Publications by authors named "Akira Shimizu"

609 Publications

Erythema nodosum-like eruption in coronavirus disease 2019: A case report and literature review of Asian countries.

J Dermatol 2021 Jul 21. Epub 2021 Jul 21.

Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.

In the worldwide coronavirus disease 2019 (COVID-19) outbreak, skin manifestations were seen in COVID-19 patients. We report a case in which a COVID-19 patient developed cutaneous lesions that were diagnosed as erythema nodosum-like lesions, which were associated with COVID-19. Nasopharyngeal swab polymerase chain reaction (PCR) confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Histopathologically, extensive inflammation was seen from the epidermis to the fat tissue. An organized thrombus and disrupted inner elastic lamina were seen in an intradermal vessel. These findings suggest septal panniculitis with cutaneous polyarteritis nodosa. The results of PCR using the specimen of skin lesion was negative. The patient took non-steroidal anti-inflammatory drugs and the skin lesion improved in 3 weeks. To characterize the skin eruption, we reviewed previous reports on COVID-19 (confirmed by the detection of SARS-CoV-2 infection) from Asian countries. The type of eruption and timing of its appearance in this case seemed rare. Differences in skin manifestations between Western and Asian countries were noted.
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http://dx.doi.org/10.1111/1346-8138.16071DOI Listing
July 2021

A case of IgA vasculitis with necrotizing arteritis in a 13-year-old girl.

CEN Case Rep 2021 Jun 30. Epub 2021 Jun 30.

Department of Pediatrics, Nippon Medical School, Tokyo, Japan.

IgA vasculitis (IgAV) is the most frequent form of vasculitis in childhood which classically presents with purpura of the lower extremities, joint pain or swelling and abdominal pain. Though it is a self-limiting disease, and its prognosis is generally good, glomerulonephritis is one of the most important complications. IgAV is classified as a small vessel vasculitis, and though glomerulonephritis develops in IgAV, necrotizing arteritis is rarely seen. Here, we present a case of a 13-year-old girl with IgAV, glomerulonephritis, and necrotizing arteritis in the small renal arteries. There have been only a few reports of adult cases of IgAV with necrotizing arteritis in the kidneys, but there have been no pediatric cases. Some previous reports showed a high mortality rate and implied the possibility of overlap with other vasculitides. In the current report, a rare case of IgAV is described which exhibited necrotizing arteritis rather than overlap with another vasculitis, with a relatively typical clinical course for IgAV and laboratory tests.
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http://dx.doi.org/10.1007/s13730-021-00617-7DOI Listing
June 2021

Changes in carnitine levels through induction chemotherapy in head and neck cancer patients as a potential cause of therapy-related malaise.

BMC Cancer 2021 Jun 28;21(1):742. Epub 2021 Jun 28.

Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University, 6-7-1 Nishishinjyuku, Shinjyuku-ku, Tokyo, Japan.

Background: Carnitine is related to malaise, and cisplatin is associated with decreased carnitine. The purpose of this study was to elucidate the effects of one course of induction chemotherapy (IC) for head and neck cancer on blood carnitine levels, focusing on free carnitine (FC).

Methods: This single-center prospective study investigated 20 patients diagnosed with primary head and neck cancer who underwent IC with cisplatin, docetaxel, and 5-fluorouracil. FC, acylcarnitine (AC), and total carnitine (TC) levels were measured before starting therapy and on Days 7 and 21 after starting IC. In addition, malaise was evaluated before and after therapy using a visual analog scale (VAS).

Results: All subjects were men and the most common primary cancer site was the hypopharynx (9 patients). FC levels before starting therapy and on Days 7 and 21 were 47.7 ± 2.2 μM/mL, 56.7 ± 2.2 μM/mL, and 41.1 ± 1.9 μM/mL, respectively. Compared with the baseline before starting therapy, FC had significantly decreased on Day 21 (p = 0.007). AC levels before starting therapy and on Days 7 and 21 were 12.5 ± 1.2 μM/mL, 13.6 ± 1.4 μM/mL, and 10.7 ± 0.7 μM/mL, respectively. TC levels before starting therapy and on Days 7 and 21 were 60.2 ± 2.5 μM/mL, 70.2 ± 3.3 μM/mL, and 51.7 ± 2.3 μM/mL, respectively. No significant differences in AC, TC or VAS were seen before the start of therapy and on Day 21.

Conclusions: After IC, a latent decrease in FC occurred without any absolute deficiency or subjective malaise.
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http://dx.doi.org/10.1186/s12885-021-08471-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237460PMC
June 2021

The severity of glomerular endothelial cell injury is associated with infiltrating macrophage heterogeneity in endocapillary proliferative glomerulonephritis.

Sci Rep 2021 Jun 25;11(1):13339. Epub 2021 Jun 25.

Department of Nephrology, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan.

Endocapillary proliferation occurs in various types of glomerulonephritis (GN), with varying prognoses. We examined 42 renal biopsy samples representing endocapillary proliferative lesions from post-streptococcal acute GN (PSAGN), Henoch-Schönlein purpura nephritis (HSPN), and lupus nephritis (LN). In PSAGN, the glomerular capillary network was maintained, although severe lesions displayed dots or short, curved lines, indicating CD34-positive capillaries and suggesting capillary obstruction. Conversely, patients with LN and HSPN displayed obstruction of CD34-positive capillaries with dissociation from the glomerular basement membrane even in mild lesions. According to computer-assisted morphologic analysis, the cell density did not differ between the diseases. However, in PSAGN, the number of capillary loops was significantly increased, with a larger glomerular capillary luminal area than in the other groups. In addition, the number and frequency of CD163-positive cells (M2 macrophages) tended to be higher in PSAGN, while there were no significant differences in the number of CD68-positive (total) macrophages. These results indicate that in PSAGN, endothelial cell damage is less severe, and angiogenesis may be promoted. The severity of endothelial cell injury in each disease may be associated with differences in infiltrating inflammatory cell phenotypes.
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http://dx.doi.org/10.1038/s41598-021-92655-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233400PMC
June 2021

Tonsillectomy Combined With Steroid Pulse Therapy Prevents the Progression of Chronic Kidney Disease in Patients With Immunoglobulin A (IgA) Nephropathy in a Single Japanese Institution.

Cureus 2021 Jun 18;13(6):e15736. Epub 2021 Jun 18.

Nephrology, Graduate School of Medicine, Nippon Medical School, Tokyo, JPN.

Background Despite the abundant experience of tonsillectomy with steroid pulse therapy (TSP) for patients with immunoglobulin A (IgA) nephropathy, the therapeutic efficacy of TSP on renal prognosis remains controversial. The purpose of this study was to evaluate the efficacy of whether TSP effectively prevents chronic kidney disease (CKD) progression. Methods This was a single-center, retrospective observational study. A total of 149 patients were enrolled in the current study who were confirmed with IgA nephropathy by renal biopsy between February 2011 and August 2019. The impact of TSP on CKD progression was compared with conservative treatment during a follow-up period of 3 years. Results In total, 110 patients received TSP and 39 patients received conservative treatment. There were no differences between the two groups in the initial CKD stages: 65.1% of patients had CKD G1-2, 32.2% had CKD G3, and 2.7% had CKD G4-5. The initial urine protein was 0.7 g/gCr, which was not different between the two groups. Kaplan-Meier analysis showed that patients with TSP had a significantly better renal prognosis than those in the conservative treatment group after one and a half years (p = 0.007). Multivariable analysis revealed that TSP had a significant impact on the prevention of CKD progression, with an adjusted odds ratio of 0.07 (95% confidence interval, 0.01-0.87; p=0.039). However, we could not confirm the predictive value of the Oxford Classification on TSP efficacy. Additionally, the initial urinary protein level was a risk factor for CKD progression. Conclusions TSP was associated with a lower risk of CKD progression. In this regard, our study supports that TSP may be a reasonable treatment option for patients with IgA nephropathy. In the featured study, it needs to be elucidated which histopathological classifications benefit from TSP treatment.
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http://dx.doi.org/10.7759/cureus.15736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212700PMC
June 2021

Life history and nesting ecology of a Japanese tube-nesting spider wasp Dipogon sperconsus (Hymenoptera: Pompilidae).

Sci Rep 2021 Jun 17;11(1):12810. Epub 2021 Jun 17.

Department of Biosphere Sciences, School of Human Sciences, Kobe College, Nishinomiya, Hyogo, 662-8505, Japan.

To clarify the life history of the Japanese spider wasp Dipogon sperconsus, bionomical studies using bamboo-cane trap nests were carried out in Japan. Based on weekly and consecutive daily surveys of trap nests and rearing of broods from collected nests, we evaluated the production of cells and eggs per day, prey spiders, and seasonal patterns of nesting activities. We found a relatively short critical period of switching from the summer generation into the overwintering generation. We also found that the voltinism is affected by the timing of egg production of the second generation in relation to this critical period. The developmental period for each generation and sex, voltinism and cell production per day were determined based on data for a large number of individuals for the first time.
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http://dx.doi.org/10.1038/s41598-021-92124-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211671PMC
June 2021

Hyaline arteriolosclerosis associated paratubular basement membrane insudative lesions in distal renal tubules.

Clin Exp Nephrol 2021 Jun 7. Epub 2021 Jun 7.

Department of Analytic Human Pathology, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan.

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http://dx.doi.org/10.1007/s10157-021-02076-xDOI Listing
June 2021

Clinical and histological features in pediatric and adolescent/young adult patients with renal disease: a cross-sectional analysis of the Japan Renal Biopsy Registry (J-RBR).

Clin Exp Nephrol 2021 May 28. Epub 2021 May 28.

Depatment of Pediatric Nephrology, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.

Background: Only a few studies have investigated epidemiological and clinicopathological information regarding pediatric and adolescent and young adult (AYA) patients with renal disease. The purpose of this study was to clarify the differences and relationship of clinicopathological findings between pediatric and AYA patients using the Japan Renal Biopsy Registry (J-RBR).

Methods: This cross-sectional study analyzed data from patients registered in the J-RBR between 2007 and 2017. Clinicopathological findings at diagnosis were analyzed for 3,463 pediatric (age < 15 years) and 6,532 AYA (age 15-30 years) patients.

Results: Although chronic nephritic syndrome was the most common clinical diagnosis at age > 5 years, nephrotic syndrome was the most frequent diagnosis at age < 4 years. The most common pathological diagnosis as classified by pathogenesis in pediatric patients was primary glomerular disease (except IgA nephropathy), whereas IgA nephropathy was increased in AYA patients. Mesangial proliferative glomerulonephritis was the most common pathological diagnosis as classified by histopathology in both pediatric and AYA patients. Minor glomerular abnormalities were the most frequent histopathologic diagnoses of nephrotic syndrome in childhood, but their frequency decreased with age.

Conclusion: To the best of our knowledge, this is the first report of clinicopathological features of pediatric and AYA patients in a large nationwide registry of renal biopsy. There were differences of clinical, pathological and histopathologic findings between pediatric and AYA patients.
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http://dx.doi.org/10.1007/s10157-021-02077-wDOI Listing
May 2021

Nationwide Survey of Post-Transplant Glomerular Diseases, Based on the Japan Renal Biopsy Registry (J-RBR).

Ann Transplant 2021 May 14;26:e931873. Epub 2021 May 14.

Department of Nephrology, Kanazawa Medical University School of Medicine, Uchinada, Ishikawa, Japan.

BACKGROUND Nationwide data on allograft kidney biopsies have been limited in number, in contrast to the large amount of accumulated data on native kidney biopsies. In this context, we have surveyed transplant biopsy data based on the nationwide database, the Japan Renal Biopsy Registry (J-RBR). MATERIAL AND METHODS A total of 2430 transplant biopsy cases were registered in the web-based J-RBR from January 2007 to January 2018. We categorized the entries regarding both the purpose of the biopsy and pathological diagnosis, and confirmed transplant glomerular diseases based on the clinical and pathological diagnosis. RESULTS Of the 2430 total transplant biopsy cases, 637 cases, including 9 cases of baseline biopsy, 216 cases of protocol biopsy, and 232 cases of episode biopsy, had a pathological diagnosis, including glomerular diseases, rejection, calcineurin inhibitor nephropathy, and interstitial fibrosis and tubular atrophy. Of these, 127 cases presented with glomerular disease, including 8 cases of baseline biopsy, 23 of protocol biopsy, 59 of episode biopsy, and 37 of unknown purpose). A total of 127 biopsies with glomerular disease revealed a high prevalence of immunoglobulin A nephropathy (n=38, 29.9%), followed by mesangial proliferative glomerulonephritis (n=29, 22.8%) and focal segmental glomerulosclerosis (n=8, 6.3%) when focused on protocol and episode biopsies. CONCLUSIONS The nationwide transplant biopsy database demonstrated the pathological characteristics of 637 cases, including 127 cases of post-transplant glomerular disease. The protocol and episode biopsies included high prevalence rates of IgAN, followed by FSGS.
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http://dx.doi.org/10.12659/AOT.931873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130503PMC
May 2021

Safety of Silk-elastin Sponges in Patients with Chronic Skin Ulcers: A Phase I/II, Single-center, Open-label, Single-arm Clinical Trial.

Plast Reconstr Surg Glob Open 2021 Apr 28;9(4):e3556. Epub 2021 Apr 28.

Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Background: Although traditional wound dressings such as collagen scaffolds promote granulation tissue formation, the efficacy of these dressings in chronic wounds is limited because of high susceptibility to bacterial growth. Biomaterials that can be applied to chronic wounds should have an anti-bacterial function. We previously reported that administering a silk-elastin solution that forms moisturizing hydrogels to wound surfaces of diabetic mice reduced bacterial growth and promoted granulation tissue formation compared with control or carboxymethyl cellulose hydrogels. We hypothesized that silk-elastin promotes wound healing in human chronic wounds by suppressing bacterial growth.

Methods: An open-label, clinical case series was conducted with a prospective, single-arm design at Kyoto University Hospital in Kyoto, Japan. In this study, 6 patients with chronic skin ulcers of any origin (2 < ulcer area (cm) < 25) on their lower extremities were included; patients with critical ischemia were excluded. Silk-elastin sponges were applied and covered with a polyurethane film without changing the dressing for 14 days. Inflammation triggered treatment discontinuation due to fear of infection. The primary study endpoint was adverse events, including inflammation and infection.

Results: Poor hydrogel formation, possibly due to continuous exudation, was observed. No serious adverse events were noted. Two patients discontinued treatment on day 6 and day 7, respectively, due to inflammation, but they were not infected. The other 4 patients completed the 14-day silk-elastin sponge treatment without infection.

Conclusion: Silk-elastin sponge is safe for chronic skin ulcers, and its ability to promote wound healing should be determined by confirmatory clinical trials.
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http://dx.doi.org/10.1097/GOX.0000000000003556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081464PMC
April 2021

Lymphoepithelial cyst mimicking pancreatic cancer: a case report and literature review.

Surg Case Rep 2021 Apr 29;7(1):108. Epub 2021 Apr 29.

Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.

Background: Pancreatic lymphoepithelial cyst (LEC) is a rare nonmalignant cyst consisting of a benign collection of keratinizing squamous epithelial cells with lymphoid tissue. Diagnosing LEC preoperatively is considered difficult because of its non-specific clinical features; therefore, LEC is generally treated the same as a malignant tumor.

Case Presentation: Our case was a 65-year-old man who underwent pancreatoduodenectomy 3 years previously for carcinoma arising from the ampulla of Vater. A pancreatic mass in the remnant pancreatic tail was detected through follow-up abdominal contrast-enhanced computed tomography (CT). This revealed two adjacent ring-enhanced masses that had been in tight contact with the left diaphragm and were enlarged. The tumors had high signal intensity in diffusion-weighted images of magnetic resonance imaging, and fluorodeoxyglucose-positron emission tomography (FDG-PET) showed abnormal uptake (standardized uptake value maximum: 17.4). Therefore, we conducted a partial resection of the remnant pancreas with concomitant resection of the left diaphragm. Microscopically, one of the tumors revealed rare fragments of apparently benign squamous epithelium on a background of keratinous debris, cyst contents, and scattered lymphocytes, and the adjacent mass revealed infiltrated neutrophils. The histopathological diagnosis was an LEC with chronic abscess. The patient recovered uneventfully and was discharged on postoperative day 10.

Conclusions: We reported a rare case of LEC with chronic abscess that was positively visualized on FDG-PET. When a pancreatic malignancy cannot be excluded, surgical resection is considered inevitable.
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http://dx.doi.org/10.1186/s40792-021-01191-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085173PMC
April 2021

Cryofibrinogen-associated glomerulonephritis accompanied by advanced gastric cancer.

CEN Case Rep 2021 Apr 27. Epub 2021 Apr 27.

The Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan.

We had a 72-year-old man with advanced gastric cancer, poorly differentiated adenocarcinoma, receiving chemotherapy with S-1 (tegafur, gimeracil, and oteracil potassium) plus oxaliplatin. Ascites developed despite remission of gastric cancer and metastasis. Given no malignant cells in ascites, leg edema, renal impairment, hypoalbuminemia, and massive proteinuria, we diagnosed as nephrotic syndrome with microscopic hematuria. Renal biopsy showed membranoproliferative glomerulonephritis with no deposition of immunoglobulins and complements. Of note, electronic microscopy found organized deposits with microtubular structures in the glomerular capillary lumens and subendothelial spaces. The liquid chromatography-tandem mass spectrometry method detected fibrinogen alpha chain, beta chain, gamma chain, and fibronectin, and we eventually diagnosed cryofibrinogen-associated glomerulonephritis. Cryofibrinogen was not detected in plasma. He was expired at 5 months following renal biopsy due to the progression of refractory nephrotic syndrome. In addition to the detailed assessment of specifically organized deposits, the analysis using liquid chromatography-tandem mass spectrometry method is useful to diagnose cryofibrinogen-associated glomerulonephritis. We should consider cryofibrinogen-associated glomerulonephritis as a differential diagnosis when the patients with malignancy showed abnormal urinalysis and renal impairment, though it is a rare disease.
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http://dx.doi.org/10.1007/s13730-021-00602-0DOI Listing
April 2021

The survival benefit of surgery for perihilar cholangiocarcinoma in octogenarians: Shinshu University experience.

J Surg Oncol 2021 Jul 12;124(1):67-78. Epub 2021 Apr 12.

Division of Gastroenterological, Department of Surgery, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Shinshu University School of Medicine, Matsumoto, Japan.

Background And Objectives: In today's aging society, surgery is increasingly performed for older patients with perihilar cholangiocarcinoma (PHCC). This study aimed to examine survival and oncological outcomes in octogenarians with PHCC who underwent surgery.

Methods: We retrospectively examined 480 consecutive PHCC patients treated for PHCC between 1991 and 2020. Two hundred forty-seven underwent resection. Patient and clinical characteristics, including postoperative complications, overall survival (OS), and disease-free survival (DFS) were analyzed.

Results: The proportion of octogenarians with PHCC undergoing surgery increased from 5.2% in 1991-2000 to 13.4% in 2016-2020. R0 resection and postoperative complication rates were comparable between octogenarians and younger patients. Five-year OS (30.0% vs. 31.7%) and DFS (20.0% vs. 29.5%) did not significantly differ. One-year OS was significantly better in octogenarians who underwent resection than those who did not (95.0% vs. 17.6%; p < .001). Two octogenarians who developed Clavien-Dindo grade III complications had undergone right hemihepatectomy (RH). Posthepatectomy liver failure and biliary leakage (Grade B) were also observed in octogenarians who underwent RH.

Conclusion: In well-selected octogenarians with PHCC, surgery offers short- and long-term outcomes comparable with those of their younger counterparts. RH may be considered in octogenarians on an individual basis.
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http://dx.doi.org/10.1002/jso.26488DOI Listing
July 2021

Monoclonal and polyclonal immunoglobulin G deposits on tubular basement membranes of native and pretransplant kidneys: A retrospective study.

Pathol Int 2021 Jun 30;71(6):406-414. Epub 2021 Mar 30.

Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.

Monoclonal tubular basement membrane immune deposits (TBMID) are associated with progression of interstitial injury in renal allograft. However, the significance of monoclonal and polyclonal TBMID in the native kidney remains unclear. We retrospectively analyzed 1894 native kidney biopsies and 1724 zero-hour biopsies performed between 2008 and 2018 in our institution. The rate of immunoglobulin G (IgG) TBMID was found to be 8.4% among native kidney biopsies and 0.4% among zero-hour biopsies. Polyclonal TBMID is common in IgG4-related tubulointerstitial nephritis (37.5%), diabetic nephropathy (31.3%) and lupus nephritis (25.5%). Monoclonal IgG TBMID was identified in seven cases, including three zero-hour biopsies. The combination of IgG1κ was observed in two cases, IgG1λ in three, and IgG2κ in two. Electron microscopy revealed powdery electron-dense deposits in all cases. Monoclonal gammopathy of undetermined significance was diagnosed in one case. Although one patient with focal segmental glomerulosclerosis developed renal failure, all others exhibited stable renal function. Monoclonal IgG TBMID in the native kidney is not associated with renal prognosis. However, this may be an interesting immunopathological finding that would help clarify the pathogenesis of TBM immune deposits. Further study for both monoclonal and polyclonal TBMID is required in the future.
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http://dx.doi.org/10.1111/pin.13092DOI Listing
June 2021

Assessment of wood provisioning in protected subtropical forest areas for sustainable management beyond the zone.

J Environ Manage 2021 Jun 19;287:112337. Epub 2021 Mar 19.

Kyushu Research Centre, Forestry and Forest Products Research Institute, 4-11-16 Kurokami, Chuo-ku, Kumamoto, Kumamoto, 860-0862, Japan. Electronic address:

Among the ecosystem services that humans use from forest ecosystems, wood resources are one of the basic services that are essential to human life. Since the use of wood resources disturbs ecosystems, overharvesting destroys local ecosystems, resulting in a decline in ecosystem services. Therefore, there is a need to balance the use of wood resources by people with the health of the ecosystem. In this study, we evaluated wood provisioning in newly established national parks in Okinawa Main Island, Japan, for future sustainable management. We clarified the spatial distribution between the forest stand volume obtained from LiDAR data, the logging sites before the national park designation, and national park zoning. We found that the buffer zone contains some forests with high stand volume that continue from the core area. There had not been much logging in recent years, but most logging sites were located in the buffer zone and within 200m from roads. Forests with aged stands and high stand volume are important as buffers to prevent isolation of the core area. Therefore, park managers need to consider not only the legal regulations for each zone but also the continuity with the surrounding natural environment to prevent isolation of the core area. Understanding the spatial distribution of wood resources and park zoning relationships at a fine-scale resolution will be useful for managing buffer zones where there is competition between conservation and resource use.
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http://dx.doi.org/10.1016/j.jenvman.2021.112337DOI Listing
June 2021

Pericardial metastasis of parotid mucoepidermoid carcinoma diagnosed by pericardial biopsy.

Auris Nasus Larynx 2021 Mar 6. Epub 2021 Mar 6.

Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University, 6-7-1, Shinjuku-ku, Tokyo, Nishishinjuku 160-0023, Japan.

A 30-year-old man presented with swelling in the lower left ear. Close examination led to a diagnosis of parotid gland cancer, T4N0M0 Stage IVA, so total resection of the left parotid gland and left neck dissection were performed. Pathological examination led to a diagnosis of high-grade malignant-type mucoepidermoid, and chemoradiotherapy was performed as postoperative treatment. Fourteen days after completion of chemoradiotherapy, the patient was admitted to the hospital with headache and lack of appetite. Echocardiography showed a pericardial effusion and complete collapse of the right ventricle; cardiac tamponade was diagnosed, and pericardiocentesis was performed. The pericardial effusion was bloody, and a metastatic lesion was suspected, but cytological examination showed class IIIa. On day 33 of the illness, respiratory distress and hypotension were observed. A clot was seen covering the lower wall of the heart, and dilatation of the lower wall was significantly impaired. Pericardiotomy was performed on day 36. Pathological examination diagnosed cardiac metastasis of mucoepidermoid carcinoma of the parotid gland. Although only 4 cases of parotid cancer have been reported as primary lesions of metastatic heart tumors, this case represents the world's first description of isolated parenchymal metastasis of mucoepidermoid carcinoma of the parotid gland diagnosed by pericardial biopsy.
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http://dx.doi.org/10.1016/j.anl.2021.02.016DOI Listing
March 2021

Glomerular Classification Using Convolutional Neural Networks Based on Defined Annotation Criteria and Concordance Evaluation Among Clinicians.

Kidney Int Rep 2021 Mar 13;6(3):716-726. Epub 2020 Dec 13.

Department of Biomedical Informatics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Introduction: Diagnosing renal pathologies is important for performing treatments. However, classifying every glomerulus is difficult for clinicians; thus, a support system, such as a computer, is required. This paper describes the automatic classification of glomerular images using a convolutional neural network (CNN).

Method: To generate appropriate labeled data, annotation criteria including 12 features (e.g., "fibrous crescent") were defined. The concordance among 5 clinicians was evaluated for 100 images using the kappa (κ) coefficient for each feature. Using the annotation criteria, 1 clinician annotated 10,102 images. We trained the CNNs to classify the features with an average κ ≥0.4 and evaluated their performance using the receiver operating characteristic-area under the curve (ROC-AUC). An error analysis was conducted and the gradient-weighted class activation mapping (Grad-CAM) was also applied; it expresses the CNN's focusing point with a heat map when the CNN classifies the glomerular image for a feature.

Results: The average κ coefficient of the features ranged from 0.28 to 0.50. The ROC-AUC of the CNNs for test data varied from 0.65 to 0.98. Among the features, "capillary collapse" and "fibrous crescent" had high ROC-AUC values of 0.98 and 0.91, respectively. The error analysis and the Grad-CAM visually showed that the CNN could not distinguish between 2 different features that had similar visual structures or that occurred simultaneously.

Conclusion: The differences in the texture or frequency of the co-occurrence between the different features affected the CNN performance; thus, to improve the classification accuracy, methods such as segmentation are required.
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http://dx.doi.org/10.1016/j.ekir.2020.11.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938073PMC
March 2021

A case of hypertensive disorders of pregnancy that developed at 9 weeks of gestation.

CEN Case Rep 2021 Mar 15. Epub 2021 Mar 15.

Department of Internal Medicine 1, Hamamatsu University School of Medicine, 1-20-1 Handayama Higashi-ku Hamamatsu, Hamamatsu, 431-3192, Japan.

Preeclampsia and superimposed preeclampsia usually develop after 20 weeks of gestation. We report a case of a 35-year-old Japanese woman who developed hypertensive disorders of pregnancy (HDP) before 20 weeks of gestation. She presented with hypertension and proteinuria at 9 and 11 weeks of gestation, respectively, and developed nephrotic syndrome at 17 weeks of gestation. She did not have definite hypertension or urinary abnormalities before pregnancy. The patient was serologically positive for the antinuclear antibody. However, the complement levels were normal and anti-phospholipid antibody was not detected. A renal biopsy performed at 18 weeks of gestation showed diffuse endotheliosis and tip lesions of secondary focal segmental glomerulosclerosis but no hypertensive changes of the arterioles. Although electron microscopic examination showed electron-dense deposits in the subendothelial lesions, they were considered nonspecific plasma exudation by mass spectrometry. An abortion was performed at 20 weeks gestation because the patient's congestive symptoms due to nephrotic syndrome had worsened and marked fetal growth restriction was observed. After delivery, the patient's symptoms resolved immediately without any additional treatment; however, continuous antihypertensive medication was required. Finally, the patient was diagnosed with HDP based on the renal biopsy findings and her clinical course after delivery. Compared to previous reports, this case describes the earliest onset of HDP. Thus, HDP should be considered as a differential diagnosis in pregnant women with hypertension or proteinuria presenting with symptoms before 20 weeks of gestation.
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http://dx.doi.org/10.1007/s13730-021-00592-zDOI Listing
March 2021

Low-Vacuum Scanning Electron Microscopy to Assess Histopathological Resolution of Class V Lupus Nephritis: A Case Report.

Case Rep Nephrol Dial 2021 Jan-Apr;11(1):36-47. Epub 2021 Feb 3.

Department of Nephrology, Hiroshima University Hospital, Hiroshima, Japan.

Lupus nephritis (LN) is most frequently associated with poor outcomes in patients with systemic lupus erythematosus (SLE). LN manifests as histopathological changes in the kidney caused by immune complex formation and deposition. In particular, immunoglobulin G (IgG) deposits are frequently observed by immunofluorescence staining, which helps to establish the diagnosis of LN. In this case report, we describe a 57-year-old woman with SLE who had been undergoing treatment on an outpatient basis for 11 years. Her first and second renal biopsies revealed class V LN with a coarsely granular pattern of IgG deposition in the peripheral capillary walls. However, her third renal biopsy showed no IgG deposition, which indicated histopathological resolution of her class V LN. We used low-vacuum scanning electron microscopy (LV-SEM) to examine the three-dimensional structural alterations in her glomerular basement membranes. In this report, we describe findings that indicated resorption of epithelial deposits, that is, resolution of LN. The results of repeated kidney biopsies confirmed by LV-SEM suggested the possibility of a state unrelated to LN.
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http://dx.doi.org/10.1159/000509470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923700PMC
February 2021

Renal Biopsy-induced Hematoma and Infection in a Patient with Asymptomatic May-Hegglin Anomaly.

J Nippon Med Sch 2021 Mar 9. Epub 2021 Mar 9.

Department of Pediatrics, Graduate School of Medicine, Nippon Medical School.

The May-Hegglin anomaly is characterized by inherited thrombocytopenia, giant platelets, and leukocyte cytoplasmic inclusion bodies. The Fechtner, Sebastian, and Epstein syndromes are associated with mutations of the MYH9-coding nonmuscle myosin heavy chain ⅡA, similar to the May-Hegglin anomaly, and are together classified as MYH9 disorders. MYH9 disorders may include symptoms of Alport syndrome, including nephritis and auditory and ocular disorders. A 6-year-old boy was diagnosed with an MYH9 disorder after incidental discovery of hematuria and proteinuria. Focal segmental glomerulosclerosis was detected on renal biopsy. However, despite no prior bleeding diatheses, he developed a large post-biopsy hematoma despite a preprocedural platelet transfusion calculated to increase the platelet count from 54,000/μL to >150,000/μL. Idiopathic thrombocytopenic purpura is a major cause of pediatric thrombocytopenia following acute infection or vaccination, and patients with MYH9 disorders may be misdiagnosed with idiopathic thrombocytopenic purpura and inappropriately treated with corticosteroids. Careful differential diagnosis is important in thrombocytopenic patients with hematuria and proteinuria for the early detection of thrombocytopenia. Patients with MYH9 disorders require close follow-up and treatment with angiotensin Ⅱ receptor blockers to prevent the onset of progressive nephritis, which may necessitate hemodialysis or renal transplantation. The need for renal biopsy in patients with MYH9 disorders should be carefully considered because there could be adverse outcomes even after platelet transfusion.
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http://dx.doi.org/10.1272/jnms.JNMS.2021_88-609DOI Listing
March 2021

Usefulness and limitation of indocyanine green fluorescence for detection of peritoneal recurrence after hepatectomy for hepatocellular carcinoma: a case report.

BMC Surg 2021 Mar 2;21(1):107. Epub 2021 Mar 2.

Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.

Background: Peritoneal recurrence of hepatocellular carcinoma (HCC) after hepatectomy occurs rarely, accounting for less than 1% of all recurrences. Reported causes of such dissemination include a history of rupture of the original HCC, needle biopsy or puncture treatment, and surgical procedures. There is no consensus on the optimal treatment strategy for peritoneal dissemination. There have been few reports on assisting resection of peritoneal dissemination by using indocyanine green (ICG) fluorescence.

Case Presentation: A 57-year-old man underwent posterior sectionectomy for HCC. Six months later, computed tomography revealed multiple nodules suspected of indicating peritoneal dissemination. Various preoperative imaging studies demonstrated only four nodules, the doubling time of the tumors being rapid at 22 days. The nodules were therefore resected. ICG (0.5 mg/kg) was injected intravenously 2 days before the procedure, enabling identification of the nodules by their brightness in the operative field under near-infrared lighting. A total of eight lesions were detected during the procedure and resected, some of which had not been identified by preoperative imaging studies. We diagnosed peritoneal dissemination of HCC based on the pathological findings and their similarity to those of the original HCC. We concluded that the recurrences were likely attributable to exposure of the tumor to the serosa at the time of the original operation.

Conclusions: Although ICG fluorescence is useful for identifying peritoneal dissemination of HCC, attention should be paid to the difficulty in detecting deep lesions and occurrence of false positives.
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http://dx.doi.org/10.1186/s12893-021-01111-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923305PMC
March 2021

Treatment outcomes of transoral robotic and non-robotic surgeries to treat oropharyngeal, hypopharyngeal, and supraglottic squamous cell carcinoma: A multi-center retrospective observational study in Japan.

Auris Nasus Larynx 2021 Jun 22;48(3):502-510. Epub 2021 Feb 22.

Department of Otorhinolaryngology-Head and Neck Surgery, Yokohama City University, School of Medicine, Yokohama, Japan.

Objectives: The aim of this multicenter retrospective cohort study was to compare efficacy and subsequent postoperative treatment between transoral robotic surgery (TORS) and any non-robotic transoral surgery in Japanese patients with early oropharyngeal squamous cell carcinoma (OPSCC), hypopharyngeal SCC (HPSCC), or supraglottic SCC (SGSCC).

Materials And Methods: Clinical information and surgical outcomes were compared between patients with early-stage OPSCC, HPSCC, and SGSCC who underwent TORS (TORS cohort) and those who underwent non-robotic transoral surgery, including transoral videolaryngoscopic surgery (TOVS), endoscopic laryngopharyngeal surgery (ELPS), and transoral laser microsurgery (TLM) (non-robotic cohort). The data of the Head and Neck Cancer Registry of Japan (registry cohort) were used to validate the comparison. The main outcomes were the presence of positive margins under pathology and the requirement for postoperative therapy, including radiotherapy or chemoradiotherapy.

Results: Sixty-eight patients in the TORS cohort, 236 patients in the non-robotic cohort, and 1,228 patients in the registry cohort were eligible for this study. Patients in the TORS cohort were more likely to have oropharyngeal tumor disease and T2/3 disease than those in the other cohorts (P<0.001 and P=0.052, respectively). The TORS cohort had significantly fewer patients with positive surgical margins than the non-robotic cohort (P=0.018), as well as fewer patients who underwent postoperative treatment, although the difference was not significant (P=0.069). In the subgroup analysis of patients with OPSCC, a total of 57 patients in the TORS cohort, 73 in the non-robotic cohort, and 171 in the registry cohort were eligible for the present study. Patients with OPSCC who underwent TORS were more likely to have lateral wall lesions than those in the other cohorts (P=0.003). The TORS cohort also had significantly fewer patients with positive surgical margins than the non-robotic cohort (P=0.026), and no patients in the TORS cohort underwent any postoperative treatment for OPSCC, although the difference was not significant (P=0.177).

Conclusions: Our results suggest that TORS leads to fewer positive surgical margins than non-robotic transoral surgeries. The clinical significance of TORS may be further validated through the results of all-case surveillance for patients who underwent TORS running in Japan in the future.
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http://dx.doi.org/10.1016/j.anl.2021.01.024DOI Listing
June 2021

Podometrics in Japanese Living Donor Kidneys: Associations with Nephron Number, Age, and Hypertension.

J Am Soc Nephrol 2021 May 24;32(5):1187-1199. Epub 2021 Feb 24.

Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia

Background: Podocyte depletion, low nephron number, aging, and hypertension are associated with glomerulosclerosis and CKD. However, the relationship between podometrics and nephron number has not previously been examined.

Methods: To investigate podometrics and nephron number in healthy Japanese individuals, a population characterized by a relatively low nephron number, we immunostained single paraffin sections from 30 Japanese living-kidney donors (median age, 57 years) with podocyte-specific markers and analyzed images obtained with confocal microscopy. We used model-based stereology to estimate podometrics, and a combined enhanced-computed tomography/biopsy-specimen stereology method to estimate nephron number.

Results: The median number of nonsclerotic nephrons per kidney was 659,000 (interquartile range [IQR], 564,000-825,000). The median podocyte number and podocyte density were 518 (IQR, 428-601) per tuft and 219 (IQR, 180-253) per 10 m, respectively; these values are similar to those previously reported for other races. Total podocyte number per kidney (obtained by multiplying the individual number of nonsclerotic glomeruli by podocyte number per glomerulus) was 376 million (IQR, 259-449 million) and ranged 7.4-fold between donors. On average, these healthy kidneys lost 5.63 million podocytes per kidney per year, with most of this loss associated with glomerular loss resulting from global glomerulosclerosis, rather than podocyte loss from healthy glomeruli. Hypertension was associated with lower podocyte density and larger podocyte volume, independent of age.

Conclusions: Estimation of the number of nephrons, podocytes, and other podometric parameters in individual kidneys provides new insights into the relationships between these parameters, age, and hypertension in the kidney. This approach might be of considerable value in evaluating the kidney in health and disease.
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http://dx.doi.org/10.1681/ASN.2020101486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259686PMC
May 2021

A cross-sectional study in patients with IgA nephropathy of correlations between clinical data and pathological findings at the time of renal biopsy: a Japanese prospective cohort study.

Clin Exp Nephrol 2021 May 17;25(5):509-521. Epub 2021 Feb 17.

Division of Kidney and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.

Background: The correlations between clinical data and pathological findings at the time of renal biopsy were investigated in IgA nephropathy patients.

Methods: 771 patients diagnosed with IgA nephropathy by renal biopsy were enrolled. The correlations between clinical variables including eGFR, daily proteinuria, mean arterial pressure (MAP), serum uric acid (UA) values, and pathological parameters were examined. These patients were further divided into three groups: children (< 19 years old), young adults (19-60 years), and elderly patients (> 60 years).

Results: Daily proteinuria was moderately correlated with all pathological parameters (Rs = 0.23-0.49). The mesangial score, the percentage of glomeruli that contained endocapillary hypercellularity, cellular/fibrocellular crescents or tuft necrosis, and segmental glomerulosclerosis (GS) affected daily proteinuria most on multiple linear regression analysis (MLRA). eGFR, MAP, and serum UA levels were mainly correlated with the degree of GS and interstitial lesions. In children, the degree of cellular/fibrocellular crescents or tuft necrosis was correlated with not only daily proteinuria, but also decreased eGFR (Rs = 0.51, - 0.24). Endocapillary hypercellularity was the only independent variable related to daily proteinuria on MLRA.

Conclusion: In all age cohorts of IgA nephropathy patients, daily proteinuria was correlated with all histological parameters, including both acute and chronic glomerular lesions, and the mesangial score. Independent variables for daily proteinuria were the meangial score, acute histological lesions, and segmental GS on MLRA, whereas the remaining independent variable in the pediatric group was endocapillary hypercellurality. The clinical pathological correlation at the time of biopsy varied depending on the age group.
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http://dx.doi.org/10.1007/s10157-021-02022-xDOI Listing
May 2021

Applicability of sentinel lymph node oriented treatment strategy for gallbladder cancer.

PLoS One 2021 12;16(2):e0247079. Epub 2021 Feb 12.

Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan.

Background: Utility of the sentinel lymph node (SLN) biopsy in some malignancies has been reported, however, research on that of gallbladder cancer (GBC) is rare. The aim of this study is to investigate whether the concept of SLN is applicable to T2/3 GBC.

Methods: A total of 80 patients who underwent resection for gallbladder cancer were enrolled in this study. Patients with GBC were stratified into two groups based on the location of tumor, peritoneal-side (T2p or 3p) and hepatic-side (T2h or 3h) groups. We evaluated the relationship between cystic duct node (CDN) and downstream lymph node (LN) status. CDN was defined as a SLN in this study.

Results: Thirty-eight patients were classified into T2, including T2p (n = 18) and T2h (n = 20), and 42 patients into T3, including T3p (n = 22) andT3h (n = 20). The incidence of LN metastasis was significantly higher in hepatic-side than peritoneal-side in both T2 and T3 (P = 0.036 and 0.009, respectively). In T2, 14 T2p had negative CDN and downstream LN, however, three T2h had negative CDN and positive downstream LNs (defined as a skipped LN metastasis) (P = 0.043). In T3, patients with skipped LN metastasis were significantly higher in T3h (n = 11) than those in T3p (n = 2) (P<0.001). There was no recurrence of the local lymph node. Disease-free survival in the T2p and T3p were significantly better than those in the T2h and T3h (P = 0.005 and 0.025, respectively).

Conclusion: The concept of SLN can be applicable to T2p GBC, where the downstream LNs dissection can be omitted.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247079PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880492PMC
February 2021

The peritumoral hypointense rim around hepatocellular carcinoma on T2*-weighted magnetic resonance imaging: radiologic-pathologic correlation.

World J Surg Oncol 2021 Feb 6;19(1):41. Epub 2021 Feb 6.

Department of Radiology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.

Background: A peritumoral hypointense rim (PTHR) is sometimes observed around hepatocellular carcinoma (HCC) on T2*-weighted images (T2*WIs). We aimed to investigate the association between the PTHR and histopathologic findings on T2*WIs.

Methods: We assessed the presence of a PTHR on T2*WIs in 39 pathologically proven HCCs from April 2012 to December 2013. Prussian blue staining was performed, and iron deposition was evaluated by semiquantitative and quantitative methods. Optical density was used in the quantitative methods. The associations between a PTHR on T2*WI and histopathologic peritumoral or background liver iron deposition were analyzed.

Results: A PTHR on T2*WI was observed in 23 of 39 (59%) HCCs. There was no significant difference in the histopathologic fibrous capsule findings (P = 0.394). In the semiquantitative methods, both peritumoral and background liver iron deposition grade were significantly higher in HCCs with a PTHR compared with HCCs without a PTHR (P < 0.001). The mean optical density in HCCs with a PTHR was significantly higher compared with HCCs without a PTHR, in the quantitative peritumoral (42,244.1 ± 20,854.9 vs. 18,739.1 ± 12,258.7, respectively; P < 0.001) and background liver iron deposition analyses (35,554.7 ± 19,854.8 vs. 17,292.4 ± 11,605.8, respectively; P < 0.001). Tumor size (P = 0.005), etiology (P = 0.001), and degree of fibrosis (P = 0.042) were significantly associated with the presence of a PTHR.

Conclusions: A PTHR in HCCs on T2*WIs was strongly associated with peritumoral iron deposition in the iron-deposited background liver but not with the fibrous capsule.
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http://dx.doi.org/10.1186/s12957-021-02152-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868021PMC
February 2021

Effects of Selective Peroxisome Proliferator Activated Receptor Agonists on Corneal Epithelial Wound Healing.

Pharmaceuticals (Basel) 2021 Jan 25;14(2). Epub 2021 Jan 25.

Department of Ophthalmology, Nippon Medical School, Bunkyo-ku, Tokyo 113-8603, Japan.

The effects of each subtype-selective peroxisome proliferator activated receptor (PPAR) agonist (α, β/δ, γ) on corneal epithelial wound healing were investigated using a rat corneal alkali burn model. After the alkali burn, each PPAR agonist or vehicle ophthalmic solution was instilled topically onto the rat's cornea. Corneal epithelial healing processes were evaluated by fluorescein staining. Pathological analyses and real-time reverse transcription polymerase chain reactions were performed to evaluate Ki67 (proliferative maker) expression and inflammatory findings. The area of the corneal epithelial defect at 12 h and 24 h after the alkali burn was significantly smaller in each PPAR group than in the vehicle group. Ki67 mRNA expression was increased in the PPARβ/δ group, whereas mRNA expressions of inflammatory cytokines were suppressed in all of the PPAR agonist groups. Nuclear factor kappa B (NF-κB) was the most suppressed in the PPARγ group. The accelerated corneal epithelial healing effects of each PPAR ligand were thought to be related to the promotion of proliferative capacity and inhibition of inflammation.
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http://dx.doi.org/10.3390/ph14020088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911852PMC
January 2021

A focal extramedullary hematopoiesis of the spleen in a patient with essential thrombocythemia presenting with a complicated postoperative course: a case report.

Surg Case Rep 2021 Jan 26;7(1):33. Epub 2021 Jan 26.

Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.

Background: Extramedullary hematopoiesis is a compensatory response occurring secondary to inadequate bone marrow function and is occasionally observed in essential thrombocythemia (ET). This disease usually presents as multifocal masses in the paravertebral or intra-abdominal region; however, formation of a focal mass in the liver or spleen is rare. In addition, ET is characterized by increased platelet count and shows a tendency toward thrombosis and, occasionally, bleeding. Serious bleeding is common in ET patients, caused by the decrease in or abnormalities of von Willebrand factor (vWF) as a consequence of the precipitous rise in platelets. Therefore, strict management of platelet count using medication is crucial in patients with ET who require invasive procedures, especially splenectomy.

Case Presentation: A 68-year-old man with ET was found to have an enlargement of a focal splenic tumor. Imaging findings revealed that the tumor was likely a hemangioma or hamartoma; however, the possibility of malignant disease could not be completely ruled out because of short-term tumor enlargement, and we conducted a splenectomy. The surgery was uneventful, but the patient presented with severe polycythemia and vWF abnormalities postoperatively, which resulted in bleeding from the drain insertion site and wound, epistaxis, and hemorrhoidal bleeding. Three months after discharge, polycythemia still persisted and the level of vWF gradually decreased. With a decrease in vWF, the patient suffered from an increased bleeding tendency. Therefore, the patient has been referred for bone marrow transplantation and is currently awaiting a suitable donor.

Conclusions: Extramedullary hematopoiesis should be listed as a differential diagnosis of focal enlarged splenic tumors, especially in patients with myeloproliferative disorders. Additionally, in splenectomy for ET patients, careful perioperative management taking into consideration the conflicting features of a tendency toward thrombus formation and bleeding is necessary.
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http://dx.doi.org/10.1186/s40792-021-01119-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838229PMC
January 2021

The Diagnostic Utility of RAS Q61R Mutation-specific Immunohistochemistry in Epithelial-Myoepithelial Carcinoma.

Am J Surg Pathol 2021 Jul;45(7):885-894

Departments of Anatomic Pathology.

Epithelial-myoepithelial carcinoma (EMC) is a rare salivary gland cancer characterized by biphasic tubular structures composed of inner ductal and outer clear myoepithelial cells. Because of its histologic variety and overlap of histologic features with other salivary gland tumors, there are broad differential diagnoses. The HRAS Q61R mutation has been reported to be frequent in and specific to EMC. We evaluated the usefulness of RAS Q61R mutant-specific immunohistochemical (IHC) staining for detecting this genetic alteration in EMC. We investigated 83 EMC cases and 66 cases of salivary gland tumors with an EMC-like component, including pleomorphic adenoma, adenoid cystic carcinoma, basal cell adenoma/adenocarcinoma, and myoepithelial carcinoma. Sanger sequencing was performed for HRAS, KRAS, and NRAS. The diffuse and membranous/cytoplasmic RAS Q61R IHC expression was observed in 65% of EMC cases, in which all cases harbored the HRAS Q61R mutation. IHC-positive cases were present only in de novo EMCs (54/76 cases, 71%) but not in EMCs ex pleomorphic adenoma. The immunoreactivity was almost always restricted to the myoepithelial cells. Conversely, all EMC cases lacking the HRAS Q61R mutation were negative on IHC. In addition, only 3% of EMC-like tumors showed the abovementioned immunopositivity. None of the cases examined carried KRAS or NRAS mutations. IHC for RAS Q61R is highly sensitive and specific for detecting the HRAS Q61R mutation in EMC. Since significant immunopositivity was almost exclusively identified in nearly two thirds of EMCs but seldom in the histologic mimics, the IHC of RAS Q61R is a useful tool for diagnosing EMC in general pathology laboratories.
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http://dx.doi.org/10.1097/PAS.0000000000001673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192334PMC
July 2021
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