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Introduction Video-assisted thoracoscopic surgery is widely used for resecting early-stage non-small cell lung cancer. Segmentectomy and subsegmentectomy require a thorough knowledge of the 3-D bronchovascular anatomy of the lung. Previously, our department reported using a 3-D pulmonary model of a patient for thoracoscopic surgical treatment of non-small cell lung cancer. This study investigates multi-segmentectomy for patients with non-small cell lung cancer. Methods Between July 2001 and January 2012, 943 patients underwent surgical resection of primary lung cancer. Of these, 11 patients had video-assisted thoracoscopic multi-subsegmentectomy. For preoperative simulation, virtual 3-D pulmonary models have been constructed since July 2001. Results The mean age of patients was 69.2 ± 11.6 years (range, 43.0–86.0 years). Histological diagnoses included adenocarcinoma in eight patients, squamous cell carcinoma in two, and large cell carcinoma (neuroendocrine tumor) in one. Tumor size was ≤ 10 mm in one patient, 11–15 mm in four, 16–20 mm in four, and 21–25 mm in two. One patient was treated without lymphadenectomy, nine patients underwent additional hilar lymphadenectomy, and one patient underwent additional hilar and mediastinal lymphadenectomy. No patients were converted to thoracotomy. All patients had a macroscopically negative surgical margin. The pathological stage of patients was IA in nine patients, IB in one, and IIA in one. No pulmonary vessel injuries were found. Three patients had a prolonged lung air leak (> 6 days). Conclusion Using a reconstructed 3-D pulmonary model, this study demonstrates that video-assisted thoracoscopic multiple subsegmentectomy is feasible with adequate margins in selected patients.

症例は51歳,男性,建築大工.釘を口に咥えて作業していた際,突然咳込み釘を何本か誤嚥した.当日は放置していたが翌日朝になり血痰が出現し当院受診.胸部X線にて左下肺野に1本,腹部X線で消化管に2本計3本の誤嚥された釘が認められた.胸部CTでは左肺S9領域,気管支内に釘と思われる影が認められ,腹部CTでは十二指腸水平脚部および空腸内に釘と思われる影が認められた.気管支内の1本に関しては,自然喀出は困難と判断,気管支鏡下異物除去術を施行.消化管内の2本については禁食にし緊急手術に備えながら自然排泄を期待して経過観察とした.気管支内の釘を除去した後には血痰はみられず,消化管内2本の釘のうち1本は入院翌日に,もう1本は6日後に自然排泄された.その後は特に問題なく退院となった.

We have reported the upregulation of MARCO, a member of the class A scavenger receptor family, on the surface of murine and human dendritic cells (DCs) pulsed with tumor lysates. Exposure of murine tumor lysate-pulsed DCs to an anti-MARCO antibody led to loss of dendritic-like processes and enhanced migratory capacity. In this study, we have further examined the biological and therapeutic implications of MARCO expression by DCs. DCs generated from the bone marrow (bm) of MARCO knockout (MARCO⁻/⁻) mice were phenotypically similar to DCs generated from the bm of wild-type mice and produced normal levels of IL-12 and TNF-α when exposed to LPS. MARCO⁻/⁻ DCs demonstrated enhanced migratory capacity in response to CCL-21 in vitro. After subcutaneous injection into mice, MARCO⁻/⁻ TP-DCs migrated more efficiently to the draining lymph node leading to enhanced generation of tumor-specific IFN-γ producing T cells and improved tumor regression and survival in B16 melanoma-bearing mice. These results support targeting MARCO on the surface of DCs to improve trafficking and induction of anti-tumor immunity.

Resection of lung metastasis from malignant tumor of liver, biliary duct and pancreas has various controversial problems. These problems are that many patients have a progressive disease and there are few patients who can have resectable lesion. Generally the prognosis of these diseases is poor. In addition, the effect of pulmonary resection for lung metastasis from malignant tumor of liver, biliary duct and pancreas is unclear. We set out to investigate the outcome and usefulness of surgery in this group.From January 1999 to November 2012, 18 patients underwent a total of 21 surgeries. There were 11 men and 7 women with mean age of 66.6±10( range, 43 to 78). Primary diseases of these patients were hepatocellular carcinoma in 5, cholangiocellular carcinoma in 1, cholangiocarcinoma in 2 and pancreatic cancer in 10 patients.Disease-free interval from 1st local therapy such as surgical treatment for primary lesion was 50.8±28.7(range, 19 to 107) months. Numbers of lung metastasis were 1 in 15, 2 in 4 patients and 3 in 1 patient. Many metastasis were in right lower lobe. Numbers of wedge resection were 13, segmentectomy were 4, lobectomy were 2 in these patients. Average of total survival time was 38±34 months. Four patients were dead. The 14 patients are alive and 7 patients had no recurrence. Adjuvant therapy such as chemotherapy was important. One-year all over survival rate after 1st pulmonary resection was 88%, 3 or 5-years was 73%. We think that it's was good result.There is a possibility that surgery for metastatic lung tumor from malignant tumor of liver, biliary duct and pancreas is useful by control of primary lesion and selecting of patients and adjuvant therapy such as chemotherapy.

Video-assisted thoracoscopic surgery is widely used for resecting early-stage non-small cell lung cancer. Segmentectomy and subsegmentectomy require a thorough knowledge of the 3-D bronchovascular anatomy of the lung. Previously, our department reported using a 3-D pulmonary model of a patient for thoracoscopic surgical treatment of non-small cell lung cancer. This study investigates multi-segmentectomy for patients with non-small cell lung cancer.Between July 2001 and January 2012, 943 patients underwent surgical resection of primary lung cancer. Of these, 11 patients had video-assisted thoracoscopic multi-subsegmentectomy. For preoperative simulation, virtual 3-D pulmonary models have been constructed since July 2001.The mean age of patients was 69.2 ± 11.6 years (range, 43.0-86.0 years). Histological diagnoses included adenocarcinoma in eight patients, squamous cell carcinoma in two, and large cell carcinoma (neuroendocrine tumor) in one. Tumor size was ≤ 10 mm in one patient, 11-15 mm in four, 16-20 mm in four, and 21-25 mm in two. One patient was treated without lymphadenectomy, nine patients underwent additional hilar lymphadenectomy, and one patient underwent additional hilar and mediastinal lymphadenectomy. No patients were converted to thoracotomy. All patients had a macroscopically negative surgical margin. The pathological stage of patients was IA in nine patients, IB in one, and IIA in one. No pulmonary vessel injuries were found. Three patients had a prolonged lung air leak ( 6 days).Using a reconstructed 3-D pulmonary model, this study demonstrates that video-assisted thoracoscopic multiple subsegmentectomy is feasible with adequate margins in selected patients.

2-(Pyrid-2'-yl)amino-3-chloro-5,6-dicyanopyrazines (IIa, IId, and IIe) and 2-(pyrid-2'-yl)amino-3-chloro-6-nitroquinoxalines (Va-c) were isolated for the first time in the course of the reaction of 2,3-dichloro-5,6-dicyanopyrazine (I) and 2,3-dichloro-6-nitroquinoxaline (IVa), respectively, with 2-aminopyridines. Furthermore, the yield of pyrido[1',2': 1,2]imidazo[4,5-b]quinoxalines was remarkably improved due to the modification of the reaction conditions

We reported that murine tumor lysate-pulsed dendritic cells (TP-DC) could elicit tumor-specific CD4(+) and CD8(+) T cells in vitro and in vivo. In some limited cases, TP-DC treatments in vivo could also result in regression of established subcutaneous tumors and lung metastases. By gene array analysis, we reported a high level of expression of a novel member of the cell surface class A scavenger receptor family, MARCO, by murine TP-DC compared to unpulsed DC. MARCO is thought to play an important role in the immune response by mediating binding and phagocytosis, but also in the formation of lamellipodia-like structures and dendritic processes. We have now examined the biologic and therapeutic implications of MARCO expressed by TP-DC. In vitro exposure of TP-DC to a monoclonal anti-MARCO antibody resulted in a morphologic change of rounding with disappearance of dendritic-like processes. TP-DC remained viable after anti-MARCO antibody treatment; had little, if any, change in production of IL-10, IL-12p70 and TNF-alpha; but demonstrated enhanced migratory capacity in a microchemotaxis assay. The use of a selective inhibitor showed MARCO expression to be linked to the p38 mitogen-activated protein kinase (MAPK) pathway. In vivo, anti-MARCO antibody treated TP-DC showed better trafficking from the skin injection site to lymph node, enhanced generation of tumor-reactive IFN-gamma producing T cells, and improved therapeutic efficacy against B16 melanoma. These results, coupled with our finding that human monocyte-derived DC also express MARCO, could have important implications to human clinical DC vaccine trials.

Northrop Grumman Corporation has made significant progress in the development of compact, high power, continuous operation solid state lasers for military applications during the past six years. The Joint High Power Solid State Laser (JHPSSL) program is nearing completion of its third phase; its key objective is to demonstrate a 100kW solid state laser with excellent beam quality. Northrop's unique scalable architecture coherently combines modular 15kW lasers to produce power levels of 100kW and beyond with excellent beam quality and run times. This paper describes the JHPSSL program history, Northrop's high power solid state laser architecture and our demonstrated results.

We are developing a 100-kW Nd:YAG cw solid-state laser system. Seven wavefrontcorrected 15-kW MOPA (master oscillator power amplifier) laser chains are phase locked to achieve a single aperture output beam with good beam quality.

A four-element fiber array has demonstrated 470 watts of coherently phased, linearly polarized light energy in a single far-field spot. Each element consists of a single-mode fiber-amplifier chain. Phase control of each element is achieved with a Lithium-Niobate phase modulator. A master laser provides a linearly polarized, narrow linewidth signal that is split into five channels. Four channels are individually amplified using polarization maintaining fiber power amplifiers. The fifth channel is used as a reference arm. It is frequency shifted and then combined interferometrically with a portion of each channel's signal. Detectors sense the heterodyne modulation signal, and an electronics circuit measures the relative phase for each channel. Compensating adjustments are then made to each channel's phase modulator. This effort represents the results of a multi-year effort to achieve high power from a single element fiber amplifier and to understand the important issues involved in coherently combining many individual elements to obtain sufficient optical power for directed energy weapons. Northrop Grumman Corporation and the High Energy Laser Joint Technology Office jointly sponsored this work.

We have developed a scalable architecture of phase-locked Nd:YAG master oscillator power amplifiers. In cw operation a 2×1 array emitted 19.0 kW with 30% optical efficiency and average beam quality of 1.73 × diffraction-limited.

The status of our coherently combined 7-element, high power fiber array will be presented. The architecture, the method of phase correction and the results obtained to date will be presented.

A four-element fiber array has been constructed to yield 8 watts of coherently phased, linearly polarized light energy in a single far field spot. Each element consists of a 2-W single-mode fiber-amplifier chain. Phase control of each element is achieved with a lithium-niobate phase modulator. A master laser provides a linearly polarized, narrow linewidth signal that is split into five channels. Four channels are individually amplified using polarization maintaining fiber power amplifiers. Frequency broadening of the signal is necessary to avoid stimulated Brillouin scattering. The fifth channel is used as a reference arm. It is frequency shifted and then combined interferometrically with a portion of each channel's signal. Detectors sense the heterodyne modulation signal, and an electronics circuit measures the relative phase for each channel. Compensating adjustments are then made to each channel's phase modulator. The stability of the optical train is an essential contributor to its success. A state-of-the-art interferometer was built with mountless optics. A lens array was constructed using nano-positioning tolerances, where each lens was individually aligned to its respective fiber to collimate its output and point it at a common far field spot. This system proved to be highly robust and handled any acoustic perturbations.

During the last decade, adoptive transfer of autologous γδ T cells has been paid much attention to as an alternative immunotherapy for several types of cancer. It has been reported that human γδ T cells have potent cytotoxic activity against many types of tumor cell lines or primary cultured cells in vitro. Clinical studies in patients with metastatic renal cell carcinoma and non-small cell lung carcinoma showed that infusion of autologous γδ T cells is feasible and well tolerated. One of the problems in this therapy, however, is the difficulty for culturing peripheral γδ T cells in patients with cancer. Compared with healthy individuals, stimulation with phosphoantigens or bisphosphonates results in less expansion of γδ T cells in some patients. The tendency can be remarkably seen especially in those who have lower number of γδ T cells in peripheral blood. It is still unclear whether it is a unique phenomenon caused by something of malignancy or just due to the culture methodology. In this study, we investigated the characteristics of peripheral Vγ9Vδ2 T cells in patients with gastrointestinal cancer including their phenotype, the percentage in PBMC, and the proliferation activity in response to synthetic phosphoantigen, 2-methyl-3-butenyl-1-pyrophosphate (2M3B1PP). PBMC were prepared from patients, and then the phenotype and the number of Vγ9Vδ2 T cells were measured by flow cytometry. To expand Vγ9Vδ2 T cells in vitro, PBMC were cultured in AIM-V medium supplemented with 100 IU/mL IL-2, 100μM 2M3B1PP, and 10% autologous plasma. The expansion of Vγ9Vδ2 T cells were also examined using flow cytometry. We found that the percentage of the Vγ9Vδ2 T cells in peripheral T cells varied a lot depending on the patients. While their percentage in healthy individual was approx. 1.5-9.0%, it exceeded 10% in some patients, and even over 20% in several patients. Phenotypic analysis revealed that almost all the Vγ9Vδ2 T cells in these particular patients were effector-memory type cells with CD45RA-/CD27-/CCR7- and they massively expanded by the stimulation with 2M3B1PP. These results suggest that Vγ9Vδ2 T cells in these patients have been constantly exposed and stimulated with some specific antigens. On the other hand, the percentage of Vγ9Vδ2 T cells in T cells of some patients was less than 1.0%, and in the conventional culture methods the cells' response to 2M3B1PP was too low for them to proliferate themselves. However, their proliferation rate markedly increased when PBMC were inoculated at the high density (i.e. 1.3 x 104 Vγ9Vδ2 T cells per cm2 or more). The high density culture for 14 days has made it possible to expand the number of Vγ9Vδ2 T cells to 100-1000 folds. We conclude that Vγ9Vδ2 T cells in patients with gastrointestinal cancer have the equivalent level of proliferation ability to healthy individual even though the initial percentage is low, and thus these cells could be a possible effector cell type in a novel immunotherapy for gastrointestinal cancer. Citation Format: Yasunobu Kobayashi, Mayuko Sakai, Izumi Fujita, Hiroshi Komine, Masanori Matsushita, Koichi Shimizu, Atsushi Aruga, Hirohito Kobayashi, Keishi Tanigawa. Phenotype and expansion profile of peripheral γδ T cells in patients with gastrointestinal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2793. doi:10.1158/1538-7445.AM2014-2793

A high average power, OPO based system has been developed for the purpose of generating output in the 2 - 5 µm mid-IR band. The system uses a cw diode array - pumped, Nd:YAG master oscillator power amplifier (MOPA) as the pump source and two tandem OPOs for wavelength conversion to the mid-IR. A Type II degenerate KTP OPO was used to convert the pump beam to 2.13 µm and a Type I near degenerate zinc germanium phosphite (ZGP) OPO was used to generate broadband radiation in the 3.7 - 4.1 and 4.4 - 4.8 µm wavelength range.

This report describes a 3-dimensional (3-D) video-assisted thoracoscopic lung resection guided by a 3-D video navigation system having a patient-specific 3-D reconstructed pulmonary model obtained by preoperative simulation. A 78-year-old man was found to have a small solitary pulmonary nodule in the left upper lobe in chest computed tomography. By a virtual 3-D pulmonary model the tumor was found to be involved in two subsegments (S1 + 2c and S3a). Complete video-assisted thoracoscopic surgery bi-subsegmentectomy was selected in simulation and was performed with lymph node dissection. A 3-D digital vision system was used for 3-D thoracoscopic performance. Wearing 3-D glasses, the patient's actual reconstructed 3-D model on 3-D liquid-crystal displays was observed, and the 3-D intraoperative field and the picture of 3-D reconstructed pulmonary model were compared.

interferometric method for studying thermal dephasing in these crystals yields preliminary estimates for average power scaling.Average power scaling of pulsed ON) devices requires a combination of greater pulse energies and higher pulse repetitionrates. Such an OPO may consist of a master oscillator and a power amplifier or a slave oscillator. The master oscillator sets thespectral and spatial properties at low power and energy levels; the power amplifier/slave oscillator provides the output scaling.Since the power amplifier/slave oscillator is exposed to a much greater thermal load, the overall efficiency depends strongly ondephasing.In LBO/BBO OPOs pumped at 308nm, pump absorption can lead to an appreciable thermal load as the average power levelincreases. As a result, the crystal may develop a temperature distribution that depends on such factors as crystal shape, thermal

Conversion efficiency, frequency shift, and thermal dephasing in beta-barium borate (BBO) and lithium borate (LBO) crystals have been investigated with ultraviolet lasers. A singly resonant, injection-seeded, BBO optical parametric oscillator (OPO) at 455 nm generated up to 0.55 W output when pumped by a frequency-tripled, Q-switched Nd:YAG laser with 2.3 W average power at 355 nm. Effects of thermal loading on BBO and LBO crystals were measured interferometrically by using a xenon chloride excimer laser as a UV source at 308 nm. Refractive index variations caused by UV absorption were analyzed to determine average power scaling limitations. OPO frequency shifts due to crystal heating by pump absorption were observed in BBO with a 308 nm pump laser. These results will be presented along with current progress on tunable visible OPO devices.

A new optical Doppler-velocimetry technique for seeded flow fields illuminated by a monochromatic laser light sheet has been developed. In contrast to conventional laser Doppler velocimetry based on scanned, point-by-point measurement, this technique yields global, simultaneous, quantitative visualization of the flow velocities over the illuminated plane. This technique is applied to a free-expansion jet at near sonic velocities in a small wind tunnel. 8 refs.

Pulsed optical parametric oscillators for generating visible and near-IR output were investigated to determine the prospects of average-power scaling. The devices used β-barium borate and lithium triborate crystals. Experimental results show that the combination of a low-energy master oscillator and a higher-energy slave oscillator can be configured for devices of medium average power.

2-(Pyrid-2'-yl)amino-3-chloro-5,6-dicyanopyrazines (IIa, IId, and IIe) and 2-(pyrid-2'-yl)amino-3-chloro-6-nitroquinoxalines (Va-c) were isolated for the first time in the course of the reaction of 2,3-dichloro-5,6-dicyanopyrazine (I) and 2,3-dichloro-6-nitroquinoxaline (IVa), respectively, with 2-aminopyridines. Furthermore, the yield of pyrido[1',2': 1,2]imidazo[4,5-b]quinoxalines was remarkably improved due to the modification of the reaction conditions

The CdHg excimer has received attention as a possible efficient visible laser medium. In the experiments described here, a pulsed tunable laser was used to excite the Cd(5 3P1) atomic state, which forms CdHg excimers in three‐body collisions with Hg and Ar. Gain and absorption measurements were performed by using an argon‐ion laser to probe several wavelengths within the 470‐nm excimer emission band. Net absorption was observed at all wavelengths investigated. Acoustic and thermal disturbances which might mimic absorption have been carefully considered and it is determined that these are not important. We conclude that the CdHg excimer exhibits net absorption within its 470‐nm emission band. These results cast considerable doubt on the possibility of efficient laser action in CdHg.

Narrowband ultraviolet radiation from a frequency‐doubled dye laser has been used to control the linewidth and polarization of a long pulse length, electron‐beam‐excited XeF laser. Linewidths of 0.004 nm have been achieved in the 353‐nm band of the XeF B→X laser transition. Over 90% of the energy in the free‐running laser pulse has been extracted in the narrowband injection‐locked pulse. Ratios of injection signal power to output laser power on the order of 1:5000 are adequate for efficient injection‐locking to occur.

Spectral correlation and phase locking properties of Raman conversion in inhomogeneous media are analyzed with a multi-mode model.

We have carried out experimental and theoretical investigations of beam quality improvement in forward Raman amplifiers. In appropriate conditions, efficient conversion of laser beams of poor spatial quality into Stokes beams with nearly diffraction-limited wave fronts can be realized. The results were obtained using a configuration with parallel copropagating pump and Stokes beams. A discharge-pumped XeCl laser with an output of 0.5 J in a 60-ns pulse was used to carry out the experiments. In the present experiments, a near diffraction-limited low-energy Stokes beam was generated in a superfluorescent oscillator. The first Stokes order output of this oscillator was injected with the pump beam in a Raman amplifier with a Fresnel number as high as 150. The wave front of the pump was distorted using aberrators of variable strength and spatial frequency content. In conditions of amplifier Fresnel number and pump beam distortion where phase distortions on the pump did not lead to significant intensity distortions in the amplifier, the Stokes beam quality was not affected by the saturated amplification process. Pulse shapes and phase front interferograms were obtained for the pump and Stokes. The results are in good agreement with 3-D wave-optics code simulations.

Pump energy conversion efficiencies of up to 50 percent have been obtained with output between 420 and 1160 nanometers using an ultraviolet excimer pump laser.

A one joule, 60 ns, XeCl laser pulse was compressed to 6 ns (FWHM) by a phase‐conjugated, stimulated‐Brillouin‐scattering compressor in SF6 with an efficiency of 50%. The Stokes seed beam was generated by focusing the pump beam into a Brillouin cell.

Tunable optical parametric oscillation in a beta-barium borate crystal has been achieved with a 308-nmXeCl pump laser source. Signal wavelengths between 422 and 477 nm have been generated by angle tuning at energy-conversion efficiencies of as much as approximately 10%.

We report the results of a theoretical and experimental investigation of two important properties of Raman converters. The first property is Raman beam cleanup, which refers to the generation of high-quality Stokes beams in a Raman amplifier pumped by laser beams of poor spatial quality. The second is nearly distortion-free amplification of aberrated Stokes beams in a Raman amplifier pumped by good-quality laser beams. A parallel beam geometry was used with collinear pump and Stokes beams. In both cases, excellent energy-conversion efficiencies into the first Stokes order, of the order of 60%, were demonstrated at high amplifier gains of 100 to 1000. The spatial characteristics of the amplified beams were found to be in good agreement with model predictions.