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Biomedical subjects

E Takai

Publications and source records attributed to E Takai.

At least 37 records · Page 2Linked to original sources

Complications and management of microwave coagulation therapy for primary and metastatic liver tumors.

Microwave coagulation therapy (MCT) has been widely used, both percutaneously and directly, as effective minimal invasive therapy for liver tumors. To facilitate the use of MCT, we describe the complications we have encountered, and their possible management and prophylaxis. MCT was performed for 42 patients with hepatocellular carcinoma (HCC) and for 29 with metastatic liver tumors, following which complications developed in 14.2% and 20.6% of the HCC and metastatic groups, respectively. The complications included abscess, biloma, bleeding, hepatic failure, and dissemination of cancer cells. In the HCC group, the mean value of tumor size and the clinical stage of patients with complications were significantly larger (P = 0.006) and higher (P = 0.032), respectively, than those of patients without complications. The incidence of complications increased significantly when the tumor size was more than 4cm (P = 0.008). Abscesses and bleeding were successfully treated using percutaneous drainage and interventional angiography, respectively, but as the other serious complications were not able to be treated effectively once induced, prophylaxis is important to facilitate MCT. Transcatheter cooling of the intrahepatic bile duct during MCT and the administration of an anticancer agent into the abdominal cavity are recommended to prevent biloma and dissemination, respectively. MCT is indicated for tumors less than 4 cm in diameter to reduce the risk of complications. The prophylaxis and treatment of these complications enhance the safety of MCT.

Aged↗

Comparison of the surgical results of lobectomy with bronchoplasty and pneumonectomy for lung cancer.

BACKGROUND: We retrospectively compared sleeve lobectomy (SL) and pneumonectomy (PN) for lung cancer in terms of surgical complications and postoperative disease-free survival, as well as incidence and pattern of recurrent disease. METHODS: From 1977 to 1993. 29 patients with primary lung cancer underwent sleeve resection at our institution. The pneumonectomy group consisted of 29 cases that had been selected during the same period according to the following criteria: (1) in a tumor located in the upper lobe, there was no invasion within 1 cm from both the carina and the orifice of the middle and the lower lobe bronchus, whereas in a tumor located in the middle or lower lobe, there was no invasion within 1 cm of the orifice of the upper bronchus, (2) there was no invasion to the trunks of the pulmonary vessels, (3) there was no invasion to any other lobes, (4) a complete resection was achieved. RESULTS: No differences were observed between the two groups regarding stage, histological population, or age. The incidence of postoperative complications was 13.7% in the SL group (2 cases each of pneumonia and arrythmia), and 24.1% in the PN group (3 bronchopulmonary fistula, 2 bleeding, 1 instance each of arrythmia and acute cardiac failure, and 2 operation-related deaths) (P < 0.05). The 3-year disease-free survival was 65.7% in SL, 58.8% in PN (no statistical significance in the log-rank test). Recurrent disease was observed in the local regions of three patients in the SL group and six patients in the PN group, and at distant organs of six patients in the SL group and seven in the PN group. CONCLUSIONS: These findings thus suggest that as a curative treatment, lobectomy with bronchoplasty may be a safer procedure than pneumonectomy for lung cancer.

Adult↗

The current status of postoperative complications and risk factors after a pulmonary resection for primary lung cancer. A multivariate analysis.

OBJECTIVE: The purpose of the present study is to identify the current postoperative complications after a pulmonary resection for primary lung cancer and the associated risk factors. METHODS: From 1988 to 1992, 291 patients with primary lung cancer, excluding T4 diseases, consecutively underwent a pulmonary resection at our institute. The observed postoperative complications were divided into non-life-threatening ones (simple arrhythmia, atelectasis, liver dysfunction, etc.) and life-threatening ones (respiratory failure, pyothorax, pneumonia, bronchopleural fistula, cardiac failure, cerebral infarction, myocardial infarction, etc.). Using logistic regression procedures, both univariate and multivariate analyses of the association between various perioperative factors and the incidence of postoperative complications were performed. RESULTS: Non-life-threatening complications occurred in 60 patients (20.6%) while life-threatening ones occurred in 36 (12.4%), and resulted in five in-hospital deaths (1.75%). Multivariate analyses showed that an age of 70 or older, a combined resection, an abnormality on preoperative ECG, and diffusing capacity of carbon monoxide (%DLco) below 70 were all independently associated with an increased non-life-threatening morbidity. On the other hand, an age of 70 or older, the need for a pneumonectomy, and a %DLco below 70 were also independently predominant risk factors for life-threatening morbidity. CONCLUSION: The risk factors for life-threatening morbidity therefore did not completely correspond to those for non-life-threatening morbidity. Since the mortality was quite low, even risk factors for life-threatening morbidity were not solely considered to be a contraindication for a major pulmonary resection.

Adult↗

Tumor-induced hypercalcemia and parathyroid hormone-related protein in lung carcinoma.

BACKGROUND: Although lung carcinoma is the most common cause of tumor-induced hypercalcemia (TIH), the precise incidence of TIH remains obscure. Furthermore, the role of parathyroid hormone-related protein (PTHrP) has not been clearly elucidated. METHODS: This study included 690 consecutive patients who were newly diagnosed as having lung carcinoma between 1989 and 1994 (379 adenocarcinomas, 207 squamous cell carcinomas, 75 small cell carcinomas, and 29 large cell carcinomas). All patients were treated for lung carcinoma and were also periodically monitored for their serum level of calcium (Ca). Hypercalcemia was defined as a serum Ca concentration higher than 11 mg/dL. The serum levels of PTHrP (109-141) were measured by a C-terminal-region-specific radioimmunoassay. RESULTS: TIH was observed in 17 of 690 patients (2.5%). All 17 patients demonstrated an advanced stage of lung carcinoma (Stage III or IV), 10 squamous cell carcinomas, 5 adenocarcinomas, 1 small cell carcinoma, and 1 large cell carcinoma. In 15 patients, the serum level of C-PTHrP (109-141) was substantially high, ranging from 99 pmol/L to 890 pmol/L (normal range, 21-50.7 pmol/L). There was no significant difference in the serum PTHrP level between patients with or without bone metastasis. The reduction of tumor burden decreased both the serum level of PTHrP and that of Ca in parallel. The median survival time after diagnosis of TIH was only 27 days. CONCLUSIONS: TIH in lung carcinoma was most likely attributable to PTHrP, and its occurrence appears to be an ominous prognostic sign.

Adult↗

Tracheal lipoma obstructing the right main bronchus: report of a case.

Most tracheal tumors are malignant, and benign neoplasms are extremely rare. We herein report the case of a 60-year-old woman with a tracheal lipoma obstructing the right main bronchus in whom a preoperative diagnosis was not able to be established. Thus, a thoracotomy was performed followed by complete resection of the tumor including two rings of the tracheal wall. Pathologic examination confirmed that the tumor was a lipoma covered with tracheal epithelium, extending between the cartilage into the outer layer of the trachea.

Bronchial Diseases↗

Skip metastasis to the mediastinal lymph nodes in non-small cell lung cancer.

BACKGROUND: Whether any difference exists in clinical characteristics between resected non-small cell lung cancer with either skip or ordinary mediastinal lymph node metastases (N2 disease) needs to be clarified. METHODS: There were 110 patients with stage IIIA N2 disease. Thirty-three patients demonstrating no metastasis at the hilar nodes [skip (+) group] were compared with the other 77 patients [skip (-) group]. To investigate the extent of nodal involvement, we classified the mediastinal lymph nodes into three regions (superior, inferior, or aortic). RESULTS: There were no significant differences regarding histologic type, T status, or the site of the primary tumors between the skip (+) and the skip (-) N2 groups. In the skip (+) group, mediastinal node metastasis was found in only one region (level 1) in 30 patients (90.9%) and in two regions (level 2) in 3 (9.1%), whereas 28 patients (36.4%) from the skip (-) group revealed mediastinal metastasis at two or three regions (level 2 or 3). The overall survival rate at 5 years after operation was 35% in the skip (+) group and 12.7% in the skip (-) group (p = 0.054). This favorable clinical outcome in the skip (+) group could be explained partially by the higher proportion of patients with level 1 metastases. Furthermore, regarding patients with level 1 disease, the skip (+) group tended to have a better prognosis than the skip (-) group (p = 0.096). CONCLUSIONS: These results suggest that patients with skip mediastinal lymph node metastases represent a unique subgroup of N2 disease.

Carcinoma, Non-Small-Cell Lung↗

The clinical significance of serum soluble interleukin-2 receptors in lung cancer.

It has been recently reported that the soluble interleukin-2 receptor (IL-2R) levels in the sera of cancer patients were higher than those of normal controls. The present study was conducted in order to clarify the clinical significance of serum soluble IL-2R in patients with lung cancer. Using commercially available EIA kits, we measured the serum levels of soluble IL-2R in 102 lung cancer patients and 18 normal controls. The serum level of IL-2R was higher than 100 pM (mean +3 S.D. in the normal controls) in 14 of 58 patients with adenocarcinoma and in 13 of 32 patients with squamous cell carcinoma. In both adenocarcinoma and squamous cell carcinoma, the mean level of soluble IL-2R was higher in advanced stages (Stages IIIA, IIIB and IV) than in early stages (Stages I and II). In contrast, no patients with small cell carcinoma exhibited a serum level of soluble IL-2R higher than 100 pM, whereas almost all of those patients were in advanced-stage diseases. These results first demonstrated that the serum level of soluble IL-2R increased in association with both the disease stage and the histological type in lung cancer.

Adult↗

Alpha-fetoprotein-producing adenocarcinoma of the lung.

We herein present a case of metachronous primary lung cancers, the first of which was adenosquamous cell carcinoma and the second of which was poorly differentiated adenocarcinoma. At the time the second lung cancer was detected 5 years after being operated on for the first cancer, a high level of serum alpha-fetoprotein (AFP) was noticed, but no elevation of other tumor markers was observed. In addition, no liver metastases, chronic liver diseases or other systemic abnormalities were seen either. The serum AFP level was 696 ng/ml, and the profile of lectin affinity showed a tumor-derived pattern. Two weeks after the operation, the serum AFP level decreased to a normal level. An immunohistochemical analysis confirmed that the exact origin of AFP was the tumor tissue. A specimen taken from the first lung cancer was not stained by the same procedures, which thus indicated this case to be a double primary lung cancer.

Adenocarcinoma↗

Interleukin-2 receptors in pulmonary adenocarcinoma tissue.

We previously reported that the serum soluble interleukin-2 receptor (sIL-2R) level increased with the advance of disease stage in non-small cell lung cancer. The present study was thus conducted to investigate the origin of serum sIL-2R in patients with pulmonary adenocarcinoma. Fresh tumor cell suspensions were prepared from surgically resected specimens of pulmonary adenocarcinoma. They were adjusted to a cell density of 5 x 10(5)/ml and then cultured for 24 h at 37 degrees C. The culture supernatants were collected and assayed to determine the sIL-2R levels using an enzyme immunoassay. The resultant cells were thereafter cytocentrifuged onto glass slides and immunochemically stained with anti-human IL-2R alpha (CD25) monoclonal antibody. In three of six cases examined, a substantial level of sIL-2R was identified in the culture supernatants. In four cases, including those three cases with the presence of sIL-2R in the culture supernatants, various proportions of tumor cells were positively stained with the anti-IL-2R alpha antibody. Further examinations revealed that tumor cells expressed IL-2R alpha (CD25) in seven of 16 cases with pulmonary adenocarcinoma. These results thus suggested that the tumor cells did express IL-2R alpha and release sIL-2R in some cases with pulmonary adenocarcinoma.

Adenocarcinoma↗

Use of a pericardial fat pad flap for preventing bronchopleural fistula: an experimental study focusing on the angiogenesis and cytokine production of the fat pad.

An experimental study was conducted to determine whether pericardial fat tissue could induce neovascularization and produce cytokines related to tissue repair. Neovascularization was examined using chick chorioallantoic membranes. Pieces of pericardial fat tissue, omentum, and intercostal muscle were individually placed on a number of chorioallantoic membranes and neovascularization induced by each material was assayed 6 days after the implantation. The intensity of neovascularization was in the order of pericardial fat > or = omentum > muscle. Cytokines, such as interleukin 1 (IL-1) alpha and beta, tumor necrosis factor-alpha (TNF alpha), interferon-gamma (IFN-gamma), and interleukin 6 (IL-6) were assayed in a culture supernatant of pericardial fat tissue. The latter was obtained 24 h after the addition of lipopolysaccharide (LPS) following various incubation times. All cytokines other than IFN gamma are known to play a part in tissue repair, whereas IFN gamma is negatively related to tissue repair because it inhibits fibroblast growth. The pericardial fat tissue incubated with LPS produced a certain amount of IL-1 on day 1, and TNF alpha on days 1 and 8, whereafter these values decreased to an undetectable level. Irrespective of the addition of LPS, a large amount of IL-6 was observed in the supernatant of pericardial fat tissue and it was detectable until day 29. On the contrary, INF gamma was not detected at any assay time. These observations suggest that a pericardial fat pad flap could possibly be beneficial in the prevention of bronchopleural fistula after pulmonary resection.

Adipose Tissue↗

The first site of recurrence after complete resection in non-small-cell carcinoma of the lung. Comparison between pN0 disease and pN2 disease.

In the present study, we assessed whether the pattern of postoperative recurrence of non-small-cell lung cancer differed between patients with pathologic N0 disease and those with pathologic N2 disease. We reviewed 231 patients with pathologic N0 disease and 63 with pathologic N2 disease, who had undergone a complete resection from 1980 to 1990, and investigated the first recurrence sites. Seventy-two patients with pathologic N0 disease and 52 with pathologic N2 disease were found to have had postoperative recurrence. Both pathologic N0 disease and pathologic N2 disease recur frequently in distant organs, and the ratio of distant metastasis to local recurrence did not differ between the two diseases. The brain, lung, and bone were the common initial metastatic sites in both pathologic N0 disease and pathologic N2 disease. The brain was the most frequent site of distant metastasis in patients with pathologic N0 disease, whereas, on the other hand, pulmonary metastasis was observed more frequently than brain metastasis in those with pathologic N2 disease. Despite histologic types, the presence of different patterns of initial metastatic sites between pathologic N0 and pathologic N2 diseases was observed. Our results suggest that the sites of metastasis after resection depend largely on such anatomic factors as drainage routes. Namely, in contrast to pathologic N0 disease, pathologic N2 disease has an additional drainage route, which is from the N2 nodes to the superior vena cava (pulmonary circulation). Therefore, the frequency of pulmonary metastasis may increase in patients with pathologic N2 disease.

Carcinoma, Non-Small-Cell Lung↗

Hepatitis B surface antigen particles of subtypes adw and adr, and compound subtype (adwr) in symptom-free carriers in Japan.

Of sera from 1,878 Japanese blood donors who carried hepatitis B surface antigen (HBsAg), 420 were subtyped as adw (22.4%) and 1,443 as adr (76.8%); only 15 (0.8%) contained HBsAg of subtype ayw or ayr. Sera with HBsAg/adr had higher HBsAg titres than those with HBsAg/adw (geometric mean of haemagglutination titre: 10.1 +/- 2.4 vs. 9.7 +/- 2.4, p less than 0.01), and a higher prevalence of hepatitis B e antigen (24% vs. 13%, p less than 0.001). Carriers of HBsAg/adr progressively predominated over those of HBsAg/adw with increasing age. Of sera from 1,863 carriers of HBsAg/adw or HBsAg/adr, 182 (9.8%) contained HBsAg particles with both subtypic determinants in the w/r allele. The presence of w and r determinants on the same particles was ascertained by sandwiching them between monoclonal antibody with the specificity for w and that with the specificity for r. HBsAg particles of compound subtype (adwr) were found more often in sera with hepatitis B e antigen than those without it (145/403 [36.0%] vs. 37/1,460 [2.5%], p less than 0.001). Sera with HBsAg/adwr particles had HBsAg titres higher than those without them (12.4 +/- 1.9 vs. 9.7 +/- 2.3, p less than 0.001). HBsAg/adwr particles arise from phenotypic mixing of the S-gene product of wild-type virus and that of mutants with point mutations for subtypic changes. The results obtained indicated that HBV strains of subtype adr have a higher replicative activity than those of adw, and suggested that mutations in the S gene for subtypic changes would be associated with an active replication of hepatitis B virus.

Adult↗

Synthetic oligopeptides bearing a common or subtypic determinant of hepatitis B surface antigen.

Two determinants of hepatitis B surface Ag (HBsAg), identified by mAb raised against polypeptide components, were characterized immunochemically. One was expressed on HBsAg irrespective of the four major subtypes, i.e., adw, adr, ayw, and ayr, whereas the other was subtypic but not identical to any of d, y, w, and r determinants. The common determinant was generated by a synthetic pentadecapeptide with a sequence of Thr-Thr-Ser-Thr-Gly-Pro-Cys-Lys-Thr-Cys-Thr-Ile-Pro-Ala-Gln representing amino acids 115-129 of the S gene product, and detected invariably in 366 HBsAg samples in sera from asymptomatic carriers in Japan. The activity of the S gene product, as well as the peptide (115-129), to bind with the mAb was not affected by alkylation alone, but was completely lost after reductive alkylation. The antigenic activity was lost when the S gene product was severed between Lys122 and Thr123 by trypsin. A microconformation maintained by the -Cys121-Cys124 bond, therefore, would be required for the common determinant. The other mAb identified an epitope of HBsAg that was mimicked by a synthetic tetradecapeptide with a sequence of Thr-Cys-Thr-Ile-Pro-Ala-Gln-Gly-Thr-Ser-Met-Phe-Pro-Ser, representing amino acids 123-136 of the S gene product. Among 16 HBsAg samples with known S gene sequences, 5 with Ile126 possessed this subtypic determinant, but the remaining 11 with Thr126 did not. The 5 hepatitis B virus genomes encoding the subtypic determinant differed less than 5.6% from each other in the entire nucleotide sequence, but by 8.0% or more from any of the other 11 genomes without the capacity to encode it.

Alkylation↗

Antigenic sites on the arginine-rich carboxyl-terminal domain of the capsid protein of hepatitis B virus distinct from hepatitis B core or e antigen.

The capsid protein of hepatitis B virus (P19) is made of 183 amino acids and carries the antigenic sites of hepatitis B core antigen (HBcAg) and hepatitis B e antigen (HBeAg) on the amino-terminal domain. The carboxyl-terminal domain of P19 (amino acids 150-183) is arginine-rich (47%) and faces the interior of the nucleocapsid for the binding with DNA. Monoclonal antibody was raised against an antigenic site on this protamine-like region of P19, which was distinct from HBcAg or HBeAg sites, and the novel antigenic site(s) was provisionally designated as hepatitis B inner core antigen (HBicAg). When P19 in a low concn (150 ng/ml) was immobilized on the solid surface, HBicAg sites were preserved, while HBcAg or HBcAg sites were no longer available on it. This allowed the detection of antibodies against HBicAg (anti-HBic), by sandwiching them between immobilized P19 and anti-IgG labeled with horseradish peroxidase. Anti-HBic was detected in sera from HBsAg carriers, typically those seropositive for antibody to HBeAg. A synthetic arginine-rich decapeptide, with a sequence of Arg-Arg-Arg-Gly-Arg-Ser-Pro-Arg-Arg-Arg, representing amino acids 150-159 of P19 and conserved in the majority of reported hepatitis B virus, absorbed the activity to bind with P19 in seven (44%) out of 16 sera containing anti-HBic. These results indicate that the decapeptide carries an HBicAg epitope and the remaining amino acid sequence of the arginine-rich carboxyl terminal domain (160-183) may be responsible for the other HBicAg epitopes.

Amino Acid Sequence↗

A synthetic peptide coded for by the pre-S2 region of hepatitis B virus for adding immunogenicity to small spherical particles made of the product of the S gene.

Small spherical particles produced in the non-permissive phase of hepatitis B virus infection, when the viral genome is integrated into the chromosome of hosts, are rich in the product of the S gene, but poor in the product of the pre-S2 region. For the purpose of adding immunogenicity to spherical particles deficient in the pre-S2 region product, they were conjugated with a synthetic peptide of 19 amino acid residues. The peptide reproduced a hydrophilic area of the pre-S2 region product encoded by viral genomes of subtypes adr, ayw and ayr. The spherical particles supplemented with the pre-S2 peptide raised antibody to the pre-S2 region product in mice, in addition to antibody to the product of the S gene. Antibody to pre-S2 region product, prepared from sera of immunized mice by absorption with the S gene product, bound to spherical particles bearing pre-S2 region product, irrespective of adr, adw, ayw or ayr subtype, and agglutinated hepatitis B virions in immune electron microscopy. Based on the results obtained, the synthetic peptide may prove useful in adding protective efficacy to small spherical particles poor in pre-S2 region product.

Absorption↗

A solid-phase enzyme immunoassay for the determination of IgM and IgG antibodies against translation products of pre-S1 and pre-S2 regions of hepatitis B virus.

The envelope of hepatitis B virus is coded for by pre-S1, pre-S2 regions and the S gene. A method was developed to determine antibody to the product of pre-S1 region (anti-pre-S1) and antibody to the product of pre-S2 region (anti-pre-S2), either of IgM or IgG class, by a solid-phase enzyme immunoassay. For the determination of anti-pre-S1, tubular particles containing translation products of pre-S1, pre-S2 regions and the S gene were broken into constituent envelope polypeptides and immobilized on a solid support. Serums were absorbed with spherical particles containing translation products of pre-S2 region and the S gene, obtained from plasma positive for hepatitis B e antigen (HBeAg) and deprived of particles carrying pre-S1 product by an affinity column. They were then tested for the binding with tubular polypeptides fixed on a solid support, and the bound antibody representing anti-pre-S1 was detected by monoclonal antibody to human IgM/mu or IgG/gamma labeled with horseradish peroxidase. For the determination of anti-pre-S2, test serums were absorbed with spherical particles containing the product of the S gene, obtained from plasma positive for antibody to HBeAg and deprived of particles bearing pre-S2 product by an affinity column. They were then tested for the binding with polypeptides, fixed on a solid support, composed of products of pre-S2 region and the S gene. The assay was applied to the determination of anti-pre-S1 and anti-pre-S2 of IgM or IgG class in asymptomatic carriers and in persons who had recovered from infection with hepatitis B virus.

Antibodies, Monoclonal↗

Polypeptides coded for by the region pre-S and gene S of hepatitis B virus DNA with the receptor for polymerized human serum albumin: expression on hepatitis B particles produced in the HBeAg or anti-HBe phase of hepatitis B virus infection.

There are four polypeptides coded for by the region Pre-S and gene S on DNA of hepatitis B virus that carry the receptor for polymerized human serum albumin (poly-HSA), i.e., P31 and P39, as well as their glycosylated counterparts P35 and P43. With the use of monoclonal antibodies directed to Pre-S(1) sequence and Pre-S(2) sequence (bearing the receptor for poly-HSA), the content of these polypeptides, as well as their expression on the surface, was determined for hepatitis B particles of various categories. P39 and P43, carrying both Pre-S(1) and Pre-S(2) sequences, were contained abundantly in Dane and tubular particles, and to a much lesser extent in small spherical particles, all of which were purified from plasma containing hepatitis B e antigen (HBeAg). P31 and P35, carrying Pre-S(2) but not Pre-S(1) sequence, were contained comparably in these three categories of hepatitis B particles. In remarkable contrast, small spherical particles derived from plasma containing antibody to HBeAg were very low in the content of any Pre-S polypeptides. P31 and P39 showed higher activities for poly-HSA receptor than their glycosylated versions. When Dane particles were digested with trypsin, the poly-HSA receptor was deprived in parallel with the loss of antigenicity for Pre-S(2) sequence. The antigenicity for Pre-S(1) sequence was much less affected, and that for the product of gene S was virtually unchanged by the digestion.

Amino Acid Sequence↗