Appropriate hinge position for prevention of unstable lateral hinge fracture in open wedge high tibial osteotomy.

AIMS: Open wedge high tibial osteotomy (OWHTO) for medial-compartment osteoarthritis of the knee can be complicated by intra-operative lateral hinge fracture (LHF). We aimed to establish the relationship between hinge position and fracture types, and suggest an appropriate hinge position to reduce the risk of this complication. PATIENTS AND METHODS: Consecutive patients undergoing OWHTO were evaluated on coronal multiplanar reconstruction CT images. Hinge positions were divided into five zones in our new classification, by their relationship to the proximal tibiofibular joint (PTFJ). Fractures were classified into types I, II, and III according to the Takeuchi classification. RESULTS: Among 111 patients undergoing OWHTOs, 22 sustained lateral hinge fractures. Of the 89 patients without fractures, 70 had hinges in the zone within the PTFJ and lateral to the medial margin of the PTFJ (zone WL), just above the PTFJ. Among the five zones, the relative risk of unstable fracture was significantly lower in zone WL (relative risk 0.24, confidence interval 0.17 to 0.34). CONCLUSION: Zone WL appears to offer the safest position for the placement of the osteotomy hinge when trying to avoid a fracture at the osteotomy site. Cite this article: Bone Joint J 2017;99B10:1313-18.

The validity of the classification for lateral hinge fractures in open wedge high tibial osteotomy.

The objective of this study was to validate the efficacy of Takeuchi classification for lateral hinge fractures (LHFs) in open wedge high tibial osteotomy (OWHTO). In all 74 osteoarthritic knees (58 females, 16 males; mean age 62.9 years, standard deviation 7.5, 42 to 77) were treated with OWHTO using a TomoFix plate. The knees were divided into non-fracture (59 knees) and LHF (15 knees) groups, and the LHF group was further divided into Takeuchi types I, II, and III (seven, two, and six knees, respectively). The outcomes were assessed pre-operatively and one year after OWHTO. Pre-operative characteristics (age, gender and body mass index) showed no significant difference between the two groups. The mean Japanese Orthopaedic Association score was significantly improved one year after operation regardless of the presence or absence of LHF (p = 0.0015, p < 0.001, respectively). However, six of seven type I cases had no LHF-related complications; both type II cases had delayed union; and of six type III cases, two had delayed union with correction loss and one had overcorrection. These results suggest that Takeuchi type II and III LHFs are structurally unstable compared with type I. Cite this article: Bone Joint J 2015;97-B:1226-31.

E-cadherin expression in the subepithelial nevus cells of the giant congenital nevocellular nevi (GCNN) correlates with their migration ability in vitro.

BACKGROUND: Giant congenital nevocellular nevi (GCNN) are histologically characterized by the broad distribution of nevus cells in the epidermis and dermis. OBJECTIVE: To characterize E-cadherin in GCNN and define its role in nevic cell migrations. METHODS: Twenty-four cases were immunohistochemically examined and in five cases cells were isolated for primary culture for migration assays. RESULTS: The nevus cells in the superficial region showed the immunoreactivity of E-cadherin in a membranous pattern, but those in the deep part of dermis had little immunoreactivity. Ultra-structural analysis of the superficial nevus cells revealed that E-cadherin immunodeposits in the fibrillar processes around the cell body in a spotted pattern. This distribution pattern is quite different from that in the adherens junction of skin squamous epithelial cells. Boyden chamber experiments were performed using primary cultures of intradermal nevus cells. EDTA pretreatment reduced cell migration to the E-cadherin positive side when the E-cadherin positive population was relatively large in the primary cultures. CONCLUSIONS: These results indicate that E-cadherin in the nevus cells may affect nevus cell motility rather than intercellular attachment.

[Consideration of surgical treatment for recurrence after the resection of hepatic metastases from colorectal cancer].

We considered treatment for recurrence following the resection of hepatic metastases from colorectal cancer. The subjects of this study were 15 of 29 patients who had undergone WHF arterial infusion following resection of hepatic metastases from colorectal cancer, in whom there was a recurrence. Of these 15 cases, 6 involved recurrence in a single organ (residual liver, 4; lung, 1; local area, 1), 7 involved two organs (residual liver and lung, 2; residual liver and local area, 2; residual liver and bone, 1; spleen and intra-abdominal lymph node, 1; intra-abdominal lymph node and peritoneum, 1) and 2 involved three organs (lung, bone and abdominal wall, 1; lung, peritoneum and distal lymph node, 1). Reresection was performed in all cases in which recurrence occurred in a single organ. For those cases in which recurrence occurred in two or more organs, reresection and infusion were performed in the 4 cases of recurrence in the residual liver and reresection was performed in the case of recurrence in the spleen and intra-abdominal lymph node (No. 16), the case of local recurrence and the case involving the abdominal wall. The 5-year survival rate of the 29 cases who underwent initial hepatic resection was 61.9%. Five years following resection, the recurrence rate in the residual liver was 38.3%. The survival rates following treatment for recurrence were 76.9, 51.3 and 25.6% for 1, 3 and 5 years, respectively. Of the 8 deaths which have occurred to date, only one was directly related to an increase in hepatic metastases. Following resection of hepatic metastases from colorectal cancer, WHF provides a high rate of prevention as well as a high survival rate. Furthermore, with regard to recurrence following WHF treatment, if the recurrence is in only one organ, there is the possibility of achieving effective treatment by reresection (WHF = 5-FU 1,000 mg/m2 5 hrs qw).

Relationship between toxicity and cadmium accumulation in rats given low amounts of cadmium chloride or cadmium-polluted rice for 22 months.

To clarify toxic effects of long-term oral administration of low dose cadmium (Cd) on the liver and kidney, six groups of female Sprague-Dawley rats were fed a diet containing Cd-polluted rice or CdCl2 at concentrations up to 40 ppm, and killed after 12, 18, and 22 months. With toxicological parameters, including histopathology, there was no evidence of Cd-related hepato-renal toxicity, despite a slight decrease of mean corpuscular volume and mean corpuscular hemoglobin of red blood cells with 40 ppm CdCl2. Dose-dependent accumulation of Cd was observed in the liver and kidneys with peak levels of 130 +/- 42 micrograms/g and 120 +/- 20 micrograms/g, respectively, at 18 months in animals treated with 40 ppm CdCl2. A dose-dependent increase in urinary Cd levels became evident with time. Induction of metallothionein (MT) was also observed in the liver and kidney with a high correlation to the corresponding Cd levels. In the proximal renal tubular epithelia of 40 ppm CdCl2-treated rats at 22 months, prominent accumulation of Cd was observed in secondary lysosomes associated with MT deposits in their exocytotic residual bodies. The results demonstrated that, in contrast to the case with high-dose Cd-administration, renal toxicity is not induced by long-term oral administration of low amounts of Cd, although tissue accumulation does occur. Possible protective mechanisms may be operating.

[Three cases in which CR was obtained in residual metastatic lesions by intrahepatic arterial infusion after resection of hepatic metastases from colorectal carcinoma].

We report three cases in which CR was maintained after infusion (WHF) was performed for residual metastatic lesions following resection of hepatic metastases from colorectal cancer. (Case 1) A 55-year-old female with sigmoidal cancer and hepatic metastases, H2 (4 lesions). Right lobectomy and partial resection of the left lobe were performed. On the third month following surgery, CT showed two lesions in the lateral segment of the left lobe, and WHF was then begun. One month after the start of infusion, the lesions calcified and following that, disappeared. Infusion was performed for 12 months and the total amount of 5-FU was 52.8 g. Eight years and nine months following surgery, the patient is currently alive and without recurrence. (Case 2) A 65-year-old male with rectal cancer and hepatic metastases, H3 (6 lesions). Four lesions were removed by hepatic resection; however, 2 deep lesions in S4 and S5 were left unresected. WHF was begun one month following surgery, following which the lesions were undetectable by either CT or US. Infusion was performed for 18 months and the total amount of 5-FU was 81 g. Two years and ten months after surgery an isolated lung metastasis was discovered in the right lung and a thoracoscopic partial resection was performed. Eight years and four months following the original surgery and five years and four months following the lung operation the patient is alive and without recurrence. (Case 3) A 55-year-old male with rectal cancer and subsequently discovered hepatic metastases, H3 (5 lesions). Resection of the lateral segment and a partial resection of the right lobe were performed; however, one deep lesion in S7 was left unresected. WHF was begun on the 10th day following surgery. At about eight months there was a change in shape and shrinkage of the lesion. Infusion was performed for 11 months and the total amount of 5-FU was 48 g. Ten months following surgery, CT showed a new lesion in S7 and a partial resection was performed. Intraoperative US confirmed the disappearance of the previous residual lesion in S7. One year and one month following the original surgery, the patient is alive and without recurrence. From these results, it is suggested that with postoperative WHF it is possible to obtain a complete cure in cases of colorectal cancer with hepatic metastases without the resection of all lesions. (*WHF: 5-FU 1,000 mg/m2/5 hrs/week).

Good's syndrome presenting with cytomegalovirus pneumonia.

A 61-year-old woman who had undergone an operation for thymoma 17 years previously suddenly became dyspneic and showed bilateral pulmonary infiltrates on a chest radiograph. In the bronchoalveolar lavage fluid cells contained characteristic cytomegalic inclusion bodies, as well as cytomegalovirus DNA demonstrated by a polymerase chain reaction. Immunological findings included hypogammaglobulinemia, deficient numbers of circulating B cells, and impaired blast transformation of peripheral blood T cells in response to mitogens in vitro. Considering all of the findings, the patient was diagnosed with Good's syndrome presenting with cytomegalovirus pneumonia.

Assessment of renal toxicity by analysis of regeneration of tubular epithelium in rats given low-dose cadmium chloride or cadmium-polluted rice for 22 months.

To determine whether low-dose oral administration of cadmium (Cd) induces renal toxicity, six groups of female Sprague-Dawley rats were fed a diet containing low amounts of CdCl2 or Cd-polluted rice at concentrations up to 40 ppm, and were killed after 12, 18, and 22 months (experiment 1). In addition to the determination of cortical Cd levels and histopathological assessment of kidneys, labeling indices (LIs) for proliferating cell nuclear antigen (PCNA) in the renal cortical tubular epithelium of Cd-treated rats were determined as a measure of regenerative activity. For comparison, the kidneys of rats given diets containing small to large amounts of CdCl2 up to 600 ppm for 4 months were similarly examined (experiment 2). Animals in experiment 1 demonstrated spontaneous chronic nephropathy and fluctuation in the tubular PCNA LI, but these findings were not correlated with renal Cd levels at 22 months. PCNA LI on the other hand, appeared to be linked to the severity of chronic nephropathy. In experiment 2, levels of CdCl2 of 200 ppm or more clearly induced degeneration and apoptosis of proximal tubules with high correlations between renal Cd levels, PCNA LI, and the severity of tubular degeneration. The results demonstrated that, in contrast to high-dose Cd administration, treatment with 40 ppm or less for 22 months did not influence tubular regeneration as a component of nonspecific chronic nephropathy, suggesting that long-term oral administration of low levels of Cd does not injure renal tubules in female rats.

Dienogest, a synthetic steroid, suppresses both embryonic and tumor-cell-induced angiogenesis.

Orally administered dienogest (17alpha-cyanomethyl-17beta-hydroxy-estra-4,9-diene-3-one) is efficacious against human hormone-dependent cancer xenografts in severely immunodeficient mice and in rats with experimental endometriosis, but its mechanisms of action remain unclear. We assessed the effect of dienogest on angiogenesis, because these two diseases that are sensitive to dienogest are known to be angiogenesis-dependent. Topical dienogest treatment dose-dependently inhibited embryonic angiogenesis, the ID(50) value being 6.4 nmol/egg. Oral administration of dienogest (1 mg kg(-1) day(-1)) for 5 consecutive days significantly suppressed angiogenesis induced by S-180 mouse tumor cells in the mouse dorsal air sac assay. In vitro experiments showed that dienogest at concentrations up to 10 microM had little or no effect on the proliferation of plasminogen activator activity or formation of tube-like structures by microvascular endothelial cells. These results suggest that dienogest is a new, orally active antagonist of angiogenesis, and that its anti-angiogenic action may be involved in its therapeutic effects on cancer xenografts and endometriosis that we observed previously.

[Cooperative study of intraarterial preventive chemotherapy after resection of hepatic metastasis from colorectal cancer].

This is a compilation of the results of preventive intraarterial infusion following resection of hepatic metastasis from colorectal cancer at four surgical centers. The cases studied included two groups: A) 76 patients who underwent normal liver resection only, and B) 78 patients who underwent resection with adjuvant chemotherapy. Methods included: 1) WHF, 50 cases; 2) other methods using 5-FU, 18 cases; and 3) intraarterial infusions other than 5-FU, 10 (2 cases, outcome unknown). Survival rates for groups A and B for 1 and 5 years were 71.2, 18.9% and 91.5, 56.2%, respectively, with the rates for the intraarterial infusion group showing far better results. The 1- and 5-year survival rates in terms of infusion methods were: 1) 90.7% and 64.6%; 2) 94.4% and 39.3%; and 3) 90% and 60%, respectively, showing no remarkable differences between methods. Total doses of 5-FU were (a) less than 5 g, 7 patients (b) 5-15 g, 16 patients (c) 15-30 g, 22 patients (d) greater than 30 g, 23 patients. A comparison of 1- and 5-year survival rates shows (a) 85.7% and 17.1%; (b) 66.5% and 44.3%; (c) 100% and 62.7%; (d) 100% and 66.5%, respectively, with doses (c) and (d) showing markedly better results than the (a) dosage. From this we conclude that the group undergoing intraarterial hepatic infusion had a markedly improved prognosis compared to the group not undergoing any type of adjuvant therapy. Also, groups receiving a dosage of 15 g or greater of 5-FU showed prolonged survival rates.

Tissue distribution of cadmium in rats given minimum amounts of cadmium-polluted rice or cadmium chloride for 8 months.

To investigate the relationship between cadmium (Cd) toxicity, intestinal absorption, and its distribution to various tissues in rats treated orally with minimum amounts of Cd, 14 female rats per dose group per time point were given diets consisting of 28% purified diet and 72% ordinary rice containing Cd-polluted rice (0. 02, 0.04, 0.12, or 1.01 ppm of Cd) or CdCl(2) (5.08, 19.8, or 40.0 ppm of Cd) for up to 8 months. At 1, 4, and 8 months after the commencement of Cd treatment, seven rats per group were euthanized for pathological examinations to determine the Cd concentrations in the liver and kidneys and metallothionein (MT) in the liver, kidneys, intestinal mucosa, serum, and urine. One week before each period of 1, 4, and 8 months, the remaining seven rats in each group were administered a single dosage of (109)Cd, a tracer, to match the amounts of the designated Cd doses (about 1.2 to 2400 microg/kg body wt). They were euthanized 5 days later to determine the distribution of Cd to various tissues. No Cd-related toxic changes were observed. The concentrations of Cd in the liver and kidneys at any time point and MT in the liver, kidney, serum, and urine at 4 and 8 months increased dose-dependently, whereas MT in the intestinal mucosa did not alter markedly at any time point. The distribution rates of Cd to the liver increased dose-dependently (40% at lower doses to 60% at higher doses), whereas those to the kidney decreased dose-dependently (20% at lower doses to 10% at higher doses). The Cd retention rates 5 days after (109)Cd administration (amounts of Cd in various tissues/amounts of Cd administered) ranged from 0.2 to 1. 0% at any time point. These results suggest that the distribution of Cd to the liver and kidneys after the oral administration vary depending on the dosage levels of Cd. The difference of the distribution pattern of Cd to the liver and kidney is probably due to the difference in the form of the absorbed Cd, i.e., free ion or Cd-MT complex, although not closely related to the MT in the intestinal mucosa.

Effect of dienogest on bleeding time, coagulation, fibrinolysis, and platelet aggregation in female rats.

We investigated the effect of dienogest on bleeding time, coagulation, fibrinolysis, and platelet aggregation in female rats compared with that of medroxyprogesterone acetate (MPA) and danazol, in order to elucidate the reason for relatively high incidence of bleeding in dienogest-treated patients with endometriosis. Dienogest caused no change in the bleeding time at a single dose of 100 mg/kg or at a repeated dose of 10 mg/kg per day for 2 weeks. The drug increased the fibrinogen level, coagulation factor II and V activities, and antithrombin III activity, but had no effect on fibrinolysis or on platelet aggregation at repeated doses of 1 and 10 mg/kg per day for 4 weeks. MPA significantly shortened the bleeding time at the same doses as dienogest. MPA increased the fibrinogen level and plasminogen activity, potentiated the platelet aggregation, and increased the platelet cholesterol-to-phospholipid ratio at a repeated dose of 10 mg/kg per day for 4 weeks. Danazol significantly shortened the bleeding time like MPA. Danazol increased the fibrinogen level, coagulation factor II, V, VII, VIII, IX, X, XI, and XII activities, and antithrombin III activity, but had no influence on the platelet aggregation at repeated doses of 10 and 100 mg/kg per day for 4 weeks. In comparison with MPA and danazol, dienogest may induce a relatively high incidence of bleeding in patients with endometriosis partially because of its minimal effect on hemostasis.

Effects of dienogest (a synthetic steroid) on coagulation, fibrinolysis, and platelet aggregation in female monkeys.

We investigated the effects of dienogest (0.1-10 mg/kg per day, p.o.) on coagulation, fibrinolysis and platelet aggregation in female rhesus monkeys. Then, we also examined those of medroxyprogesterone acetate (MPA, 10 mg/kg per day, p.o.) or danazol (10-1000 mg/kg per day, p.o.) on these parameters in the same species. In addition, we assessed the effects of dienogest (1 and 3 mg/kg per day, p.o.) or MPA (10 mg/kg per day, p.o.) on platelet aggregation and platelet lipids in female cynomolgus monkeys. At doses of 0.3 mg/kg or greater, dienogest increased the levels of several coagulation and anticoagulation factors, but had no effect on the prothrombin time, activated partial thromboplastin time, fibrinolysis, or platelet aggregation. MPA (10 mg/kg) had no effect on coagulation or fibrinolysis, but significantly potentiated platelet aggregation in response to ADP and collagen and also increased the platelet cholesterol-to-phospholipid ratio. Danazol (10 mg/kg or more) increased the activities of coagulation factors V, VII, VIII, X, XI, and XII in comparison to dienogest and MPA. Consequently, dienogest caused less potentiation of platelet aggregation than MPA and less potentiation of coagulation than danazol.

[Intra-arterial preventive chemotherapy for residual liver after resection of hepatic metastasis from colorectal cancer].

We treated 18 cases with intra-hepatic arterial infusion chemotherapy after resection of hepatic metastasis from colorectal cancer (June 1991-September 1997). Eight cases were H1, 7 were H2, and 3 were H3. Hepatic lobectomy was done in 3 cases, lobectomy + partial resection in 2 cases, and partial resection in 13 cases. All cases received high-dose intermittent 5-FU infusion (WHF = 5-FU 1,000 mg/m2/5 hrs/w) on an outpatient basis. The total frequency of WHF was 4-54 times (average 29), and total 5-FU doses ranged from 6.0 to 81.0 g (average 40 g). The 1- and 5-year cumulative survival rates were 100% and 77.5% in all patients 100% and 87.5% in H1 group and 100% and 64.3% in H2 + H3 group, respectively. There was no significant difference of survival between the H1 and H1 + H3 groups. The 1- and 5-year recurrence rates in residual liver were 5.9% and 14.4%, respectively. One of 2 cases with residual liver recurrence was resected for metastasis again, and the patient is now in a disease-free state. WHF after resection of hepatic metastasis from colorectal cancer has a preventive effect for their survival, not only in H1 group but also in H2 + H3 group.

Effects of dienogest, a synthetic steroid, on experimental endometriosis in rats.

OBJECTIVE: Dienogest, a synthetic steroid with progestational activity, is used as a component of oral contraceptives and is currently being evaluated clinically for the treatment of endometriosis. The present study was conducted to confirm the effects of dienogest on experimental endometriosis in rats and to elucidate its mechanism of action. DESIGN: Experimental endometriosis induced by autotransplantation of endometrium in rats. METHODS: Endometrial implants, immune system, and bone mineral were investigated after 3 weeks of medication. RESULTS: Dienogest (0.1-1 mg/kg per day, p.o.) reduced the endometrial implant volume to the same extent as danazol (100 mg/kg per day, p.o.). Simultaneously, dienogest ameliorated the endometrial implant-induced alterations of the immune system: i.e. it increased the natural killer activity of peritoneal fluid cells and splenic cells, decreased the number of peritoneal fluid cells, and decreased interleukin-1beta production by peritoneal macrophages. In contrast, danazol (100 mg/kg per day, p.o.) and buserelin (30 microg/kg per day, s.c.) had none of these immunologic effects. Additionally, combined administration of dienogest (0.1 mg/kg per day) plus buserelin (0.3 microg/kg per day) suppressed the bone mineral loss induced by buserelin alone, with no reduction of the effect on endometrial implants. In vitro studies on dienogest revealed an antiproliferative effect on rat endometrial cells due to inhibition of protein kinase C activity plus a partial progestational effect. CONCLUSIONS: Dienogest appears to be a potent agent with mechanisms of action different from those of danazol and GnRH agonists currently available for the treatment of endometriosis.

Design considerations of stacked multilayers of diffractive optical elements for optical network units in optical subscriber-network applications.

The detailed design process and experimental results of stacked multilayer diffractive optical elements are reported for an optical network unit used in optical subscriber-network applications. The optical network unit accepts two incoming light beams of 1.3- and 1.55-microm wavelengths through a single-mode optical fiber. A laser diode is also placed for bidirectional communications. The optical network unit consists of five diffractive optical elements that perform the following functions: collimation of incoming beams, focusing of the outgoing 1.55-microm beam, 3-dB splitting of the 1.3-microm beam, focusing of the 1.3-microm beam onto the photodiode, and collimation of the light emitted from a laser diode. Possible cost reductions as a result of mass production and the ease of alignment of the stacked diffractive optical elements could be ideal for constructing low-cost optical network units.

Preventive effect of ritodrine hydrochloride and/or urinary trypsin inhibitor against lipopolysaccharide-induced preterm delivery in mice.

BACKGROUND: The purpose of this study was to confirm the preventive effect of ritodrine hydrochloride (ritodrine) alone or ritodrine plus urinary trypsin inhibitor (UTI) in a mouse model of preterm delivery. METHODS: On day 17 of pregnancy, female C3H/HeN mice impregnated by male B6D2F1 mice were given two intraperitoneal injections of lipopolysaccharide (LPS) (50 micrograms/kg) at a 3-hour interval, which induced a 100% incidence of preterm delivery within 25 hours of the second dose. Ritodrine (1, 3, or 10 mg/kg, p.o.), UTI (25 X 10(4) units/kg, i.p.), ritodrine (3 mg/kg, p.o.) plus UTI (25 x 10(4) units/kg, i.p.), distilled water (10 ml/kg, p.o.), or distilled water (10 mg/kg, p.o.) plus saline solution (10 ml/kg, i.p.) were administered to the pregnant animals 10 times at 1-hour intervals from 8:00 AM to 5:00 PM on day 18 of pregnancy. In addition, the preventive effect of ritodrine, UTI, or ritodrine plus UTI was examined on LPS-induced contraction of uterine muscle strips isolated from pregnant mice on day 17 of gestation. RESULTS: The incidence of preterm delivery decreased significantly in a dose-dependent fashion with ritodrine treatment, and there was a significant and synergistic decrease after combined treatment with ritodrine plus UTI. The in vitro uterine contraction induced by LPS was significantly suppressed by both ritodrine and UTI. CONCLUSIONS: Combination therapy with ritodrine plus UTI may be helpful for preventing preterm delivery in humans without the cardiovascular side effects that often accompany treatment with ritodrine alone.

[Evaluation of intra-arterial infusion chemotherapy for liver metastasis from gastric cancer].

We evaluated the result of intra-arterial infusion chemotherapy on liver metastasis from gastric cancer. Of 92 cases of metastatic liver tumor, 17 cases received intra-arterial infusion chemotherapy after primary resection. For comparison, we assigned the 17 cases to two groups according to the infused agents. One group was treated with the combination therapy of 5-FU, epirubicin and MMC (FEM group: n = 7), and another with other antineoplastic agents (non-FEM group: n = 10). In the FEM group, the response rate, 1-year survival rate and 50% survival period were 33.3%, 51.4%, 430 days, respectively, while those of the non-FEM group were 10.0%, 10.0%. 147 days. Although there was no significant difference (p = 0.0951), improvements in survival rate and survival period were observed. This implies the possibility that intra-arterial infusion chemotherapy, especially the combination therapy of FEM, is an effective treatment for liver metastasis from gastric cancer.

[Complication due to arterial infusion chemotherapy for liver metastasis from colorectal cancer].

OBJECTIVES: Arterial infusion chemotherapy is considered to be an extremely effective treatment for liver metastasis from colorectal cancer in terms of its tumor reduction and preventing recurrence in residual liver after resection. However, there still remain some unclear points as to the influence on hepatic artery and bile duct when this treatment is used over the long term. We report some conclusions obtained by examining cases of hepatic arterial occlusion (stenosis) and biliary complication who received this treatment. MATERIALS AND METHODS: Thirty-six cases who received this treatment over 3 months were the objects of this study, with the aim of direct effect against metastatic focus (21 cases) and prevention of recurrence in residual liver (15 cases). The ages were from 27 to 81; 22 cases were male and 14 were female. Indwelling routes of catheter were gastroduodenal artery (GDA) in 28 cases and femoral artery (FA) in 8 cases. Intermittent high-dose infusion (WHF: 5-FU 1,000 mg/m2/5 hrs qw) was adopted as the method. RESULTS: Hepatic arterial occlusion or stenosis was observed in 12 cases (GDA: 10; FA: 2). There seemed to be no correlation with the total dosage of 5-FU or the number of administrations. Even when hepatic arterial occlusion or stenosis occurred, no change was observed in liver function, and there no death was caused by this. However, CT showed a low-density area followed by atrophy in the right lobe in one case with right hepatic arterial stenosis, despite normal portal blood flow. Of the 6 cases which developed obstructive jaundice, 4 were due to the increase of metastatic focus or lymph nodes, and 1 case without dilatation of bile duct died from suspected sclerosing cholangitis. In this case, ALP had been increasing since 1 month before the onset of jaundice. Another case which developed biloma accompanied by the increase of serum bilirubin improved by discontinuance of chemotherapy. CONCLUSION: Since arterial infusion chemotherapy for liver metastasis from colorectal cancer causes hepatic arterial occlusion (stenosis) at a high rate, early detection of abnormalities by liver function test and imaging diagnosis which leads to early treatment is important.

Trophoblastic apoptosis in mice with preterm delivery and its suppression by urinary trypsin inhibitor.

OBJECTIVE: To investigate histopathologic changes of the placenta in mice with preterm delivery induced by lipopolysaccharide and the effect of urinary trypsin inhibitor. METHODS: Female C3H/HeN mice impregnated by male B6D2F1 mice were treated with lipopolysaccharide (50 micrograms/kg, intraperitoneally) or lipopolysaccharide plus urinary trypsin inhibitor (25 x 10(4) U/kg, intraperitoneally). At 3, 6, 9, and 18 hours after the second dose of lipopolysaccharide, and at delivery in the control and urinary trypsin inhibitor-treated groups, the concentrations, of interleukin-1 alpha and tumor necrosis factor-alpha were determined in serum and amniotic fluid. Subsequently, the placentas were examined. In the same manner, we examined mice treated with interleukin-1 alpha (250 micrograms/kg, subcutaneously) on day 15 of pregnancy and intact mice on days 15 and 18 of pregnancy as well as at delivery. To assess the direct action of cytokines, we cultured placental slices with tumor necrosis factor-alpha, interleukin-1 alpha, or tumor necrosis factor-alpha plus urinary trypsin inhibitor and examined them morphologically. RESULTS: Control mice were characterized by trophoblastic apoptosis and increased serum levels of tumor necrosis factor-alpha and interleukin-1 alpha. In contrast, urinary trypsin inhibitor-treated mice showed suppression of apoptosis and lower cytokine levels. Interleukin-1 alpha induced trophoblastic apoptosis and increased the serum level of tumor necrosis factor-alpha. The in vitro study showed that tumor necrosis factor-alpha directly induced trophoblastic apoptosis in placental slices. CONCLUSION: We demonstrated that trophoblastic apoptosis occurs in the placentas of a mouse model with preterm delivery induced by lipopolysaccharide. We postulated that apoptosis may lead to placental abruption, and its development may be prevented by treatment with urinary trypsin inhibitor.