BACKGROUND: To investigate the efficacy of thin-section oblique axial T2-weighted images in the assessment of parametrial invasion by cervical carcinoma. METHODS: One hundred parametria of 50 patients with cervical carcinoma were evaluated with pathologic correlation. We compared the sensitivity, specificity, and diagnostic accuracy in the assessment of parametrial invasion by cervical carcinoma between axial T2-weighted images and thin-section oblique axial T2-weighted images. RESULTS: Thin-section oblique axial T2-weighted images provided accurate cross sections of the cervix with excellent detail and detected parametrial invasion more accurately than did axial T2-weighted images showing cross sections of the trunk. Although the sensitivity, specificity, and accuracy for parametrial invasion were 46.4%, 91.7%, and 79.0%, respectively, on axial T2-weighted images, the corresponding values were 67.9%, 97. 2%, and 89.0%, respectively, on thin-section oblique axial T2-weighted images. There were statistically significant differences in the sensitivity (p = 0.014), specificity (p = 0.046), and accuracy (p = 0.002) in detecting parametrial invasion between these two types of images. CONCLUSIONS: Thin-section oblique axial T2-weighted images are useful for the assessment of parametrial invasion by cervical carcinoma.

Adenocarcinoma↗

PubMedDate not supplied

Sclerosing stromal tumor of the ovary: US, MR, and dynamic MR findings.

The US, MR, and dynamic MR findings in four patients with sclerosing stromal tumor of the ovary are reported. US showed a tumor with multilocular cystic components and irregularly thickened septa and tumor walls or a solid tumor including several small cystic components. On T2-weighted MR images, signal intensities of the cystic components were high and those of the solid components were inhomogeneous, ranging from intermediate-high to high. Dynamic MRI demonstrated marked early enhancement of the solid components.

Adolescent↗

PubMedDate not supplied

Inhibition of liver metastases from neuraminidase-treated colon 26 cells by an anti-Thomsen-Friedenreich-specific monoclonal antibody.

Thomsen-Friedenreich antigen (TF; Galbeta1-3GalNAcalpha1-) is expressed on many human carcinomas. Evidence suggests that TF-carrying tumor cells specifically bind asialoglycoprotein receptors on hepatocytes resulting in metastasis formation in the liver. We used an animal model to examine the feasibility of preventing metastasis formation by an antibody to TF. Treatment of Colon 26 cells with neuraminidase led to the exposure of TF, and consequently to a higher frequency of liver metastases in syngeneic Balb/c mice. This could be prevented by an antibody to TF (A78-G/A7), but not by a control antibody. The results may open up a new strategy for the prophylaxis of metastatic spread to the liver.

Animals↗

PubMedDate not supplied

Two cases of histopathologically advanced (stage IV) early gastric cancers.

We report two cases of early gastric cancer with distant metastases (stage IV). At our institute 1428 cases of primary gastric cancer were resected between 1980 and 1997; 536 were diagnosed as early gastric cancer based on the resected specimens (304 cases of mucosal cancer, Tis--TNM classification--and 232 of submucosal cancer, T1). 528 of these 536 cases were classified as histological stage I, six as stage II, none as stage III and two as stage IV. The incidence of stage IV early gastric cancer was 0.14% of all gastric cancers and 0.37% of the early gastric cancers. The two patients with stage IV early gastric cancer were women. Both tumors were defined as early cancer because they were confined to the submucosa. One was a type 0 IIc + III early cancer, histologically classifiable as a small, moderately differentiated adenocarcinoma (tub2 according to the Japanese Classification of Gastric Carcinoma, G2; TNM classification: ICD-O C16), size 10 x 8 mm; the other was a surface spreading type 0 IIc, classifiable as a signet-ring cell carcinoma (sig, G3), size 50 x 35 mm. Stage IV factors were N3 in the first and ovarian metastasis (Krukenberg tumor) in the second case.

Adenocarcinoma↗

PubMedDate not supplied

Midazolam for continuous sedation in Japanese critical care patients: phase II study.

This prospective study was undertaken to evaluate the efficacy and safety of midazolam as a sedative agent in 14 critically ill patients without coma admitted to the intensive care unit at Nihon University Itabashi Hospital, Japan. Adequate sedation (sedation score [SS] 4-6) was induced with 0.058- 0.372 mg/ kg midazolam and maintained with a dose range of 0.03-0.4 mg/kg per h. Most burn or trauma patients required higher midazolam doses than patients with cardiovascular disease. The most frequent adverse events observed were hypotension, heart-rate fluctuation and electrocardiogram abnormalities. Pharmacokinetic analysis of the population suggested that lower drug clearance rates correlated with presence of complications. Plasma concentrations (EC50) of SS 5, estimated by logistic regression analysis, varied among patients (mean 194 ng/ml). Midazolam infusion achieved successful sedation in this critical care setting, but the optimum dose differed by patient and was influenced by the presence of complications.

Adult↗

PubMedDate not supplied

Intrahepatic interleukin-2 with chemotherapy for unresectable liver metastases: a randomized multicenter trial.

BACKGROUND/AIMS: A pilot study of Interleukin-2 (IL-2) with chemotherapy for unresectable colorectal liver metastases revealed a favorable response rate (76%). This prospective, randomized, multicenter study was conducted to evaluate the efficacy of this treatment protocol. METHODOLOGY: Over a period of 32 months, 46 patients with unresectable liver metastases were randomly assigned to 1 of 3 treatment groups: group A: chemotherapy alone, group B: chemotherapy plus high-dose, intermittent IL-2 (2.1 x 10(6) U twice weekly) or group C: chemotherapy plus low-dose, continuous IL-2 (7 x 10(5) U daily). Treatment continued for 4 weeks in the hospital and on an outpatient basis according to the clinical response. No crossover between treatment arms was permitted. RESULTS: IL-2 combined with chemotherapy produced a higher complete and partial response rate of 40% in group A, 60% in group B, and 78% in group C. Toxicity related to IL-2 included fever, chills, malaise, and eosinophilia. CONCLUSIONS: Hepatic arterial infusion of chemotherapy plus IL-2 resulted in an increased tumor response when compared with chemotherapy alone. To confirm the efficacy of this treatment protocol, we have started a large-scale, randomized, multi-institution trial.

Adult↗

PubMedDate not supplied

Endometrial carcinoma: multisection dynamic MR imaging using a three-dimensional FLASH technique during breath holding.

PURPOSE: Our aim was to investigate the usefulness of multisection dynamic MR imaging using a 3D FLASH technique during breath holding in assessing myometrial invasion by endometrial carcinoma. MATERIALS AND METHODS: Twenty-eight endometrial carcinomas were evaluated with pathologic correlation. Dynamic MR imaging was performed using the 3D FLASH technique during breath holding. We compared accuracy in the assessment of myometrial invasion by endometrial carcinoma between T2-weighted images, contrast-enhanced T1-weighted images, and dynamic MR images. RESULTS: The accuracy rates in estimating myometrial invasion with T2-weighted images, contrast-enhanced T1-weighted images, and dynamic MR images were 64.3%, 67.8%, and 85.7%, respectively. Statistically significant differences were seen between dynamic MR images and both T2-weighted images and contrast-enhanced T1-weighted images. CONCLUSION: Multisection dynamic MR imaging using the 3D FLASH technique during breath holding is useful for the evaluation of myometrial invasion by endometrial carcinoma with polypoid growth or an unclear junctional zone on T2-weighted images.

Contrast Media↗

PubMedDate not supplied

Interleukin-2 as a modulator of 5-fluorouracil in hepatic arterial immunochemotherapy for liver metastases.

BACKGROUND/AIMS: Hepatic arterial infusion of interleukin-2-based immunochemotherapy has yielded a high response rate (> 75%) in patients with unresectable liver metastases. In order to clarify the mechanisms that underlie the apparent benefit of combination treatment, the role of IL-2 as a modulator of 5-fluorouracil metabolism was investigated. METHODOLOGY: A single dose of 5-fluorouracil (50 mg/kg) with or without IL-2 (3500 Japan Reference Units/kg) was given via the hepatic artery to rats bearing liver metastases. Thirty minutes later samples of liver metastatic foci or surrounding normal liver tissue were removed for the measurement of thymidylate synthase, thymidine kinase and dihydropyrimidine dehydrogenase activity, and 5-fluorouracil content. RESULTS: 5-fluorouracil levels in tumor were significantly higher than in normal liver. Although the addition of IL-2 reduced 5-fluorouracil levels in both tumor and normal liver tissues by the activation of dihydropyrimidine dehydrogenase, the ratio of tumor/normal liver 5-fluorouracil levels was unchanged. Both thymidylate synthase and thymidine kinase activities were significantly inhibited in tumor tissue when the combination of 5-fluorouracil and IL-2 was administered. CONCLUSIONS: IL-2 increases 5-fluorouracil cytotoxicity through the inhibition of thymidylate synthase/thymidine kinase activities in the hepatic arterial infusion.

Adenocarcinoma↗

PubMedDate not supplied

Clinicopathological evaluation of T2-gastric cancer among age groups.

BACKGROUND/AIMS: Although the recent results of surgical treatments for T2-gastric cancer (defined as: tumor invasion of the muscularis propria or the subserosa) have been comparatively favorable, frequency of lymph node metastasis is high and recurrence often happens. METHODOLOGY: A retrospective study on T2-gastric cancer in 347 patients who underwent curative resection between 1975 and 1995 was performed to address this issue. These 347 patients were divided into 3 groups according to age: group I (72 cases) < 50 years old; group II (202 cases) not < 50 years but < 70 years old; and group III (73 cases) > or = 70 years old. RESULTS: There was an apparent tendency that gastric cancer in aged patients is more likely to become differentiated cancer and spread easily to the liver. CONCLUSIONS: The data suggest that aged patients should be more carefully followed for any hematogenous metastases including liver metastases. Removal of hepatic metastases or regional hepatic infusion chemotherapy may then salvage some patients even elderly patients.

Adult↗

PubMedDate not supplied

Hepatic arterial infusions of interleukin-2-based immunochemotherapy in the treatment of unresectable liver metastases from colorectal cancer.

In preclinical studies, hepatic arterial infusion of interleukin-2 (IL-2) in dogs significantly induced lymphocyte proliferation and augmented antitumor killing activity in the liver. Based on these findings, a pilot study of hepatic arterial infusions of IL-2-based immunochemotherapy was conducted in 21 patients (15 men, 6 women) with unresectable liver metastases from colorectal cancer, to determine whether the addition of IL-2 improved the therapeutic efficacy of chemotherapy alone. Interleukin-2 was given to all patients as 7 to 8 x 10(5) Japanese reference units (JRU) in addition to 5-fluorouracil (5-FU) 250 mg daily and mitomycin C (MMC) 4 mg once weekly, through a subcutaneous port for 3 weeks. After completion of the initial course, patients were discharged from the hospital and continued on a modified regimen for outpatient therapy: IL-2, 2.0 to 2.1 x 10(6) JRU and 5-FU 250 mg twice weekly; MMC 4 mg once weekly. Patient response rate was 76%, and the median survival from initiation of treatment was 24 months. Toxicity of the combined regimen was minimal. Peripheral lymphocyte phenotype study showed notable decreases in CD8+, CD16+, and CD57+ cells and an increase in CD4+ cells (ie, elevation of 4:8 ratio) during therapy. Electron microscopic analysis of the resected liver of a patient receiving the IL-2-mitomycin-C/5-fluorouracil (IL-2.MF) infusion showed a pronounced accumulation of lymphocytes, penetrating from the space of Disse, around the cancer cells. The present study explores hepatic arterial infusion of IL-2-based immunochemotherapy as a new strategy, based on the activation of liver-associated immune response; this technique may provide improved response and survival for unresectable liver metastases.

Adult↗

PubMedDate not supplied

Locoregional immuno-chemotherapy in liver carcinoma--present and future.

Locoregional infusion therapy has several theoretical advantages over systemic therapy for the treatment of primary or metastatic liver tumors. At present, hepatic arterial infusion (HAI) chemotherapy clearly improves the response rate over systemic therapy (approximately 40-60% vs. 10-20%). However, no definite survival benefit has been demonstrated. We have utilized immuno-chemo-combined locoregional therapy to treat liver malignancies, and are convinced that such therapy will bring promising results in liver malignancies for the following reasons: First, the liver is a large immunologic organ and possesses a large amount of lymphocytes/macrophages (Kupffer cells), whose antitumor activities are enhanced in a tumor-bearing state. Our strategy is to anticipate growth inhibition of the tumor and use combined chemotherapy at relatively low doses so as not to impair the anti-tumor activities of the lymphocytes. Moreover, some kinds of chemotherapeutic agents induce immunoaugmentation when low to moderate doses are used. Based on these reasons, we have conducted a pilot study of IL-2-based immunochemotherapy for the treatment of unresectable liver metastases, and have obtained promising results. In this review, we have tried to delineate the locoregional immuno-chemotherapy in liver malignancies at present and future perspectives.

Animals↗

PubMedDate not supplied

Adjuvant hepatic arterial IL-2 and MMC, 5-FU after curative resection of colorectal liver metastases.

BACKGROUND/AIMS: Based on our favorable results of interleukin-2-based immuno-chemotherapy in the treatment of unresectable liver metastases from colorectal cancer, we utilized this therapy for the prevention of liver recurrence after liver resection. MATERIALS AND METHODS: Eighteen patients with colon cancer metastatic to the liver underwent successful hepatic resection and adjuvant immunochemotherapy that included hepatic arterial infusion of interleukin-2 and mitomycin C, 5-fluorouracil. The regimen consisted of weekly interleukin-2 (1.4-2x 10(6) units), 5-fluorouracil (250 mg) by 2-hour infusion and bolus mitomycin C (4 mg) for 6 months. RESULTS: Fourteen of 18 patients are alive and disease-free with a median postoperative follow-up of 28.5 months. Recurrent cancer has developed in 4 of the 18 patients (22%). The site of first recurrence was the lung in three patients (17%) and the pelvis in one (6%); no patients recurred in the liver. CONCLUSIONS: We recommend this adjuvant immuno-chemotherapy for the prevention of liver recurrence after curative resection of colorectal liver metastases.

Antibiotics, Antineoplastic↗

PubMedDate not supplied

Interleukin 12 augments the liver-associated immunity and reduces liver metastases.

BACKGROUND/AIMS: It has been reported recently that in vivo administration of interleukin-12 (IL-12) augments the cytotoxic activity of natural killer (NK)/T cells and shows a powerful anti-tumor activity. In this study, we evaluated that the IL-12 effect on liver-associated immunity and in vivo efficacy on the hepatic metastases in a rat model. MATERIALS AND METHODS: Varying amounts of mouse recombinant IL-12 were injected intraperitoneally for 5 days to adult male Fischer rats and hepatic sinusoidal lymphocytes (HSL) were collected. Purified HSL are spontaneously cytolytic to both conventional NK-sensitive target (YAC-1) and NK-resistant target (RCN-H4) tumor cells. RESULTS: IL-12 was found to increase the number of HSL and the cytolytic activity against these target cells in a dose-dependent fashion. Flow cytometric analysis showed that IL-12 caused an increase of CD8+ subpopulation in HSL and a double staining study revealed that the increased subpopulation was not CD3+8+ (cytotoxic T cell) fraction, but actually CD3-8+ (NK cell) fraction. Experimental liver metastases was markedly reduced in rats treated intraperitoneally with IL-12. CONCLUSION: These results demonstrate that IL-12 augments the cytolytic activity of HSL and suggests this cytokine as an attractive choice for liver metastases therapy.

Adjuvants, Immunologic↗