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Biomedical subjects

Susumu Satomi

Publications and source records attributed to Susumu Satomi.

At least 19 recordsLinked to original sources
PubMed2007

Investigation of major genetic polymorphisms in the Renin-Angiotensin-aldosterone system in subjects with young-onset hypertension selected by a targeted-screening system at university.

Although polymorphisms in renin-angiotensin-aldosterone (RAA) system genes for angiotensinogen (AGT M235T), angiotensin-converting enzyme (ACE I/D), angiotensin II type 1 receptor (AT1 A/C1166), and aldosterone synthase (CYP11B2-344T/C) have been major targets for genetic investigation in association with essential hypertension (EH), the influence of these genetic factors is still to be determined. Because patients with young-onset EH are thought to possess a stronger genetic background than EH patients who show elevated BP relatively late in life, the targeted screening of hypertensive students in Tohoku University was completed for the selection of subjects for genetic investigation. Out of 16,434 students (12,794 males and 3,670 females) younger than 30, 22 students showed a high blood pressure (BP) (systolic and diastolic BP of 140 and/or 90 mmHg or greater, respectively, on two occasions and more than 135 and/or 85 mmHg, respectively, at a third measurement during casual BP measurements at the Tohoku University Health Center. These 22 students were asked to measure their BP at home (HBP). Six of the students had a systolic HBP of more than 135 mmHg and/or a diastolic HBP of more than 85 mmHg, and these students subsequently received medical examinations at Tohoku University Hospital and were diagnosed with EH. Genotyping for the four major genetic polymorphisms mentioned above was performed on the six students with EH and on 12 of the remaining 16 students whose HBP was within the normal range (white coat hypertension: WCH). Neither the EH nor the WCH students showed a different distribution of genotypes and allelic frequencies, compared to those found in the general Japanese population. Hence, the present study suggests that none of the major genetic polymorphisms in the RAA system strongly influence the onset of EH.

Adolescent↗
PubMed2006

The model for end-stage liver disease score is useful for predicting economic outcomes in adult cases of living donor liver transplantation.

BACKGROUND: The model for end-stage liver disease (MELD) is useful for assessing the recipients of liver transplants, namely, deceased-donor transplantation. The application of MELD for living donor liver transplantation (LDLT) is under investigation. Thus, the aim of this study was to analyze the impact of the MELD score in LDLT in Japan. METHODS: Seventeen adult cases of LDLT during 2001 to 2005 were enrolled. Indications for LDLT were primary biliary cirrhosis, seven; liver cirrhosis, two; hepatocellular carcinoma (HCC), three; metabolic liver disease, one; primary sclerosing cholangitis, two; Caroli's disease, one; and biliary atresia, one. Total medical charges during the operative periods were retrospectively evaluated. The united network of organ sharing (UNOS) modified was obtained using preoperative clinical data. RESULTS: The average medical expense of the 17 cases was approximately 97,901 US dollar. The UNOS-modified MELD score was 22.1. A statistically significant positive correlation was found between the MELD score and medical expense (P = 0.0086, rho = 0.657), and between the MELD score and the length of stay in the intensive care unit (ICU) (P = 0.0396, rho = 0.515). The cause of the liver disease leading to transplantation was not related to MELD score, medical expense, or length of ICU stay. CONCLUSIONS: Although not originally designed for the application to LDLT, the MELD score is useful for predicting medical expenses in LDLT. Similar to those of deceased-donor liver transplantation, the disadvantage of high medical expenses associated with a high MELD score allow consideration of an earlier elective operation in suitable cases.

Adult↗
PubMed2006

Lithium effectively complements vasopressin V2 receptor antagonist in the treatment of hyponatraemia of SIADH rats.

BACKGROUND: Although, pharmacological intervention with a selective arginine vasopressin (AVP) V(2) receptor antagonist has been demonstrated to be effective for syndrome of inappropriate secretion of antidiuretic hormone (SIADH), its long-term administration has some therapeutic limitations. Lithium, a drug for bipolar disorders, has been known to cause nephrogenic diabetes insipidus by reducing kidney-specific apical water channel, aquaporin 2 (AQP2) expression in the collecting ducts. However, its pharmacological efficacy for SIADH still remains to be elucidated. METHODS: Hyponatraemia was induced in male Sprague-Dawley rats by water loading and subcutaneous infusion of 1-deamino-8-D-arginine vasopressin. For the treatment, lithium chloride (LiCl) was administered singly or in combination with OPC-31260 and/or furosemide for 7 days. Protein expression of AQP2 was examined by western blotting at the end of the observation period. RESULTS: The LiCl administration elevated serum sodium levels in a dose-dependent manner. The therapeutic effect started 3 days after the initial administration and gradually increased. Western blot analysis at the end of the treatment demonstrated dose-dependent reduction of AQP2 protein expression. Additional administration of LiCl (100 mg/kg/day, the dose demonstrated to maintain serum lithium concentration within therapeutic range) to low dose OPC-31260 maintained well the initial elevation of serum sodium level during the treatment. Western blot analysis after combination therapy demonstrated the absence of re-increase in AQP2 expression noted at the end of OPC-31260 treatment. However, further additive effect could not be obtained even when both LiCl and furosemide were added together to low dose OPC-31260. CONCLUSIONS: Although the single effect of therapeutic dose of lithium was weak, it effectively and safely compensated for the therapeutic limitations of a low dose of AVP V(2) receptor antagonist for SIADH by reducing AQP2 expression.

Animals↗
PubMed2006

Vasohibin prevents arterial neointimal formation through angiogenesis inhibition.

Vasohibin is a VEGF-inducible angiogenesis inhibitor in vascular endothelium. Here we examined the presence of vasohibin in human arterial wall, and found it in endothelium of adventitial microvessels in atherosclerotic lesion. Adventitial angiogenesis is involved in the progression of neointimal formation. Even in the presence of endogenous angiogenesis inhibitors, pathological angiogenesis persists. However, the supplementation of exogenous angiogenesis inhibitors can prevent pathological angiogenesis. We evaluated the potential role of vasohibin in neointimal formation. Adenovirus-mediated human vasohibin gene transfer in mouse liver resulted in the release of vasohibin in plasma and exhibited anti-angiogenic effects at remote sites. This gene transfer inhibited adventitial angiogenesis, macrophage infiltration, and neointimal formation after cuff placement on mouse femoral artery. Vasohibin exhibited no direct effect on migration and proliferation of smooth muscle cells. Thus, vasohibin has an activity to prevent neointimal formation by inhibiting adventitial angiogenesis.

Adult↗
PubMed2006

The elevated level of circulating matrix metalloproteinase-9 in patients with abdominal aortic aneurysms decreased to levels equal to those of healthy controls after an aortic repair.

Matrix metalloproteinase-9 (MMP-9) is abundantly expressed in abdominal aortic aneurysms (AAAs), and it is considered to play a pivotal role in aneurysmal formation. Elevated circulating concentrations of MMP-9 have been reported in patients with AAA, but the influence of an operation on circulating MMP-9 is unclear. Therefore, to clarify the influence of an operation on circulating MMP-9 levels and to determine the role of MMP-9 in the progression of AAA, we measured serum MMP-9 levels in patients before and after AAA repair. Blood samples were obtained from 53 patients with AAA; 22 patients underwent AAA operations, including 17 patients with arterial occlusive disease (AOD), and nine normal control subjects. Serum MMP-9 levels were determined by an enzyme-linked immunosorbent assay. The serum MMP-9 concentration was significantly higher in AAA patients (622.0 +/- 400.2 ng/mL) than in either AOD patients (284.3 +/- 151.4 ng/mL) or healthy controls (280.8 +/- 165.5 ng/mL) (p < 0.001). The mean serum MMP-9 levels in patients undergoing surgery for AAA (268.1 +/- 215.9 ng/mL) was significantly lower than that in AAA patients (p < 0.01). Among the 10 patients whose sera were obtained preoperatively and postoperatively, the serum MMP-9 concentration fell significantly after the patients underwent the operation (p = 0.004). No significant difference was identified in serum MMP-9 concentrations among AOD patients, controls, and postoperative patients. These studies suggest that MMP-9 plays a pivotal role in aneurysm formation, and the circulating MMP-9 level is thus considered to reflect the biological behavior of the aneurysm.

Aged↗
PubMed2006

Liver laceration associated with severe seizures after living donor liver transplantation.

Hemorrhagic complications commonly occur early after liver transplantation (LT), sometimes requiring emergent relaparotomy. However, active bleeding from the liver graft itself is a rare but life-threatening complication after living donor liver transplantation (LDLT). We report an unusual case of liver laceration with massive bleeding, associated with severe epileptic seizures as a result of tacrolimus-induced leukoencephalopathy, after LDLT. The patient was successfully rescued by conventional surgical management without a second transplantation. In conclusion, to our knowledge this is the first reported case of graft rupture due to immunosuppression-associated leukoencephalopathy after LT.

Adolescent↗
PubMed2006

Effect of portocaval shunt on residual extreme small liver after extended hepatectomy in porcine.

BACKGROUND: When residual liver volume is extremely small after extended hepatectomy, postoperative hepatic failure may ensue. The cause of the hepatic failure is likely associated with the portal hypertension after hepatectomy. We investigated the effects of portocaval shunt on portal hypertension in producing sinusoidal microcirculatory injury after extended hepatectomy in pigs. METHODS: Fourteen pigs were divided into two groups: a group without a shunt, in which extended hepatectomy was carried out (i.e., residual volume was 17% of the whole liver), and a group with a shunt, in which extended hepatectomy was carried out and a portocaval shunt was inserted. The portocaval shunt was placed by side-to-side anastomosis between the portal vein and the inferior vena cava. RESULTS: In the group without a shunt, all pigs died of hepatic failure within postoperative day 3. In the group with a shunt, all pigs were alive for more than 4 days, and 4 pigs survived longer than 7 days. Portal vein pressure after hepatectomy was 15.9 +/- 3.8 mmHg in the group without a shunt and 10.5 +/- 0.6 mmHg in the group with a shunt (P < 0.01). The portal vein flow after 83% hepatectomy in the group without a shunt increased significantly more than at laparotomy and in the group with a shunt (P < 0.01). In the group without a shunt, remarkable destruction of the sinusoidal lining and edema of the portal triad and hydropic change of hepatocytes were observed 1 hour after hepatectomy, but these findings were not observed in the group with a shunt. CONCLUSIONS: These results indicate that, after extended hepatectomy, overload of portal flow is one of the most significant risk factors of hepatic failure by sinusoidal microcirculatory injury.

Animals↗
PubMed2006

Obstructive jaundice caused by biliary stone formation around the stent after liver transplantation.

We report an unusual case of obstructive jaundice caused by a biliary stone, which developed in the stump of a Roux-en-Y hepaticojejunostomy after undergoing LT. The patient was a 13-yr-old male. At 74 days after birth, a hepaticojejunostomy (Kasai's procedure) was performed for the treatment of biliary atresia. He underwent a reduced size deceased donor LT in the left subphrenic space twice at the age of one and three years in Australia. Eleven years after his second LT, he developed liver dysfunction and jaundice with a low grade fever. Computed tomography showed a marked jejunal loop enlargement by a rugby ball-shaped stone and the bile duct in the graft was thus dilated. A surgical exploration revealed the jejunal loop to be bent sharply while its stump side was dilated by stagnated bile including a biliary stone. The stone included a stent that had been previously used for the hepaticojejunostomy. This case suggests that a retained stent used for hepaticojejunostomy had thus caused biliary stone formation because of a combination of various conditions in the jejunal loop.

Anastomosis, Surgical↗
PubMed2006

Characteristics of young-onset hypertension identified by targeted screening performed at a university health check-up.

Since the prevalence and clinical characteristics of young-onset hypertension are still to be elucidated, we performed targeted-screening at an annual university health check-up for two consecutive years. Out of 16,464 subjects in 2003 and 17,032 in 2004 that were aged less than 30 years, 22 and 26 students (all males) exhibited high blood pressure (BP), respectively, on three occasions during casual BP measurements at the Tohoku University Health Center (systolic and diastolic BP of 140 and/or 90 mmHg or greater, respectively). These students were asked to measure their BP at home, and 9 subjects in total were diagnosed as having essential hypertension (EH). The remaining students were diagnosed as having white coat hypertension (WCH). In 8 out of 9 EH students, their father and/or mother had also been treated with antihypertensive medication. Adjustment by attendance ratio for each BP measurement suggested that the incidence of EH was around 0.1% and that of hypertension (EH and WCH) was around 0.5% in university students aged less than 25 years, since most of the subjects and hypertensive students were between 18 and 24 years old. Body mass index of the EH, which was more than 25 kg/m2 (overweight), was significantly higher than that with WCH. In conclusion, the combination of repeated casual BP measurements and home BP effectively identified young-onset EH. The clinical parameters indicated that male gender, genetic background, and excessive weight were risk factors for young-onset hypertension.

Adolescent↗
PubMed2006

Usage of deoxyspergualin on steroid-resistant acute rejection in living donor liver transplantation.

Deoxyspergualin (DSG) is an immunosuppressive agent used to treat steroid-resistant acute rejection after kidney transplantation. But in the case of acute rejection after liver transplantation, DSG was reported effective in just a few cases. From July 1991 to November 2005, 96 patients underwent living donor liver transplantation (LDLTx) in our institution. Of them, 9 patients, including 4 ABO incompatible recipients, are presented. Rejection symptoms that did not respond to steroid pulse therapy (methylprednisolone, 10-20 mg/kg/day for 3 days) and were treated with DSG (3 or 5 mg/kg/day) for 4 to 14 days together with a maintenance dose of the steroid. Among them, five responded to treatment with DSG, two did not respond and the other two patients were not evaluated. Six of the nine patients are symptom free at present. Complications such as leukopenia and thrombocytopenia were successfully treated with granulocyte-colony stimulating factor or by platelet transfusion. No recipient died as a direct consequence of the complications induced by DSG. DSG proved effective and safe for some of the LDLTx recipients with steroid-resistant acute rejection but it was not effective for the treatment of accelerated humoral rejection in ABO incompatible recipients.

ABO Blood-Group System↗
PubMed2006

Risk factors and impact of beta-D glucan on invasive fungal infection for the living donor liver transplant recipients.

Invasive fungal infection is a fatal complication in liver transplantation and it is very difficult to diagnose at the early stage. The aim of this study was to review our experience with invasive fungal infections in living donor liver transplantation (LDLT) and to analyze the risk factors and the impact of beta-D glucan. From 1991 to 2005, 96 LDLTs were performed in our institution and we measured the serum level of beta-D glucan in order to clarify the diagnosis. Invasive fungal infection was diagnosed based on clinical symptoms, culture, radiological evidence and beta-D glucan. Active fungal infection was treated with fluconazole, amphotericin B, flucytosine and micafungin. Risk factors both pre- and post- LDLT were analyzed. Candida albicans was the most frequently isolated species (70%). The risk factors identified by univariate analysis include the following four conditions: acute blood purification (plasma exchange with or without continuous hemodiafiltration), hepatic vein complications, renal failure and respiratory failure. By logistic regression analysis, hepatic vein complications and respiratory failure were identified as independent risk factors. The risk factors for invasive fungal infection of LDLT in Japan have not been well analyzed and this report will provide valuable information for the prevention of the fungal infection.

Adolescent↗
PubMed2006

Heterogeneous expression of DNA-dependent protein kinase in esophageal cancer and normal epithelium.

Esophageal cancer tissues and adjacent normal mucosae in 13 patients with primary esophageal cancer were examined for quantitative differences in DNA-dependent protein kinase (DNA-PK) activity and for expressions of Ku70, Ku80 and DNA-PKcs proteins by Western blotting and immunohistochemistry. The tumor tissues showed higher DNA-PK activity than the normal mucosae. Protein levels of Ku70, Ku80 and DNA-PKcs correlated with DNA-PK activities in the tumor tissues. Immunohistochemical analysis revealed that Ku70, Ku80 and DNA-PKcs located predominantly in the nuclei in both the tumor tissues and normal mucosae. In the normal epithelium, Ku70, Ku80 and DNA-PKcs were expressed only in the nuclei of the basal cell layers and not in those of the lumenal cell layers. In the tumor tissues, the expressions of DNA-PK proteins showed intratumoral heterogeneity. The different portions in the same tumor showed different expression levels of DNA-PK proteins, and even each tumor cell showed different expression levels. These results suggest that cell differentiation and tumor progression affect cellular DNA-PK protein levels and its activity. Furthermore, the intratumoral heterogeneity of DNA-PK protein expression in esophageal cancer cells/ tissues also suggests the difficulty in prediction of radio- or chemo-sensitivity of the tumor through estimation of DNA-PK activity/protein levels in tumor specimens.

Cells, Cultured↗
PubMed2005

Transient body fluid accumulation and enhanced NKCC2 expression in gerbils with brain infarction.

BACKGROUND: Enhanced expression of a kidney-specific sodium co-transporter (NKCC2: Na-K-2Cl co-transporter) in the thick ascending limb of Henle has been identified in rat models of congestive heart failure and liver cirrhosis, suggesting that high NKCC2 expression underlies edema formation. An increased abundance of NKCC2, however, has also been noted in rats with the syndrome of inappropriate secretion of antidiuretic hormone; hyponatremia without edema. In the present study, we examined NKCC2 expression in non-edematous disease, such as a brain infarction, and investigated the physiological and/or pathological characterization of NKCC2 expression. METHODS: We initially examined NKCC2 expression in an animal model of brain infarction. Mongolian gerbils (around 60 g body weight) underwent bilateral clamping of the common carotid arteries for 5 min for the induction of brain infarction. NKCC2 and apical water channel (AQP2) protein levels in the collecting duct were examined by Western blotting in kidney tissues 2, 7, and 14 days after the brain infarction. Gerbils with brain infarction were then fed either a normal low-sodium diet (0.3 g/kg/day) or a high-sodium diet (3.0 g/kg/day), and body weight, urine volume and urinary osmolality were examined daily. Blood parameters were measured on day 14 after the brain infarction. RESULTS: Histochemical examination of the brain confirmed the presence of brain infarction, as manifested by altered cresyl violet staining in the hippocampus. Protein levels of NKCC2 were significantly increased in gerbils with brain infarction on days 2 and 7 after brain infarction, whereas AQP2 protein signals remained unaltered. However, the increased NKCC2 intensity disappeared on day 14. Body weight gain was slightly, but significantly greater in gerbils with brain infarction than in sham-operated gerbils up to 7 days after the brain infarction. The high-sodium diet resulted in significant urinary concentration and enhanced weight gain in infarcted gerbils. CONCLUSION: We noted increased NKCC2 abundance in non-edematous disease, which enhanced body fluid accumulation, likely via the sodium loading-dependent concentration of the urine. These results suggest that the physiological process of edema formation is based on specific NKCC2 expression. The transient duration of these findings in the present animal model suggests two different characteristics of specific NKCC2 expression, an immediate, transient appearance as a common response in serious conditions and more chronic expression that leads to edema formation.

Animals↗
PubMed2005

Excessive portal flow causes graft failure in extremely small-for-size liver transplantation in pigs.

AIM: To evaluate the effects of a portocaval shunt on the decrease of excessive portal flow for the prevention of sinusoidal microcirculatory injury in extremely small-for-size liver transplantation in pigs. METHODS: The right lateral lobe of pigs, i.e. the 25% of the liver, was transplanted orthotopically. The pigs were divided into two groups: graft without portocaval shunt (n = 11) and graft with portocaval shunt (n = 11). Survival rate, portal flow, hepatic arterial flow, and histological findings were investigated. RESULTS: In the group without portocaval shunt, all pigs except one died of liver dysfunction within 24 h after transplantation. In the group with portocaval shunt, eight pigs survived for more than 4 d. The portal flow volumes before and after transplantation in the group without portocaval shunt were 118.2+/-26.9 mL/min/100 g liver tissue and 270.5+/-72.9 mL/min/100 g liver tissue, respectively. On the other hand, in the group with portocaval shunt, those volumes were 124.2+/-27.8 mL/min/100 g liver tissue and 42.7+/-32.3 mL/min/100 g liver tissue, respectively (P<0.01). As for histological findings in the group without portocaval shunt, destruction of the sinusoidal lining and bleeding in the peri-portal areas were observed after reperfusion, but these findings were not recognized in the group with portocaval shunt. CONCLUSION: These results suggest that excessive portal flow is attributed to post transplant liver dysfunction after extreme small-for-size liver transplantation caused by sinusoidal microcirculatory injury.

Animals↗
PubMed2005

Two functional coding single nucleotide polymorphisms in STK15 (Aurora-A) coordinately increase esophageal cancer risk.

STK15/Aurora-A is a serine/threonine kinase essential for chromosome segregation and cytokinesis, and is considered to be a cancer susceptibility gene in mice and humans. Two coding single nucleotide polymorphisms in Aurora-A, 91T>A [phenylalanine/isoleucine (F/I)] and 169G>A [valine/isoleucine (V/I)], create four haplotypes, 91T-169G, 91A-169G, 91T-169A, and 91A-169A. We evaluated the association between these coding single nucleotide polymorphisms and esophageal cancer risk by genotyping 197 esophageal cancer cases and 146 controls. Haplotype 91A-169A (I31/I57) was observed to be statistically more frequent in cancer cases (odds ratio, 3.1452; 95% confidence interval, 1.0258-9.6435). Functional differences among the four isoforms were then analyzed to reveal the source of the cancer risk. Kinase activity levels of I31/I57 and F31/I57 were reduced to 15% and 40% compared with I31/V57 in vivo and in vitro. We considered the differences between the kinase activities and divided individuals into four categories of Aurora-A haplotype combination. Category I had 57.5% or less kinase activity compared with the most common category, category III, and had a significantly higher estimated cancer risk (odds ratio, 5.5328; 95% confidence interval, 1.8149-16.8671). Abnormal nuclear morphology, a characteristic of genomic instability, was observed to be 30 to 40 times more frequent in human immortalized fibroblast cells overexpressing I31/I57 or F31/I57 compared with the others. Furthermore, significantly higher levels of chromosomal instability were observed in cancers in category I (homozygote 91T-169A) than those in category III (homozygous 91A-169G). These results indicate that the less kinase active Aurora-A haplotype combinations might induce genomic instability and increase esophageal cancer risk either in a recessive or a dominant manner.

Aurora Kinase A↗
PubMed2005

Successful use of anti-CD20 monoclonal antibody (rituximab) for ABO-incompatible living-related liver transplantation.

BACKGROUND: Humoral rejection after ABO-incompatible liver transplantation often causes graft loss and a life-threatening situation. We used rituximab, which can eliminate B cells highly selectively, as an additional therapy for ABO-incompatible living-related liver transplantation. CASES: Patient 1 was a 1-year-old girl with biliary atresia. Her blood type was O, and the donor's was A. She underwent two plasma exchanges before liver transplantation and had triple immunosuppressants (mycophenolate mofetil, tacrolimus, and methylprednisolone). She was diagnosed with humoral rejection by needle biopsy on postoperative day 6. Rituximab was used for 3 days at 375, 187, and 187 mg/m(2) and successfully reduced the antibody titer, transaminase, and CD19(+) cells count in peripheral blood lymphocytes. The patient has not had any severe rejection, infection, or serious complications 2 years posttransplantation. Patient 2 was a 42-year-old woman with primary biliary cirrhosis. The blood type was O, and the donor's was B. She received three plasma exchanges, triple immunosuppressants, splenectomy, intraarterial anticoagulant therapy, and rituximab (375 mg/m(2) immediately after transplantation). The titer and CD19(+) cells count remained persistently low throughout the recovery course. She did not develop humoral rejection 1 year after transplantation. CONCLUSIONS: Rituximab efficiently reduces anti-ABO antibody titer by selectively eliminating B cells and is safe and effective against humoral rejection after ABO-incompatible liver transplantation.

ABO Blood-Group System↗
PubMed2005

Hepatic resection of giant metastatic tumor from clear cell carcinoma of the ovary.

All cancer patients, particularly those treated for colorectal cancer, should be monitored for the presence of liver metastases, but liver metastases from ovarian clear cell carcinoma are quite rare. We report a patient subjected to extended left hepatectomy due to a giant metastasis 5 years after surgical treatment for an ovarian neoplasm that was histopathologically diagnosed as clear cell carcinoma. A 58-year-old woman had undergone hysterectomy and bilateral salpingo-oophorectomy due to ovarian cancer (stage Ic). Four years and 8 months after the operation, a computed tomography (CT) scan demonstrated a giant tumor in the left lobe of the liver. The tumor compressed the inferior vena cava (IVC), but it was not clear whether it invaded the vessel. She received chemotherapy for 4 months; however, the tumor did not decrease in size. She was subsequently referred to our institution and was submitted to operation after it was confirmed that there were no distant metastases. After being subjected to an extended left hepatectomy and cholecystectomy, the patient recovered from the surgery without any complications. She has been carefully followed for 17 months and has presented no evidence of recurrence.

Adenocarcinoma, Clear Cell↗