A new predictive parameter for dose-volume metrics in intensity-modulated radiation therapy planning for prostate cancer: Initial phantom study.

BACKGROUND: Organ-at-risk (OAR) sparing is often assessed using an overlap volume-based parameter, defined as the ratio of the volume of OAR that overlaps the planning target volume (PTV) to the whole OAR volume. However, this conventional overlap-based predictive parameter (COPP) does not consider the volume relationship between the PTV and OAR. PURPOSE: We propose a new overlap-based predictive parameter that consider the PTV volume. The effectiveness of proposed overlap-based predictive parameter (POPP) is evaluated compared with COPP. METHODS: We defined as POPP = (overlap volume between OAR and PTV/OAR volume) × (PTV volume/OAR volume). We generated intensity modulated radiation therapy (IMRT) based on step and shoot technique, and volumetric modulated arc therapy (VMAT) plans with the Auto-Planning module of Pinnacle3 treatment planning system (v14.0, Philips Medical Systems, Fitchburg, WI) using the American Association of Physicists in Medicine Task Group (TG119) prostate phantom. The relationship between the position and size of the prostate phantom was systematically modified to simulate various geometric arrangements. The correlation between overlap-based predictive parameters (COPP and POPP) and dose-volume metrics (mean dose, V70Gy, V60Gy, and V37.5 Gy for rectum and bladder) was investigated using linear regression analysis. RESULTS: Our results indicated POPP was better than COPP in predicting intermediate-dose metrics. The bladder results showed a trend similar to that of the rectum. The correlation coefficient of POPP was significantly greater than that of COPP in < 62 Gy (82% of the prescribed dose) region for IMRT and in < 55 Gy (73% of the prescribed dose) region for VMAT regarding the rectum (p < 0.05). CONCLUSIONS: POPP is superior to COPP for creating predictive models at an intermediate-dose level. Because rectal bleeding and bladder toxicity can be associated with intermediate-doses as well as high-doses, it is important to predict dose-volume metrics for various dose levels. POPP is a useful parameter for predicting dose-volume metrics and assisting the generation of treatment plans.

[Indocyanine Green Fluorescence Intraoperative Imaging for Fistula Identification of Pleuroperitoneal Communication by Continuous Ambulatory Peritoneal Dialysis:Report of a Case].

A 64-year-old female with chronic renal failure had been receiving continuous ambulatory peritoneal dialysis (CAPD). She developed acute hydrothorax in the right pleural cavity 1 year after the commencement of CAPD. Scintigraphy revealed a diagnosis of pleuroperitoneal communication, and we performed video-assisted thoracoscopic surgery. We infused a dialysis solution containing indocyanine green (ICG) through CAPD catheter. Near-infrared fluorescence thoracoscopy revealed a fistula that could not be identified by white light. We sutured the fistula covered with a polyglycolic acid sheet and fibrin glue. The CAPD was able to be resumed 8 days after surgery, and there was no recurrence of pleural effusion 10 months since surgery. Identification of the diaphragmatic fistula is important in the treatment of pleuroperitoneal communication. This technique using near-infrared fluorescence thoracoscopy with ICG was useful in identifying the fistula, and it emitted sufficient fluorescence even at low concentration ICG.

[Surgical Treatment to Castleman's Disease after Embolization of Feeding Vessels].

A 48-year-old woman with an abnormal shadow on chest X-ray was referred to our institution. Contrast-enhanced chest computed tomography( CT) showed a large mass, 4.4 cm in diameter, in the right upper mediastinum. Castleman's disease was suspected, and several vessels flowing into the tumor were identified. Since severe intraoperative bleeding was expected, preoperative embolization of the feeding vessels was performed, followed by thoracotomy and tumor extirpation. The amount of blood loss was 50 ml. The pathological diagnosis was Castleman's disease, hyaline vascular type.

Hand preference in unimanual and bimanual coordinated tasks in wild western lowland gorillas (Gorilla gorilla gorilla) feeding on African ginger (Zingiberaceae).

OBJECTIVES: Bimanual coordinated behaviors are critical for detecting robust individual hand preference in nonhuman primates but are particularly challenging to observe in the wild. This study focuses on spontaneous feeding behavior on African ginger (Aframomum sp. and Renealmia sp.), which involves a unimanual task (reaching and pulling out a ginger stem) and a bimanual coordinated task (extracting pith from a ginger stem) by wild western lowland gorillas. MATERIALS AND METHODS: Study subjects were 21 gorillas in the Moukalaba-Doudou National Park, Gabon. We examined whether they exhibit significant hand preference at the individual and group levels for both tasks. RESULTS: Sixteen gorillas showed significant hand preference in the unimanual task, whereas all 21 individuals showed significant hand preference in the bimanual coordinated task. Hand preference was significantly stronger in the bimanual coordinated task than in the unimanual task. It is noteworthy that gorillas showed a significant right-hand preference at the group level for the bimanual task (roughly 70% of the subjects). DISCUSSION: This study confirmed that bimanual coordinated tasks are more sensitive in detecting hand preferences in nonhuman primates. In addition to the bimanual nature of the task, the precision grip for processing and the importance of African ginger as a food resource might influence the expression of hand preference. Evidence of a group-level right-hand preference may support the "postural origins theory." Because all wild African great apes feed on the pith of African ginger, comparing this task and its hand preferences can contribute toward a better understanding of the evolution of handedness in Hominidae.

A method to identify pulmonary intersegmental planes with intravenous vitamin B2 injection.

PURPOSE: The present study investigated whether the pulmonary intersegmental planes could be identified with the intravenous injection of vitamin B2 using a fluorescent camera and whether this method can be used instead of the inflation-deflation technique or the intravenous indocyanine green (ICG) method. METHODS: In experiment 1, the vitamin B2 was intravenously injected to visualize the pulmonary intersegmental plane and perform segmentectomy, and the visualized pulmonary intersegmental line was then compared to the inflation-deflation line in six pigs. In experiment 2, using six pigs, the fluorescent area and duration of fluorescence were compared after the intravenous injection of vitamin B2 and ICG in the same animals. RESULTS: In all animals in experiment 1, it was possible to clearly detect yellow-green fluorescence in the lung, in segments other than the one intended for resection, for at least 60 min. Moreover, the line visualized with vitamin B2 fluorescence matched the inflation-deflation line in all animals. In experiment 2, the area of vitamin B2 fluorescence corresponded to the area of ICG fluorescence in each animal. CONCLUSIONS: The visualization of fluorescence after the intravenous injection of vitamin B2 using a fluorescent camera was a simple, safe, and accurate method for detecting intersegmental planes in a pig model. This method can be an alternative to the inflation-deflation technique and the intravenous ICG method.

Quantum Walks of a Phonon in Trapped Ions.

We report the observation of the quantum walks of a phonon, a vibrational quantum, in a trapped-ion crystal. By employing the capability to prepare and observe the localized wave packet of a phonon, the propagation of a single radial local phonon in a four-ion linear crystal is observed with single-site resolution. The results show an agreement with numerical calculations, indicating the predictability and reproducibility of the phonon system. These characteristics may contribute advantageously in the advanced studies of quantum walks, as well as boson sampling and quantum simulation.

Dynamic-Ventilatory Digital Radiography in Air Flow Limitation: A Change in Lung Area Reflects Air Trapping.

OBJECTIVE: The aim of this study was to determine the utility of dynamic-ventilatory digital radiography (DR) for pulmonary function assessment in patients with airflow limitation. METHODS: One hundred and eighteen patients with airflow limitation (72 patients with lung cancer before surgery, 35 patients with chronic obstructive pulmonary disease [COPD], 6 patients with asthma, and 5 patients with asthma-COPD overlap syndrome) were assessed with dynamic-ventilatory DR. The patients were instructed to inhale and exhale slowly and maximally. Sequential chest X-ray images were captured in 15 frames per second using a dynamic flat-panel imaging system. The relationship between the lung area and the rate of change in the lung area due to respiratory motion with respect to pulmonary function was analyzed. RESULTS: The rate of change in the lung area from maximum inspiration to maximum expiration (Rs ratio) was associated with the RV/TLC ratio (r = 0.48, p < 0.01) and the percentage of the predicted FEV1 (r = -0.33, p < 0.01) in patients with airflow limitations. The Rs ratio also decreased in an FEV1-dependent manner. CONCLUSION: The rate of change in the lung area due to respiratory motion evaluated with dynamic DR reflects air trapping. Dynamic DR is a potential tool for the comprehensive assessment of pulmonary function in patients with COPD.

Extractive foraging on hard-shelled walnuts and variation of feeding techniques in wild Japanese macaques (Macaca fuscata).

Extractive foraging is considered a key selective pressure for the evolution of primate cognitive abilities-the extractive foraging hypothesis. Although tool-use and substrate-use are representatives of the foraging strategy, some primates engage in extractive foraging without external objects. Manual processing skills of prickly foods have been described in some species, whereas there are few studies on other type of food defenses. Here, I describe extractive foraging of hard-shelled walnuts by wild Japanese macaques (Macaca fuscata), focusing on whether they accomplish the tasks only by their physical strength or require manual and/or oral processing skills to crack open the walnut shells. The study subjects comprised all members of troop B1 and three nontroop males in Kinkazan Island, Japan. Walnut feeding was observed during the main walnut seasons (September-December) when the troop visited walnut patches for 79 days in 2 years. I categorized the walnut feeding behavior into complete cracking and partial cracking. The number of times the five behavioral elements in the cracking stage occurred were counted from complete cracking. All six adult males and 11 of the 17 adult/adolescent females showed complete cracking, while the remaining females were never observed exhibiting this activity, despite their physical maturity. I observed four clearly distinguishable cracking methods during walnut feeding in the 17 subjects. The compositions of five behavioral elements were different in each method. These results suggest that walnut feeding by Japanese macaques is not only by brute force but requires the acquisition of at least one of four cracking methods for the achievement of complete cracking. In particular, females need to compensate for their physical inferiority by increasing walnut manipulations. To my knowledge, this is the first detailed description on feeding techniques in primates to overcome hard-shelled obstacles without the use of tools and even substrates.

Quantitative analysis of treatments using real-time image gated spot-scanning with synchrotron-based proton beam therapy system log data.

A synchrotron-based real-time image gated spot-scanning proton beam therapy (RGPT) system with inserted fiducial markers can irradiate a moving tumor with high accuracy. As gated treatments increase the beam delivery time, this study aimed to investigate the frequency of intra-field adjustments corresponding to the baseline shift or drift and the beam delivery efficiency of a synchrotron-based RGPT system. Data from 118 patients corresponding to 127 treatment plans and 2810 sessions between October 2016 and March 2019 were collected. We quantitatively analyzed the proton beam delivery time, the difference between the ideal beam delivery time based on a simulated synchrotron magnetic excitation pattern and the actual treatment beam delivery time, frequency corresponding to the baseline shift or drift, and the gating efficiency of the synchrotron-based RGPT system according to the proton beam delivery machine log data. The mean actual beam delivery time was 7.1 min, and the simulated beam delivery time in an ideal environment with the same treatment plan was 2.9 min. The average difference between the actual and simulated beam delivery time per session was 4.3 min. The average frequency of intra-field adjustments corresponding to baseline shift or drift and beam delivery efficiency were 21.7% and 61.8%, respectively. Based on our clinical experience with a synchrotron-based RGPT system, we determined the frequency corresponding to baseline shift or drift and the beam delivery efficiency using the beam delivery machine log data. To maintain treatment accuracy within ± 2.0 mm, intra-field adjustments corresponding to baseline shift or drift were required in approximately 20% of cases. Further improvements in beam delivery efficiency may be realized by shortening the beam delivery time.

Analysis of treatment process time for real-time-image gated-spot-scanning proton-beam therapy (RGPT) system.

We developed a synchrotron-based real-time-image gated-spot-scanning proton-beam therapy (RGPT) system and utilized it to clinically operate on moving tumors in the liver, pancreas, lung, and prostate. When the spot-scanning technique is linked to gating, the beam delivery time with gating can increase, compared to that without gating. We aim to clarify whether the total treatment process can be performed within approximately 30 min (the general time per session in several proton therapy facilities), even for gated-spot-scanning proton-beam delivery with implanted fiducial markers. Data from 152 patients, corresponding to 201 treatment plans and 3577 sessions executed from October 2016 to June 2018, were included in this study. To estimate the treatment process time, we utilized data from proton beam delivery logs during the treatment for each patient. We retrieved data, such as the disease site, total target volume, field size at the isocenter, and the number of layers and spots for each field, from the treatment plans. We quantitatively analyzed the treatment process, which includes the patient load (or setup), bone matching, marker matching, beam delivery, patient unload, and equipment setup, using the data obtained from the log data. Among all the cases, 90 patients used the RGPT system (liver: n = 34; pancreas: n = 5; lung: n = 4; and prostate: n = 47). The mean and standard deviation (SD) of the total treatment process time for the RGPT system was 30.3 ± 7.4 min, while it was 25.9 ± 7.5 min for those without gating treatment, excluding craniospinal irradiation (CSI; head and neck: n = 16, pediatric: n = 31, others: n = 15); for CSI (n = 11) with two or three isocenters, the process time was 59.9 ± 13.9 min. Our results demonstrate that spot-scanning proton therapy with a gating function can be achieved in approximately 30-min time slots.

[Surgical Treatment of Pectus Excavatum in Patients with Marfan Syndrome Associated with Vertebral or Cardiovascular Disease].

Surgical treatment is often required in patients with Marfan syndrome presenting with scoliosis or cardioaortic disease. If these patients present with pectus excavatum, surgery for spinal deformity correction or chest wall closure during cardioaortic surgery can cause thoracic organ compression secondary to narrowing of the thorax resulting in hemodynamic and respiratory compromise. Cardiovascular complications serve as prognostic factors in patients with Marfan syndrome, and surgical treatment is often required in these cases. In our case series involving 4 patients, 2 patients with pectus excavatum and scoliosis underwent a Nuss procedure followed by safe and successful spinal correction surgery 6 months later. A Nuss procedure was also performed in a patient complicated with sinus of Valsalva dilatation, and thoracotomy was performed before cardioaortic surgery. Another patient with a complication of pectus excavatum and acute deterioration of cardiac status underwent concomitant repair with sternal elevation using an AO plate and cardioaortic surgery. In patients with Marfan syndrome presenting with pectus excavatum complicated by scoliosis or cardioaortic disease, it is necessary to consider concomitant or staged repair depending on the disease condition.

Patient-derived xenograft models of non-small cell lung cancer for evaluating targeted drug sensitivity and resistance.

Patient-derived xenograft (PDX) models are a useful tool in cancer biology research. However, the number of lung cancer PDX is limited. In the present study, we successfully established 10 PDX, including three adenocarcinoma (AD), six squamous cell carcinoma (SQ) and one large cell carcinoma (LA), from 30 patients with non-small cell lung cancer (NSCLC) (18 AD, 10 SQ, and 2 LA), mainly in SCID hairless outbred (SHO) mice (Crlj:SHO-Prkdcscid Hrhr ). Histology of SQ, advanced clinical stage (III-IV), status of lymph node metastasis (N2-3), and maximum standardized uptake value ≥10 when evaluated using a delayed 18 F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) scan was associated with successful PDX establishment. Histological analyses showed that PDX had histology similar to that of patients' surgically resected tumors (SRT), whereas components of the microenvironment were replaced with murine cells after several passages. Next-generation sequencing analyses showed that after two to six passages, PDX preserved the majority of the somatic mutations and mRNA expressions of the corresponding SRT. Two out of three PDX with AD histology had epidermal growth factor receptor (EGFR) mutations (L858R or exon 19 deletion) and were sensitive to EGFR tyrosine kinase inhibitors (EGFR-TKI), such as gefitinib and osimertinib. Furthermore, in one of the two PDX with an EGFR mutation, osimertinib resistance was induced that was associated with epithelial-to-mesenchymal transition. This study presented 10 serially transplantable PDX of NSCLC in SHO mice and showed the use of PDX with an EGFR mutation for analyses of EGFR-TKI resistance.

[Utility of Partial Splenic Embolization Prior to Lung Resection in Patients Demonstrating Platelet Transfusion Refractoriness Due to Hypersplenism].

It is often difficult to control perioperative bleeding in patients with liver cirrhosis and concurrent thrombocytopenia and coagulation factor deficiency. Partial splenic embolization (PSE), an auxiliary treatment strategy in management of liver cirrhosis and hepatocellular carcinoma, can not only increase platelets but also improve liver function. With advances in interventional radiology, PSE is a safer and more reliable procedure compared to a splenectomy. We present the case of a 69-year-old man diagnosed with left lung cancer, with thrombocytopenia, and hepatitis C virus-related cirrhosis. Although he was administered prophylactic platelet transfusion prior to operation, he was noted to be refractory to platelet transfusion. PSE was performed to improve his thrombocytopenia, following which we could safely perform left upper lobectomy of the lung and ND2a-1 lymph node dissection without any major bleeding. PSE is useful induction therapy to provide a wider choice of treatment options for patients with thrombocytopenia.

[Congenital Bronchial Atresia Requiring Differentiation from Intralobar Sequestration].

We reported a case of bronchial atresia requiring differentiation from the intralobar sequestration. A 42-year-old man was referred to our institution with suspicion of intralobar sequestration, based on a 3-dimensional computed tomography (CT) angiography that showed abnormal blood vessels from the right inferior phrenic artery flowing into the right lower lobe. CT revealed a lesion between S9 and S10 wherein there were refluxed blood vessels from A9 without an accompanying bronchus, with polycysts and emphysematous changes. Ventilation-perfusion scintigraphy revealed a reduction in uptake in the same sites. He was diagnosed as congenital bronchial atresia preoperatively, and we performed a right basal segmentectomy. Pathological examination confirmed the bronchiectasis and emphysematous changes in the lung parenchyma, but malignant findings were not confirmed.

[A Recurrent Case of Thymic Adenocarcinoma Effectively Treated with S-1 Over a Long-Term Period].

A 61-year-old woman with an abnormal radiograph shadow in her anterior mediastinum was admitted to our hospital and underwent an extended thymectomy. The pathological diagnosis of the tumor was a non-papillary adenocarcinoma of the thymus in pathological stage IV b using the Masaoka classification owing to mediastinal lymph node metastasis. We found parasternal lymph node metastases 5 months after her first operation, and subsequently, she underwent surgery and adjuvant radiotherapy. We found systemic lymph node metastases and metastatic lesions in distant organs, including her lungs, brain, and kidney 27 months after her first operation. Systemic chemotherapy, such as carboplatin plus paclitaxel and an ADOC regimen were not very effective, so we performed immunohistochemical staining of the primary thymic adenocarcinoma. The levels of both thymidylate synthase and dihydropyrimidine dehydrogenase were low; therefore, we started S-1 100mg/body (2 weeks of administration, 1 week of withdrawal)31 months after her first operation. She entered complete remission 6 months after the initiation of S-1. We surgically resected her solitary lung metastasis 13 months after initiation of S-1, and then continued the S-1 treatment. There was no recurrence for more than 2 years after the lung surgery. We believe that when the expression levels of thymidylate synthase or dihydropyrimidine dehydrogenase are low in cases of recurrent thymic adenocarcinoma, S-1 may be able to induce an effective response.

Lymph node ratio as a prognostic factor in patients with pathological N2 non-small cell lung cancer.

BACKGROUND: The aim of this study was to investigate whether the lymph node ratio (LNR) was associated with the prognosis of patients, who underwent surgery for pathological N2 non-small cell lung cancer (NSCLC). METHODS: A total of 182 patients were diagnosed with pathological N2 disease and underwent complete resection surgeries with systematic lymphadenectomies. We counted the number of positives and removed lymph nodes to calculate a ratio between them (LNR). We also investigated the association between skip mediastinal lymph node metastasis and survival. RESULTS: Univariate analysis of survival in patients with N2 NSCLC showed that the T factor, clinical N factor, and LNR were significant prognostic factors. Multivariate analyses showed that the clinical N stage and LNR were significant independent prognostic factors for patients with pathological N2 NSCLC. Patients with a clinical lymph node status of 0 (cN0) and LNR ≤0.22 showed a significantly higher survival rate than patients with a cN1-2 and LNR ≥0.22 and 5-year survival rates were 47.1 and 10.3%, respectively (p < 0.0001). CONCLUSIONS: LNR is an important prognostic factor for poor outcome following surgery in patients with N2 disease. The combination of the LNR and cN status provides a valuable prognostic tool.

[Lung Cancer Incidentally Detected by a Subcutaneous Nodule at the Drainage Site for Pneumothorax].

A 43-year-old male patient underwent thoracic drainage for the treatment of right pneumothorax. After 6 months, the patient visited our department because of a subcutaneous nodule found at the drainage site. Chest computed tomography revealed a mass lesion associated with a cavity in the right upper lobe of the lung and a subcutaneous nodule. Surgical resection was performed and both the pulmonary lesion and subcutaneous nodule were found to be adenocarcinoma. Although immunohistochemical analysis suggested that the pulmonary lesion was primary lung cancer, there were neither intrathoracic exposure of the tumor nor tumor cells in the pleural lavage cytology. The expression pattern of subcutaneous tumor in the right chest was slightly different from that of the lung lesion by immunohistochemistry. Therefore, it was difficult to determine whether this subcutaneous nodule was a tumor implantation through the drainage procedure or subcutaneous metastasis from the primary tumor.

Intrathoracic vagus nerve tumor: case report and review of the literature.

We present the case of a 23-year-old female with benign intrathoracic vagal neurofibroma associated with von Recklinghausen's disease. We reviewed 87 other neurogenic tumors of the intrathoracic vagus nerve and discuss the incidence rate of complications, especially the relationship between tumor location, tumor size, and preservation of the nerve in this case report.

Death of a one-armed blackback male due to severe injuries in a group of wild western lowland gorillas (Gorilla gorilla gorilla) in Moukalaba-Doudou National Park, Gabon.

The survival of limb-disabled primates in the wild has been widely reported. Nevertheless, their ultimate fate is little documented. It is important to understand the influence of limb disability on primate survival from a conservation perspective, as many African great apes suffer from limb injuries caused by entrapment in snares. Here, we report the death of a one-armed blackback male in a large one-male group of wild western lowland gorillas. The subject was a blackback male (14 years old) named Dodo, who lost his right forearm in August 2008. On 8 December 2019, Dodo was found to have suffered serious bleeding injuries to the front of his body, including large lacerations and puncture wounds. On 14 December his corpse was found in the forest. We provide evidence to suggest that his injuries were more likely caused by intraspecific aggression, though a predatory attack by a leopard could not be completely ruled out. His one-armed disability could have made him more vulnerable to attack from either a gorilla or leopard and led to his fatal injury. This report shows that a gorilla who had previously overcome a disability in one arm in childhood may die prematurely, in part, owing to this disability in young adulthood.

Prognostic Significance of CONUT Score in Elderly NSCLC.

PURPOSE: This study evaluated the Controlling Nutritional Status (CONUT) score as a prognostic predictor in elderly non-small cell lung cancer (NSCLC) patients with surgical resection. METHODS: Overall, 114 patients over 80 years old undergoing curative resection for NSCLC were retrospectively analyzed. Receiver operating characteristic (ROC) analysis was conducted to evaluate the capacity of immune-inflammatory markers to predict overall survival (OS). Cox-proportional hazards regression analysis was implemented to investigate prognostic markers for OS. RESULTS: Based on ROC curves, the CONUT score was found to be the most valuable prognostic marker (area under the curve = 0.716). The high CONUT (≥2) group included 54 patients, and the low CONUT (0 or 1) group included 60 patients. The high CONUT group had poorer prognosis rates compared to the low CONUT group with regard to OS (5-year OS: 46.3% vs. 86.0%, p = 0.0006). In the multivariate data analysis, histology, lymphatic invasion, and CONUT score (hazard ratio: 4.23, p = 0.0003) were found to be exclusive and independent prognostic markers for OS. CONCLUSION: Preoperatively, the CONUT score can be used as a novel prognostic marker in elderly NSCLC patients. CONUT evaluations can also be used to design nutritional interventions to improve patient outcomes.