Ten-Year Clinical Observation of Immunoglobulin G4-Related Coronary Periarteritis with Aneurysms.

Coronary periarteritis with aneurysms has been reported as a cardiovascular manifestation of immunoglobulin G4 (IgG4) -related disease. We report a 10-year clinical observation of a patient with IgG4-related coronary periarteritis (IgG4-rCP) characterized by multiple thickening of periarterial tissue and coronary artery aneurysms (CAAs).A 60-year-old man with a history of IgG4-related autoimmune pancreatitis had an incidental detection of a total of 5 tumor-like lesions surrounding the right and left coronary arteries on coronary computed tomography angiography (CCTA) in 2012. Among them, 3 lesions were located at the middle to the distal portions of the right coronary artery (RCA) and the most proximal lesion was accompanied by a CAA. Although corticosteroid therapy was continued, 4-year follow-up of CCTA in 2016 showed the most proximal lesion gradually increased from 33 to 45 mm and the CAA enlarged from 9 to 22 mm. In order to avoid aneurysmal rupture, the patient underwent resection of the most proximal lesion with an enlarged aneurysm concomitant with coronary artery bypass grafting (CABG). Histopathological findings were coincident with IgG4-rCP. CCTA in 2018, however, showed the remaining distal tumor-like lesion of RCA had slightly enlarged and a new CAA developed despite the corticosteroid therapy. Follow-up CCTA in 2022 revealed the CAA increased to 13 mm, which showed rapid enlargement by 4 mm/year. A second operation through a re-median sternotomy was planned. The residual lesions with the CAA were resected followed by CABG. The other lesions at the left coronary artery remained stable without aneurysmal change, but careful follow-up has been continued.

A case of intraductal tubulopapillary neoplasm of the pancreas in a branch duct: a rare case report and literature review.

BACKGROUND: Intraductal tubulopapillary neoplasm (ITPN) of the pancreas is a new disease concept defined by the World Health Organization in 2010. ITPN progresses with tubulopapillary growth in the pancreatic duct and is known to have a fair prognosis. Localization in the main pancreatic duct (MPD) is one characteristic. There are few case reports of ITPN in a branch of the pancreatic duct (BD). CASE PRESENTATION: We encountered a case of ITPN localized in BD. An 85-year-old man was followed after colonic surgery for rectal carcinoma. An abdominal computed tomography scan revealed a cystic mass in the pancreatic head and further examination was done. A T2 weighted intension picture in magnetic resonance imaging showed a 20 mm cystic lesion with an internal mass of 15 mm. Duodenal papilla were slightly open and endoscopic retrograde pancreatography revealed mild and diffuse dilatation of the main pancreatic duct and mucin in the MPD. In consideration with the image examinations, we diagnosed the tumor as an intraductal papillary mucinous neoplasm with carcinoma because of its large mural nodule (> 10 mm in size) in a cyst. Consequently, a pancreaticoduodenectomy was performed. Macroscopically, a white solid tumor sized 2.5 × 1.8 × 1.0 was identified in the head of the pancreas. The cut surface of the resected pancreas showed a side-branch type intraductal tumor with tubulopapillary architecture without mucin secretion. Immunohistochemical staining was positive for MUC1, and negative for MUC2 and MUC5AC. The final diagnosis was determined to be pancreatic ITPN from BD. At the time of this report (48 months post-surgery), the patient remains disease-free without evidence of recurrence. CONCLUSION: ITPNs localized in BD are rare and diagnosis prior to surgery is difficult. In our case, the shape was round, not papillary, and with little fluid. These characteristics are different from a branch duct type IPMN and can be a clue to suspect ITPN in BD.

[Prognostic Value of Basal Marker Expression in Early Stage Breast Cancer].

The expression of basal marker could be a significant factor for poor prognosis in early stage breast cancer. We evaluated the prognostic value of basal marker in each breast cancer subtype. According to immunohistochemistry assay, CK5/6-posi- tive and/or EGFR-positive was defined as basal marker-positive. A total of 497 consecutive, non-metastatic invasive breast cancers were evaluated, and 166 cases(33%)were defined as basal marker-positive. Overall, basal marker expression was not a significant prognostic factor for breast cancer recurrence. However, according to Cox regression analysis, basal markerpositivity was significantly associated with poor recurrence-free survival in 63 cases with TNBC(hazard ratio: 2.9, 95% confidence interval: 1.5-5.8, p=0.001). Therefore, evaluation of basal marker expression could be useful for the risk estimation of recurrence in TNBC.

Long-term follow-up study of gastric adenoma; tumor-associated macrophages are associated to carcinoma development in gastric adenoma.

BACKGROUND: Some gastric adenomas may progress to adenocarcinoma in a short time, but others remain as adenoma for a long time. METHODS: Among 1138 cases diagnosed as adenoma by biopsy at Kure Medical Association Hospital between 1990 and 2010, 51 adenomas were enrolled. Of these, 28 adenomas (group A) were followed for 60 months or longer with no progression to adenocarcinoma within 60 months, and the other 23 adenomas (group B) were upgraded to carcinoma by consecutive biopsies performed within 1 year after the first biopsy. These adenomas were compared clinicopathologically and immunohistochemically. RESULTS: Macroscopically, the mean size of group B adenomas was significantly larger than that of group A adenomas (18.6 vs. 9.9 mm) at the first biopsy. The frequency of a depressed area in the adenoma was significantly higher in group B than group A. Microscopically none of group A but 7 (30.4%) of 23 group B adenomas showed severe atypia. Each of a highly proliferative gland measured by Ki-67 labeling, cellular atypical grade, gastric phenotype defined by MUC5AC and MUC6 and CD204-positive tumor-associated macrophage (TAM) was a significant risk factor for adenocarcinoma development in gastric adenoma by univariate analysis. Only moderate or severe atypia of adenoma cells and the TAM number in the stroma of adenomas were independent risk factors by multivariate analysis. CONCLUSIONS: As independent risk factors, cellular atypia may reconfirm the importance of morphological analysis, and the TAM number may indicate the significance of TAM function in gastric adenoma.

Serum transferrin as a predictor of prognosis for hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma.

AIM: We recently reported that the iron chelator deferoxamine (DFO) is efficacious in advanced hepatocellular carcinoma (HCC) patients. Iron regulation may thus have an important impact in HCC therapy. Because transferrin is a native chelator that regulates iron homeostasis, it may act as an anticancer agent in a similar manner as DFO. The objective of this study was to evaluate serum transferrin as a prognostic predictor in advanced HCC patients undergoing hepatic arterial infusion chemotherapy (HAIC). METHODS: We retrospectively studied 44 patients receiving HAIC and analyzed various parameters for their possible use as prognostic predictors. RESULTS: The 1-, 2- and 3-year cumulative survival rates were 36.4%, 18.2% and 8.5%, respectively, and the median survival time (MST) was 7.0 months. The survival rates of patients who had serum transferrin of 190 mg/dL or more (MST, 12.0 months) were significantly better than those of patients who had serum transferrin of less than 190 mg/dL (MST, 4.9 months). Multivariate analysis identified serum transferrin of 190 mg/dL or more (hazard ratio [HR], 0.282; 95% confidence interval [CI], 0.132-0.603; P = 0.001) and Child-Pugh score B (HR, 1.956; 95% CI, 1.034-3.700; P = 0.039) as independent prognostic predictors. There was a significant correlation between serum transferrin level and therapeutic effect (P < 0.001). CONCLUSION: Serum transferrin could be useful as a prognostic predictor in advanced HCC patients before HAIC treatment.

Association of tyrosine with insulin resistance in hepatitis C virus-related chronic liver disease.

AIM: Insulin resistance (IR) increases during the early stages of hepatitis C virus (HCV)-related chronic liver disease and is a sign of poor prognosis as well as a risk factor for hepatic fibrosis and hepatocellular carcinoma. We aimed to determine the factors affecting IR in HCV-related chronic liver disease. METHODS: We retrospectively examined 71 patients with HCV-related chronic liver disease and analyzed various parameters, including amino acids, as possible predictors of IR. IR was assessed using the Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR). Amino acids were assayed by examining branched-chain amino acids (BCAA), tyrosine level, and the ratio of BCAA to tyrosine level (BTR). RESULTS: HOMA-IR was significantly correlated with body mass index, platelet count, prothrombin time, hemoglobin, total bilirubin, total protein, albumin, total cholesterol, fasting glucose, BTR (r = -0.46, P = 0.0001) and tyrosine (r = 0.55, P < 0.0001). However, BCAA were not significantly correlated with HOMA-IR (r = -0.21, P = 0.082). In multivariate analysis, only two factors were identified as independent parameters contributing to a HOMA-IR of 2.5 or more: total cholesterol (odds ratio [OR], 6.511; 95% confidence interval [95% CI], 1.554-27.284; P = 0.010) and tyrosine (OR, 4.839; 95% CI, 1.087-21.549; P = 0.039). CONCLUSION: Serum tyrosine levels may be associated with IR in patients with HCV-related chronic liver disease.

Pulmonary tuberculoma-induced cyst formation leading to repeated pneumothorax: a case report.

Most cases of secondary spontaneous pneumothorax in patients with active pulmonary tuberculosis are caused by rupturing of the visceral pleura caused by Mycobacterium tuberculosis. The check-valve airway mechanism in the lungs is generally involved in the formation of pulmonary cysts, which often cause spontaneous pneumothorax. Herein, we describe a rare case of repeated spontaneous pneumothorax suspected to have been caused by pulmonary cyst formation as a result of a tuberculoma. The patient was a man with a family history of pulmonary tuberculosis. Pulmonary cysts were gradually enlarged on the peripheral side of a lung mass in the upper lobe of the patient's right lung, who experienced two spontaneous pneumothoraxes in the area. Exploratory surgery was performed to diagnose the lung mass and treat the pneumothorax, resulting in a final diagnosis of pulmonary tuberculoma. A check-valve mechanism caused by the pulmonary tuberculoma was suspected based on the patient's clinical course.

Metastatic Metaplastic Breast Cancer Successfully Treated with Adriamycin and Cisplatin.

Metaplastic breast cancer (MBC) is characterized by the histological presence of a mixture of epithelial and mesenchymal-like elements. However, MBC responds poorly to chemotherapy. Due to its rarity, there is no well-defined treatment for MBC. Herein, we report the case of a 56-year-old woman who underwent a mastectomy and was diagnosed with MBC with osseous differentiation classified as pT4N0M1. After the operation, she was treated with adriamycin and cisplatin, which are standard osteosarcoma treatments, resulting in a partial response. However, to determine the proper chemotherapy treatment, knowledge of the metaplastic elements of the tumor is required.

Invasive Mucinous Adenocarcinoma with Acute Respiratory Distress Syndrome Diagnosed by Autopsy Findings.

We herein report a fatal case of invasive mucinous adenocarcinoma (IMA) with acute respiratory distress syndrome (ARDS) diagnosed based on autopsy findings. A 76-year-old man presented with severe respiratory discomfort on admission. Computed tomography (CT) revealed a peripheral distribution of consolidation. Although his respiratory status improved after steroid therapy, re-exacerbation occurred, and the patient died on day 131. A bronchoscopic lung biopsy had shown organizing pneumonia, but a post-mortem examination surprisingly revealed IMA with organizing pneumonia. IMA presenting with ARDS as the first symptom is extremely rare.

Transcriptomic Analysis of Annexin A10 and Chemosensitivity in Gastric Adenocarcinoma Cells.

BACKGROUND/AIM: Gastric cancer (GC) is the third-leading cause of cancer-related deaths worldwide; thus, novel diagnostic and therapeutic biomarkers are needed. Annexin A10 (ANXA10) is a calcium- and phospholipid-binding protein. As far as we are aware, there are no reports describing the detailed functions of ANXA10 in GC. Therefore, we investigated the downstream mRNA variation and the effects of ANXA10 on chemoresistance in GC cell lines. MATERIALS AND METHODS: ANXA10 knockout GC cell lines were generated, and we performed functional analyses, chemosensitivity drug testing, and microarray analyses. Additionally, immunohistochemistry for ANXA10 was performed on 40 patients with GC who had received 5-fluorouracil (5-FU)-based chemotherapy to compare their prognosis and clinicopathological factors. RESULTS: ANXA10 knockout GC cells showed significantly increased proliferation, invasion, and sensitivity to 5-FU. The overall survival of ANXA10-positive cases was considerably lower than that of ANXA10-negative cases in GC patients who received 5-FU-based chemotherapy. Microarray analysis revealed candidate pathways regulated by ANXA10 and claudin 1 (CLDN1), keratin 80 (KRT80), RANBP2-type and C3HC4-type zinc finger containing 1 (RBCK1), and solute carrier family 7 member 5 (SLC7A5) genes. CONCLUSION: ANXA10 knockout increased the susceptibility of GC cell lines to 5-FU; ANXA10 may be a predictive indicator for response to 5-FU treatment in GC cases. ANXA10 may be involved in the pathogenesis of GC, in collaboration with CLDN1, KRT80, RBCK1, and SLC7A5.

Lymphangitis carcinomatosa from gallbladder cancer.

A 61-year-old woman was admitted to our hospital with productive cough and fever. Computed tomography images revealed ground glass opacities in both lung fields, and a space-occupying lesion in the gallbladder. Transbronchial lung biopsy revealed a poorly differentiated adenocarcinoma with invasion of the lymph ducts; accordingly, a diagnosis of lymphangitis carcinomatosa was made. We could not administer chemotherapy due to poor performance status, and the patient died of respiratory failure 30 days after admission. Owing to pathological autopsy findings of poorly differentiated adenocarcinoma in the gallbladder, we diagnosed this as a rare case of gallbladder cancer presenting with lymphangitis carcinomatosa.

High Annexin A10 expression is correlated with poor prognosis in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is the third-leading cause of cancer-related death. Owing to its poor prognosis, new molecular biomarkers for PDAC are needed. Annexin A10 (ANXA10) is a calcium-/phospholipid-binding protein belonging to the annexin family of proteins. ANXA10 is not only associated with gastric phenotypes, but also acts an independent prognostic factor in several cancers. However, the role of ANXA10 in PDAC remains unknown. Therefore, we examined the relationship between ANXA10 and the prognosis of PDAC. We analyzed the expression of ANXA10 using data from public databases, and performed immunohistochemistry analysis for 81 PDAC cases. We then investigated the relationship between ANXA10 expression and clinicopathological features. ANXA10 was detected in 47 of 81 PDAC cases (58%). High expression of ANXA10 was significantly related to poor overall survival (OS; p=0.011). Univariate analysis of OS revealed three prognostic parameters: tumor grade (p=0.046), perineural invasion (p=0.017), and ANXA10 expression (p=0.012). Multivariate analysis indicated that ANXA10 expression (p<0.01) alone was a prognostic factor in PDAC cases. Our findings suggest that ANXA10 expression is an independent prognostic factor in PDAC cases and shows promise as a new biomarker in PDAC.

Histopathology and Cytology of Pulmonary Myoepithelial Neoplasms: 2 Cases.

Myoepithelial neoplasms (MNs) of the lung are extremely rare tumors. Approximately 40 cases of pulmonary MNs have been reported to date. Herein, we report extremely rare cases of different types of pulmonary MN, including cytological features. Case 1 is an 18-year-old female, and case 2 is a 73-year-old female patient. They presented to our hospital with nodules of the lung. Histological examination revealed tumor cells with round to oval nuclei and acidophilic cytoplasm that formed nests or fascicles with mild hyalinized stroma in case 1 and tumors containing the bi-phasic components of a nest-like and fascicle pattern with pleomorphism in case 2. Immunohistochemically, these tumors were positive for cytokeratin (CK) AE1/AE3, CK5/6, vimentin, calponin, and EMA, and focal positive for S-100a protein and alpha smooth muscle actin. The pathological diagnoses in cases 1 and 2 were myoepithelioma and myoepithelial carcinoma, respectively. In conclusion, we encountered two cases of extremely rare MNs that occurred in the lung. This disease can be diagnosed by collecting appropriate cytological and histological findings and should be listed as a differential diagnosis.

Anterior Mediastinal Leiomyosarcoma: A Case Report and Literature Review.

Primary mediastinal sarcomas are extremely rare. Additionally, mediastinal leiomyosarcomas account for approximately 9% of mediastinal sarcoma cases. Until date, only few cases of anterior mediastinal leiomyosarcomas have been reported. Herein, we report a case of an 85-year-old female with an anterior mediastinal mass of 15 mm. Histological examination revealed spindle tumor cells showing a fascicular growth pattern. Immunohistochemically, the tumor cells were focal positive for desmin, calponin, and α-smooth muscle actin. The pathological diagnosis was leiomyosarcoma. In conclusion, we encountered a case of a very rare leiomyosarcoma that occurred in the anterior mediastinum, and our report may contribute to the understanding of this disease.

Annexin A10 Expression Is Associated With Poor Prognosis in Small Bowel Adenocarcinoma.

BACKGROUND/AIM: Small bowel adenocarcinoma (SBA) is a relatively rare malignant epithelial neoplasm. Thus, little is known about prognostic biomarkers of SBA. Annexin A10 (ANXA10) is a member of the annexin family. The significance of ANXA10 expression in SBA is unclear. This is the first study to examine the expression of ANXA10 in SBA. MATERIALS AND METHODS: We immunohistochemically evaluated ANXA10 expression of SBA and studied the relationship between ANXA10 expression and clinicopathological factors. RESULTS: ANXA10 expression was detected in 17 (56.7%) of 30 SBA cases and was significantly associated with poor overall survival. Univariate predictors for poor prognosis were tumour size (p=0.017) and ANXA10 expression (p=0.026). In multivariate analysis, ANXA10 expression (p=0.038) and tumour size (p=0.024) were found to be independent predictors of poor prognosis. CONCLUSION: ANXA10 could be a new prognostic biomarker for SBA.

Systemic Inflammatory Score Predicts Response and Prognosis in Patients With Lung Cancer Treated With Immunotherapy.

AIM: This study aimed to investigate useful prognostic factors of immunotherapy in patients with lung cancer. PATIENTS AND METHODS: We retrospectively observed 73 patients who underwent immunotherapy (nivolumab, pembrolizumab, and atezolizumab) for lung cancer. The systemic inflammatory score (SIS) was calculated as the sum of the following factors scored one point each: Hemoglobin <12.5 g/dl and serum albumin <3.6 g/dl, resulting in scores of 0-2. We examined the correlation between the SIS and initial tumor response and progression-free and overall survival with other existing markers, namely tumor programmed death-ligand 1 (PD-L1) expression level; neutrophil-to-lymphocyte ratio (NLR); modified Glasgow prognostic score; and prognostic nutritional index, etc. Results: SIS ≤1 was significantly associated with better initial tumor response. In multivariate analysis, PD-L1 expression ≥50% (p=0.010), SIS ≤1 (p=0.028) and NLR <5.6 (p=0.047) were significantly associated with longer progression-free survival, and SIS ≤1 (p=0.030) and NLR <5.6 (p=0.037) were associated with longer overall survival. CONCLUSION: SIS is a useful marker of the efficacy of immunotherapy that can be obtained via routine blood tests.

Loss of Annexin A10 Expression Is Associated with Poor Prognosis in Early Gastric Cancer.

Gastric cancer (GC) is the third most common cause of cancer-related mortality. The diagnosis and treatment of early GC is a crucial strategy for prognostic improvement of GC. Annexin A10 (ANXA10), a calcium-/phospholipid-binding protein, is a member of the annexin family. The significance of ANXA10 expression in early GC remains unclear. This is the first report to investigate ANXA10 expression in early GC. We performed immunohistochemistry to evaluate ANXA10 expression in early GC, and the correlation between ANXA10 and clinicopathological factors. The loss of ANXA10 expression was detected in 63 (61.2%) of 103 early GC cases and significantly correlated with poor overall survival in patients. Sex, pT stage, pN stage, histology, and ANXA10 expression were associated with poor survival. Sex, histology, and ANXA10 expression were determined as independent predictors of survival in early GC patients. ANXA10 immunostaining could be a new decision-making biomarker in GC.

Intramucosal Poorly Differentiated Adenocarcinomas Detected in a Patient with Long-Standing Ulcerative Colitis.

We report a case of long-standing ulcerative colitis with intramucosal well- and poorly differentiated adenocarcinomas detected over a 6-month duration. A Japanese man in his sixties with a 31-year history of ulcerative colitis had a 1.1-cm-sized intramucosal well-differentiated tubular adenocarcinoma in the rectum resected by endoscopic submucosal dissection. At the follow-up colonoscopy, a biopsy near the endoscopic submucosal dissection scar revealed poorly differentiated adenocarcinoma, and a total proctocolectomy was performed 6 months after the endoscopic submucosal dissection. The whole colorectal pathological exam showed 2 flat foci of intramucosal poorly differentiated adenocarcinoma, 4 and 2 mm in size each, near the endoscopic submucosal dissection scar in the rectum, and an increased number of Paneth cells, thickened muscularis mucosa, and widening of the distance between the gland base and muscularis mucosa in the transverse colon to the rectum. Adenocarcinomas were not found in areas where architecturally severe changes of the mucosa or the highest number of Paneth cells proliferation were detected. Multiple biopsies using magnifying narrow band imaging or crystal violet staining around the initial high-grade dysplasia or intramucosal adenocarcinoma were effective to find other lesions, such as poorly differentiated adenocarcinoma foci in the mucosa in a long-standing ulcerative colitis patient.

CD204-Positive Tumor-associated Macrophages Relate to Malignant Transformation of Colorectal Adenoma.

BACKGROUND/AIM: Colorectal adenoma is well known as a precursor lesion of colorectal adenocarcinoma (ADC). We recently reported the significance of CD204 (+) tumor-associated macrophages (TAMs), a vital component of the tumor microenvironment, in the carcinoma development of gastric adenoma. The aim of the present study was to clarify the roles of TAM in the malignant transformation of colorectal adenoma. MATERIALS AND METHODS: We immunohistochemically assessed the TAM number in 88 tubular or tubulovillous adenomas that were classified into L (low-grade adenomas) or H (high-grade adenomas). RESULTS: Larger adenoma size, higher frequency of villous structure, loss of proliferation polarity, p53 expression, larger TAM numbers and larger microvessel density (MVD) were detected in Group H than in Group L adenomas. Positive relations were observed between TAM and MVD, proliferation polarity and the expression of p53. CONCLUSION: CD204 (+) TAM is a novel component in the malignant transformation of colorectal adenoma.