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Objectives: The management of patients with locally advanced thymic malignancies remains controversial. Differing combinations of surgical resection, chemotherapy and radiation are used in the management of initial and relapsed disease. Treatment-related toxicities and quality of life could inform therapeutic options. This study describes health utility scores (HUS) in survivors with locally advanced thymic malignancies and investigates the impact of multimodality regimens on HUS., Methods: In a cross-sectional study (2014-2017), patients with Masaoka Stage II-IVa thymic malignancies completed various self-reported questionnaires, including EuroQol-5-Dimensions with visual analogue scale (VAS), Eastern Cooperative Oncology Group (ECOG) and Edmonton Symptom Assessment Scale tools. Trimodality versus uni- or bimodality regimens and aggressive versus non-aggressive management of recurrent disease were compared using regression analyses., Results: Of the 72 patients, 43 (60%) were male with a median age of 58 years, 65 (90%) had thymoma while 7 (10%) had thymic carcinomas; and median time since diagnosis was 50.5 months (range: 3-266). Median HUS and VAS did not differ between groups (trimodality n = 24 vs uni- or bimodality n = 48: HUS = 0.77 vs 0.80, P = 0.29; VAS = 80 vs 75, P = 0.79, respectively). The distributions of patient-reported ECOG were also similar (P = 0.86). Edmonton Symptom Assessment Scale scores for every assessed symptom were similar for different modalities of therapy. Median scores on these tools were also similar regardless of recurrence status or management of relapsed disease (aggressive versus non-aggressive)., Conclusion: Survivors with Stage II-IVa thymic malignancies report favourable HUS, VAS and self-reported ECOG with minimal symptom burden. These outcomes may be independent of number and type of initial treatment modalities or management of recurrence.

Tumours show an increased interstitial fluid pressure, which correlates with various pathophysiological features. Moreover, interstitial fluid pressure is a prognostic factor for cervical and lung cancer. However, there have been no reports on the usefulness of measuring interstitial fluid pressure in thymic epithelial tumours. Therefore, this study aimed to examine the relationship between interstitial fluid pressure and the clinicopathological characteristics of thymic epithelial tumours. Interstitial fluid pressure was prospectively measured at the centre of the tumour using a 1-Fr Mikro-Tip sensor catheter in 44 patients with thymic epithelial tumours, 40 with thymomas and 4 with thymic carcinomas. Data from these 44 patients were analysed for correlations between interstitial fluid pressure and clinicopathological and demographic factors including sex, age, tumour size, World Health Organization histological subtypes, myasthenia gravis, capsular invasion, mediastinal pleura invasion, lung invasion, pericardium invasion, dissemination, Masaoka-Koga stage, maximal standardized uptake value and recurrence-free survival (RFS). The mean interstitial fluid pressure was 11.3 mmHg; interstitial fluid pressure was significantly correlated with maximal standardized uptake value, lung invasion, dissemination and Masaoka-Koga stage. Low interstitial fluid pressure (≤14 mmHg) showed a tendency for better RFS compared with high interstitial pressure (P = 0.053). Lung invasion, dissemination and Masaoka-Koga stage were correlated with RFS in univariable analysis; lung invasion was selected as an independent prognostic factor in multivariable analysis. On the basis of these results, interstitial fluid pressure of thymic epithelial tumours has been shown to correlate with their clinicopathological features., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: It is known that opioids may decrease subjective dyspnea. The recent finding that opioid binding sites are present in the peripheral bronchus supports the possibility of a local action of opioids. However, the clinical benefit of nebulized morphine is controversial. The purpose of this study was to confirm the feasibility of nebulized morphine and to evaluate its clinical benefits., Patients and Methods: Fifteen cancer patients with dyspnea in the Thoracic Oncology Division and Palliative Care Unit in the National Cancer Center Hospital East were given 20 mg of morphine hydrochloride dissolved in 5 ml of normal saline through an ultranebulizer. The subjective effects were evaluated using a visual analog scale (VAS) immediately before and 60 min after inhalation. Respiratory rate (RR), hemoglobin oxygen saturation (SpO2) and blood pressure also were measured twice at these two time points. A questionnaire about adverse reactions was included., Results: No major adverse reactions such as respiratory depression, sleepiness, nausea or vomiting were observed. VAS was significantly decreased after nebulization (p = 0.005) without any significant change in RR or SpO2. In eight of 15 patients, dyspnea was improved as measured by a decrease in VAS of more than 10%. This correlated with the desire of the patients to continue its use., Conclusion: Our preliminary data confirmed the feasibility of nebulized morphine and suggested its possible clinical benefit for dyspneic patients. A randomized controlled study is warranted to exclude a placebo effect and to compare the clinical benefits of nebulized morphine with those of other methods of treatment.

Three hundred ninety patients who underwent thymectomy for myasthenia gravis (MG) were followed up to investigate the development of associated malignancies. There were 102 patients with thymoma and 288 without thymoma. Malignant neoplasms were detected in ten patients, four of whom already had the tumor at the time MG was diagnosed. Thus, malignancy developed after thymectomy in six patients. Malignant fibrous histiocytoma (MFH) developed in three patients, as well as gastric cancer, gastric leiomyosarcoma, rectal cancer, liver cancer, lung cancer, breast cancer, and thymic carcinoid in one patient each. Nine of the ten malignancies developed in the thymoma group, and only one in the non-thymoma group. The predicted number of patients with malignancy was 2.63 in the thymoma group and 2.65 in the non-thymoma group. Our findings suggest that the presence of thymoma facilitates the occurrence of extrathymic malignancy, and that thymectomy never enhances the occurrence of malignancy but possibly inhibits it.

Bone marrow transplantation (BMT) experiments were conducted using B10.Thy 1 congenic mice to explore the nature of bone marrow-thymus interactions during thymic lymphomagenesis induced by fractionated whole-body X-irradiation (FX). BMT from normal Thy 1 congenic donors into FX-treated recipients one day after FX-treatment resulted in the suppression of tumor development; the suppression being exponentially proportional to the increasing number of bone marrow cells injected. The suppression of tumor development by BMT was shown to be due to prevention of the appearance of prelymphoma cells. BMT from FX-treated donors, which are deficient in pre T cells, into lethally (9 Gy) irradiated Thy 1 congenic recipients resulted in the development of high incidence of thymic lymphomas most of which (approximately 76%) were host-derived, whereas no lymphomas were recovered from the recipients of normal bone marrow. These results suggest that intrathymic T cell precursors which initially repopulate the depleted thymus are prone to undergo preneoplastic changes in the absence of recruitment of more primitive T cell precursors (pre T cells) from the bone marrow but they undergo normal differentiation when large number of pre T cells are available. It was concluded that primary cause of the FX-induced thymic lymphomagenesis was a shortage in supply of pre T cells from the bone marrow to the depleted thymus, which caused differentiation arrest of the progeny of regenerating intrathymic T cell precursors, followed by development of prelymphoma cells that eventually evolve into autonomous lymphoma cells within the thymus.

Thirteen independently derived murine thymic lymphosarcoma lines were assayed for various aspects of sensitivity to glucocorticoid-induced cytolysis. All tumor lines were sensitive to cytolysis, as evidenced by profound tumor regression after pharmacologic doses of cortisol. All tumor lines contained about 20,000 high-affinity, dexamethasone binding sites/cell. Between 55 and 88% of these presumptive receptor sites underwent nuclear translocation during a 30-minute incubation at 37 degrees C. Dissociation constants (Kd) for the dexamethasone-receptor complex were between 1.5 and 3.6 nM in all cases. Kd for the triamcinolone acetonide-receptor complex were determined for a few tumor lines and were between 0.5 and 0.9 nM. Cytolysis-resistant subpopulations were selected by prolonged glucocorticoid treatment of BALB/c pi mice bearing tumors from seven of the lymphosarcoma lines. All seven resistant subpopulations contained about 20,000 high-affinity, dexamethasone binding sites/cell. Between 57 and 80% of these presumptive receptor sites underwent nuclear translocation under standard assay conditions. No resistant variants exhibited significantly reduced dexamethasone binding or nuclear translocation properties.

The results of thymectomy in the treatment of myasthenia gravis (MG) are reviewed in the light of a personal series of 662 MG patients, operated upon during the last 15 years. In 500 MG patients without thymoma, the following results have been achieved: remission 37.9%, improvement 49.4%, unchanged or worse 7.4%, dead 5.2%. There is no sex prevalence and the remission rate is higher in patients under 40 years of age (P less than 0.01), with mild disease (P less than 0.05), with a MG duration of less than 1 year (P less than 0.05) and with a follow-up length of between 5 and 10 years (P less than 0.01). No correlations are found between outcome and thymic histology. The results of 162 MG patients with thymoma are: remission rate 15.7%, improvement 60.3%, unchanged or worse 3.7% and dead 20.1%. The remission rate is higher with mild symptoms (P less than 0.05) and when the tumour is encapsulated (P less than 0.02). The postoperative mortality is 0.8% (none in the last 5 years) for non-thymomatous MG and 4.9% for thymomatous MG (2 of 8 patients died of pancytopaenia and 1 of pulmonary embolism).

Interleukin 2 (IL-2) production was studied in a subclone of the murine thymoma EL 4. Phenotypic characterization revealed the EL 4-17-2 line to be Thy-1.2+, Lyt-1.2+, and Lyt-2.2-. Costimulation with 500 ng 12-O-tetradecanoylphorbol 13-acetate (TPA)/ml and 5 micrograms concanavalin A (Con A)/ml induced optimal levels of IL-2. Three related phorbol esters stimulated comparable levels of IL-2 when used in conjunction with Con A. Kinetic experiments indicated that IL-2 first became detectable at 2 hours in TPA-treated cultures, whereas in cultures stimulated with Con A alone IL-2 production was not evident until 8 hours. Flow cytometry indicated that TPA and its related phorbol esters cause a perturbation in the cycling of the cell which may be related to increased IL-2 production. Under the conditions examined, no interferon-gamma (IFN-gamma) was detectable. Conversely, both granulocyte-macrophage colony-stimulating factor (CSF-GM) and interleukin-3 (IL-3) were found under conditions that led to stimulation of IL-2 synthesis. CSF-GM was produced in cultures treated singly with 500 ng TPA/ml or with Con A. IL-3 production was similar to IL-2 production, because optimal levels were found in cultures after combined treatment with phorbol ester and mitogen.