Localization of macrophages and dendritic cells in human thoracic lymph nodes: An immunohistochemical study using surgically obtained specimens.

Both dendritic cells (DCs) and macrophages are bone marrow-derived cells that perform antigen presentation. The distribution of DCs and CD68-positive macrophages were immunohistochemically examined in 103 thoracic nodes obtained from 23 lung cancer patients (50-84 years old) without metastasis. Among three antibodies tested initially-CD209/DCsign, fascin, and CD83-DCsign was chosen as the DC marker. For comparison, 137 nodes from 12 patients with cancer metastasis were also examined histologically. In patients without metastasis, DCs were found as (1) clusters along the subcapsular sinus and in a border area between the medullary sinus and cortex (mean sectional area of multiple nodes at one site, 8.4%) and, (2) rosette-like structures in the cortex (mean number in multiple nodes at one site, 20.5). Notably, DC clusters and rosettes contained no or few macrophages and were surrounded by smooth muscle actin (SMA)-positive, endothelium-like cells. The subcapsular linear cluster corresponded to 5%-85% (mean, 34.0%) of the nodal circumferential length and was shorter in older patients (p = 0.009). DC rosettes, solitary, or communicating with a cluster, were usually connected to a paracortical lymph sinus. Few differences were found between nodes with or without metastasis, but DC cluster sometimes contained abundant macrophages in cancer metastasis patients. The subcapsular DC cluster is not known in the rodent model, in which the subcapsular sinus is filled with macrophages. This quite different, even complementary, distribution suggests no, or less, cooperation between DCs and macrophages in humans.

Respiratory motion tracking of spine stereotactic radiotherapy in prone position.

PURPOSE: The CyberKnife system is a specialized device for non-coplanar irradiation; however, it possesses the geometric restriction that the beam cannot be irradiated from under the treatment couch. Prone positioning is expected to reduce the dose to normal lung tissue in spinal stereotactic body radiotherapy (SBRT) owing to the efficiency of beam arrangement; however, respiratory motion occurs. Therefore, the Xsight spine prone tracking (XSPT) system is used to reduce the effects of respiratory motion. The purpose of this study was to evaluate the motion-tracking error of the spine in the prone position. MATERIALS AND METHODS: Data from all 25 patients who underwent spinal SBRT at our institution between April 2020 and February 2022 using CyberKnife (VSI, version 11.1.0) with the XSPT tracking system were retrospectively analyzed using log files. The tumor motion, correlation, and prediction errors for each patient were examined. Furthermore, to assess the potential relationships between the parameters, the relationships between the tumor-motion amplitudes and correlation or prediction errors were investigated using linear regression. RESULTS: The tumor-motion amplitudes in each direction were as follows: superior-inferior (SI), 0.51 ± 0.39 mm; left-right (LR), 0.37 ± 0.29 mm; and anterior-posterior (AP), 3.43 ± 1.63 mm. The overall mean correlation and prediction errors were 0.66 ± 0.48 mm and 0.06 ± 0.07 mm, respectively. The prediction errors were strongly correlated with the tumor-motion amplitudes, whereas the correlation errors were not. CONCLUSIONS: This study demonstrated that the correlation error of spinal SBRT in the prone position is sufficiently small to be independent of the tumor-motion amplitude. Furthermore, the prediction error is small, contributing only slightly to the tracking error. These findings will improve the understanding of how to compensate for respiratory-motion uncertainty in the prone position.

Fiducial marker position affects target volume in stereotactic lung irradiation.

PURPOSE: Real-time tracking systems of moving respiratory targets such as CyberKnife, Radixact, or Vero4DRT are an advanced robotic radiotherapy device used to deliver stereotactic body radiotherapy (SBRT). The internal target volume (ITV) of lung tumors is assessed through a fiducial marker fusion using four-dimensional computed tomography (CT). It is important to minimize the ITV to protect normal lung tissue from exposure to radiation and the associated side effects post SBRT. However, the ITV may alter if there is a change in the position of the fiducial marker with respect to the tumor. This study investigated the relationship between fiducial marker position and the ITV in order to prevent radiation exposure of normal lung tissue, and correct target coverage. MATERIALS AND METHODS: This study retrospectively reviewed 230 lung cancer patients who received a fiducial marker for SBRT between April 2015 and September 2021. The distance of the fiducial marker to the gross tumor volume (GTV) in the expiratory (dex ) and inspiratory (din ) CT, and the ratio of the ITV/V(GTVex ), were investigated. RESULTS: Upon comparing each lobe, although there was no significant difference in the ddiff and the ITV/V(GTVex ) between all lobes for dex  < 10 mm, there was significant difference in the ddiff and the ITV/V(GTVex ) between the lower and upper lobes for dex ≥ 10 mm (p < 0.05). Moreover, there was significant difference in the ddiff and the ITV/V(GTVex ) between dex ≥10 mm and dex  < 10 mm in all lung regions (p < 0.05). CONCLUSION: The ITV that had no margin from GTVs increased when dex was ≥10 mm for all lung regions (p < 0.05). Furthermore, the increase in ITV tended to be greater in the lower lung lobe. These findings can help decrease the possibility of adverse events post SBRT, and correct target coverage.

Plan comparison of prostate stereotactic radiotherapy in spacer implant patients.

In prostate stereotactic body radiation therapy (SBRT), hydrogel spacers are increasingly used. This study aimed to perform a dosimetry comparison of treatment plans using CyberKnife (CK), commonly used for prostate SBRT, Helical TomoTherapy (HT), and TrueBeam (TB) in patients with hydrogel spacer implantations. The data of 20 patients who received hydrogel spacer implantation for prostate SBRT were retrospectively analyzed. The prescription dose was 36.25 Gy in five fractions to 95% of the planning target volume (PTV; D95). The conformity index (CI), gradient index (GI), homogeneity index (HI), and dose-volume histogram (DVH) were analyzed for the three modalities, using the same PTV margins. The monitor unit (MU) and the beam-on-time (BOT) values were subsequently compared. The CI of TB (0.93 ± 0.02) was significantly superior to those of CK (0.82 ± 0.03, p < 0.01) and HT (0.86 ± 0.03, p < 0.01). Similarly, the GI value of TB (3.59 ± 0.12) was significantly better than those of CK (4.31 ± 0.43, p < 0.01) and HT (4.52 ± 0.24, p < 0.01). The median doses to the bladder did not differ between the CK and TB (V18.1 Gy: 16.5% ± 4.5% vs. 15.8% ± 4.4%, p = 1.00), but were significantly higher for HT (V18.1 Gy: 33.2% ± 7.3%, p < 0.01 vs. CK, p < 0.01 vs. TB). The median rectal dose was significantly lower for TB (V18.1 Gy: 5.6% ± 4.5%) than for CK (V18.1 Gy: 11.2% ± 6.7%, p < 0.01) and HT (20.2% ± 8.3%, p < 0.01). TB had the shortest BOT (2.6 min; CK: 17.4 min, HT: 6.9 min). TB could create treatment plans dosimetrically comparable to those of CK when using the same margins, in patients with hydrogel spacers.

Stereotactic body radiotherapy for second primary lung cancer and intra-parenchymal lung metastasis in patients previously treated with surgery: evaluation of indications and predictors of decreased respiratory function.

BACKGROUND: The adaptation criteria for administration of stereotactic body radiotherapy (SBRT) to patients with lung cancer who previously underwent surgery and subsequently developed a second primary lung cancer (SPLC) or intra-parenchymal lung metastasis (IPLM) are controversial, unlike the criteria for repeat surgery. We aimed to evaluate the feasibility of SBRT for these patients. Factors associated with decreased respiratory function were also evaluated. MATERIAL AND METHODS: Sixty-nine patients with 89 lesions who underwent SBRT between 2008 and 2017 were analyzed. Of these, 29 were diagnosed with SPLC while the remaining 40 had IPLM. The distribution of histological types was as follows: squamous cell carcinoma (n = 13 lesions); adenocarcinoma (n = 25); non-small cell carcinoma (n = 1); unknown histological type (n = 49). The prescribed doses to the planning target volume (PTV) were 50 Gy in five fractions for 85 lesions and 60 Gy in 10 fractions for four lesions at PTV mean. RESULTS: Over a median follow-up period of 55 months, the 4-year overall survival and local control rates were 50.3% and 87.6%, respectively. Six patients experienced grade 2 radiation pneumonitis and one experienced grade 3. Two patients experienced grade 5 pulmonary fibrosis. Decreased respiratory function was observed in 10 patients (15.1%). On multivariate analysis, the presence of pulmonary disease before SBRT was the only statistically significant factor associated with decreased respiratory function. CONCLUSIONS: SBRT is safe and feasible in patients with SPLC or IPLM previously treated surgically. Pre-existing pulmonary disease was a predictive factor for decreased respiratory function.

Targeting the ERK signaling pathway as a potential treatment for insulin resistance and type 2 diabetes.

Extracellular signal-regulated kinase (ERK) has been implicated in the development of insulin resistance associated with obesity and type 2 diabetes mellitus. We have now examined the potential of pharmacological targeting of the ERK pathway with MEK (ERK kinase) inhibitors (PD184352 and PD0325901) for the treatment of obesity-associated insulin resistance. The effects of PD184352 and PD0325901 on the expression of adipocytokines and lipolysis activity were thus examined in 3T3-L1 adipocytes maintained in long-term culture as a model of adipocyte hypertrophy. Leptin receptor-deficient (db/db) mice and high-fat diet-fed KKAy mice, both of which are models of type 2 diabetes, were also treated orally with PD184352 to examine its effects on the diabetic condition. ERK activity was increased in hypertrophic 3T3-L1 adipocytes as well as in adipose tissue of db/db mice and high-fat diet-fed KKAy mice, and this enhanced ERK signaling was associated with dysregulation of adipocytokine expression and increased lipolysis activity. Specific blockade of the ERK pathway in hypertrophic 3T3-L1 adipocytes by MEK inhibitors ameliorated the dysregulation of adipocytokine expression and suppressed the enhanced lipolysis activity. Furthermore, repeated oral administration of PD184352 normalized hyperglycemia and hyperlipidemia and improved insulin sensitivity and glucose tolerance in the diabetic mice. These results suggest that sustained activation of the ERK pathway in adipocytes is associated with the pathogenesis of type 2 diabetes and that selective blockade of this pathway with MEK inhibitors warrants further study as a promising approach to the treatment of insulin resistance and type 2 diabetes.

Hypofractionated stereotactic radiotherapy for brain metastases from lung cancer : Evaluation of indications and predictors of local control.

AIM: To evaluate the efficacy and toxicity of hypofractionated stereotactic radiotherapy (HSRT) for brain metastases (BMs) from lung cancer, and to explore prognostic factors associated with local control (LC) and indication. PATIENTS AND METHODS: We evaluated patients who were treated with linac-based HSRT for BMs from lung cancer. Lesions treated with stereotactic radiosurgery (SRS) in the same patients during the same periods were analysed and compared with HSRT in terms of LC or toxicity. There were 53 patients with 214 lesions selected for this analysis (HSRT: 76 lesions, SRS: 138 lesions). For HSRT, the median prescribed dose was 35 Gy in 5 fractions. RESULTS: The 1­year LC rate was 83.6 % in HSRT; on multivariate analysis, a planning target volume (PTV) of <4 cm(3), biologically effective dose (BED10) of ≥51 Gy, and adenocarcinoma were significantly associated with better LC. Moreover, in PTVs ≥ 4 cm(3), there was a significant difference in LC between BED10 < 51 Gy and ≥ 51 Gy (p = 0.024). On the other hand, in PTVs < 4 cm(3), both HSRT and SRS had good LC with no significant difference (p = 0.195). Radiation necrosis emerged in 5 of 76 lesions (6.6 %) treated with HSRT and 21 of 138 (15.2 %) lesions treated with SRS (p = 0.064). CONCLUSION: Linac-based HSRT was safe and effective for BMs from lung cancer, and hence might be particularly useful in or near an eloquent area. PTV, BED10, and pathological type were significant prognostic factors. Furthermore, in BMs ≥ 4 cm(3), a dose of BED ≥ 51 Gy should be considered.

[Metastatic Lung Tumor Diagnosed as Primary Lung Cancer due to its Accompanying Lesion Mimicking Atypical Adenomatous Hyperplasia by Intraoperative Needle Biopsy Findings;Report of a Case].

We reported a case of metastatic lung tumor, which was suspected as being a primary lung cancer because of its accompanying lesion mimicking atypical adenomatous hyperplasia(AAH) based on intraoperative needle biopsy findings. AAH is a preinvasive lesion or marginal lesion of primary lung cancer that is not accompanied by metastatic tumor. However, it needs to be distinguished pathologically from secondary changes of inflammation or fibrosis. In our case, the needle biopsy revealed AAH-like pathological findings, which indicates a primary lung cancer, and the standard lobectomy with lymph node dissection was performed, however, the final diagnosis turned out to be metastatic tumor. The rapidly enlarging tumor led to surrounding obstructive pneumonitis, which may have caused pathological changes mimicking AAH findings. In the case of obstructive pneumonitis, we must be careful to diagnose AAH, in addition to decisions about the surgical procedure especially when based on frozen section diagnosis.

Treatment outcomes of the patients with early glottic cancer treated with initial radiotherapy and salvaged by conservative surgery.

OBJECTIVE: This retrospective study analyzed the oncological and treatment outcomes of the patients with T1-T2N0 glottic cancer, who were treated with radiotherapy as initial treatment and salvaged by conservative surgery for radiation failure. METHODS: Between May 1999 and December 2010, 115 patients with glottic laryngeal cancer were treated at Kobe University Hospital. At presentation, 54 patients had stage T1a disease, 26 had stage T1b disease and 35 had stage T2 disease. Seventy-nine patients were treated with conventional radiotherapy and 36 patients were treated with hyperfractionated radiotherapy as initial treatment. RESULTS: Median duration of follow-up was 61 months. Five-year local control rates of radiotherapy were 92% in T1a, 83% in T1b and 86% in T2. Of 12 patients who developed local recurrence, larynx was successfully preserved in 3 patients by laryngomicrosurgery, 7 patients by vertical partial laryngectomy and one patient by subtotal laryngectomy. Ultimate 5-year laryngeal preservation rate and local control rate of all cases were 99 and 100%, respectively. CONCLUSIONS: Present results suggest that initial treatment with radiotherapy salvaged by organ preservation surgery is an effective strategy for laryngeal preservation in the treatment of T1-T2N0 glottic laryngeal cancer.

Clinical implication of human leukocyte antigen (HLA)-F expression in breast cancer.

Human leukocyte antigen (HLA)-F is one of the non-classical HLA class I molecules that protects the fetus in pregnancy. HLA-F expression was immunohistochemically examined and the association between clinical parameters and HLA-F expression was analyzed. Cancerous HLA-F and stromal HLA-F-positive infiltrating cells were detected in 91 (40.0%) and 186 (81.6%) cases, respectively. HLA-F positivity in cancer cells was significantly associated with tumor size (P < 0.05). There was a weak correlation between HLA-F positivity of cancer cells and HLA-F positive infiltrative cells (P < 0.01, r = 0.11). HLA-F positivity did not affect patients' survival in 209 breast cancer. However, confined to stage II breast cancer, the HLA-F positive group showed significantly poorer outcomes than the HLA-F negative group (P < 0.05). The present study provides the first evidence that HLA-F positivity in breast carcinoma affects clinicopathological factors and could be selected as a prognostic marker for limited clinical stage.

Evaluation of robustness of optimization methods in breast intensity-modulated radiation therapy using TomoTherapy.

Intensity-modulated radiation therapy (IMRT) has become a popular choice for breast cancer treatment. We aimed to evaluate and compare the robustness of each optimization method used for breast IMRT using TomoTherapy. A retrospective analysis was performed on 10 patients with left breast cancer. For each optimization method (clipping, virtual bolus, and skin flash), a corresponding 50 Gy/25 fr plan was created in the helical and direct TomoTherapy modes. The dose-volume histogram parameters were compared after shifting the patients anteriorly and posteriorly. In the helical mode, when the patient was not shifted, the median D1cc (minimum dose delivered to 1 cc of the organ volume) of the breast skin for the clipping and virtual bolus plans was 52.2 (interquartile range: 51.9-52.6) and 50.4 (50.1-50.8) Gy, respectively. After an anterior shift, D1cc of the breast skin for the clipping and virtual bolus plans was 56.0 (55.6-56.8) and 50.9 (50.5-51.3) Gy, respectively. When the direct mode was used without shifting the patient, D1cc of the breast skin for the clipping, virtual bolus, and skin flash plans was 52.6 (51.9-53.1), 53.4 (52.6-53.9), and 52.3 (51.7-53.0) Gy, respectively. After shifting anteriorly, D1cc of the breast skin for the clipping, virtual bolus, and skin flash plans was 55.6 (54.1-56.4), 52.4 (52.0-53.0), and 53.6 (52.6-54.6) Gy, respectively. The clipping method is not sufficient for breast IMRT. The virtual bolus and skin flash methods were more robust optimization methods according to our analyses.

[Nine myasthenia gravis cases of thoracoscopic extended thymectomy].

The indication of thoracoscopic excision of mediastinal tumor at our department is benign tumor or noninvasive thymoma diagnosed before surgery. For myasthenia gravis, thoracoscopic extended thymectomy is performed with a bilateral thoracic approach using a laparolift, and this procedure is indicated for cases with complication of thymoma with a tumor size up to 5 cm. We performed thoracoscopic extended thymectomy in 9 myasthenia gravis patients between January and October 2011, and achieved favorable postoperative courses with no development of major complications so far. However,surgery required a long time compared to the conventional extended thymectomy employing median sternotomy, showing that further modification of the surgical procedure and improvement of the surgical skill are necessary. We report the details of thoracoscopic extended thymectomy with a bilateral thoracic approach for 9 myasthenia gravis patients performed at our department.

Human lymph node degeneration in the thoracic region: A morphometric and immunohistochemical analysis using surgically obtained specimens.

Lymph node degeneration was examined in 539 mediastinal and intrapulmonary nodes removed from 78 patients, aged 49-82 years, without cancer metastasis. Medullary sinus hyalinization observed in 36.2% of the hilar and 38.5% of the interlobar nodes. Early and smaller lesions were eosinophilic and factor VIII-positive, whereas advanced and large lesions contained a bulky mass of collagenous fiber bundles with few slender cells positive for smooth muscle actin (SMA) and factor VIII, as well as anthracotic macrophages. Subcapsular sinus hyalinization, observed in 4.3% of hilar nodes, was detected as a thick fibrous layer (over 0.2 mm) between the surface cortex and the thickened capsule. The fibrous layer contained SMA-positive slender cells, whereas the thickened capsule contained fibers positive for elastin and factor VIII. These hyalinization lesions occupied 3.6% and 0.8% of the sectional areas of hilar and lower paratracheal nodes, respectively. Areas of early and small cortical degeneration, surrounded by fibers positive for SMA and vimentin, did not contain lymphocytes and macrophages, but contained abundant small stromal cells. Silver staining suggested that advanced cortical degeneration was composed of collagen fibrils other than type I. Fatty tissues, seen in 47.8% of hilar nodes, often extended into and replaced medullary sinus tissue. Island-like remnants of medullary sinuses in areas of fatty degeneration contained various stromal cells positive for SMA, elastin, factor VIII and/or CD34. These degenerative morphologies, however, did not correlate with either age or smoking index. The present cortical degeneration usually seemed to follow hyalinization, but both were likely to occur independently.

Predicting factors of symptomatic radiation pneumonitis induced by durvalumab following concurrent chemoradiotherapy in locally advanced non-small cell lung cancer.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) followed by durvalumab is the standard of care for unresectable locally-advanced non-small cell carcinoma (LA-NSCLC). However, a major concern about administration of durvalumab after CCRT is whether the incidence of symptomatic radiation pneumonitis (RP) may increase or not. In the present analysis, we report the initial results of CCRT followed by durvalumab in patients with LA-NSCLC in a real-world setting with focus on predicting factors for symptomatic RP. METHODS: Patients who were pathologically diagnosed as NSCLC and initiated treatment with CCRT followed by durvalumab between July 2018 to December 2019 were eligible for this study. Patients were included if they completed the planned CRT course and administered at least one course of durvalumab. We retrospectively investigated the preliminary survival outcome and incidence and predicting factors for symptomatic RP. RESULTS: Of the 67 patients who planned CCRT, 63 patients completed the entire CCRT course. Of these, 56 patients proceeded to consolidation with durvalumab. The median time to eternal discontinuation of durvalumab was 9.7 months. The cumulative proportion of the patients who exhibited symptomatic RP was 30, 40 and 44% at 3, 6 and 12 months, respectively. In multivariate analyses, pulmonary fibrosis score and lung V40 were significant predictive factors for symptomatic RP (p < 0.001, HR: 7.83, 95% CI: 3.38-18.13, and p = 0.034, HR: 3.17, 95% CI: 1.09-9.19, respectively). CONCLUSIONS: Pulmonary fibrosis sore and lung V40 were significant predictive factors for symptomatic RP. We should be cautious about the administration of durvalumab for patients having subclinical pulmonary fibrosis. To our best knowledge, this is one of the first report showing the predictive value of high dose volumes to the lung in patients with LA-NSCLC who received CCRT followed by durvalumab.

Systemic Supplementation of Collagen VI by Neonatal Transplantation of iPSC-Derived MSCs Improves Histological Phenotype and Function of Col6-Deficient Model Mice.

Collagen VI is distributed in the interstitium and is secreted mainly by mesenchymal stromal cells (MSCs) in skeletal muscle. Mutations in COL6A1-3 genes cause a spectrum of COL6-related myopathies. In this study, we performed a systemic transplantation study of human-induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) into neonatal immunodeficient COL6-related myopathy model (Col6a1 KO /NSG) mice to validate the therapeutic potential. Engraftment of the donor cells and the resulting rescued collagen VI were observed at the quadriceps and diaphragm after intraperitoneal iMSC transplantation. Transplanted mice showed improvement in pathophysiological characteristics compared with untreated Col6a1 KO /NSG mice. In detail, higher muscle regeneration in the transplanted mice resulted in increased muscle weight and enlarged myofibers. Eight-week-old mice showed increased muscle force and performed better in the grip and rotarod tests. Overall, these findings support the concept that systemic iMSC transplantation can be a therapeutic option for COL6-related myopathies.

Collagen-VI supplementation by cell transplantation improves muscle regeneration in Ullrich congenital muscular dystrophy model mice.

BACKGROUND: Mesenchymal stromal cells (MSCs) function as supportive cells on skeletal muscle homeostasis through several secretory factors including type 6 collagen (COL6). Several mutations of COL6A1, 2, and 3 genes cause Ullrich congenital muscular dystrophy (UCMD). Skeletal muscle regeneration deficiency has been reported as a characteristic phenotype in muscle biopsy samples of human UCMD patients and UCMD model mice. However, little is known about the COL6-dependent mechanism for the occurrence and progression of the deficiency. The purpose of this study was to clarify the pathological mechanism of UCMD by supplementing COL6 through cell transplantation. METHODS: To test whether COL6 supplementation has a therapeutic effect for UCMD, in vivo and in vitro experiments were conducted using four types of MSCs: (1) healthy donors derived-primary MSCs (pMSCs), (2) MSCs derived from healthy donor induced pluripotent stem cell (iMSCs), (3) COL6-knockout iMSCs (COL6KO-iMSCs), and (4) UCMD patient-derived iMSCs (UCMD-iMSCs). RESULTS: All four MSC types could engraft for at least 12 weeks when transplanted into the tibialis anterior muscles of immunodeficient UCMD model (Col6a1KO) mice. COL6 protein was restored by the MSC transplantation if the MSCs were not COL6-deficient (types 1 and 2). Moreover, muscle regeneration and maturation in Col6a1KO mice were promoted with the transplantation of the COL6-producing MSCs only in the region supplemented with COL6. Skeletal muscle satellite cells derived from UCMD model mice (Col6a1KO-MuSCs) co-cultured with type 1 or 2 MSCs showed improved proliferation, differentiation, and maturation, whereas those co-cultured with type 3 or 4 MSCs did not. CONCLUSIONS: These findings indicate that COL6 supplementation improves muscle regeneration and maturation in UCMD model mice.

Supratentorial glioblastoma treated with radiotherapy: use of the Radiation Therapy Oncology Group recursive partitioning analysis grouping for predicting survival.

OBJECTIVE: This study aimed to evaluate the usefulness of recursive partitioning analysis model established by the Radiation Therapy Oncology Group for predicting the survival of patients with supratentorial glioblastoma treated with radiotherapy and to determine prognostic factors for the subgroups of this prognostic model. METHODS: A total of 108 glioblastoma patients treated with radiotherapy between January 1987 and December 2005 were retrospectively reviewed. Recursive partitioning analysis classes III, IV, V and VI included 8, 29, 32 and 39 patients, respectively. These classes were divided into two subgroups: a good prognostic group containing classes III-IV and a poor prognostic group containing classes V-VI. The median radiation dose was 60 Gy. Seventy-five patients received chemotherapy and/or immunotherapy. RESULTS: The overall survival differed significantly among classes III, IV, V and VI, with median survival times of 34, 15, 11 and 7 months, respectively. Among the good prognostic group, patients with basal ganglia invasion showed poorer survival outcomes than patients without basal ganglia invasion. Among the poor prognostic group, patients with tumor sizes of <5 cm and patients treated with nimustine hydrochloride showed better survival outcomes than those with tumor sizes of > or =5 cm and those without treatment with nimustine hydrochloride, respectively. CONCLUSIONS: This study confirms the prognostic value of the recursive partitioning analysis grouping. Basal ganglia invasion could be a useful predictive factor for survival in the good prognostic group, whereas tumor size and treatment with nimustine hydrochloride could be useful predictive factors in the poor prognostic group.

Prenatal sonographic findings and prognosis of craniosynostosis diagnosed during the fetal and neonatal periods.

The aim of the study was to explore the sonographic findings of fetuses with craniosynostosis and investigate their prognosis. We conducted a 5-year, multicenter retrospective study and collected data on patients with craniosynostosis diagnosed in the perinatal period. Of 41 cases, 30 cases (73%) were syndromic craniosynostosis, eight cases (20%) were non-syndromic craniosynostosis and the other three cases (7%) were secondary craniosynostosis of chromosomal deletion syndromes. The prenatal ultrasound detection rate was 61%. Half of the cases of syndromic craniosynostosis detected during the perinatal period were Pfeiffer syndrome; there were also six cases of Apert syndrome, three cases of Crouzon syndrome and other rare form of syndromic craniosynostosis (Beare-Stevenson syndrome, Saethre-Chotzen syndrome, cranioectodermal dysplasia, and thanatophoric dysplasia). Abnormal shape of the skull was the most common finding leading to prenatal diagnosis of craniosynostosis. Abnormal head biometry, which was the second most frequent finding, was closely correlated with deformation of the cranial shape. Three cases presented with ventriculomegaly and exophthalmos but normal cranial shape and size. The overall survival rate of infants with syndromic craniosynostosis was 79%, while all of the infants with non-syndromic craniosynostosis survived. In conclusion, prenatal diagnosis of craniosynostosis is difficult, especially when dysmorphic change of the fetal cranium is not evident. Abnormal head biometry and ventriculomegaly could potentially be additional markers of fetal craniosynostosis and consequently increase the prenatal detection rate.

Pattern of recurrence after CyberKnife stereotactic body radiotherapy for peripheral early non-small cell lung cancer.

BACKGROUND: The treatment efficacy after CyberKnife stereotactic body radiotherapy (SBRT) have not been adequately addressed. The purpose of this study was to investigate pattern of recurrence according to irradiation field after CyberKnife SBRT for early-stage non-small cell lung cancer (NSCLC). METHODS: This retrospective study included patients with peripheral cT1/2N0M0 NSCLC that was treated with SBRT using a CyberKnife between May 2013 and March 2016 at single institute and followed up by more than two imaging examinations. Both operable and inoperable patients were included. Overall survival (OS) and progression-free survival (PFS) curves were estimated using the Kaplan-Meier method with 95% confidence intervals (CI). Cumulative incidence curves of recurrence were calculated and compared using the Gray's test. RESULTS: Total 71 patients were included and analyzed in this study. The median follow-up period for surviving patients was 34 months (range, 7-64 months). The 2-year OS and PFS rate were 93% (95% CI: 83-97%) and 77% (95% CI: 65-86%), respectively. The 2-year cumulative incidence rate of infield recurrence and out-of-field recurrence were 6% (95% CI: 2-14%) and 17% (95% CI: 9-27%), respectively. Gross tumor volume (GTV) ≥9 mL and diagnosis-to-treatment interval (DTI) ≥90 days were significantly associated with infield recurrence (P<0.001 and P=0.007), and epidermal growth factor receptor (EGFR) mutation was significantly associated with out-of-field recurrence (P=0.014). CONCLUSIONS: Treatment efficacy after CyberKnife SBRT for peripheral early-stage NSCLC was identical to previous conventional linac-based SBRT reports. With short follow-up period, it was found that GTV and DTI were the significant predictive factor of infield recurrence, and EGFR mutation was the significant predictive factor of out-of-field recurrence.

Clinical impact of the callosal angle in the diagnosis of idiopathic normal pressure hydrocephalus.

The utility of measuring the corpus callosal angle (CA) for the diagnosis of idiopathic normal pressure hydrocephalus (INPH) was investigated. Three-dimensional magnetic resonance imaging (MRI) was performed in 34 INPH patients, 34 Alzheimer's disease (AD) patients, and 34 normal control (NC) subjects. Measurement of the CA on the coronal MR images of the posterior commissure perpendicular to the anteroposterior commissure plane was performed for all subjects. The CA of the INPH group (mean +/- SD, 66 +/- 14 degrees) was significantly smaller than those of the AD (104 +/- 15 degrees) and NC (112 +/- 11 degrees) groups. When using the threshold of the mean - 2SD value of the NC group (= 90 degrees), an accuracy of 93%, sensitivity of 97%, and specificity of 88% were observed for discrimination of INPH from AD patients. Measuring the CA helps in differentiating INPH patients from AD and normally aged subjects.