Search

A 75‐year‐old woman underwent thoracoscopic right upper lobectomy for lung cancer. A histopathological examination showed adenocarcinoma, pT1aN0M0 stage IA1. At six months after surgery, chest computed tomography (CT) revealed pericardial nodules that had not been detected before pulmonary resection. Postoperative CT performed two months later revealed that the nodules were growing and F18 fluorodeoxyglucose‐positron emission tomography showed a maximum standardized uptake of 9.87. Blood tests revealed no elevated tumor markers, with the exception of a mildly elevated interleukin‐2. Based on the above results, thoracoscopic biopsy was performed due to the suspected recurrence of lung cancer or malignant lymphoma. The histopathological examination of the nodule revealed immunoglobulin G4 (IgG4)‐related inflammatory pseudotumor. The serum IgG4 levels were elevated (358 mg/dL, normal: 4.5–117.0 mg/dL). No additional treatment was required because all nodules were observed to have disappeared naturally on a follow‐up CT scan performed two months after the surgical biopsy. The patient has been followed‐up for two years without recurrence. Key points Significant findings of the study We report a case of pericardial immunoglobulin G4‐related inflammatory pseudotumor that appeared after right upper lobectomy for lung cancer, and which naturally disappeared without any treatment. What this study adds There was an immunoglobulin G4‐related inflammatory pseudotumor which appeared as multiple nodules in the pericardial space, and this should be kept in mind when considering the differential diagnosis of intrapericardial nodules., We report a case of pericardial immunoglobulin G4‐related inflammatory pseudotumor that appeared after right upper lobectomy for lung cancer, and which naturally disappeared without any treatment.

Several authors have previously reported that patients with pulmonary combined large cell neuroendocrine cancer ( LCNEC) have a poor prognosis and there is no consensus on the treatment strategy for combined LCNEC as well as LCNEC. Here, we report the case of a long‐term survivor with pulmonary combined LCNEC. The patient was a 60‐year‐old man who underwent thoracoscopic right lower lobectomy. The final histopathology and staging of the tumor showed LCNEC combined with squamous cell carcinoma and T2aN0M0 stage IB. Multimodality treatments including chemotherapy, radiotherapy and surgery for several recurrences were performed after the pulmonary surgery. After immune checkpoint inhibitor (ICI) therapy with nivolumab, all the metastatic lesions shrunk and a partial response was maintained at five years after the first surgery. In our case, ICI after multimodality therapy combining cytotoxic anticancer drugs and radiotherapy was effective in LCNEC with metachronous multiple metastases. Key points Significant findings of the study Immune checkpoint inhibitor after multimodality therapy combining cytotoxic anticancer drugs and radiotherapy was effective in LCNEC with metachronous multiple metastases. The patient survived over five‐years after the first surgery. What this study adds Immune checkpoint inhibitor may be effective in some LCNEC patients.

The nymphalid butterfly Araschnia burejana and the papilionid butterfly Papilio xuthus exhibit seasonal diphenism comprising spring-morphs that develop from diapause pupae and summer-morphs that develop from non-diapause pupae. The development of seasonal morphs in A. burejana is regulated by the timing of secretion of ecdysteroids for adult development, whereas that in P. xuthus is regulated by the secretion of summer-morph-producing hormone, which is present in the brains and is under control of the photoperiod. We investigated whether a cerebral factor derived from brains plays a significant role in the regulation of seasonal morph development in A. burejana using surgical operations. Pairs of chilled diapause pupae that had been chilled for more than 3 months at 4°C were joined surgically to each other and then developed into spring-morph or spring-like-morph adults. Chilled diapause pupae that were joined with 1-day-old non-diapause pupae developed into summer-morph or summer-like-morph adults. When the brains of non-diapause pupae were removed surgically 6-8 hr after pupation with and without injection of 20-hydroxyecdysone, a large portion of them developed into spring-morph or spring-like-morph adults, respectively. Furthermore, 90% of non-diapause pupae developed into spring-morph or spring-like-morph adults when the neck was ligated within 5 min after pupation. These results indicated that a cerebral factor showing summer-morph-producing hormone activity, which is secreted from the brain in the early pupal stage, in addition to 20-hydroxyecdysone for adult development, play a significant role in the determination of summer-morph development in non-diapause pupae of A. burejana.

Three species of nymphalid butterflies, Vanessa cardui, V. indica and Nymphalis xanthomelas japonica, do not exhibit seasonal polyphenism in wing coloration. To determine whether seasonal non-polyphenic butterflies possess a cerebral factor affecting wing coloration, we used a Polygonia c-aureum female short-day pupal assay for detection of summer-morph-producing hormone (SMPH) activity in P. c-aureum. When 2% NaCl extracts of 25 brain-equivalents prepared from the pupal brains of V. cardui, V. indica or N. xanthomelas japonica were injected into Polygonia female short-day pupae, all recipients developed into summer-morph adults with dark-yellow wings, and the average grade score (AGS) of summer morphs showing SMPH activity was 3.8, 3.7 and 4.0, respectively. In contrast, when acetone or 80% ethanol extracts prepared from pupal brains were injected into Polygonia pupae, all recipients developed into autumn-morph adults with a dark-brown coloration and each exhibited an AGS of less than 0.5. Our results indicate that a cerebral factor showing SMPH activity is present in the pupal brain of seasonal non-polyphenic nymphalid butterflies, suggesting that a SMPH and cerebral factor showing SMPH activity occur widely among butterfly species. This finding will improve our understanding of the presence of cerebral factors showing interspecific actions of SHPH.

BACKGROUND Glucocorticoid was used in thymomas. The purpose of the study was to evaluate the efficacy of intravenous high-dose glucocorticoid (steroid pulse) therapy in patients with previously untreated advanced thymoma. Causes were also sought for a possible underlying mechanism of the effect of steroid on thymoma. METHODS Seventeen patients with invasive thymoma who had not received previous chemotherapy or radiation therapy were enrolled in the study. All cases were treated with 2 courses of glucocorticoid therapy before surgery. Tumor response was assessed by computed tomography (CT) scan 1 week after the steroid pulse therapy. Lymphocytes associated with thymoma were analyzed for their CD4/CD8 phenotype and glucocorticoid receptor (GR). TdT-mediated dUTP-biotin nick-end labeling (TUNEL) staining was used to analyze the apoptotic lymphocytes and epithelial cells. RESULTS The overall response rate to the steroid pulse therapy was 47.1% (8 of 17). The reduction in tumor size was most prominent in type B1 thymomas; there were significant differences between type AB and type B1 thymomas (P = .0234) and type B1 and type B3 thymomas (P = .0068). The reduction in tumor size was accompanied with a marked reduction in the CD4+8+ double-positive immature thymocytes that expressed higher levels of glucocorticoid receptor. Apoptotic changes were observed in both neoplastic epithelial cell and lymphocyte components after glucocorticoid therapy. CONCLUSIONS The efficiency of preoperative steroid pulse therapy in type B1 thymoma was most prominent, which is probably related to the specific effect on GR-rich CD4+8+ double-positive immature lymphocytes, which are abundant in this type of thymoma. Cancer 2006. © 2006 American Cancer Society.

Much evidence has accumulated that the epidermal growth factor receptor (EGFR) and its family members are strongly implicated in the development and progression of lung cancers. Somatic mutations of the EGFR gene were found in about 25–40% of Japanese lung cancer patients. More recently, erbB2 mutations are found in about 4% of European-derived lung cancer patients. We have investigated EGFR and erbB2 mutation status in 95 surgically treated nonsmall cell lung cancer (NSCLC) cases from Nagoya City University Hospital. Seventy-five adenocarcinoma cases were included. The presence or absence of EGFR and ernB2 mutations of kinase domains were analyzed by reverse transcription polymerase chain reaction (RT-PCR) amplifications and direct sequences. We have also investigated erbB2 mutation status in 27 surgically treated NSCLC cases followed by treatment with gefitinib from Kinki-chuo Chest Medical Center. EGFR mutations (CTGfiCGG; L858R) were found from 14 of 95 lung cancer patients. We also detected the deletion 1a-type mutations from 9 patients and deletion 4-type mutations from 6 patients in exon 19. In exon 20, 4 mutations including 2 novel mutations were found. Total EGFR mutations were present in 35 patients (36.8%). These mutation statuses were significantly correlated with gender (women 73.3% vs. men 20%, p < 0.0001), smoking status (never smoker 69.4% vs. smoker 16.9%, p < 0.0001), pathologic subtypes (adenocarcinoma 45.1% vs. nonadenocarcinoma 12.5%, p 5 0.0089) and differentiation status of the lung cancers (well 51% vs. moderately or poorly 18.4%, p 5 0.0021). On the other hand, erbB2 mutation was only found from 1 of 95 patients, at exon 20. This patient was female and a never smoker with adenocarcinoma. This 12 nucleotide insertion mutation (2324–2325 ins ATACGTGATGGC) was located in the exon 20 at kinase domain (775–776 ins YVMA). There was no erbB2 mutation in 27 gefitinib-treated NSCLC patients. In total, we have found only 1 erbB2 mutation from 122 (0.8%) Japanese NSCLC patients. There was a significantly higher erbB2 positive (21/31) ratio in EGFR mutant patients (13/25, 52.0%) compared to EGFR wild-type patients (10/ 62, 16.1%; p 5 0.0247). The NSCLC specimen with erbB2 mutation showed 11 immunoreactivity. The EGFR mutation status might correlate with the clinicopathologic features related to good response to gefitinib, such as gender, smoking history and pathologic subtypes of lung cancers. However, erbB2 mutation is rare from Japanese lung cancer and is of limited value for molecular target therapy. ' 2005 Wiley-Liss, Inc.

In the butterfly, Polygonia c-aureum, development of seasonal forms controlled by the photoperiod and temperature was shown to involve a neuroendocrine system of the brain-corpus cardiacum-corpus allatum complex. For analysis of the neuroendocrine system concerned, the innervation of the complex was investigated first by cobalt chloride perfusion staining and then by severance of axons, ablation of the candidate cells, injection of a homogenate of these cells and transplantation of corpora cardiaca using pupae programmed to be either summer-form or autumn-form adults. The results suggested that medial nerve cells produce what is called material producing the summer form. The seasonal forms of the Asian comma butterfly, Polygonia c-aureum L., summer and autumn forms (Fig. la, b), are determined by the photoperiod and the temperature during the larval period (1–3). Previous studies have given the following results on the physiological mechanism involved in the effect of environmental factors in inducing these seasonal forms. First, the mechanism involves neurosecretory cells located somewhere in the brain (2). Second, the nervous connections between the brain and the corpus cardiacum (NCC I+II (4)) and between the right and left brain lobes are indispensable for the effect (2, 5–7). The present study consisted of two series of experiments. One was designed to demonstrate morphologically the axonal connection of the corpus cardiacum with the corpus allatum in this butterfly, like that shown in several other insects (8–13). The other series was designed to locate the neurosecretory cells producing material related to the seasonal form and to see if this material is also present in the corpus cardiacum.

In Polygonia c-aureum, there are two seasonal forms, viz., the summer form and the autumn form. Previous experiments (Endo, 1970) showed that the corpora allata of the summer form accelerate the maturation of ovarian follicles soon after imaginal ecdysis. On the other hand, the corpora allata of the autumn form do not stimulate ovarian maturation during a period of 2 to 3 weeks after the emergence. In the summer form (S) as well as in the autumn form (A), the corpora allata remained in an inactive state for about 15 days after emergence when they had been isolated microsurgically from the brain and the corpora cardiaca during the larval period. Further, when separation of the brain into the right and left hemispheres or ablation of the medial neurosecretory group cells of the pars intercerebralis had been carried out on S-pupae of 28 hr after pupation or of earlier ages, they developed into autumn form in respect to wing pattern and their corpora allata did not stimulate ovarian maturation until 2 to 3 weeks after emergence. On the other hand, when the above operations had been performed 34 hr after the pupation or of later ages, they developed into summer form in respect to wing pattern and ovarian maturation was evident soon after the emergence. In these cases, stimulation of the corpora allata is closely connected with the development of seasonal-forms of wing pattern. From these experiments, it is clear that the medial neurosecretory group cells of the pars intercerebralis in S-insects stimulate the corpora allata about 30 hr after pupation by way of the nervi corporis cardiaci and the activated corpora allata promote ovarian maturation throughout adult life. In A-insects, on the other hand, the medial neurosecretory group cells of the brain are inactive and fail to activate the corpora allata which in turn have no influence on ovarian maturation.

In summer form adults of Polygonia c-aureum, the ovary develops soon after emergence and eggs mature a few days later. However, in autumn form adults, having been kept in laboratory conditions, only several mature eggs are found about four weeks after emergence. The allatectomy during the larval period prevents egg maturation in adults of both forms. When the corpora allata from the summer form of both sexes are transplanted into allatectomized adults of the autumn or summer form, the ovary develops as in the case of summer form adults. But the corpora allata of both sexes of the autumn form are not effective in inducing the ovarian maturation. Environmental factors, especially day-length and temperature during the larval period, may act through the neuroendocrine system to induce the activity of the corpora allata in the adult life.