Evaluation of treatment response to enzyme replacement therapy with Velaglucerase alfa in patients with Gaucher disease using whole-body magnetic resonance imaging.

OBJECTIVE: This was a retrospective data analysis to evaluate the treatment response to enzyme replacement therapy (ERT) with Velaglucerase alfa using whole-body magnetic resonance imaging (MRI). MATERIALS AND METHODS: A baseline and follow-up MRI were performed on 18 Gaucher Type 1 patients at an interval of 11.6 months. The MRI score systems determined the Bone-Marrow-Burden (BMB) score, the Düsseldorf-Gaucher score (DGS), and the Vertebra-Disc-Ratio (VDR). The Severity Score Index Type 1 (GD-DS3) was also assessed. RESULTS: The baseline MRI medians were: BMB, 7.00; DGS, 3.00; and VDR: 1.70; while, the follow-up MRI medians were: BMB, 7.00; DGS, 3.00; and VDR: 1.73. The baseline GD-DS3 median was 2.40 (BMB excl.: 0.50) and the follow-up median was 2.00 (BMB excl.: 0.50). There was weak statistical significance with the Wilcoxon signed-rank test for the DGS (p=0.034) and GD-DS3 (p=0.047) between both MRIs. CONCLUSION: Velaglucerase alfa therapy is a effective long-term treatment for Gaucher Type 1 patients who are newly diagnosed or switching therapies. Measurements with whole-body MRI and an objective scoring system were reliable tools for detecting early stage bone marrow activity. Further research is needed to evaluate the "Booster-Effect" of Velaglucerase alfa therapy in Gaucher skeletal disease.

Evaluation of Bone Marrow Infiltration in Non-Neuropathic Gaucher Disease Patients with Use of Whole-Body MRI--A Retrospective Data Analysis.

PURPOSE: To evaluate whole-body magnetic resonance imaging (WB-MRI) for the assessment of bone marrow infiltration in patients with confirmed Gaucher disease type 1 under long-term enzyme replacement therapy (ERT). MATERIALS AND METHODS: This retrospective data analysis included 38 patients in two subgroups. Group A: 10 females, 9 males, 15-29 years, mean age 22 years and Group B: 11 females, 8 males, 29-77 years, mean age 49 years, all treated with alglucerase or imiglucerase for at least 12.5 years. Whole-body MRI was carried out in all patients using a standard MRI protocol. Two radiologists assessed all MR images retrospectively with the use of three different MRI score systems: The bone marrow burden (BMB) score, the Düsseldorf-Gaucher score (DGS) and the vertebra disc ratio (VDR). As a clinical component, severity score index type 1 (GD-DS3) was determined. RESULTS: In both groups the MR scores showed low to moderate pathologic levels but no statistically significant difference was found between both groups. The median scores in group A/group B were 7.00/9.00 for the BMB score (p=0.07), 4.00/3.00 for the DGS score (p=0.062) and 1.54/1.62 for the VDR score (p=0.267). The GD-DS3 score was statistically significantly different between both groups (1.6/3.9, p=0.000) and osseous Gaucher disease complications were only found in group B. CONCLUSION: Bone marrow involvement and typical clinical manifestations are reduced to a minimum, when ERT starts immediately after the confirmed diagnosis of Gaucher disease type 1. The applied MR scores are useful markers to control bone marrow infiltration under enzyme replacement therapy in older patients. Pathologic MR scores in young patients may reflect postponed fat conversion of the juvenile bone marrow. This issue has to be examined in further studies. KEY POINTS: Whole-body MRI is valuable for the staging of Gaucher disease type 1. Osseous complications are reduced to a minimum in early treated patients. MR score systems have to be adjusted in young Gaucher patients.

Morphologic assessment of thoracic deformities for the preoperative evaluation of pectus excavatum by magnetic resonance imaging.

OBJECTIVE: To assess whether MRI is a suitable modality for the preoperative assessment and quantification of pectus excavatum. METHODS: A total of 69 patients (57 male, 12 female; median age 15 years, range 5-35 years) with pectus excavatum were evaluated preoperatively using standardized MRI sequences on 1.5- and 3-Tesla systems (T2-HASTE/inspiration and expiration, T1-VIBE, T2-TRUFI free-breathing, T2-BLADE). The MR sequences were analysed for quality semiquantitatively. The Haller index, correction index, sternal rotation angle and asymmetry index were assessed; correlations between these indices and changes in inspiration and expiration were evaluated. RESULTS: T2-HASTE was the best sequence to assess pectus excavatum morphology, with a higher quality at 3 T than at 1.5 T. All indices could be assessed in every patient. A total of 37 patients had a symmetric deformity, 32 patients an asymmetric deformity. The Haller index correlated significantly (p < 0.001) with the correction index, both becoming higher in expiration. The asymmetry index correlated with the sternal rotation angle (p < 0.001) and did not change significantly in expiration (p = 0.28). CONCLUSIONS: Thoracic MRI is suitable for the preoperative evaluation of patients with pectus excavatum. An exact morphologic assessment is possible without radiation exposure as well as the determination of several indices to quantify the deformities.

The prognostic value of lymph node ratio and updated TNM classification in rectal cancer patients with adequate versus inadequate lymph node dissection.

BACKGROUND: The aim of this study was to clarify whether the lymph node ratio (LNR) is superior to the updated TNM classification regarding the prognosis of stage III rectal cancer patients who have not undergone neoadjuvant therapy. The TNM system is based on the absolute number of lymph nodes involved, and the LNR takes into account involved and examined nodes. METHODS: In 237 patients with stage III rectal cancer, we evaluated prognostic factors for 5-year overall survival (OS), disease-free survival (DFS), and risk of distant metastases (DM) using the Kaplan-Meier method, with patients divided based on adequate versus inadequate lymph node dissection (≥12 vs. <12 lymph nodes examined). The updated TNM divides patients into four groups (1, 2-3, 4-6, and ≥7 involved nodes), while LNR divides patients into quartiles. Multivariate Cox regression analyses were performed. RESULTS: Among patients with adequate lymph node dissection, the distributions within the two systems were in agreement in 141/178 (79.2 %, kappa 0.721), and the predictive values for OS, DFS, and DM were similar. In patients with inadequate lymph node dissection, the classifications of both systems were concordant in only 13/59 (22 %, kappa 0.021). The pN system significantly under-staged patients, while the LNR classification was a better predictor of OS, DFS, and DM. CONCLUSIONS: In patients with adequate lymph node dissection, LNR staging does not add substantial information to the predictions of updated TNM lymph node staging. However, in patients with inadequate lymph node harvesting, the LNR compensates for the under-staging of the TNM classification and provides a better estimation of prognosis than the updated TNM system.

Persistent hypertension after successful adrenal operation.

BACKGROUND: Up to 80% of patients with adrenocortical tumors comprising Conn's or Cushing's syndrome and patients with pheochromocytomas suffer from hypertension. Its implications in cardiovascular disease and its impact on quality of life make it the most important aim in therapeutic efforts. The aim of our study was to assess the long-term results in postoperative blood pressure after adrenalectomy and to evaluate potential risk factors for persistent hypertension. METHODS: Forty four patients with adrenal hypertension operated on between April 1986 and April 1991 underwent follow-up consisting of exact history, hormonal analysis, and adrenal imaging. RESULTS: Forty three patients were reexamined, which showed 11 patients (26%) with hypertension at dismissal from hospital and 17 patients (40%) with hypertension after a median of 2 years. Except for two recurrent tumors in adrenocortical carcinoma all patients were surgically cured. Antihypertensive medication could be reduced in 13 of 17 patients with persistent hypertension. Persistent hypertension did not correlate with the degree of preoperative blood pressure elevation, age, and gender, but it did correlate strongly with history of hypertension. Patients with normal blood pressure level after operation had a mean history of 5.7 years versus 11.5 years in patients with persistent hypertension (p < 0.03). CONCLUSIONS: The success of surgical treatment for adrenal hypertension strongly depends on early diagnosis and surgical intervention.