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Although the SpyGlass Direct Visualization System can be clinically useful for diagnosing indeterminate biliary stricture, it employs SpyBite forceps, which typically obtain only a small amount of tissue and have a low sampling rate. An improved forceps biopsy device for SpyGlass DS has recently been released (SpyBite MAX). The aim of this prospective registration study was to assess the diagnostic yield and efficacy of histological biopsy tissue obtained with SpyBite MAX forceps compared with SpyBite forceps in patients with indeterminate biliary stricture.The primary outcome of the study was the diagnostic accuracy of biopsy specimens obtained by SpyBite MAX forceps. The secondary outcomes were tissue size, number of forceps biopsies, rate of obtaining adequate tissue, and adverse events in the SpyBite MAX forceps group compared with the SpyBite group.Forceps biopsies using SpyBite MAX (n = 47) and SpyBite (n = 50) were performed successfully in all patients. The number of biopsies performed before visible core tissue was obtained was significantly lower in the SpyBite (mean, 1.5 ± 0.7) than in the SpyBite forceps group (mean, 2.3 ± 1.1 mm; P .001). Tissue sample size was larger in the SpyBite MAX group (mean, 1.8 ± 1.6 mmImprovements in dedicated forceps for biopsy in SpyGlass DS may contribute to improving the rates of adequate tissue and tissue sample size obtained, and to reducing the number of forceps biopsies required.

Glucocorticoids (GCs) are highly effective yet problematic agents against bronchopulmonary dysplasia (BPD). The dimeric trans-activation of GCs induces unfavorable effects, while monomeric trans-repression suppresses inflammation-related genes. Recently, non-steroidal-selective glucocorticoid-receptor agonists and modulators (SEGRAMs) with only the trans-repressive action have been designed.Using a bleomycin (Bleo)-induced alveolar simplification newborn rat model (recapitulating arrested alveolarization during BPD), we evaluated the therapeutic effects of compound-A (CpdA), a SEGRAM. Sprague-Dawley rats were administered Bleo from postnatal day (PD) 0 to 10 and treated with dexamethasone (Dex) or CpdA from PD 0 to 13. The morphological changes and mRNA expression of inflammatory mediators, including interleukin (IL)-1β, C-X-C motif chemokine ligand 1 (CXCL1), and C-C motif chemokine 2 (CCL2) were investigated.Similar to the effects of Dex, CpdA exerted protective effects on morphological derangements and inhibited macrophage infiltration and production of pro-inflammatory mediators in Bleo-treated animals. The effects of CpdA were probably mediated by GC receptor (GR)-dependent trans-repression, because unlike the Dex-treated group, anti-inflammatory genes specifically induced by GR-dependent trans-activation (such as "glucocorticoid-induced leucine zipper, GILZ") were not upregulated.CpdA improved lung inflammation, inhibited the arrest of alveolar maturation, and restored histological and biochemical changes in a Bleo-induced alveolar simplification model.SEGRAMs have attracted widespread attention because they are expected to not exhibit unfavorable effects of GCs. Compound A, one of the SEGRAMs, improved lung morphometric changes and decreased lung inflammation in a bleomycin-induced arrested alveolarization, a newborn rat model representing one of the main features of BPD pathology. Compound A did not elicit bleomycin-induced poor weight gain, in contrast to dexamethasone treatment. SEGRAMs, including compound A, may be promising candidates for the therapy of BPD with less adverse effects compared with GCs.

Supplementary Figure 1 from Development of Gastric Tumors in ApcMin/+ Mice by the Activation of the β-Catenin/Tcf Signaling Pathway

Supplementary Figure 2 Legend from Development of Gastric Tumors in ApcMin/+ Mice by the Activation of the β-Catenin/Tcf Signaling Pathway

Supplementary Table 1 from Development of Gastric Tumors in ApcMin/+ Mice by the Activation of the β-Catenin/Tcf Signaling Pathway

Supplementary Figure 1 Legend from Development of Gastric Tumors in ApcMin/+ Mice by the Activation of the β-Catenin/Tcf Signaling Pathway

Although several lines of evidence suggest the involvement of the Wnt pathway in the development of gastric cancers, the functional significance of the pathway in gastric carcinogenesis is still poorly defined. To examine the role of the Apc/β-catenin signaling pathway in the development of gastric cancers, we investigated the gastric mucosa of the ApcMin/+ mouse, which is a murine model for familial adenomatous polyposis, carrying a germ-line mutation at codon 850 of Apc. We found that aged ApcMin/+ mice spontaneously develop multiple tumors in the stomach, which are accompanied by loss of heterozygosity of Apc. Such tumors consisted of adenomatous glands with strong nuclear accumulation of β-catenin. Even a single adenomatous gland already showed nuclear accumulation of β-catenin, suggesting that Apc/β-catenin pathway is an initiating event in gastric tumorigenesis in ApcMin/+ mice. Myc and cyclin D1 expressions, which are transcriptional targets of β-catenin/Tcf, increased in the adenomatous lesions. Furthermore, β-catenin/Tcf reporter transgenic mice with ApcMin allele showed higher levels of the transcriptional activity of β-catenin/Tcf in the gastric tumors. We also treated ApcMin/+ and wild-type mice with N-methyl-N-nitrosourea (MNU), an alkylating agent that induces adenomas and adenocarcinomas in the stomach. Consequently, MNU-treated ApcMin/+ mice significantly enhanced the tumor development in comparison with ApcMin/+ mice or MNU-treated wild-type mice. Several gastric tumors in MNU-treated ApcMin/+ mice showed invasion into the submucosal layer. These results indicate that the Apc/β-catenin pathway may play an important role in at least subset of gastric carcinomas. In addition, ApcMin/+ mice combined with MNU could be a useful short-term model to investigate multistage carcinogenesis in the stomach. [Cancer Res 2007;67(9):4079–87]

ObjectiveTo address the pathomechanism of microscopic polyangiitis (MPA) complicated by interstitial lung disease (ILD) using serum biomarker profile and pulmonary histopathology.MethodsSerum biomarkers from patients with MPA-ILD (n = 32), MPA without ILD (n = 17), and healthy controls (n = 10) were examined. Based on the biomarker profiles, principal component analysis (PCA) and cluster analysis were performed to classify patients with MPA-ILD into subgroups. Clinical characteristics and prognosis were assessed for each subgroup. Two lung biopsies were examined following H&E staining and immunostaining.ResultsT cell and macrophage polarization was skewed toward the T helper (Th) 2 cells and M2 macrophages in the MPA-ILD group relative to that in MPA without ILD group. The PCA allowed classification of the 19 biomarker profiles into 3 groups: (1) B cell– and neutrophil-related cytokines, vascular angiogenesis-related factors, extracellular matrix-producing factors; (2) Th1-driven cytokines, M1 macrophage-driven cytokines, and Th2-driven cytokines; and (3) M2 macrophage-induced and driven cytokines. The cluster analysis stratified the patients with MPA-ILD into clinically fibrotic-dominant (CFD) and clinically inflammatory-dominant (CID) groups. Notably, severe infections were significantly higher in the CFD group than in the CID group. Immunohistochemical staining demonstrated intense CXC motif chemokine ligand 13 staining in B cells and Th2 cells in the interstitium of the lungs of patients with MPA-ILD.Conclusion.The activation of M2 macrophages, Th2 cells, and B cells plays a key role in the pathomechanism of MPA-ILD. Classification of MPA-ILD based on serum biomarker profile would be useful in predicting the disease activity and the complications of severe infection in MPA-ILD.

There has been accumulating evidence for the clinical benefit of chemoradiation therapy (CRT), whereas mechanisms in CRT-recurrent clones derived from the primary tumor are still elusive. Herein, we identified an aberrant BUB1B/BUBR1 expression in CRT-recurrent clones in bladder cancer (BC) by comprehensive proteomic analysis. CRT-recurrent BC cells exhibited a cell-cycle-independent upregulation of BUB1B/BUBR1 expression rendering an enhanced DNA repair activity in response to DNA double-strand breaks (DSBs). With DNA repair analyses employing the CRISPR/cas9 system, we revealed that cells with aberrant BUB1B/BUBR1 expression dominantly exploit mutagenic nonhomologous end joining (NHEJ). We further found that phosphorylated ATM interacts with BUB1B/BUBR1 after ionizing radiation (IR) treatment, and the resistance to DSBs by increased BUB1B/BUBR1 depends on the functional ATM. In vivo, tumor growth of CRT-resistant T24R cells was abrogated by ATM inhibition using AZD0156. A dataset analysis identified FOXM1 as a putative BUB1B/BUBR1-targeting transcription factor causing its increased expression. These data collectively suggest a redundant role of BUB1B/BUBR1 underlying mutagenic NHEJ in an ATM-dependent manner, aside from the canonical activity of BUB1B/BUBR1 on the G2/M checkpoint, and offer novel clues to overcome CRT resistance.

Graft-versus-host disease (GVHD) is a physiological response of the graft to allogeneic hosts. However, the effector cells, affected organ(s), and cytokines in the GVHD remain controversially discussed, without having determined a particular cytotoxic activity of the graft against the host. After

It has been well recognized that the tumor microenvironment serves important roles in the progression and invasion of cancer. The desmoplastic reaction (DR) is a fibrous tissue reaction around tumor cells, and the prognostic significance of DR in colorectal cancer (CRC) has been established. Tumor deposits (TD) are also an important prognostic indicator of CRC. Notably, immature type DR has been linked to poor prognosis. In addition, immature type DR is significantly associated with a higher pT stage, presence of lymphovascular invasion and lymph node metastasis; however, to the best of our knowledge, the association between DR and TD has not yet been examined. The present study aimed to clarify this association. This study included 443 consecutive patients with pT3 or pT4 CRC who underwent surgical resection. The histopathological features, including DR and TD, were evaluated. Statistical analyses of the presence of TD, DR and other clinicopathological parameters were performed. The present cohort included 205 female and 238 male patients; 293 (66.1%) and 150 (33.9%) patients were classified as pT3 and pT4, respectively. Immature, intermediate and mature DR were noted in 282 (63.7%), 91 (20.5%) and 70 patients (15.8%), respectively. TD was observed in 93 (21.0%) patients. Immature type DR was significantly associated with a higher pT stage (P0.0001), presence of lymph node metastasis (P0.0001), lymphatic (P=0.0007), venous (P0.0001) and perineural invasion (P0.0001), and higher tumor budding (TB) (P0.0001). Moreover, immature type DR was significantly associated with the presence of TD (P0.0001). The present study demonstrated a significant association between immature type DR and the presence of TD, and suggested a close relationship between lymphovascular invasion, DR, TB and TD. Additional studies are required to analyze the detailed mechanism underlying the development of immature DR in CRC to define novel treatment strategies.

Background: Bronchogenic cyst is a congenital malformation of the bronchial tree, detected as a cystic and/or mass lesion in the thoracic cavity. Although its occurrence in distant locations, such as the skin and retroperitoneum, has been reported, the components and phenotypes of the epithelium that line a bronchogenic cyst in rare sites have scarcely been evaluated.Case presentation: We reviewed 34 available bronchogenic cysts that were surgically resected at Osaka Medical and Pharmaceutical University Hospital from 1998 to 2020. We found several bronchogenic cysts in rare sites, and reconfirmed their diagnoses based on the following anatomopathological criteria: the presence of pseudostratified, ciliated, and/or columnar epithelium together with at least one of the following – cartilage, smooth muscle, or seromucous glands. The phenotypes of the epithelium lining the cyst were characterized using immunohistochemical analysis. Six bronchogenic cysts in rare sites (two cases in the retroperitoneum, two cases in the skin, one case in the cervical spinal cord, and one case in the pericardial cavity) met the criteria for the reconfirmation of the diagnoses. The epithelium lining the cyst stained positive for cytokeratin CK7 and thyroid transcription factor 1 (a marker expressed in thyroid follicle, and bronchial epithelium), and negative for CK20, indicating that the phenotypes were similar to those of the respiratory epithelium. Conclusions: This study shows that a bronchogenic cyst could occur in rare sites, such as the retroperitoneum, skin, spinal cord, and pericardial cavity, suggesting that it should be listed as a differential diagnosis before surgical resection in order to apply relevant management modalities.

Objective To summarize the diagnosis and treatment outcomes of basal cell adenocarcinoma (BCAC) of the parotid gland, a rare low-grade malignancy, at a single institution, and to investigate the treatment approach for this rare malignancy. Methods We conducted a retrospective analysis of 9 patients with BCAC during 20 years from September 1999 to December 2019. Forty-five patients with basal cell adenoma (BCA), who were treated during the same time period, were used for comparison. The clinical characteristics of BCAC, diagnostic imaging, the usefulness of fine-needle aspiration cytology (FNAC) and frozen section biopsy (FSB), histological assessment of malignancy, and treatment outcomes were investigated. Results There were no marked differences in sex, age, tumor diameter, or tumor location between BCAC and BCA cases. Among the 9 patients with BCAC, one patient was noted with pain/tenderness, and two patients were observed with adhesion to the surrounding tissues. Only one patient was diagnosed as malignant based on MRI/US. FNAC for BCAC was suspicious for malignancy in 6 of the 9 cases, which included one patient with the correct grade of malignancy, one patient with malignancy only, and 4 patients suspicious for malignancy. FSB was suspicious for malignancy in 8 of the 9 cases. Malignancy grade was determined based on infiltration to the surrounding tissues and expression of Ki-67, p53, and bcl-2. One patient with infiltration to the surrounding tissue was diagnosed as intermediate-grade malignancy, while the remaining 8 patients were diagnosed as low-grade malignancy. The BCAC cases included 7 patients with T2 and 2 patients with T1. Conservative resection was performed for all patients, and all cases are surviving cancer-free. Conclusion The malignancy of BCAC can be suspected before surgery based on symptoms/signs, diagnostic imaging, and FNAC. FSB enables the diagnosis of not only malignancy but also the grade of malignancy, which may help determine the appropriate surgical resection. Although all 9 patients with BCAC are surviving free from cancer, a long-term follow-up is warranted.

Objective The objective of this study was to evaluate nailfold videocapillaroscopy (NVC) as a useful tool for assessing the disease activity of ANCA-associated vasculitis (AAV). Methods This study enrolled 51 patients with AAV and 21 healthy controls. We scored NVC findings semiquantitatively, and compared them between AAV patients and controls. We examined the association of NVC findings with disease activity indicators, histopathological findings of skin biopsies, and high-resolution CT (HRCT) scores in AAV. Additionally, we repeatedly rated the NVC findings 3 months after immunosuppressive therapy. Results Of the 51 enrolled patients, 36 (70.6%) showed a microangiopathy pattern and 4 (7.8%) showed a scleroderma pattern in AAV. The scores for microhaemorrhage, capillary loss, neoangiogenesis, and tortuosity were significantly higher in the AAV group than in the control group. NVC abnormalities correlated with the severity of skin, lung and kidney involvement. The scores of giant capillaries significantly correlated with the total BVAS and the chest BVAS; the scores of capillary loss correlated with the chest BVAS and the renal BVAS. The scores of microhaemorrhage significantly correlated with perivascular inflammatory cell infiltrations in the upper dermis of the purpura and tended to correlate with the total ground-glass opacity and consolidation scores on HRCT. In addition, capillary loss scores had a significant positive correlation with serum creatinine levels. Additionally, the microhaemorrhage scores were significantly reduced after 3 months of immunosuppressive therapy. Conclusion In AAV patients, NVC abnormalities are significantly associated with disease severity. This result suggests that NVC is a useful tool for assessing the disease activity and treatment response in AAV.

Highlights • The first reported case of Trousseau’s syndrome associated with rapidly emerging pancreatic cancer potentially triggered esophagectomy. • The aggressively emerging pancreatic cancer with mucin production may be a potential mechanism for cancer-related thrombosis. • When a patient with cancer encountered small, multiple cerebral infarctions postoperatively, the body should be checked for occult malignancy., Introduction Trousseau’s syndrome is characterized as an unexpected, cancer-associated thrombotic event. We describe the first reported case of Trousseau’s syndrome associated with rapidly emerging pancreatic cancer potentially triggered by esophagectomy. Presentation of case A 79-year-old asymptomatic male with clinical stage I esophageal squamous cell carcinoma underwent thoracoscopic subtotal esophagectomy. On postoperative day 46, the patient presented with weakness of his left upper extremity due to multiple cerebral and cerebellar infarctions, with no evidence of atherosclerotic or cardiogenic thrombi. An abdominal computed tomography (CT) showed a pancreatic tumor with multiple liver metastases. Extremely high D-dimer and the CT findings suggested Trousseau’s syndrome associated with a rapidly emerging neoplasm as the etiology of the brain infarction. Although further thrombotic events did not occur, his condition deteriorated rapidly and died on the 31st days of onset. The autopsy revealed multiple small infarctions, with multiple thrombi in the cerebral hemispheres, brain stem, and cerebellum. Histological evaluation revealed pancreatic adenocarcinoma with nodal and liver metastases. Discussion A hypercoagulable state associated with the aggressively emerging pancreatic adenocarcinoma, accompanied by cancer cell production of mucin, may be a potential mechanism for cancer-related thrombosis. Conclusion In patients who received intensive surgical treatment and encountered unexplained brain infarctions in the multi-arterial territory, Trousseau’s syndrome should be considered, and investigation for occult malignancy is required.

Objective The temporal fascia has been widely used in tympanoplasty. In addition, the preserved fascia has been also used in the ear surgery. In this study, we planned the experiments to determine whether physical and chemical properties of the fascia preserved at a low temperature. Methods Preserved temporal fasciae from 21 patients were used in this study. The thickness of the temporal fascia was measured under a 3D laser microscope. The tensile strength was evaluated using a tensile tester. In addition, the chemical property evaluated was the biologic antioxidative potential of samples. Results The results showed that the strength of the fascia was not affected by the retention period. The thick fascia tended to show the less tensile strength. The intensity was highest in middle-aged donors when compared to young and older donor. The antioxidative potentials did not affect the preservation. Conclusion The results suggested that the preserved temporal fascia could be safely used for tympanoplasty.

Reversible post-translational modification of serine and threonine residues by O-linked N-acetylglucosamine (O-GlcNAc), termed O-GlcNAcylation has been indicated to regulate the activities of a number of different proteins. Augmented O-GlcNAcylation contributes to the etiologies of type 2 diabetes mellitus (T2DM) and cancer. Moreover, diabetic conditions increase the risk of colorectal cancer. However, the effect of O-GlcNAcylation in patients with colorectal cancer and concurrent T2DM has not been elucidated. The current study evaluated the level of O-GlcNAcylation in patients with colorectal cancer with or without T2DM. Notably, O-GlcNAcylation levels were significantly higher in tissues from patients with T2DM compared with those in patients without T2DM, and higher in cancer tissues compared with corresponding adjacent tissues. O-GlcNAcylation and cancer stage were more strongly correlated in cancer tissues from patients with T2DM compared with those from patients without T2DM. Additionally, distant metastasis was significantly correlated with O-GlcNAcylation in cancer tissues from patients with T2DM. β-catenin levels in colorectal cancer tissues were the highest in patients with advanced-stage cancer and concurrent T2DM. In SW480 human colon cancer cells, thiamet G (TMG) treatment and OGA silencing, which increased O-GlcNAcylation, significantly increased β-catenin and SNAIL in high-glucose, but not during normal-glucose conditions. These data suggest that O-GlcNAcylation is closely associated with distant metastasis, most likely through upregulation of the β-catenin/SNAIL signaling pathway in colorectal cancer patients with T2DM.

The malignancy of parotid carcinoma varies, and accurate preoperative assessment of malignancy is important for selecting the appropriate treatment. However, the preoperative diagnosis of low/intermediate-grade carcinoma is difficult, and surgery may sometimes be performed without any prior knowledge of malignancy. The results of fine-needle aspiration cytology (FNA), imaging studies (MRI and US), physical examination, and frozen section biopsy (FSB) were evaluated in 112 patients with low/intermediate-grade parotid carcinoma. The result of FNA was benign/inadequate specimen in 44.6% of the patients. In addition, the tumor was diagnosed as benign by MRI/US in 21.4% of the patients and 37.5% had no symptoms/signs of malignancy on physical examination. The rate of misdiagnosis as benign decreased when FNA was combined with imaging and physical findings. However, malignancy could not be diagnosed by FNA and FSB in 12.5% of the patients who were only found to have malignant tumors by the final pathological examination. FNA shows a high misdiagnosis rate of malignancy in patients with low/intermediate-grade cancer. Therefore, it is necessary to carefully evaluate the findings of imaging studies and physical examination, and FSB should be conducted if such findings suggest the possibility of malignancy.

Background: The immune checkpoint ligand programmed death ligand-1 (PD-L1) is expressed by various cancers, including those of the head and neck. However, the role of PD-L1 is still unknown.Objectives: To investigate the relationship between PD-L1 expression and survival rate in parotid carcinoma.Methods: PD-L1 expression was investigated by immunohistochemical analysis in 127 patients with parotid carcinoma. The relationship between PD-L1 expression and stage, histological grade, and survival was assessed.Results: PD-L1 expression was found in 28.3% of parotid carcinomas, with the expression being higher in tumors with a higher stage, a higher-grade, and node positive cases. However, the 5-year disease-specific survival rate was 82.2% for the patients with PD-L1 positive and 86.9% for those with PD-L1 negative tumors, showing no significant difference.Conclusions: PD-L1 expression was positive in approximately 50% of high- grade carcinomas, which was similar to the level in head and neck squamous cell carcinoma. In patients with other cancers, it has been reported that an anti-PD-1 monoclonal antibody was more effective against tumors with higher PD-L1 expression. Therefore, it could be a possible new therapeutic option for patients with highly malignant parotid tumors that have a poor prognosis.

Mucoepidermoid carcinoma (MEC) is the most common malignancy of the parotid gland, but the outcome depends on the histological grade. Therefore, the aim of this study was to evaluate MEC on the basis of histological grade.Retrospective analysis.We performed a retrospective analysis of data from patients whose initial treatment for MEC of the parotid gland was performed at our department between 1999 and 2021. We examined the association between the Armed Forces Institute of Pathology (AFIP) grade and outcome.The AFIP grades were as follows: low, 26 cases; intermediate, 9 cases; and high, 31 cases. About 50% of cases were correctly diagnosed as malignant, and both grade and histology were accurately determined by fine-needle aspiration cytology in 20% of cases. The 5-year disease-free survival rate was 95.5% and 53.8% in the low-/intermediate- and high-grade cases, respectively. In the high-grade group, cases with recurrence were found to have a higher rate of lymph nodes metastasis than cases without recurrence. Furthermore, in this high-grade group, total sacrifice of the facial nerve did not reduce local recurrence. However, radical resection in the cases without tumor invasion to the nerve has decreased the local recurrence rate. The CRTC1-MAML2 fusion gene was expressed in 42.3% of low-/intermediate- and 14.3% of high-grade cases.The survival rate in MEC was quite different between the low-/intermediate- and high-grade cases. However, the rate of correct assessment of the grade by fine-needle aspiration cytology was poor. In high-grade cases, total sacrifice of the facial nerve may improve the rate of local recurrence in cases without invasion of the main trunk of the nerve. Expression of the CRTC1-MAML2 fusion gene could be helpful in not only the assessment of grade but the prediction of recurrence.4.

Objective Surgery for recurrent pleomorphic adenoma of the parotid gland is challenging since there is a considerable risk of facial nerve injury and a high re-recurrence rate. We investigated surgery for recurrent pleomorphic adenoma, focusing on management of the facial nerve. Methods We reviewed 29 patients who underwent surgery for recurrent benign pleomorphic adenoma of the parotid gland at our department between 1999 and 2018. We examined clinicopathologic features and risk factors for facial nerve injury during reoperation. Results Factors associated with difficulty in identifying the main trunk of the facial nerve during surgery were bilobar tumors, multiple tumors, and use of an S-shaped skin incision at the previous operation. When the facial nerve was identified intraoperatively, it could be preserved in 2/3 of patients, while the nerve was only preserved in 1/3 of patients when it was not identified. Factors related to permanent postoperative paralysis included recurrence in the deep lobe or both lobes and multiple tumors. Conclusion The probability of successfully preserving the facial nerve is relatively high if the nerve can be identified during surgery for recurrent pleomorphic adenoma, although intentional resection is necessary in some patients. Factors associated with difficulty in identifying the facial nerve are similar to those related to permanent postoperative paralysis, including bilobar tumors and multiple tumors. In patients with recurrent pleomorphic adenoma, preservation of the facial nerve is difficult, when they may have undergone previous extensive resection or have multiple tumors requiring subtotal or more extensive resection.

Mammary analogue secretory carcinoma (SC) of the parotid gland is a relatively uncommon cancer associated with the ETV6–NTRK3 fusion product similar to breast cancer. The clinical characteristics and outcome of treatment were reviewed for patients with this tumor at our hospital. In this retrospective case series, 24 patients with a diagnosis of acinic cell carcinoma (AcCC) of the parotid gland were classified as having either SC or AcCC based on analysis of the ETV6–NTRK3 fusion gene. These two groups were compared with respect to their clinical and imaging characteristics (MRI/US), cytologic findings, accuracy of fine-needle aspiration cytology and frozen section, treatment outcomes, and immunohistochemical findings. Based on re-classification by ETV6–NTRK3 fusion gene analysis, the diagnosis was SC in 14 patients and AcCC in 10 patients. The SC group had a significantly higher proportion of male patients and was also significantly younger than the AcCC group. Imaging studies revealed that SC was significantly more likely to show internal heterogeneity. Correct grading of both tumors was comparable by fine needle aspiration, with the rate being 60% for AcCC and 50% for SC. Diagnosis by frozen section biopsy diagnosis obtained the correct grade in 90% of the AcCC group and 93% of the SC group. In 24 patients previously diagnosed with AcCC, re-analysis of the ETV6–NTRK3 fusion product indicated that 14 patients actually had SC. Although AcCC and SC show similarities of their biological aggressiveness and prognosis, patients with SC were significantly more likely to be male and younger.

Severe ventricular arrhythmias such as high-grade atrioventricular block and ventricular tachycardia may cause lethal conditions or sudden death in patients with cardiac sarcoidosis (CS). Physicians should examine patients carefully for these conditions and treat them appropriately. As arrhythmias are being better diagnosed and treated, physicians are increasingly aware of atrial arrhythmias, which have not been focused upon as CS-related conditions, in patients with CS. This article reports a case of atrial flutter in sarcoidosis, and discusses literature findings on atrial arrhythmias and atrial involvement of CS. It is highly likely that atrial arrhythmia and supraventricular conduction disorder associated with or caused by CS are more common than previously thought. Physicians should pay careful attention for these conditions in the diagnosis and treatment of CS.

Background: Neoadjuvant chemotherapy for advanced gastric cancer is expected to improve prognoses. However, as there is no method to evaluate neoadjuvant chemotherapeutic efficacy before gastrectomy, some patients at high risk for a poor prognosis undergo gastrectomy. The aim of the present study was to investigate whether endoscopy could be useful for assessing the efficacy of neoadjuvant chemotherapy. Methods: In this retrospective study, we analyzed the data of 41 patients who received neoadjuvant chemotherapy followed by gastrectomy at our institution to investigate whether responsiveness to neoadjuvant chemotherapy, as assessed with endoscopy, can serve as a surrogate marker for histological grades 1b or higher in the Japanese Classification of Gastric Carcinoma (JCGC) scheme. Results: There were 32 (78.0%) responders and 9 (22.0%) nonresponders to neoadjuvant chemotherapy, as observed in endoscopic evaluations. Among the endoscopic responders, 24 (75.0%) had cancer of histological grade 1b or higher, and 15 (46.9%) had cancer of grade 2 or higher. Among the endoscopic nonresponders, 1 (11.1%) patient had histological grade 1b cancer. Compared with endoscopic nonresponders, endoscopic responders were more likely to show a histological response (chi-square test: p = 0.0005 for JCGC grade 1b or higher; p = 0.0099 for JCGC grade 2 or higher). Conclusions: Most endoscopic responders showed JCGC histological responses. Evaluation of neoadjuvant chemotherapeutic efficacy by endoscopy in gastric cancer may be useful before gastrectomy. As this was a retrospective study, further investigations are required. The protocol was approved by the ethics review committee at Osaka Medical College (No. 2422) and was registered in the University Hospital Medical Information Network Clinical Trial Registry (UMIN000033088).

Objective To investigate the clinical feature of the poorly differentiated thyroid papillary carcinoma. Methods We investigate retrospectively 276 thyroid papillary carcinoma patients who underwent initial treatment at our Department who underwent initial treatment at our Department during the 13-year period from 2000 to 2012. We examine the pathological samples of papillary carcinoma retrospectively to investigate the prevalence of a poorly differentiated component in the tumor. Then the disease-specific survival rate, metastasis-free survival rate, and relapse-free survival rate were compared between patients with or without a poorly differentiated component. In addition, well differentiated carcinoma and poorly differentiated carcinoma were compared in relation to the age, sex, TNM stage, and recurrent laryngeal nerve infiltration. Results It was considered appropriate to define tumors with a poorly differentiated component of 10% or more as poorly differentiated carcinoma. There was a significant difference of the T classification but not the N classification between well and poorly differentiated thyroid papillary carcinomas. The disease-specific survival rate, metastasis-free survival rate, and relapse-free survival rate of patients with poorly differentiated carcinoma was significantly lower than that of patients with well differentiated carcinoma, and we considered that this might be due to the higher frequency of local infiltration in patients with poorly differentiated tumors. Conclusion The higher relapse rate compared with well differentiated carcinoma suggests that careful postoperative follow-up of patients with poorly differentiated carcinoma is important, particularly surveillance of distant metastasis.