Review of combination of peritoneal dialysis and hemodialysis as a modality of treatment for end-stage renal disease.

Because the contribution of residual renal function (RRF) to total solute clearance is often significant in continuous ambulatory peritoneal dialysis (CAPD), loss of RRF over time can lead to inadequate dialysis if appropriate prescription management strategies are not pursued. Additionally, declines in ultrafiltration caused by increases in peritoneal permeability may limit continuation of CAPD therapy. Peritoneal dialysis and hemodialysis (PD + HD) combination therapy (complementary dialysis therapy) is an alternative method. This therapy allows the patient to maintain daily activities, as with CAPD, while undergoing once-a-week HD supplements for the insufficient removal of solutes and water. This therapy allows for the continuation of PD without shifting to total HD in PD patients who continue to have uremic symptoms even after individualization of the PD prescription. This treatment option is psychologically more acceptable to patients and may be expected to provide such accompanying beneficial effects as peritoneal resting, improvement of QOL and reduction in medical cost.

Interleukin-10 suppresses proliferation and remodeling of extracellular matrix of cultured human skin fibroblasts.

When we previously examined the participation of local expression of interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNFalpha) in wound healing of an intestinal anastomosis under septic conditions in mice, we found that IL-10 and TNFalpha expressions were markedly enhanced around the anastomosis and that wound healing was impaired in this animal model. The purpose of the present study was to investigate the combined effect of IL-10 on proliferation and remodeling of the extracellular matrix (ECM) of cultured human skin fibroblasts. Human skin fibroblasts were cultured for 48 h with IL-10 and/or TNFalpha at various concentrations, then the proliferation rates were determined using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The concentration of transforming growth factor-beta1 (TGFbeta1) in cell culture supernatants was measured by enzyme-linked immunosorbent assay, and type I collagen protein and matrix metalloproteinase-I (MMP-I) were detected by indirect immunofluorescence in cultured cells incubated for 48 h with 10 ng/ml of IL-10 and/or 10 ng/ml of TNFalpha. IL-10 itself had no effect on fibroblast proliferation, but reduced TNFalpha-induced fibroblast proliferation. The concentration of TGFbeta1 in cell culture supernatants was significantly lower in the presence of TNFalpha and IL-10 than in the presence of TNFalpha alone. Immunolabeling of fibroblasts for type I collagen protein was decreased in cells incubated with IL-10 and/or TNFalpha compared to controls. MMP-I immunolabeling was increased in cells incubated with IL-10, IL-10 and TNFalpha compared to control and cells incubated with TNFalpha. It is suggested that IL-10 is an inhibitory factor for the remodeling of the ECM during wound healing.

Is preoperative portal vein embolization effective in improving prognosis after major hepatic resection in patients with advanced-stage hepatocellular carcinoma?

BACKGROUND: The impact of the use of preoperative portal vein embolization (PVE) on long-term survival after surgery was evaluated by retrospective analysis of prognostic factors in patients with advanced-stage hepatocellular carcinoma (HCC) who had undergone hepatic resection with or without PVE. METHODS: The portal embolization group (Group P) consisted of 26 patients who had undergone major hepatectomy (more extensive than right hepatectomy) with PVE, and the nonembolized group (Group N) consisted of 43 patients who had undergone major hepatectomy without PVE. All patients were diagnosed with advanced HCC graded as Stage III or IV according to the International Union Against Cancer TNM classification system. Patient survival rates, recurrence rates, and recurrence sites after surgery in the two groups were evaluated and compared. RESULTS: The 1-year, 3-year, and 5-year cumulative disease specific survival rates in patients with TNM Stage III HCC, respectively, were 96.0%, 64.4%, and 52.7% in Group N and 92.9%, 57.1%, and 45.7% in Group P, whereas the corresponding values in patients with Stage IV HCC were 53.5%, 40.1%, and 26.8% in Group N and 63.5%, 50.8%, and 19.1% in Group P. There were no statistically significant differences in survival rates between Group P and Group N. Multivariate analysis showed that PVE was not a significant prognostic factor. The 1-year, 3-year, and 5-year cumulative recurrence rates for patients with both stages of disease combined were 44.1%, 80.2%, and 86.8% in Group N, respectively, and 39.9%, 72.2%, and 72.2% in Group P, respectively, with no statistically significant differences between the two groups. To date, 35 patients in Group N and 16 patients in Group P have had tumor recurrences in the liver remnant; of these, 27 patients in Group N and 12 patients in Group P had multiple recurrence foci in the liver remnant. No significant difference was seen between the two groups; however, 10 of 16 patients in Group P (62.5%) had remote organ metastasis in addition to recurrence in the liver remnant compared with only 6 of 35 patients in Group N (17.1%): This difference was significant statistically (P = 0.012). CONCLUSIONS: PVE during major hepatic resection neither improves nor worsens long-term prognosis but allows resection in a patient group that, otherwise, is considered as unresectable. Remote metastasis involving the lung, bone, or stomach was seen more frequently postoperatively in Group P compared with Group N, raising a possibly important issue regarding the use of this approach for the treatment of patients with hepatic malignancies, especially HCC.

Retrohepatic vena cava replacement of hepatic malignancies without using total hepatic vascular exclusion or extracorporeal bypass.

Total hepatic vascular exclusion and venovenous bypass are frequently used surgical procedures when concomitant resection of the inferior vena cava is required during surgery of liver cancer involving the retrohepatic inferior vena cava close to the hepatic veins. However, the duration of total hepatic vascular exclusion is limited due to the risk of hepatic ischemia. Three patients presented with severely compressed inferior vena cava and/or hepatic veins due to liver cancer. The surgical procedure involved initial taping of the inferior vena cava just below the hepatic veins by extrahepatic division and taping of the hepatic veins. After taping the inferior vena cava, hepatectomy with caval resection was performed by simply clamping the retrohepatic inferior vena cava, without the need for total hepatic vascular exclusion or venovenous bypass. In all patients the retrohepatic inferior vena cava were safely replaced with a prosthetic graft under stable hemodynamics. Duration of the inferior vena cava clamping was 31, 66, 75 minutes, respectively. No graft-related complications occurred, but 2 of the 3 patients showed temporal renal dysfunction associated with renal congestion postoperatively. The surgical procedure described herein is effective for the treatment of retrohepatic inferior vena cava in some patients. However, when the case is complicated by chronic nephropathy or simultaneous nephrectomy is required, venovenous bypass should be performed.

Hyperosmotic stimuli induces recruitment of aquaporin-1 to plasma membrane in cultured rat peritoneal mesothelial cells.

Aquaporin-1 (AQP-1) has been reported to play an important role in peritoneal dialysis. To determine the precise mechanism involved, we used cultured rat peritoneal mesothelial cells (RPMCs) to examine the translocation of AQP-1 to the plasma membrane induced by hyperosmotic stimuli. Cultured RPMCs obtained from male Sprague-Dawley rats were incubated at room temperature in Dulbecco modified Eagle medium/F12 (DMEM/F12) with and without glucose or mannitol as the hyperosmotic stimulus. The plasma membrane was then extracted by the Percoll gradient method. Finally, the abundance AQP-1 molecules in the membrane fraction was determined by Western blot analysis. Significant enhancement of AQP-1 abundance (p < 0.05) was observed within 2.5 minutes of the addition of 5% glucose to the medium. The increase was sustained in its abundance through 15 minutes. Abundance of AQP-1 was also increased (p < 0.05) by the addition of 5% mannitol. These results suggest that hyperosmotic stimuli could generate increased AQP-1 abundance in the plasma membrane by translocation of AQP-1 protein from recycling endosomes or early endosomes to the plasma membrane, rather than by protein synthesis via newly expressed mRNA. The latter mechanism would be expected to take more time.

Long-term survival after resection for small cell carcinoma of the esophagus.

We describe the rare case of a patient with esophageal small cell carcinoma who was completely cured. A 77-year-old man had small cell carcinoma of the esophagus with extensive lymph node metastases. Treatment comprised a subtotal esophagectomy and extended lymph node dissection. He has survived for more than 7 years with no evidence of recurrent disease. We suggest that radical operations should be considered for future patients if curative resection can be expected.

Effects of a vitamin E-modified dialysis membrane on neutrophil superoxide anion radical production.

Activation of neutrophil by the dialysis membrane and peroxidative stress plays an important role on the pathogenesis of complications in hemodialysis (HD) patients. Vitamin E is one of the potent scavengers for reactive oxygen species. Recent studies suggest that a vitamin E-modified multilayer membrane (Excebrane, CL-EE dialyzer) has an inhibitory effect on serum lipids peroxidation in HD patients. To determine the effect of CL-EE on biocompatibility in clinical use, we measured the superoxide anion radical producing ability (SOPA) of polymorphonuclear leukocytes (PMNLs), the plasma hydroxyl radical producing ability (OHPA) and superoxide anion radical scavenging activity (SSA). SOPA was measured after stimulation of PMNLs with phorbol myristate acetate using electron paramagnetic resonance (EPR) method. Plasma OHPA and SSA were also determined using the EPR method. In addition, the plasma concentrations of malondialdehyde (MDA) and oxidized low-density lipoprotein (LDL), as the parameters for lipid peroxidation, were measured. SOPA was decreased in patients who used conventional filter membrane compared with healthy controls. In the patients using the CL-EE membrane, SOPA gradually increased and reached control levels after six months. However, no significant increase was observed in patients who used a conventional filter membrane. OHPA of HD patients was significantly decreased compared with controls. In the CL-EE membrane patient group, OHPA was significantly increased at six months. SSA was significantly higher in the conventional filter membrane group than controls. In the CL-EE membrane patient group, SSA gradually decreased at six months. Plasma MDA and oxidized LDL levels were significantly higher in HD patients compared with controls. These values slowly decreased, and significant differences were found after nine months of using the CL-EE membrane. These findings suggest that activation of PMNLs and plasma OHPA and SSA in HD patients is attenuated by antioxidant effects of the CL-EE.

Changes in arterial and portal perfusion in embolized and nonembolized hepatic lobes after portal vein embolization evaluated by helical computed tomography.

We evaluated the changes in hepatic arterial and portal perfusion in nonembolized as well as in embolized lobes after portal venous branch embolization (PVE) with dynamic helical computed tomography (CT). Six patients with hepatic malignancies, who underwent PVE prior to a subsequent hepatectomy, were the subjects of this study. We performed CT examinations before PVE and 2 weeks after PVE to make a volumetric analysis. At the same time, we performed single-location dynamic sequences after the injection of a 50-ml bolus of contrast medium, and we then created time-density curves from circular regions of interest drawn over the aorta, parenchyma of the right and left lobe of the liver, and spleen. We calculated the arterial perfusion index (ml/min per ml of tissue) and the portal perfusion index by dividing the maximum rate of enhancement of the liver before and after the splenic peak by the peak aortic enhancement. We then calculated the arterial and portal flows (ml/min) from the perfusion index and values of CT volumetry. In the right lobe, where the portal flow was occluded, the arterial perfusion index and flow increased significantly after PVE. In contrast, the arterial perfusion index and flow both decreased in the left lobe after PVE in a reverse response to the increase in the portal perfusion index and flow. The total arterial flow of the liver thus seemed to slightly increase; however, the change was not significant. By performing PVE an increased arterial perfusion was induced in the embolized lobe, with a concomitant decrease in arterial perfusion in the nonembolized lobe.

Preventive effect of preoperative portal vein ligation on endotoxin-induced hepatic failure in hepatectomized rats is associated with reduced tumour necrosis factor alpha production.

BACKGROUND: Preoperative portal vein embolization successfully reduces the incidence of postoperative hepatic failure in which endotoxin is postulated to be involved. To identify the mechanism of this preventive effect, the relationship of endotoxin-induced liver injury with tumour necrosis factor (TNF) alpha and nitric oxide production in the peripheral blood, liver and spleen of rats subjected to preoperative portal vein branch ligation (PVL) was compared with that in rats undergoing sham operation. METHODS: Rats with PVL and those that underwent sham operation were subjected to resection of ligated liver lobes (PVL-Hx rats) and two-thirds hepatectomy (noPVL-Hx rats) respectively at day 5, followed by intravenous administration of endotoxin 200 microgram/kg body-weight at day 7. At various time intervals after endotoxin injection, the peripheral blood, liver and spleen tissues were harvested and analysed for TNF-alpha and nitric oxide production. RESULTS: The survival rates of noPVL-Hx and PVL-Hx rats at 48 h after endotoxin administration were 40 and 100 per cent respectively. The former rats showed more extensive liver injury as represented by higher serum aminotransferase and hyaluronate levels than the latter. Plasma concentrations of TNF-alpha at 1.5 h after endotoxin treatment were significantly higher in noPVL-Hx rats (mean(s.e.m.) 22 125(2175) pg/ml; n = 6) than PVL-Hx rats (8344(4076) pg/ml; n = 6) (P < 0.01). Consistent with this, expression of TNF-alpha messenger RNA in the liver and spleen was suppressed in PVL-Hx rats. In two-thirds hepatectomized rats, plasma TNF-alpha concentrations after endotoxin administration at 1, 2 and 3 days (14 350(2186), 26 375(2478) and 23 000(3745) pg/ml respectively; n = 6 each) were significantly higher than that before operation (9067(1559) pg/ml; n = 6) (P < 0.05), whereas those at 5 and 7 days (10 102(3616) and 8580(1427) pg/ml respectively; n = 6 each) showed no significant increase. Furthermore, nitric oxide production in peripheral blood and liver was suppressed by preoperative PVL. CONCLUSION: Prevention of endotoxin-induced liver failure by preoperative PVL is associated with reduced production of TNF-alpha in the later phase of liver regeneration.

Extent of pathologic invasion of the inferior vena cava in resected liver cancer compared with possible caval invasion diagnosed by preoperative images.

The extent of cancerous invasion of the inferior vena cava (IVC) determined from resected liver cancer was examined pathologically. Ten patients presenting with liver cancer (metastatic liver cancer, five patients; hepatocellular carcinoma, three; and cholangiocellular carcinoma, two) were diagnosed with positive IVC invasion using preoperative imaging techniques of extracorporeal ultrasonography, computed tomography, magnetic resonance imaging, and vena cavography. The diagnostic criterion for positive IVC invasion by preoperative imaging was longitudinal IVC compression measuring over 50 mm, or transverse IVC compression extending to more than half the circumference of the IVC, or the presence of lesions protruding into the IVC lumen, or the presence of developed collateral veins. All patients underwent combined resection of the IVC. However, pathology results revealed that four of the ten patients had no cancerous invasion of the IVC, and that the extent of invasion along both the longitudinal and transverse axes of the IVC was much smaller than the compression shown by imaging results. We believe that detailed preoperative assessment, using a more precise imaging technique, as well as further intraoperative examination, is required to predict the full pathological extent of cancerous invasion of the IVC.

Measurement of serum hyaluronate as a predictor of human liver failure after major hepatectomy.

Serum hyaluronate can be used as an index of hepatic sinusoidal endothelial cell function. This study was designed to evaluate its application as a predictor of liver failure after major hepatectomy. Thirty-six patients who underwent right liver lobectomy after percutaneous transhepatic right branch portal vein embolization were divided into two groups based on their postoperative clinical course (groups 1 and 2, with and without postoperative liver failure, n = 6 and n = 30, respectively). We serially measured serum hyaluronate levels using a sandwich binding protein assay system before and after hepatectomy and determined relations with progression of the underlying chronic liver disorder, portal venous pressure, and liver growth of the left lobe after portal embolization. Serum hyaluronate levels were significantly elevated, in line with the degree of severity of the underlying chronic liver disorder, and correlated well with the portal venous pressure and the hypertrophic ratio of the left lobe subsequent to portal embolization. Serum hyaluronate levels in group 1 were significantly higher than those in group 2 before surgery and increased steeply during the early period after hepatectomy. These results suggest that the serum hyaluronate reflects the hepatic functional reserve, and serial measurement of this parameter after hepatectomy can serve as a simple indicator for early detection of posthepatectomy liver failure.

Indications for portal vein embolization combined with major hepatic resection for advanced-stage hepatocellular carcinomas. A preliminary clinical study.

BACKGROUND: Criteria for selection of patients for portal vein embolization (PVE) before major hepatectomy for advanced-stage hepatocellular carcinoma (HCC) have not been clarified in detail. This study was aimed at defining those benefiting from this therapy in a retrospective fashion. PATIENTS AND METHODS: Firstly, to determine liver functional criteria for applying this approach 26 patients with stage III (17 patients) or IV (9 patients) disease, who underwent major hepatectomies after PVE, were divided into those without major complications (20 patients) and a postoperative liver failure group (6 patients). Clinical, analytical, and hemodynamic parameters obtained before and after PVE were compared between the groups. Secondly, to define the application of this approach with regard to tumor progression survival rates of patients were also obtained, taking into account factors which affect tumor development, i.e. lesion size, intrahepatic metastasis and vascular invasion. RESULTS: With regard to liver function 4 nonindications were obtained: (1) a portal pressure measured right after PVE >25 cm H(2)O; (2) post-PVE serum hyaluronate >200 ng/ml; (3) pre-PVE serum cholinesterase <150 U/l; (4) post-PVE serum cholinesterase <150 U/l. In view of the tumor progression in patients with HCCs featuring intrahepatic metastasis spread to more than 3 segments (IM3) 1-, 3- and 5-year survival rates were low (42.9, 28.6 and 0%) with a statistical significance, compared to those in patients with intrahepatic metastasis limited in the same lobe (76.9, 46.2 and 24.6%). CONCLUSIONS: When laboratory data fulfill 3 or more of the criteria, the extent of hepatic resection may have to be carefully reconsidered. Patients with HCCs featuring IM3 intrahepatic metastasis may not benefit from the aggressive approach described here.

[Outcomes of home anti-cancer chemotherapy--estimation of hepatic arterial infusion chemotherapy for patients with multiple liver metastases].

A total of 18 patients (13: colon cancer, 5: gastric cancer) with multiple liver metastases (H3) underwent hepatic arterial infusion chemotherapy (HAI) using an implanted arterial port with portable syringe pumps in our outpatient clinic. Clinical perspective: overall response rate was 22.2% (CR: 1 case, PR: 3 cases (1 case: hepatectomy after HAI), NC: 12 cases, PD: 2 cases), however, 7 of 12 cases of NC were long NC (more than 6 months). No major complications with HAI were experienced. Patient Perspective: After HAI in our outpatient clinic, the 50% survival was 341 days, 50% hospital free days were 319 days and home stay rate was 92.9%. Societal Perspective: cost and hospital stay days were significantly reduced. Home anti-cancer chemotherapy using HAI for gastrointestinal cancer patients with multiple liver metastases was safe and efficient from the viewpoint of medical outcomes.

Lidocaine-metabolizing activity after warm ischemia and reperfusion of the rat liver in vivo.

The effect of warm ischemia on lidocaine-metabolizing activity was examined in vivo. Total liver ischemia was produced for 1 hr in Sprague-Dawley rats by clamping the portal vein and hepatic artery at the hilum. Livers were then reperfused, and liver microsomes were prepared before and 0, 2, 6, and 24 hr, and 3, 6, and 10 days after reperfusion. Microsomal lidocaine-metabolizing activity and cytochrome P-450 content were examined. Lidocaine N-deethylase activity was decreased from 2.25 +/- 0.33 to 0.97 +/- 0.21 nmol/mg protein/min (mean +/- SD) 24 hr after reperfusion. This inhibition was prolonged, and activity gradually recovered after 10 days. The cytochrome P-450 content showed the same tendency. On the other hand, serum levels of alanine aminotransferase increased significantly 2 hr after reperfusion and returned to control levels 3 days after reperfusion. Liver blood flow recovered rapidly after unclamping and reached baseline levels within 6 hr. Our results suggest that after warm ischemia, prolonged hepatic dysfunction in drug metabolism, which cannot be detected by evaluating serum enzymes or liver blood flow, exists at the microsomal level.

Recurrent mesenteric desmoid tumors with multiple peritoneal dissemination: a case report and review of desmoid in Japan.

We report, herein, on the first case of a mesenteric desmoid tumor with multiple peritoneal dissemination. A 73 year-old Japanese woman, who had a history of uterine cancer that was treated with hysterectomy followed by a high dose of irradiation 25 years ago, had an unknown stenosis of the sigmoid colon, which was treated with partial resection of the stenosed colon 6 years ago, and then resulted in multiple small bowel obstructions due to the recurrence of mesenteric desmoids. The clinical behavior of this tumor is considered to be unpredictable. We emphasize that mesenteric desmoid tumors should be considered as one of the causes of stenosis of the colon and small bowel, and patients should receive careful follow-up after unknown stenosis.

[A case of Fabry's disease with chronic renal failure].

Fabry's disease is a genetic disorder caused by the absence of alpha-galactosidase (alpha-Gal), the gene of which is carried on the long arm of the X chromosome. This enzymatic defect leads to an accumulation of glycosphingolipids in the plasma and lysosomes of endothelial, perithelial, and smooth muscle cells, especially involving those of the cardiovascular, renal and cerebrovascular systems. We report one male case of Fabry's disease with renal deterioration. A 36-year-old man who was a classic case with acroparesthesia, angiokeratoma, and hypohidrosis from 10 years of age, was diagnosed to be a hemizygote of Fabry's disease at 27 years as a result of severe decreased alpha-Gal activity of his peripheral white blood cells. This patient was found to have a point mutation of a G to A transition in exon 1. In May, 1989, he was reported to have proteinuria with normal renal function and admitted to our hospital due to renal deterioration in September, 1993. Laboratory examinations revealed a serum urea nitrogen of 65 mg/dl and creatinine value of 6.9 mg/dl. Urinary protein excretion was 3.9 g/day and urinary sugar was negative. On the renal biopsy specimens, light microscopic examinations revealed multiple sclerosing and collaptic lesions in glomeruli without severe tubulo-interstitial damage, but with stenotic change of the small arteries and arterioles. Electron microscopic examinations revealed a large number of electron dense deposits in the tubules. We diagnosed this case as Fabry's disease with chronic renal failure, however the pathogenesis of this renal progressive deterioration remained obscure. In this case, degenerative changes in the renal vessels due to Fabry's disease may be associated with rapid deterioration in renal function.