Surgery for pulmonary lesions in patients with a history of urinary tract transitional cell carcinoma.

BACKGROUND: There has been little information on the actual diagnosis of pulmonary lesions in patients with a history of urinary tract transitional cell carcinoma (TCC) and short- and long- outcomes of pulmonary resection for these patients. METHODS: In the present study, the data of 37 consecutive patients with a history of TCC who underwent pulmonary resection for solitary pulmonary lesions were reviewed, and the clinical factors and short- and long-term outcomes were analyzed. RESULTS: The study population included 35 male patients, and 2 female patients. The mean age was 72.5 years. Twenty patients (80%) were smokers and showed a high incidence of chronic obstructive pulmonary disease. Pulmonary lesions and primary TCC were detected simultaneously in 5 patients and metachronously in 32 patients. The median interval between treatment for primary TCC and the detection of pulmonary lesion was 43 months. The mean tumor diameter was 23 mm. The types of resection included lobectomy (n = 19), segmentectomy (n = 8), and partial resection (n = 10). Twelve of 37 patients (32%) developed postoperative complications. The pathological diagnoses included primary lung cancer (n = 28), pulmonary metastasis from TCC (n = 7), and others (n = 2). The 5-year overall survival rate for all patients was 72%. The 5-year overall survival rate of patients with primary lung cancer was 74%, while that of patients with pulmonary metastasis from TCC was 57%. CONCLUSIONS: Surgery can be proactively considered for treating pulmonary lesions in patients with a previous history of TCC, as it provides favorable long-term outcomes.

Familial multiple endocrine neoplasia type 1 with intrathoracic low-grade fibromyxoid sarcoma.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is a hereditary tumor syndrome characterized by endocrine tumors with mainly a parathyroid, pancreatic, or anterior pituitary origin. Low-grade fibromyxoid sarcoma (LGFMS) is a rare low-grade soft tissue tumor. There is one known report of a patient with MEN1 complicated by LGFMS, which is very rare. Our report represents the second documented case, providing valuable insights. CASE PRESENTATION: A 31-year-old man with the chief complaint of a cough underwent chest contrast-enhanced computed tomography, which revealed a giant hypoabsorptive tumor with a maximum diameter of 23 cm in the left thoracic cavity. The patient was diagnosed with MEN1, as he also possessed a pancreatic neuroendocrine tumor and parathyroid tumor, and because his father had been found to have MEN1. To control hypercalcemia, surgery for the parathyroid tumor was initially performed, followed by surgical resection of the giant thoracic tumor for diagnosis and treatment. Histopathological examination findings of the tumor resulted in a diagnosis of LGFMS. CONCLUSION: We experienced a very rare MEN1 with LGFMS. Although endocrine tumors generally occur more frequently in MEN1, non-endocrine tumors such as the present case should also be noted, reinforcing the importance of systemic imaging scrutiny in addition to early diagnosis and long-term follow-up of MEN1 patients.

In vivo induction of activin A-producing alveolar macrophages supports the progression of lung cell carcinoma.

Alveolar macrophages (AMs) are crucial for maintaining normal lung function. They are abundant in lung cancer tissues, but their pathophysiological significance remains unknown. Here we show, using an orthotopic murine lung cancer model and human carcinoma samples, that AMs support cancer cell proliferation and thus contribute to unfavourable outcome. Inhibin beta A (INHBA) expression is upregulated in AMs under tumor-bearing conditions, leading to the secretion of activin A, a homodimer of INHBA. Accordingly, follistatin, an antagonist of activin A is able to inhibit lung cancer cell proliferation. Single-cell RNA sequence analysis identifies a characteristic subset of AMs specifically induced in the tumor environment that are abundant in INHBA, and distinct from INHBA-expressing AMs in normal lungs. Moreover, postnatal deletion of INHBA/activin A could limit tumor growth in experimental models. Collectively, our findings demonstrate the critical pathological role of activin A-producing AMs in tumorigenesis, and provides means to clearly distinguish them from their healthy counterparts.

Label-free multiphoton excitation imaging as a promising diagnostic tool for breast cancer.

Histopathological diagnosis is the ultimate method of attaining the final diagnosis; however, the observation range is limited to the two-dimensional plane, and it requires thin slicing of the tissue, which limits diagnostic information. To seek solutions for these problems, we proposed a novel imaging-based histopathological examination. We used the multiphoton excitation microscopy (MPM) technique to establish a method for visualizing unfixed/unstained human breast tissues. Under near-infrared ray excitation, fresh human breast tissues emitted fluorescent signals with three major peaks, which enabled visualizing the breast tissue morphology without any fixation or dye staining. Our study using human breast tissue samples from 32 patients indicated that experienced pathologists can estimate normal or cancerous lesions using only these MPM images with a kappa coefficient of 1.0. Moreover, we developed an image classification algorithm with artificial intelligence that enabled us to automatically define cancer cells in small areas with a high sensitivity of ≥0.942. Taken together, label-free MPM imaging is a promising method for the real-time automatic diagnosis of breast cancer.

Equivalence between inverted regions of the energy gap law and inverted regions of donor-acceptor distances in photoinduced electron transfer processes in flavoproteins.

In the present work, we discuss about the relationship between the energy gap law and extended Dutton law in flavoproteins. The extend Dutton law is defined herein as the dependence of logarithmic rates (ln Rate) of photoinduced electron transfer (ET) from aromatic amino acids to excited isoalloxazine (Iso*) on donor-acceptor distances (Rcs). Both functions of ln Rate vs. negative values of the standard free energy gap and ln Rate vs. Rc display a parabolic behavior, when the ET rates are ultrafast. The negative values of the standard free energy gap at peaks of ln Rate [X m(ES)] were obtained for FMN-binding protein, wild-type pyranose 2-oxidase, T169S (Thr169 is replaced by Ser) pyranose 2-oxidase, and medium-chain acyl-CoA dehydrogenase. The values of Rc at peaks of ln Rate [X m(Rc)] were also obtained for these flavoproteins. The negative values of the standard free energy gap decreased with approximate linear functions of Rc. The negative values of standard free energy gap [X m(ESRc)] at Rc = X m(Rc) were evaluated using the linear functions of the negative standard free energy gap with Rc. The values of X m(ESRc) were mostly in very good agreement with the values of X m(ES). This implies that the energy gap law and the extend Dutton law are equivalent. X m(ES) values in ET donors displaying the linear extend Dutton law with Rc were obtained by energy gap law, and then X m(Rc) values were evaluated with the negative standard free energy gap. Thus, the obtained X m(Rc) values were much smaller than the Rc range obtained by the method of molecular dynamics simulation. This suggests that ET processes with linear profiles of the extend Dutton law could be parabolic when Rc becomes much shorter than the Rc range obtained by the method of molecular dynamics simulation.

Thymic Metastasis of Ovarian Cancer 33 Years After Primary Surgery.

This report describes a case of an extremely late recurrence of thymic metastasis after radical resection of ovarian cancer. Chest computed tomography demonstrated anterior mediastinal nodules with a smooth marginal area in a 56-year-old woman who had undergone an oophorectomy for ovarian cancer 33 years earlier. Because imaging findings suggested a thymic epithelial tumor, a partial thymectomy was performed. Histopathologic results led to the diagnosis of thymic metastasis of ovarian cancer. In patients with a medical history of ovarian cancer, thymic metastasis should be considered in the differential diagnosis of thymic tumor.

A case of repeat resection for recurrent pulmonary metastasis from sebaceous gland carcinoma.

BACKGROUND: Sebaceous gland carcinoma (SGC) of the eyelid is an aggressive malignant eyelid tumor, and it can metastasize to the regional lymph nodes and distant organs. There have been only a few reported cases of patients who underwent pulmonary metastasectomy for metastatic SGC. We herein report a patient who underwent repeat pulmonary metastasectomies for recurrent pulmonary metastases from SGC. CASE PRESENTATION: Bilateral small pulmonary nodules were detected in a 59-year-old woman with a history of eyelid SGC. She underwent wide wedge resection of the left lower lobe, and the disease was diagnosed as pulmonary metastases from SGC. Six months after the first pulmonary resection, CT showed that the nodules of right S2 and S10 had increased in size, and three small nodules had newly appeared in the right lung. The patient therefore underwent six wide wedge resections of the right lung through thoracotomy. After that, she underwent pulmonary metastasectomy 2 times. Ninety months after the first pulmonary resection, the patient is doing well without disease. CONCLUSIONS: Given that a long-term survival was ultimately achieved in the present case, repeat pulmonary metastasectomy may be beneficial for recurrent pulmonary metastasis from SGC.

Nonlinear Optics with Near-Infrared Excitation Enable Real-Time Quantitative Diagnosis of Human Cervical Cancers.

Histopathologic analysis through biopsy has been one of the most useful methods for the assessment of malignant neoplasms. However, some aspects of the analysis such as invasiveness, evaluation range, and turnaround time from biopsy to report could be improved. Here, we report a novel method for visualizing human cervical tissue three-dimensionally, without biopsy, fixation, or staining, and with sufficient quality for histologic diagnosis. Near-infrared excitation and nonlinear optics were employed to visualize unstained human epithelial tissues of the cervix uteri by constructing images with third-harmonic generation (THG) and second-harmonic generation (SHG). THG images enabled evaluation of nuclear morphology in a quantitative manner with six parameters after image analysis using deep learning. It was also possible to quantitatively assess intraepithelial fibrotic changes based on SHG images and another deep learning analysis. Using each analytical procedure alone, normal and cancerous tissue were classified quantitatively with an AUC ≥0.92. Moreover, a combinatory analysis of THG and SHG images with a machine learning algorithm allowed accurate classification of three-dimensional image files of normal tissue, intraepithelial neoplasia, and invasive carcinoma with a weighted kappa coefficient of 0.86. Our method enables real-time noninvasive diagnosis of cervical lesions, thus constituting a potential tool to dramatically change early detection. SIGNIFICANCE: This study proposes a novel method for diagnosing cancer using nonlinear optics, which enables visualization of histologic features of living tissues without the need for any biopsy or staining dye.

Total thymectomy for thymic lymphoepithelioma-like carcinoma-report of two cases.

BACKGROUND: Thymic carcinoma has been classified into 12 subtypes, thymic lymphoepithelioma-like carcinoma (LELC) is a type of them, and has a pathological organization similar to that of lymphoepithelioma, an undifferentiated type of nasopharyngeal carcinoma. According to a report from the International Thymic Malignancy Interest Group (ITMIG), thymic LELC is a rare tumor and accounts for 6% of all thymic carcinoma cases. We report two cases of surgical resection for thymic LELC and perform a search of other reports of thymic LELC, and clinical manifestations and follow-up data thus obtained are summarized. CASE PRESENTATION: Two patients underwent surgical resection for thymic LELC. In both, tumors were detected in the anterior mediastinum and a total thymectomy was performed. Each was diagnosed with thymic LELC and classified in accordance with the Masaoka staging system as modified stage II. In recent examinations, one patient was doing well after undergoing total resection, whereas early recurrence of distant lymph node metastasis was noted in the other at 5 months after the total resection procedure and died thereafter from a different disease. CONCLUSION: We report two cases of surgical resection for thymic LELC. A successful total resection may positively affect prognosis: thus, long-term follow-up examinations must be performed.

Comparative studies on picosecond-resolved fluorescence of d-amino acid oxidases from human with one from porcine kidney. Photoinduced electron transfer from aromatic amino acids to the excited flavin.

Fluorescence dynamics of human d-amino acid oxidase (hDAAO) and its five inhibitors have been studied in the picoseconds time domain, and compared with one in d-amino acid oxidase from porcine kidney (pkDAAO) reported. The fluorescence lifetimes were identified as 47 ps in the dimer, 235 ps in the monomer, which are compared with those of pkDAAO (45 ps-185 ps). The fluorescence lifetimes of the hDAAO did not change upon the inhibitor bindings despite of modifications in the absorption spectra. This indicates that the lifetimes of the complexes are too short to detect with the picosecond lifetime instrument. Numbers of the aromatic amino acids are similar between the both DAAOs. The fluorescence lifetimes of hDAAO were analysed with an ET theory using the crystal structure. The difference in the lifetimes of the dimer and monomer was well described in terms of difference in the electron affinity of the excited isoalloxazine (Iso*) between the two forms of the protein, though it is not known whether the structure of the monomer is different from the dimer. Three fastest ET donors were Tyr314, Trp52 and Tyr224 in the dimer, while Tyr314, Tyr224 and Tyr55 in the monomer, which are compared to those in pkDAAO, Tyr314, Tyr224 and Tyr228 in the dimer, and Tyr224, Tyr314 and Tyr228 in the monomer. The ET rate from Trp55 in hDAAO dimer was much faster compared to the rate in pkDAAO dimer. A rise component with negative pre-exponential factor was not observed in hDAAO, which are found in pkDAAO.

Separation between the chest wall and subpleural lung lesions: A two-step method to preoperatively exclude invasion or focal pleural adhesion by multidetector computed tomography.

PURPOSE: To develop and assess a non-invasive two-step method for evaluating the relationship between the parietal pleura and peripheral pulmonary lesions to preoperatively exclude invasion or focal pleural adhesion by multidetector computed tomography (CT). METHODS: Twenty-six patients with pulmonary peripheral lesions who underwent surgical lung resection between May and December 2017 were enrolled in this study. Routine CT was performed in the inspiratory phase in the supine position. Additional CT examinations were performed both in inspiratory and expiratory phases in the affected-side-up lateral position. Axial, sagittal, and coronal images were reconstructed from the CT data. In the first-step analysis, we evaluated the separation between the chest wall and subpleural lung lesions (separation) by comparing inspiratory- and expiratory-phase images obtained in the affected-side-up lateral position. When the separation was absent, we performed a second-step analysis, where we compared images obtained in the supine position during routine CT with those obtained in the affected-side-up lateral position and subsequently assessed the presence and absence of the separation. RESULTS: In the first-step analysis, the separation was observed in 21 lesions, which were categorised as showing "no invasion" or "no focal adhesion" on the basis of histological findings. After the second-step analysis, the separation was absent in three lesions and present in two; the latter two lesions were categorised as showing "no invasion" or "no focal adhesion" on the basis of operative and histological findings. Of the three lesions that did not exhibit the separation in either step of the analysis, two were diagnosed as exhibiting parietal pleural invasion on the basis of histological findings, while the third was categorised as showing "no invasion" or "no focal adhesion" on the basis of operative and histological findings. The sensitivity, specificity, positive and negative predictive values, and accuracy of this two-step method were 96% (95% confidence interval [CI]: 79-100%), 100% (95% CI: 16-100%), 100%, 67% (95% CI: 23-93%), and 96% (95% CI: 80-100%), respectively. CONCLUSIONS: Our two-step method is especially useful for excluding the parietal pleural involvement of peripheral pulmonary lesions. Even when the separation between the chest wall and subpleural lung lesions was limited, the change in position was useful for observing the separation and excluding parietal pleural involvement. This novel two-step method also has the advantage of being simple, cost-effective, and universally available.

[Three Cases of Advanced Gastric Cancer with Peritoneal Dissemination Successfully Treated with S-1 and Docetaxel Combination Chemotherapy].

Case 1: A 74-year-old man underwent total gastrectomy for gastric cancer, but peritoneal dissemination(P1c)was con- firmed intraoperatively in July 2011. Postoperatively, S-1/docetaxel(DTX)combination chemotherapy was administered; after 32 courses of treatment, S-1 was continued as monotherapy. However, in November 2013, CT scan showed a portal vein tumor. We modified the chemotherapy regimen, but he died 3 years and 7 months after the operation. Case 2: A 77-year-old man underwent distal gastrectomy for gastric cancer with peritoneal dissemination(P1b)in September 2013. He was treated with S-1/DTX/trastuzumab(Tmab)combination chemotherapy. After 5 courses of treatment, S-1was continued as monotherapy until October 2015. He has since survived without recurrence. Case 3: A 75-year-old woman was diagnosed with gastric cancer with peritoneal dissemination(P1c)by laparotomy in September 2014. She was treated with S-1/DTX combination chemotherapy. After 23 courses of treatment, chemotherapy was discontinued according to the patient's wish. She died 2 years and 6 months after the surgery. We suggest S-1/DTX combination chemotherapy as an option for advanced gastric cancer with peritoneal dissemination.

Dynamics of the protein structure of T169S pyranose 2-oxidase in solution: Molecular dynamics simulation.

Pyranose 2-oxidase (P2O) from Trametes multicolor contains FAD as cofactor, and forms a tetramer. The protein structure of a mutated P2O, T169S (Thr169 is replaced by Ser), in solution was studied by means of molecular dynamics simulation and analyses of photoinduced electron transfer (ET) from Trp168 to excited isoalloxazine (Iso*), and was compared with wild type (WT) P2O. Hydrogen bonding between Iso and nearby amino acids was very similar as between T169S and WT protein. Distances between Iso and Tyr456 were extremely heterogeneous among the subunits, 1.7 (1.5 in WT) in subunit A (Sub A), 0.97 (2.2 in WT) in Sub B, 1.3 (2.1 in WT) in Sub C, 1.3 nm (2.0 in WT) in Sub D. Mean values of root of mean square fluctuation over all residues were greater by four times than those in WT. This suggests that the protein structure of T169S is much more flexible than that of WT. Electrostatic (ES) energies between Iso anion in one subunit and ionic groups in the entire protein were evaluated. It was found that more than 50% of the total ES energy in each subunit is contributed from other subunits. Reported fluorescence decays were analyzed by a method as WT, previously reported. Electron affinities of Iso* in T169S were appreciably higher than those in WT. Static dielectric constants near Iso and Trp168 were also quite higher in T169S than those in WT.

[A Case of Surgical Treatment of Pulmonary Metastasis from Gastric Cancer].

An 87-year-old woman was diagnosed with advanced gastric cancer and primary lung cancer in November 2012. She underwent distal gastrectomy for the gastric cancer in December 2012, and right upper wedge resection for the primary lung cancer in February 2013. After surgery, the patient received S-1 chemotherapy. However, she subsequently experienced adverse effects, and so S-1 chemotherapy was stopped. In February 2016, a computed tomographic scan of the chest showed a nodular shadow at S8 in the left lung. Because the nodular shadow gradually increased in size, we suspected that the diagnosis would be either primary lung cancer or metastatic lung cancer arising from gastric cancer. In July 2016, we performed left lower wedge resection. Histopathological examination of the resected specimen resulted in a diagnosis of metastatic lung cancer arising from gastric cancer. After pulmonary resection, the patient had no recurrent tumor. It is thought that surgery is an effective treatment for solitary pulmonary metastasis arising from gastric cancer.

Cavernous hemangioma in the thymus: a case report.

Cavernous hemangioma is not a neoplasm, but rather a congenital venous malformation with the potential to develop in all parts of the body, though it is very rarely seen in the thymus. We report a case of cavernous hemangioma in the thymus partially resected. A 71-year-old woman presented with pericardial discomfort, and chest computed tomography (CT) showed a left lateral mediastinal mass which was 2.0 × 1.2 × 1.8 cm in size, with border regularity and without calcification. Its interior was partially enhanced. Three-dimensional chest computed tomography image showed a tortuous vessel connecting to the tumor. Surgical resection was performed for the purpose of providing a definitive diagnosis and treatment because a mediastinal tumor such as thymoma or teratoma was suspected. Partial resection of the thymus including the mass was done by utilizing a three-port, left-sided video-assisted thoracic surgery (VATS) approach with hoisting of the third rib with the patient in a spinal position. A wine-colored mass bulging from the surface of the left lobe of the thymus was identified along with the communicating vessel which could only be cut with an energy device. It is considered that thymic partial resection using VATS is a better option for small and non-infiltrative lesions.

Boiling effect in liquid nitrogen directly cooled Yb³âº:YAG laser.

Liquid nitrogen (LN2) behavior on the surface of excited Yb(3+):YAG is investigated using fluorometry. From the time-resolved temperature variations and integrated fluorescence spectra intensity on this directly cooled Yb(3+):YAG surface, we observe a phase transition of LN2 from nucleate boiling to film boiling. As a result of this pool boiling, good beam quality should occur when the temperature and heat flux at an excited surface of Yb(3+):YAG are below 95 K and 15.8 W/cm2, respectively. That is, the LN2 should remain in a steady state of nucleate boiling to produce good beam quality using pool boiling.

Classification of the mechanisms of photoinduced electron transfer from aromatic amino acids to the excited flavins in flavoproteins.

In many flavoproteins photoinduced electron transfer (ET) efficiently takes place from aromatic amino acids such as tryptophan or tyrosine to the excited isoalloxazine, so that the fluorescence lifetimes of isoalloxazine in some flavoproteins become ultrashort. The mechanism of ET in the flavoproteins was classified into four classes from the relationship between logarithmic ET rates (ln Rate) and the donor-acceptor distances (Rc), using reported data. The physical quantity, GT, is defined as the sum of solvent reorganization energy, electrostatic energy between a donor cation and an Iso anion, the standard free energy gap between the photoproducts and reactants, and net electrostatic energy between the photoproducts and other ionic groups in the flavoproteins (NetES). When GT fluctuates around zero with Rc, the ET rate becomes fastest (faster than 1 ps(-1)) in Kakitani and Mataga rates. In the ultrafast ET processes, the ln Rate becomes a parabolic function (category 1) of Rc as in FMN binding proteins and pyranose 2-oxidase at the shorter emission wavelengths, when NetES is negligible compared to the other quantities in the GT function. In the ultrafast ET processes, the ln Rate does not display any clear function of Rc (category 2) when NetES is dominant in the GT function, because of no direct relation between NetES and Rc. ET in flavodoxin from Helicobacter pylori may be classified into category 2. When GT linearly varies with Rc around a certain positive value, the ET rates become much slower (<1 ps(-1)). In this case the ln Rate linearly decreases with Rc (category 3), as Tyr224 in d-amino acid oxidase dimers. It is also conceivable that the ln Rate decreases with much scattered function of Rc (category 4), when NetES is dominant in the GT function, as Tyr314 in d-amino acid oxidase dimers. In ET processes of category 1, ET rates decrease as Rc becomes shorter than the distance at the maximum values of ln Rates, where GT is negative. Conditions and physical meanings were discussed for the GT-negative region.

Ultrafast fluorescence upconversion technique and its applications to proteins.

The basic principles and main characteristics of the ultrafast time-resolved fluorescence upconversion technique (conventional and space-resolved), including requirements for nonlinear crystals, mixing spectral bandwidth, acceptance angle, etc., are presented. Applications to flavoproteins [wild-type (WT) FMN-binding protein and its W32Y, W32A, E13R, E13K, E13Q and E13T mutants] and photoresponsive proteins [WT photoactive yellow protein and its R52Q mutant in solution and as single crystals] are demonstrated. For flavoproteins, investigations elucidating the effects of ionic charges on ultrafast electron transfer (ET) dynamics are summarized. It is shown that replacement of the ionic amino acid Glu13 and the resulting modification of the electrostatic charge distribution in the protein chromphore-binding pocket substantially alters the ultrafast fluorescence quenching dynamics and ET rate in FMN-binding protein. It is concluded that, together with donor-acceptor distances, electrostatic interactions between ionic photoproducts and other ionic groups in the proteins are important factors influencing the ET rates. In WT photoactive yellow protein and the R52Q mutant, ultrafast photoisomerization dynamics of the chromophore (deprotonated trans-p-coumaric acid) in liquid and crystal phases are investigated. It is shown that the primary dynamics in solution and single-crystal phases are quite similar; hence, the photocycle dynamics and structural differences observed at longer time scales arise mostly from the structural restraints imposed by the crystal lattice rigidity versus the flexibility in solution.