Prediction of necrosis after chemotherapy of advanced germ cell tumors: results of a prospective multicenter trial of the German Testicular Cancer Study Group

PURPOSE: We evaluated the prognostic parameters of necrotic residual tumors after chemotherapy of advanced germ cell tumors to improve on the current indications for surgery. MATERIALS AND METHODS: Between January 1996 and January 2000, in 8 centers of the German Testicular Cancer Study Group, preoperative parameters were assessed to predict necrosis in the residual tumors of 261 patients with retroperitoneal residual tumor resection after first (92%) and second line (8%) chemotherapy. RESULTS: Of 232 evaluable patients 39 had pure seminoma and 5 had viable cancer (1 with seminoma) in the residual tumor. Of the remaining 193 patients with nonseminoma 35% had necrosis, 34% teratoma and 31% had viable carcinoma in the residual tumor. After multivariate analysis and exclusion of patients with seminoma, the 3 parameters independently predictive of necrosis were alpha-fetoprotein before chemotherapy less than 20 ng/ml, and tumor volume before and after chemotherapy. A mathematical model to predict necrosis yielded a test accuracy of 75%, a sensitivity to predict necrosis of 52% and a specificity of 87%. CONCLUSIONS: Patients with pure seminoma should not undergo residual tumor resection because 97% of patients who received adequate chemotherapy were found to have no residual seminoma. In cases of nonseminoma alpha-fetoprotein values before chemotherapy less than 20 ng/ml and a high percentage of shrinkage during chemotherapy reliably predicted only 19% of cases of necrosis. Therefore, this model is clinically irrelevant and patients with minimal residual disease should undergo surgery. New methods are necessary to improve the preoperative selection of patients after chemotherapy.     

High‐sensitive Troponin T measurements early after heart transplantation predict short‐ and long‐term survival

Following heart transplantation, cardiac biomarkers remain elevated for several weeks eventually as a result of membrane leakage of the donor organ. We now test the predictive power of blood levels of troponin T (TNT) measured by the new hsTNT assay (Roche Diagnostics, Roche Diagnostics, Mannheim, Germany) early after heart transplantation. TNT was determined in 141 cardiac allograft recipients and 40 controls. Our findings demonstrate that patients who died within the first year after transplantation had significantly higher median hsTNT serum levels 6 weeks after transplantation (156 ng/l ± 203 vs. 29 ng/l ± 21, P = 0.0002). Using ROC analysis, a serum hsTNT concentration of 33.55 ng/l 6 weeks after transplantation was found to be the best cutoff to predict death at 1 year (HR 0.16, 95%CI:0.05–0.46, P = 0.001) with a sensitivity of 90.91% and a specificity of 70.97%. In addition, survival at 5 years (HR 0.15, 95% CI 0.06–0.35, P < 0.0001) was significantly better among patients below that cutoff value. In multivariate analysis, hsTNT serum level 6 weeks after transplantation emerged as an independent predictor for first‐year mortality (hsTNT–HR 0.90, 95% CI: 0.81–1.00, P = 0.03). Cardiac troponin T concentrations early after transplantation as measured with a highly sensitive assay represent a strong and independent risk predictor of death after heart transplantation.     

Increased expression of CD44 in hypertrophied ligamentum flavum and relevance of splice variants CD44v5 and CD44v6

Background  

The most common spinal disorder in the elderly is lumbar spinal stenosis (LSS), which results in part from ligamentum flavum (LF) hypertrophy. Although prior histologic and immunochemical studies have been performed in this area, the pathophysiology of loss of elasticity and hypertrophy is not completely understood. The purpose of this immunohistological study is to elucidate the role of CD44 and its splice variants CD44v5 and CD44v6 in the hypertrophied LF obtained from patients with lumbar spinal stenosis (LSS).     

Mental health 15 years after the killings in Rwanda: Imprisoned perpetrators of the genocide against the Tutsi versus a community sample of survivors

Objectives of this study were to compare rates of mental health disorders in Rwandan genocide perpetrators with those of genocide survivors and to investigate potential predictors of symptoms of posttraumatic stress disorder (PTSD) and depression for both groups. We expected high rates of mental disorders in both study groups and hypothesized that symptom severity would be predicted by female gender, older age, lower level of education, higher level of trauma exposure, lower level of agreement to reconciliation, and the participation in killing. Structured clinical interviews were carried out with 269 imprisoned perpetrators (66% men) and 114 survivors (64% women). Significantly more survivors than perpetrators met symptom criteria for PTSD (46% vs. 14%) and suffered from anxiety symptoms (59% vs. 36%). A substantial proportion of both groups suffered from clinically significant depression (46% vs. 41%). PTSD severity in perpetrators was associated with trauma exposure, high levels of agreement to reconciliation, and no participation in killing; the severity of depression was associated with trauma exposure and no participation in killing. In the survivor sample, the severity of PTSD and depression were both correlated with female gender, trauma exposure, and low levels of agreement to reconciliation. Results suggest that both groups exhibit considerable psychiatric morbidity.     

Efficacy and safety of everolimus in elderly patients with metastatic renal cell carcinoma: an exploratory analysis of the outcomes of elderly patients in the RECORD-1 Trial

Background

Elderly patients with metastatic renal cell carcinoma (mRCC) may require special treatment considerations, particularly when comorbidities are present. An understanding of the efficacy and safety of targeted agents in elderly patients with mRCC is essential to provide individualized therapy.

Objective

To evaluate the efficacy and safety of everolimus in elderly patients (those ≥65 and ≥70 yr of age) enrolled in RECORD-1.

Design, setting, and participants

The multicenter randomized RECORD-1 phase 3 trial (Clinicaltrials.gov identifier, NCT00410124; http://www.clinicaltrials.gov) enrolled patients with mRCC who progressed during or within 6 mo of stopping sunitinib and/or sorafenib treatment (n = 416).

Intervention

Everolimus 10 mg once daily (n = 277) or placebo (n = 139) plus best supportive care. Treatment was continued until disease progression or unacceptable toxicity.

Measurements

Median progression-free survival (PFS), median overall survival (OS), and time to deterioration in Karnofsky performance status (TTD-KPS) were assessed using the Kaplan-Meier method; the log-rank test was used to compare treatment arms. Other outcomes evaluated included reduction in tumor burden, overall response rate (ORR), and safety.

Results and limitations

In RECORD-1, 36.8% of patients were ≥65 yr and 17.5% were ≥70 yr of age. PFS, OS, TTD-KPS, reduction in tumor burden, and ORR were similar in the elderly and the overall RECORD-1 population. Everolimus was generally well tolerated in elderly patients, and most adverse events were grade 1 or 2 in severity. The toxicity profile of everolimus was generally similar in older patients and the overall population; however, peripheral edema, cough, rash, and diarrhea were reported more frequently in the elderly regardless of treatment. The retrospective nature of the analyses was the major limitation.

Conclusions

Everolimus is effective and tolerable in elderly patients with mRCC. When selecting targeted therapies in these patients, the specific toxicity profile of each agent and any patient comorbidities should be considered.     

Muscarinic receptor subtypes in porcine detrusor: comparison with humans and regulation by bladder augmentation

The properties of muscarinic acetylcholine␣receptors of porcine and human bladder detrusor were␣compared in radioligand binding studies using [³H]quinuclidinylbenzylate as the radioligand. The receptor affinity for the radioligand and the density of␣muscarinic receptors was similar in male and female pigs and in humans (K _d = 35 ± 8 pM, B _max = 153 ± 30 fmol/mg protein). Atropine and subtype-selective antagonists had steep and monophasic competition curves in porcine and human detrusor with a rank order of potency of atropine ≫ hexahydro-sila-difenidol ≥ AF-DX 116 ≥ pirenzepine, indicating the presence of a␣homogeneous population of M₂ muscarinic receptors. In female pigs bladder outflow obstruction generated by partial urethral ligation or its surgical treatment by ileum augmentation or autoaugmentation did not significantly alter expression of muscarinic receptors or of α_2A-adrenoceptors, but the power was insufficient to exclude alterations of less than 60%. We conclude that porcine and human detrusor express muscarinic receptors of the M₂ subtype; despite these qualitative similarities the use of the porcine model may be limited by large biological variance with regard to quantitative receptor expression. Received: 9 June 1997 / Accepted: 27 October 1997     

Scientific Presentation Award: The impact of magnetic resonance imaging on surgical treatment of invasive breast cancer

Background

The purpose of this study was to examine the relationship between magnetic resonance imaging (MRI) and surgical treatment of invasive breast cancer (IBC).

Method

The IBC patients treated from January 2003-June 2008 were reviewed by a single institution.

Results

A total of 814 patients were treated, out of which 562 (69%) underwent breast conservation therapy (BCT), 151 (19%) chose mastectomy alone (M), and 101 (12%) chose mastectomy with reconstruction (M+ R). The mean age was comparatively low in M + R patients (P ≤ 0.001). The mean tumor size was the lowest in BCT patients (P ≤ 0.001). MRI use increased with no significant difference in type of surgery as noted by year. In multivariate analysis, type of surgery was significantly associated with tumor size, multifocality, age, and MRI use. The factors associated with MRI performance were: multifocality, younger age, tumor size, lobular histology, body mass index, and genetic testing.

Conclusions

The use of MRI in IBC patients has increased over the past 5 years, without any observable impact on surgical treatment. Similar factors are associated with mastectomy and MRI performance.     

Does magnetic resonance imaging accurately predict residual disease in breast cancer?

Background

The accuracy of magnetic resonance imaging (MRI) in identifying residual disease after breast conservation therapy (BCT) is unclear.

Method

Review of an institutional database identified patients with positive or close (≤2 mm) margins undergoing MRI before re-excision. Histopathologic correlation was performed.

Results

Forty-three women underwent MRI after BCT. MRI suggested residual disease in 29 patients, of whom 20 (69%) had residual carcinoma pathologically. Nine patients had false-positive MRI as seen by benign pathology findings. Fourteen MRIs indicated no residual disease, of which 6 had residual disease pathologically. The sensitivity and positive predictive value of MRI was 77% and 69%, respectively. MRI conducted within 28 days of the original surgery was 85% sensitive. MRI performed after 28 days was 69% sensitive.

Conclusions

MRI is able to detect residual disease among most patients undergoing re-excision. False-positive results may be caused by inflammatory processes that resemble residual disease.     

Leukocyte Depletion in Allogeneic Blood Transfusion Does Not Change the Negative Influence on Survival Following Transthoracic Resection for Esophageal Cancer

Background  Perioperative transfusion of allogeneic blood has been hypothesized to have an immunomodulatory effect and influence survival in several cancer types. This study evaluates the association between receipt of leucocyte-depleted and non-depleted allogeneic blood and survival following esophagectomy for cancer. Methods  A retrospective analysis was performed including 291 patients with esophageal cancers who underwent transthoracic en bloc esophagectomy and extended mediastinal lymphadenectomy. Neoadjuvant chemoradiation was administered in 152 (52.2%) patients. Perioperative blood transfusions were quantified and the potential prognostic cutoff for transfused units was calculated according to LeBlanc. Results  The median number of perioperative blood transfusions was 2 (0–24), and 106 patients (36.4%) received no transfusions. Patients with one or less blood transfusion showed a significantly improved survival compared to patients receiving more than one unit (p < 0.009). In multivariate analysis, blood transfusion categories showed significance (p < 0.015) next to pT, pN, pM category, and residual tumor categories (R-categories). Separate analysis of 183 patients treated after the mandatory introduction of leukocyte-depleted blood transfusions detected a strong tendency, but no significant difference in survival for patients getting one or less or more than one transfusion (p = 0.056). Receipt of leukocyte-depleted versus non-depleted units, however, had no influence on survival (p = 0.766). Conclusions  The need for perioperative allogeneic blood transfusions is significantly associated with poorer survival following resection for esophageal cancer by univariate and multivariate analysis. Our data suggest that the reduction of leukocytes in allogeneic transfusions is not sufficient to overcome the negative influence on survival. This paper was presented at DDW 2008 in the San Diego Convention Center, San Diego, CA, May 17–22, 2008.