Disseminated intravascular coagulation in a man with metachronous bone metastasis from gastric-cancer - case-report

We report on a case of multiple bone metastasis and disseminated intravascular coagulation (DIG) in a 49-year-old Japanese man. He underwent total gastrectomy for advanced gastric cancer in July 1992, He was diagnosed as a case of multiple bone metastasis in August 1993. Severe anemia, thrombocytopenia, and elevated fibrinogen degradative products were indicative of DIG. He was treated with sequential i.v. administration of methotrexate (MTX) and 5-fluorouracil (5-FU) and continuous i.v. infusion of heparin and gabexate mesilate. After two weeks of treatment with MTX combined with 5-FU, the findings of DIC disappeared and his general condition improved dramatically.     

Multiple tumor-suppressor-1 gene and esophageal-carcinoma

The multiple tumor suppressor 1 (MTS1) gene is homozygously deleted frequently in cell lines derived from a wide variety of tumors. We investigated the deletion of the MTS1 gene in esophageal cancer cell lines and primary esophageal squamous carcinomas using the polymerase chain reaction. Sixteen and 15 of 23 esophageal cancer cell lines showed homozygous deletion of MTS1 exon 1 and exon 2, respectively, while none of 21 primary esophageal carcinomas showed the deletion. An analysis of MTS1 gene mutations was carried out by direct DNA sequencing in 8 cell lines and 21 primary carcinomas showing no homozygous deletion. In contrast to previous reports of esophageal carcinoma, there were no mutations recognized in the region sequenced. Our study suggests that the inactivation of the MTS 1 gene may play an important role in esophageal carcinoma cell lines but may be less important in primary carcinomas of the human esophagus.     

The significance of stromal desmoplasia in intrahepatic cholangiocarcinoma: a special reference of 'scirrhous-type' and 'nonscirrhous-type' growth.

Fifty-eight surgically resected cases of intrahepatic cholangiocarcinoma (ICC) were examined grossly and microscopically. We microscopically categorized the ICC into two groups, "scirrhous-type" ICC (SICC) and "nonscirrhous-type" ICC (NSICC), according to the degree of the stromal desmoplasia in the tumor. We next assessed the histologic characteristics including proliferative activities and prognoses. Additionally, the prognostic factors of ICC were examined by univariate and multivariate analyses. Histologically, the incidences of lymphatic permeation and perineural invasion in SICC (85.7% and 100.0%, respectively) were significantly higher than those in NSICC (47.7% and 45.6%, respectively). The mean MIB-1 labeling index of SICC (mean+/-standard deviation, 29.9%+/-14.3%) was significantly higher than that of NSICC (mean+/-standard deviation, 19.1%+/-14.3%). Additionally, the 1- and 3-year survival rates of the SICC were 64.3% and 22.0%, respectively, and those of NSICC were 72.8% and 55.8%, respectively. The survival rate of SICC was significantly lower than that of NSICC. Overall, lymphatic permeation, intrahepatic metastasis, and lymph node metastasis were all considered to be independent prognostic factors for a worse prognosis based on the multivariate analyses, whereas our new category based on stromal desmoplasia or other variables were not. Our study thus indicates that lymphatic permeation, perineural invasion, and a higher proliferative activity of tumor cells carry a poorer prognosis in SICCs than in NSICCs. Although the overall independent prognostic factors were lymphatic permeation, intrahepatic permeation, and lymph node metastasis based on a multivariate analysis, a detailed histologic examination related to the stromal desmoplasia in the tumor is also considered to be useful for evaluating the biologic behavior of the ICC.     

Assessment of hepatic graft injury by graft effluent in rodents: N-acetyl-β-glucosaminidase and type III procollagen peptide

We studied the significance of N-acetyl--glucosaminidase (-NAG) and type III procollagen peptide (P-III-P) in the effluent of rodent hepatic grafts. After total hepatectomy, the livers were preserved in chilled, lactated Ringer's solution and then divided into five groups (n=10 each): group 1, 4 h preservation only; group 2, 4 h preservation and rewarming; group 3, 6 h preservation only; group 4, 6 h preservation and rewarming; and group 5, minimal preservation only. The -NAG of groups 2 and 4 was significantly higher than that of groups 1 and 3 (0.98±0.5 U/l vs 0.21±0.12 U/l; P<0.01 and 1.76±0.67 U/l vs 0.38±0.25 U/l, respectively; P<0.01), while that of group 4 was significantly higher than that of group 2 (1.76±0.67 U/l vs 0.98±0.50 U/l; P<0.05). The P-III-P of group 4 was significantly higher than that of group 2 (0.133±0.008 U/ml vs 0.110±0.015 U/ml; P<0.01). We conclude that -NAG is a novel parameter of parenchymal and nonparenchymal cells, while P-III-P reflects the integrity of the hepatic sinusoidal extracellular matrix.     

Spontaneous submucosal dissection of the esophagus. A case report

A forty year-old Japanese woman complained of slight hematemesis and severe pain on swallowing. Fluoroscopic examination showed typical esophagograms of "double barreled esophagus" or "mucosal stripe". An esophageal ulceration, probably where the dissection re-entered the usual lumen, was endoscopically evident at the lower end of the mucosal bulging. A large, shallow ulcer of unknown cause was also identified in the just anal area from the esophago-gastric junction. She recovered with conservative treatment of fasting, cimetidine and sodium alginate.     

Phase II study of (2" R)-4'-O-tetrahydropyranyladriamycin (THP) in patients with advanced or recurrent gastric cancer. Clinical study group of THP for gastric cancer in Japan

A multi-institutional collaborative phase II study of (2"R)-4-O-tetrahydropyranyladriamycin (THP) was performed by intravenous administration to patients with advanced or recurrent gastric cancer. The administration schedules were (1) 40-60 mg/body every 3 or 4 weeks and (2) 20-40 mg/body once a week. Of 58 registered patients, 49 cases were eligible and 37 cases were evaluable for response. The therapeutic results were 1 CR, 4 PR, 14 NC and 18 PD. The response rate of the evaluable cases was 13.5%. The side effects were mainly bone marrow suppression and digestive symptoms. In particular, the frequency of leukopenia was a high 75.5%, while there was a decrease in hemoglobin in 38.8% and anorexia in 30.6%. The frequency and severity of alopecia, which is a known problem with anthracyclines, were slight, and no abnormal electrocardiograms were observed.     

Domino liver transplantation from a living related donor

BACKGROUND: Although domino liver transplantations (OLT) from cadaveric donors have been performed in about 50 cases since 1995, only one case in the Japanese literature has been reported on a domino OLT from a living related donor. The difficulties of the later surgery lie in the small size of the graft volume and the short length of the vascular cuffs in the graft. METHODS: The left lobe graft was procured from a 43-year-old younger brother of a familial amyloidotic polyneuropathy (FAP) patient. Next, the left lobe graft (510 g, 44% of the estimated standard liver volume of the FAP patient) was implanted into the 48-year-old female FAP patient. At surgery for the FAP patient, a sufficient length of the vascular cuffs was secured by an extended left lobe resection, although the right lobe graft was able to maintain sufficient vascular cuffs. The right lobe graft (720 g, 54% of the recipient's estimated standard liver volume) was then implanted in the 43-year-old male patient with liver cirrhosis and hepatocellular carcinoma (stage IV-A). RESULTS: The two recipients were discharged from the hospital 1 month after OLT. At 7 months after OLT, they are both doing well and the domino recipient is free of any tumor recurrence. CONCLUSION: A domino OLT from the living related donor can therefore be done safely when careful attention is paid to the graft volume and the length of the vascular cuffs for anastomosis.     

Randomized controlled trial comparing oral doxifluridine plus oral cyclophosphamide with doxifluridine alone in women with node-positive breast cancer after primary surgery.

PURPOSE: We compared the therapeutic usefulness of doxifluridine (5'-DFUR) alone and a combination of 5'-DFUR plus cyclophosphamide (CPM), both of which are considered effective against advanced and recurrent breast cancer, to determine which treatment is more beneficial as postoperative adjuvant chemotherapy. PATIENTS AND METHODS: A total of 1,131 women with node-positive primary breast cancer were randomly assigned after primary surgery to receive 5'-DFUR alone or 5'-DFUR plus CPM. All patients initially received 5'-DFUR in an oral dose of 1,200 mg/d for 4 weeks, starting 4 weeks after surgery. Chemotherapy was then not given for 2 weeks. Patients in the 5'-DFUR group subsequently received five 4-week cycles of treatment consisting of oral 5'-DFUR (1,200 mg/d) for the first 2 weeks and no chemotherapy for the next 2 weeks. Those assigned to the 5'-DFUR plus CPM group also received oral CPM 100 mg/d for the first 2 weeks and no chemotherapy for the next 2 weeks. Women 50 years or older concurrently received 20 mg/d of tamoxifen for 2 years in both groups. RESULTS: Of the 1,088 eligible women, 546 were assigned to receive 5'-DFUR alone and 542 were assigned to receive 5'-DFUR plus CPM. Overall disease-free survival was significantly better in women who received 5'-DFUR plus CPM than in those who received 5'-DFUR alone (log-rank test, P =.021). Toxic effects occurred in 20.0% of patients (109 of 546) in the 5'-DFUR group and 32.3% of patients (175 of 542) in the 5'-DFUR plus CPM group (chi(2) test, P <.001). CONCLUSION: Combination therapy with 5'-DFUR plus CPM is more effective in preventing recurrence than 5'-DFUR alone.     

Modulation of platelet aggregation after percutaneous transluminal angioplasty of the iliac artery for atherosclerosis obliterans

BACKGROUND: Platelet aggregation is modulated by blood flow. We investigated whether platelet function is altered during percutaneous transluminal balloon angioplasty in patients with atherosclerosis obliterans. METHODS: Blood samples were obtained from the iliac artery in 9 lower limbs of 7 patients undergoing percutaneous balloon angioplasty of the iliac artery. An agonists-induced platelet aggregation test was performed with an aggregometer. Femoral blood flow was measured with a Doppler velocimeter before and after the procedure. RESULTS: Before dilatation, the maximum platelet aggregation rates (+/- SEM) induced by adenosine phosphate, epinephrine, and arachidonic acid were 54.7% +/- 5.8%, 64.8% +/- 4.3%, and 60.5% +/- 6.1%, respectively. After angioplasty, these values reduced to 36.7% +/- 4.1%, 36.1% +/- 8.6%, and 40.1% +/- 5.0%, respectively (P < .05). The pre-procedural ankle-brachial pressure index, mean flow rate, mean velocity, and shear stress variation were 0.63 +/- 0.1, 218.1 +/- 32.1 mL/min, 9.4 +/- 1.1 cm/sec, and 60.6 +/- 17.7 dyne/cm2, respectively. The mean velocity at the stenotic lesion was 215.1 +/- 83.9 cm/sec, which was significantly greater than those of the distal artery or after angioplasty (P < .01). Both ankle-brachial pressure index and shear stress variation increased after angioplasty to 0.99 +/- 0.07 (P < .05) and 139.8 +/- 17.0 (P < .05) dyne/cm2, but the mean flow rate and the mean velocity (198.3 +/- 24.5 mL/min and 8.8 +/- 1.2 cm/sec after angioplasty) did not change significantly. CONCLUSIONS: These results indicate that activated platelet function at a stenosed artery was decreased after angioplasty, possibly because of normalized blood flow with reduction of stenotic lesion.     

Bucolome, a potent binding inhibitor for furosemide, alters the pharmacokinetics and diuretic effect of furosemide: potential for use of bucolome to restore diuretic response in nephrotic syndrome.

To determine whether bucolome (5-n-butyl-1-cyclohexyl-2,4,6-trioxoperhydropyrimidine), a nonsteroidal anti-inflammatory agent, can reverse diuretic resistance of furosemide in patients with nephrotic syndrome, we examined the inhibitory effect of bucolome on the protein binding of furosemide in serum and urine. Bucolome significantly inhibited the protein binding of furosemide not only in serum but also in urine of preparation albumin (UPA), which mimics urinary albumin concentration in patients with nephrotic syndrome by ultrafiltration method. The binding percentage of furosemide to albumin was approximately 70% in UPA. With coadministration of bucolome to healthy volunteers, renal clearance of furosemide was increased, reflecting the increase of the free fraction of furosemide in serum. Furthermore, coadministration of bucolome caused a significant increase of urine volume and sodium concentration in urine. Even at higher urine levels of furosemide, the inhibitory effect of bucolome on the protein binding of furosemide in UPA remains constant, and changes in pH at weakly acidic pH levels (pH 5.5-6.5) did not alter the inhibitory effect of bucolome. Interestingly, coadministration of bucolome with furosemide in doxorubicin (Adriamycin)-induced nephrotic syndrome model rats alleviated the diuretic resistance. These results suggest that bucolome has a potent inhibitory effect on the protein binding of furosemide in the urine and can partially restore the diuretic response of furosemide in patients with nephrotic syndrome by increasing the free fraction of furosemide at the site of action.