Sequential 99mTc-hydrazinonicotinamide-annexin V imaging for predicting response to chemotherapy.

This study was undertaken to evaluate changes in relative (99m)Tc-hydrazinonicotinamide (HYNIC)-annexin V tumor uptake over time in patients undergoing chemotherapeutic treatment at baseline and at 5-7 h and 40-44 h after treatment initiation. Imaging results are related to clinical outcomes, as assessed with response evaluation criteria in solid tumors (RECIST). METHODS: We prospectively included 20 patients (11 men and 9 women; mean age, 59.8 y; range, 22-75 y) scheduled for chemotherapy (n = 19) or bisphosphonate treatment (n = 1). Curable disease was present in 5 patients. The other patients had metastatic disease and were treated in a palliative setting. Three of the 20 enrolled patients were excluded from analysis: 1 patient ultimately refused the proposed chemotherapy treatment; because of difficulties with the labeling procedure, 1 patient did not receive a pretreatment scan; and 1 patient presented with an allergic reaction (rash and nausea) to the (99m)Tc-HYNIC-annexin V formulation. The remaining 17 patients underwent 3 scintigraphic scans with (99m)Tc-HYNIC-annexin V: before treatment and 5-7 h and 40-44 h after treatment initiation. The tumor response was evaluated with RECIST and related to observed changes in the ratios of tumor activity to background activity for the largest known lesion; values exceeding 25% the baseline value on either the 5- to 7-h scan or the 40- to 44-h scan were considered significant. RESULTS: With the proposed sequential imaging protocol and a 25% change threshold, responders to treatment could be separated from nonresponders with a 94% accuracy (16/17 patients). CONCLUSION: Sequential (99m)Tc-HYNIC-annexin V imaging may allow for assessment of the response to chemotherapy within 3 d after treatment initiation.     

Buchbesprechungen

Ohne Zusammenfassung     

Response of proopiomelanocortin and gonado- or lactotroph systems to in-vitro fertilisation procedures stress

Objective

To analyse for the first time the response of the corticotroph-type and the melanotroph-type pituitary proopiomelanocortin (POMC) system with regard to in-vitro fertilisation (IVF) treatment using self-developed highly specific non-cross-reacting radioimmunoassay.

Study design

Setting: University hospital. Patients: A total of 28 patients undergoing IVF oocyte retrieval. Cross sectional exploratory study, one factorial design with repeated measurements on one factor, non-parametric tests. Blood was collected before anaesthesia (t_A) (n = 28) and immediately after oocyte retrieval (t_B) (n = 28). Main outcome measure(s): β-endorphin immunoreactive material (IRM), acetyl-N-β-endorphin IRM, β-lipotropin IRM, ACTH, cortisol, estradiol, progesterone, prolactin, luteinizing hormone, and follicle-stimulating hormone. For determination of authentic β-endorphin [β-endorphin (1–31)] a highly specific two-site fluid phase immunoprecipitation radioimmunoassay was developed, which did not cross-react with any β-endorphin derivative or any other opioid peptide tested.

Results

No response of acetyl-N-β-endorphin IRM and of authentic β-endorphin (1–31) was observed to oocyte retrieval in contrast to a significant increase of corticotroph-type proopiomelanocortin derivatives. A significant rise in prolactin plasma concentration indicates a pronounced lactotroph response to oocyte retrieval stress. No significant correlation between POMC derivates and prolactin and between POMC derivatives and gonadotropins or sexual steroids except for ACTH and progesterone and for β-endorphin IRM and estradiol was observed.

Conclusion

IVF treatment stress led to significant corticotroph-type POMC and lactotroph responses, but not to responses of authentic β-endorphin or melanotroph-type POMC in women undergoing oocyte retrieval.     

Improving results of the modified Fontan operation in patients with heterotaxy syndrome

BACKGROUND: Historically the Fontan operation in patients with single ventricle heterotaxy syndrome and atrial isomerism has been associated with high mortality. We studied whether recent modifications of the surgical technique have improved outcome. METHODS: A retrospective review of 135 patients with heterotaxy syndrome who underwent a Fontan operation between 1981 and 2000 was performed. RESULTS: There were 93 patients with right isomerism and 42 with left isomerism. Anomalies of venous return included 25 patients with extracardiac pulmonary venous connection (19%) and 37 patients with an interrupted inferior vena cava (27%). Thirty-six patients (27%) had at least moderate atrioventricular valve regurgitation. The type of Fontan procedure included 17 patients with an atriopulmonary Fontan connection, 67 with a lateral tunnel modification, 19 with an intraatrial tube graft, 25 with an extracardiac tubegraft, and 7 with an intra-extra atrial tube graft. A fenestration was placed in 93 patients (78%). Early mortality was 19% before 1991, 3% since 1991, and no patient has died early since 1993. Ten-year survivals were 70% for Fontan operations before 1990 and 93% for Fontan operations after 1990. Thirty-two patients (23%) had prolonged pleural effusions. Risk factors for death included anomalous pulmonary venous connection (p = 0.02) and higher preoperative pulmonary vascular resistance (p = 0.002). Sixty-two patients (47%) had some form of early postoperative arrhythmia. At 10 years, freedom from late bradyarrhythmia and late tachyarrhythmia were 78% and 70%, respectively. Preoperative arrhythmias, older age at operation, and anatomic features were each independent predictors of late arrhythmia. CONCLUSIONS: The Fontan operation can now be performed in patients with heterotaxy syndrome with excellent survival. However, morbidity in terms of postoperative arrhythmias and prolonged pleural effusions remains significant. Fontan staging, appropriate choice of Fontan modification, aggressive treatment of concomitant malformations, and use of a baffle fenestration contribute to improved outcome.     

Different prognostic importance of elevated troponin I after percutaneous coronary intervention in acute coronary syndrome and stable angina pectoris

OBJECTIVES: To investigate the prognostic importance of cardiac troponin I (cTnI) elevation after percutaneous coronary intervention (PCI) in different clinical settings. DESIGN: The study includes 238 patients presenting with acute coronary syndrome (ACS) and 194 patients with stable angina pectoris (SAP). The composite end point of death or hospitalization due to non-fatal myocardial infarction, repeated revascularization or unstable angina, was determined during one year of follow-up. RESULTS: cTnI elevation after PCI was more frequent in ACS patients than SAP patients. ACS patients with cTnI elevation after PCI had significantly higher number of events than patients with unchanged cTnI status after PCI. SAP patients had generally lower event rate than ACS patients. The event rate was also significantly higher among ACS patients than SAP patients at comparable degrees of cTnI elevation after PCI. There was no difference in events among SAP patients with or without cTnI elevation after PCI. CONCLUSION: cTnI elevation after PCI predicts adverse outcome after one year in patients with ACS, but not in patients with SAP.     

The musculocutaneous nerve: ultrasound appearance for peripheral nerve block

BACKGROUND AND OBJECTIVES: To gain complete anesthesia of the forearm, block of the musculocutaneous nerve is necessary. Variations in its course and position make localization of the musculocutaneous nerve problematic. The aim of the study is to describe the ultrasound appearance of the musculocutaneous nerve in the axilla and to suggest potential areas to target neural block. METHODS: We scanned the axillary regions of 19 volunteers and assessed the size and shape of 34 musculocutaneous nerves at entry into, exit from, and in the center of the coracobrachialis muscle. Furthermore, we measured the depth of the musculocutaneous nerve under the skin surface and its distance from the axillary artery at those 3 measurement points. RESULTS: As it travels through the coracobrachialis muscle, the musculocutaneous nerve changes in shape from oval to flat-oval to triangular. During this course, the musculocutaneous nerve also separates from the axillary artery and becomes more lateral while changing its depth from the surface. The musculocutaneous nerve increases its transverse area along this nerve path. In 2 subjects, the musculocutaneous nerve could not be visualized unilaterally within the course of the coracobrachialis muscle. CONCLUSIONS: Knowledge of its ultrasound appearance facilitates localization and successful block of the musculocutaneous nerve. Because the distance between the musculocutaneous nerve and brachial plexus varies, different locations of musculocutaneous nerve puncture during ultrasound-guided regional anesthesia can be chosen.     

BRAF and NRAS mutations are frequent in nodular melanoma but are not associated with tumor cell proliferation or patient survival

Previous studies have shown frequent mutations in the BRAF (V-raf murine sarcoma viral oncogene homolog B1) or NRAS (neuroblastoma RAS viral [V-ras] oncogene homolog) genes in cutaneous melanoma, but the relationship between these alterations and tumor cell proliferation has not been examined in human melanoma. In our study of 51 primary nodular melanomas and 18 paired metastases, we found mutations in BRAF (codon 600, previously denoted 599) in 15 primary tumors (29%) and eight metastases (44%). The figures for NRAS mutations were 27% and 22%, respectively. Mutations in BRAF and NRAS genes were mutually exclusive in all but one case, and were maintained from primary tumors through their metastases. Mutations, however, were not associated with tumor cell proliferation by Ki-67 expression, tumor thickness, microvessel density, or vascular invasion, and there were no differences in patient survival. Although BRAF and NRAS mutations are likely to be important for the initiation and maintenance of some melanomas, other factors might be more significant for proliferation and prognosis in subgroups of aggressive melanoma.