Nodular regenerative hyperplasia: a controversial indication for orthotopic liver transplantation

Nodular regenerative hyperplasia of the liver is an uncommon cause of portal hypertension. Patients with nodular regenerative hyperplasia have signs and symptoms of portal hypertension, without evidence of hepatocellular failure or encephalopathy. We report the case of a 44-year-old woman with recurrent esophageal bleeding and refractory ascites who had a history of hemosiderosis, hepatitis C, and chronic renal allograft rejection. Our preoperative diagnosis was cirrhotic end-stage liver disease and end-stage renal disease for which the patient underwent combined hepatic and renal transplantation. Her portal hypertension symptoms resolved, and her renal function has been normal for 18 months of follow-up. Histologic examination of the liver revealed nodular regenerative hyperplasia, and a review of the literature regarding the surgical management of patients with nodular regenerative hyperplasia revealed that various shunting procedures are generally recommended. After the failure of medical management in patients with nodular regenerative hyperplasia, portosystemic shunting may be indicated before proceeding to hepatic transplantation.     

Nodular hyperplasia surrounding fibrolamellar carcinoma

We report a case of acetaminophen-induced liver necrosis in a 14-year-old girl. At autopsy, a 9 cm subcapsular nodule was present in the right lobe of the liver which showed distinct zonation: a central greyish white area of fibrolamellar carcinoma with a peripheral fleshy, tan-coloured rim ranging from 1 to 2 cm in thickness. This peripheral zone consisted of nodular, hyperplastic parenchyma resembling the changes seen in focal nodular hyperplasia, and stood out from the adjacent necrotic parenchyma. The sparing of this zone from the deleterious effects of acetaminophen provides indirect evidence of a predominantly arterial rather than portal blood supply to this region. The arterial supply was most probably derived from the tumour vasculature and may explain the parenchymal hyperplasia sometimes reported adjacent to a fibrolamellar carcinoma. Awareness of this phenomenon is essential when evaluating a needle biopsy, as sampling of this region may lead to a false negative diagnosis.     

Direct injections of calcitriol into enlarged parathyroid glands in chronic dialysis patients with severe parathyroid hyperfunction

Summary: Severe secondary hyperparathyroidism in chronic dialysis patients has been recently treated by supraphysiological concentration of calcitriol achieved through pulse therapy. However, there are many patients resistant to this therapy, who usually have larger parathyroid gland(s). to overcome this resistance, calcitriol was injected directly into the enlarged glands under ultrasonographic guidance. We injected 70–90% of the calculated gland volume of calcitriol solution (1 μg/mL) into the glands of 7 patients three times per week for 2 weeks. the parathyroid hormone (PTH) levels decreased significantly after 2 weeks of direct injections of calcitriol. Following a further 4 weeks of calcitriol pulse therapy, PTH levels remained suppressed and serum alkaline phosphatase activity and the volume of parathyroid glands also decreased. During the long-term follow up, five patients remained well controlled with calcitriol pulse therapy, while two patients needed ethanol injections to control hyperparathyroidism. Although we could not completely rule out a toxic effect of the vehicle, direct injection of calcitriol into parathyroid glands may be another treatment option for chronic dialysis patients. Our data further support the important role of resistance of parathyroid cells to calcitriol in the pathogenesis of parathyroid hyper function in uraemic patients.     

Nifedipine aggravates cyclosporine A-induced gingival hyperplasia

Gingival hyperplasia is a common side-effect of immunosuppression with cyclosporine A. Nifedipine is often used to control hypertension in kidney graft recipients. Analysis of gingival status in 106 children transplanted at our centre, and treated either with azathioprine, cyclosporine A or both, revealed significantly higher degrees of gingival overgrowth in those children receiving a combination of cyclosporine A and nifedipine compared with those children treated with cyclosporine A or nifedipine alone. Seven children undergoing gingivectomy at our centre over the past few years had received this combination. After a change in the antihypertensive regimen, avoiding long-term nifedipine medication, and improved dental care with chlorhexidine gel, we noted a reduction in the degree of gingival hyperplasia. In the majority of patients, nifedipine could be replaced by a single drug, usually hydralazine. We therefore recommend avoiding calcium channel blockers in the long-term management of hypertension in patients receiving cyclosporine.     

Rapid drop in serum testosterone after bilateral subcapsular orchiectomy.

Bilateral subcapsular orchiectomy was performed in six patients with metastatic prostatic carcinoma. In these patients the serum levels of testosterone were determined serially up to twenty-four hours. Castrate levels of testosterone were achieved in about two and one-half hours. This is the first published report of such a rapid decrease in serum testosterone. Castrate levels of serum testosterone using the luteinizing hormone releasing hormone (LH-RH) agonists are achieved in fourteen to twenty-one days. The relative cost of orchiectomy and LH-RH agonists, for thirty-six months, was $2,042.00 and $12,780.00, respectively. LH-RH agonists may be effective for only a year. Urologists are urged to continue using bilateral subcapsular orchiectomy and not use LH-RH agonists in the management of metastatic prostatic carcinoma.     

微血管密度测定在子宫内膜癌病变发展中的价值

目的　探讨血管生成活性在子宫内膜癌发展中的价值。方法　采用Ⅷ因子相关抗原为标志物 ,以免疫组化技术对正常子宫内膜、不典型增生内膜 ,子宫内膜癌组织进行微血管密度 (MVD)测定。结果　①正常组与内膜癌组比较 (P <0 .0 1) ,正常组与不典型增生组比较 (P <0 .0 5 ) ;从正常内膜、不典型增生到内膜癌组织内MVD逐渐增多 (P <0 .0 5 )。②内膜癌组织内MVD与肿瘤细胞分化程度有关 (P <0 .0 5 )。结论　临床采用MVD测定对子宫内膜增生病变发展和追随检查具有重要价值 ,同时MVD测定可作为判断子宫内膜癌预后的指标之一。     

Modulators of growth in primary culture of rat proximal tubular cells II

Summary: The present studies assessed the effects of manipulating extracellular sodium (Na) concentration and Na transport on cellular hypertrophy and hyperplasia in primary culture of rat proximal tubular cells. A concentration-dependent effect on thymidine incorporation and protein content was observed with cell culture media Na concentration of 130, 140 and 150 mmol/L. This effect was independent of osmolality (matched with mannitol) and no stimulatory effect occurred if choline was substituted for Na. Cells derived from sham-operated (Sx) animals exposed to a higher media concentration of Na (150 vs 140 mmol/L) had both stimulated thymidine incorporation to 186.8 ± 35.41% (P<0.05) and enhanced cell protein content to 134.7 ± 135% (P<0.05). This effect was more pronounced in cell cultures derived from unilaterally nephrectomized (Nx) animals, being 212.8 ± 31.5% (P<0.01) for thymidine incorporation (P<0.05 vs cells from sham-operated animals grown in high Na media) and 114.4 ± 3.2% (P<0.001) for protein content (P=0.11 vs sham-operated cells grown in similar conditions). the addition of 10^?4 mmol/L ethylisopropyl amiloride hydrochloride (EIPA) to Nx cells in a normal or high Na concentration media resulted in a decrease in cellular protein content to 82.6 ± 6.8% (P<0.05) and 85.5 ± 0.2% (P<0.0001) compared to respective controls. 10^?4 mol/L EIPA in media supplemented with insulin-like growth factor (IGF-1) blocked the proliferative response normally seen in response to this growth factor from 156.6 ± 13.7 to 27.5 ± 3.1% (P<0.0001) compared to control. However, the presence of EIPA did not abrogate the hypertrophic response elicited by IGF-1 (cell protein content 128.1 ± 13.1% of control with IGF-1 vs 124.9 ± 12.5 with IGF-1 and EIPA; P= n.s.). Addition of 10^?4 mol/L EIPA to 10% serum derived from either Sx or Nx animals blocked the growth response to the sera, limiting the cellular protein content to 76.6 ± 5.5% (P<0.0001) and 89.7 ± 4.4% (P<0.0001) and thymidine incorporation to quiescent levels of 0.2 ± 0.1% (P<0.0001) and 0.4 ± 0.1% (P<0.0001) compared to respective controls. In summary, rat renal proximal tubular cell growth is influenced by Na concentrations in the cell culture environment and inhibited in the presence of EIPA. This supports a role for altered epithelial transport in the cellular growth response to a number of stimuli.     

Association of multiple liver cell adenomas with spontaneous intrahepatic portohepatic shunt

The association of multiple liver cell adenomas containing foci of focal nodular hyperplasia with a spontaneous intrahepatic portohepatic venous shunt is reported in a 13-year-old male patient. At least eight nodules less than 10 cm in diameter were recognized and proved by means of surgical resection or surgical biopsies. These lesions were heterogeneous and hypodense on precontrast computed tomographic (CT) scans, and were slightly enhanced after injection of contrast medium. At magnetic resonance (MR) imaging, the signal intensity of these nodules varied. It was either hyperintense or hypointense on T1-weighted SE images. Sonography and angiography demonstrated a portohepatic venous shunt and hepatic arterialization was observed. These findings emphasize the hypothesis that hepatic arterialization may cause the development of liver cell adenomas. Moreover, it is suggested that liver cell adenoma and focal nodular hyperplasia have a common pathogenesis.