Impact of patient positioning uncertainty in noncoplanar intracranial stereotactic radiotherapy.

The aim of this study is to evaluate the patient positioning uncertainty in noncoplanar stereotactic radiosurgery or stereotactic radiotherapy (SRS/SRT) for intracranial lesions with the frameless 6D ExacTrac system. In all, 28 patients treated with SRS/SRT of 70 treatment plans at our institution were evaluated in this study. Two X-ray images with the frameless 6D ExacTrac system were first acquired to correct (XC) and verify (XV) the patient position at a couch angle of 0º. Subsequently, the XC and XV images were also acquired at each planned couch angle for using noncoplanar beams to detect position errors caused by rotating a couch. The translational XC and XV shift values at each couch angle were calculated for each plan. The percentages of the translational XC shift values within 1.0 mm for each planned couch angle for using noncoplanar beams were 77.86%, 72.26%, and 98.47% for the lateral, longitudinal, and vertical directions, respectively. Those within 2.0 mm were 98.22%, 97.96%, and 99.75% for the lateral, longitudinal, and vertical directions, respectively. The maximum absolute values of the translational XC shifts among all planned couch angles for using noncoplanar beams were 2.69, 2.45, and 2.17 mm for the lateral, longitudinal, and vertical directions, respectively. The overall absolute values of the translational XV shifts were less than 1.0 mm for all directions except for one case in the longitudinal direction. The patient position errors were detected after couch rotation for using noncoplanar beams, and they exceeded a planning target volume (PTV) margin of 1.0-2.0 mm used commonly in SRS/SRT treatment. These errors need to be corrected at each planned couch angle, or the PTV margin should be enlarged.

Dose distribution comparison in volumetric-modulated arc therapy plans for head and neck cancers with and without an external body contour extended technique.

AIM: This study compared volumetric-modulated arc therapy (VMAT) plans for head and neck cancers with and without an external body contour extended technique (EBCT). BACKGROUND: Dose calculation algorisms for VMAT have limitations in the buildup region. MATERIALS AND METHODS: Three VMAT plans were enrolled, with one case having a metal artifact from an artificial tooth. The proper dose was calculated using Eclipse version 11.0. The body contours were extended 2 cm outward from the skin surface in three-dimensional space, and the dose was recalculated with an anisotropic analytical algorithm (AAA) and Acuros XB (AXB). Monitor units (MUs) were set, and the dose distributions in the planning target volume (PTV), clinical target volume, and organ at risk (OAR) and conformity index (CI) with and without an EBCT were compared. The influence of a metal artifact outside of the thermoplastic head mask was also compared. RESULTS: The coverage of PTV by the 95% dose line near the patient's skin was increased drastically by using an EBCT. Plan renormalization had a negligible impact on MUs and doses delivered to OARs. CI of PTV with a 6-MV photon beam was closer to 1 than that with a 10-MV photon beam when both AAA and AXB were used in all cases. Metal artifacts outside the head mask had no effect on dose distribution. CONCLUSIONS: An EBCT is needed to estimate the proper dose at object volumes near the patient's skin and can improve the accuracy of the calculated dose at target volumes.

[Hyaline vascular-type Castleman disease of the pulmonary hilum that expanded during two years].

A 15-year-old asymptomatic girl had an abnormal shadow pointed out on a chest roentgenogram during a school medical health check. Her chest X-ray films showed a mass in the left pulmonary hilum that had increased in size during the past 2 years. Chest computed tomography (CT) showed a mass, which showed slight accumulation on FDG-PET in the left pulmonary hilum. Left lower lobectomy was performed for diagnosis, and the histopathological diagnosis was hyaline vascular-type Castleman disease. We report a case of hyaline vascular-type Castleman disease in the right pulmonary hilum which increased quite rapidly.

[A case of transcatheter coil embolization for pulmonary arteriovenous malformation complicated with hepatic arteriovenous malformation].

A 57-year-old woman in whom pulmonary arteriovenous malformation (PAVM) associated with hereditary hemorrhagic telangiectasia (HHT) had been diagnosed after a chest X-ray film showed an abnormal shadow at the age of 39. After diagnosis, she suffered two ischemic brain attacks, presumably caused by PAVM. She was admitted to our hospital for evaluation and treatment of PAVM on February 9, 2008. We confirmed two PAVMs in right S(3)a and left S(9)a by chest CT scan and angiography. In addition, abdominal CT revealed hepatic arteriovenous malformation (HAVM). HAVM were thought to increase venous return to the right heart, (which might cause pulmonary hypertension after the embolization of PAVMs), leading to right heart failure. In order to prevent neurological events in future, we performed an embolization of PAVM with individual coils at monthly intervals. Six months after the last embolization treatment, she showed no symptoms of right heart failure and the size of PAVMs decreased. It is considered important for a patient with PAVM associated with HHT to undergo a thorough examination for arteriovenous malformation in other organs, before coil embolization.

[A case of solitary splenic metastasis following operation for pulmonary pleomorphic carcinoma: detected at an early stage by FDG-PET].

A 58-year-old man was admitted our hospital. Chest computed tomography (CT) showed a nodular opacity in the left upper lobe and a swollen lymph node in the left hilar region. 18-fluorodeoxyglucose positron emission tomography (FDG-PET) showed abnormal uptakes in the same field. Since thoracoscopic lung biopsy revealed that the tumor was poorly differentiated adenocarcinoma, a left upper lobectomy and lymph node dissection were performed. Histological findings showed numerous spindle cells, thus it was diagnosed as pleomorphic carcinoma, pT2N1M0. After three months, a FDG-PET was performed, which detected a tiny lesion in the spleen. However an abdominal CT scan and ultrasonography (US) performed in the same period showed no abnormal findings. After about 2 months, a solitary low density area (5.0 cm) was seen in the spleen on an abdominal CT scan. We performed splenectomy under a diagnosis of a solitary splenic metastasis of the lung cancer. Pathological confirmation was obtained. Our findings demonstrated that whole-body scanning by FDG-PET was able to detect a rare postoperative splenic recurrence earlier than CT or US scan.

Nivolumab-related myasthenia gravis with myositis and myocarditis in Japan.

OBJECTIVE: To report the clinical features of myasthenia gravis (MG) induced by treatment with immune checkpoint inhibitors using 2-year safety databases based on postmarketing surveys in Japan. METHODS: We studied 10,277 patients with cancer who had received monotherapy with either nivolumab or ipilimumab between September 2014 and August 2016. As the control group, 105 patients with idiopathic MG were used. RESULTS: There were 12 MG cases (0.12%) among 9,869 patients with cancer who had been treated with nivolumab, but none among 408 patients treated with ipilimumab. These 12 patients included 6 men and 6 women with a mean age of 73.5 ± 6.3 years. MG onset occurred in the early phase after nivolumab treatment and rapidly deteriorated. Nivolumab-related MG (nivoMG) included 4 patients with mild involvement and 8 patients with severe involvement. Bulbar symptoms and myasthenic crisis were observed more frequently in nivoMG than idiopathic MG. Ten patients were positive for anti-acetylcholine receptor antibodies. Serum creatine kinase levels were markedly elevated to an average level of 4,799 IU/L. Among the 12 patients with nivoMG, 4 had myositis and 3 had myocarditis, with 1 of these patients having both. Immunosuppressive therapy was effective. Postintervention status showed that pharmacologic remission or minimal manifestations were obtained in 4 patients; however, 2 patients died. Immune-related adverse events triggered by nivolumab impaired the patients' daily living activity. CONCLUSIONS: The prompt and correct recognition of MG following treatment with immune checkpoint inhibitors in patients with cancer is important.

[A case of sarcoidosis with primary pulmonary cavitation].

A 30-year-old woman presented with multiple nodular shadows which enclosed a cavity on a chest radiograph. Chest computed tomographic (CT) images showed mediastinal lymphadenopathy, and multiple nodular opacities enclosing a cavity. Histopathological findings of biopsy specimens from the lung and mediastinal lymph nodes revealed noncaseating epithelioid cell granulomas without any evidence of Mycobacterium or fungal growth. The lesion in the lung included granulomatous vasculitis. Even without corticosteroid or any other therapy, the lung lesions resolved and the cavity disappeared. We report a case of sarcoidosis with primary acute cavitation.

Systemic lymph node tuberculosis presenting with an aseptic psoas abscess caused by a paradoxical reaction after nine months of antituberculosis treatment: a case report.

INTRODUCTION: A paradoxical reaction during antituberculosis treatment is defined as the worsening of pre-existing tuberculosis lesions or the appearance of a new tuberculosis lesion in patients whose clinical symptoms improved with antituberculosis treatment. The median onset time to the development of a paradoxical response has been reported to be about 60 days after the start of treatment. We report the case of a patient with a paradoxical reaction presenting as a psoas abscess after nine months of antituberculosis treatment. To the best of our knowledge, this manifestation has not previously been reported. CASE PRESENTATION: A 23-year-old Japanese man presented to our hospital with lower abdominal pain. Computed tomography showed that he had mediastinal and abdominal para-aortic lymph node swellings. Fluorine-18 fluorodeoxyglucose positron emission tomography showed hot spots in these lymph nodes and in his right cervical lymph node, suggesting a lymphoma. The examination of an abdominal lymph node biopsy specimen showed lymph node tuberculosis, so antituberculosis treatment was started. However, after nine months of treatment, he experienced right flank pain. Abdominal computed tomography showed a right psoas abscess and abdominal para-aortic lymph node swelling. The abscess was treated by percutaneous drainage. After repeated drainage, the psoas abscess subsided and disappeared. The purulent fluid yielded no microorganisms, suggesting a paradoxical reaction. CONCLUSION: Attention should be paid to paradoxical reactions occurring during antituberculosis treatment for systemic lymph node tuberculosis.

Pulmonary nontuberculous mycobacterial infection caused by Mycobacterium szulgai in a young healthy woman.

A 20-year-old woman with no history of pulmonary disease had no symptom and her chest CT scans demonstrated adhesive small multiple nodules in the bronchial lung biopsy specimen showed epithelioid cell granuloma containing Langhans giant cells, therefore she was diagnosed as pulmonary mycobacteriosis caused by M. szulgai. This is the youngest case of this rare condition occurring in a healthy subject without underlying pulmonary diseases.

Gefitinib-induced interstitial lung disease showing improvement after cessation: disassociation of serum markers.

Gefitinib (ZD1839), a small-molecule epidermal growth factor receptor tyrosine kinase inhibitor, is an anticancer agent for patients with non-small cell lung carcinoma. Recently, however, as a result of accumulating evidence, it has been recognized that gefitinib can give rise to lethal lung toxicity. The authors report a case of interstitial lung disease (ILD) induced by gefitinib, which improved promptly following cessation of the administration of the agent. Clinical signs suggesting a good prognosis were noted, namely, findings similar to acute eosinophilic pneumonia on CT and a disassociation in the elevation of specific serum markers of ILD. At the time of onset of ILD, serum concentrations of surfactant protein (SP)-A and SP-D were significantly increased, whereas that of KL-6 was not increased. A previous study of three cases of lethal lung toxicity resulting from gefitinib administration revealed a significant and almost equal increase in KL-6, SP-A and SP-D. These results suggest that SP-A and SP-D may be indicators of gefitinib-induced ILD and that KL-6 is a predictor of outcome. Using a combination of these markers may help to establish a differential prognosis in patients with gefitinib-induced ILD.

Circulating interleukin-18 and osteopontin are useful to evaluate disease activity in patients with tuberculosis.

BACKGROUND: T helper type 1 (Th1) responses have been implicated in the protective immunity, pathophysiology and development of tuberculosis. However, it is still unclear which molecule(s) reflect disease activity in patients with tuberculosis. METHODS: By specific enzyme immunoassays, circulating interferon-gamma. (IFN-gamma), interleukin-12 (IL-12), IL-18 and osteopontin (OPN) were measured in 47 patients with pulmonary tuberculosis and 7 patients with miliary tuberculosis before anti-tuberculosis therapy, and also measured in 19 patients with tuberculosis before and after anti-tuberculosis therapy. RESULTS: Circulating IFN-gamma, IL-18 and OPN levels were significantly higher in patients with pulmonary tuberculosis than in healthy controls, while there was no significant difference in levels of circulating IL-12 between tuberculosis patients and controls. Circulating IFN-gamma, IL-12, IL-18 and OPN paralleled the extent of lung lesions, and circulating IFN-gamma, IL-18 and OPN paralleled the magnitude of fever in patients with pulmonary tuberculosis. Patients with miliary tuberculosis had extremely high levels of circulating OPN, IFN-gamma and IL-18. Circulating IL-18 and OPN were significantly decreased with anti-tuberculosis therapy, whereas circulating IL-12 and IFN-gamma were not. CONCLUSIONS: Among Th1 response associated molecules, circulating levels of IL-18 and OPN, but not IFN-gamma or IL-12, reflect disease activity in patients with tuberculosis.

Acute lung injury as an adverse event of gefitinib.

Gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor, is an effective treatment for patients with non-small cell lung cancer (NSCLC). Some investigators have recently reported several patients complicated by acute lung injury after the initiation of gefitinib administration. In this report, we investigated the efficacy and adverse events during treatment with gefitinib. The subjects of this study were all of the 110 patients with NSCLC who were treated in our hospital and its eight branch hospitals. Patients received gefitinib at a dose of 250 mg once daily. The response rate was 30%. The frequently reported adverse events were skin disorders, gastrointestinal disturbances, liver dysfunction and acute lung injury. Five of the 12 patients who were considered to have suffered acute lung injury died of progressive respiratory failure. Of the nine patients who had pulmonary fibrosis before use of gefitinib, five developed acute lung injury during the treatment. Sera from three of the 12 patients were evaluated and all three showed increases of surfactant protein (SP)-A, SP-D and KL-6. We conclude that gefitinib was clinically useful. However, several patients suffered acute lung injury which could have been caused by gefitinib. A detection system including SP-A, SP-D and KL-6 as prime candidates as markers should be established as promptly as possible. Clinicians should be aware that treatment of NSCLC with gefitinib involves the risk of acute lung injury and therefore careful consideration should be given before deciding whether or not gefitinib is indicated for treatment. Further study is necessary to elucidate the mechanism of acute lung injury by gefitinib.

Polymorphism of Clara cell 10-kD protein gene of sarcoidosis.

Clara cell 10-kD protein (CC10) exhibits potent antiinflammatory properties. G38A polymorphism was found in the CC10 gene. We investigated the genetic influence of the allele on the development of sarcoidosis using case control analysis in a Japanese population (265 sarcoidosis cases and 258 control subjects). The A allele frequency in sarcoidosis cases (45.1%) was significantly higher than healthy control subjects (34.9%, p = 0.0002). According to outcomes, we divided 223 patients with follow-up periods of 3 years or more into two subgroups (55 progressive and 168 regressive disease). The A allele frequency in patients with progressive disease was significantly higher than control subjects (odds ratio = 4.55; 95% confidence interval, 2.97-6.97; p < 0.0001), whereas that of regressive disease was not. The A/A genotypes had significantly lower bronchoalveolar lavage fluid CC10 levels than the G/G (nonsmokers, p = 0.0054, and smokers, p = 0.0045) and G/A genotypes (nonsmokers, p = 0.0022, and smokers, p = 0.0402). The reporter gene assay showed significantly lower reporter activities in the presence of interferon-gamma for the 38A construct than the 38G construct (p = 0.0177). The G38A polymorphism in the CC10 gene may influence protein expression and be associated with the development of progressive sarcoidosis.