Factors associated with cavity formation after stereotactic body radiation therapy for peripheral early-stage lung cancer.

PURPOSE: This retrospective study aimed to identify the factors associated with cavity formation after SBRT in peripheral early-stage lung cancer patients. We analyzed the occurrence of cavity changes after SBRT. MATERIALS AND METHODS: We examined 99 cases with T1-T2aN0 peripheral non-small cell lung cancer treated with SBRT from 2004 to 2021. Patients underwent respiratory function tests, including diffusing capacity for carbon monoxide (DLco), before treatment. The median observation period was 35 months (IQR 18-47.5 months). Treatment involved fixed multi-portal irradiation in 67% of cases and VMAT in 33%. The total radiation doses ranged from 42 to 55 Gy, delivered over 4 to 5 fractions. RESULTS: Cavity formation occurred in 14 cases (14.1%), appearing a median of 8 months after SBRT. The cavity disappeared in a median of 4 months after formation. High DLco and total radiation dose were identified as factors significantly associated with cavity formation. There have been no confirmed recurrences to date, but one patient developed a lung abscess. CONCLUSION: Although cavity formation after SBRT for peripheral early-stage lung cancer is infrequent, it can occur. This study showed high DLco and total radiation dose to be factors significantly associated with cavity formation. These findings can be applied to optimizing radiation therapy (RT) and improving patient outcomes. Further research is needed to determine the optimal radiation dose for patients with near-normal DLco for whom surgery is an option. This study provides valuable insights into image changes after RT.

PGC-1α regulates airway epithelial barrier dysfunction induced by house dust mite.

BACKGROUND: The airway epithelial barrier function is disrupted in the airways of asthmatic patients. Abnormal mitochondrial biogenesis is reportedly involved in the pathogenesis of asthma. However, the role of mitochondrial biogenesis in the airway barrier dysfunction has not been elucidated yet. This study aimed to clarify whether the peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α), a central regulator of mitochondrial biogenesis, is involved in the disruption of the airway barrier function induced by aeroallergens. METHODS: BEAS-2B cells were exposed to house dust mite (HDM) and the expressions of PGC-1α and E-cadherin, a junctional protein, were examined by immunoblotting. The effect of SRT1720, a PGC-1α activator, was investigated by immunoblotting, immunocytochemistry, and measuring the transepithelial electrical resistance (TEER) on the HDM-induced reduction in mitochondrial biogenesis markers and junctional proteins in airway bronchial epithelial cells. Furthermore,the effects of protease activated receptor 2 (PAR2) inhibitor, GB83, Toll-like receptor 4 (TLR4) inhibitor, lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS), protease inhibitors including E64 and 4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) on the HDM-induced barrier dysfunction were investigated. RESULTS: The amounts of PGC-1α and E-cadherin in the HDM-treated cells were significantly decreased compared to the vehicle-treated cells. SRT1720 restored the expressions of PGC-1α and E-cadherin reduced by HDM in BEAS-2B cells. Treatment with SRT1720 also significantly ameliorated the HDM-induced reduction in TEER. In addition, GB83, LPS-RS, E64 and AEBSF prevented the HDM-induced reduction in the expression of PGC1α and E-cadherin. CONCLUSIONS: The current study demonstrated that HDM disrupted the airway barrier function through the PAR2/TLR4/PGC-1α-dependent pathway. The modulation of this pathway could be a new approach for the treatment of asthma.

Sweet proteins lysozyme and thaumatin are protein-type agonists for the calcium-sensing receptor.

In addition to the maintenance of Ca2+ homeostasis, the calcium-sensing receptor (CaSR) is involved in many diverse physiological functions in the mammalian body. The receptor works as a kokumi taste receptor in taste buds and as a nutrient sensor in the gut, where it regulates the secretion of glycemic response and appetite-related hormones. To identify novel human CaSR (hCaSR) activators from food ingredients, we conducted a screening using a cell-based hCaSR assay. Hen egg-white lysozyme, which is a sweet protein, was found to be a novel orthosteric agonist of hCaSR with an EC50 value of 592 µM. Lysozyme hydrolysate was not able to activate hCaSR, thus suggesting that the protein structure of lysozyme is necessary for hCaSR activation. Thaumatin, which is another sweet protein, also activated hCaSR with an EC50 value of 71 µM. This is the first report that shows hCaSR activation by proteins with molecular weights exceeding 10,000 Da. These results provide a new avenue for the development of hCaSR activators, which could be applicable in food or drugs that modulate taste perception, appetite, or glucose tolerance, in addition to Ca2+ homeostasis.

N-terminal [Glu]3 moiety of γ-glutamyl peptides contributes largely to the activation of human calcium-sensing receptor, a kokumi receptor.

γ-glutamyl peptides have been suggested to impart kokumi properties to foods by activating human calcium-sensing receptor (hCaSR). In this study, the relationship between γ-glutamyl peptide structure and hCaSR activity was systematically analyzed using γ-[Glu](n=0-4)-α-[Glu](n=0-3)-Tyr. Our results suggest that N-terminal [Glu]3 moiety is very important for hCaSR activities of γ-glutamyl peptides.

Roles of Ki-67 and p16 as biomarkers for unknown primary head and neck squamous cell carcinoma.

PURPOSE: Treatment guidelines have not been established for unknown primary head and neck squamous cell carcinoma (SCC). For these patients, chemoradiotherapy (CRT) can provide a better prognosis than that for patients with other head and neck cancers. The presence of HPV in the tumor is associated with a better outcome. However, not all patients with HPV-positive unknown primary head and neck SCC experience good treatment outcomes in actual clinical settings. METHODS: We thus retrospectively determined the Ki-67 proliferation index and p16 expression status to assess the associations of these parameters with treatment outcomes of patients with unknown primary head and neck SCC. RESULTS: The subjects were 13 patients who underwent CRT after surgery or excision biopsy between 1999 and 2016. The 2- and 5-year overall survival (OS) rate was 76.9% and 68.4%, respectively. The prognostic factor was age. There was no significant difference in survival between patients with a high Ki-67 vs. low Ki-67 or between patients with p16-positive vs. p16-negative metastases OS. However, all p16-positive patients with low Ki-67 showed good locoregional control. CONCLUSIONS: The combination of ki67 expression and p16 expression status may allow prediction of local control more accurately than p16 expression status alone.

Heart valve surgery in hemodialysis-dependent patients: nutrition status impact on surgical outcome.

Valve surgery in hemodialysis-dependent patients is associated with postoperative complications and a high mortality rate, and such patients frequently suffer cachexia. This study aimed to determine pre- and intraoperative risk factors associated with in-hospital mortality and long-term survival in hemodialysis-dependent patients undergoing heart valve surgery from the viewpoint of nutrition status. Eighty-seven hemodialysis-dependent patients who underwent valve surgery between January 1998 and October 2015 were retrospectively reviewed. Thirty-seven potential perioperative risk factors were evaluated. The in-hospital mortality rate was 12.6 % (11 patients). Univariate analysis identified New York Heart Association Functional Classification III or IV, emaciation (body mass index <17.6 kg/m(2)), total cholesterol <120 mg/dl, serum albumin <3.0 mg/dl, emergent/urgent surgery, and intraoperative blood transfusion >3000 ml as predictors of in-hospital death. Multivariate logistic regression analysis confirmed low serum albumin <3.0 mg/dl (hazard ratio 7.22; p = 0.032) and emergent/urgent operation (hazard ratio 43.57; p = 0.035) as independent predictors of in-hospital death. The 1- and 3-year actuarial survival rates were 64.9 ± 5.4 and 51.8 ± 5.8 %, respectively. Long-term survival estimated by log-rank test was negatively impacted by anemia (hemoglobin <10 mg/dl), low serum albumin, emergent/urgent operation, and infective endocarditis. Multivariate analysis using Cox proportional hazards modeling indicated low serum albumin (hazard ratio 2.12; p = 0.047) and emergent/urgent operation (hazard ratio 8.97; p = 0.0002) as independent predictors of remote death. Hypoalbuminemia and emergent/urgent operation are strong predictors of in-hospital and remote death. Malnutrition before surgery should be considered for operative risk estimation, and adequate preoperative nutrition management may improve surgical outcomes for hemodialysis-dependent patients.

Nondestructive elemental depth-profiling analysis by muonic X-ray measurement.

Elemental analysis of materials is fundamentally important to science and technology. Many elemental analysis methods have been developed, but three-dimensional nondestructive elemental analysis of bulk materials has remained elusive. Recently, our project team, dreamX (damageless and regioselective elemental analysis with muonic X-rays), developed a nondestructive depth-profiling elemental analysis method after a decade of research. This new method utilizes a new type of probe; a negative muon particle and high-energy muonic X-rays emitted after the muon stops in a material. We performed elemental depth profiling on an old Japanese gold coin (Tempo-Koban) using a low-momentum negative muon beam and successfully determined that the Au concentration in the coin gradually decreased with depth over a micrometer length scale. We believe that this method will be a promising tool for the elemental analysis of valuable samples, such as archeological artifacts.

Successful Pregnancy and Delivery After Radiation With Ovarian Shielding for Acute Lymphocytic Leukemia Before Menarche.

Total body irradiation is performed as a preconditioning regimen to inhibit graft-versus-host disease after bone marrow transplantation and to eradicate remaining tumor cells. However, these regimens result in delayed secondary sex characteristics and failure of ovarian function recovery, leading to amenorrhea and infertility. Herein, we report a case of an 11-year-old girl diagnosed with acute lymphocytic leukemia who received induction chemotherapy and prophylactic cranial irradiation. For bone marrow transplantation, she received total body irradiation of 12 Gy with uterine and ovarian shielding at 13 years of age. The patient remained in remission and menarche began at 14 years of age. At 23, she became pregnant and delivered a baby naturally with no abnormalities.

[Left Ventricular Rupture during Both Mitral and Aortic Valve Replacements].

A 73-year-old woman on hemodialysis was transferred to our hospital for surgical treatment of heart valve disease. She required both mitral and aortic valve replacement with mechanical valves, associated with tricuspid annuloplasty. After aortic de-clamping, a massive hemorrhage from the posterior atrioventricular groove was observed. Under repeated cardiac arrest, the left atrium was reopened, the implanted mitral prosthetic valve was removed and a type I left ventricular rupture (Treasure classification) was diagnosed. The lesion was directly repaired with mattress stitches and running sutures, using reinforcement materials such as a glutaraldehyde-treated bovine pericardium. To avoid mechanical stress by the prosthetic valve on the repaired site, a mechanical valve was implanted using a translocation method. The patient suffered from aspiration pneumonia and disuse atrophy for 3 months. However, she was doing well at 1 year post-operation.

[Surgical Treatment of Prosthetic Valve Endocarditis].

Between 2003 and 2014, at Jichi Medical University Hospital, 11 patients with prosthetic valve endocarditis (PVE) underwent re-operation. There was 1 in-hospital death and 2 late deaths. The cause of death was cirrhosis, heart failure and sepsis, respectively. Emergency surgery, previous double valve replacement (DVR) and Staphylococcus infection were common risk factors for all 3 cases. Two cases of patients that survived who underwent mitral valve replacement (MVR) and DVR for PVE after DVR were treated with multiple antibiotic courses for bacteremia associated with hemodialysis and colon cancer. One patient who underwent DVR after mitral valve plasty which was complicated with cerebral hemorrhage, had survived and was discharged. Of the aortic PVE patients, 2 cases of aortic valve replacement (AVR) using a mechanical valve, 1 case of aortic root replacement (ARR) using a mechanical valve, and 1 ARR using the homograft, were considered cured and never relapsed. A patient with aortic PVE, who underwent AVR after cesarean section for heart failure in birth period, has received ARR twice with the mechanical valve for recurrent pseudo-aneurysm of the left ventricular outflow tract. Since hemodialysis and colon cancer is a risk factor for recurrent PVE, it is necessary to consider the long-term administration of antibiotics after surgery.

Development of a non-destructive depth-selective quantification method for sub-percent carbon contents in steel using negative muon lifetime analysis.

The amount of C in steel, which is critical in determining its properties, is strongly influenced by steel production technology. We propose a novel method of quantifying the bulk C content in steel non-destructively using muons. This revolutionary method may be used not only in the quality control of steel in production, but also in analyzing precious steel archaeological artifacts. A negatively charged muon forms an atomic system owing to its negative charge, and is finally absorbed into the nucleus or decays to an electron. The lifetimes of muons differ significantly, depending on whether they are trapped by Fe or C atoms, and identifying the elemental content at the muon stoppage position is possible via muon lifetime measurements. The relationship between the muon capture probabilities of C/Fe and the elemental content of C exhibits a good linearity, and the C content in the steel may be quantitatively determined via muon lifetime measurements. Furthermore, by controlling the incident energies of the muons, they may be stopped in each layer of a stacked sample consisting of three types of steel plates with thicknesses of 0.5 mm, and we successfully determined the C contents in the range 0.20-1.03 wt% depth-selectively, without sample destruction.

[Obesity is a risk factor of young onset of acute aortic dissection and postoperative hypoxemia].

We reviewed the effect of obesity in the repair of type A acute aortic dissection (AAD). Between January, 2009 and June, 2010, repair of type A AAD was performed in 51 patients. We divided these patients into 2 groups according to body mass index( BMI). Twenty-two patients whose BMI was≥25 were classified as group O, and 29 patients whose BMI was<25 were classified as group N. The mean age of group O was younger than that in group N(60.2±11.9 versus 68.3±10.2 years, p=0.01). The incidence of postoperative hypoxemia was greater in group O than that in group N(81.8% versus 53.6 %, p=0.036). The intubation period was longer in group O than that in group N(8.0±7.1 days versus 3.7±3.1 days, p=0.014), and the intensive care unit (ICU) stay was longer in group O than that in group N(13.7±8.8 days versus 9.3±5.9 days, p=0.04). Obesity is thought to be a risk of young-onset of AAD and postoperative hypoxemia, as well as a prolonged intubation period and ICU stay.

[Primary pulmonary malignant melanoma].

The patients was 63-year-old man. He had a chest abnormally shadow pointed out in examination of March, 2012 and referred to our hospital for a close inspection. The chest computed tomography(CT)revealed a mass shadow of 60 mm in left lung. Bronchoscopic examination was done and it was diagnosed as non-small-cell lung cancer by cytology. The clinical stage was cT2bN1M0 and video-assistedthoracic surgery (VATS) left pneumonectomy with mediastinal lymph node dissection was performed. A lot of neoplastic cells which contained melanin in cytoplasm were recognized by pathology and the diagnosis of malignant melanoma was comfirmed. Lymph node metastasis were recognized in #10, #11, #12 and the pathological stage of a disease was pT2bN1M0, pStage IIB. Further examination to find another lesion after surgery was in vain suggesting primary site to be left lung. A adjuvant chemotherapy has not been done. Surgical resection of primary pulmonary malignant melanoma is reported with reference to literatures.

Characterization of Paecilomycescinnamomeus from the camellia whitefly, Aleurocanthus camelliae (Hemiptera: Aleyrodidae), infesting tea in Japan.

The whitefly, Aleurocanthus camelliae Kanmiya and Kasai (Hemiptera: Aleyrodidae), is an invasive species in Japan that was first discovered in 2004 on tea in Kyoto. Soon after its arrival epizootics of an entomopathogenic fungus were observed in populations of the whitefly in many tea-growing regions. Here we identify this fungus as Paecilomyces cinnamomeus (Petch) Samson and W. Gams (Hypocreales: Clavicipitaceae) based on morphological characteristics and molecular analyses. This is the first record of P. cinnamomeus in Japan and also the first time it has been recorded from the genus Aleurocanthus. A isolate of P. cinnamomeus caused greater than 50% and 90% infection in whitefly nymphs at 1×10(6) and 1×10(7)conidia/ml respectively, while the commercial mycoinsecticides Preferd® (Isaria fumosorosea) and Mycotal® (Lecanicillium muscarium) caused <10% infection at their recommended field rates (5×10(6) and 9×10(6)conidia/ml, respectively), suggesting that P. cinnamomeus may be more useful as a control agent than the currently available mycoinsecticides. Optimum and upper limit temperatures for in vitro growth of P. cinnamomeus isolates were 22.5-25°C and 32.5°C, respectively. At field rates, the fungicide thiophanate-methyl caused some inhibition of in vitro growth of P. cinnamomeus isolates, and the bactericide copper oxychloride and the insecticides tolfenpyrad and methidathion were strongly inhibitory. The findings obtained in this study will be useful in the development of microbial control programs using P. cinnamomeus against A. camelliae.

[Reoperative off-pump coronary revascularization via left thoracotomy using the PAS-Port system to the descending thoracic aorta: report of a case].

We performed redo-off-pump coronary artery bypass grafting( OPCAB) via a left thoracotomy using the PAS-Port system for proximal vein graft anastomoses in a patient with posterolateral myocardial ischemia. The patient was a 76-year-old man who had undergone coronary artery bypass grafting (CABG)[ left internal thoracic artery( LITA)-left anterior descending artery( LAD), saphenous vein graft(SVG)-posterior descending artery( 4PD), and SVG-postero-lateral branch( PL)] 14 years previously. Coronary angiogram showed that the LITA-LAD graft was patent but that the SVG-PL, left main trunk( LMT) and proximal right coronary artery(RCA) were occluded, and that there were 90% stenoses of LAD #7 and SVG-4PD anastomotic site. With catheter intervention therapy, stenosis of the SVG-#4PD was dilated. We then performed revascularization from the descending aorta to the second diagonal (D2) and PL with a saphenous vein graft via left thoracotomy using off-pump technique. To avoid descending aortic clamping, we used the PAS-Port system for proximal anastomosis. The postoperative course was uneventful and the patient was discharged on postoperative day 28. A redo-CABG is thought to be with high risk. Our procedure, however is safe and useful and can be an option for redo-CABG in the posterolateral area.

[Mitral valve repair for active infectious endocarditis].

Between December 2005 and November 2011, 11 patients with mitral valve regurgitation (MVR) resulting from native valve endocarditis underwent mitral valve plasty (MVP). These patients were aged 44.4 ± 11.3 years. The mean follow-up period of the patients was 3.1 ± 0.63 years. Five patients were men. Emergency or urgent surgery was required in 5 patients. Three patients were categorized as New York Heart Association( NYHA) functional class IV. Infection of the mitral valve, occurred in the anterior leaflet in 3 patients, the posterior leaflet in 5 patients, and the anterior-posterior leaflet in 3 patients. Nine patients had a resection suture technique. One patient had chordae replacement with expanded polytetrafluoroethylene (ePTFE), and 1 patient had replacement using the pericardium. All patients received ring annuloplasty with a partial flexible ring. After surgery, all patients were categorized as NYHA functional class I. There were no valve associated complications, no hospital deaths, no late deaths, and no reoperations. We conclude that MVP is an effective treatment for active infective endocarditis( AIE) with mitral regurgitation.

[Acute radiation injury].

Cell death due to DNA damage by ionizing radiation causes acute radiation injury of tissues and organs. Frequency and severity of the injuries increase according to dose increase, when the dose becomes more than threshold dose. The threshold dose of acute human radiation death is 1 Gy and LD50 of human is 4 Gy. Human dies due to the cerebrovascular syndrome, the gastrointestinal syndrome or the hematopoetic syndrome, when he received more than 20 Gy, 10-20 Gy or 3-8 Gy to his total body, respectively. Any tissue or organ, including embryo and fetus, does not show the acute injury, when it received less than 100 mSv. Acute injuries are usually reversible, and late injuries are sometimes irreversible.

[Emergency stent placement after descending aortic replacement with chronic aortic dissection].

A 49-year-old man with asymptomatic chronic aneurysmal dissection was admitted to our hospital. He had undergone ascending aortic replacement for type A aortic dissection 7 months before. We performed descending aortic replacement for chronic aneurysmal dissection. Renal dysfunction appeared 1 day after the operation. Contrast-enhanced computed tomography indicated that the true lumen was severely compressed by a false lumen, and that the origins of the renal artery were occluded. We performed emergency endovascular stent placement to dilate the true lumen. Immediately after this procedure, renal ischemia improved. The postoperative course was uneventful. An endovascular approach using bare stent can be a treatment option that is less invasive and prompter for a patient with renal ischemia resulting from aortic dissection.

[Aortic root rupture during an operation in a patient with acute aortic dissection].

A 73-year-old woman with acute aortic dissection (DeBakey type II) and cardiac tamponade was transferred to our emergency unit. She had a temporary blackout during transfer. An emergency operation was performed. We started core cooling with the superior vena cava, inferior vena cava, and transapical aortic cannulation. When the bladder temperature was 30.5 degrees C, esophageal temperature was 28.7 degrees C, and rectal temperature was 30.5 degrees C, the aortic root suddenly ruptured. We changed the arterial cannulation sites from the apex to the dissecting ascending aorta, and the ascending aorta was cross-clamped. However, the patient's pupils became dilated. Therefore, we started selective cerebral perfusion to avoid prolonged cerebral malperfusion. This procedure took approximately 30 minutes, from the aortic root rupture to selective perfusion. We performed both aortic root and ascending aortic replacement. After the operation, the patient had no neurological or other organ complications and she was discharged 11 days after surgery.