Chikao Yasunaga

Surgical manipulation of VX2 carcinoma in the rabbit liver evokes enhancement of metastasis

To search for possible untoward effects of surgical manipulation of a malignant tumor, a series of experiments was carried out using VX2 carcinoma of rabbits. Fourteen days after inoculation of VX2 carcinoma into the liver, the rabbits were separated into two groups: Group I, manual manipulation during relaparotomy; and Group II, relaparotomy alone without manual manipulation of the tumor. After these procedures, the tumor was surgically removed and histologic examinations were made. The incidence of vascular permeation of liver tumor cells into the hepatic vein was significantly higher in Group I (P less than 0.01). On the 14th day after resection of the tumor, the number of metastatic nodules in the lungs was significantly increased in Group I (P less than 0.01). Survival time of rabbits after resection of tumor was significantly shorter in Group I (P less than 0.01). These results are taken to mean that manual manipulation of a tumor may well enhance metastasis.

Peculiar histiocytic lesions with massive lanthanum deposition in dialysis patients treated with lanthanum carbonate.

Pathologic lesions caused by lanthanum carbonate (LC), a recently developed phosphate-binding agent, have not been recorded. A peculiar gastroduodenal histiocytic lesion associated with a mucosal lanthanum overload was reported. Our routine gastrointestinal biopsy series included 6 cases with heavy lanthanum burden in the gastroduodenal mucosa. In addition to routine histopathologic examinations, a series of immunohistochemical analysis and electron microscopic examinations associated with x-ray diffraction and elemental analysis were performed. Six cases, 3 of male and 3 of female individuals with ages from 59 to 69 years, were all patients of end-stage renal diseases managed under dialysis and treated with LC for >21 months. Endoscopic examinations demonstrated gastric erosions in 3, gastric polyps in 2, and duodenal ulcer in 1. In the mucosal layer, there were numerous non-Langerhans cell histiocytes, stained with CD68 but not S100 protein, engulfing a large amount of mineral-like materials. An electron microscopic and elemental analysis revealed a similar distribution of lanthanum and phosphorus in the histiocytes. Long-standing LC administration can cause massive mucosal accumulation of lanthanum in the tissue histiocytes associated with several forms of gastroduodenal lesions. A long-standing outcome is not clear at present; hence, careful follow-up studies of these patients may be needed.

Effects of a parathyroidectomy on the immune system and nutritional condition in chronic dialysis patients with secondary hyperparathyroidism

BACKGROUND Parathyroid hormone (PTH) has an adverse effect on the immune system and may cause immunologic disorders in patients with chronic renal failure. The in vivo effects of a parathyroidectomy on the immunologic parameters was examined. METHODS Thirty-four patients under dialysis therapy received a parathyroidectomy (PTx) for secondary hyperparathyroidism (HPT). They were prospectively studied regarding serum immunoglobulins, complements, CD markers, and serum soluble IL-2 receptor (sIL-2R) until 12 months after PTx. RESULTS The serum levels of IgG, IgA and IgM showed significant increase until 12 months after PTx (P<0.001, respectively). C3, C4, and CH50 also indicated significant increase at 12 months after PTx. In cellular immunity, only serum sIL-2R showed significant increase 2 weeks after PTx (P = 0.028). The hematocrit and serum albumin also improved significantly at 12 months. CONCLUSIONS PTx showed beneficial effects on humoral immunological markers. The effects are probably due to the remarkable PTH reduction and partly improved nutritional state after PTx.

Myelolipoma of the liver. A case report

We treated a 56 year‐old woman with myelolipoma originating from the liver. Hepatic imagings, including ultrasound and computed tomography (CT), demonstrated characteristic features of a fat‐enriched tumor. Since this tumor was symptomatic, hepatic resection was done, with good results. The histology revealed tissues mainly composed of fat and bone marrow elements. The diagnosis was hepatic myelolipoma.

Early development of Epstein-Barr virus-associated T-cell lymphoma after a living-related renal transplantation.

We herein report a case of Epstein-Barr virus (EBV)-associated T-cell lymphoma that developed within a month after a kidney transplantation. The recipient was a 37-year-old man who had evidence of a previous EBV infection. Cyclosporine, methylprednisolone, and azathioprine were used for immunosuppression, and acute rejection was treated with high-dose methylprednisolone. The lactate dehydrogenase level started to increase on day 24 and thereafter peaked on day 37 while also demonstrating progressive jaundice and a bleeding tendency. A transplant nephrectomy was done on day 37; however, the patient could not recover and eventually died of respiratory failure as a result of diffuse pulmonary edema. A pathological examination of the resected kidney revealed a diffuse proliferation of large atypical lymphoid cells in the parenchyma. Immunohistochemically, the tumor cells were positive for CD45 and T-cell marker, CD45RO, but negative for B-cell markers. EBV-encoded RNA was demonstrated within the neoplastic cells by in situ hybridization.

Early effects of parathyroidectomy on erythropoietin production in secondary hyperparathyroidism

BACKGROUND Secondary hyperparathyroidism (2-HPT) has an adverse effect on renal anemia and may cause a hyporesponsiveness to recombinant human erythropoietin (rHuEpo) in patients with chronic renal failure. The early effects of parathyroidectomy (PTx) on renal anemia, erythropoietin production, and nutritional state were examined. METHODS Twenty-nine patients under hemodialysis therapy received a PTx for 2-HPT. They were prospectively studied regarding hematological parameters, rHuEpo use, plasma erythropoietin levels, and nutritional condition until 12 months after PTx. RESULTS The hemoglobin level showed a significant increase from 3 months after PTx (10.2% +/- 1.5% to 11.2% +/- 1.3%; P <0.01), associated with a consistent increase of the reticulocyte count. These changes lasted until 12 months after PTx. The plasma erythropoietin level showed a gradual increase of up to about 5 times the level of the preoperative value, until 12 months after PTx (22.6 +/- 10.1 to 106.3 +/- 112.1 mU/mL; P <0.001). The weekly dose of rHuEpo administration decreased after 3 months. The serum levels of albumin and total protein also significantly and gradually improved until 12 months after PTx. CONCLUSIONS PTx caused a significant early improvement in renal anemia in patients with secondary hyperparathyroidism. This effect may be caused by an enhanced erythropoietin production and may also be partially due to the improved nutritional state after PTx.

Impaired Taste Acuity in Patients with Diabetes mellitus on Maintenance Hemodialysis

Aims: It has been reported that taste acuity for the four primary tastes, sour, sweet, salty and bitter, is impaired in hemodialysis (HD) patients. However, there have been no studies reported on taste acuity of diabetic HD patients. The present study aimed to quantify and compare the taste acuity of diabetic and non-diabetic HD patients, and further to determine if there were correlations between diminished taste acuity and certain blood serum parameters typically askew in hemodialysis patients. Methods: In a test group of 24 diabetic and 24 non-diabetic HD patients matched for age, body mass index and duration of HD, taste acuity for the four tastes was determined by asking patients to identify them at varying concentrations. Results: Statistical analyses indicate that bitter and total taste acuity were significantly impaired in diabetic HD patients. In diabetic HD patients, correlation was found between sweet, salty or total taste acuity and blood urea nitrogen or normalized protein catabolic rate. Conclusions: We conclude that taste acuity is partially impaired in diabetic HD patients, and suggest this contributes to reduced appetite, leading to malnutrition and poor prognoses.

Successful Surgical Treatment of Hepatocellular Carcinoma Invading Into Biliary Tree

A 41-year-old woman was admitted to hospital with obstructive jaundice. Computed tomography showed a large mass in the right hepatic lobe and marked dilatation of the biliary tree in the left lateral segment of the liver. Angiography showed evidence of neovascularity. Percutaneous transhepatic cholangiography revealed complete obstruction of the common bile duct just below the bifurcation. The serum level of alpha-fetoprotein on admission was 1,080,000 ng/ml. These findings suggested to us a primary hepatocellular carcinoma invading the intrahepatic bile duct. Extended right lobectomy and hepaticojejunostomy for bile drainage was carried out. The patient is doing well 3 years after surgery. Hepatocellular carcinoma (HCC) invading to the portal vein is not so rare, but invasion into the bile duct is much less common. In 1947, Mallory1 described a single case of HCC invading the gallbladder and obstructing extrahepatic bile ducts. In 1975, Lin2 termed this HCC “Icteric type hepatoma”. The incidence of such HCC in Japan was reported to be 1.9-9%2,3. Obstructive jaundice is a clinical manifestation of the terminal stage in HCC. We describe here our treatment of a woman with HCC invading the common bile duct. Right extended lobectomy and reconstruction of hepaticojejunostomy were effective.

Extracellular and cell-associated localizations of plasminogen activators and plasminogen activator inhibitor-1 in cultured endothelium

The extracellular localizations of urokinase-type plasminogen activator (uPA), tissue-type plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) were examined in cultured bovine capillary endothelial cells (BCEs) by an immunofluorescence method using BCEs treated with or without saponin and focal contact preparations. The specific immunofluorescence of cell surface uPA showed a patchy or strand-like distribution and was colocalized with vinculin strands indicating that uPA secreted from BCEs was mainly deposited at the cell surface of focal contacts. BCEs at a subconfluent density showed a higher intensity of specific immunofluorescence for uPA than when they were at a confluent density. tPA was observed over the dorsal surface of cultured BCEs and accentuated at their margins, suggesting that tPA was diffusely distributed on the luminal surface of BCEs in vivo. PAI-1 was distributed in the extracellular matrix under cultured BCEs. These findings suggest that uPA and PAI-1 are located under BCEs participating in the regulation of proteolytic activities provoked by plasminogen-PAs-plasmin system in vivo. The localization of tPA appears to be consistent with its function, which is to maintain the fluidity of the blood and to initiate thrombolysis in vivo.

Evaluation of Parathyroidectomy for Secondary and Tertiary Hyperparathyroidism by the Parathyroid Surgeons’ Society of Japan

Secondary hyperparathyroidism (SHPT) remains a serious complication in patients with chronic kidney disease, and some patients require parathyroidectomy. The Parathyroid Surgeons’ Society of Japan (PSSJ) evaluated parathyroidectomy for SHPT and tertiary hyperparathyroidism (THPT) in Japan. The annual numbers of parathyroidectomies between 2004 and 2013 were evaluated using questionnaires. Since 2010, the PSSJ has registered the patients. In total, 826 patients from 42 institutions were registered. The annual number of parathyroidectomies for SHPT and THPT in Japan increased from 2004 to 2007 and then decreased markedly after 2007, with 296 operations performed in 2013. The number of women and men was almost equal (397/427). Median (interquartile range) age of these patients was 59.0 (24–87) years, the duration of hemodialysis before parathyroidectomy was 10.83 (0.0–38.7) years, and diabetic nephropathy was 87/826 (10.5%). Of these patients 59.6% were treated with cinacalcet at undergoing parathyroidectomy. In 75.3% of patients, a total parathyroidectomy with forearm autograft was performed. In 77.7% of patients, four or more parathyroid glands were removed during the initial operation. The incidences of husky voice and wound hemorrhage were 2.9% and 1.1%, respectively.