The impact of movement sonification on haptic perception changes with aging.

Combining multisensory sources is crucial to interact with our environment, especially for older people who are facing sensory declines. Here, we examined the influence of textured sounds on haptic exploration of artificial textures in healthy younger and older adults by combining a tactile device (ultrasonic display) with synthetized textured sounds. Participants had to discriminate simulated textures with their right index while they were distracted by three disturbing, more or less textured sounds. These sounds were presented as a real-time auditory feedback based on finger movement sonification and thus gave the sensation that the sounds were produced by the haptic exploration. Finger movement velocity increased across both groups in presence of textured sounds (Rubbing or Squeaking) compared to a non-textured (Neutral) sound. While young adults had the same discrimination threshold, regardless of the sound added, the older adults were more disturbed by the presence of the textured sounds with respect to the Neutral sound. Overall, these findings suggest that irrelevant auditory information was taken into account by all participants, but was appropriately segregated from tactile information by young adults. Older adults failed to segregate auditory information, supporting the hypothesis of general facilitation of multisensory integration with aging.

On the correlation between perceptual inundation caused by realistic immersive environmental auditory scenes and the sensory gating inventory in schizophrenia.

BACKGROUND: In schizophrenia, perceptual inundation related to sensory gating deficit can be evaluated "off-line" with the sensory gating inventory (SGI) and "on-line" during listening tests. However, no study investigated the relation between "off-line evaluation" and "on-line evaluation". The present study investigates this relationship. METHODS: A sound corpus of 36 realistic environmental auditory scenes was obtained from a 3D immersive synthesizer. Twenty schizophrenic patients and twenty healthy subjects completed the SGI and evaluated the feeling of "inundation" from 1 ("null") to 5 ("maximum") for each auditory scene. Sensory gating deficit was evaluated in half of each population group with P50 suppression electrophysiological measure. RESULTS: Evaluation of inundation during sound listening was significantly higher in schizophrenia (3.25) compared to the control group (2.40, P<.001). The evaluation of inundation during the listening test correlated significantly with the perceptual modulation (n=20, rho=.52, P=.029) and the over-inclusion dimensions (n=20, rho=.59, P=.01) of the SGI in schizophrenic patients and with the P50 suppression for the entire group of controls and patients who performed ERP recordings (n=20, rho=-.49, P=.027). CONCLUSION: An evaluation of the external validity of the SGI was obtained through listening tests. The ability to control acoustic parameters of each of the realistic immersive environmental auditory scenes might in future research make it possible to identify acoustic triggers related to perceptual inundation in schizophrenia.

High-impedance wire grid method to study spatiotemporal behavior of hot electron clump generated in a plasma.

High-impedance Wire Grid (HIWG) detector has been developed to study spatiotemporal behavior of a hot electron clump generated in an electron cyclotron resonance (ECR) plasma. By measuring the floating potentials of the wire electrodes, and generating structure matrix made of geometrical means of the floating potentials, the HIWG detector reconstructs the spatial distribution of high-temperature electron clump at an arbitrary instant of time. Time slices of the spike event in floating potential revealed the growth and decay process of a hot spot occurs in an ECR plasma.

Development of a high power supercontinuum source in the 1.7 µm wavelength region for highly penetrative ultrahigh-resolution optical coherence tomography.

We developed a high power supercontinuum source at a center wavelength of 1.7 µm to demonstrate highly penetrative ultrahigh-resolution optical coherence tomography (UHR-OCT). A single-wall carbon nanotube dispersed in polyimide film was used as a transparent saturable absorber in the cavity configuration and a high-repetition-rate ultrashort-pulse fiber laser was realized. The developed SC source had an output power of 60 mW, a bandwidth of 242 nm full-width at half maximum, and a repetition rate of 110 MHz. The average power and repetition rate were approximately twice as large as those of our previous SC source [20]. Using the developed SC source, UHR-OCT imaging was demonstrated. A sensitivity of 105 dB and an axial resolution of 3.2 µm in biological tissue were achieved. We compared the UHR-OCT images of some biological tissue samples measured with the developed SC source, the previous one, and one operating in the 1.3 µm wavelength region. We confirmed that the developed SC source had improved sensitivity and penetration depth for low-water-absorption samples.

Experimental studies on ion acceleration and stream line detachment in a diverging magnetic field.

The flow structure of ions in a diverging magnetic field has been experimentally studied in an electron cyclotron resonance plasma. The flow velocity field of ions has been measured with directional Langmuir probes calibrated with the laser induced fluorescence spectroscopy. For low ion-temperature plasmas, it is concluded that the ion acceleration due to the axial electric field is important compared with that of gas dynamic effect. It has also been found that the detachment of ion stream line from the magnetic field line takes place when the parameter |f(ci)L(B)∕V(i)| becomes order unity, where f(ci), L(B), and V(i) are the ion cyclotron frequency, the characteristic scale length of magnetic field inhomogeneity, and the ion flow velocity, respectively. In the detachment region, a radial electric field is generated in the plasma and the ions move straight with the E×B rotation driven by the radial electric field.

Immunoglobulin G subclass antibody profiles in Porphyromonas gingivalis-associated aggressive and chronic periodontitis patients.

BACKGROUND/AIMS: The immunoglobulin G (IgG) antibody response is considered to be protective and beneficial for the control of periodontal lesions. This study analysed IgG subclass antibody levels of Porphyromonas gingivalis in patients with both aggressive periodontitis (AgP) and chronic periodontitis (CP). METHODS: Subgingival plaque and peripheral blood samples were collected from patients with localized AgP (n = 13), generalized AgP (n = 28) and generalized CP (n = 27) and from 14 periodontally healthy controls. P. gingivalis was identified in subgingival pockets using a polymerase chain reaction. Simultaneously, serum IgG subclass antibody against P. gingivalis whole cells/P. gingivalis fimbriae were measured using enzyme-linked immunosorbent assay. RESULTS: P. gingivalis was frequently detected in periodontitis patients. Anti-P. gingivalis whole cell IgG1 was elevated in all P. gingivalis-positive patients in the three periodontitis groups. Although increased anti-P. gingivalis IgG1 was also observed in the bacterium-positive healthy controls, the level was lower than that found in the three periodontitis groups. Levels of IgG1, IgG2, IgG3 and IgG4 to P. gingivalis did not differ among bacterium-positive patients in the three periodontitis groups; a significant increase of IgG2 level was not observed in localized AgP. Anti-fimbriae IgG subclass levels of IgG1, IgG2 and IgG4 did not differ among bacterium-positive subjects in all groups, while the anti-fimbriae IgG3 level in generalized CP was significantly higher than that in localized and generalized AgP. CONCLUSIONS: P. gingivalis infection elicited an IgG subclass antibody response in both periodontitis patients and healthy subjects, while higher anti-P. gingivalis IgG1 levels were found in the three periodontitis groups compared with the healthy control group.

Expression of CD14, CD16 and CD45RA on monocytes from periodontitis patients.

BACKGROUND AND OBJECTIVE: Peripheral blood monocytes are a heterogeneous population, with phenotypes that change on activation or differentiation. Most of the monocytes express lipopolysaccharide (LPS) receptor, CD14 intensely, and do not express Fc gamma receptor III, CD16 (CD14++CD16- monocytes). But monocytes expressing CD16 with reduced CD14 (CD14+CD16+ monocytes) increase in inflammatory diseases as well as sepsis and bacteremia in hemodialysis patients. CD45RA is expressed on activated monocytes, and is regarded as an activation marker of peripheral blood monocytes. The purpose of this study was to determine the phenotypic and functional alteration of monocytes in periodontitis patients. METHODS: Peripheral blood was collected from 33 aggressive periodontitis patients (22 females, 11 males), 55 chronic periodontitis patients (35 females, 20 males) and 30 healthy subjects (16 females, 14 males), and the expression of CD14, CD16 and CD45RA on monocytes was determined using flow cytometry. The production of interleukin-6 (IL-6) by CD16+ and CD16- monocytes stimulated with LPS from Escherichia coli and Actinobacillus actinomycetemcomitans was also examined using flow cytometry. RESULTS: The percentage of CD14+CD16+ monocytes was significantly increased in chronic periodontitis patients. Percentage of monocytes expressing CD45RA was significantly increased in aggressive periodontitis patients compared to healthy subjects. CD16+ and CD16- monocytes produced IL-6 in response to LPS from E. coli and A. actinomycetemcomitans, and the percentage of IL-6 producing cells was higher in CD16+ monocytes than CD16- monocytes, suggesting that CD14+CD16+ monocytes represent a hyper-reactive phenotype. CONCLUSIONS: The present study demonstrated that CD14+CD16+ monocytes and CD45RA+ monocytes were increased in chronic and aggressive periodontitis, respectively. These findings suggest that alteration of monocytes in periodontitis patients could be evaluated by monitoring the surface expression of CD14, CD16 and CD45RA on monocytes.

LPS-stimulated human gingival fibroblasts inhibit the differentiation of monocytes into osteoclasts through the production of osteoprotegerin.

Periodontitis is an inflammatory bone disease caused by Gram-negative anaerobic bacteria, but the precise mechanism of bone destruction remains unknown. Activated T lymphocytes secrete receptor activator of NF-kappaB ligand (RANKL) and support the differentiation of monocytes into mature osteoclasts. The purpose of this study was to examine the expression of RANKL and its inhibitor, osteoprotegerin (OPG), in inflamed gingival tissue and to clarify the role of human gingival fibroblasts (HGFs) in osteoclastogenesis regulated by RANKL. HGFs and gingival mononuclear cells (GMCs) were obtained from chronic periodontitis patients during routine periodontal surgery. Expression of OPG and RANKL mRNA in gingival tissue and HGFs was examined with RT-PCR. OPG production was measured using ELISA. Expression of RANKL, CD4, CD8 and CD69 on GMCs was determined by flow-cytometry using RANK-Fc fusion protein and the respective monoclonal antibodies. Osteoclastogenesis by RANKL was assayed by counting the number of tartarate-resistant acid phosphatase (TRAP)-positive cells after culturing human peripheral blood monocytes with recombinant human RANKL and macrophage-colony stimulating factor (M-CSF) for 10 days. OPG and RANKL mRNA were expressed in 80% (16/20) and 25% (5/20) of periodontitis lesions, respectively. OPG, but not RANKL, mRNA was expressed within HGFs. OPG mRNA expression and production by HGFs was augmented by LPS stimulation. All GMC samples expressed CD69, and two of five GMC samples expressed RANKL. The culture supernatant of LPS-stimulated gingival fibroblasts significantly reduced the number of TRAP positive cells generated by culturing monocytes with RANKL and M-CSF. The present study suggests that LPS-stimulated HGFs inhibit monocyte differentiation into osteoclasts through the production of OPG.

Right hepatic artery interruption and prostaglandin E1 in total or proximal pancreatectomy for pancreatobiliary malignancy.

BACKGROUND/AIMS: Advanced hepato-biliary-pancreatic malignancy can frequently involve the hepatic artery. We evaluated the use of prostaglandin E1 in total or proximal pancreatectomy with the right hepatic artery interruption. METHODOLOGY: A Consecutive seven of 117 patients (6.0%) in whom the right hepatic artery was interrupted and not reconstructed were reviewed retrospectively. Four of them received prostaglandin E1 (10-20 ng/kg/min) until the fifth postoperative day, while, the remaining three did not. The effect of prostaglandin E1 was compared concerning complication and hepatic function. RESULTS: The right hepatic artery was intentionally resected because of cancer invasion in five patients with biliary tract carcinoma, while, accidentally transected in two with pancreatic carcinoma. Operative deaths did not occur. The biliary leakage was identified in one patient treated without prostaglandin E1. Although a marked rise in glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and lactate dehydrogenase levels was observed, hepatic dysfunction was successfully treated conservatively in all patients. The glutamic oxaloacetic transaminase and lactate dehydrogenase values were significantly lower (P < 0.05) in patients treated with prostaglandin E1 compared with those without prostaglandin E1. CONCLUSIONS: The prostaglandin E1 infusion can be helpful for biliary anastomosis and hepatic function in radical hepato-biliary-pancreatic surgery with the right hepatic artery interruption.

Expansion of an ablated site and induction of apoptosis after microwave coagulation therapy in rat liver.

BACKGROUND/PURPOSE: Microwave coagulation therapy (MCT), one of the ablation therapies, has been widely used to treat liver cancers, yielding excellent clinical results. Despite its efficacy, the precise events that take place in the ablated liver after MCT remain unknown. We investigated sequential histologic changes around MCT sites and the relationship between MCT and apoptosis in rat liver. METHODS: One session of MCT at 30 W was applied to rat liver. The rats were killed at 0, 2, 6, 12, 24, 72, and 168 h after MCT. The liver surface area was measured for sequential evaluations of the size of the impaired field (i.e., the liver surface affected by MCT). The size of the impaired field was assessed by measuring the area that showed macroscopic changes in color with a relatively clear border. To assess apoptosis, we examined terminal deoxynucleotidyl transferase d-uridine triphosphate nick end labeling stained sections, determined the positive cell count for DNA fragmentation, and observed DNA ladder formation by gel electrophoresis. Caspase-3 activity at the ablated margin was measured for the enzymatic evaluation of apoptosis. RESULTS: The impaired field gradually expanded through 12 h after MCT. Caspase-3 activity increased four fold from the baseline, peaking at 2 h after MCT, and DNA fragmentation, confirmed by DNA ladder formation, was significantly increased at 6 h. CONCLUSIONS: Alterations in the ablated liver tissue indicated that the activation of caspase-3 around the MCT site was followed by apoptosis and expansion of the impaired field. The expansion continued until 12 h after MCT, and this may be beneficial for the local control of liver cancer.

Evaluation of the cost for laparoscopic-assisted Billroth I gastrectomy.

BACKGROUND: Despite the rapid spread of laparoscopic gastric surgery in Japan, no one has yet evaluated the costs for this new technique. The aim of this study was to analyze and compare the hospital charges for laparoscopic-assisted gastrectomy with those for conventional open gastrectomy. METHODS: The study included 48 consecutive patients who underwent laparoscopic-assisted Billroth I gastrectomy and 43 who had a conventional open Billroth I gastrectomy for cure of early gastric cancer between May 1994 and April 2000. Hospital charges covered all costs incurred during the hospital stay; they were divided into charges for consultation, prescription, injection, nursing care, operating theater, laboratory, radiology, ward and meal, and others. RESULTS: The patients who underwent laparoscopic gastrectomy were similar to those who had open gastrectomy in terms of symptoms, concurrent illness, operation time, proximal resection margin, number of harvested lymph nodes, and stage of the disease. Hospital stay after laparoscopic gastrectomy was shorter than that after open gastrectomy (16.1 vs 20.5 days, p < 0.01). Charges for nursing care, charges for ward and meal, and total hospital charges were less in the laparoscopic group than in the open group ( yen5800 vs yen8010, p < 0.01; yen461 x 10(3) vs yen512 x 10(3), p < 0.05; yen1336 x 10(3) vs yen1411 x 10(3), p = 0.072). When we compared laparoscopic gastrectomies performed during 1994-96 with those done during 1997-2000, we found a decrease in charges for ward and meal and total hospital charges ( yen498 x 10(3) vs yen421 x 10(3), p < 0.01; yen1390 x 10(3) vs yen1277 x 103, p < 0.01). CONCLUSION: Laparoscopic-assisted Billroth I gastrectomy is less expensive than conventional open Billroth I gastrectomy because both the postoperative recovery period and the hospital stay are shorter. In patients who undergo gastrectomy, the additional costs of the disposable instruments can be fully offset by the lower charges for ward and meal and nursing care associated with laparoscopic gastrectomy.

Clinicopathologic study of mixed hepatocellular and cholangiocellular carcinoma: modes of spreading and choice of surgical treatment by reference to macroscopic type.

BACKGROUND AND OBJECTIVES: Clinicopathologic features and the choice of surgical treatment for mixed hepatocellular and cholangiocellular carcinoma (MHC) remain controversial. METHODS: We evaluated the clinicopathological features of seven cases of MHC (one autopsied and six surgically resected cases). MHCs were divided into two classes by reference to macroscopic appearance: four were of the single nodular (SN) type and three were of the multinodular (MN) type. RESULTS: The mean age of patients and mean preoperative level of serum alpha-fetoprotein were 44.5 years and 56,457 ng/ml for the SN type and 63.7 years and 1,227 ng/ml for the MN type, respectively. Histologically, invasion of the portal vein, the hepatic vein, and the perineural space was found in three, two, and zero cases of SN type tumors and in three, three, and one cases of MN type tumors, respectively. Lymph node metastases were found only in two patients with MN type MHC. CONCLUSIONS: MHC of the SN type had a pattern of infiltration similar to hepatocellular carcinoma. By contrast, MHC of the MN type resembled intrahepatic cholangiocellular carcinoma. It is suggested that lymphadenectomy might be necessary for treatment of selected MHC, in particular MHC with a multinodular appearance.

Laparoscopy-assisted Billroth I gastrectomy compared with conventional open gastrectomy.

BACKGROUND: Although several studies compare surgical results of laparoscopic and open colonic resections, there is no study of laparoscopic gastrectomy compared with open gastrectomy. HYPOTHESIS: When compared with conventional open gastrectomy, laparoscopy-assisted Billroth I gastrectomy is less invasive in patients with early-stage gastric cancer. DESIGN: Retrospective review of operative data, blood analyses, and postoperative clinical course after Billroth I gastrectomy. SETTING: University hospital in Japan. PATIENTS: The study included 102 patients who were treated with Billroth I gastrectomy for early-stage gastric cancer from January 1993 to July 1999: 49 with laparoscopy-assisted gastrectomy and 53 with conventional open gastrectomy. MAIN OUTCOME MEASURES: Demographic features examined were operation time; blood loss; blood cell counts of leukocytes, granulocytes, and lymphocytes; serum levels of C-reactive protein, interleukin 6, total protein, and albumin; body temperature; weight loss; analgesic requirements; time to first flatus; time to liquid diet; length of postoperative hospital stay; complications; proximal margin of the resected stomach; and number of harvested lymph nodes. RESULTS: Significant differences (P<.05) were present between laparoscopy-assisted and conventional open gastrectomy when the following features were compared: blood loss (158 vs 302 mL), leukocyte count on day 1 (9.42 vs 11.14 x 10(9)/L) and day 3 (6.99 vs 8.22 x 10(9)/L), granulocyte count on day 1 (7.28 vs 8.90 x 10(9)/L), C-reactive protein level on day 7 (2.91 vs 5.19 mg/dL), interleukin 6 level on day 3 (4.2 vs 26.0 U/mL), serum albumin level on day 7 (35.6 vs 33.9 g/L), number of times analgesics given (3.3 vs 6.2), time to first flatus (3.9 vs 4.5 days), time to liquid diet (5.0 vs 5.7 days), postoperative hospital stay (17.6 vs 22.5 days), and weight loss on day 14 (5.5% vs 7.1%). There was no significant difference between laparoscopy-assisted and conventional open gastrectomy with regard to operation time (246 vs 228 minutes), proximal margin (6.2 vs 6.0 cm), number of harvested lymph nodes (18.4 vs 22.1), and complication rate (8% vs 21%). CONCLUSIONS: Laparoscopy-assisted Billroth I gastrectomy, when compared with conventional open gastrectomy, has several advantages, including less surgical trauma, less impaired nutrition, less pain, rapid return of gastrointestinal function, and shorter hospital stay, with no decrease in operative curability. When performed by a skilled surgeon, laparoscopy-assisted Billroth I gastrectomy is a safe and useful technique for patients with early-stage gastric cancer.

Postoperative complications of repeat hepatectomy for liver metastasis from colorectal carcinoma.

BACKGROUND/AIMS: When a repeat hepatectomy is possible, it is the most effective treatment modality for recurrent colorectal liver metastasis. The aim of this study was to evaluate the surgical risks of repeat hepatectomy for liver metastasis from colorectal carcinoma. METHODOLOGY: Between 1986 and 1996, 60 patients with hepatic metastasis from colorectal carcinoma underwent surgery in the Department of Surgery I, Oita Medical University. Ten of them underwent a repeat hepatectomy. The cases of these 10 patients were studied retrospectively; in particular, postoperative complications and intraoperative blood loss were compared between the initial and second operation. RESULTS: During the second surgery, recurrence was detected adjacent to the hepatic stump in 9 of the 10 patients. During the initial surgery, 6 underwent non-anatomic resections, and 4 had anatomic resection, including 1 extended lobectomy, 1 lobectomy, and 2 segmentectomies. For the second surgery, 3 had anatomic resections, including 2 lobectomies, and 1 segmentectomy, and 7 underwent non-anatomic resections. There were no mortalities during the initial or second operation. There was no morbidity following the initial surgeries and 7 postoperative complications (intraabdominal abscess, 4 cases; biloma, 3 cases) following the second surgeries. Mean blood loss during the second operation (1044 mL) was significantly greater than during the initial operation (561 mL). CONCLUSIONS: The present results show that repeat hepatectomy for recurrent liver metastasis from colorectal carcinoma resulted in significantly greater intraoperative blood loss and postoperative complications than those of the initial surgeries. The blood loss and complications in the second operation, the one for the recurrence, were directly associated with the fact that the recurrence was so close to the hepatic stump. Since the resection line in the second surgery was adjacent to the hepatic hilus, resection of the lesion caused much more injury to the main bile duct and main portal vein than that caused by the.

Individual diversities in interferon gamma production by human peripheral blood mononuclear cells stimulated with periodontopathic bacteria.

Polarization of type 1 (Th1) or type 2 (Th2) immune responses determines the prognosis of many infectious diseases. Interferon gamma (IFN-gamma) and IL-4 are key cytokines for the development of type 1 and type 2 immune responses, respectively. The aim of this study was to examine individual diversities in the polarization of type 1 and type 2 responses against periodontopathic bacteria. Peripheral blood mononuclear cells (PBMCs) from adult periodontitis (AP) patients and healthy (H) subjects were stimulated with Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans and Bacteroides forsythus with or without polymyxin-B, CTLA-4 Ig and anti-IL-12 antibody. IFN-gamma, IL-4 and IL-12 in the culture supernatant were measured. IFN-gamma and IL-4 producing cells were also examined using a multiparameter flow cytometric assay. Bone resorption rate in AP patients was calculated using Schei's method, and the probing pocket depth was also measured. PBMCs from AP patients and H subjects produced IFN-gamma and IL-12, whereas the production of IL-4 was rarely observed. Among the bacteria tested, A. actinomycetemcomitans was the most potent inducer of IFN-gamma and IL-12, and the reaction was inhibited by polymyxin-B. IFN-gamma was found to be produced by T cells in the PBMCs, and the production was significantly reduced by CTLA-4 Ig and anti-IL-12 neutralizing antibody. The amount of IFN-gamma produced by the PBMCs of AP patients and H subjects varied among individuals, and was significantly correlated with the amount of IL-12 produced in a particular individual. The production of IFN-gamma was not related with periodontal condition which was evaluated using bone resorption and pocket depth. These results suggest that polarization of type 1 response against periodontopathic bacteria is dependent on the production of IL-12 by monocytes, and that IL-12 stimulates IFN-gamma production. However, individual diversities of IFN-gamma production might not be directly related to the severity of periodontitis.

Choledochoduodenostomy: simple side-to-side anastomosis.

Choledochoduodenostomy, using a simple side-to-side anastomosis technique, was performed in a 74-year-old woman with common bile duct stones. She had chronic heart failure and chronic obstructive lung disease. The choledochoduodenostomy was performed with a cholecystectomy. A 2-cm-longitudinal incision was made in the common bile duct, and an adjacent longitudinal incision was made in the first portion of the duodenum. The first sutures to be placed were the two corner sutures of the posterior anastomotic wall. Then the two sides were sutured, one from the hepatic side corner of the common duct to the anal side corner of the duodenum, and the other from the duodenal side corner of the common duct to the oral side corner of the duodenum. This anastomosis was performed with one layer of interrupted 4-0 adsorbable sutures. The anterior wall of the anastomosis was constructed in a similar manner. The patient recovered uneventfully, and had no complaints of abdominal pain or fever. This procedure, our original method, is technically simple and safe, and results in minimal tension of the anastomosis.

Treatment for extrahepatic metastasis of hepatocellular carcinoma following successful hepatic resection.

BACKGROUND/AIMS: Recent advances in both the diagnosis and treatment of hepatocellular carcinoma (HCC) have improved its prognosis. Intrahepatic recurrence after hepatectomy can be treated with repeated hepatectomy, transhepatic arterial embolization (TAE), percutaneous ethanol injection therapy (PEIT), or microwave coagulo-necrotic therapy. However, treatment for extrahepatic recurrence is also important in prolonging survival in some patients. METHODOLOGY: After radical hepatectomy in 155 patients, extrahepatic recurrences were found in 15 patients that underwent subsequent treatment. The interval between completing treatment for the primary tumor and the discovery of metastasis, the location and mode of treatment of the metastasis, and the outcomes were analyzed. RESULTS: Distant metastasis was detected at a mean of 7 months after radical resection of the primary tumor. Location of the metastasis included lung, bone, and adrenal gland. Four patients had no intrahepatic recurrence and 11 patients had simultaneous intrahepatic recurrence. Six patients with intrahepatic and extrahepatic recurrence that underwent systemic chemotherapy had poor prognoses, and all died within 12 months as a result of progression of the intrahepatic tumor. Five patients with intra- and extrahepatic recurrence that underwent systemic chemotherapy combined with hepatic arterial infusion chemotherapy had relatively good outcomes; all survived for more than 12 months. CONCLUSIONS: These results suggest that to obtain a good prognosis for extrahepatic metastasis coexisting with intrahepatic recurrence, intrahepatic recurrence should be controlled by locoregional therapy, and extrahepatic metastasis should be controlled by systemic chemotherapy and/or irradiation therapy.

Augmentative effect of cyclosporin A on rat liver regeneration: influence on hepatocyte growth factor and transforming growth factor-beta(1).

We investigated the effect of cyclosporin A (CsA) on rat liver regeneration following partial hepatectomy with reference to cytokine production. Rats were divided into two groups: those without CsA pretreatment (group 1) and those with CsA pretreatment (group 2). Animals were given olive oil vehicle or CsA (10 mg/kg) dissolved in olive oil daily by gavage from 4 to 1 days before hepatectomy. The ratio of regenerating liver weight to initial body weight in group 2 was significantly higher than that in group 1 at 72 h. Although a peak 5-bromo-2-deoxyuridine labeling index was found at 24 h after hepatectomy in both groups, the peak value in the CsA-treated animals was significantly higher than in controls. In both groups, hepatocyte growth factor concentrations in both plasma and liver tissue showed maximal values at 12 h. Liver tissue values in group 2, however, were significantly higher from 1 to 12 h compared to group 1. Transforming growth factor-beta(1) (TGF-beta(1)) concentrations showed minimal serial changes in group 1, while those in liver tissue of group 2 rats were significantly lower than in group 1. Plasma TGF-beta(1) concentrations did not differ. These results suggest that upregulation of hepatic regeneration with CsA pretreatment might be attributed in part to changes in production of these mitogenic and mitoinhibitory cytokines.