A case of urothelial carcinoma,lipid cell variant

The lipid cell variant of urothelial carcinoma is a rare variant of urinary bladder cancer, comprised of lipoblast‐like cells. In this report, we describe a case of the lipid cell variant of aggressive urothelial carcinoma. A 78‐year‐old man was admitted to the hospital because of gross hematuria. On cystoscopy, an ulcerative lesion, non‐papillary architecture, was observed in the lateral wall of the bladder. Transurethral resection was performed. Histopathological findings of the bladder tumor indicated neoplastic cells forming irregular solid nests and sheets. Lipoblast‐like neoplastic cells that had eccentric nuclei and cytoplasmic vacuoles were observed, not only in the resected specimen, but also in urine samples. On mucin histochemistry, the tumor cell cytoplasm contained no neutral or acidic mucus. The lipoblast‐like cells were positive for cytokeratins (AE1/AE3, CK7) and adipophilin, known as a protein associated with neutral lipid synthesis. In general, it is difficult to prove the existence of intracytoplasmic lipid in formalin‐fixed paraffin‐embedded materials. This is the first report in which the presence of lipid in vacuoles of the lipid cell variant has been verified by immunohistochemistry.     

Multifocal and microscopic chromophobe renal cell carcinomatous lesions associated with ‘capsulomas’ without FCLN gene abnormality

Chromophobe renal cell carcinoma (RCC) accounts for approximately 5% of renal epithelial neoplasms. Multiple and/or bilateral chromophobe RCCs in an individual are generally rare but frequently occur in patients with Birt–Hogg–Dubé syndrome (BHDS) and in patients with tuberous sclerosis complex (TSC). The responsible genes in both BHDS and TSC act as tumor suppressors. Therefore, it seems that some genetic backgrounds are required for the generation and progression of multiple chromophobe RCCs. Here, we report a case of multiple and bilateral chromophobe RCCs along with several small‐sized capsular angiomyolipomas known as ‘capsulomas’ in a 39‐year‐old woman who had neither a particular medical history nor specific gene mutation. There has been no report of sporadic multiple chromophobe RCCs and ‘capsulomas’ developing in a patient without genetic features, having potential for novel genetic variation.     

Evaluation of bioartificial renal tubule device prepared with human renal proximal tubular epithelial cells cultured in serum-free medium

Bioartificial renal tubule devices (BTD) use cell therapy to improve conditions commonly observed in recipients of artificial kidneys for treatment of kidney diseases. We previously reported significant improvement of the condition of acute kidney injury (AKI) animals after treatment with BTD prepared with lifespan-extended human renal proximal tubular cells (hRPTEC). However, a major obstacle to use of BTD for patients is their biological safety, because hRPTEC are cultured in medium containing fetal calf serum. To establish the biological safety of BTD, we prepared BTD with lifespan-extended hRPTEC cultured in a newly developed serum-free medium and compared these with BTD prepared with hRPTEC cultured in serum-containing conventional medium. Lifespan-extended hRPTEC cultured in serum-free medium (hRPTEC-SFM) can proliferate similar to hRPTEC cultured in serum-containing conventional medium (hRPTEC-CM). Comparison of leakage and of reabsorption of small molecules for BTD prepared with hRPTEC-SFM (BTD-SFM) with those for our previous BTD prepared with hRPTEC-CM (BTD-CM) showed transportation in these two types of BTD was almost identical. When AKI goats were treated with BTD-SFM for 26 h, increase of survival time and reduction of cytokine expression in blood cells were almost same as for AKI goats treated with BTD-CM. Quantification of the expression of some genes of hRPTEC in BTD revealed significant changes during BTD treatment for AKI goats. In conclusion, lifespan-extended hRPTEC-SFM work as well as hRPTEC-CM, and the biological safety of BTD for patients could be elevated without loss of function by preparation from hRPTEC-SFM.     

Controlled assembly of filamentous viruses into hierarchical nano- to microstructures at liquid/liquid interfaces

Recently, viruses have been regarded as useful molecular assemblies for materials applications rather than as disease-causing agents. The orderly assembled structures of the viruses are highly related to the resultant properties and functions of the assemblies; however, methods to control the assembly are still limited. Here, we demonstrated the assembly of filamentous viruses into hierarchical nano- to microstructures at liquid/liquid interfaces through emulsification in a controlled manner. The viruses form fibrous nanostructures of several micrometers length, which are much longer than the original virus. Subsequently, the fibers self-assemble into well-packed ordered microstructures. Furthermore, the resultant hierarchically assembled structures showed long-term stability and potential applicability through the desired functionalization.

Assembly of filamentous viruses into hierarchical nano- to microstructures in a controlled manner was demonstrated using the liquid/liquid interface.     

Quantification of Pancreatic Stiffness on Intraoperative Ultrasound Elastography and Evaluation of its Relationship With Postoperative Pancreatic Fistula

“Soft pancreas” has often been reported as a predictive factor for postoperative pancreatic fistula (POPF) after pancreatectomy. However, pancreatic stiffness is judged subjectively by surgeons, without objective criteria. In the present study, pancreatic stiffness was quantified using intraoperative ultrasound elastography, and its relevance to POPF and histopathology was investigated. Forty-one patients (pancreatoduodenectomy, 30; distal pancreatectomy, 11) who underwent intraoperative elastography during pancreatectomy were included. The elastic ratio was determined at the pancreatic resection site (just above the portal vein) and at the remnant pancreas (head or tail). Correlations between the incidence of POPF and patient characteristics, operative variables, and the elastic ratio were examined. In addition, the relationship between the elastic ratio and the percentage of the exocrine gland at the resection stump was investigated. For pancreatoduodenectomy patients, main pancreatic duct diameter < 3.2 mm and elastic ratio < 2.09 were significant risk factors for POPF. In addition, the elastic ratio, but not main pancreatic duct diameter, was significantly associated with the percentage of exocrine gland area at the pancreatic resection stump. Pancreatic stiffness can be quantified using intraoperative elastography. Elastography can be used to diagnose “soft pancreas” and may thus be useful in predicting the occurrence of POPF.Key words: Elastography, Exocrine gland, Pancreatectomy, Pancreatic stiffness, Postoperative pancreatic fistulaDespite current advances in surgical techniques, pancreatectomy is a very difficult procedure associated with the risk of multiple postoperative complications. The morbidity and mortality are reported to be 20–50% and 1–5%, respectively.¹ In particular, a postoperative pancreatic fistula (POPF) can sometimes lead to life-threatening complications, such as hemoperitoneum and sepsis. The worldwide incidence of POPF is reported to be 5–50%. Several predictive factors for POPF have been reported to date, and, of these, “soft pancreas” has often been mentioned.^2–4 However, in all of these reports, evaluation of pancreatic stiffness has depended on subjective judgment by the surgeon, without objective parameters as criteria.Elastography has recently been developed to enable real-time visualization of the relative stiffness of tissue elasticity, and its usefulness in various clinical disciplines for tumor diagnosis and differential diagnosis has been described.⁵ In gastroenterology, evaluation of liver fibrosis and diagnosis of pancreatic tumors and chronic pancreatitis using endoscopic ultrasound (EUS) have been reported,^6,7 but the use of elastography in surgery has not been reported. An objective assessment of pancreatic stiffness as a predictive risk factor for POPF can help in choosing the intraoperative surgical technique and in planning the postoperative management strategy. Therefore, in the present study, pancreatic stiffness was quantified using intraoperative ultrasound elastography, and its relevance to POPF and histopathology was investigated.     

Hemostatic plug formation in normal and von Willebrand pigs: the effect of the administration of cryoprecipitate and a monoclonal antibody to Willebrand factor

Hemostatic plug (HP) formation was investigated in the ear bleeding time incision in normal and von Willebrand pigs. HP volume was calculated by integrating the areas of serial sections. In normal pigs (n = 11), platelets immediately formed a layer on the surface of the cut channel. Platelet aggregates formed at the ends of transected vessels and gradually enlarged. Finally, all transected vessels were occluded by HP and bleeding stopped. In contrast, large HPs were formed in the incision in von Willebrand's disease (vWD) pigs (n = 4); these HPs did not cover the ends of the transected vessels, which continued to bleed, allowing the formation of large hemostatically ineffective platelet aggregates in the incision. Canals traversed these HPs, and bleeding from the open vessels may have continued through them. After infusion of cryoprecipitate into a vWD pig, the bleeding time shortened, and the morphological findings of the HPs were similar to those of normal pigs. In normal pigs (n = 3) infused with an anti- Willebrand factor monoclonal antibody, which prolonged the bleeding time, a large HP formed in the incision, similar to that observed in the vWD pig. The volume of the normal and vWD HPs increased with time. These in vivo findings suggest that Willebrand factor is involved in the localization of the HP to the damaged vessel and may also play a role in platelet-platelet interaction. A computerized morphometric technique was used for measuring the volume of the hemostatic plugs and the distance of sequential points on the perimeter of the HP from the center of selected bleeding vessels.