Fused radical SAM and αKG-HExxH domain proteins contain a distinct structural fold and catalyse cyclophane formation and ß-hydroxylation.

Two of nature's recurring binding motifs in metalloproteins are the CxxxCxxC motif in radical SAM enzymes and the 2-His-1-carboxylate motif found both in zincins and α-ketoglutarate and non-haem iron enzymes. Here we show the confluence of these two domains in a single post-translational modifying enzyme containing an N-terminal radical S-adenosylmethionine domain fused to a C-terminal 2-His-1-carboxylate (HExxH) domain. The radical SAM domain catalyses three-residue cyclophane formation and is the signature modification of triceptides, a class of ribosomally synthesized and post-translationally modified peptides. The HExxH domain is a defining feature of zinc metalloproteases. Yet the HExxH motif-containing domain studied here catalyses ß-hydroxylation and is an α-ketoglutarate non-haem iron enzyme. We determined the crystal structure for this HExxH protein at 2.8 Å, unveiling a distinct structural fold, thus expanding the family of α-ketoglutarate non-haem iron enzymes with a class that we propose to name αKG-HExxH. αKG-HExxH proteins represent a unique family of ribosomally synthesized and post-translationally modified peptide modifying enzymes that can furnish opportunities for genome mining, synthetic biology and enzymology.

Frequency of use and cost in Japan of first-line palliative chemotherapies for recurrent or metastatic squamous cell carcinoma of the head and neck.

BACKGROUND: Over the last decade, novel anticancer drugs have improved the prognosis for recurrent or metastatic squamous cell carcinoma of the head and neck (RM-SCCHN). However, this has increased healthcare expenditures and placed a heavy burden on patients and society. This study investigated the frequency of use and costs of select palliative chemotherapy regimens in Japan. METHODS: From July 2021 to June 2022 in 54 healthcare facilities, we gathered data of patients diagnosed with RM-SCCHN and who had started first-line palliative chemotherapy with one of eight commonly used regimens. Patients with nasopharyngeal carcinomas were excluded. The number of patients receiving each regimen and the costs of each regimen for the first month and per year were tallied. RESULTS: The sample comprised 907 patients (674 were < 75 years old, 233 were ≥ 75 years old). 330 (36.4%) received Pembrolizumab monotherapy, and 202 (22.3%) received Nivolumab monotherapy. Over 90% of patients were treated with immune checkpoint inhibitors as monotherapy or in combination with chemotherapy. Treatment regimens' first-month costs were 612 851-849 241 Japanese yen (JPY). The cost of standard palliative chemotherapy until 2012 was about 20 000 JPY per month. The incremental cost over the past decade is approximately 600 000-800 000 JPY per month, a 30- to 40-fold increase in the cost of palliative chemotherapy for RM-SCCHN. CONCLUSION: First-line palliative chemotherapy for RM-SCCHN exceeds 600 000 JPY monthly. Over the last decade, the prognosis for RM-SCCHN has improved, but the costs of palliative chemotherapy have surged, placing a heavy burden on patients and society.

Identification of Ppy-lineage cells as a novel origin of pancreatic ductal adenocarcinoma.

The Ppy gene encodes pancreatic polypeptide (PP) secreted by PP- or γ-cells, which are a subtype of endocrine cells localised mainly in the islet periphery. For a detailed characterisation of PP cells, we aimed to establish PP cell lines. To this end, we generated a mouse model harbouring the SV40 large T antigen (TAg) in the Rosa26 locus, which is expressed upon Ppy-promoter-mediated Cre-loxP recombination. Whereas Insulin1-CreERT-mediated TAg expression in beta cells resulted in insulinoma, surprisingly, Ppy-Cre-mediated TAg expression resulted in the malignant transformation of Ppy-lineage cells. These mice showed distorted islet structural integrity at 5 days of age compared with normal islets. CK19+ duct-like lesions contiguous with the islets were observed at 2 weeks of age, and mice developed aggressive pancreatic ductal adenocarcinoma (PDAC) at 4 weeks of age, suggesting that PDAC can originate from the islet/endocrine pancreas. This was unexpected as PDAC is believed to originate from the exocrine pancreas. RNA-sequencing analysis of Ppy-lineage islet cells from 7-day-old TAg+ mice showed a downregulation and an upregulation of endocrine and exocrine genes, respectively, in addition to the upregulation of genes and pathways associated with PDAC. These results suggest that the expression of an oncogene in Ppy-lineage cells induces a switch from endocrine cell fate to PDAC. Our findings demonstrate that Ppy-lineage cells may be an origin of PDAC and may provide novel insights into the pathogenesis of pancreatic cancer, as well as possible therapeutic strategies. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Predicting isocitrate dehydrogenase status among adult patients with diffuse glioma using patient characteristics, radiomic features, and magnetic resonance imaging: Multi-modal analysis by variable vision transformer.

OBJECTIVES: To evaluate the performance of the multimodal model, termed variable Vision Transformer (vViT), in the task of predicting isocitrate dehydrogenase (IDH) status among adult patients with diffuse glioma. MATERIALS AND METHODS: vViT was designed to predict IDH status using patient characteristics (sex and age), radiomic features, and contrast-enhanced T1-weighted images (CE-T1WI). Radiomic features were extracted from each enhancing tumor (ET), necrotic tumor core (NCR), and peritumoral edematous/infiltrated tissue (ED). CE-T1WI were split into four images and input to vViT. In the training, internal test, and external test, 271 patients with 1070 images (535 IDH wildtype, 535 IDH mutant), 35 patients with 194 images (97 IDH wildtype, 97 IDH mutant), and 291 patients with 872 images (436 IDH wildtype, 436 IDH mutant) were analyzed, respectively. Metrics including accuracy and AUC-ROC were calculated for the internal and external test datasets. Permutation importance analysis combined with the Mann-Whitney U test was performed to compare inputs. RESULTS: For the internal test dataset, vViT correctly predicted IDH status for all patients. For the external test dataset, an accuracy of 0.935 (95% confidence interval; 0.913-0.945) and AUC-ROC of 0.887 (0.798-0.956) were obtained. For both internal and external test datasets, CE-T1WI ET radiomic features and patient characteristics had higher importance than other inputs (p < 0.05). CONCLUSIONS: The vViT has the potential to be a competent model in predicting IDH status among adult patients with diffuse glioma. Our results indicate that age, sex, and CE-T1WI ET radiomic features have key information in estimating IDH status.

Identifying key factors for predicting O6-Methylguanine-DNA methyltransferase status in adult patients with diffuse glioma: a multimodal analysis of demographics, radiomics, and MRI by variable Vision Transformer.

PURPOSE: This study aimed to perform multimodal analysis by vision transformer (vViT) in predicting O6-methylguanine-DNA methyl transferase (MGMT) promoter status among adult patients with diffuse glioma using demographics (sex and age), radiomic features, and MRI. METHODS: The training and test datasets contained 122 patients with 1,570 images and 30 patients with 484 images, respectively. The radiomic features were extracted from enhancing tumors (ET), necrotic tumor cores (NCR), and the peritumoral edematous/infiltrated tissues (ED) using contrast-enhanced T1-weighted images (CE-T1WI) and T2-weighted images (T2WI). The vViT had 9 sectors; 1 demographic sector, 6 radiomic sectors (CE-T1WI ET, CE-T1WI NCR, CE-T1WI ED, T2WI ET, T2WI NCR, and T2WI ED), 2 image sectors (CE-T1WI, and T2WI). Accuracy and area under the curve of receiver-operating characteristics (AUC-ROC) were calculated for the test dataset. The performance of vViT was compared with AlexNet, GoogleNet, VGG16, and ResNet by McNemar and Delong test. Permutation importance (PI) analysis with the Mann-Whitney U test was performed. RESULTS: The accuracy was 0.833 (95% confidence interval [95%CI]: 0.714-0.877) and the area under the curve of receiver-operating characteristics was 0.840 (0.650-0.995) in the patient-based analysis. The vViT had higher accuracy than VGG16 and ResNet, and had higher AUC-ROC than GoogleNet (p<0.05). The ED radiomic features extracted from the T2-weighted image demonstrated the highest importance (PI=0.239, 95%CI: 0.237-0.240) among all other sectors (p<0.0001). CONCLUSION: The vViT is a competent deep learning model in predicting MGMT status. The ED radiomic features of the T2-weighted image demonstrated the most dominant contribution.

Distant recurrence in the cerebellar dentate nucleus through the dentato-rubro-thalamo-cortical pathway in supratentorial glioma cases.

BACKGROUND: Distant recurrence can occur by infiltration along white matter tracts or dissemination through the cerebrospinal fluid (CSF). This study aimed to clarify the clinical features and mechanisms of recurrence in the dentate nucleus (DN) in patients with supratentorial gliomas. Based on the review of our patients, we verified the hypothesis that distant DN recurrence from a supratentorial lesion occurs through the dentato-rubro-thalamo-cortical (DRTC) pathway. METHODS: A total of 380 patients with supratentorial astrocytoma, isocitrate dehydrogenase (IDH)-mutant (astrocytoma), oligodendroglioma, IDH mutant and 1p/19q-codeleted (oligodendroglioma), glioblastoma, IDH-wild type (GB), and thalamic diffuse midline glioma, H3 K27-altered (DMG), who underwent tumor resection at our department from 2009 to 2022 were included in this study. Recurrence patterns were reviewed. Additionally, clinical features and magnetic resonance imaging findings before treatment, at the appearance of an abnormal signal, and at further progression due to delayed diagnosis or after salvage treatment of cases with recurrence in the DN were reviewed. RESULTS: Of the 380 patients, 8 (2.1%) had first recurrence in the DN, 3 were asymptomatic when abnormal signals appeared, and 5 were diagnosed within one month after the onset of symptoms. Recurrence in the DN developed in 8 (7.4%) of 108 cases of astrocytoma, GB, or DMG at the frontal lobe or thalamus, whereas no other histological types or sites showed recurrence in the DN. At the time of the appearance of abnormal signals, a diffuse lesion developed at the hilus of the DN. The patterns of further progression showed that the lesions extended to the superior cerebellar peduncle, tectum, tegmentum, red nucleus, thalamus, and internal capsule along the DRTC pathway. CONCLUSION: Distant recurrence along the DRTC pathway is not rare in astrocytomas, GB, or DMG at the frontal lobe or thalamus. Recurrence in the DN developed as a result of the infiltration of tumor cells through the DRTC pathway, not dissemination through the CSF.

Imaging findings of arrested pneumatisation and differentiation from other skull base lesions.

OBJECTIVES: Arrested pneumatisation (AP) is an anatomic variant of the sphenoid sinus. Since AP remains underrecognised, otolaryngologists and radiologists may mistake AP for a lesion and perform follow-up imaging studies. We investigated the imaging findings of CT, MRI, and F-18 fludeoxyglucose (FDG)-positron emission tomography (PET) for AP, and discussed the differences between AP and other skull base lesions. METHODS: We reviewed multidetector low CT imaging of 442 patients (285 men and 157 women; age range, 19-93 years; mean age, 67.8 years) who underwent FDG-PET/CT for head and neck tumours between January 2019 and December 2019. The imaging findings of AP were reviewed on CT, MRI, FDG-PET/CT, and compared with those of fibrous dysplasia, chordoma, chondrosarcoma, multiple myeloma, and bone invasion of nasopharyngeal carcinoma. RESULTS: AP was identified in 22 patients (14 men and 8 women; age range, 24-93 years; mean age, 67.0 years) based on criteria from previous reports. AP manifested with well-circumscribed sclerotic margins on CT, without evidence of expansion. AP showed high-signal intensity on T1-/T2 weighted MRI. FDG-PET revealed non-significant uptake [maximum standardised uptake value (SUVmax): 0.85 (range, 0.4-1.27)] in AP. Contrastingly, skull base lesions showed expansion, poorly circumscribed boundaries without osteosclerotic margins, and moderate-to-severe FDG uptake (SUVmax: 1.8-8.4). CONCLUSIONS: The characteristic imaging findings of AP, namely non-expansile on CT and non-uptake on FDG-PET, may aid in its differentiation from other skull base lesions.

Human papillomavirus-related multiphenotypic sinonasal carcinoma.

Human papillomavirus-related multiphenotypic sinonasal carcinoma (HMSC) is a rare primary tumor of the sinonasal tract that has been reported recently. It is reportedly associated with human papillomavirus infection. The tumor presents with glandular cyst-like histology, but some cases exhibit squamous epithelialization and are positive on p16 immunohistochemical staining. The clinical picture and treatment of this disease have not been established. However, this report describes a recurrent case of this disease treated with salvage surgery. The patient was a 61-year-old woman who presented to the previous doctor with a chief complaint of nasal obstruction. A localized tumor was found in the left nasal cavity and was resected under endoscopic guidance. The postoperative pathological diagnosis was HMSC. Twenty-one months after the surgery, local recurrence was observed, and the patient was referred to our hospital. Since the recurrent lesion had widely infiltrated outside the nasal cavity, extensive resection and reconstructive surgery were performed. Postoperative radiotherapy was performed as an additional treatment. Notably, 13 months have passed since the salvage surgery, and no recurrence has been observed to date.

Immunohistochemical Analysis of Common Cancer Antigens in Head and Neck Squamous Cell Carcinoma.

BACKGROUND/AIM: The prognosis of recurring and metastatic head and neck squamous cell carcinoma (HNSCC) is poor. Although immune checkpoint inhibitors have expanded the treatment options for HNSCC, the response rates are low. Alternatively, cancer vaccines and T-cell therapies are being developed. Identification of useful common cancer antigens and confirmation of human leukocyte antigen (HLA) class I expression are required. MATERIALS AND METHODS: Immunohistochemistry analyses were performed for 10 antigens (FOXM1, TGFBI, SPARC, HSP105α, WT1, AFP, GPC3, PP-RP, KIF20A, KM-HN-1) and HLA class I using specimens of 56 surgical cases. Staining intensity, percentage of stain-positive areas, and localization of staining in the tumor cells and normal tissue were evaluated. RESULTS: Staining of FOXM1, TGFBI, SPARC, and HSP105α was more predominant in tumor cells than that in normal cells. The expression rates of these antigens in tumor cells were 60.7%, 58.9%, 73.2%, and 50.0%, respectively. Regarding sites, the expression rates of these antigens in oral cancer were high at 57.1%, 71.4%, 81.0%, and 66.7%, respectively. Furthermore, the expression of HLA class I was 83.9% in all cases. Of these, 68.1% showed expression on the plasma membrane. CONCLUSION: FOXM1, TGFBI, SPARC, and HSP105α could be useful common cancer antigens, and HLA class I is expressed on the plasma membrane of cancer cells in many cases. The results suggest that cancer vaccines and T-cell therapy may be clinically viable options for HNSCC treatment.

Comparison between three age-stratified cohorts reveals poor prognosis of young patients with tongue carcinoma.

Objectives: Investigation of the prognosis of young patients with tongue carcinoma has been the focus of several recent studies aimed at improving future precision treatment. Most studies have been two-cohort investigations comparing young and older patients, who have wide discrepancies in prognosis. Older patients, especially those aged >70 years, often have a poor general condition. This affects the prognosis of the older cohort and accounts for the discrepancies observed in two-cohort studies. Accordingly, in this study, older patients (aged ≥71 years) were separated and compared to young and middle-aged patients. Methods: A total of 257 patients with oral tongue carcinoma referred during 2011-2017 were analyzed. Patients were sorted into young (aged ≤40 years), middle-aged (aged ≥41 and ≤70 years), and older (aged ≥71 years) groups. Overall survival (OS) and disease-free survival (DFS) were compared among the groups. Furthermore, patterns of recurrence rates were compared. Results: Compared with young patients, there was no difference in OS or DFS for older patients (hazard ratio [HR]: 1.2, 95% confidence interval [CI]: 0.5-2.7 and HR: 0.7, 95% CI: 0.4-1.2, respectively) in a multivariate analysis. There was also no difference in OS (HR: 0.6, 95% CI: 0.3-1.3) for middle-aged patients. However, middle-aged patients had low recurrence rates (HR: 0.5, 95% CI: 0.3-0.8). With respect to the recurrence type, middle-aged patients had a low local recurrence rate (HR: 0.3, 95% CI: 0.1-0.7). Conclusion: Three-cohort studies should be conducted to evaluate whether the prognosis of young patients with tongue carcinoma is truly poor in terms of future precision treatment.

The Biosynthetic Landscape of Triceptides Reveals Radical SAM Enzymes That Catalyze Cyclophane Formation on Tyr- and His-Containing Motifs.

Peptide-derived cyclophanes inhabit a unique niche in the chemical space of macrocyclic peptides with several examples of pharmaceutical importance. Although both synthetic and biocatalytic methods are available for constructing these macrocycles, versatile (bio)catalysts able to incorporate a variety of amino acids that compose the macrocycle would be useful for the creation of diverse peptide cyclophanes. In this report, we synergized the use of bioinformatic tools to map the biosynthetic landscape of radical SAM enzymes (3-CyFEs) that catalyze three-residue cyclophane formation in the biosynthesis of a new family of RiPP natural products, the triceptides. This analysis revealed 3940 (3113 unique) putative precursor sequences predicted to be modified by 3-CyFEs. Several uncharacterized maturase systems were identified that encode unique precursor types. Functional studies were carried out in vivo in Escherichia coli to identify modified precursors containing His and Tyr residues. NMR analysis of the products revealed that Tyr and His can also be incorporated into cyclophane macrocycles by 3-CyFEs. Collectively, all aromatic amino acids can be incorporated by 3-CyFEs, and the cyclophane formation strictly occurs via a C(sp2)-C(sp3) cross-link between the (hetero)aromatic ring to Cß. In addition to 3-CyFEs, we functionally validated an Fe(II)/α-ketoglutarate-dependent hydroxylase, resulting in ß-hydroxylated residues within the cyclophane rings. This study reveals the potential breadth of triceptide precursors and a systematic approach for studying these enzymes to broaden the diversity of peptide macrocycles.

Is elective neck dissection necessary for patients with cT3-4N0 parotid gland cancer?

OBJECTIVE: Management of the cervical lymph nodes in patients with cT3-4N0 parotid gland cancer (PGC) has been controversial. This study investigated the need for elective neck dissection (END) in patients with cT3-4N0 PGC. METHODS: We retrospectively examined cervical lymph node metastasis, overall survival (OS), and disease-free survival (DFS) rates in 40 patients with cT3-4N0 PGC according to whether or not END was performed. RESULTS: Cervical lymph node metastasis occurred in 27.5% of patients and level II was the most common area. Recurrence could be treated by salvage neck dissection. There was no significant difference in OS (P=0.581) or DFS (P=0.728) between the group that underwent END and the group that did not. CONCLUSION: END at level II is worth performing because of the occult lymph node metastasis rate. The area of neck dissection should be limited because there is no evidence that END improves the prognosis of cT3-4N0 PGC.

A case of Epstein-Barr virus-positive mucocutaneous ulcer of the hypopharynx: a mimicker of hypopharyngeal squamous cell carcinoma.

Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) is a new disease, described by the World Health Organization in 2017. It has been recognized as a specific type of immunodeficiency-associated lymphoproliferative disorder. Since patients with EBVMCU present with only cutaneous or mucosal ulcers, it is difficult to clinically distinguish them from carcinoma. A 72-year-old man, who took methotrexate (MTX) (12 mg/week) for rheumatoid arthritis, was referred to our hospital because endoscopy revealed an ulcerated mass in the left pyriform sinus, suggesting hypopharyngeal squamous cell carcinoma. Contrast-enhanced computed tomography and magnetic resonance imaging revealed an ill-defined mass in the left pyriform sinus without lymphadenopathy in the head and neck region. A biopsy of the ulcerative lesion in the hypopharynx was performed, and lymphoproliferative disease was suspected, based on the histopathological findings. Two weeks after MTX withdrawal, the lesions in the hypopharynx disappeared. The patient was diagnosed with EBVMCU, based on the clinical and histopathological findings. This is the first case report of EBVMCU of the hypopharynx. EBVMCU should be considered as a differential diagnosis in immunocompromised patients with hypopharyngeal mucosal ulcers without lymph node or organ involvement.

High diagnostic accuracy for lymph node metastasis of oral squamous cell carcinoma using PET/CT with a silicon photomultiplier.

OBJECTIVE: The higher sensitivity of the new-generation positron emission tomography/computed tomography (PET/CT) with silicon photomultiplier (SiPM) may increase false-positive rates in detecting metastatic lymph nodes (LNs). This study aimed to clarify the usefulness of the SiPM PET scanner in diagnosing LN metastasis of oral squamous cell carcinoma (SCC). METHODS: We retrospectively reviewed consecutive F-18 fluorodeoxyglucose PET/CT images of 39 SCC patients using SiPM PET and 31 SCC patients using non-SiPM PET. We measured the maximum standardized uptake value (SUVmax) of the LNs on PET images and maximum short-axis diameter on transverse CT images. RESULTS: The sensitivity and specificity of SiPM PET were 86.2% and 95.6%, respectively (cut-off SUVmax, 4.6). The area under the curve (AUC) of SiPM PET (0.977; 95% confidence interval [CI], 0.958-0.995) was significantly higher than that of non-SiPM PET (0.825; 95% CI 0.717-0.934) (P < 0.01). In a size-limited analysis of diameter, the AUC of SiPM PET (≥ 0.96 for all diameters) was significantly higher than that of non-SiPM PET (tended to decrease as the LN diameter decreased) for the diagnosis of LN metastasis by SUVmax. CONCLUSION: SiPM PET had higher diagnostic accuracy for LN metastasis of oral SCC than non-SiPM PET, even for small LN metastasis without increasing false-positives.

Value of intraoperative pathological diagnosis in decision-making regarding resection of well-differentiated retropharyngeal liposarcoma: A case report.

INTRODUCTION AND IMPORTANCE: Preoperative diagnosis of well-differentiated liposarcoma (WDLS) in the retropharyngeal space is challenging because of the difficulty in obtaining a biopsy tissue specimen that will yield the microscopic findings necessary for a definitive pathological diagnosis. This report describes a case of retropharyngeal WDLS that was successfully diagnosed intraoperatively, which allowed radical resection. CASE PRESENTATION: The patient was a 60-year-old man suspected of having a lipomatous tumor in the retropharyngeal space. On imaging, the tumor contained linear septum-like structures that were prominent behind the larynx. Pathological examination was performed using fine-needle aspiration cytology and core needle biopsy specimens. However, no malignant features were found. Given that partial biopsy of the retropharyngeal tumor by puncture was anatomically limited, we decided to collect appropriate tissue specimens for intraoperative pathological examination. During the operation, we biopsied the tumor, including the hard portion behind the larynx, anticipating inclusion of the septum-like structures seen on imaging. A pathological diagnosis of WDLS was successfully made and the tumor was completely excised. CLINICAL DISCUSSION: The fibrous septum with induration is important for intraoperative diagnosis of WDLS. The fibrous septum within the tumor was palpable as a rubbery hard portion. CONCLUSION: WDLS in the retropharyngeal space could be successfully resected surgically by making a rapid intraoperative pathological diagnosis using appropriately selected tissue sampled from a hard portion of the tumor.

Preoperative Endovascular Embolization in an Easily Bleeding Respiratory Epithelial Adenomatoid Hamartoma of the Olfactory Cleft: A Case Report.

Respiratory epithelial adenomatoid hamartomas (REAHs) are rare tumors occurring in the nasal cavity and sinuses, and their etiology is unknown. REAH is a relatively recently established lesion and is often misdiagnosed as nasal polyposis or other tumors. Preoperative endovascular embolization for sinonasal tumors is now widely accepted as an effective method to reduce blood loss, soften the tumor, and facilitate surgical procedures. However, to the best of our knowledge, there are no reports of the requirement for preoperative embolization in the management of REAH. Here, we present a 70-year-old man with an easily bleeding REAH of the olfactory cleft, vascularized by branches of the bilateral internal and external carotid arteries. We removed the tumor endoscopically after preoperative embolization of the bilateral sphenopalatine arteries. Histological investigation revealed an intratumoral hemorrhage accompanying the REAH, with no evidence of a residual or recurrent tumor during the last follow-up at 3 months. In conclusion, accurate preoperative diagnosis and proper preoperative interventions such as embolization are needed for safe and adequate treatment of REAHs that have an abundant blood flow.

A Case of Ectopic Thyroid Presenting as a Superior Mediastinal Mass.

We report a very rare case of an ectopic thyroid in the superior mediastinum, which was detected incidentally using imaging. The case was a 50-year-old woman patient. She had an orthotopic thyroid and normal thyroid function. This superior mediastinum mass obviously lacked continuity with the orthotopic thyroid. Its computed tomography density was lower than that of the orthotopic thyroid, and an enhancement was heterogeneously observed. In the cytodiagnosis, only large and small lymphocytes were observed, and malignant diseases such as malignant lymphoma could not be ruled out, so surgical resection was performed through a cervical incision. Combined resection of the thyroid was unnecessary, and ligation of the feeding vessels from the thorax side was able to be carried out without incident.

Assessment and agreement of the CT appearance pattern and its severity grading of radiation-induced lung injury after stereotactic body radiotherapy for lung cancer.

PURPOSE: Radiographic severity of radiation-induced lung injury (RILI) has not been well-studied. The goal of this study was to assess the CT appearance pattern and severity of RILI without consideration of the clinical presentation. MATERIAL AND METHODS: A total of 49 patients, 41 with primary lung cancer and 8 with metastatic lung cancer, were treated by 4-fraction stereotactic body radiotherapy (SBRT). RILI after SBRT was separately assessed by two observers. The early and late CT appearance patterns and CT-based severity grading were explored. RESULTS: The median follow-up period was 39.0 months. In the early CT findings of observers 1 and 2, there was diffuse consolidation in 15 and 8, diffuse ground glass opacity (GGO) in 0 and 0, patchy consolidation and GGO in 17 and 20, patchy GGO in 3 and 3, and no changes in 10 and 14, respectively (kappa = 0.61). In late CT findings of observer 1 and 2, there were modified conventional pattern in 28 and 24, mass-like pattern in 8 and 11, scar-like pattern in 12 and 12, and no changes in 1 and 2, respectively (kappa = 0.63). In the results of the CT-based grading by observers 1 and 2, there were grade 0 in 1 and 2, grade 1 in 10 and 14, grade 2 in 31 and 29, grade 3 in 7 and 4, and none of grade 4 or more, respectively (kappa = 0.66). According to multivariate analyses (MVA), the significant predicting factors of grade 2 or more CT-based RILI were age (p = 0.01), oxygen dependence (p = 0.03) and interstitial shadow (p = 0.03). CONCLUSIONS: The agreement of the CT appearance and CT-based grading between two observers was good. These indicators may be able to provide us with more objective information and a better understanding of RILI.

Prognostic Value of Radiation Pneumonitis After Stereotactic Body Radiotherapy: Effect of Pulmonary Emphysema Quantitated Using CT Images.

BACKGROUND: The aim of this study was to determine the prognostic factors of radiation pneumonitis (RP) after stereotactic body radiotherapy (SBRT). PATIENTS AND METHODS: A total of 50 patients (36 male and 14 female) were treated with SBRT for 42 primary lung cancers and 8 metastatic lung cancers. SBRT was performed with 48 Gy in 4 fractions to the isocenter or with 40 Gy in 4 fractions covering 95% of the planning target volume. Percentage of low attenuation area (%LAA) was defined as percentage of the lung area with attenuation of -860 Hounsfield units (HU) or lower (%LAA-860) or of -960 HU or lower (%LAA-960). The dosimetric parameter of V20 Gy, which means percentage volume of the lung receiving 20 Gy or more, was recalculated. RP was assessed using Common Terminology Criteria for Adverse Events version 4.0. RESULTS: The median follow-up period was 39.0 months (range, 7.2-94.5 months). RP of Grade 0, Grade 1, and Grade 2 to 3 was diagnosed in 11, 29, and 10 patients, respectively. Multivariate analyses (MVA) for Grade 1 showed that higher %LAA-860 and higher %LAA-960 were significantly associated with a lower rate of Grade 1 RP. MVA for Grade 2 to 3 showed that lower Brinkman index and lower lung V20 Gy were significantly associated with a lower rate of Grade 2 to 3 RP, and, in contrast, %LAA-860 and %LAA-960 had no association with Grade 2 to 3 RP. CONCLUSION: This result suggests that high %LAA is associated with radiological changes (Grade 1) but that %LAA has no correlation with Grade 2 to 3 RP because symptomatic RP might also be affected by other factors.