased burden of illness, with higher incidence and mortality rates and more severe morbidity in cerebrovascular disease, heart disease, several cancers, diabetes, and many other ailments. Healthy People 2010, the federal government's health plan, calls for eliminating health disparities by race, ethnicity, gender, education, income, disability, geographic location, or sexual orientation. Research aimed at increasing our understanding of these health disparities and designing and evaluating interventions to improve African-American health is hampered by a liberal, classless approach. The authors argue for a theoretical framework in this research that recognizes that class exploitation sets the stage for and interacts with racial discrimination to determine racial inequities in health.