Long-term results after 12-year follow-up of patients treated with whole-breast and boost irradiation after breast-conserving surgery

Purpose

The long-term outcomes of whole-breast and boost irradiation after breast-conserving surgery (BCS) for patients with breast cancer were retrospectively analyzed.

Materials and methods

Patients who received whole-breast and boost irradiation after BCS from 1990 to 2002 were included. Boost irradiation was administered to each tumor bed, regardless of the surgical margin status. The median doses of whole-breast and boost irradiation were 45 Gy in 25 fractions (range 36–45 Gy), and 14 Gy in 7 fractions (range 0–14 Gy), respectively.

Results

Data for 306 patients were analyzed. With a median follow-up time of 144 months, the 10-year overall survival, disease-free survival, ipsilateral breast tumor recurrence (IBTR), and metachronous contralateral breast cancer (MCBC) occurrence rates were 93.0, 84.1, 2.1, and 4.1 %, respectively. In the multivariate analysis, pT2 was a significant risk factor for IBTR (p = 0.041), while age ≤ 50 years and pT2 were significant risk factors for MCBC occurrence (p = 0.003 and 0.043, respectively). One patient (0.3 %) developed angiosarcoma in the irradiated region 120 months after the completion of radiation therapy.

Conclusion

The 12-year outcome of breast-conserving therapy using whole-breast and boost irradiation with doses of 45 and 14 Gy, respectively, was favorable.

     

Primary renal neuroblastoma with metastasis and matrix metalloproteinase‐14 expression

We herein report the rare case of a 4‐year–5‐month‐old boy who presented with primary renal neuroblastoma. The patient developed repeated lung and liver metastatic recurrences, but, following a combination of chemotherapy, radiation therapy and aggressive surgical resection, the patient is now in remission. To investigate the pathogenesis of lung metastasis, immunohistochemistry was performed for matrix metalloproteinase‐9 and ‐14 (MMP‐9 and MMP‐14), molecular markers of invasion, metastasis and angiogenesis in neuroblastoma. In the present case, MMP‐9 expression was not observed, but MMP‐14 expression was detected in the primary lesion and was more highly expressed in the metastatic lesion compared with the primary one. Given the MMP‐14 staining in other cases, expression of MMP‐14 may be associated with the aggressiveness of the tumor. This suggests that selected clones with high MMP‐14 expression in the primary tumor might metastasize and form MMP‐14‐rich lesions.     

Chronic Hyponatremia Causes Neurologic and Psychologic Impairments

Hyponatremia is the most common clinical electrolyte disorder. Once thought to be asymptomatic in response to adaptation by the brain, recent evidence suggests that chronic hyponatremia may be linked to attention deficits, gait disturbances, risk of falls, and cognitive impairments. Such neurologic defects are associated with a reduction in quality of life and may be a significant cause of mortality. However, because underlying diseases such as adrenal insufficiency, heart failure, liver cirrhosis, and cancer may also affect brain function, the contribution of hyponatremia alone to neurologic manifestations and the underlying mechanisms remain unclear. Using a syndrome of inappropriate secretion of antidiuretic hormone rat model, we show here that sustained reduction of serum sodium ion concentration induced gait disturbances; facilitated the extinction of a contextual fear memory; caused cognitive impairment in a novel object recognition test; and impaired long-term potentiation at hippocampal CA3–CA1 synapses. In vivo microdialysis revealed an elevated extracellular glutamate concentration in the hippocampus of chronically hyponatremic rats. A sustained low extracellular sodium ion concentration also decreased glutamate uptake by primary astrocyte cultures, suggesting an underlying mechanism of impaired long-term potentiation. Furthermore, gait and memory performances of corrected hyponatremic rats were equivalent to those of control rats. Thus, these results suggest chronic hyponatremia in humans may cause gait disturbance and cognitive impairment, but these abnormalities are reversible and careful correction of this condition may improve quality of life and reduce mortality.     

Clinical Effect of Switching from a Luteinizing Hormone-Releasing Hormone Agonist to an Antagonist in Patients with Castration-Resistant Prostate Cancer and Serum Testosterone Level ≥ 20 ng/dl

Introduction

The efficacy of conversion from a luteinizing hormone-releasing hormone agonist to an antagonist was evaluated prospectively in patients with castration-resistant prostate cancer.

Materials and Methods

From October 2012 to December 2014, 8 cases with a serum testosterone level ≥ 20 ng/dl during following androgen deprivation therapy were enrolled and received degarelix monthly. The primary end-pointgoal was to determine the effective prostate-specific antigen response rate. The secondary end-pointgoal was to assess the proportion of cases with a decrease in serum testosterone level to < 20 ng/ml.

Results

One patient achieved a complete response, with a prostate-specific antigen level of 0.02 ng/ml at the nadirend of the study. The effective response rate was 25.0% (2/8), and the proportion of cases with prostate-specific antigen decline was 62.5% (5/8). In 5/8 cases (5/8, 62.5%), serum testosterone levels declined to < 20 ng/dl.

Conclusion

Switching to a luteinizing hormone-releasing hormone antagonist in patients with testosterone levels ≥ 20 ng/dl may be an option in sequential androgen deprivation therapy for some patients.Key Words: Castration-resistant, Degarelix, Prostatic neoplasms, Luteinizing hormone-releasing hormone, Testosterone     

Low frequency of promoter methylation of O6-methylguanine DNA methyltransferase and hMLH1 in ulcerative colitis-associated tumors: comparison with sporadic colonic tumors

To cast light on the contribution of methylation to genesis of ulcerative colitis (UC)-associated tumors, promoter methylation and expression of O6-methylguanine DNA methyltransferase (MGMT), hMLH1, p16INK4, and E-cadherin were examined in 14 low-grade dysplasias (LGDs), 15 high-grade dysplasias (HGDs), and 14 adenocarcinomas associated with UC and, for comparison, in 30 sporadic adenomas with LGD, 30 adenomas with HGD, and 60 adenocarcinomas, using methylation-specific polymerase chain reaction and immunohistochemical analysis. The frequency of MGMT and hMLH1 methylation in UC-associated tumors was low, with a significant difference between HGD and sporadic adenomas with HGD of the left hemicolon. The methylation frequency of p16INK4 in UC-associated tumors was also relatively low compared with sporadic colonic tumors. For E-cadherin, methylation was limited in both types of tumor. Decrease of expression of MGMT, hMLH1, and p16INK4 was significantly correlated with methylation. Thus, compared with the sporadic type, contribution of methylation to UC-associated tumorigenesis seems to be low.     

Neural adjustment in the activation of the lower leg muscles through daily physical exercises in community-based elderly persons

Reflecting the rapidly aging population, community-based interventions in the form of physical exercise have been introduced to promote the health of elderly persons. Many investigation studies have focused on muscle strength in the lower leg as a potent indicator of the effect of physical exercises. The objective of this study was to assess the effect of long-term daily exercises on neural command in lower leg muscle activations. Twenty-six community-based elderly persons (13 men and 13 women; 69.8 +/- 0.5 years old) participated in this study. Daily exercise was comprised of walking for more than 30 min, stretching, muscle strengthening and balance exercise, and was continued for three months. Muscle strength and surface electromyography of the tibia anterior, rectus femoris, and biceps femoris were measured in maximum isometric voluntary contraction both before and after the intervention. The mean frequency of the firing of motor units was calculated based on fast Fourier transformation of the electromyography. As the results of the intervention, muscle strength increased significantly only in biceps femoris, whereas the mean frequency of motor units decreased significantly in every muscle, indicating that motor unit firing in lower frequency efficiently induces the same or greater strength compared with before the intervention. Thus, synchronization of motor units compensates for the lower frequency of motor unit firing to maintain muscular strength. In conclusion, long-term physical exercises in the elderly can modulate the neural adjustment of lower leg muscles to promote efficient output of muscle strength.