A phase II trial of stereotactic body radiotherapy in 4 fractions for patients with localized prostate cancer.

PURPOSE/OBJECTIVE(S): To report results from our phase II study of stereotactic body radiotherapy (SBRT) delivering 36 Gy in 4 fractions for patients with localized prostate cancer. MATERIALS/METHODS: We enrolled 55 patients treated with SBRT delivering 36 Gy in 4 fractions between 2015 to 2018. All patients were categorized as low-risk (n = 4), intermediate-risk (n = 31) or high-risk (n = 20) according to National Comprehensive Cancer Network criteria. Median age was 73 years (range 54-86 years). Two-thirds of patients (n = 37) had received androgen-deprivation therapy for 3-46 months (median, 31 months). Median duration of follow-up was 36 months (range 1-54 months). We used Radiation Therapy Oncology Group and National Cancer Institute-Common Toxicity Criteria version 4 for toxicity assessments. Quality of life (QOL) outcomes were also evaluated using the Expanded Prostate Cancer Index Composite (EPIC). RESULTS: Protocol treatments were completed for all patients. Six patients experienced biochemical failures. Among these six patients, three patients experienced clinical failure. One patient showed bone metastasis before biochemical failure. One patient died of gastric cancer. The 3-year biochemical control rate was 89.8%. Acute grade 2 genitourinary (GU) and gastrointestinal (GI) toxicities were observed in 5 patients (9%) and 6 patients (11%), respectively. No grade 3 or higher acute toxicities were observed. Late grade 2 GU and GI toxicities were observed in 7 patients (13%) and 4 patients (7%), respectively. Late grade 3 GU and GI toxicities were observed in 1 patient (1.8%) each. EPIC scores decreased slightly during the acute phase and recovered within 3 months after treatment. CONCLUSION: Our phase II study showed that SBRT delivering 36 Gy in 4 fractions was safe and effective with favorable QOL outcomes, although this regimen showed slightly more severe toxicities compared to current standards.

A randomised controlled trial of pectoral nerve-2 (PECS 2) block vs. serratus plane block for chronic pain after mastectomy.

Thoracic interfascial plane blocks are effective for post-mastectomy acute analgesia. However, their effects on chronic pain are uncertain. We randomly allocated 80 women equally to pectoral nerve-2 (PECS 2) block or serratus plane block. The pectoral nerve-2 block reduced the rate of moderate or severe chronic pain from 13/40 (33%) with the serratus plane block to 4/40 (10%), p = 0.03, adjusted odds ratio (95%CI) 0.23 (0.07-0.80), p = 0.02. The rates of pain-free women at six postoperative months were indeterminate, 10/40 (25%) after serratus plane block vs. 19/40 (48%) after pectoral nerve-2 block, p = 0.06, adjusted odds ratio (95%CI) 2.9 (1.1-7.5), p = 0.03. Health-related quality of life at six postoperative months was similar after serratus plane and pectoral nerve-2 blocks, mean (SD) EQ-5D-3L scores 0.87 (0.15) vs. 0.91 (0.14), respectively, p = 0.21. The pectoral nerve-2 block reduced median (IQR [range]) morphine consumption in the first 24 postoperative hours from 6 (3-9 [1-25]) mg to 4 (2-7 [0-37]) mg, p = 0.04. However, acute pain scores after serratus plane and pectoral nerve-2 blocks were similar, median (IQR [range]) 23 (11-35 [0-70]) mm vs. 18 (11-27 [0-61]) mm, respectively, p = 0.44. Pectoral nerve-2 block reduced chronic pain 6 months after mastectomy compared with serratus plane block.

A Report on the Positive Response to an Outdoor Nature Challenge of a Snow Camp for Young Liver Transplant Patients.

OBJECTIVES: More than two decades have passed since the first living donor liver transplantation was performed in Japan in 1989. There are many reports about problems in adherence to taking medication and medical follow-ups in children who received liver transplants, because there is no transition strategy for those children and parents or guardians. The objective of this study is to measure the effect of nature and outdoor activity to improve children's medical adherence. METHODS: We recruited participants from 9-year-old children who are attending the outpatient liver transplant clinic in a stable condition (no event such as rejection or surgical procedure within 6 months). We took participants to a snow camp and measured its effect by using the IKIRU CHIKARA (IKR) tool, which contain 28 items divided into 3 categories: psychosocial ability, moral fitness, and physical ability. Children were tested on three occasions, before, just after, and 1 month after the camp. RESULTS: Eight patients participated in the snow camp and 7 patients were eligible for the study. The average age was 12.6 with a range 10 to 17 years. There were 3 girls and 4 boys. The average IKR scores before, just after, and 1 month after the camp were 127.9, 131.5, and 126.6, respectively. CONCLUSION: An outdoor activity such as a snow camp can be safely conducted, and it is an acceptable option to incorporate within a pediatric liver transplant program. There were no significant changes in IKR scores during this short observation. Longer observation is needed to measure the effect of nature and outdoor activities.

Multi-drug-resistant Staphylococcus aureus and future chemotherapy.

Staphylococcus (S.) aureus silently stays as our natural flora, and yet sometimes threatens our life as a tenacious pathogen. In addition to its ability to outwit our immune system, its multi-drug resistance phenotype makes it one of the most intractable pathogenic bacteria in the history of antibiotic chemotherapy. It conquered practically all the antibiotics that have been developed since 1940s. In 1961, the first MRSA was found among S. aureus clinical isolates. Then MRSA prevailed throughout the world as a multi-resistant hospital pathogen. In 1997, MRSA strain Mu50 with reduced susceptibility to vancomycin was isolated. Vancomycin-intermediate S. aureus (VISA), so named according to the CLSI criteria, was the product of adaptive mutation of S. aureus against vancomycin that had long been the last resort to MRSA infection. Here, we describe the genetic basis for the remarkable ability of S. aureus to acquire multi-antibiotic resistance, and propose a novel paradigm for future chemotherapy against the multi-resistant pathogens.

Brain structural changes as vulnerability factors and acquired signs of post-earthquake stress.

Many survivors of severe disasters, even those without posttraumatic stress disorder (PTSD), need psychological support. To understand the pathogenesis of PTSD symptoms and prevent the development of PTSD, the critical issue is to distinguish neurological abnormalities as vulnerability factors from acquired signs of PTSD symptoms in the early stage of adaptation to the trauma in the normal population. The neurological underpinnings of PTSD have been well characterized, but the causal relationships with the traumatic event are still unclear. We examined 42 non-PTSD subjects to find brain morphometric changes related to the severity of PTSD symptoms in a longitudinal magnetic resonance imaging study extending through the Great East Japan Earthquake. We found that regional grey matter volume (rGMV) in the right ventral anterior cingulate cortex (ACC) before the earthquake, and decreased rGMV in the left orbitofrontal cortex (OFC) through the earthquake were negatively associated with PTSD symptoms. Our results indicate that subjects with smaller GMV in the ACC before the earthquake, and subjects with decreased GMV in the OFC through the earthquake were likely to have PTSD symptoms. As the ACC is involved in processing of fear and anxiety, our results indicate that these processing are related to vulnerability for PTSD symptoms. In addition, decreased OFC volume was induced by failing to extinct conditioned fear soon after the traumatic event. These findings provide a better understanding of posttraumatic responses in early stage of adaptation to the trauma and may contribute to the development of effective methods to prevent PTSD.

Type I IFN-mediated enhancement of anti-leukemic cytotoxicity of gammadelta T cells expanded from peripheral blood cells by stimulation with zoledronate.

BACKGROUND: In order to establish efficient gammadelta T-cell based tumor immunotherapy, we explored a method to enhance the cytotoxicity of gammadelta T cells against leukemia cells by stimulating gammadelta T cells with type I IFN. METHODS: Gammadelta T cells were expanded from normal PBMC by culturing with zoledronate and a low concentration of IL-2 for 2 weeks. For the activation of gammadelta T cells, gammadelta T cells were cultured with type I IFN (HLBI, IFN-alpha2b and IFN-beta) for 1-3 days. The cytotoxicity of HLBI-activated gammadelta T cells against leukemia cell lines and fresh leukemia cells was evaluated by 51Cr-release assay. RESULTS: Gammadelta T cells, which were expanded and purified with magnetic beads using an anti-gammadelta TCR MAb, were demonstrated to be cytotoxic against leukemia cell lines of both lymphoid and myeloid origin and fresh myeloid leukemia cells. By culturing expanded gammadelta T cells with type I IFN, the expression of the activation marker CD69 was increased and the cytometric bead array showed an elevated production of IFN-gamma by gammadelta T cells. In addition, the cytotoxicity of gammadelta T cells against leukemia cells was definitely enhanced by culturing gammadelta T cells with HLBI. DISCUSSION: The present study has demonstrated that type I IFN could enhance the anti-leukemic cytotoxicity of expanded gammadelta T cells, which implies that in vitro bisphosphonate (such as zoledronate)-expanded and type I IFN-activated gammadelta T cells could be applied to immunotherapy for hematologic malignancies such as leukemia and lymphoma.

Prevalence of periodontal bacterial infection in non-obese Japanese type 2 diabetic patients: relationship with C-reactive protein and albuminuria.

The aim of the present study was to investigate the relationship between periodontal bacteria infection ( Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Prevotella intermedius) and C-reactive protein (CRP) and albuminuria in non-obese Japanese type 2 diabetic patients. One hundred and thirty-four non-obese Japanese type 2 diabetic patients without evidence of current acute illness including clinically significant acute infectious disease were enrolled into the study. The degree of periodontal bacterial infection was evaluated using IgG titer against Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, or Prevotella intermedius. The bacterial sonic extracts were used as antigens. High-sensitivity CRP (hCRP), glucose, glycosylated hemoglobin (HbA (1c)), and lipids were also measured after an overnight fast. Urinary albumin excretion rate as a ratio of urinary albumin and urinary creatinine was assessed in a morning spot urine sample using a commercial enzymatic immunoassay. The prevalence of Porphyromonas gingivalis infection was 52.2 % and that of Actinobacillus actinomycetemcomitans and Prevotella intermedius was 7.5 and 14.2 %, respectively. IgG titer against Porphyromonas gingivalis significantly correlated with CRP (r = 0.225, p < 0.001) and albuminuria (r = 0.185, p < 0.05), while IgG titer against Actinobacillus actinomycetemcomitans or Prevotella intermedius was not associated with either parameter. These results suggest that among periodontal bacteria, Porphyromonas gingivalis infection is associated with atherosclerosis in non-obese Japanese type 2 diabetic patients.

Successful surgical management of a tracheopulmonary artery fistula caused by an intratracheal expandable metal stent.

We describe a boy who underwent slide tracheoplasty and relocation of the left pulmonary artery at 3 months of age to treat pulmonary artery sling with congenital tracheal stenosis. Persisting tracheal stenosis required that he have a Palmaz stent inserted on postoperative day 77. He developed massive hemoptysis after the fourth attempt to expand the stent balloon and immediate computed tomography showed a tracheopulmonary artery fistula. Using cardiopulmonary bypass, we conducted emergency surgery to successfully manage the fistula. He currently depends on mechanical ventilation.

Direct closure of ostium primum defect in the repair of atrioventricular septal defect.

BACKGROUND: Patch closure is generally performed for atrial septation of an atrioventricular septal defect. We recently developed a new surgical technique for repairing atrioventricular septal defects that avoids the use of any patch material for closing the atrial septal defect. We report our experience with this procedure. METHODS: Seven patients (complete type: 5, partial type: 2) underwent this new operation. The diameters of the atrial septal defects were measured by transesophageal echocardiography. The preoperative electrocardiograms were compared with those taken after the operations. RESULTS: Diameters of the atrial defects ranged from 3 to 10 mm. Electrocardiograms before and after the operations did not change. No significant atrioventricular valve regurgitation and no residual shunts were detected by postoperative echocardiography. CONCLUSIONS: This method simplifies the repair of atrioventricular septal defects. In the short-term results, no arrhythmia and no valve regurgitation was seen.

Quantitative analysis of hypertrophy in cardiac chambers in cyanotic tetralogy of Fallot.

Although early total corrective repair for cyanotic tetralogy of Fallot is now safely performed at many institutions, long-term complications after surgical repair have been demonstrated. Therefore, the optimal procedure and timing for surgical treatment remain controxersial. In the present study, we conducted a quantitative analysis of the hypertrophy of all four chambers of 87 autopsied hearts of cyanotic tetralogy of Fallot and 71 normal control hearts utilizing the myocardial mass index, and evaluated the progression of lesions with advancing age. In cyanotic tetralogy of Fallot, hypertrophy of the right ventricle progresses immediately after birth, with that of the right atrium developing soon after. The left side of the heart is normal or slightly atrophied which could be corrected by sufficient palliative intervention or total corrective repair. The growth curves of both ventricles were parallel to those of normal hearts for the period studied. Pulmonary atresia, palliative operation, and total corrective repair have been shown to have some influence on the morphological characteristics of hearts of cyanotic tetralogy of Fallot.

A new pathway in the reaction of disilene with carbonyl compounds: an 'ene' reaction instead of cycloaddition.

The 3H-disilagermirene, (tBu2MeSi)4GeSi2, reacts with alpha-hydrogen containing carbonyl compounds (acetophenone, butane-2,3-dione) by an 'ene'-reaction pathway followed by isomerization or insertion reactions, representing a new mode in the reaction of disilenes with carbonyl compounds.

Severity of hyperemesis gravidarum correlates with serum levels of reverse T3.

To investigate the possible physiological relevance of extra-thyroidal production of reverse T3 (rT3) in hyperemesis gravidarum, measurements of serum rT3, free T3 (FT3), free T4, (FT4), and nonesterified fatty acids (NEFA) were correlated with weight loss of hyperemetic women. All the thyroid hormones, NEFAs and weight loss were significantly higher in hyperemesis gravidarum than in control subjects, and also higher than in those with milder symptoms of morning sickness (p < 0.05). Elevations of FT3, FT4 and NEFAs correlated with the extent of weight loss, the latter taken as the index of the severity of hyperemesis gravidarum (p < 0.05). Only rT3 correlated with both weight loss and the rate of lipolysis, as reflected by elevations of NEFAs (p < 0.05). The data are consistent with a shift from T3 to rT3 as products of 5'-monodeiodination of thyroxine in hyperemesis gravidarum. Because reverse T3 is physiologically inactive a control mechanism may be postulated wherein T3 production is minimized, thereby reducing weight loss and lipolysis in patients with hyperemesis gravidarum.

[Modified extended septoplasty for left ventricular outflow tract obstruction after repair of double-outlet right ventricle report of a case].

A three-year-old boy with residual VSD and LVOTO after repair of double outlet right ventricle underwent modified extended septoplasty successfully. Preoperative left ventriculography showed a residual VSD and LVOTO. The peak systolic pressure gradient between the left ventricle and aorta was 38 mmHg. Operation aimd not only at relief of the obstruction, but also at streamlining of the LVOT by removal of protrusions. We modified the extended septoplasty reported by Belli et al in 1996. The postoperative course was uneventful and patient was discharged at 15 postoperative day. The most recent echocargiogram revealed no residual LVOTO.

Long-term results of the fenestrated Fontan operation. Progress of patients with patent fenestrations.

The fenestrated Fontan operation was introduced as a modification of the "completed" Fontan operation for patients with high risk factors, and low operative mortality has frequently been reported. However, use of the umbrella device is now restricted, and this procedure should be performed without subsequent closure. In this paper, we review our clinical experience with this procedure and discuss ongoing problems. Sixteen patients (4 tricuspid atresia and 12 other cardiac anomalies including 5 cases of univentricular heart) underwent the fenestrated Fontan operation (7 atriopulmonary and 9 total cavopulmonary connection). All of them have some risk factors for a completed Fontan operation. There were three early deaths of the 16. Two experienced an anticipated thromboembolic accident, one of which involved the pulmonary aspect while the other involved the arterial aspect. Patients who survived the operation have progressed well and have a clinical status of New York Heart Association class I, with the exception of one late death due to congestive heart failure. There have been no thromboembolic accidents in this group during the late follow-up period. Spontaneous closures of the fenestrations were noted in two patients. The late mean Qp/Qs value in patients with patent fenestrations was 0.80 +/- 0.1, SaO2 was 88.8 +/- 5.6%, and right atrial pressure was 9.7 +/- 3.8 mmHg. No major problems have been encountered in patients with a patent fenestration over extended periods. A modified Fontan operation to fit a permanently open fenestration may be considered as a final surgical option for certain high-risk patients.

Tight interaction between densely methylated DNA fragments and the methyl-CpG binding domain of the rat MeCP2 protein attached to a solid support.

In a previous report we have found that a number of short DNA fragments methylated at CpG sequences bound more tightly to a methyl-CpG binding column than DNA fragments having a larger number of methyl-CpG sequences. The column consists of a polypeptide comprising the DNA binding domain of the rat MeCP2 protein attached to a solid support. In the present study, we have investigated the features of short DNA fragments which bind tightly to a methyl-CpG binding column. Tight binding was observed when the DNA fragment had a high density of methyl-CpG sequences. Many of these fragments, derived from human genomic DNA, contained Alu repeated sequences supporting the previous observation that the highly-abundant Alu sequences are highly methylated. Our results suggest that methyl-CpG density is an important factor in the interaction between DNA fragments and the DNA binding domain of MeCP2 attached to a solid support.

[A case of large congenital right ventricular outflow aneurysm].

A rare case of large congenital right ventricular outflow aneurysm is reported. A 5-year-old girl had been diagnosed as having atrial septal defect and pulmonary valvular stenosis. A large cavity in front of right ventricular outflow was noticed by her follow-up echocardiography. The non-contracting cavity was confirmed as an aneurysm originating from right ventricular outflow tract by angiocardiogram. Surgical resection was performed successfully with concomitant atrial septal defect closure and pulmonary valvular commissurotomy. Histological examination revealed that the wall of the ventricular outflow aneurysm consisted of dense fibrous tissue, contained no myocardium, and the cavity was lined with endocardium. It is reported that rupture of congenital ventricular aneurysm may occur even if there is no symptom. Surgical resection will be recommended especially when increasing in size is diagnosed.