Publications by authors named "Tadashi Hasegawa"

383 Publications

Case Report: Disappearance of Coronary Anastomotic Aneurysm by Steroid Therapy in Takayasu Arteritis: Pseudorepair of Pseudoaneurysm?

Front Cardiovasc Med 2021 4;8:683216. Epub 2021 Jun 4.

Department of Cardiovascular Surgery, Sapporo, Japan.

Takayasu arteritis (TA) is a large vessel vasculitis of unknown etiology characterized by chronic inflammatory changes of the aorta and its major branches. Complications such as anastomotic aneurysm and valve detachment have been reported in active TA patients who received aortic valve replacement and graft replacement of aorta. A 61-year-old man with a history of emergency aortic valve replacement and patch closure of the noncoronary sinus of Valsalva due to acute heart failure induced by acute aortic regurgitation and ruptured sinus of Valsalva 4 years ago was referred for exertional dyspnea. Dilatation of the sinus of Valsalva together with protrusion of the right sinus of Valsalva and ostial stenosis of the left coronary artery were newly found by computed tomography (CT). A Bentall operation with concomitant coronary artery bypass grafting was successfully performed with a composite graft. Diagnosis of TA was made on the basis of histological analyses of the resected sinus of Valsalva, though other arterial manifestations were not detected by F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography. Three months later, a follow-up study revealed left coronary ostial pseudoaneurysm at the anastomotic site together with strong F-FDG uptake, leading to commencement of steroid therapy. Eight months later, disappearance of left coronary ostial pseudoaneurysm was found by a follow-up CT scan. This is a rare TA case in whom spontaneous resolution of coronary anastomotic aneurysm by steroid therapy was found without reconstructive surgery.
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http://dx.doi.org/10.3389/fcvm.2021.683216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212995PMC
June 2021

Expression of programmed cell death ligand 1 (PD-L1) at in situ and invasive extramammary Paget's disease and literature review.

Australas J Dermatol 2021 May 12. Epub 2021 May 12.

Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo, Japan.

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http://dx.doi.org/10.1111/ajd.13607DOI Listing
May 2021

Possible effect of blonanserin on gambling disorder: A clinical study protocol and a case report.

World J Clin Cases 2021 Apr;9(11):2469-2477

Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.

Background: Gambling disorder is characterized by excessive and recurrent gambling and can have serious negative social consequences. Although several psychotherapeutic and pharmacological approaches have been used to treat gambling disorder, new treatment strategies are needed. Growing evidence suggests that dopamine D3 receptor plays a specific role in the brain reward system.

Aim: To investigate if blonanserin, a dopamine D3 receptor antagonist, would be effective in reducing gambling impulses in patients with gambling disorder.

Methods: We developed a study protocol to measure the efficacy and safety of blonanserin as a potential drug for gambling disorder, in which up to 12 mg/d of blonanserin was prescribed for 8 wk.

Results: A 37-year-old female patient with gambling disorder, intellectual disability, and other physical diseases participated in the pilot study. The case showed improvement of gambling symptoms without any psychotherapy. However, blonanserin was discontinued owing to excessive saliva production.

Conclusion: This case suggests that blonanserin is potentially an effective treatment for patients with gambling disorder who resist standard therapies, but it also carries a risk of adverse effects. Further studies are needed to confirm the findings.
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http://dx.doi.org/10.12998/wjcc.v9.i11.2469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040182PMC
April 2021

Oxytocin system dysfunction in patients with treatment-resistant schizophrenia: Alterations of blood oxytocin levels and effect of a genetic variant of OXTR.

J Psychiatr Res 2021 06 30;138:219-227. Epub 2021 Mar 30.

Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan.

Treatment-resistant schizophrenia (TRS) has a quite complex pathophysiology that includes not only severe positive symptoms but also other symptom domains. Much attention has been devoted to the overlapping psychological and biological profiles of schizophrenia and autistic spectrum disorder (ASD). We compared TRS patients (n = 30) with schizophrenia patients in remission (RemSZ, n = 28) and ASD patients (n = 28), focusing on general cognitive and social cognitive impairment and oxytocin system dysfunction. Our analyses revealed that there was no difference in oxytocin concentration among the three groups. The TRS patients' oxytocin blood concentrations were positively correlated with their processing speed and theory-of-mind scores, whereas the RemSZ and ASD groups had no significant relation with any measures. Rs53576, a single nucleotide polymorphism on the oxytocin receptor gene, affected social cognition abilities in the schizophrenia group. Although the overall findings are preliminary, they indicate that oxytocin system dysfunction could be involved in the serious cognitive deficits in TRS patients. Further, these results suggest that patients with TRS might have early neurodevelopmental abnormalities based on their shared biological features with ASD patients.
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http://dx.doi.org/10.1016/j.jpsychires.2021.03.053DOI Listing
June 2021

Successful hemostasis of bleeding gastric inflammatory fibroid polyp by endoscopic treatment in a patient with severe COVID-19.

Clin J Gastroenterol 2021 Aug 11;14(4):1008-1013. Epub 2021 Apr 11.

Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, 063-8543, Japan.

The coronavirus disease-2019 (COVID-19) has rapidly become a pandemic, resulting in a global suspension of non-emergency medical procedures such as screening endoscopic examinations. There have been several reports of COVID-19 patients presenting with gastrointestinal symptoms such as diarrhea and vomiting. In this report, we present a case of successful hemostasis of bleeding gastric inflammatory fibroid polyp by endoscopic treatment in a patient with severe COVID-19. The case was under mechanical ventilation with extracorporeal membrane oxygenation (ECMO), and the airway was on a closed circuit. This indicates that COVID-19 is associated with not only lung injury but also intestinal damage, and that proper protective protocols are essential in guaranteeing the best outcomes for patients and clinical professionals during this pandemic.
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http://dx.doi.org/10.1007/s12328-021-01402-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038534PMC
August 2021

A case of radio-insensitive SMARCA4-deficient thoracic undifferentiated carcinoma with severe right heart failure.

Respir Med Case Rep 2021 18;32:101364. Epub 2021 Feb 18.

Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, 060-8638, Japan.

SMARCA4-deficient thoracic sarcomatoid tumors were characterized by inactivating mutations of SMARCA4 and often found in the chest of young and middle-aged males with a smoking history. Recently, SMARCA4-deficient thoracic sarcomatoid tumors were reported to represent primarily smoking-associated undifferentiated/de-differentiated carcinomas rather than primary thoracic sarcomas. The main complication of this tumor is compression of the respiratory tract and/or blood vessels. A 39-year-old man presented with a 2-month history of fever and dyspnea. Computed tomography revealed a mediastinal tumor invading the right and left pulmonary arteries. Because of severe right heart failure, we considered him ineligible for bronchoscopy. We scheduled palliative irradiation with 40 Gy/20 Fr to improve hemodynamics and perform endobronchial ultrasound transbronchial needle aspiration later. However, irradiation was ineffective, and his general condition deteriorated quickly and he died after a 7-week hospitalization. An autopsy revealed that the diagnosis was SMARCA4-deficient thoracic undifferentiated carcinoma. It has been reported that this tumor is insensitive to radiotherapy and there were some cases which responded to an immune checkpoint inhibitor. Therefore, when caring for patients with mediastinal tumors that invade and compress the trachea and large vessels, it is important to consider this tumor as a differential diagnosis and try to make a pathological diagnosis as soon as possible.
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http://dx.doi.org/10.1016/j.rmcr.2021.101364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906892PMC
February 2021

Epithelioid granulomatous lesions express abundant programmed death ligand-1 (PD-L1): a discussion of adverse events in anti-PD-1 antibody-based cancer immunotherapy.

Hum Vaccin Immunother 2021 07 11;17(7):1940-1942. Epub 2021 Feb 11.

Department of Pathology, Sapporo Medical University, School of Medicine, Sapporo, Japan.

The immune system is often called a double-edged sword, due to the inextricable link between cancer immunity and allergy/autoimmunity. Intriguingly, a growing number of cases have been reported in which PD-1 blockade triggers the exacerbation of tuberculosis (TB), an organ-invasive granulomatous disease caused by bacterial infection. As a result, the exacerbation of TB is now considered a severe adverse effect of nivolumab and pembrolizumab. In this letter, we report the strong expression of PD-L1 in epithelioid granulomatous lesions in tuberculosis, sarcoidosis, Crohn's disease, and foreign body granuloma. In addition, we discussed the exacerbation of tuberculosis after anti-PD-1 antibody-based cancer immunotherapy.
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http://dx.doi.org/10.1080/21645515.2020.1870364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189068PMC
July 2021

Cardiac Angiosarcoma and Hepatic Hemangioma.

Circ J 2021 Feb 4;85(3):318. Epub 2021 Feb 4.

Department of Cardiovascular Surgery, Nagasaki University Graduate School of Biomedical Sciences.

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http://dx.doi.org/10.1253/circj.CJ-20-1235DOI Listing
February 2021

Identification of characteristic subepithelial surface granulomatosis in immune-related adverse event-associated enterocolitis.

Cancer Sci 2021 Mar 18;112(3):1320-1325. Epub 2021 Jan 18.

Department of Pathology, School of Medicine, Sapporo Medical University, Sapporo, Japan.

Immune checkpoint inhibitors (ICIs) have provided an additional treatment option for various types of human cancers. However, ICIs often induce various immune-related adverse events (irAEs). Enterocolitis is a major irAE with poorly understood histopathological characteristics. In this study, we retrospectively investigated the histopathology of colon tissue samples from 17 patients treated with ICIs. There were two major histological patterns of colitis: an ulcerative colitis-like pattern and a graft vs host disease-like pattern. Although these two patterns of colitis were mutually exclusive, both patterns often showed a characteristic that we call "subepithelial surface granulomatosis" (SSG), which has not been reported in other types of colitis. SSG was found even in colon tissue without symptoms or endoscopic findings of colitis. Given the increasing reports of sarcoid reaction or exacerbation of tuberculosis after treatment with ICIs, granuloma formation could be a histological hallmark of systemic immune activation by ICIs. Although statistical significance was not obtained, probably because of the small sample size, SSG may be a surrogate biomarker of systemic anticancer immune activation. We propose that a prospective study with larger sample size be performed.
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http://dx.doi.org/10.1111/cas.14773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935803PMC
March 2021

Stroke Mimics and Chameleons from the Radiological Viewpoint of Glioma Diagnosis.

Neurol Med Chir (Tokyo) 2021 Feb 29;61(2):134-143. Epub 2020 Dec 29.

Department of Neurosurgery, Sapporo Medical University, Sapporo, Hokkaido, Japan.

Gliomas are sometimes difficult to differentiate from strokes and are often misdiagnosed on magnetic resonance imaging (MRI); thus, the terms "stroke mimics" and "stroke chameleons" have been introduced. In this study, we analyzed stroke mimics and stroke chameleons in glioma and discussed the diagnostic perplexity.We retrospectively reviewed cases that were removed from lesions that were considered to be brain tumors. This study enrolled 214 patients who underwent tumor resection for suspected glioma. Clinical characteristics and radiological findings of the patients were compared between the masquerade findings group, which was further divided into two groups: the stroke chameleons and stroke mimics according to their final diagnosis, and the intelligible findings group.Stroke chameleons and stroke mimics were significantly higher in age and smaller in lesion size than the intelligible findings group. In the multivariate analysis, the predictive factor of the masquerade finding group was higher age and smaller size. Stroke mimics group has a tendency to be higher rate of hyperintensity lesion on diffusion-weighted imaging (DWI) compared with stroke chameleons group. The average period from initial diagnosis to pathological diagnosis was 13.50 days in the stroke chameleons and 61.50 days in the stroke mimics, which proved significantly different.Proper diagnosis of glioma and stroke affects a patient's prognosis, and should be diagnosed as soon as possible. However, stroke mimics and stroke chameleons caused by glioma can occur. Thus, the diagnosis of a stroke should take into consideration the possibility of a glioma in real clinical situations.
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http://dx.doi.org/10.2176/nmc.oa.2020-0309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905296PMC
February 2021

Primary capicua transcriptional repressor-rearranged sarcoma of the lung.

Jpn J Clin Oncol 2021 Apr;51(4):654-656

Department of Thoracic Surgery, National Hospital Organization, Hokkaido Cancer Center, Sapporo, Japan.

A 60-year-old man had a malignant left lower lung tumour with no metastases and underwent video-assisted thoracoscopic left lower lobectomy and lymphadenectomy. Pathological examination led to a diagnosis of capicua transcriptional repressor (CIC)-rearranged sarcoma. He has had 3.5 years of recurrence-free survival. CIC-rearranged sarcoma is a Ewing-like sarcoma that shows pathological findings similar to Ewing sarcoma. Most of CIC-rearranged sarcoma is CIC-double homeobox 4 protein (DUX4) fusion. Pulmonary CIC-rearranged sarcoma is extremely rare and has an unfavourable prognosis. However, complete resection can produce prognosis of long-term survival, and thus, surgery is an important option.
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http://dx.doi.org/10.1093/jjco/hyaa240DOI Listing
April 2021

Rare case of acinar cell carcinoma with multiple lesions in the pancreas.

JGH Open 2020 Dec 29;4(6):1242-1243. Epub 2020 Jun 29.

Department of Medical Oncology Sapporo Medical University Sapporo Japan.

We present the first case of pancreatic acinar cell carcinoma (PACC) with multiple lesions. A 55-year-old man with a pancretic tail mass on abdominal computed tomography (CT) was admitted to our hospital. Endoscopic ultrasound (EUS) showed a hypoechoic mass, and EUS-guided fine-needle aspiration (EUS-FNA) revealed the mass to be PACC. The patient underwent distal pancreatectomy, and two masses were identified in the pancreatic tail and body. Histologically, both masses had tumor cells similar to acinar cells and were positive for BCL-10. The patient was thus diagnosed with synchronous PACC. Ten months after the surgery, abdominal CT revealed a mass in the remnant pancreas. EUS showed a hypoechoic mass, and EUS-FNA determined it to be PACC. The patient underwent total remnant pancreatectomy. The histological imaging results were similar to those of the first resection. Finally, the patient was diagnosed with synchronous and metachronous PACC. The possibility of multiple occurrences in the pancreas should be considered with PACC.
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http://dx.doi.org/10.1002/jgh3.12380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731799PMC
December 2020

Differential diagnosis of fibroma of tendon sheath and giant cell tumor of tendon sheath in the finger using signal intensity on T2 magnetic resonance imaging.

Acta Radiol 2020 Dec 7:284185120976915. Epub 2020 Dec 7.

Department of Orthopedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan.

Background: The differential diagnosis of fibroma of tendon sheath (FTS) and giant cell tumor of tendon sheath (GCTTS) on the basis of clinical and radiographic characteristics remains difficult.

Purpose: To evaluate the quantitative measurement of signal intensity (SI) obtained by magnetic resonance imaging (MRI) for the differential diagnosis of FTS and GCTTS in just the finger.

Material And Methods: We retrospectively identified patients with FTS (n = 6) and GCTTS (n = 22) of the finger who were treated at our hospitals between April 2011 and August 2019. Two researchers independently reviewed the MRIs and measured the regions of interest (ROIs) in the tumor and flexor tendon from the same image. The SI ratio obtained for the tumor and tendon ROIs was measured and compared using receiver-operating characteristic curve analyses. Sensitivity and specificity analyses were performed.

Results: The SI ratios (mean ± SD) of FTS and GCTTS were 1.83 ± 0.64 and 6.34 ± 3.16 for researcher 1 and 1.82 ± 0.60 and 6.10 ± 3.22 for researcher 2, respectively. The areas under the curve were 0.970 and 0.970 for researchers 1 and 2, respectively. The cut-off values of the SI ratio as determined by researchers 1 and 2 for differentiating FTS from GCTTS were 3.00 and 3.00, respectively (sensitivity = 95.5%, specificity = 100%).

Conclusions: The SI ratio is useful for differentiating FTS from GCTTS independent of a combination of tumor signal and shape.
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http://dx.doi.org/10.1177/0284185120976915DOI Listing
December 2020

Case series of three patients with hereditary diffuse gastric cancer in a single family: Three case reports and review of literature.

World J Gastroenterol 2020 Nov;26(42):6689-6697

Department of Medical Oncology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Hokkaido, Japan.

Background: Hereditary diffuse gastric cancer (HDGC) is a familial cancer syndrome often associated with germline mutations in the gene. However, the frequency of mutations is low in patients with HDGC in East Asian countries. Herein, we report three cases of HDGC harboring a missense variant, c.1679C>G, from a single Japanese family.

Case Summary: A 26-year-old female (Case 1) and a 51-year-old male (father of Case 1), who had a strong family history of gastric cancer, were diagnosed with advanced diffuse gastric cancer. After genetic counselling, a 25-year-old younger brother of Case 1 underwent surveillance esophagogastroduodenoscopy that detected small signet ring cell carcinoma foci as multiple pale lesions in the gastric mucosa. Genetic analysis revealed a c.1679C>G variant in all three patients.

Conclusion: It is important for individuals suspected of having HDGC to be actively offered genetics evaluation. This report will contribute to an increased awareness of HDGC.
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http://dx.doi.org/10.3748/wjg.v26.i42.6689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673959PMC
November 2020

Arteriovenous malformation in the pancreatic head initially mimicking a hypervascular mass treated with duodenum-preserving pancreatic head resection: a case report.

Surg Case Rep 2020 Dec 1;6(1):301. Epub 2020 Dec 1.

Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, 291 Minami-1-jo Nishi 16-chome, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan.

Background: The mainstay treatment for arteriovenous malformation in the pancreatic head (Ph-AVM) is standard pancreatectomy, especially pancreaticoduodenectomy (PD), or interventional endovascular treatment. We report the first case of Ph-AVM treated with duodenum-preserving pancreatic head resection (DPPHR) performed to preserve the periampullary organs.

Case Presentation: A 59-year-old man presenting with back pain underwent contrast-enhanced computed tomography followed by angiography of the anterior superior pancreaticoduodenal artery. He was diagnosed with Ph-AVM and indicated for DPPHR with preservation of the periampullary organs; Ph-AVM's benign nature seldom requires lymph node dissection. During the operation, the right colon was mobilized and the omental bursa was released to expose the periampullary structures. The pancreas was transected just above the superior mesenteric vein. The inferior pancreaticoduodenal artery and papillary arteries branching from the posterior superior pancreaticoduodenal artery were carefully preserved to maintain the blood flow to the lower bile duct and papilla of Vater. The remnant pancreas was reconstructed with pancreaticogastrostomy using the modified Blumgart method. Pathological examination of the resected specimen revealed an irregular course of the arteries and veins concomitant with marked dilation throughout the pancreatic head. The patient was pathologically diagnosed with Ph-AVM. He developed hematemesis caused by a rupture of the pseudoaneurysm on postoperative day 20 and underwent coil embolization. A bilio-enteric fistula and stenosis of the common bile duct were found and treated by placement of an endoscopic biliary stent. At the 8-month follow-up, the Ph-AVM had not recurred.

Conclusions: Compared to PD, DPPHR confers the clinical benefit of preserving the periampullary organs, although further studies are needed to confirm this. Therefore, the choice of this procedure should be based on the surgical morbidities and long-term outcome of the patient.
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http://dx.doi.org/10.1186/s40792-020-01075-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708544PMC
December 2020

Response to 'Is the case really a SMARCA4-deficient thoracic sarcoma?'

Thorac Cancer 2021 01 18;12(1):141. Epub 2020 Nov 18.

Department of Surgical Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.

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http://dx.doi.org/10.1111/1759-7714.13751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779208PMC
January 2021

Aberrant expression of junctional adhesion molecule-A contributes to the malignancy of cervical adenocarcinoma by interaction with poliovirus receptor/CD155.

Cancer Sci 2021 Feb 5;112(2):906-917. Epub 2020 Dec 5.

Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.

Recent studies have shown that aberrant expression of tight junction proteins (TJP) contributes to malignant potential of various cancers. In the present study, we investigated the expression of junctional adhesion molecule-A (JAM-A), one of the transmembrane TJP, in uterine cervical adenocarcinoma and the significance of its expression for malignancy. Immunohistochemistry on human surgical specimens showed that JAM-A was aberrantly expressed in neoplastic regions including adenocarcinoma in situ (AIS). Knockout of JAM-A significantly suppressed cell proliferation and colony-forming and migration abilities. We also showed that an antibody specific to an extracellular region of JAM-A reduced cell proliferation ability and that loss of JAM-A increased drug sensitivity of cervical adenocarcinoma cells. Based on a comprehensive proteome analysis, we found that poliovirus receptor (PVR/CD155) was regulated by JAM-A and formed a physical interaction with JAM-A. In human surgical specimens, PVR/CD155 expression was significantly correlated with some clinicopathological features and prognosis of cervical adenocarcinoma. Interestingly, most of the PVR/CD155-positive cases expressed a high level of JAM-A, and patients with the expression pattern of PVR/CD155 positive/JAM-A high had significantly shorter periods of relapse-free survival (P = .00964) and overall survival (P = .0204) than those for the other patients. Our observations suggest that aberrant expression of JAM-A promotes malignancy of uterine cervical adenocarcinoma by regulation of PVR/CD155, and JAM-A is therefore a potential therapeutic target for this malignancy.
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http://dx.doi.org/10.1111/cas.14734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893988PMC
February 2021

Comparing the extent of breast cancer tumors through contrast-enhanced ultrasound vs B-mode, opposed with pathology: evergreen study.

Breast Cancer 2021 Mar 29;28(2):405-413. Epub 2020 Oct 29.

Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, S 1, W 16, Chuo-ku, Sapporo, 060-8543, Japan.

Background: To prove the efficacy of contrast-enhanced ultrasound (CEUS) in determining the extent of resection, more evidence about B-mode and CEUS as opposed to pathology is required. We compared maximum tumor width measured on B-mode/CEUS images with that determined pathologically.

Methods: In this retrospective multicenter study, 152 operable breast cancer patients who had undergone both B-mode and CEUS were analyzed. Maximum tumor width on B-mode and CEUS, and on the postoperative pathological examination (P), was measured by the participating investigators. In addition, maximum width was assessed in B-mode and CEUS image sets by independent reviewers blinded to all patient information. We analyzed differences in maximum width between CEUS, B-mode and P.

Results: The mean widths as measured by the participating investigators were 15 ± 7 mm (B-mode), 19 ± 8 mm (CEUS), and 17 ± 9 mm (P). The difference subtracted P from B-mode was - 3 ± 7 mm (p < 0.0001), and that from CEUS was 1 ± 6 mm (p = 0.0163). The mean widths as measured by the independent reviewers were 16 ± 7 mm (B-mode) and 18 ± 7 mm (CEUS). The difference subtracted P from B-mode was - 2 ± 8 mm (p = 0.0114), while that from CEUS was 1 ± 7 mm (p = 0.1921).

Conclusions: Maximum lesion width measurement showed a tendency to increase in the order of B-mode, to P and CEUS. The difference in measurement between P and B-mode was significant, but there was no significant between CEUS and P. These results provide additional information of tendency patterns in measuring the maximum lesion width through enhancement on CEUS.
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http://dx.doi.org/10.1007/s12282-020-01176-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925467PMC
March 2021

Myoepithelioma of soft tissue and bone, and myoepithelioma-like tumors of the vulvar region: Clinicopathological study of 15 cases by PLAG1 immunohistochemistry.

Pathol Int 2020 Dec 17;70(12):965-974. Epub 2020 Sep 17.

Department of Surgical Pathology, Sapporo Medical University, School of Medicine, Hokkaido, Japan.

We demonstrated the clinicopathological findings of 13 myoepitheliomas of soft tissue and bone (MESTBs) and two myoepithelioma-like tumors of the vulvar region (MELTVRs), focusing on the association between nuclear atypia and clinical course, and the utility of immunohistochemistry (IHC) of pleomorphic adenoma gene 1 (PLAG1) for the pathological diagnosis of these tumors. Of the 13 MESTBs, eight, one and four cases exhibited mild, moderate and severe nuclear atypia, respectively. Two cases with venous invasion showed severe nuclear atypia and both died of advanced disease. Two MELTVR cases showed moderate nuclear atypia and had no evidence of disease after surgery. On IHC, 12 of 13 (92.3%) MESTBs showed PLAG1 immunoreactivity and none of the MELTVRs expressed PLAG1. In addition, MELTVRs showed loss of INI1 expression. In contrast, all MESTBs retained INI1 expression. Fluorescence in situ hybridization detected EWSR1, FUS and PLAG1 rearrangement in 5 (38.5%), 0 (0%) and 2 (15.4%) of the 13 MESTBs, respectively. No EWSR1, FUS and PLAG1 rearrangement were observed in the METLVRs. In conclusion, MESTBs with both severe nuclear atypia and venous invasion would be indicative of malignant potential. PLAG1 might be a useful IHC marker in MESTB diagnosis.
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http://dx.doi.org/10.1111/pin.13017DOI Listing
December 2020

Two cases of osteoblastic bone metastasis from muscle-invasive bladder cancer with discrepancy in response to chemotherapy: problems and limitations of bone biopsy.

Int Cancer Conf J 2020 Oct 24;9(4):235-239. Epub 2020 Jul 24.

Department of Urology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, 060-8543 Japan.

We report two cases of muscle-invasive bladder cancer (MIBC) with increasing multiple osteoblastic bone lesions but shrinking other lesions in response to chemotherapy. Case 1 had MIBC and received radical cystectomy followed by adjuvant gemcitabine plus cisplatin chemotherapy (GC). Three years after, follow computed tomography (CT) showed development of multiple lymph node metastasis, and then we performed GC as a first-line systemic chemotherapy. After two cycles of GC, CT showed de novo multiple osteoblastic lesions although metastatic lymph nodes were shrunk. Biopsy of the sternum revealed metastatic urothelial carcinoma. Case 2 had MIBC with multiple osteoblastic lesions on CT and bone scintigraphy, which was initially diagnosed as cT3bN0M1. After one cycle of GC, the number of osteoblastic lesions obviously increased although bladder tumor was regressed. Since the clinical course was unusual, biopsy of the clavicle was done. The histological diagnosis was benign osteoblastic bone disease, then the clinical diagnosis was revised to non-metastatic MIBC, and radical cystectomy was performed. Ten months after surgery, the patients complained worsening backache and CT showed increase in number of osteoblastic lesions. Eventually, ilium biopsy revealed bone metastasis of urothelial carcinoma. In case of atypical finding and unusual clinical course, biopsy of suspected metastatic lesion may be informative although adequate sampling should be secured.
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http://dx.doi.org/10.1007/s13691-020-00435-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450022PMC
October 2020

Osteofibrous dysplasia-like adamantinoma treated via intercalary segmental resection with partial cortex preservation using pedicled vascularized fibula graft: a case report.

World J Surg Oncol 2020 Aug 13;18(1):203. Epub 2020 Aug 13.

Department of Orthopedic Surgery, Sapporo Medical University School of Medicine, West 16, South 1, Chuo- ku, Sapporo, Hokkaido, 060-8543, Japan.

Background: Morphologically, osteofibrous dysplasia-like adamantinoma is thought to be intermediate between osteofibrous dysplasia and adamantinoma. Its treatment is not well established owing to its rarity.

Case Presentation: We report about of a 10-year-old girl with osteofibrous dysplasia-like adamantinoma initially diagnosed as osteofibrous dysplasia and treated via intercalary segmental resection with partial cortex preservation using a pedicled vascularized fibula graft for reconstruction. Bone union was observed 9 weeks after surgery. Twenty-two months after the definitive surgery, no recurrence was observed.

Conclusion: This case illustrates the upgrade from osteofibrous dysplasia to osteofibrous dysplasia-like adamantinoma. The surgical method may aid the treatment of osteofibrous dysplasia-like adamantinoma with incomplete cortex involvement of the tumor.
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http://dx.doi.org/10.1186/s12957-020-01983-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427073PMC
August 2020

Prognostic value of FoxP3 and CTLA-4 expression in patients with oral squamous cell carcinoma.

PLoS One 2020 12;15(8):e0237465. Epub 2020 Aug 12.

Department of Oral Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.

Background: Tumor-infiltrating lymphocytes include tumor-reactive lymphocytes and regulatory T-cells. However, the prognostic value of tumor-infiltrating lymphocytes in oral squamous cell carcinoma (OSCC) remains unclear.

Methods: We used immunohistochemistry to evaluate the presence of tumor-infiltrating FoxP3⁺ T-cells and CTLA-4⁺ cells in four distinct histological compartments (tumor parenchyma and stroma at the tumor center, and parenchyma and stroma at the invasive front) and assessed the association between the prevalence of these cells and the histopathological status of 137 patients with OSCC.

Results: Five-year overall survival, disease-specific survival, and recurrence-free survival were favorable in patients with high numbers of FoxP3⁺ T-cells in the parenchyma of the invasive front. Recurrence-free survival and metastasis-free survival were decreased in patients with high numbers of CTLA-4⁺ cells in the parenchyma of the invasive front.

Conclusions: The presence of FoxP3⁺ T-cells in the parenchyma of the invasive front may be a useful prognostic factor. Our results indicate that FoxP3⁺ T-cells may exert site-specific anti-tumor effects but may not play an immunosuppressive role in OSCC. In addition, our results suggest that CTLA-4+ cells suppress the function of FoxP3+ T-cells and promote anti-tumor immunity in OSCC.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237465PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423125PMC
October 2020

Autistic traits and cognitive profiles of treatment-resistant schizophrenia.

Schizophr Res Cogn 2020 Dec 27;22:100186. Epub 2020 Jul 27.

Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan.

The complex pathophysiology of treatment-resistant schizophrenia (TRS) includes severe positive symptoms but also other symptom domains. The overlapping psychological profiles of schizophrenia and autistic spectrum disorder (ASD) are not established. We compared TRS patients (n = 30) with schizophrenia patients in remission (RemSZ, n = 28) and ASD patients (n = 28), focusing on both neurodevelopmental aspects and general and social cognitive impairments. The TRS group performed the worst on general neurocognition (measured by the MATRICS Consensus Cognitive Battery) and social cognition (measured by the theory of mind and emotional expression). The RemSZ group performed the best among the three groups. Regarding autistic traits, all measurements by the Autism-Spectrum Quotient/Autism Screening Questionnaire/Pervasive Developmental Disorder Assessment Rating Scale showed that (1) the ASD patients had the highest autistic traits (2) the TRS patients' scores were less severe than the ASD group's, but (3) the overall trends placed the TRS group between the ASD and the RemSZ group. These findings indicate that TRS patients and remitted patients could have distinctive neurodevelopmental and cognitive profiles. Further, the degrees of social cognitive dysfunction and autistic traits in TRS patients could be close to those of ASD patients, suggesting similarities between TRS and ASD.
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http://dx.doi.org/10.1016/j.scog.2020.100186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390750PMC
December 2020

Borderline Microenvironment Fibrosis Is a Novel Poor Prognostic Marker of Oral Squamous Cell Carcinoma.

Anticancer Res 2020 Aug;40(8):4319-4326

Department of Pathology, Sapporo Medical University School of Medicine, Hokkaido, Japan.

Background/aim: The tumor microenvironment (TME) balances tumor growth and suppression through humoral factors and cell-cell interactions. In oral squamous cell carcinoma (OSCC), TMEs have been associated with prognosis of cancer patients and are evaluated by microscopy; however, these methods of evaluation vary among studies.

Materials And Methods: To evaluate the TME, borderline microenvironment fibrosis (bMF) was evaluated histologically in 236 OSCC cases and used to determine the clinicopathological status.

Results: bMF was observed in 47% (110 in 236 cases) of OSCC cases and associated with higher T category, N category, stage, histological grade and mode of invasion. bMF-positive was related to overall survival (OS) and progression-free survival (PFS). Multivariate analysis revealed that bMF-positive was an independent factor for OS in all cases [n=226; HR=1.683 (1.018-2.781); p=0.042], especially in T1+T2 cases [n=186; HR=1.926 (1.079-3.440); p=0.024], and PFS in all cases [n=226; HR=2.254 (1.397-3.637); p=0.001].

Conclusion: bMF may act as a novel biomarker for OSCC.
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http://dx.doi.org/10.21873/anticanres.14434DOI Listing
August 2020

Fatal fulminant hepatitis induced by combined ipilimumab and nivolumab therapy despite favorable histologic response and confirmed by autopsy in a patient with clear cell renal cell carcinoma.

Immunol Med 2021 Jun 7;44(2):136-141. Epub 2020 Jul 7.

Department of Pathology, School of Medicine, Sapporo Medical University, Sapporo, Japan.

Effective management of immune-related adverse events in patients receiving immunotherapy for cancer is problematic. In this report, we present the case of a 58-year-old man with advanced clear cell renal cell carcinoma who responded well to a combination of ipilimumab and nivolumab. However, after two courses of treatment, he developed fulminant hepatitis and died. An autopsy confirmed that the primary lesion in the left kidney was more than 99% necrotic with only six small residual tumor lesions. These lesions were infiltrated by large numbers of CD8-positive/TIA-1-positive lymphocytes. However, a metastatic lesion in the right kidney harbored few lymphocytes. Furthermore, the tumor cells in the metastatic lesion and one of the residual lesions showed decreased expression of HLA class I molecules, which are a prerequisite for cytotoxic T-lymphocyte-mediated immunotherapy in tumor cells. In this patient, more than 80% of hepatocytes were destroyed and the parenchyma was infiltrated with CD8-positive/TIA-1-positive lymphocytes. The patient had polyuria, which was attributed to neurohypophysitis caused by the infiltration of CD8-positive/TIA-1-positive lymphocytes. We believe that this is an instructive case for immuno-oncologists.
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http://dx.doi.org/10.1080/25785826.2020.1788229DOI Listing
June 2021

Aldolase A promotes epithelial-mesenchymal transition to increase malignant potentials of cervical adenocarcinoma.

Cancer Sci 2020 Aug 30;111(8):3071-3081. Epub 2020 Jun 30.

Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.

Recent studies have revealed that metabolic reprogramming is closely associated with epithelial-mesenchymal transition (EMT) during cancer progression. Aldolase A (ALDOA) is a key glycolytic enzyme that is highly expressed in several types of cancer. In this study, we found that ALDOA is highly expressed in uterine cervical adenocarcinoma and that high ALDOA expression promotes EMT to increase malignant potentials, such as metastasis and invasiveness, in cervical adenocarcinoma cells. In human surgical specimens, ALDOA was highly expressed in cervical adenocarcinoma and high ALDOA expression was correlated with lymph node metastasis, lymphovascular infiltration, and short overall survival. Suppression of ALDOA expression significantly reduced cell growth, migration, and invasiveness of cervical cancer cells. Aldolase A expression was partially regulated by hypoxia-inducible factor-1α (HIF-1α). Shotgun proteome analysis revealed that cell-cell adhesion-related proteins were significantly increased in ALDOA-overexpressing cells. Interestingly, overexpression of ALDOA caused severe morphological changes, including a cuboidal-to-spindle shape shift and reduced microvilli formation, coincident with modulation of the expression of typical EMT-related proteins. Overexpression of ALDOA increased migration and invasion in vitro. Furthermore, overexpression of ALDOA induced HIF-1α, suggesting a positive feedback loop between ALDOA and HIF-1α. In conclusion, ALDOA is overexpressed in cervical adenocarcinoma and contributes to malignant potentials of tumor cells through modulation of HIF-1α signaling. The feedback loop between ALDOA and HIF-1α could become a therapeutic target to improve the prognosis of this malignancy.
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http://dx.doi.org/10.1111/cas.14524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419050PMC
August 2020

Less correlation between mismatch repair proteins deficiency and decreased expression of HLA class I molecules in endometrial carcinoma: a different propensity from colorectal cancer.

Med Mol Morphol 2021 Mar 14;54(1):14-22. Epub 2020 May 14.

Department of Pathology, School of Medicine, Sapporo Medical University, Sapporo, Japan.

Mismatch repair protein deficiency (dMMR) is a favorable prognostic factor in colorectal cancer. It is also associated with aberrant expression of HLA class I molecules, which are required for cytotoxic T lymphocyte-mediated cancer immunotherapy. Because dMMR is frequently also found in endometrial cancers (ECs), we retrospectively investigated the expression of mismatch repair proteins and HLA class I molecules in 127 EC patients. In this study, EC patients being treated in our hospital were recruited from 2005 to 2009 and observed until December 2017. Lesion specimens were evaluated via immunohistochemistry for MSH6 and PMS2 (mismatch repair proteins) and HLA class I molecules. Expression of these molecules was statistically related to clinical and pathological factors and prognosis. dMMR was detected in 33 patients and did not correlate with the expression level of HLA class I molecules (P = 0.60). On the other hand, unexpectedly, multivariate analysis revealed that intact expression of HLA class I molecules was associated with p53 overexpression (P = 0.004). Neither dMMR nor decreased expression of HLA class I molecules were prognostic factors. These results are inconsistent with previous findings for colorectal cancer. A distinctive local tissue immune microenvironment would underlie the discrepancy in the results between EC and colorectal cancer.
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http://dx.doi.org/10.1007/s00795-020-00254-6DOI Listing
March 2021

Detection of VHL deletion by fluorescence in situ hybridization in extraneuraxial hemangioblastoma of soft tissue.

Pathol Int 2020 07 17;70(7):473-475. Epub 2020 Apr 17.

Department of Surgical Pathology, School of Medicine, Sapporo Medical University, Hokkaido, Japan.

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http://dx.doi.org/10.1111/pin.12935DOI Listing
July 2020
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