Primary mediastinal apocrine adenocarcinoma is extremely rare, with only one case reported to date. Here, we report a surgical case of primary mediastinal apocrine adenocarcinoma. An anterior mediastinal cystic tumor with calcification was identified on chest computed tomography scan in a 51-year-old female patient undergoing maintenance hemodialysis. The tumor was 19 mm in size, did not invade the adjacent organs or show distant metastases, and was surgically removed. Microscopic examination revealed that the tumor cells exhibited cribriform or solid proliferation patterns with thick fibrous capsules. The tumor cells had an abundant eosinophilic cytoplasm, and decapitation secretion was noted. Immunohistochemistry revealed positivity for GCDFP-15 and androgen receptors, with Ki-67 positivity at 10%. The cyst wall exhibited extensive fibrosis and keratinized material, with bone and bronchial glands identified at the cyst periphery; the tumor cells were contiguous with those structures. The patient was diagnosed with apocrine adenocarcinoma arising from a mature cystic teratoma. The patient has maintained a recurrence-free status without adjuvant therapy for 6 years after surgery. This case presents a small primary mediastinal apocrine adenocarcinoma that achieved remarkable long-term survival.
{"title":"Apocrine adenocarcinoma arising from mature cystic teratoma in the anterior mediastinum: A case report.","authors":"Takuya Ueda, Kazuya Takamochi, Taichiro Yoshimoto, Tomohiro Ichikawa, Takeshi Matsunaga, Takuo Hayashi, Kenji Suzuki","doi":"10.1111/pin.13495","DOIUrl":"10.1111/pin.13495","url":null,"abstract":"<p><p>Primary mediastinal apocrine adenocarcinoma is extremely rare, with only one case reported to date. Here, we report a surgical case of primary mediastinal apocrine adenocarcinoma. An anterior mediastinal cystic tumor with calcification was identified on chest computed tomography scan in a 51-year-old female patient undergoing maintenance hemodialysis. The tumor was 19 mm in size, did not invade the adjacent organs or show distant metastases, and was surgically removed. Microscopic examination revealed that the tumor cells exhibited cribriform or solid proliferation patterns with thick fibrous capsules. The tumor cells had an abundant eosinophilic cytoplasm, and decapitation secretion was noted. Immunohistochemistry revealed positivity for GCDFP-15 and androgen receptors, with Ki-67 positivity at 10%. The cyst wall exhibited extensive fibrosis and keratinized material, with bone and bronchial glands identified at the cyst periphery; the tumor cells were contiguous with those structures. The patient was diagnosed with apocrine adenocarcinoma arising from a mature cystic teratoma. The patient has maintained a recurrence-free status without adjuvant therapy for 6 years after surgery. This case presents a small primary mediastinal apocrine adenocarcinoma that achieved remarkable long-term survival.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"34-39"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2024-12-11DOI: 10.1111/pin.13498
Takahiro Matsui
Histopathological diagnosis is the definitive method for the evaluation of disease status; however, some problems need to be solved, such as invasiveness, time consumption, and difficulty in three-dimensional observation. To overcome these problems, a novel observation method, distinct from conventional histology, using tissue sections and glass slides is desirable. Fluorescence imaging of human tissues with multiphoton excitation imaging (MpEI), which was originally used for intravital imaging in biological research, is a promising method. Label-free MpEI, which requires only near-infrared excitation, can construct images with autofluorescent signals from fresh tissues, as well as nonlinear optical phenomena. It is possible to perform real-time three-dimensional imaging of human tissues without any tissue removal, fixation, or staining. This method has been reported to be useful for histopathological classification in multiple organs and tissues. Moreover, it is very compatible with quantitative image analyses, including artificial intelligence. Based on these characteristics, label-free MpEI has sufficient potential for clinical applications such as in endoscopy and intraoperative rapid diagnosis. The clinical application of label-free MpEI will bring changes not only to histopathology examination but also the clinical bedside and will contribute to the further development of histopathology.
{"title":"Optical histopathology based on the nonlabeling analysis with multiphoton excitation imaging.","authors":"Takahiro Matsui","doi":"10.1111/pin.13498","DOIUrl":"10.1111/pin.13498","url":null,"abstract":"<p><p>Histopathological diagnosis is the definitive method for the evaluation of disease status; however, some problems need to be solved, such as invasiveness, time consumption, and difficulty in three-dimensional observation. To overcome these problems, a novel observation method, distinct from conventional histology, using tissue sections and glass slides is desirable. Fluorescence imaging of human tissues with multiphoton excitation imaging (MpEI), which was originally used for intravital imaging in biological research, is a promising method. Label-free MpEI, which requires only near-infrared excitation, can construct images with autofluorescent signals from fresh tissues, as well as nonlinear optical phenomena. It is possible to perform real-time three-dimensional imaging of human tissues without any tissue removal, fixation, or staining. This method has been reported to be useful for histopathological classification in multiple organs and tissues. Moreover, it is very compatible with quantitative image analyses, including artificial intelligence. Based on these characteristics, label-free MpEI has sufficient potential for clinical applications such as in endoscopy and intraoperative rapid diagnosis. The clinical application of label-free MpEI will bring changes not only to histopathology examination but also the clinical bedside and will contribute to the further development of histopathology.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"1-10"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
An ovarian mucinous cystic tumor where fundic glands were broadly and evenly distributed. All components were FOXA2-positive. The diagnosis is difficult between "mucinous cystadenoma with fundic gland differentiation" and "monodermal cystic teratoma composed of gastric tissue derived from endoderm".
{"title":"Ovarian mucinous cystic tumor with an overwhelming fundic gland differentiation.","authors":"Satoe Numakura, Yuko Sasajima, Teppei Morikawa, Takayuki Ichinose, Kazunori Nagasaka, Masahiro Kato, Hiroshi Uozaki","doi":"10.1111/pin.13493","DOIUrl":"10.1111/pin.13493","url":null,"abstract":"<p><p>An ovarian mucinous cystic tumor where fundic glands were broadly and evenly distributed. All components were FOXA2-positive. The diagnosis is difficult between \"mucinous cystadenoma with fundic gland differentiation\" and \"monodermal cystic teratoma composed of gastric tissue derived from endoderm\".</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"50-52"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CD5 expression is seen in 5%-10% of de novo diffuse large B-cell lymphomas (DLBCLs). Primary large B-cell lymphoma of the central nervous system (PCNS-LBCL) also exhibits CD5 expression in a minority of cases, however, clinicopathological and molecular features remain largely unclarified. Here we present the clinical, molecular, and pathological features of 11 CD5-positive (+) PCNS-LBCL cases, occupying 6.7% of all 165 PCNS-LBCLs diagnosed in our institutions. While CD5+ systemic DLBCL has been recognized as a distinctive subgroup showing an aggressive clinical course, no obvious differences were found between CD5+ and CD5-negative subgroups among the present CNS patients clinically. MYD88 p.L265P and CD79B p.Y196 mutations were detected in eight (73%) and seven (64%) cases, respectively, supporting previous reports. Notably, the microenvironmental immune cells were universally PD-L1/CD274-positive, and the higher levels tended to present favorable overall survival, as already evidenced in the PCNS-LBCL series. In contrast, neoplastic PD-L1/CD274 expression was undetectable in all cases. Indeed, no structural variations or copy number alterations involving PD-1 ligands were detected by targeted-capture sequencing and fluorescence in situ hybridization. While further studies are warranted, we may have confirmed similarity between PCNS-LBCLs and intravascular large B-cell lymphomas from a molecular standpoint.
{"title":"Primary large B-cell lymphoma of the central nervous system: A reappraisal of CD5-positive cases based on clinical, pathological, and molecular evaluation.","authors":"Seiji Yamada, Akira Satou, Yuta Tsuyuki, Sachiko Iba, Yuka Okumura, Eri Ishikawa, Hideaki Ito, Yasunori Kogure, Naoe Goto, Motoki Tanikawa, Kazuyuki Shimada, Tetsuya Tsukamoto, Kennosuke Karube, Hideaki Yokoo, Keisuke Kataoka, Akihiro Tomita, Mitsuhito Mase, Shigeo Nakamura","doi":"10.1111/pin.13496","DOIUrl":"10.1111/pin.13496","url":null,"abstract":"<p><p>CD5 expression is seen in 5%-10% of de novo diffuse large B-cell lymphomas (DLBCLs). Primary large B-cell lymphoma of the central nervous system (PCNS-LBCL) also exhibits CD5 expression in a minority of cases, however, clinicopathological and molecular features remain largely unclarified. Here we present the clinical, molecular, and pathological features of 11 CD5-positive (<sup>+</sup>) PCNS-LBCL cases, occupying 6.7% of all 165 PCNS-LBCLs diagnosed in our institutions. While CD5<sup>+</sup> systemic DLBCL has been recognized as a distinctive subgroup showing an aggressive clinical course, no obvious differences were found between CD5<sup>+</sup> and CD5-negative subgroups among the present CNS patients clinically. MYD88 p.L265P and CD79B p.Y196 mutations were detected in eight (73%) and seven (64%) cases, respectively, supporting previous reports. Notably, the microenvironmental immune cells were universally PD-L1/CD274-positive, and the higher levels tended to present favorable overall survival, as already evidenced in the PCNS-LBCL series. In contrast, neoplastic PD-L1/CD274 expression was undetectable in all cases. Indeed, no structural variations or copy number alterations involving PD-1 ligands were detected by targeted-capture sequencing and fluorescence in situ hybridization. While further studies are warranted, we may have confirmed similarity between PCNS-LBCLs and intravascular large B-cell lymphomas from a molecular standpoint.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"11-20"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
REV7 is a multifunctional protein essential for promoting cellular tolerance to DNA damage. REV7 expression is associated with disease progression and prognosis in several human malignant tumors. This study aimed to evaluate the clinical and biological significance of REV7 in gastric adenocarcinoma (GAD). REV7 expression in 167 resected GADs was immunohistochemically assessed and examined the association with clinicopathological features. Positive expression of REV7 was significantly associated with tumor undifferentiation (p < 0.001), lymphatic invasion (p = 0.035), recurrence (p = 0.042), and mortality (p = 0.031). The Kaplan-Meier curves with log-rank tests revealed significantly poorer progression-free survival (p = 0.049), overall survival (p = 0.037), and post-progression survival (p = 0.038) in the REV7-positive group. Multivariate analysis using the Cox proportional hazard model identified REV7 as an independent prognostic factor for overall survival (p = 0.028). REV7-depleted GAD cell lines demonstrated enhanced sensitivity to cisplatin compared with control cells. Additionally, the expression levels of REV7 in residual tumors from surgical specimens of patients who received preoperative chemotherapy were higher than those in samples without chemotherapy (p = 0.029), suggesting that REV7-positive tumors are chemoresistant. These results indicate that REV7 is a predictive biomarker for the prognosis and chemosensitivity of GAD.
{"title":"High levels of REV7 expression are associated with poor prognosis and chemoresistance in gastric adenocarcinoma.","authors":"Yurika Kesen, Masaaki Ichinoe, Shoko Hayashi, Atsuko Umezawa, Yoshiko Numata, Taro Kogami, Masahiro Matsushita, Itaru Sanoyama, Akiyoshi Hoshino, Yasutaka Sakurai, Takuya Kato, Yoshiki Murakumo","doi":"10.1111/pin.13504","DOIUrl":"10.1111/pin.13504","url":null,"abstract":"<p><p>REV7 is a multifunctional protein essential for promoting cellular tolerance to DNA damage. REV7 expression is associated with disease progression and prognosis in several human malignant tumors. This study aimed to evaluate the clinical and biological significance of REV7 in gastric adenocarcinoma (GAD). REV7 expression in 167 resected GADs was immunohistochemically assessed and examined the association with clinicopathological features. Positive expression of REV7 was significantly associated with tumor undifferentiation (p < 0.001), lymphatic invasion (p = 0.035), recurrence (p = 0.042), and mortality (p = 0.031). The Kaplan-Meier curves with log-rank tests revealed significantly poorer progression-free survival (p = 0.049), overall survival (p = 0.037), and post-progression survival (p = 0.038) in the REV7-positive group. Multivariate analysis using the Cox proportional hazard model identified REV7 as an independent prognostic factor for overall survival (p = 0.028). REV7-depleted GAD cell lines demonstrated enhanced sensitivity to cisplatin compared with control cells. Additionally, the expression levels of REV7 in residual tumors from surgical specimens of patients who received preoperative chemotherapy were higher than those in samples without chemotherapy (p = 0.029), suggesting that REV7-positive tumors are chemoresistant. These results indicate that REV7 is a predictive biomarker for the prognosis and chemosensitivity of GAD.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"21-33"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142910129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A 50-year-old male with a pancreatic tail tumor underwent distal pancreatectomy. At 14 and 27 months after the primary surgery, metachronous liver metastases were identified and partial hepatectomies were performed for each. Pathologic findings of the primary pancreatic tumor were heterogeneous, but they essentially categorized into two components based on their cytologic features: (i) clear cell component and (ii) epithelioid cell component. The metastatic hepatic tumor was entirely composed of the epithelioid cell component. SMARCB1 expression was lost by immunohistochemistry and heterozygous deletion of SMARCB1 was identified by fluorescence in situ hybridization for both the primary and metastatic tumors. Targeted DNA sequencing of a metastatic hepatic tumor sample was performed and SMARCB1 loss was identified. Based on the morphologic, immunohistochemical, and molecular analyzes, the present case was difficult to classify into any of the existing entities. SMARCB1 deficiency might play a key role in the tumorigenesis.
一名患有胰尾肿瘤的 50 岁男性接受了胰腺远端切除术。在原发手术后 14 个月和 27 个月,发现了并发的肝转移瘤,并分别进行了肝部分切除术。原发性胰腺肿瘤的病理结果各不相同,但根据细胞学特征,基本上可分为两类:(i) 透明细胞成分和 (ii) 上皮样细胞成分。转移性肝肿瘤完全由上皮样细胞组成。免疫组织化学检测发现,原发性肿瘤和转移性肿瘤都失去了SMARCB1的表达,荧光原位杂交也发现了SMARCB1的杂合性缺失。对转移性肝肿瘤样本进行了DNA靶向测序,发现了SMARCB1缺失。根据形态学、免疫组化和分子分析,本病例难以归入任何现有实体。SMARCB1缺失可能在肿瘤发生中起着关键作用。
{"title":"SMARCB1-deficient malignant neoplasm of the pancreas with heterogeneous morphologies that cannot be classified into existing histologic types.","authors":"Yusuke Kouchi, Nozomu Sakai, Sakurako Harada-Kagitani, Ryotaro Eto, Takashi Mishima, Shigetsugu Takano, Katsuhiro Nasu, Jun-Ichiro Ikeda, Masayuki Ohtsuka, Takashi Kishimoto","doi":"10.1111/pin.13489","DOIUrl":"10.1111/pin.13489","url":null,"abstract":"<p><p>A 50-year-old male with a pancreatic tail tumor underwent distal pancreatectomy. At 14 and 27 months after the primary surgery, metachronous liver metastases were identified and partial hepatectomies were performed for each. Pathologic findings of the primary pancreatic tumor were heterogeneous, but they essentially categorized into two components based on their cytologic features: (i) clear cell component and (ii) epithelioid cell component. The metastatic hepatic tumor was entirely composed of the epithelioid cell component. SMARCB1 expression was lost by immunohistochemistry and heterozygous deletion of SMARCB1 was identified by fluorescence in situ hybridization for both the primary and metastatic tumors. Targeted DNA sequencing of a metastatic hepatic tumor sample was performed and SMARCB1 loss was identified. Based on the morphologic, immunohistochemical, and molecular analyzes, the present case was difficult to classify into any of the existing entities. SMARCB1 deficiency might play a key role in the tumorigenesis.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"691-696"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Widespread benign HNF1β-positive solid nests from the urethral diverticulum to the bladder neck: Is it a mesonephric remnant?","authors":"Takahiro Kirisawa, Akiko Miyagi Maeshima, Tomoya Okuno, Ayumu Matsuda, Yoshiyuki Matsui","doi":"10.1111/pin.13486","DOIUrl":"10.1111/pin.13486","url":null,"abstract":"","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"714-717"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-11-11DOI: 10.1111/pin.13492
Yukiko Shishido-Hara
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by JC virus (JCV) infection. Although recognized as an AIDS complication in the 1980s, PML has emerged as a serious adverse event of immunosuppressive therapies since 2005, particularly disease-modifying drugs (DMDs) for multiple sclerosis (MS). PML can also occur in patients with collagenous diseases receiving steroid therapy or with age-related immunosuppression. In some cases, the etiology of immunosuppression remains unclear. These cases often present with early manifestations of PML, which, while common, are less well recognized, as PML was identified at more advanced stages in AIDS-related cases. Early diagnosis poses difficulty due to unfamiliar magnetic resonance (MR) images and low viral loads in cerebrospinal fluid (CSF), and brain biopsy may be conducted. This review summarizes the PML pathology identified through biopsy. Early cytopathological changes of JCV-infected cells, with the importance of dot-shaped inclusions associated with promyelocytic leukemia nuclear bodies (PML-NBs), are described. The variability of host immune responses, including PML immune reconstitution inflammatory syndrome (PML-IRIS), is addressed. The potential role of immune checkpoint inhibitors (ICIs), such as pembrolizumab, is also explored. Understanding the pathology of early PML helps to optimize diagnostic strategies and therapeutic interventions, ultimately improving prognosis.
{"title":"Brain biopsy and pathological diagnosis for drug-associated progressive multifocal leukoencephalopathy (PML) with inflammatory reactions.","authors":"Yukiko Shishido-Hara","doi":"10.1111/pin.13492","DOIUrl":"10.1111/pin.13492","url":null,"abstract":"<p><p>Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by JC virus (JCV) infection. Although recognized as an AIDS complication in the 1980s, PML has emerged as a serious adverse event of immunosuppressive therapies since 2005, particularly disease-modifying drugs (DMDs) for multiple sclerosis (MS). PML can also occur in patients with collagenous diseases receiving steroid therapy or with age-related immunosuppression. In some cases, the etiology of immunosuppression remains unclear. These cases often present with early manifestations of PML, which, while common, are less well recognized, as PML was identified at more advanced stages in AIDS-related cases. Early diagnosis poses difficulty due to unfamiliar magnetic resonance (MR) images and low viral loads in cerebrospinal fluid (CSF), and brain biopsy may be conducted. This review summarizes the PML pathology identified through biopsy. Early cytopathological changes of JCV-infected cells, with the importance of dot-shaped inclusions associated with promyelocytic leukemia nuclear bodies (PML-NBs), are described. The variability of host immune responses, including PML immune reconstitution inflammatory syndrome (PML-IRIS), is addressed. The potential role of immune checkpoint inhibitors (ICIs), such as pembrolizumab, is also explored. Understanding the pathology of early PML helps to optimize diagnostic strategies and therapeutic interventions, ultimately improving prognosis.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"673-681"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11636588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}