Publications by authors named "Yukihiro Imai"

175 Publications

Appropriate indication and procedure for random skin biopsy in the diagnosis of intravascular large B-cell lymphoma.

Australas J Dermatol 2021 May 18;62(2):225-227. Epub 2020 Dec 18.

Department of Dermatology, Kobe City Medical Centre General Hospital, Kobe, Japan.

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http://dx.doi.org/10.1111/ajd.13487DOI Listing
May 2021

Cytogenetic complexity and heterogeneity in intravascular lymphoma.

J Clin Pathol 2021 Apr 6;74(4):244-250. Epub 2020 Aug 6.

Department of Pathology, Kobe City Medical Center General Hospital, Kobe, Japan.

Aims: To characterise the karyotypic abnormalities and heterogeneities in intravascular lymphoma (IVL).

Methods: G-banded karyotyping was performed on biopsy specimens from a single-centre IVL cohort comprising intravascular large B-cell lymphoma (IVLBCL, n=12) and NK/T-cell lymphoma (IVNKTCL, n=1).

Results: Five IVLBCL cases and one IVNKTCL case (total 46%) were found to have normal karyotypes, and the cytogenetic abnormalities observed in the other seven IVLBCL cases (54%) were investigated further. These seven karyotypes were uniformly complex with an average of 13 aberrations. The seven cases all had abnormalities involving chromosome 6, with 57% involving structural abnormalities at 6q13, and chromosome 8, with 43% involving abnormalities at 8p11.2. In addition, 71% had aberrations at 19q13. On average, 4.4 chromosomal gains and losses were detected per case. Cytogenetic heterogeneities were observed in six cases (86%) and tetraploidy in three cases (43%). There was no significant difference in progression-free survival (p=0.92) and overall survival (p=0.61) between the IVLBCL cases with complex and normal karyotypes.

Conclusion: Approximately half of IVLBCL cases had a highly heterogeneous pattern of karyotypes with different clonal numerical and structural chromosome aberrations.
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http://dx.doi.org/10.1136/jclinpath-2020-206573DOI Listing
April 2021

Successful Treatment of a Mixed Neuroendocrine-Nonneuroendocrine Neoplasm of the Colon with Metastases to the Thyroid Gland and Liver.

Case Rep Otolaryngol 2020 13;2020:5927610. Epub 2020 Feb 13.

Department of Otolaryngology, Head and Neck Surgery, Kobe City Medical Center General Hospital, 2-1-1 Minatojima Minami-machi, Chuo-ku, Kobe 650-0047, Japan.

Patients with mixed neuroendocrine-nonneuroendocrine neoplasms (MiNENs) of the colon have poor prognosis. Herein, we report a patient with MiNEN of the colon with metastases to the liver and the thyroid gland, with long-term survival. A 45-year-old man presented with anterior neck swelling. Histopathological examination of the thyroid tumor revealed neuroendocrine carcinoma (NEC), suggesting that a primary NEC in another organ had metastasized to the thyroid gland. Computed tomography to identify a primary NEC revealed two tumors: one in the liver and one in the transverse colon. A biopsy revealed that the histopathology of the liver and colon tumors was NEC and adenocarcinoma, respectively. Thereafter, the patient underwent surgical resection of the colon tumor and was finally diagnosed as colon MiNEN with metastases to the thyroid and liver. The surgical resection of the metastatic liver tumor was performed after several courses of systemic chemotherapy, and the patient survives presently without any recurrence for approximately seven years after the diagnosis. Surgical resection of each metastatic lesion combined with systematic chemotherapy apparently improved the prognosis of MiNEN of the colon with distant metastases.
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http://dx.doi.org/10.1155/2020/5927610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040413PMC
February 2020

Real-time imaging of head and neck squamous cell carcinomas using confocal micro-endoscopy and applicable dye: A preliminary study.

Auris Nasus Larynx 2020 Aug 20;47(4):668-675. Epub 2020 Feb 20.

Department of Neural Regeneration and Cell Communication, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu 514-8507, Japan.

Objectives: Confocal laser endomicroscopy (CLE) is a technology that enables microscopic visualization of lesions in real-time (optical biopsy) and has been successfully applied for clinical use in gastroenterology. Recently, it was also introduced for head and neck squamous cell carcinoma (HNSCC) diagnostics. We previously designed a self-made CLE, which can provide bichrome images, with topical contrast agents that are safe for use in patients. Herein, we report findings of a pilot study using our self-made CLE to image pairs of normal and cancerous tissues. This study aimed to characterize the features of HNSCC compared with normal mucosa and to establish a methodology of in vivo real-time optical biopsy of HNSCCs.

Methods: HNSCC tissues were acquired from 10 patients who underwent surgical resection. Dissected specimens were first evaluated for their auto-fluorescence spectral profiles with 473 nm laser excitation and further optical observation. While obtaining the image, auto-fluorescence spectrum and intensity of the reflectance fluorescent signals were measured in real-time by a spectrometer. Subsequently, acriflavine was applied to the specimen to fluorescently label the nuclei and observe the difference between normal and cancerous tissues with 473 nm laser excitation. Finally, double staining with acriflavine and edible Food Red No.106 was performed to observe both nuclei and the cytoplasm of normal and cancerous tissues at 473 nm and 561 nm laser excitation.

Results: Lower signals were detected from auto-fluorescence images of cancer tissues than normal tissues with 473 nm laser excitation. After acriflavine application, there was a clear difference between cancer and normal mucosa in the uniformity of nuclear size and shape. In normal mucosa, cells were arranged in an orderly manner, with each cell resembling a frog's egg. By contrast, in cancer tissues, the cell density was higher, and the cellular arrangement was less orderly. Using both acriflavine and Food Red No.106, images became more vivid, but more complicated because red dye staining of the cytoplasm emerged as fluorescence at different wavelengths.

Conclusions: Real-time in vivo imaging using the newly developed CLE and conditions may be used to distinguish cancer tissue from normal mucosa without invasive biopsy.
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http://dx.doi.org/10.1016/j.anl.2020.02.001DOI Listing
August 2020

Tumour content ratio matters for detecting epidermal growth factor receptor mutation by cobas test in small biopsies; a retrospective study.

BMC Cancer 2020 Feb 6;20(1):104. Epub 2020 Feb 6.

Department of Respiratory Medicine, Kobe City Medical Center General Hospital, 2-1-1 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.

Background: Recent studies indicate the benefit of treatment with osimertinib over that with conventional epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) for untreated EGFR-mutated non-small cell lung cancer (NSCLC). Cobas ver2 is the only companion diagnostic method for detecting EGFR mutations with osimertinib treatment. We clinically experience false negative cases with this test, but its actual sensitivity is unknown. Moreover, no study has suggested the importance of tumour dissection, and most facilities do not routinely perform them on small biopsies. The purpose of this study was to evaluate the sensitivity of cobas in clinical practice and clarify the role of dissection as a component of the cobas testing.

Methods: We examined 132 patients with EGFR-mutated NSCLC diagnosed by bronchoscopy and confirmed with PCR clamp. Patients were tested with cobas and the EGFR-positive rate was calculated. Samples with undetected EGFR mutations were retested after tumour dissection and the rate of samples whose EGFR mutation was corrected to positive was assessed. To evaluate tumour cellularity, the tumour content ratio was assessed by calculating tumour cell count over the total cell count on the slide.

Results: The positive rate of EGFR mutation identification was 76% with cobas, although EGFR mutation-negative patients retained responses to TKI therapy equivalent to positive patients did; however, the tumour content ratio of negative samples was significantly lower than that of positive samples. Twenty-nine negative samples underwent dissection and 24% were corrected to positive. Moreover, 53% of the samples with a tumour content ratio below 10% was negative for cobas, but 33% of these turned positive after dissection.

Conclusions: Cobas had a high false negative rate in clinical practice, and tumour content ratio might be associated with this rate. Dissection could improve the sensitivity of cobas, especially in samples with low tumour cellularity.
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http://dx.doi.org/10.1186/s12885-020-6603-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7006383PMC
February 2020

[A Case of Renal Oncocytosis with Bilateral Multiple Renal Masses].

Hinyokika Kiyo 2019 Apr;65(4):111-116

The Department of Pathology, Kobe City Medical Center General Hospital.

A 63-year-old man with microscopic hematuria underwent contrast-enhanced CT, which showed multiple bilateral renal masses. Percutaneous biopsy results indicated renal oncocytosis. The tumors remained unchanged for 3 years. Renal oncocytosis is a very rare tumor, but it is an established disease entity characterized by numerous oncocytic tumors and diffuse (sporadic) renal parenchymal epithelial oncocytic changes on an analysis histopathology. Although renal oncocytosis can be sporadic or part of Birt-Hogg-Dube syndrome (BHDS), our case did not associate with BHDS because of absence of lung cyst.
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http://dx.doi.org/10.14989/ActaUrolJap_65_4_111DOI Listing
April 2019

Intravascular NK/T-cell lymphoma: clinicopathological and integrated molecular analysis of two cases provides a clue to disease pathogenesis.

J Clin Pathol 2019 Sep 23;72(9):642-646. Epub 2019 May 23.

Department of Diagnostic Pathology, Kobe City Medical Center General Hospital, Kobe, Japan

Aims: To elucidate the clinicopathological and molecular features of intravascular NK/T-cell lymphoma (IVNKTCL).

Methods: Two cases of IVNKTCL were retrieved from a single-centre cohort composed of 25 intravascular lymphomas. Whole-exome and RNA sequencing and immunohistochemistry were performed.

Results: We identified somatic mutations in the following epigenetic regulators: four histone genes (, , and histone deacetylase (), two helicases ( and ), two methylation-related enzymes ( and ) and the SNI/SWF pathway (). Copy number analysis identified driver gene alterations comprising the loss of , and , and the gain of and histone clusters. RNA sequencing analysis did not indicate the presence of any fusion gene. Both cases were positive for Epstein-Barr virus (EBV) and showed strong expression of programmed death-ligand 1 (PD-L1).

Conclusions: This study raises the possibility that, at least for some patients, IVNKTCL may be considered an epigenetic disease with EBV infection-associated aetiopathogenesis.
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http://dx.doi.org/10.1136/jclinpath-2019-205727DOI Listing
September 2019

Substantial improvement in immune thrombocytopenic purpura associated with T-cell/histiocyte-rich B-cell lymphoma treated with chemotherapy: A case report.

Mol Clin Oncol 2019 Apr 27;10(4):441-445. Epub 2019 Feb 27.

Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe City Hospital Organization, Kobe, Hyogo 650-0047, Japan.

Immune thrombocytopenic purpura (ITP) is characterized by antibody and immune platelet destruction, occasionally leading to life-threatening hemorrhage. ITP is a frequent complication of chronic lymphoid leukemia, but is rarely associated with diffuse large B-cell lymphoma (DLBCL). We herein describe a case of ITP associated with T-cell/histiocyte-rich B-cell lymphoma (T/HRBCL), which is a rare variant of DLBCL. A 54-year-old man presented with fever, multiple lymphadenopathies, petechial purpura and intraoral mucosal hemorrhage. Laboratory data revealed thrombocytopenia, normal white blood cell count, mild anemia, no active viral infections, and no autoimmune antibodies. Multiple lymphadenopathies were observed on computed tomography. A bone marrow biopsy revealed minor hypercellularity with increased number of megakaryocytes; however, there were no pathological cells or phagocytic cells. The patient was diagnosed with ITP; concurrently, he was also diagnosed with T/HRBCL via lymph node biopsy, and was treated accordingly with a chemotherapeutic regimen comprising rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone. Prompt reduction in the size of the superficial lymph nodes and an increase of the platelet count were observed simultaneously. To the best of our knowledge, this is the first report of T/HRBCL complicated by ITP. The findings strongly suggest a causative association between ITP and T/HRBCL.
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http://dx.doi.org/10.3892/mco.2019.1816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425504PMC
April 2019

Clinical Value of Fused PET/MRI for Surgical Planning in Patients With Oral/Oropharyngeal Carcinoma.

Laryngoscope 2020 02 21;130(2):367-374. Epub 2019 Mar 21.

Department of Head and Neck Surgery, Kobe City Medical Center General Hospital, Kobe, Japan.

Objectives/hypothesis: To evaluate the usefulness of fused positron emission tomography (PET)/magnetic resonance (MR) images for surgical planning in patients with oral/oropharyngeal cancer and suspected mandibular invasion.

Study Design: Individual cohort study.

Methods: Eleven of 17 patients with suspected mandibular invasion of squamous cell carcinoma of the lower gingiva, oropharynx, and buccal mucosa who underwent 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) and contrast-enhanced MR imaging (MRI) and had fused PET/MR images were enrolled in this study. The area for surgical resection was determined based on the fused images. The usefulness of these images was confirmed by comparing them with the histopathologic findings in the resected tumors.

Results: Histopathologic evaluation of the surgical specimens revealed that nine of the 11 patients had invasion into the mandible and/or medial pterygoid muscle. All patients had a negative surgical margin. The sensitivity and specificity for detection of mandibular/medial pterygoid muscle invasion was 100%/40% and 83%/100% by fused PET/MRI, respectively, and 100%/20% and 100%/60% by PET/CT, respectively. Interobserver reproducibility between two radiologists/nuclear medicine physicians and two head and neck surgeons showed that the only statistically significant κ values were for PET/MRI.

Conclusions: PET/MRI can be easily understood by head and neck surgeons, who are not diagnostic imaging professionals, and can be used when planning the area to be surgically resected in patients with oral/oropharyngeal cancer and clinically suspected mandibular invasion. Considering the expense of a hybrid PET/MRI system, creation of a fused PET/MR image would provide a reasonable and reliable tool for clinical use in these patients.

Level Of Evidence: 2b Laryngoscope, 130:367-374, 2020.
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http://dx.doi.org/10.1002/lary.27911DOI Listing
February 2020

The impact of early diagnosis on the prognosis of extranodal NK/T-cell lymphoma with massive lung involvement: a case report.

BMC Pulm Med 2019 Feb 21;19(1):48. Epub 2019 Feb 21.

Department of Hematology, Kobe City Medical Center General Hospital, 2-1-1, Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan.

Background: Pulmonary non-Hodgkin lymphoma (NHL) is rare. The most frequent subtype of pulmonary NHL is low-grade B-cell lymphoma, such as lymphoma of mucosa-associated lymphoma tissue. Extranodal natural killer cell/T-cell lymphoma, nasal type (ENKL) is characterized by predominant extranodal involvement and association with Epstein-Barr virus (EBV). ENKL with massive lung involvement has been infrequently reported, and its prognosis is extremely poor.

Case Presentation: A 20-year-old Japanese man presented with intermittent fever lasting for 2 months. Radiological imaging demonstrated multiple nodules of uneven shape and size in both lungs. Video-assisted thoracic surgical lung biopsy showed abnormal lymphocyte infiltration, which was positive for CD3, CD56, and perforin. In situ hybridization for EBV-encoded RNA was positive. From these findings, he was diagnosed with ENKL with lung involvement. The patient was successfully treated with intensive combinational chemotherapy followed by allogeneic cord blood transplantation. He has been alive with continuous complete remission for 1 year after diagnosis.

Conclusions: Although ENKL involving the lung has been reported to have dismal outcomes, our patient showed long-term survival after intensive chemotherapy and up-front allogeneic hematopoietic transplantation. The present case highlights the importance of early diagnosis as well as allogeneic transplantation.
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http://dx.doi.org/10.1186/s12890-019-0815-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6385406PMC
February 2019

Clinicopathological analysis of clinically occult extrapulmonary lymphangioleiomyomatosis in intra-pelvic and para-aortic lymph nodes associated with pelvic malignant tumors: A study of nine patients.

Pathol Int 2019 Jan;69(1):29-36

Department of Pathology, Kobe City Medical Center General Hospital, Kobe, Japan.

The clinicopathological and immunohistochemical characteristics of clinically occult extrapulmonary lymphangioleiomyomatosis in lymph nodes (LN-LAM) being dissected during surgical staging of pelvic malignancy have not been well investigated. We assessed samples from nine female patients (median age, 61). None had past or familial history of tuberous sclerosis and had LAM lesions other than LN such as lung. The primary malignancies included four endometrial endometrioid carcinomas, one endometrial carcinosarcoma, three ovarian serous carcinomas and one urothelial carcinoma. Median follow-up was 43 months. The number of affected LNs ranged from 1 to 15 (median, 2) with sizes ranging from 1 to 13 mm (median, 3.0). Six cases had clinically occult LN-LAM only within the pelvic LNs, two only within para-aortic LNs, and one within both pelvic and para-aortic lymph nodes. Immunohistochemically, LAM cells exhibited a strong diffuse positivity for β-catenin and E-cadherin in all nine cases. Clinically occult LN-LAM mainly affects peri- or post-menopausal women. On rare occasions, occult LN-LAM may manifest as systemic LAM, including in the lung. β-catenin and E-cadherin carry potential utility as additional diagnostic markers.
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http://dx.doi.org/10.1111/pin.12749DOI Listing
January 2019

Case Report: Acute Generalized Exanthematous Pustulosis Caused by Praziquantel.

Am J Trop Med Hyg 2019 03;100(3):700-702

Department of General Internal Medicine, Kobe City Medical Center General Hospital, Kobe, Japan.

Praziquantel is widely used for treating parasitic infections globally, especially in countries with endemic schistosomiasis. However, severe hypersensitivity to praziquantel has rarely been reported. We report the case of a 30-year-old Japanese man who developed acute generalized exanthematous pustulosis (AGEP), which is a rare and severe cutaneous reaction usually triggered by drugs, after taking praziquantel. During medical examination, eggs of were found in his stool. He took praziquantel 600 mg for 1 day and developed skin rashes and fever the next day. Pruritic generalized maculopapular erythematous eruptions were observed over the entire body. He had elevated white blood cell count, liver enzymes, and C-reactive protein level. We prescribed acetaminophen, fexofenadine hydrochloride, loxoprofen sodium, and topical ointments including difluprednate and hydrocortisone. Over the next 3 days, he developed pinhead-sized, non-follicular pustules on his diffusely erythematous skin. Histological findings of the pustular lesion showed spongiform subcorneal pustules with perivascular inflammatory cells. Approximately 8 days after taking praziquantel, the pustules resolved with desquamation. He became afebrile on day 9 and his laboratory parameters returned to normal levels on day 16. He was diagnosed with AGEP caused by praziquantel. Physicians need to be aware that praziquantel could cause AGEP, although it is generally considered a safe drug.
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http://dx.doi.org/10.4269/ajtmh.18-0832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6402890PMC
March 2019

Encapsulating peritoneal sclerosis in a patient after allogeneic hematopoietic stem cell transplantation: a case report.

BMC Gastroenterol 2019 Jan 21;19(1):12. Epub 2019 Jan 21.

Department of Hematology, Kobe City Hospital Organization, Kobe City Medical Center General Hospital, 2-1-1 Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan.

Background: Encapsulating peritoneal sclerosis (EPS) is a chronic clinical syndrome of acute or subacute gastrointestinal obstruction seen mainly in patients undergoing peritoneal dialysis. Although there are a few reports on EPS developing in non-peritoneal dialysis patients, it has not been reported in patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT). Here, we report a case of EPS after a second HSCT.

Case Presentation: A 46-year-old man with myelodysplastic syndrome showed relapse after HSCT and received a second HSCT. The patient was diagnosed with chronic graft-versus-host disease (cGVHD)-associated serositis because of persistent ascites. His ascites improved gradually and disappeared without immunosuppressive therapy. He presented with nausea, weight loss, and constipation 1 year after improvement of ascites. Computed tomography revealed no organic obstruction, but did reveal dilated, thickened, and adhered small bowel loops with a mass-like appearance. He was diagnosed with EPS on the basis of clinical symptoms and image findings. He received corticosteroid therapy (20 mg/body) without any improvement in symptoms. He developed recurrence of myelodysplastic syndrome at 1 month after initiation of corticosteroid therapy. This progressed into acute myeloid leukaemia after 3 months. He died 31 months after the second HSCT. At autopsy, the small and large intestines had formed extensive adhesions and showed signs of progressive fibrosis with peritoneal sclerosis, fibroblast swelling, fibrin deposition, and inflammatory cell infiltration, which confirmed the diagnosis of EPS.

Conclusion: This case suggests that EPS may complicate patients with cGVHD-associated serositis. Although the mechanism of EPS development is not clear, clinicians should be aware of this eventuality.
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http://dx.doi.org/10.1186/s12876-019-0933-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341688PMC
January 2019

Effectiveness of Crizotinib for Inflammatory Myofibroblastic Tumor with ALK mutation.

Intern Med 2019 Apr 19;58(7):1029-1032. Epub 2018 Nov 19.

Department of Medical Oncology, Kobe City Hospital Organization Kobe City Medical Center General Hospital, Japan.

Inflammatory myofibroblastic tumor (IMT), a rare sarcoma, is primarily treated via resection of the mass. However, in cases of recurrence or unresectable tumors, no standard care exists. While crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, is only approved for non-small-cell lung cancer with ALK mutation, it is reportedly effective for other malignant tumors with ALK mutation. We herein report a case involving a 37-year-old woman with retroperitoneal IMT with ALK mutation, who experienced recurrence after complete resection, in whom crizotinib treatment resulted in complete response. ALK-inhibitor efficacy against malignancies with ALK mutations should be investigated in future.
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http://dx.doi.org/10.2169/internalmedicine.1640-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478978PMC
April 2019

Starvation-induced Liver Enzyme Elevation after Initiation of Feeding.

Intern Med 2019 Mar 17;58(5):749-753. Epub 2018 Oct 17.

Department of Anesthesia and Critical Care, Kobe City Medical Center General Hospital, Japan.

Exacerbation of liver enzymes after the initiation of feeding in malnourished patients is caused by refeeding syndrome or persistent starvation. There are no definite clinical markers for distinguishing between the two conditions. We herein report a 63-year-old woman with starvation-induced liver enzyme elevation. Her body weight was inversely associated with the liver enzyme levels after refeeding, which was a different course from refeeding syndrome. Normalization of liver enzymes ensued as the caloric intake increased and weight gain progressed. Daily changes in body weight can be a useful clinical marker for distinguishing between refeeding syndrome and starvation-induced liver enzyme elevation.
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http://dx.doi.org/10.2169/internalmedicine.1663-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443550PMC
March 2019

Therapeutic strategy for pineal parenchymal tumor of intermediate differentiation (PPTID): case report of PPTID with malignant transformation to pineocytoma with leptomeningeal dissemination 6 years after surgery.

J Neurosurg 2018 Jul 1:1-7. Epub 2018 Jul 1.

1Department of Neurosurgery and Stroke Center, Shinko Hospital.

Pineal parenchymal tumor of intermediate differentiation (PPTID) is rare. The WHO first classified PPTID in 2000 as a pineal parenchymal tumor (PPT) with an intermediate prognosis between pineocytoma (PC) and pineoblastoma (PB). It is considered an intermediate-grade tumor and divided into WHO grade II or III.The number of available reports about PPTID is presently limited, and the appropriate management for this tumor has not yet been determined.The authors report a rare case of PC in a 63-year-old woman who presented with lower-extremity weakness and gait disturbance. A pineal mass lesion was detected on MRI. A diagnosis of PC was established after microsurgical gross-total tumor resection, and the patient received no adjuvant therapy after surgery. Two years after surgery, a partial recurrence was recognized and Gamma Knife radiosurgery was performed. Fours years later, the patient developed diffuse leptomeningeal dissemination. She was successfully treated with craniospinal irradiation. Leptomeningeal dissemination may develop 6 years after the initial diagnosis of PC. A histopathological study of the recurrent tumor revealed a malignant change from PC to PPTID.The present case shows the importance of long-term follow-up of patients with PPTs following resection and the efficacy of craniospinal irradiation in the treatment of leptomeningeal dissemination.
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http://dx.doi.org/10.3171/2018.2.JNS171876DOI Listing
July 2018

Fistula Formation Secondary to Mucinous Appendiceal Adenocarcinoma May Be Related to a Favorable Prognosis: A Case Report and Literature Review.

Intern Med 2018 Oct 6;57(20):2945-2949. Epub 2018 Jun 6.

Department of Gastroenterology and Hepatology, Kobe City Medical Center West Hospital, Japan.

A 90-year-old man was referred to our hospital because of a positive fecal occult blood test. Colonoscopy revealed a lesion with multiple nodules covered with abundant mucus at the hepatic flexure. Computed tomography showed a dilated appendix attached distally to the hepatic flexure. Right hemicolectomy was performed, and the pathological examination revealed a mucinous appendiceal adenocarcinoma infiltrating the hepatic flexure without pseudomyxoma peritonei. The patient is doing well without recurrence 12 months postoperatively. Extraperitoneal drainage of the malignant ascites caused by the fistula may allow for an early diagnosis, while also making it possible to successfully resect the lesion, thus resulting in a favorable outcome.
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http://dx.doi.org/10.2169/internalmedicine.0694-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232025PMC
October 2018

Development of Antiresorptive Agent-Related Osteonecrosis of the Jaw After Dental Implant Removal: A Case Report.

J Oral Implantol 2018 Oct 5;44(5):359-364. Epub 2018 Jun 5.

1   Department of Oral and Maxillofacial Surgery, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan.

Dental implant treatment is a highly predictable therapy, but when potentially lethal symptoms or complications occur, dentists must remove the implant fixture. Recently, reports on antiresorptive agent-related osteonecrosis of the jaw have increased in the field of dental implants, although the relationship between dental implant treatment and antiresorptive agents remains unclear. Here, we report a case of antiresorptive agent-related osteonecrosis of the jaw that developed after dental implant removal. A 67-year-old Japanese woman with a medical history of osteoporosis and 7 years of oral bisphosphonate treatment was referred to our hospital with a chief complaint of painful right mandibular bone exposure. A family dentist removed the dental implants from the right mandible using a trephine drill without flap elevation in August 2016. However, the healing was impaired; she was referred to our hospital 3 months after the procedure. We performed a sequestrectomy of the mandible under general anesthesia. In conclusion, this patient's course has two important implications: First, the removal of dental implants from patients who are prescribed oral bisphosphonates for long durations can cause antiresorptive agent-related osteonecrosis of the jaw. Second, meticulous procedures are required to prevent and treat the development of antiresorptive agent-related osteonecrosis of the jaw after dental implant removal.
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http://dx.doi.org/10.1563/aaid-joi-D-18-00032DOI Listing
October 2018

Choriocarcinoma with multiple lung metastases from complete hydatidiform mole with coexistent fetus during pregnancy.

J Obstet Gynaecol Res 2018 Aug 29;44(8):1476-1481. Epub 2018 May 29.

Department of Obstetrics and Gynecology, Kobe City Medical Center General Hospital, Kobe, Japan.

Gestational trophoblastic neoplasm (GTN) is a serious morbidity of complete hydatidiform mole with coexistent fetus (CHMCF) and usually develops after termination of pregnancy. Here we report a case of choriocarcinoma derived from CHMCF during pregnancy. A 33-year-old multiparous woman with suspected CHMCF was admitted with a severe cough. Computed tomography revealed multiple lung metastases. Cesarean section and hysterectomy were performed at 31 weeks of gestation on diagnosis of high-risk GTN from International Federation of Gynecology and Obstetrics (FIGO) scoring. A live female infant weighing 1390 g was delivered. Choriocarcinoma was diagnosed from pathological findings. The patient received multi-agent chemotherapy and was discharged on the 40th postoperative day. In conclusion, CHMCF can result in high-risk GTN during pregnancy. For a suspected GTN, diagnosis from FIGO scoring should determine treatment strategy. If patients with CHMCF wish to continue their pregnancy, careful follow-up, including regular chest radiography and ultrasonography, is warranted.
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http://dx.doi.org/10.1111/jog.13677DOI Listing
August 2018

Programmed Cell Death Ligand 1 Expression in Non-Small-cell Lung Cancer Patients With Interstitial Lung Disease: A Matched Case-control Study.

Clin Lung Cancer 2018 09 5;19(5):e667-e673. Epub 2018 May 5.

Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Hyogo, Japan.

Background: Programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) checkpoint inhibitors have demonstrated antitumor activity, and immunohistochemical analysis of PD-L1 expression has been used to identify the response in patients with non-small-cell lung cancer (NSCLC). Recently, considerable interest has ensued toward extending the benefit of these inhibitors to high-risk patients, such as those with NSCLC and interstitial lung disease (ILD). However, no studies have compared PD-L1 expression in NSCLC patients with and without ILD. Therefore, we conducted a case-control study to evaluate PD-L1 expression and stromal CD8 lymphocyte density in these patients.

Materials And Methods: The data from patients with pathologic stage I or II NSCLC who had undergone surgery from January 2007 to January 2016 were analyzed.

Results: We identified 62 patients with pathologic stage I or II NSCLC and ILD. We compared these patients with 1:1-matched cohort. In both groups with and without ILD, approximately 60% were PD-L1. Tumor cell PD-L1 expression was similar between the groups (median, 1%; interquartile range, 0%-5%; vs. median, 1%; interquartile range, 0%-5%; P = .49). The proportion of patients with positive (≥ 1%) and strongly positive (≥ 50%) PD-L1 expression was also similar between the 2 groups (P = .46 and P = 1.00, respectively). Additionally, the CD8 lymphocyte density did not differ between patients with and without ILD.

Conclusion: PD-L1 expression and stromal CD8 lymphocyte density were comparable between the NSCLC patients with and without ILD. PD-1 axis inhibitors might be effective for NSCLC patients with ILD.
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http://dx.doi.org/10.1016/j.cllc.2018.04.012DOI Listing
September 2018

A Punctate Magnetic Resonance Imaging Pattern in a Patient with Systemic Lupus Erythematosus Is an Early Sign of Progressive Multifocal Leukoencephalopathy: A Clinicopathological Study.

Intern Med 2018 Sep 27;57(18):2727-2734. Epub 2018 Apr 27.

Department of Neurology, Kobe City Medical Center General Hospital, Japan.

A 37-year-old woman with systemic lupus erythematosus presented with gait disturbance and cognitive dysfunction. Brain magnetic resonance imaging (MRI) revealed small, punctate, T2-/fluid-attenuated inversion recovery-hyperintense and T1-hypointense lesions without gadolinium enhancement, which is atypical for progressive multifocal leukoencephalopathy (PML). On a pathological examination of biopsied brain tissues, JC virus-infected cells were hardly detected via immunohistochemistry but were certainly detected via in situ hybridization, conclusively verifying the PML diagnosis. After tapering off the immunosuppressant and mefloquine administration, the MRI findings revealed gradual improvement, and she has been stable for over 18 months. A punctate MRI pattern is not specific to natalizumab-associated PML but may be a ubiquitous early sign useful for the early diagnosis of PML.
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http://dx.doi.org/10.2169/internalmedicine.0696-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191581PMC
September 2018

Sleeve lobectomy for lung adenocarcinoma treated with neoadjuvant afatinib.

J Thorac Dis 2018 Mar;10(3):E170-E174

Department of Thoracic Surgery, Kobe City Medical Center General Hospital, Kobe, Japan.

Afatinib, the second-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has been postulated to be associated with improved inhibition of EGFR-dependent tumor growth compared with first-generation EGFR-TKIs for advanced non-small cell lung cancer (NSCLC). We present a case of lung adenocarcinoma (cT3N0M0) treated with neoadjuvant afatinib and sleeve lobectomy. Because of the location of the tumor, reduced FEV1 value, and the presence of EGFR mutation, the patient was planned to be prescribed afatinib (30 mg daily) for 3 weeks as neoadjuvant therapy and underwent sleeve lobectomy to avoid pneumonectomy as much as possible. Although the patient presented with grade 3 diarrhea and dose reduction of afatinib to 20 mg daily was needed, several image findings showed a partial response of the tumor on Day 20. Oral administration of afatinib was discontinued on Day 22. A right upper sleeve lobectomy combined with partial resection of lower lobe was performed after oral administration of afatinib on Day 24. The patient's postoperative course was uneventful and she has been free of recurrence for 26 months. This strategy could reduce the risk of pneumonectomy with acceptable side effects. The treatment, clinical course and pathological findings of the patient are discussed.
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http://dx.doi.org/10.21037/jtd.2018.02.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906324PMC
March 2018

[A Case of Chromophobe Renal Cell Carcinoma Associated with Birt-Hogg-Dubé Syndrome].

Hinyokika Kiyo 2018 Mar;64(3):107-110

The Department of Urology, Kobe City Medical Center General Hospital.

A 61-year-old man with a left renal mass, which was detected by ultrasound during a routine health examination, was referred to our department. The patient had a surgical history of two pneumothorax operations, and the patient's brother also had a history of pneumothorax surgery. A case of Birt-Hogg-Dubé (BHD) syndrome was suspected based on patient history. The pathological diagnosis of the resected tumor, which used robot-assisted laparoscopic partial nephrectomy, was determined to be chromophobe renal cell carcinoma (grade 2, pT1a). BHD syndrome was confirmed by genetic testing, where a nonsense mutation of exon 9 in the FOLLICULIN (FLCN) gene was detected. The patient is currently alive 10 months after surgery.
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http://dx.doi.org/10.14989/ActaUrolJap_64_3_107DOI Listing
March 2018

Reduced Tumour Proportion Scores for Programmed Cell Death Ligand 1 in Stored Paraffin Tissue Sections.

Anticancer Res 2018 03;38(3):1401-1405

Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan.

Background/aim: We evaluated the effects of storage of formalin-fixed, paraffin-embedded (FFPE) sections on the tumour proportion score (TPS) for programmed cell death ligand 1 (PD-L1), as indicator in non-small cell lung cancer (NSCLC) tissues of treatment efficacy.

Materials And Methods: NSCLC postoperative specimens with PD-L1 TPS ≥50% were obtained and cut into five serial sections. One section was stained immediately, and four were stored at 4°C for 2, 4, 6, or 8 weeks. Slides were subjected to PD-L1 immunohistochemistry using the anti-PD-L1 clone 28-8. PD-L1 TPS were blindly evaluated by two independent pathologists.

Results: Twelve specimens (60 slides) were evaluated. After slide storage for 2, 4, 6, and 8 weeks, a TPS of <50% was obtained in five (41%), four (33%), seven (58%), and eight (67%) patients, respectively.

Conclusion: TPS values for PD-L1 were reduced by long-term slide storage of FFPE specimens. Sectioned slides should be stained for PD-L1 without delay.
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http://dx.doi.org/10.21873/anticanres.12363DOI Listing
March 2018

Correlation of Expression Levels of Copper Transporter 1 and Thymidylate Synthase with Treatment Outcomes in Patients with Advanced Non-small Cell Lung Cancer Treated with S-1/Carboplatin Doublet Chemotherapy

Asian Pac J Cancer Prev 2018 Feb 26;19(2):435-441. Epub 2018 Feb 26.

Laboratory of Pathology, Department of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma, Kobe, Hyogo, Japan. Email:

Background: Copper transporter 1 (CTR1) is a critical determinant of the uptake and cytotoxic effect of the platinum drugs carboplatin and cisplatin. Thymidylate synthase (TS) is an enzyme involved in DNA synthesis and is associated with resistance of tumor cells to 5-fluorouracil. We investigated the correlation between CTR1 and TS expression levels and treatment outcomes in patients with advanced non-small-cell lung cancer (NSCLC) treated with S-1/carboplatin doublet chemotherapy. Methods: Twenty-nine patients were enrolled in this study. Tumor expression of CTR1 and TS was measured immunohistochemically and analyzed for correlation with tumor response, progression-free survival (PFS), and overall survival (OS). Results: Tumor response was significantly better in patients with CTR1High tumors than in patients with CTR1Low tumors (64% vs. 18%, P = 0.02). Patients with TSLow tumors had a significantly longer OS (median 21.2 vs. 8.5 months, P = 0.02), but not PFS, than patients with TSHigh tumors. When CTR1 and TS co-expression was analyzed, patients with either CTR1High or TSLow tumors showed a significantly better tumor response (50% vs. 0%, P = 0.01), longer PFS (median 4.2 vs. 2.1 months, P = 0.03), and longer OS (median 21.2 vs. 8.5 months, P = 0.01) than patients with both CTR1Low and TSHigh tumors. Conclusions: Our study suggests that combined CTR1/TS expression status has the potential to be an important predictor of good treatment outcomes in patients with advanced NSCLC treated with S-1/carboplatin doublet chemotherapy.
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http://dx.doi.org/10.22034/APJCP.2018.19.2.435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980931PMC
February 2018

Programmed death-ligand 1 expression according to epidermal growth factor receptor mutation status in pretreated non-small cell lung cancer.

Oncotarget 2017 Dec 1;8(69):113807-113816. Epub 2017 Dec 1.

Division of Integrated Oncology, Institute of Biomedical Research and Innovation Hospital, Kobe, Japan.

Background: Current clinical trials have suggested poorer efficacies of anti-programmed death-1 (PD-1)/PD-ligand 1 (PD-L1) immunotherapies for non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor () mutations, implying lower PD-L1 expression in -mutant NSCLC than in -wild type.

Methods: We retrospectively analyzed correlation between PD-L1 expression and status in clinical samples of pretreated NSCLC. PD-L1 immunohistochemistry was performed using the 28-8 anti-PD-L1 antibody for tumor cell membrane staining. H-score was adopted to evaluate both percentage and intensity. We investigated H-scores ≥1, ≥5, and ≥10 as PD-L1+ cut-offs. H-score ≥10 was defined as strong PD-L1+.

Results: We investigated 96 available histologic samples in 77 pretreated patients with NSCLC. Median H-score in -mutant samples (n=65) was 3 (range, 0-150), whereas -wild-type (n=31) was 8 (range, 0-134) (p=0.0075). Using H-scores ≥1, ≥5, and ≥10 cut-offs, incidence of PD-L1+ in -mutant vs. -wild-type samples were: 85% (55/65) vs. 94% (29/31) (p=0.2159); 42% (27/65) vs. 74% (23/31) (p=0.0027); and 22% (14/65) vs. 48% (15/31) (p=0.0074), respectively. Patient-oriented (n=77) univariate analysis for strong PD-L1+ found age of sample (p=0.0226) and mutation status (p=0.0490) as significant factors. Multivariate analysis identified mutation status as the only significant factor (p=0.0121, odds ratio 2.99) for strong PD-L1+. H-scores of PD-L1 expression varied in all 11 cases receiving multiple rebiopsies, and categories of positivity migrated in 10 (91%) of 11 patients.

Conclusions: PD-L1 expression was significantly lower in -mutant NSCLC samples than in wild-type samples. Its expression could be dynamic and affected by age of sample.
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http://dx.doi.org/10.18632/oncotarget.22837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768364PMC
December 2017

[Durable remission attained by long-term brentuximab vedotin administration in a relapsed post-allogeneic bone marrow transplant Hodgkin lymphoma patient].

Rinsho Ketsueki 2017;58(12):2397-2401

Department of Hematology, Kobe City Medical Center General Hospital.

The prognosis for relapsed Hodgkin lymphoma after allogeneic hematopoietic cell transplantation (HSCT) is poor, partly because of limited treatment options. Here we present a case of a Hodgkin lymphoma patient who relapsed after allogeneic HSCT but remains in complete remission (CR) at 38 months from the start of extended brentuximab vedotin (BV) dosing. A 33-year-old man with refractory and relapsed nodular sclerosis classical Hodgkin lymphoma who underwent previous treatments, including adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) ; seven combination regimens; and autologous HSCT, prior to allogeneic HSCT achieved CR after three cycles of BV. BV was continued for 26 cycles and then discontinued because of a neurogenic bladder. The other adverse effects were mild paresthesia in the fingers, mild dysgeusia, and fatigue. The patient still remains in CR at 38 months from the start of BV. Thus, extended BV dosing may be a treatment option for relapsed and refractory Hodgkin lymphoma after allogeneic HSCT.
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http://dx.doi.org/10.11406/rinketsu.58.2397DOI Listing
June 2018