Doxorubicin, cisplatin, and fluorouracil combination therapy for metastatic esophageal squamous cell carcinoma.

The chemotherapy regimen currently used for treating esophageal and gastric carcinoma has been either epirubicin, cisplatin, and fluorouracil (5-FU) or docetaxel, cisplatin, and 5-FU. Here, we report the efficacy and toxicity of doxorubicin, cisplatin, and 5-FU for only esophageal squamous cell carcinoma (ESCC). Between January 2000 and October 2008, a total of 41 ESCC patients with a distant metastasis were enrolled. The most common sites of metastasis were liver (26, 63.4%), lung (9, 22.0%), and bone (8, 19.5%). Doxorubicin was administered on day 1 at 30 mg/m(2) , cisplatin on days 1-5 at 14 mg/m(2)/day, and 5-FU on days 1-5 at 700 mg/m(2)/day. The median number of cycles was 2.0 (range 1-8). The dose intensities of doxorubicin, cisplatin, and 5-FU were 92.9, 92.4, and 92.5%, respectively. The overall response rate was 43.9%; one showed complete response, 17 showed partial response, 13 showed a stable disease, and 10 showed progressive disease (PD). The median survival time was 306 days (95% CI = 74-935) and the 1-year survival rate was 37.6%. Grade 3 neutropenia was seen in seven patients and grade 4 in one patient. Grade 3 fatigue, anorexia, mucositis, and diarrhea were observed in three, two, two, and one patient, respectively. This regimen is effective as a first-line therapy for ESCC with distant metastasis.

Magnifying chromoendoscopy of the esophagus: in-vivo pathological diagnosis using an endocytoscopy system.

BACKGROUND AND STUDY AIMS: The aim of the present study was to observe the endoscopic characteristics of cells on the surface layer of superficial esophageal carcinomas in vivo using an endocytoscopy system and to compare the findings with those in normal squamous epithelium. PATIENTS AND METHODS: Superficial esophageal cancers in 12 patients were examined with methylene blue staining using an endocytoscopy system. RESULTS: The endocytoscopy system and methylene blue staining made it possible to observe cells on the surface of the squamous epithelium in normal esophageal mucosa. Normal cells were arranged homogeneously, and the nucleus cytoplasm ratio was uniform and low. In esophageal cancers, the density of cells was found to be much greater than that in normal squamous epithelium. The cell distribution was also irregular and the cells were extremely heterogeneous, with the nuclei having different staining, size, and shape characteristics. The nucleus cytoplasm ratio was also very irregular. CONCLUSIONS: Examining esophageal tissue using the endocytoscopy system described here makes it possible to observe detailed histological alterations in esophageal lesions in vivo.

[Extracardiac fontan procedure in adult: report of a case].

We report a case of a 28-year-old female who underwent an extracardiac Fontan procedure. The subject was diagnosed as an atrioventricular septal defect (Rastelli classification: type C), a double outlet right ventricle, pulmonary artery stenosis, a hypoplasty of left ventricle, total anomalous venous return (Darling: Ib + IIb), and atrial flutter. She underwent a Blalock shunt and an aorto-pulmonary shunt at the ages of 3 and 9 years, respectively. Under a total CPB, an extracardiac total cavo-pulmonary connection (TCPC), using a 26 mm Hemashield graft, was completed. The postoperative course was uneventful. The complicated atrial anatomy and atrial arrhythmia indicated TCPC in this adult patient.

[Increased IL-2 and sIL-2R in sera of infants with HTLV-I infection from mother].

In our laboratory, children born to women are known to be infected with Human T-cell Leukemia Virus type-1 (HTLV-I) have been followed using, detect of gene by PCR and antibody by Western Blot Assay (WB) and Immunofluorescence Assay (IFA) test from 1990 through 1996. Four children out of 123 delivery cases have been confirmed to be infected with HTLV-I. We analyzed the correlation between the concentration of cytokines (IL-2, sIL-2R, IFN-gamma) and HTLV-I infection. IL-2 and sIL-2R in sera increased after HTLV-I infection. There was no correlation between the concentration of IFN-gamma and HTLV-I infection. These result suggested that detection of IL-2 and sIL-2R might be the marker of HTLV-I infection.

The inhibitory effect of the crude extract from a seaweed of Dygenea simplex C. Agardh on the in vitro cytopathic activity of HIV-1 and it's antigen production.

The crude water extract (NS-1) from a seaweed (Digenea simplex C. Agardh Rhodomelaceae) exhibited anti-human immunodeficiency virus (HIV)-1 activity in vitro. The inhibitory effect of the extract on the cytopathic activity of HIV-1 and it's antigen production was examined using a microplate method, immunofluorescent assay, and an HIV antigen detection kit (Abbott). NS-1 inhibited both the cytopathic effect of HIV-1 to MT-4 cells and the giant cell formation of Molt-4 cells infected with HIV-1.

White matter hyperintensity in neurologically asymptomatic subjects.

Recent advances in magnetic resonance imaging (MRI) technology have had a great impact on the delectability of minute, asymptomatic lesions of the central nervous system. The clinical significance and treatment modes of these lesions, such as white matter hyperintensity (WMH) lesions detected by T2 MRI, remain controversial. To address these problems, we retrospectively evaluated WMH lesions in relation to clinical parameters for 240 neurologically asymptomatic persons who had visited a hospital for a medical check-up of the brain. Proton and T2-weighted MRI were obtained using a 0.5 T superconducting MR imager using the spin echo technique with a repetition time (TR) of 2800 msec. An echo delay times (TE) of 40 msec was used for the proton MRI, and a TE of 100 msec was used for the T2-weighted MRI. The images were visually analyzed according to a four-point grading system. The MRI findings were correlated with clinical parameters including age, gender, presenting symptoms, and hypertension. The overall frequency of WMH increased with age. Grades 2 and 3 of WMH were more frequent in aged persons, whereas the occurrence of grade 1 WMH remained relatively constant across age groups. Based on multiple regression analysis, age was the most significant variable influencing the frequency of WMH, followed by hypertension. These results imply that WMH lesions may simply be a phenomenon of aging, or may be an indicator of prepathologic state in an ischemic brain.

[Studies on maternal transmission of HIV-1].

To investigate HIV-1 transmission from mother to child, samples taken from 3 HIV-1 sero-positive pregnant mothers, 3 children born by caesareans from their mothers and therapeutic abortion from 2 HIV-1 sero-positive mothers were tested for HIV-1 antibody by westernblot, p24 antigen by antigen captured ELISA, proviral DNA by Nested-PCR and isolation of HIV-1 virus from peripheral blood, cord blood, amniotic fluid and placenta. HIV-1 proviral DNA was detected in the peripheral blood of all mothers, but p24 antigen and virus isolation were not detected. None of the HIV-1 markers, except for antibody, was detected in the samples from their children and placenta. These facts strongly suggest that there was no HIV-1 transmission from mother to child.

[Linkage analysis in a Japanese long QT syndrome family].

Romano-Ward syndrome is an autosomal dominant trait disease, which is characterized by QT prolongation and normal hearings and shows predisposal to sudden death from cardiac arrhythmia. Recently, Keating et al. reported that Harvey ras-1 locus (H-ras-1) was closely linked to long QT syndrome (LQTS), being located on the short arm of chromosome 11. In this study we have examined a three-generation Japanese family whose members had recurrent fainting with prolongation of the QT interval on electrocardiogram. Using the H-ras-1 probe as DNA marker, we could not determine that the H-ras-1 gene was linked to LQTS. LQTS seems to be a genetically heterogeneous disease. Further study is needed to clarify the chromosomal location of the LQTS.

Risk factors for brain abscess in patients with congenital cyanotic heart disease.

Brain abscess is a serious complication of congenital cyanotic heart disease. We retrospectively evaluated the risk factors for brain abscess in 21 such patients treated between 1975 and 1990 in comparison with a control group. The mean arterial oxygen saturation, arterial partial pressure of O2, arterial blood oxygen content, and base excess in patients with brain abscess were significantly lower than in the control patients. The mean arterial partial pressure of CO2, pH, hematocrit, hemoglobin, and red blood cell content in patients with brain abscess were not significantly different. Patients with congenital cyanotic heart disease may develop minute encephalomalacia due to severe hypoxemia and increased blood viscosity resulting from compensatory polycythemia. The increased blood viscosity and reduced blood flow in the microcirculation may induce cerebral thrombosis or exaggerate minute encephalomalacia during dehydration or cardiac dysfunction, and shunted blood containing infectious organisms at such sites may be followed by focal cerebritis.

[Sequential MTX and 5-FU therapy of gastric cancer with systemic bone metastasis and disseminated intravascular coagulation].

UNLABELLED: Sequential therapy consisting of methotrexate (MTX) and 5-FU was performed together with the administration of heparin and FOY in 10 cases of gastric cancer with disseminated intravascular coagulation (DIC) causing systemic bone metastasis. The ages of the subjects ranged from 29 to 65 years (median: 49 years) with systemic bone metastasis and bone marrow carcinosis observed in all cases. Histological types consisted of 6 cases of poorly differentiated adenocarcinoma, 2 cases of signet-ring cell carcinoma, and one case each of mucocellular and tubular adenocarcinoma. Therapy consisted of intravenous injection of 30 mg-100 mg/m2 (one case, 20 mg) of MTX followed three hours later by intravenous injection of 600 mg/m2 of 5-FU weekly. Determination of DIC was made in accordance with the DIC diagnostic standards of the Ministry of Health and Welfare, and determination of tumor effectiveness was based on gastric cancer handling codes. RESULTS: PR was observed in 3 cases. Diffuse metastasis observed in the entire lung field disappeared in one case, while remarkable improvement was observed in systemic bone metastasis in scintigram findings for the other 2 cases. All 3 cases were able to be discharged. Reduction of DIC score and absence of pain were observed in 8 cases. Based on the above, aggressive implementation of this treatment method is suggested.

[Breast carcinoma metastasis to perineal neurofibroma].

A 51-year-old woman as admitted to our department because of multiple palpable tumors that were noted on the left breast, the perineum, and the neck, shoulders, arms, and legs. The breast tumor showed ulceration on the surface. The perineal tumor was 30 x 15 cm in size and had group slowly for 17 years. A chest X-ray revealed a bilateral coin lesion. She was diagnosed as having a left breast cancer with a skin lung metastasis and a perineal benign tumor. A simple mastectomy and a resection of the perineal tumor were performed. A postoperative examination revealed an adenocarcinoma of the breast and a fibroneurinoma of the perineum with a metastasis from the breast cancer.

[A case of metastatic carcinoma of the spermatic cord due to cholangioma].

Tumor in the spermatic cord is infrequent. Further, among such cases, it is extremely rare to encounter a carcinoma other than a nonepithelial malignant tumor; almost all are metastatic tumors. We recently experienced an interesting case of spermatic cord tumor in a 78-year-old male. He entered our hospital with the chief complaint of a right inguinal tumor. He underwent 2 operations to excise the tumor. The extirpated tumor mass from the right spermatic cord was composed of adenocarcinoma with abundant fibrous stroma, which is considered to be metastasis from the other viscerae. We were unable to find the primary focus in spite of extensive clinical and pathological examinations. In an autopsy about four months after the 2nd operation, the tumor was confirmed to be primary intrahepatic bile duct carcinoma, which is called cholangioma. There have been only 20 cases of metastatic spermatic cord tumor reported in Japan. However, we considered that this is the 1st case caused by cholangioma in Japan and even in other countries.

Kinetic studies on the cleavage of oligouridylic acids and poly U by bovine pancreatic ribonuclease A.

Kinetic parameters, Km and Vmax for the transesterification of oligouridylic acid, (Up)nU greater than p (n=0-4), by RNase A were measured spectrophotometrically at pH 7.0 and 25 degrees C. The kinetic parameters, pKm and log Vmax increased with increase in the chain length (n), and seemed to be almost constant with substrates having n greater than or equal to 2. The contribution of each subsite to the binding was estimated according to Hiromi's theory. The subsite affinities for (B1, R1, P1)+(B2, R2, P2) and (B3, R3, P3) are 8.03 kcal and 0.72 kcal/mol, respectively, and those for (B4, R4, P4) and (B5, R5, P5) are less than 0.5 kcal/mol. Therefore, we postulate that the size of the RNase A active site is about 3 nucleotides in length. Transesterification of poly U by RNase A was followed spectrophotometrically. The reaction is markedly influenced by ionic strength. At lower ionic strength, the v0-S curve of poly U cleavage was sigmoidal and cooperative, and it became less cooperative at higher ionic strength. Since the estimated Vmax value for poly U cleavage at ionic strength of 0.1 was more than 20 times larger than that of oligouridylic acids cleavage, we propose a non-specific interaction of poly U anion with cationic groups on the surface of the enzyme, modulating the conformation of active site, and thus increasing the activity at low ionic strength. The interaction decreases at higher ionic strength due to the interaction of counter anions with the non-specific sites.