Does Additional Doxorubicin Chemotherapy Improve Outcome in Patients with Hepatocellular Carcinoma Treated by Liver Transplantation?

The aim of this prospective randomized study was to determine whether additional doxorubicin chemotherapy improves outcome in patients with hepatocellular carcinoma (HCCA) treated by liver transplantation. Stratification parameters were tumor stage (UICC I-IVa), gender, age 50 years, α-fetoprotein 20 ng/mL, cirrhosis and HbsAg status. For pre-operative chemotherapy doxorubicin (15 mg/m²) was given biweekly, intra-operative chemotherapy was a single dose administered before surgical manipulation. Post-operative chemotherapy from day 10 was as given preoperatively for a total dosage of 300 mg/m². Outcome parameters were overall survival (OS) and disease-free survival. Of the 75 consecutive patients who received liver transplantation for treatment of HCCA, 62 patients were enrolled. Thirty-four patients were randomized in the chemotherapy group; 28 patients were in the control group and transplanted only. OS rates at 5 years were 38% in the chemotherapy group and 40% in the control group, disease-free survival rates at 5 years 43% and 53%, respectively. Tumor stage and vascular invasion were identified as independent risk factors for recurrence of disease. Doxorubicin chemotherapy did not improve organ survival and disease-free survival in patients undergoing liver transplantation for HCCA.     

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Wilson's disease tremor is associated with magnetic resonance imaging lesions in basal ganglia structures.

Wilson's disease (WD) is an inherited disorder of copper metabolism yielding marked motor deficits, including a severely disabling tremor. As a structural correlate of the disease, a variety of cerebral abnormalities has been revealed. However, the relationship between motor deficits and cerebral lesions has remained largely unknown. Here, we investigated correlation between WD tremor and cerebral magnetic resonance imaging (MRI) findings. Cerebral MRI abnormalities in 6 symptomatic WD patients were compared to findings in 6 asymptomatic WD patients and 10 healthy controls. All patients were treated with long-term copper chelating therapy. Motor symptoms including tremor were determined by Unified Parkinson's Disease Rating Scale Part III (UPDRS-III). MRI findings in symptomatic WD patients revealed significant symmetric T2*-weighted hypointense signal alterations of globus pallidus, head of the caudate nucleus, and substantia nigra. In contrast, MRI of asymptomatic WD patients did not differ from healthy controls. Correlation analysis revealed a significant positive correlation between MRI basal ganglia lesions and UPDRS action tremor score. Our results demonstrate for the first time that Wilson's disease tremor is associated with lesions of the globus pallidus, the head of the caudate nucleus, and the substantia nigra.     

Bilateral carcinomas of the breast with local recurrence: analysis of genetic relationship of the tumors.

Local recurrence of bilateral breast carcinomas is rare, but of biological interest, since it is unclear as to which tumor the local recurrence is related to, the ipsilateral or the contralateral, or whether it is an independent neoplasm. The aim of this study was to investigate the genetic relationship of bilateral breast carcinomas to each other and to their local recurrences. Eight cases of bilateral breast carcinomas, five with and three without local recurrence were analyzed using a microsatellite assay for 13 microsatellite loci. The presence of loss of heterozygosity and microsatellite instability in the various tumors was used for clonal analysis. All eight bilateral breast carcinomas showed divergent alterations in at least two microsatellite loci, which ruled out a genetic relationship. Four of five local recurrences were genetically related to the ipsilateral tumor and unrelated to the contralateral tumor. Only one local recurrence that occurred 11.8 years after the surgery of an infiltrative lobular carcinoma simultaneously with distant metastases was genetically related to the contralateral breast carcinoma. Although the number of cases in our study is limited, there is evidence that local recurrence of bilateral breast carcinoma frequently arises from the ipsilateral tumor.     

Promotion of mindfulness in psychotherapists in training: preliminary study.

This study examined whether the promotion of mindfulness in psychotherapists in training can influence the treatment results of their patients. The therapeutic course and treatment results of 196 inpatients, who were treated during a nine week period by nine psychotherapists in training, were compared: in the first phase of the study, the treatment group without (CG, historical control group, n=55), and in the second phase the treatment group with, (MFG, n=58) therapists who were currently practicing Zen meditation. The results of treatment were examined (according to the intent-to-treat principle) with the Session Questionnaire for General and Differential Individual Psychotherapy (STEP), the Questionnaire of Changes in Experience and Behaviour (VEV) and the Symptom Checklist (SCL-90-R), and showed significantly better results in the MFG.     

Urothelial carcinoma of the upper urinary tract: inverted growth pattern is predictive of microsatellite instability

Urothelial carcinoma of the renal pelvis and ureter may develop as a manifestation of hereditary nonpolyposis colorectal cancer syndrome (HNPCC), a disorder characterized by mutation or inactivation of a number of DNA mismatch repair genes and detectable as microsatellite instability (MSI). Some urothelial carcinomas display areas of endophytic, or inverted, growth. In this study, urothelial cancers of the upper urinary tract (n = 132) from patients treated at 2 tertiary care centers were studied to identify an association between growth pattern and MSI. Thirty-five neoplasms were microsatellite unstable (26.5%), and MSI was more frequent in papillary lesions than in sessile urothelial cancers (P = .033). The amount of inverted growth was estimated as a percentage of the total tumor. The interobserver and intraobserver concordance in recognizing inverted growth was good, and 65.7% of microsatellite-unstable tumors exhibited at least 20% of an inverted growth component, compared with only 17.5% of microsatellite-stable tumors (P < .0001). In this series, inverted growth predicted MSI with a sensitivity and specificity of .82. Inverted growth in urothelial carcinomas of the upper urinary tract may serve as a marker lesion for MSI and may help identify patients who should be offered testing for HNPCC.     

Microsatellite analysis of breast carcinoma and corresponding local recurrences

Local recurrence is a serious complication of breast carcinoma that reduces quality of life and influences prognosis. The aim of this study was to determine whether local recurrences of breast carcinoma are genetically related to the primary tumours. Forty cases of locally recurrent breast carcinomas (median onset: 3.6 years after primary surgery) were analysed: 22 patients had undergone breast-conserving therapy and 18 mastectomy. Eighteen microsatellites on chromosomes 2p, 3p, 5q, 10q, 11p, 11q, 13q, 17q, 17p, 18p were amplified by PCR using fluorescent-labelled primers, automatically detected after polyacrylamide gel electrophoresis and analysed for loss of heterozygosity (LOH) or microsatellite instability (MSI). Follow-up data were available for 39 cases with a median value of 89 months. All LOH and MSI found in the primary tumours were also present in the corresponding recurrences, indicating that they are genetically related to the primary tumours and not secondary malignancies in the same breast. MSI was found in three cases, of which one harboured MSI at more than two loci. The median value of LOH per case was significantly higher in the recurrent (four per case) compared to the primary tumours (two per case; p < 0.001, Mann-Whitney test), reflecting the genotype of tumour progression. Early local recurrence was associated with specific LOH for TP53.15 (p = 0.018, log-rank test) in the primary tumours. LOH on D13S1699 or D17S855 was associated with lymph node metastases (p = 0.024 and p = 0.019, respectively; chi-square test). In addition, tumour grade, lack of oestrogen or progesterone receptor expression, young patient age and early appearance of local recurrence significantly correlated with poor survival. The development of local recurrence despite clear resection margins may result from residual DCIS distant from the invasive carcinoma, homing of circulating tumour cells, or genetically altered, histologically normal breast tissue not immediately adjacent to the invasive carcinoma.