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Biomedical subjects

Takeshi Shiraishi

Publications and source records attributed to Takeshi Shiraishi.

At least 19 recordsLinked to original sources

Postradiation sarcoma of the chest wall: report of two cases.

Postradiation sarcoma is a rare late complication of external radiotherapy. We herein present two cases with this disease. A 54-year-old man had undergone a lobectomy and chest wall resection for Pancoast type lung cancer 7 years previously. He had undergone irradiation with a total dose of 50 Gy. Computed tomography (CT) demonstrated a tumorous expansion of the right lateral thoracic wall. A pathological examination confirmed a diagnosis of osteosarcoma. A 60-year-old woman had undergone a resection of the lateral chest wall mass, which was diagnosed to be Hodgkin's disease in 1991. Chemotherapy was given postoperatively. A tumorous lesion arose again and irradiation was performed with a total dose of 110 Gy. In 2000, two tumors appeared in the irradiation field. A pathological examination showed a sarcoma with divergent differentiation. In 2003, a tumor recurred and was diagnosed to be a liposarcoma. Patients who have received radiotherapy should therefore be followed up while taking into consideration the possible development of postradiation sarcoma.

Biopsy, Fine-Needle↗

Risk analysis in resection of thoracic esophageal cancer in the era of endoscopic surgery.

BACKGROUND: Surgical outcomes after thoracoscopic esophagectomy were compared with those after open esophagectomy, and the prognostic values of factors potentially related to mortality and morbidity were evaluated. METHODS: We performed a retrospective chart review of 153 patients who underwent esophagectomy for thoracic esophageal cancer. The thoracic surgical procedures were categorized into the following three groups: esophagectomy under standard thoracotomy (n = 37), assisted thoracoscopic esophagectomy with utility minithoracotomy (n = 38), and complete thoracoscopic esophagectomy (n = 78). Mortality and morbidity were compared among the three groups. Then, in a separate multivariate analysis, data on 14 potentially prognostic variables were extracted, and the relation to postoperative outcomes was examined. RESULTS: Respiratory complications were the most frequent complications in all three groups, and their rate of occurrence was not significantly among the three groups. The 30-day and in-hospital mortality rates were significantly higher in the open group than in the other groups. Multivariate analysis demonstrated that patient age, sex, induction chemoradiation, and forced expiratory volume were independently significant contributing factors for respiratory complications, while the serum total protein concentration and open esophagectomy were significant factors for in-hospital mortality. CONCLUSIONS: Our results demonstrated that respiratory complications are still the main cause of operative morbidity when using the thoracoscopic esophagectomy protocol and that use of the thoracoscopic procedure does not decrease the risk of respiratory complications. The use of the thoracoscopic procedure improved postoperative in-hospital mortality. The advantages of thoracoscopic esophagectomy should be investigated further. At this point in time, however, thoracoscopic esophagectomy can be considered a feasible, safe, and advantageous surgical option.

Endoscopy↗

A novel method for preserving human lungs using a super-cooling system.

PURPOSE: To ensure the suitable preservation of isolated lungs, a super-cooling system was used to cool water to temperatures as low as -5 degrees C without freezing. DESCRIPTION: After lung tissues were obtained from patients with lung cancer, they were kept at -5 degrees C or 4 degrees C for as many as 5 days, and then they were histologically and biochemically examined. To evaluate biochemical stability, tissues after storage were passively sensitized with immunoglobulin E and then incubated with anti-immunoglobulin-E antibody. EVALUATION: Although tissues preserved at -5 degrees C for 5 days had an almost normal appearance with intact cilia on bronchial epithelium and normal endothelium, tissues stored at 4 degrees C showed degradation of these structures. Single-stranded DNA, a sign of DNA cleavage, was frequently noted in tissues stored at 4 degrees C, but only rarely observed at -5 degrees C. A significant amount of cysteinyl-leukotrienes was generated from tissues stored at -5 degrees C for 3 days, but there was no response to antibody stimulation from tissues stored at 4 degrees C. CONCLUSIONS: Super-cooling systems may provide useful applications as a novel preserving method.

Aged↗

Video-assisted thoracoscopic surgery lobectomy for c-T1N0M0 primary lung cancer: its impact on locoregional control.

BACKGROUND: The outcomes of a video-assisted thoracoscopic surgery lobectomy for lung cancer, with a special focus on its locoregional control, were compared with a conventional lobectomy. METHODS: We performed a retrospective review of 160 patients who had undergone a lobectomy either by means of thoracoscopic surgery (n = 81) or a standard thoracotomy (n = 79) for clinical T1N0M0 nonsmall-cell lung cancer. The overall, disease-free, and locoregional recurrence-free survival were compared. In a separate multivariate analysis, the ability of numerous clinical and surgical factors, including the surgical approach, to predict locoregional recurrence was investigated. RESULTS: The total recurrence of the primary disease occurred in 28 cases (12 locoregional and 14 distant). In the 12 documented local recurrences, 8 belonged to the thoracoscopic surgery group and 4 were in the standard thoracotomy group, without significant differences (p = 0.229). The overall 5-year survival rates associated with the thoracoscopic and standard procedure were 89.1% and 77.7%, respectively (p = 0.149). No significant differences in the disease-free or locoregional recurrence-free survivals were observed between the groups. The results of a multivariate analysis for the incidence of total and locoregional recurrence demonstrated that two covariates, lymph node metastasis and the surgical side (right or left lung), were significant factors for both total and locoregional recurrence. No significant relationship was found between thoracoscopic surgery or standard thoracotomy, and the incidence of locoregional recurrence. CONCLUSIONS: Our findings suggest that thoracoscopic surgery is not inferior regarding its ability to achieve locoregional control in comparison with the standard procedure.

Aged↗

Human pulmonary dirofilariasis: a case report and review of the recent Japanese literature.

Human pulmonary dirofilariasis is a rare zoonotic infection caused by the dog heartworm Dirofilaria immitis, which is transmitted via a vector/intermediate host, generally the mosquito. The authors present a case of histologically diagnosed human pulmonary dirofilariasis, in which the lesion was resected using video-assisted thoracic surgery (VATS). The authors also review 24 cases of such zoonosis reported in Japan from 1998 to 2004. Of these 24 patients with human pulmonary dirofilariasis, 12 (50%) were men (mean age 54 years, range 29-80 years) and 67% were asymptomatic. Most patients (83%) had a solitary lung nodule, 95% of the lesions were <30 mm and 13% had a pleural effusion. VATS was performed to obtain a histopathological diagnosis in the majority (61%) of patients whom the authors reviewed. VATS would appear to be the best method for diagnosing pulmonary dirofilariasis.

Aged↗

[Inflammatory myofibroblastic tumor of the trachea; report of a case].

A 45-year-old female with a complaint of dyspnea was admitted to our hospital. Computed tomography (CT) and bronchoscopy revealed a 10 mm intraluminal polypoid tumor with a smooth surface and hemorrhagic tendency located in the tracheal wall 2.0 cm distal from the vocal cords. For pathological diagnosis, airway management and hemorrhage control, tumor resection was performed using a rigid bronchoscope and neodymium yttrium aluminum garnet (Nd-YAG) laser under general anesthesia. Histologically, the tumor was diagnosed as an inflammatory myofibroblastic tumor of the trachea. Inflammatory myofibroblastic tumor is typically a benign tumor that develops in such sites as the lung, stomach, and mesentery. To the best of our knowledge, this is the first reported case of an inflammatory myofibroblastic tumor arising in the trachea.

Female↗

Familial cancer associated with a polymorphism in ARLTS1.

BACKGROUND: The finding of hemizygous or homozygous deletions at band 14 on chromosome 13 in a variety of neoplasms suggests the presence of a tumor-suppressor locus telomeric to the RB1 gene. METHODS: We studied samples from 216 patients with various types of sporadic tumors or idiopathic pancytopenia, peripheral-blood samples from 109 patients with familial cancer or multiple cancers, and control blood samples from 475 healthy people or patients with diseases other than cancer. We performed functional studies of cell lines lacking ARLTS1 expression with the use of both the full-length ARLTS1 gene and a truncated variant. RESULTS: We found a gene at 13q14, ARLTS1, a member of the ADP-ribosylation factor family, with properties of a tumor-suppressor gene. We analyzed 800 DNA samples from tumors and blood cells from patients with sporadic or familial cancer and controls and found that the frequency of a nonsense polymorphism, G446A (Trp149Stop), was similar in controls and patients with sporadic tumors but was significantly more common among patients with familial cancer than among those in the other two groups (P=0.02; odds ratio, 5.7; 95 percent confidence interval, 1.3 to 24.8). ARLTS1 was down-regulated by promoter methylation in 25 percent of the primary tumors we analyzed. Transfection of wild-type ARLTS1 into A549 lung-cancer cells suppressed tumor formation in immunodeficient mice and induced apoptosis, whereas transfection of truncated ARLTS1 had a limited effect on apoptosis and tumor suppression. Microarray analysis revealed that the wild-type and Trp149Stop-transfected clones had different expression profiles. CONCLUSIONS: A genetic variant of ARLTS1 predisposes patients to familial cancer.

ADP-Ribosylation Factors↗

Inflammatory myofibroblastic tumor of the posterior mediastinum: an older adult case with anaplastic lymphoma kinase abnormalities determined using immunohistochemistry and fluorescence in situ hybridization.

Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm that usually occurs in children and young adults. Anaplastic lymphoma kinase (ALK) abnormalities in IMT, determined using immunohistochemistry and/or molecular genetic studies, including fluorescence in situ hybridization (FISH), have almost been limited to children and young adults. In elderly cases of IMT, these ALK abnormalities are very rare. We report on a case of IMT arising in the posterior mediastinum of a 59-year-old Japanese man that showed ALK abnormalities determined using immunohistochemistry and FISH, suggesting the neoplastic nature of a subset of IMTs in older patients similar to those in younger ones and the presence of an additional mechanism(s) that allows them to start to grow late.

Anaplastic Lymphoma Kinase↗

Minimally invasive esophagectomy for stage I and II esophageal cancer.

BACKGROUND: To evaluate whether thoracoscopic and video-assisted dissections are appropriate modalities, we assessed the mortality, morbidity, and survival of patients who underwent a thoracoscopic esophagectomy for esophageal cancer. METHODS: Between November 1995 and December 2004, thoracoscopic and video-assisted esophagectomies were performed on 112 (72.7%) patients out of 154 who underwent surgical resection for thoracic and abdominal esophageal cancer. The histologic type of cancer was squamous cell carcinoma in 109 (97.4%) patients and adenocarcinoma in 3 (2.6%). RESULTS: Intraoperative complications occurred in 4 (3.6%) patients: tracheal injury in 3 (2.7%) and azygos vein injury in 1 (0.8%). The 30-day mortality rate was 0.8%. Early postoperative complications occurred in 29 (25.9%) patients including the following: recurrent nerve palsy in 10 (8.9%), respiratory complication in 7 (6.3%), anastomotic leakage in 9 (8.0%) with major leakage requiring reanastomosis in 4 (3.6%) of these 9, and chylothorax in 3 (2.7%). Induction chemoradiotherapy, preoperative concomitant disease, and reconstruction using the colon did not increase morbidity. Port site recurrence occurred in 3 (2.7%) patients. The overall 5-year survival rate was 52%. For stage I disease, the 5-year survival rate of patients was 87.2%. In stage II disease, it was 70.2%. CONCLUSIONS: Thoracoscopic and video-assisted esophagectomy are considered feasible and safe options for the treatment of esophageal cancer, but further investigation is necessary. The survival of patients with stage I and II disease is satisfactory at the present time.

Adenocarcinoma↗

Prevention of acute lung allograft rejection in rat by the janus kinase 3 inhibitor, tyrphostin AG490.

BACKGROUND: Tyrphostin AG490 (AG490) potently and selectively inhibits gammac/Janus kinase 3-dependent signaling pathways, including downstream Stat5a/b activation and subsequent T cell proliferation by alloantigen stimulation. We evaluated the effects of AG490 on acute rat lung allograft rejection. METHODS: A 7-day course of an intraperitoneal (IP) injection with 10 mg/kg, 15 mg/kg, or 20 mg/kg AG490 was administered to inhibit the rejection of orthotopically transplanted Brown Norway (RT1n) rat lung allografts in Fischer 344 (RT1(1vl)) rat recipients. The progression of allograft rejection was evaluated by X-ray with a semi-quantitative scoring system and was evaluated histologically with a semi-quantitative rejection scoring system for acute lung allograft rejection. Moreover, to determine whether AG490 regulates CD4+ T cell differentiation during acute rejection, flow cytometry was used to investigate Th1 (interferon-gamma) and Th2 (interleukin [IL]-4, IL-10) intracellular cytokine profiles and the CD4+CD25+ T cell population in recipient splenocytes. RESULTS: Results of radiology and histology confirmed that treatment with AG490 significantly suppressed acute lung allograft rejection. Furthermore, the splenocytes of the AG490-treated recipients had significantly lower production of interferon-gamma and relatively higher production of IL-10, implying that a Th2 shift was induced by AG490. In addition, AG490-treated recipients had a significantly increased population of CD4+CD25+ T cells in their splenocytes on Day 6 after transplantation. CONCLUSION: These findings suggest that treatment with AG490 prevents acute lung allograft rejection in rats. The effects of AG490 may contribute to development of CD4+CD25+ T cells and a Th2 shift of CD4+ T cells.

Acute Disease↗

Possible mechanism of metastasis in lung adenocarcinomas with a micropapillary pattern.

Micropapillary differentiation in adenocarcinomas has recently been associated with poor prognosis because these tumors are more likely to metastasize. However, no clear explanation exists as to why the presence of a micropapillary pattern is associated with metastasis. A case of primary lung adenocarcinoma with a prominent micropapillary pattern is presented here, with special reference to the immunohistochemical expression of the E-cadherin-mediated system and IQGAP1. Histologically, the tumor was diagnosed as a moderately differentiated papillary adenocarcinoma, showing an extensive micropapillary pattern, with intrapulmonary metastases, pulmonary disseminations, lymphovascular invasions, and lymph node metastases. Immunohistochemically, positive staining for the adhesion molecules E-cadherin, alpha-catenin, and beta-catenin was detected in both the micropapillary and non-micropapillary areas, whereas IQGAP1 was detected in the micropapillary, but not in the non-micropapillary, area. The adhesive function of E-cadherin depends on the integrity of the entire cadherin-catenin-actin network, and thus the expression of IQGAP1 may lead to adherens junction disassembly, and consequently, the release of carcinoma cells organizing in a micropapillary pattern. This is the first report to suggest correlation between adenocarcinoma with a micropapillary pattern and the presence of adhesion molecules, and offers an intriguing first glimpse on the role of the micropapillary pattern in the process of metastasis.

Adenocarcinoma↗

Stenting for critical airway stenosis under percutaneous cardiopulmonary support.

Airway stenting for severe central airway stenosis is inherently a dangerous procedure. There is the risk of critical airway obstruction due to bleeding, tumor debris, and airway perforation during the procedure. Once such situations occur, percutaneous cardiopulmonary support (PCPS) can be one of the most valuable rescue options to prevent critical hypoxic complications. At our institute, four of 49 patients who received stenting or other airway intervention required PCPS support (8%). Two of these cases required PCPS to be performed in an emergency setting during the procedure while the procedure was elective in the other 2. All procedures were performed effectively and safely without any complications caused by PCPS, including massive airway bleeding due to anticoagulant treatment. Patients were able to be weaned off PCPS uneventfully. PCPS is considered to be a valuable procedure in remedying critical hypoxic situations during airway intervention.

Adolescent↗

Results of video-assisted thoracic surgery for stage I/II non-small cell lung cancer.

OBJECTIVE: The best indicators for VATS are not well known. Therefore, we review here a series of patients who underwent VATS lobectomy and segmentectomy at our hospital, and we attempt to identify the factors that influence the survival of VATS patients and the backgrounds of such patients. METHODS: A thoracoscopic curative approach was attempted in 140 patients (100 lobectomy, 40 segmentectomy) from January 1994 to December 2002. We retrospectively reviewed the VATS patients with non-small cell lung cancer (NSCLC). All patients were subject to lobectomy or segmentectomy, including dissection of hilar and mediastinal lymph nodes that were in pathological stage (p-Stage) I or II. Our VATS approach was a hybrid technique, employing three ports and a small (7 cm diameter) utility thoracotomy to allow access for the instrument and a view. RESULTS: The Kaplan-Meier probabilities of survival at 5 years were VATS, 77.3%. According to a univariate analysis of survival curves, the significant prognostic factors (P < 0.05) in the patients with VATS in p-Stage I and II were gender, type of histology, and T factor. In addition, the grades of differentiation, surgical procedure (lobectomy vs. segmentectomy), and extent of metastasis to the hilar lymph node (N0 vs. N1) in VATS were not found to be significant prognostic factors. A multivariate prognostic factor in VATS showed that the histologic cell type, gender, and T factor were predominant. All of the VATS cases that included these three favorable factors (adenocarcinoma, T1, female) were alive. CONCLUSION: Stringent selection of candidates for VATS in NSCLC at pathological stages I and II could be an acceptable and valuable approach.

Aged↗

A gene-expression signature can quantify the degree of hepatic fibrosis in the rat.

BACKGROUNDS/AIMS: A more accurate and objective quantification of hepatic fibrosis would provide clinically useful information for the monitoring of chronic liver disease progression and therapy recommendation. METHODS: Using a cDNA microarray of 14,814 clones, we analyzed the gene-expression profiles of fibrotic livers in a rat model. RESULTS: We identified 750 up- and 345 down-regulated genes by combining a signal-to-noise score and a random permutation test (P<0.01). The functions of these genes provided insight into the underlying molecular mechanisms of both structural remodeling and functional deficits in cirrhosis. To quantify the extent of liver fibrosis, we have generated for the first time a 'genetic fibrosis index' based on gene-expression profiling of 95 genes by combining a Pearson correlation coefficient and a 'leave-one-out' cross-validation procedure. This technique based on a supervised learning analysis correctly quantified the various degrees of fibrosis in both 20 training samples (R(2)=0.829, P<0.001) and 6 test samples (R(2)=0.822, P<0.05). CONCLUSIONS: Our method will assist researchers in identifying rational targets for intervention and might help clinicians to objectively monitor the severity of liver fibrosis.

Animals↗

Prediction of 5'-deoxy-5-fluorouridine sensitivity in colorectal cancer cases by thymidine phosphorylase activity and preliminary identification of susceptibility related genes.

We confirmed that the enzyme activity of thymidine phosphorylase (TP) can substitute for 5'-deoxy-5-fluorouridine (5'-dFUR) sensitivity in clinical colorectal cancer (CRC) tissues. Moreover, the idenfication of susceptible genes other than TP will be desired for prediction or treatment of 5'-dFUR. We initially established conditions for the MTT assay system in vivo to compare the growth inhibition rate and TP activity in 18 cases of CRC. TP activity levels were concordant with 5'-dFUR sensitivity in the CRCs (p<0.05). In 18 CRC cases, 4 cases of high sensitivity and 3 cases of low sensitivity to 5'-dFUR were compared to analyze expression profiles of 9437 genes on cDNA microarray chips. As a result, a cluster of genes related to the sensitivity were identified and another cluster of genes related to the insensitivity of 5'-DFUR were also listed. We determined that TP expression can precisely predict 5'-dFUR sensitivity in CRCs and found susceptibility related genes.

Aged↗

Fragile site orthologs FHIT/FRA3B and Fhit/Fra14A2: evolutionarily conserved but highly recombinogenic.

Common fragile sites are regions that show elevated susceptibility to DNA damage, leading to alterations that can contribute to cancer development. FRA3B, located at chromosome region 3p14.2, is the most frequently expressed human common fragile site, and allelic losses at FRA3B have been observed in many types of cancer. The FHIT gene, encompassing the FRA3B region, is a tumor-suppressor gene. To identify the features of FHIT/FRA3B that might contribute to fragility, sequences of the human FHIT and the flanking PTPRG gene were compared with those of murine Fhit and Ptprg. Human and mouse orthologous genes, FHIT and Fhit, are more highly conserved through evolution than PTPRG/Ptprg and yet contain more sequence elements that are exquisitely sensitive to genomic rearrangements, such as high-flexibility regions and long interspersed nuclear element 1s, suggesting that common fragile sites serve a function. The conserved AT-rich high-flexibility regions are the most characteristic of common fragile sites.

Acid Anhydride Hydrolases↗

MAL gene expression in esophageal cancer suppresses motility, invasion and tumorigenicity and enhances apoptosis through the Fas pathway.

We isolated the MAL (T-lymphocyte maturation associated protein) gene from differentially expressed products of esophageal epithelium relative to esophageal carcinoma tissues. The Mal protein has been demonstrated as being a component of the protein machinery for apical transport in epithelial polarized cells. In this study, we describe the reduced expression of MAL in all 39 cases of esophageal carcinoma tested and 60 other human carcinomas. MAL gene transcription was induced in three out of 13 esophageal carcinoma cell lines by treatment with the demethylating agent 5-aza-2'-deoxycytidine (DAC), and in nine additional cell lines by simultaneous treatment with trichostatin A, an inhibitor of deacetylation, and DAC. We established a stable MAL gene transfectant whose expression was regulated by subcutaneous doxycycline injection in nude mice. Tumor growth was suppressed in cells expressing TE3-MAL compared with TE3 parent cells or cells not expressing TE3-MAL with doxycycline injection (20 microg/body) (P<0.01). Additionally, the TE3-MAL transfectant cells exhibited decreased cellular motility, a G1/S transition block and increased levels of apoptosis, concomitant with increased expression of Fas receptor in vitro. The apoptotic staining in MAL-expressing tumors was confirmed by TUNEL assay. Therefore, we conclude that expression of MAL was frequently decreased or diminished in gastrointestinal tract cancers, and that Mal expression confers reduced tumorigenicity in vivo to tumor TE3 cells through the induction of apoptosis via the Fas signaling pathway.

Animals↗

Phase II clinical study of photodynamic therapy using mono-L-aspartyl chlorin e6 and diode laser for early superficial squamous cell carcinoma of the lung.

Photofrin is the most commonly used photosensitizer for photodynamic therapy (PDT). The major side effect of Photofrin is cutaneous photosensitivity. A second generation photosensitizer, mono-L-aspartyl chlorin e6 (NPe6) has shown anti-tumor efficacy and rapid clearance from skin. Therefore, we conducted a phase II clinical study to investigate the anti-tumor effects and safety of NPe6 in patients with early superficial squamous cell carcinoma of the lung. Enrollment criteria consisted of endoscopically evaluated early stage lung cancer with normal chest X-ray and CT images, no lymph node or distant metastasis. Tumors were located no more peripherally than subsegmental bronchi, the peripheral margin had to visible, and the tumor size had to not more than 2 cm in diameter. The histologic type of the tumor had to squamous cell carcinoma. Laser irradiation (100 J/cm2) using a diode laser was performed at 4 h after administration of NPe6 (40 mg/m2). Among 41 patients with 46 lesions, 40 with 45 lesions were eligible for safety evaluation, and 35 patients with 39 lesions were judged as eligible for efficacy evaluation. No serious adverse drug reactions were observed. Disappearance of skin photosensitivity was recognized within 2 weeks in 28 of 33 patients (84.8%) and in all the other seven patients first tested at 15-18 days. Complete response (CR) was seen in 84.6% of lesions (82.9% of patients). This study demonstrated excellent anti-tumor effects and safety, especially low skin photosensitivity in patients with early stage lung cancer. PDT using the second generation photosensitizer NPe6 and a diode laser will likely become a standard modality of PDT for central type early superficial squamous cell carcinoma of the lung.

Aged↗