Successful Treatment in a Case of Massive Hepatocellular Carcinoma with Paraneoplastic Syndrome

Paraneoplastic syndromes of hepatocellular carcinoma (HCC) are not uncommon. However, the prognosis is poor and follow-up and improvement of paraneoplastic syndromes with treatment have been reported rarely. We report a successful case in an aged man of a massive HCC with paraneoplastic syndrome, treated by combined intraarterial chemotherapy and hepatic resection. Paraneoplastic syndrome (erythrocytosis and hyperlipidemia) was monitored throughout the treatment and erythropoietin (EPO) mRNA also was analyzed in the resected liver. The hemoglobin level and serum levels of EPO and total cholesterol (T-cho) decreased dramatically with treatment, along with a decrease in serum levels of α-fetoprotein and protein induced by vitamin vitamin K absence II (PIVKA-II). Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) revealed that the residual cancer expressed EPO RNA but the nontumor tissue did not. This was a rare case of paraneoplastic syndrome of HCC that was treated successfully. This case indicates that paraneoplastic syndrome reflected tumor progression and that serum levels of both EPO and T-cho might be used as tumor markers

Novel Strategy for Diagnosis of Focal Nodular Hyperplasia Using Gadolinium Ethoxybenzyl Diethylenetriaminepentaacetic Acid: Enhanced Magnetic Resonance Imaging and Magnetic Resonance Elastography

Focal nodular hyperplasia (FNH) is the second most frequent benign liver tumor, and it is a fiber-rich stiff lesion. Typically, FNH can be diagnosed by imaging without biopsy. However, liver biopsy and diagnostic resection may be required to differentiate atypical FNH from other liver tumors, such as hepatocellular adenoma (HCA). Therefore, improved noninvasive diagnostic methods are needed. We experienced 2 cases where combination of magnetic resonance elastography (MRE) and gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) helped diagnose FNH. A 36-year-old woman and 17-year-old boy with liver tumors measuring 40 mm in diameter each showed hypointense nodule centers, indicating a central scar, surrounded by hyperintense signals during the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI. To rule out HCA, we performed MRE and liver biopsy. On MRE, the mean stiffness of the mass was 11.6 kPa (mean stiffness of the background liver was 1.7 kPa) and 11.1 kPa (mean stiffness of the background liver was 2.4 kPa) in the first and second patients, respectively. Histological examination of both specimens showed CK7-positive bile-ductular proliferations, abundant fibrous tissue, and few Ki-67-positive cells. Based on these results, we diagnosed these tumors as FNH. Combination of Gd-EOB-DTPA-enhanced MRI and MRE can evaluate the character and stiffness of lesion and help in the diagnosis of FNH

Hepatic progenitor cells of biliary origin with liver repopulation capacity

Hepatocytes and cholangiocytes self-renew following liver injury. Following severe injury hepatocytes are increasingly senescent, but whether hepatic progenitor cells (HPCs) then contribute to liver regeneration is unclear. Here, we describe a mouse model where the E3 ubiquitin ligase Mdm2 is inducibly deleted in more than 98% of hepatocytes, causing apoptosis, necrosis and senescence with nearly all hepatocytes expressing p21. This results in florid HPC activation, which is necessary for survival, followed by complete, functional liver reconstitution. HPCs isolated from genetically normal mice, using cell surface markers, were highly expandable and phenotypically stable in vitro. These HPCs were transplanted into adult mouse livers where hepatocyte Mdm2 was repeatedly deleted, creating a non-competitive repopulation assay. Transplanted HPCs contributed significantly to restoration of liver parenchyma, regenerating hepatocytes and biliary epithelia, highlighting their in vivo lineage potency. HPCs are therefore a potential future alternative to hepatocyte or liver transplantation for liver disease

ブラダー・ウイリー ショウコウグン ニオケル セイチョウ ホルモン リョウホウ ト ソクワンショウ トノ カンケイ

成長ホルモン(GH)療法がプラダー・ウイリー症候群(PWS)の低身長に対して適応され5年が経過し,様々な効果が報告されてきている.しかし一方で, GH治療が側弯症を誘発または増悪させる可能性が問題になってきている.今回我々は,獨協医科大学越谷病院小児科でフォロー中のPWS患者72名(男性46名,女性26名,年齢1歳から49歳)を対象にGH治療と側弯症の関係を検討した.対象の72名中, GH療法を受けた者は41名,受けなかった者は31名であった. 72名中33名(45.8%)にコブ角10度以上の側弯症を認めた.側弯症は, GH療法を受けた41名中20名(48.8%)に, GH療法を受けなかった31名中13名(41.9%)に認められ,両群間に統計学的有意差は認められなかった. GH療法を受けた患者中,側弯症あり群となし群間でのGH療法開始後1年目の身長増加の比較では,それぞれ8.59±1.92cmと10.70±2.54cmであった.側弯なし群のGH療法開始後1年目の身長は側弯あり群より有意に増加していた.したがって,統計学上では身長の加速は側弯症を悪化させていなかった. GH開始年齢と側弯症発症との関係では,側弯症なし群でGH療法開始年齢が有意に低かった(p=0.029). GH療法を受けている群で,側弯症を認めた20名のコブ角の経過は,変動なし10名,増悪6名,増悪軽快1名,軽快3名であった. PWS患者においてGH療法は身長増加をもたらすが側弯症増悪因子になっていないと考えられた.Growth hormone (GH) therapy for Prader-Willi syndrome (PWS) has started worldwide and various favorable effects have been reported. But the possibility of progression of scoliosis is being new problems for GH treatment. In this study we analyzed 72 patients who are followed at our hospital (46 males and 26 females, aged from 1 year old to 49 years old, 41 patients with GH use and 31 without GH). We studied 1. The overall frequency of scoliosis in PWS, 2. The frequency of scoliosis with and without GH therapy, 3. The two factors (i.e. height velocity of the first year of GH therapy and the starting age of GH) which may be related to the progression of scoliosis, and 4. The prognosis of the scoliosis. The results are ; 1. Out of 72 patients, 33 patients (45.8%) showed scoliosis more than 10 degree of Cobb angle. 2. Out of 41 patients with GH therapy 20 patients (48.8 %) had scoliosis and out of 31 patients without GH therapy 13 patients (41.9 %) showed scoliosis. No statistical difference was detected between two groups. 3. Height velocities of the first year of treatment were 8.59±1.92 cm and 10.70±2.54 cm with and without scoliosis, respectively (p<0.001). GH therapy was started earlier in patients without scoliosis than with scoliosis (p<0.0001). 4. Out of 20 patients with scoliosis and GH use, the degree of scoliosis progressed in six patients, improved in three, and fluctuated in one during the GH treatment. Our results show that there is a high frequency of scoliosis in PWS with and without GH treatment, Increased height velocity by GH does not develop scoliosis, and early start of GH is not an exacerbating factor of scoliosis. Many patients showed progression of scoliosis with age irrespective of the use of GH and at least some patients improved their scoliosis in degree by GH

A Case of Pancreatic Schwannoma Diagnosed Preoperatively by Endoscopic Ultrasonography-Guided Fine Needle Aspiration and Treated with Laparoscopic Surgery

Background: Pancreatic tumors are often difficult to diagnose in atypical cases, and a pancreatic schwannoma is very rare. We present a case of pancreatic schwannoma with calcification diagnosed preoperatively by endoscopic ultrasonography (EUS)-guided fine needle aspiration (FNA) and treated with laparoscopic distal pancreatectomy. Presentation: A 72-year-old-woman was admitted to our hospital due to a 6 &#215; 4.5 cm large tumor in the pancreatic tail. Imaging modalities revealed that the tumor was hypovascular and gradually enhanced with calcification, but was without cystic lesions. EUS revealed the tumor had a clear boundary with a low echoic mass. EUS-FNA was performed and spindle-shaped cells that were immunopositive for S-100 and negative for c-kit, CD34, and desmin were detected, resulting in a diagnosis of schwannoma. Laparoscopic distal pancreatectomy with splenectomy was safely performed without recurrence for a year. Conclusions: Schwannoma is very rare; however, characteristics of the tumor, such as calcification, can help the diagnosis and, if possible, EUS-FNA should be performed for an appropriate treatment decision

Clinical trials using mesenchymal stem cells in liver diseases and inflammatory bowel diseases

Abstract Mesenchymal stem cell (MSC) therapies have been used in clinical trials in various fields. These cells are easily expanded, show low immunogenicity, can be acquired from medical waste, and have multiple functions, suggesting their potential applications in a variety of diseases, including liver disease and inflammatory bowel disease. MSCs help prepare the microenvironment, in response to inflammatory cytokines, by producing immunoregulatory factors that modulate the progression of inflammation by affecting dendritic cells, B cells, T cells, and macrophages. MSCs also produce a large amount of cytokines, chemokines, and growth factors, including exosomes that stimulate angiogenesis, prevent apoptosis, block oxidation reactions, promote remodeling of the extracellular matrix, and induce differentiation of tissue stem cells. According to ClinicalTrials.gov, more than 680 clinical trials using MSCs are registered for cell therapy of many fields including liver diseases (more than 40 trials) and inflammatory bowel diseases (more than 20 trials). In this report, we introduce background and clinical studies of MSCs in liver disease and inflammatory bowel diseases