Radiofrequency Ablation of Invasive Breast Carcinomas: A Phase II Trial

Background Local ablative therapy of breast cancer represents the next frontier in the minimally invasive breast-conservation treatment. We conducted a phase II trial to evaluate radiofrequency ablation (RFA) of invasive breast carcinomas. Methods Consecutive patients from two Mexican Institutions with invasive breast cancers < 4 cm, with no multicentric tumors and no previous chemotherapy were included in this trial. Under ultrasound guidance, the tumor and a 5 mm margin of surrounding breast tissue were ablated with saline-cooled RFA electrode followed by surgical resection. Routine pathologic analysis and viability evaluation with NADPH-diaphorase stain were performed to assess tumor ablation. Procedure-associated morbidity was recorded. Results Twenty-five patients were included. Mean patient age was 55.3 years (range 42–89 years). Mean tumor size was 2.08 cm (range 0.9–3.8 cm). Fourteen tumors (56%) were <2 cm. The mean ablation time was 11 minutes using a mean power of 35 W. During ablation, the tumors become progressively echogenic that corresponded with the region of severe RFA injury at pathologic examination. Of the 25 patients treated, NADPH stain showed no evidence of viable malignant cells in 19 patients (76%), with significant difference between tumors <2 cm (complete necrosis in 13 of 14 cases, 92.8%) vs. those >2 cm (complete necrosis 6 of 11 cases, 54.5%) (P < .05). No significant morbidity was recorded. Conclusions RFA is a promising minimally invasive treatment of small breast carcinomas, as it can achieve effective cell killing with a low complication rate. Further studies are necessary to optimize the technique and evaluate its future role as local therapy for breast cancer.     

Barriers in the help-seeking process: a multiple-case study of early-onset dysthymia in Sweden

The aim of this study was to investigate barriers to diagnosis and adequate treatment of patients with early-onset dysthymia by studying how understandings of illness by patients and providers have evolved and how treatments have been negotiated over time. A theory-testing and explorative multiple-case study design was used with developmental cognitive theory as framework. Data pertaining 10 non-remission dysthymic patients were analyzed using five sources: 1) case records, 2) interviews, 3) self-report questionnaires, 4) observations, and 5) life-charting, eliciting life events, course and treatments. The analysis comprised qualitative content analysis and a coding scheme of knowledge structures. Barriers could be explained by misunderstandings as patients mainly expressed illness in concrete, perceptually bound knowledge structures and providers focused on one aspect, instead of on the complexity of concurrent aspects. Another barrier, associated to comorbid personality disorder, was a core pattern of concealing due to fear of rejection and mistrust. Other barriers were connected to providers' attitudes and contextual factors such as access problems and lack of follow-up. A theoretical model that involves patients' understanding of illness in preoperational thinking and providers' cognitive errors can explain communication barriers. Means of shared understanding and treatment planning are suggested. Future treatment research could elucidate the impact of the core belief of rejection with associated strategy of concealing by assessing these variables as predictors and as targets for change.     

The inflammatory reflex and risk for rheumatoid arthritis: a case-control study of human vagotomy

Recent data suggest remarkable effects of vagus stimulation (reduction) and vagotomy (exacerbation) on acute inflammation in rats, the so-called "inflammatory reflex". Its role in humans remains unknown. Therefore, the aim was to explore whether surgical vagotomy in humans would affect the risk of a prototype inflammatory disease, rheumatoid arthritis. This was a case-control study. Assessment of the relative risk (RR) of developing rheumatoid arthritis after surgical vagotomy during 1964-2001 in 63,092 prevalent rheumatoid arthritis cases versus 125,404 matched controls from the general population and in 2548 incident rheumatoid arthritis cases versus 24,357 matched controls from the general population, respectively, was done. For comparison, we assessed RRs for hospitalisation for gastric disorders not including vagotomy. Data on exposures and rheumatoid arthritis were retrieved from population-based and prospectively recorded Swedish registers. A pre-rheumatoid arthritis vagotomy was not significantly associated with an increased risk for rheumatoid arthritis (RR = 1.17, 95% CI 0.97 to 1.40). RRs in the same range were observed for several other pre-rheumatoid arthritis gastric conditions that do not include vagotomy (eg, gastric ulcer RR = 1.21, 95% 1.11 to 1.33). Vagotomy has no specific effect on the risk of developing rheumatoid arthritis in humans. Gastroduodenal ulcers occur more often than expected even before the occurrence of rheumatoid arthritis.     

Differential sensitivities of the NCX1.1 and NCX1.3 isoforms of the Na+-Ca2+ exchanger to alpha-linolenic acid

OBJECTIVE: Dietary intake of omega-3 polyunsaturated fatty acids (PUFA) like alpha-linolenic acid (ALA) is antiarrhythmic and cardioprotective. PUFA may also be beneficial in hypertension. Altered Na(+)-Ca(2+) exchanger (NCX) activity has been implicated in arrhythmias, hypertension and heart failure and may be a target for PUFA. Thus, we tested the effects of ALA and other distinct fatty acids on the cardiac (NCX1.1) and vascular (NCX1.3) NCX isoforms. METHODS: HEK293 cells stably expressing NCX isoforms were ramped from +60 to -100 mV (over 1600 ms) in the absence and presence of 25 microM oleic acid (OA, omega-9), linoleic acid (LA, omega-6), ALA (omega-3), or eicosapentaenoic acid (EPA, omega-3). NiCl(2) (5 mM) was used to inhibit and therefore identify the NCX current. The effect of 25 microM ALA on NCX1.1 and NCX1.3 activity was also assessed in adult rat ventricular cardiomyocytes and rabbit aortic vascular smooth muscle cells (VSMC) by measuring [Ca(2+)](i) following substitution of [Na(+)](o) with Li(+). RESULTS: Application of Ni(2+) had no effect in non-transfected cells. ALA and EPA (25 microM) reduced the Ni(2+)-sensitive forward NCX1.1 current (at -100 mV) by 64% and reverse current (at +60 mV) by 57%, and inhibited the Ni(2+)-sensitive NCX1.3 forward and reverse currents by 79% and 76%, respectively. Neither OA nor LA (25 microM) affected the NCX1.1 currents, but both partially inhibited the forward and reverse mode NCX1.3 currents. Inhibition of NCX1.3 by ALA occurred at a much lower IC(50) ( approximately 19 nM) than for NCX1.1 ( approximately 120 nM). In cardiomyocytes and VSMC, ALA significantly reduced the Li(+)-induced rise in intracellular [Ca(2+)]. CONCLUSIONS: NCX1.3 is more sensitive to inhibition by ALA than NCX1.1. In addition, only omega-3 PUFA inhibits NCX1.1, but several classes of fatty acids inhibit NCX1.3. The differential sensitivity of NCX isoforms to fatty acids may have important implications as therapeutic approaches for hypertension, heart failure and arrhythmias.     

Activated ERK1/2 expression in glioblastoma multiforme and in peritumor tissue

Anomalies of growth factor signaling have been reported in malignant human gliomas. The extracellular signal-regulated kinases (ERKs) play a crucial role in transducing growth factor signals to the nucleus and are involved in a wide range of biological responses, including cell proliferation, differentiation and motility. ERK1/2 is expressed and activated in glioblastoma multiforme (GBM). However, no information is available in literature concerning the presence and activity of ERK1/2 in the peritumor tissue. In the present study, we evaluated by immunohistochemistry total and phosphorylated (t and p) ERK1/2 expression in 31 cases of primary GBM and in tissue surrounding the enhanced lesion at different distances up to 3.5 cm from the tumor margin. Total ERK1/2 was, as expected, uniformly expressed not only in GBM but in the areas around the tumor also, which showed higher levels of immunolabeling. ERK1/2 activation was observed in GBM as well as in peritumor tissue, with no statistical difference in the level of the enzymatic activities. In particular, in the peritumor tissue pERK1/2 was present independently of neoplastic cells not only in reactive astrocytes, but in apparently normal glial cells also. These results indicate that ERK1/2 pathway may participate in GBM growth and progression. In addition, they strongly suggest that ERK1/2 stimulation may be linked not only to tissue reactivity to tumor invasion, but also to cell motility or represent per se a sign of transformation. Finally, our findings highlight the meaning of the extension of neoplasm fingers beyond the outer margin of GBM. Patients with neoplastic cells at <10% or without neoplastic cells in peritumor areas showed a higher survival time compared with those with neoplastic elements at > or = 10%. In addition, a percentage > or = 10 of neoplastic elements in peritumor tissue was associated with an approximately 4-fold increased death risk.     

Developing an outcome measurement for meaning-making intervention with Chinese cancer patients

Psychosocial programs designed for cancer patients often facilitate the search for meaning as one of the therapeutic components. This study aimed to develop a self-report instrument, namely Chinese Cancer Coherence Scale (CCCS), which measures the patients' meaning-making process with reference to the concept of coherence. A panel of eight veteran social workers and psychologists generated statements pertaining to the cancer experience. Results from a two-phase study involving 390 breast cancer patients revealed a two-factor structure of the CCCS, namely incoherent-embittered and coherent-enlightened. The use of the CCCS by practitioners and researchers is recommended in order to understand how Chinese cancer patients make sense of their cancer experience.     

Optimization of energy-window settings for scatter correction in quantitative (111)In imaging: comparison of measurements and Monte Carlo simulations

Activity quantification in nuclear medicine imaging is highly desirable, particularly for dosimetry and biodistribution studies of radiopharmaceuticals. Quantitative (111)In imaging is increasingly important with the current interest in therapy using (90)Y radiolabeled antibodies. One of the major problems in quantification is scatter in the images, which leads to degradation of image quality. The aim of this study was to optimize the energy-window settings for quantitative (111)In imaging with a camera that enabled acquisition in three energy windows. Experimental measurements and Monte Carlo simulations, using the SI-MIND code, were conducted to investigate parameters such as sensitivity, image contrast, and image resolution. Estimated scatter-to-total ratios and distributions, as obtained by the different window settings, were compared with corresponding simulations. Results showed positive agreement between experimental measurements and results from simulations, both quantitatively and qualitatively. We conclude that of the investigated methods, the optimal energy-window setting was two windows centered at 171 and 245 keV, together with a broad scatter window located between the photopeaks.     

Dosimetry for (90)Y-DOTATOC therapies in patients with neuroendocrine tumors

The aim of this study was to determine the inter- and intrapatient variability of absorbed dose to the whole body, kidneys, and tumor, as well as the question of whether the first therapy could serve as a guide for future therapies. Fifty (50) (90)Y-DOTATOC therapies were given to 30 patients diagnosed with refractory stage IV neuroendocrine tumors (20 patients received two therapies, 10 patients received one therapy). The first and second therapies were delivered at standard intervals. (90)Y-activity was prescribed by surface area (3.7 GBq/m(2)), and approximately 100 MBq (111)In-DOTATOC was administered concurrently for imaging purposes. Amino acid coadministration for renal protection was performed. Measurements of activity in whole-body and single-photon emission computed tomography images were acquired at various time points after the administration of the radiopharmaceutical. The dosimetry for whole body, kidneys, and tumor was based on these data. The interpatient variability (the ratio of the maximum absorbed dose per injected activity for all patients) was larger than the intrapatient variability (the ratio of absorbed dose per injected activity for subsequent therapies in the same patient for whole body, kidneys, and tumor. These results imply that the first therapy could serve as a guide for future therapies. This approach might allow for targeted radionuclide therapy to be delivered by prescribed absorbed dose, rather than by administered activity.