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Animal experiments cannot predict the probability of idiosyncratic drug toxicity; consequently, an important goal of the pharmaceutical industry is to develop a new methodology for preventing this form of drug reaction. Although the mechanism remains unclear, immune reactions are likely involved in the toxic processes underlying idiosyncratic drug toxicity: the drug is first activated into a chemically reactive metabolite that binds covalently to proteins and then acts as an immunogen. Therefore, screening tests to detect chemically reactive metabolites are conducted early during drug development and typically involve trapping with glutathione. More quantitative methods are then used in a later stage of drug development and frequently employ (14)Cor (3)H-labeled compounds. It has recently been demonstrated that a zone classification system can be used to separate risky drugs from likely safe drugs: by plotting the amount of each protein-bound reactive metabolite in vitro against the dose levels in vivo, the risk associated with each drug candidate can be assessed. A mechanism for idiosyncratic drug-induced hepatotoxicity was proposed by analogy to virus-induced hepatitis, in which cytotoxic T lymphocytes play an important role. This mechanism suggests that polymorphism in human leukocyte antigens is involved in idiosyncrasy, and a strong correlation with a specific genotype of human leukocyte antigens has been found in many cases of idiosyncratic drug toxicity. Therefore, gene biomarkers hold promise for reducing the clinical risk and prolonging the life cycle of otherwise useful drugs.

Idiosyncratic drug toxicity has led to the market withdrawal of many drugs in the past. Since animal experiments are not predictive of such toxicity, the pharmaceutical industry continues to seek new methodologies for the prevention of such effects. Although the mechanism of idiosyncratic drug toxicity remains unclear, immune reactions are likely involved. Although drugs with low molecular weights are typically not themselves immunogenic, these drugs may become haptens after being converted to chemically reactive metabolites and becoming covalently cross-linked to proteins. Therefore, screening tests to detect chemically reactive metabolites, most typically by trapping with glutathione, are carried out at early stages of drug development. More quantitative methods are used in later stages of drug development; radioassays for covalent binding (using (14)Cor (3)H-labeled compounds) are most frequently employed. A zone classification system created by combining previous assessment criteria for the chemically reactive metabolites in vitro (

Ecotype hydraulic turbines can be utilized small and distributed water resources with little civil engineering works and without environmental burdens. In Japan, network of agricultural waterway extends 400 thousands kilometers, this abundance of waterpower has a high expectations for electric power generation to supply to agricultural facilities. This promotes local production for local consumption of electricity. Four types of turbine, Savonius turbine, waterfall turbine, jet turbine and undershot turbine, were investigated and demonstrated in some fields. We have been also investigated the standalone smart grid system which can harness a several types of ecotype turbines. It can control the amount of generation power and supplying electricity. In this manuscript, we summarize our results of the investigation of ecotype hydraulic turbines.

Vortex levitation can achieve non-contact handling by blowing air into a vortex cup through a tangential nozzle to generate a swirling flow. In this paper, we focused on the relationship between the sucking pressure and the flow dynamics when gap distance from the cup to a work piece changes. Then simultaneous measurement of a pressure and a flow field in the cup was performed. As a result, the mean pressure changes and the pressure fluctuation inside the cup enhances with increasing gap height. Especially, periodic pressure perturbation is observed with wide gap height and it synchronizes with an eccentric rotation of the swirling flow. It is also found that the rotation axis of swirling flow steadily inclines against the central axis of the cup for appropriate gap height., Article, JOURNAL OF VISUALIZATION. 13(4):319-326 (2010)

The aim of this investigation was to develop an environmentally friendly nano-hydraulic turbine utilizing waterfalls. A model of an impulse type hydraulic turbine constructed and tested with an indoor type waterfall to arrive at an optimum installation condition. Effects of an installation parameter, namely distance between the rotor and the waterfall on the power performance were studied. The flow field around the rotor was examined visually to clarify influences of installation conditions on the flow field. The flow visualization showed differences of flow pattern around the rotor by the change of flow rate and rotational speed of the rotor. From this study it was found that the power performances of the rotor were changed with the distance between the rotor and the waterfalls. The maximum power coefficient of this turbine is approximately 60%. Also, to respond to changes in the waterfall flow rate, we placed a flat plate on the upper side of the rotor to control the water flow direction. As a result, we found that the coefficient of this turbine is increased with the flow rate and power could be obtained even when the flow rate changed by 3.5 times if the plate was placed on the upper side of the rotor. Although the power coefficient decreased when the plate was installed, the power coefficient still is from 53 to 58%., Article, Renewable Energy. 35(1):293-300 (2010)

The aim of this work is to provide an impulse type hydraulic turbine to utilize unexploited water resources as nano hydropower in the mountainous area. The turbine is simplified to make cheap energy and uses inexpensive components for widespread utilization. The turbine model is tested experimentally to reveal the power characteristics. The flow visualization and numerical simulation are conducted to clarify the behavior of free surface flow in the runner with different nozzle positions. The experimental results show that the maximum runner efficiency of the prototype turbine is 0.56. Numerical simulation shows that the output power depends on the nozzle positions with tbe impingement of the tail of the jet portion to the backside of the blade. This study gives the fundamental information of the turbine performance to acquire a guideline for future practical applications., Article, Journal of Fluid Science and Technology 4(3):567-577 (2009)

For revealing the transition process in a flat plate boundary layer subjected to a weak free stream turbulence, flow visualization and hot-wire measurements were performed. A weak free stream turbulence was generated by a turbulence grid mounted upstream of the contraction. The flow visualization clearly displayed a transition scenario in which a local two-dimensional wave packet rapidly forms a Λ shape structure and then breaks down to turbulence, resulting in the generation of a turbulent spot. Quantitative measurements performed by using a hot-wire anemometer also confirmed the existence of local Tollmien-Schlichting waves that agreed with the parallel linear theory in terms of their frequency, phase velocity, and the wall-normal distribution of band-pass-filtered fluctuations. For comparison, a boundary layer subjected to a moderate-intensity free stream turbulence was investigated. This investigation showed that streaky structures play an important role in the boundary layer transition, as shown by Matsubara et al. [J. Fluid Mech., 430, (2001), 149-168.] A drastic change occurred in the transition process and this change could be sensitively determined by employing the intensity and/or spectra of the free stream turbulence.

R-125224 is a novel humanized anti-human Fas monoclonal antibody prepared from HFE7A, which is a monoclonal mouse IgG anti-Fas antibody, by grafting the mouse complementarity-determining regions to human IgG, presently being developed as a drug for treatment of rheumatoid arthritis. In the present study, we investigated the tissue distribution of radioactivity in cynomolgus monkeys with collagen-induced arthritis at the arm joint (CIA monkeys) after intravenous administration of (125)I-labeled R-125224 ((125)I-R-125224). At 168 h after administration, we observed a high radioactivity in the bone marrow, thymus, lungs, liver, adrenals, spleen, ovaries, axillary lymph node and mesenteric lymph node compared to the radioactivity in the plasma. These tissues and organs in human are reported to express Fas antigen, strongly suggesting a specific binding of (125)I-R-125224 to Fas antigen in cynomolgus monkeys. Semi-micro autoradioluminograms of arm joint showed that radioactivity is detected in pharmacological site, such as the bone marrow and articular cavity at 168 h. The kinetics in binding of R-125224 to activated monkey lymphocytes and hepatocytes was also investigated. K(d) values of activated lymphocytes and hepatocytes were 1.51+/-0.08 and 0.60+/-0.11 nM, respectively, which were similar to those values in human lymphocytes and hepatocytes, demonstrating that R-125224 cross-reacts with the monkey Fas antigen.

We investigated the tissue distribution of a humanized anti-human Fas monoclonal antibody, R-125224, in SCID mice transplanted with synovial tissues from patients with rheumatoid arthritis (SCID-HuRAg mice). The binding kinetics of R-125224 was also determined, using isolated human synovial cells.Tissue distribution was assessed at 1, 24 and 168 h after intravenous administration of (125)I-R-125224 to SCID-HuRAg mice (0.4 mg/kg). The in vitro binding of (125)I-R-125224 to isolated human synovial cells was investigated.After intravenous administration of (125)I-R-125224 to SCID-HuRAg mice, the radioactivity distributed to various tissues at 1 h. Thereafter, the radioactivity in the tissues gradually decreased except for the transplanted synovial tissues, in which the radioactivity increased in a time-dependent manner, and at 168 h, the tissue/plasma concentration ratio was about 1. The in vitro binding affinity of (125)I-R-125224 to human synovial cells was high with a dissociation constant of 1.32 +/- 0.62 nM and the binding was inhibited by non-labeled R-125224 in a concentration-dependent manner.R-125224, a candidate compound for treating rheumatoid arthritis, specifically distributed to the pharmacological target site, human synovium transplanted in SCID mice, with high affinity.

Article, JSME INTERNATIONAL JOURNAL SERIES B-FLUIDS AND THERMAL ENGINEERING. 49(4): 988-994 (2006)

To obtain basic data for ballast water management, we examined the lethal effects of shock waves on a marine Vibrio. In the present experiment, shock waves were generated by hitting a projectile, which had been accelerated with a single-stage light gas gun, in an aluminum container having a cylindrical well where cell suspension was tightly maintained. We compared the shock wave effects to the isolate by use of two types of target containers with 5 and 25 mm well depths respectively. In the case of the shallow well, a lethal effect of shock compression was readily observed, but this did not occur for the deep well. Detailed pressure histories showed completely different peak patterns for the two well types. The propagation process of the shock wave was also analyzed theoretically and numerically. Results suggested that the lethal effects of shock waves are closely related to a narrow, rapid pressure change that occurs initially or a broad pressure change after the initial peak, rather than to the maximum pressure value.

Background and Objectives: The quality of life of patients with vertebral metastases from breast cancer treated with surgery was evaluated. Methods: Seven such patients underwent surgery for vertebral metastases following chemoendocrine treatment. They presented with pain and some with neurological compromise. Results: Following posterior stabilization with a segmental instrument, pain was alleviated in all seven women, two showed improvements in neurological compromise, and performance status was improved in five. In no patient was there neurological deterioration secondary to surgical intervention. They were out of bed on the 4th postoperative day and discharged on the 14th day on average. Conclusions: The quality of life was improved for these surgically treated patients. We recommend surgical stabilization for selected patients with a vertebral metastasis from breast cancer.

Despite the growing number of major surgical procedures being performed for patients on maintenance hemodialysis, few reports focus on the management and outcome of such patients, especially those undergoing major abdominal surgery. We conducted a retrospective review of 30 patients on maintenance hemodialysis who underwent abdominal surgery, 20 of whom underwent an elective operation and 10, an emergency operation. The indications of elective surgery included gastrointestinal cancer, biliary tract disease, and abdominal aortic aneurysm, while those for emergency surgery mainly involved gastrointestinal perforation or bleeding. There were no statistically significant differences between the elective group and the emergency group regarding either the mean time on hemodialysis or the preoperative clinical data. The morbidity and mortality rates were 15% and 10%, respectively, for the patients who underwent elective surgery and 50% and 70%, respectively, for those who underwent emergency surgery (P

This paper presents an experimental investigation of characteristics of the two kinds of wall jets issuing from a rectangular orifice with an aspect ratio of 5. One is the jet with a flat plate set along the long side of the exit (long side wall jet), and the other along the short side of the exit (short side wall jet). Measured results include mean velocities, intensities of streamwise turbulence and visualization of jet flow and the surface flow on the flat plate. The following results are obtained. The maximum mean velocities on the symmetric plane decay similarly as the free jet at the downstream region. In the case of the long side wall jet, the intermediate region between the potential core region and the downstream region appears longer than the others and the spread is strongly restricted near the wall. The saddlebacked mean velocity profiles are observed also for both of the wall jets. The visualizations of the flow by the smoke of dry-ice are consistent with the measured results, and the reattachments following the separation at the exit are confirmed on the plate by the oil-film method.

The purpose of this paper is to control edge tone generated by flow of a jet-wedge system. An attempt to control the edge tone has been carried out by attaching projecting objects to the nozzle exit. It is found that the edge tone is reduced even though a pair of projecting objects is attached to the nozzle exit. In addition, the effect of attached projecting objects upon the spectrum intensity of predominant frequency of the pressure fluctuation at the wedge is examined. We also found that the spectrum intensity decreases with the increase of the number of projecting objects. The spectrum intensity is minimized at the point which is located downstream from the position of the attached projecting objects.

Background: In this study, we investigated the induction of apoptosis by ultrasound in the presence of the photochemically active chlorine, 4-formyloximeetylidene-3-hydroxyl-2-vinyl-deuterio-porphynyl (IX)-6-7-diaspartic acid (ATX-S10). Methods: HL-60 cells were exposed to ultrasound for up to 3 min in the presence and absence of ATX-S10, and the induction of apoptosis was examined by analyzing cell morphology, DNA fragmentation, and caspase-3 activity. Results: Cells treated with 80μM ATX-S10 and ultrasound clearly showed membrane blebbing and cell shrinkage, whereas significant morphologic changes were not observed in cells exposed to either ultrasound or ATX-S10 alone. Also, DNA ladder formation and caspase-3 activation were observed in cells treated with both ultrasound and ATX-S10 but not in cells treated with ultrasound or ATX-S10 alone. In addition, the combination of ATX-S10 and the same acoustical arrangement of ultrasound substantially enhanced nitroxide generation by the cells. Sonodynamically induced apoptosis, caspase-3 activation, and nitroxide generation were significantly suppressed by histidine. Conclusions: These results indicate that the combination of ultrasound and ATX-S10 induces apoptosis in HL-60 cells. The significant reduction in sonodynamically induced apoptosis, nitroxide generation, and caspase-3 activation by histidine suggests active species such as singlet oxygen are important in the sonodynamic induction of apoptosis. General significance: The results reported in this paper are experimental, but they significantly support the possibility of sonodynamic treatment for cancer using the induction of apoptosis.

In this study, the sonodynamically induced antitumor effect of pyrrolidine tris-acid fullerene (PTF) was investigated. Sonodynamically induced antitumor effects of PTF by focused ultrasound were investigated using isolated sarcoma-180 cells and mice bearing ectopically-implanted colon 26 carcinoma. Cell damage induced by ultrasonic exposure was enhanced by 5-fold in the presence of 80 µM PTF. The combined treatment of ultrasound and PTF suppressed the growth of the implanted colon 26 carcinoma. Ultrasonically induced 2,2,6,6-tetramethyl-4-piperidone-1-oxyl (4oxoTEMPO) production in the presence and absence of PTF was assessed, and it was shown that 80 µM PTF enhanced 4oxoTEMPO production as measured by ESR spectroscopy. Histidine, a reactive oxygen scavenger, significantly reduced cell damage and 4oxoTEMPO generation caused by ultrasonic exposure in the presence of PTF. These results suggest that singlet oxygen is likely to be involved in the ultrasonically induced cell damage enhanced by PTF.

思春期以降のアトピー性皮膚炎患者に認められる顔面紅皮症型皮疹に関与している証を, 〓血と熱証が主役と考えて, 駆〓血剤と清熱剤の合方による効果を検討した。顔面紅皮症型皮疹を有するAD患者20例中15例 (75%) が全身的〓血状態, 5剤 (25%) が全身的非〓血状態であった。15剤の全身的〓血状態の症例のうち, 著明な便秘傾向を有する7例 (46.7%) に清熱剤 (白虎加人参湯あるいは黄連解毒湯) と桃核承気湯を合方して使用した結果, 全例で有効以上が示された。便秘傾向がないか, 明らかでない8例 (53.3%) では, 清熱剤 (白虎加人参湯あるいは黄連解毒湯) と桂枝茯苓丸を合方して全例で有効以上が示された。全身的非〓血状態であっても, 駆〓血剤を清熱剤に合方した方が有効な症例が認められたことから, アトピー性皮膚炎の顔面紅皮症型皮疹には, 原則として駆〓血剤と清熱剤の合方を考慮すべきと思われた。

Microdose (MD) clinical trials have been introduced to obtain human pharmacokinetic data early in drug development. Here we assessed the cost-effectiveness of microdose integrated drug development in a hypothetical model, as there was no such quantitative research that weighed the additional effectiveness against the additional time and/or cost. First, we calculated the cost and effectiveness (i.e., success rate) of 3 types of MD integrated drug development strategies: liquid chromatography-tandem mass spectrometry, accelerator mass spectrometry, and positron emission tomography. Then, we analyzed the cost-effectiveness of 9 hypothetical scenarios where 100 drug candidates entering into a non-clinical toxicity study were selected by different methods as the conventional scenario without MD. In the base-case, where 70 drug candidates were selected without MD and 30 selected evenly by one of the three MD methods, incremental cost-effectiveness ratio per one additional drug approved was JPY 12.7 billion (US$ 0.159 billion), whereas the average cost-effectiveness ratio of the conventional strategy was JPY 24.4 billion, which we set as a threshold. Integrating MD in the conventional drug development was cost-effective in this model. This quantitative analytical model which allows various modifications according to each company's conditions, would be helpful for guiding decisions early in clinical development.

To assess the features of multicentric occurrence in hepatocellular carcinoma, we analyzed 10 of 72 patients (14%) who had undergone hepatic resection for hepatocellular carcinoma from May 1989 to October 1992 both clinically and pathologically. The multicentric occurrence of hepatocellular carcinoma was defined among the simultaneously detected small tumors as (a) at least one tumor consisting of extremely well-differentiated (grade I) hepatocellular carcinoma growing in a replacing pattern or (b) one of a group of hepatocellular carcinomas growing in an area of adenomatous hyperplasia. Of the 10 patients, the tumors in 9 were diagnosed as synchronous multicentric hepatocellular carcinomas, whereas the tumor in 1 was considered metachronous. All patients had cirrhosis; one of them had hepatitis B virus infection and nine patients had HCV infection. The inflammatory findings in the parenchyma were determined on the basis of serum enzyme values (AST, 89 +/- 27 IU/L; ALT, 96 +/- 43 IU/L). One or two tumors in 9 of 10 patients had thin trabecular or trabecular patterns showing replacing growth. In addition, one of the two tumors in two of nine patients was observed growing in areas of adenomatous hyperplasia. Recurrences were found in 4 of 10 patients. The 3-yr disease-free survival rate was 23%. Multiple recurrences were recognized in the two patients, and in the patients who underwent repeat surgery, grade I tumors were also found. Even though these tumors were small and well-differentiated, the recurrence rate was high. Therefore to detect the recurrence of metachronous multicentric hepatocellular carcinoma at an earlier stage, careful follow-up after surgery should be carried out.

The aim of this investigation is to develop an open type cross-flow runner for environmentally friendly nano-hydraulic turbine utilizing extremely low head waterfalls. The waterfall condition is strongly affected by weather, so flow rate changes frequently. It causes a decrease in runner performance because it does not have any flow adjusting mechanisms. It is, therefore, important to evaluate the runner performance against the change of flow condition for stable power generation. This study focused on the influence of waterfall flowing position and its thickness on the runner performance. An open type cross-flow runner was applied for waterfall generation. As a result, we found that the runner characteristic varied with the waterfall condition. In particular, the waterfall thickness has great influence on the runner performance. The value of CPmax reaches the highest value of 0.61 at Q = 3.0×10−3 m3 /s.Copyright © 2011 by JSME

This paper describes the mechanism of the deflection of the main jet in a fluid amplifier caused by closing the exit of the output channel. The process of the jet deflection is visualized using the hydrogen bubble method, and the deflection time of the jet is measured. It was found that the jet deflection was accompanied by the formation of a vortex. Using the method proposed by Horikosi, we carried out model analysis of the jet deflection. Considering the formation of the vortex which accompanies the jet deflection, we calculated the streamline from the complex potential. The deflection time, which is calculated using the model analysis, and the experimental value agree with the same order.

内シャントの静脈に狭窄をきたし, 血液透析が不十分となった3症例に対し, Nd-YAGレーザーを用いて経管的にアンジオプラスティーを試み, その有用性を検討した. 初期の2例に対しては, 直径2mmのラウンド型フロスト加工サファイヤティップを使用し, 他の1例に対しては我々が試作した直径3mmおよび4mmの同型のティップを使用した. レーザー出力は15から40 watts, 1回照射時間は3秒とし, プローブティップが狭窄部を通過するまで接触照射した. レーザーアンジオプラスティーの前後で, 電磁血流計による平均血流量測定, 血管造影および血管内視鏡による狭窄部の変化を観察した. 3例ともプローブティップはレーザー照射により狭窄部を通過可能であった. 直径2mmのティップを使用した2例中1例は, レーザーアンジオプラスティー後の血流量が十分増加せず, 術後5か月目に再狭窄をきたして外科手術を施行した. 直径3mmおよび4mmのプローブティップを使用した1例では, 満足すべき開存口径が得られた. 少数例ではあるが, 内シャント狭窄に対するレーザーアンジオプラスティーは, 静脈壁温存の点から有用であると考えられた. また十分な効果を得るには, 今後プローブティップの改良等が必要であろう.

It is known that the combination of ultrasound and sonodynamic sensitizer (SDS) is effective in noninvasive tumor treatment, referred to as sonodynamic therapy (SDT). Microbubbles have been used in ultrasound therapy as well. The purpose of this paper is to clarify the effect of microbubbles on SDT. Sarcoma 180 cells were suspended in air-saturated phosphate-buffered saline and exposed to ultrasound with the SDS rose bengal derivative (RBD) in standing wave mode in the presence and absence of microbubbles [sonazoid (SZ)]. The ultrasonically induced cytotoxicity with RBD and SZ was about 20 times higher than without either, and about 80% of the SZ microbubbles were destructed by ultrasonic exposure in as short as five seconds. Since microbubbles induce significant cytotoxicity even with short duration, low intensity ultrasound, the application of microbubbles in SDT shows promise in anti-tumor treatment.

The CS-023 concentration in plasma after administration by infusion to healthy volunteers at a dose of 700 mg was decreased, with a half-life of 1.7 h, and the cumulative urinary excretion was 59.4% of the dose. The total clearance, renal clearance, and volume of distribution were 8.12 liters/h, 4.14 liters/h, and 17.2 liters, respectively.

An experimental study is presented of the jet flow, effusing with a velocity profile of developed turbulent flow, and of the flow control by means of sound emission. The impinging distance, defined as the distance between the exit and the cylinder, is xi, the slit width h is 10mm, and the cylinder diameter d is 20mm. The exit velocity of two-dimensional turbulent air jet is settled at 20m/s. Measurements include pressures around the cylinder, and the velocity of the jet flow. An oscillation of impinging jet is induced by inserting a cylinder over a range of the impinging distance, 3 < xi/h < 10, even when the jet effuses with a profile of developed turbulent flow. At the impinging distance of xi/h = 8, the oscillation process of mean velocity field is shown by means of the contours of mean velocity and arranged as an animation. The sound emission with the same frequency as that of natural oscillation stabilizes the periodic motion of the original oscillation. The jet flow is controlled to oscillate at a deviated frequency in the case when the intense sound was emitted within an extent of frequency deviation from the natural frequency. The flow with two peak frequencies, observed in the spectrum at xi/h = 10, is also controlled by emitting the sound with either of the frequencies. The free jet, effusing with a profile of developed turbulent flow, might be controlled by various frequencies.

This study focused on the development of an undershot open cross-flow turbine that is applicable in extremely low head hydropower conditions, especially in rapid and shallow streams such as agricultural waterways in mountain areas. A model of the cross-flow turbine was constructed and examined experimentally. The authors evaluated the effect of the flow conditions on undershot wheel power performance. The effect of the number of blades and the blade thickness on runner performance was also investigated. It was found that the power coefficient changed drastically with varying impinging flow thickness and runner installation height. Power could be generated when the impinging flow thickness was less than 28% of the runner diameter. The maximum power coefficient, CPmax, increased as the impinging flow thickness was decreased. Furthermore, a higher CPmax was obtained as the runner installation height was lowered. This was because the water flow was inclined between the runner and the bottom wall of the channel. In this study, the highest CPmax obtained was 0.401.

Axillofemoral bypass grafts (AxFG) are widely used in the management of poor-risk patients with aortoiliac occlusive disease. On the other hand, AxFGs are associated with a variety complications to the upper extremity (UE). UE thromboembolism represents a significant and specific complication of occluded AxFGs in our series (2.6% of patients,33.3% of occluded grafts). This article describes two cases of late axillary artery thrombosis caused by the occlusion of externally-supported AxFGs. The two patients were treated by graft disconnection, a distal embolectomy, and patch angioplasty of the axillary artery. Their postoperative courses were uneventful. Based on the authors' experience and a review of the literature, they suggest that an occluded AxFG represents a high risk for use of a donor artery and that such patients must therefore be very carefully followed. To prevent late UE thromboembolism in patients with occluded grafts, the authors strongly advise that such patients undergo a surgical operation with careful followup after surgery.

We report herein the case of a 46-year-old-man with small cell neuroendocrine carcinoma (NEC) concomitant with large villous adenoma of the rectum, who underwent abdominoperineal resection with regional lymphnode dissection. The resected specimen was histologically found to contain a small lesion of NEC confined to the submucosa in the large adenoma. A computed tomography scan done 4 months postoperatively revealed recurrences in the liver, lymph nodes, and bone. Therefore, two cycles of sequential intravenous combined chemotherapy with standard doses of cisplatin and 5-fluorouracil (5-FU) were administered, after which the size of each tumor decreased remarkably. Nevertheless, the patient died 8 months after the operation. As there was a fair response of this tumor to the combined chemotherapy of cisplatin and 5-FU, this regimen against NEC of the colon and rectum should be given consideration.

To determine if peritoneal collagen type IV levels could serve as a parameter for predicting metastasis and the subsequent course of disease, the concentration of collagen IV in the peritoneal fluid of 85 patients with adenocarcinoma of the gastrointestinal tract, including 50 with gastric cancer and 35 with colorectal cancer, was measured radioimmunologically. The peritoneal collagen type IV levels were elevated in 13 (26%) of the patients with gastric cancer, in 8 (23%) of those with colorectal cancer, and in none of the control subjects. The mean concentration of collagen type IV in tumors characterized by peritoneal dissemination was significantly higher than that in those without metastasis; however, there were no significant differences in the collagen type IV levels between tumors with and those without liver metastasis, or between those with and those without lymph node metastasis. There was a significant correlation between the peritoneal collagen type IV level and survival time in patients with clinically evident peritoneal dissemination. A positive correlation was also found between collagen type IV and carcinoembryonic antigen levels. In conclusion, the levels of peritoneal collagen type IV provide evidence of peritoneal dissemination, and can aid in the prediction of life expectancy in patients with adenocarcinomas of the gastrointestinal tract.

To evaluate the benefits of performing laparoscopic cholecystectomy (LC) in patients with cirrhosis, data on 13 patients with liver cirrhosis who underwent cholecystectomy for gallstones between 1989 and 1995 were retrospectively collected from charts filed at Fukuoka City Hospital. These 13 patients were classified into two groups; one, comprised of 7 who underwent LC, and anothe, comprised of 6 who underwent open cholecystectomy (OC). No statistical differences were observed in the duration of surgery or the intraoperative blood loss between the two groups; however, the C-reactive protein (CRP) level in the serum was significantly higher in the OC group than in the LC group. LC was followed by a significantly earlier resumption of a normal diet (P

A 51-year-old male with a recurrent medullary thyroid carcinoma (MTC) showed high serum levels of calcitonin (CT) and carcinoembryonic antigen (CEA) but with concomitant normocalcemia. The CT activities of the patient's serum in vivo (hypocalcemic activity in rats) and in vitro (cyclic AMP-increasing activity in cultured human mammary tumor, T47D) were much lower than those expected from the patient's CT level. High performance liquid chromatography (HPLC) with radioimmunoassay (RIA) detection gave a broad spectrum of molecular weights of CT-like polypeptides in the 3 kDa to 200 kDa range with separation from CEA, suggesting that the mechanism for CT production in MTC is an obscure one.

Objective: To predict disseminated microscopic foci or occult micrometastases in the peritoneal cavity in patients with gastric cancer. Design: Randomly selected patients with gastric cancer had peritoneal washings performed at the beginning of laparotomy. Patients: Thirty-nine patients with gastric carcinoma and 10 patients with other benign disease as a control group. Setting: Inpatients in a surgical department. Interventions: The concentration of collagen type IV in the irrigated peritoneal fluid was measured radioimmunologically. Intraoperative peritoneal cytologic examination and measurements of carcinoembryonic antigen (CEA) levels were also performed. Main Outcome Measurements: Results of the quantitative analyses of the collagen type IV concentrations as related to the clinicopathological characteristics and comparison of these results with regard to those of the peritoneal cytologic examination and CEA and collagen type IV levels. Results: There were eight patients with elevated collagen type IV concentrations. They had carcinomas with serosal invasion (pT3 and pT4) and metastatic spread (pN2, M1). Patients with clinically evident peritoneal disseminated metastases had significantly higher collagen type IV concentrations compared with those without metastases. The collagen type IV levels were more sensitive than peritoneal cytologic examination or CEA values in detecting disseminated metastases. There was an early peritoneal recurrence in the form of ovarian metastases in one patient with negative cytologic results and an elevated collagen type IV level. Linear regression analysis showed a statistically significant correlation between the collagen type IV and CEA levels. Conclusion: Quantitative detection of abnormal collagen type IV levels may be useful for predicting the presence of disseminated metastases in patients with gastric cancer. (Arch Surg. 1995;130:769-773)

background To determine a feasible postoperative adjuvant chemotherapy for patients with hepatocellular carcinoma, orally-administered chemotherapy (OC) and prophylactic lipiodolization (selective regional cancer chemotherapy using lipid contrast medium plus an anticancer drug) (PL) were compared prospectively. patients and methods Forty-eight patients who had undergone hepatic resection from 1989 to 1992 were divided into three groups: the control group (n = 19), given no chemotherapy; the OC group (n = 12), given 300 to 400 mg/d of 5-FU derivatives (either 1-hexylcarbamoyl-5-fluorouracil or uracil and tegafur, mean total dosage: 188 g, mean administrative duration: 18 months); and the PL group (n = 17), who underwent prophylactic lipiodolization 1.8 times on average using a 44-nig mean dose of epirubicin per treatment. results No statistical differences were found either in the 25 variables studied as a background analysis, or among the survival curves of the 3 groups. Recurrence was found in 23 remnant livers of the 48 patients. The 3-year, disease-free survival rate was 15%, 50%, and 86% in the control, OC, and PL groups, respectively. The disease-free survival curve of the PL group was significantly higher compared to either the control ( P = 0.001) or the OC group ( P = 0.025). conclusions Prophylactic lipiodolization was found to be an effective treatment for patients with hepatocellular carcinoma for reducing intrahepatic recurrence after resection.

To estimate the effectiveness of hepatic resection on hepatocellular carcinoma (HCC) in the elderly.Comparison with younger patients.A municipal hospital and a large university hospital in Japan.The study included 39 patients (ageor = 70 years [the elderly group]) and 229 patients (age70 years [the younger group]) who underwent hepatic resection from April 1985 to March 1993. The preoperative clinical features (Child's classification, association of cirrhosis and liver functions) were comparable between two groups. The positive rate for hepatitis C virus antibody was higher in the elderly group (88% vs 59%; P = .016).Morbidity and survival following operation and the pathological features of HCC.The incidence of postoperative hepatic failure was higher in the elderly group (10% vs 2%; P = .018). However, the incidence of operative death in the elderly group (5% vs 1%) as well as the incidence of other postoperative complications and rates of long-term survival (75.9% vs 51.6% at 5 years) and disease-free survival (30.4% vs 31.0% at 5 years) were similar to those in the younger group. The pathological features of HCC were identical between the two groups.The outcome of surgical treatment of HCC in the elderly group was satisfactory when compared with that in the younger group.