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Biomedical subjects

Katsunobu Kawahara

Publications and source records attributed to Katsunobu Kawahara.

At least 19 recordsLinked to original sources

PIK3CA and TFRC located in 3q are new prognostic factors in esophageal squamous cell carcinoma.

BACKGROUND: Amplification of the chromosome 3q seems to occur frequently in esophageal squamous cell carcinoma (ESCC). This study analyzed the clinical effect of messenger RNA (mRNA) expression for PIK3CA (the gene that encodes phosphatidylinositol-3 kinase catalytic alpha-polypeptide) and TFRC (the gene that encodes the transferrin receptor), which map within chromosome 3q in ESCC. METHODS: Formalin-fixed, paraffin-embedded ESCC tissues were examined. Total RNAs were extracted, and reverse transcription products were subjected to polymerase chain reaction amplification of beta-actin, PIK3CA, and TFRC. RESULTS: Expression of beta-actin mRNA was detected in 67 (55.8%) of 120 samples, with PIK3CA mRNA expression in 22 (32.8%) of these 67 samples and TFRC mRNA expression in 15 (22.4%) of the 67 samples. PIK3CA mRNA expression correlated with regional lymph node metastasis (P = .04). TFRC mRNA expression correlated with distant metastasis (P = .04). Patients with positive results for either PIK3CA or TFRC mRNA displayed a significantly worse prognosis than patients with negative results (PIK3CA, P = .045; TFRC, P = .009). TFRC mRNA expression represented an independent prognostic factor in multivariate analysis (P = .0233), but PIK3CA did not (P = .7585). CONCLUSIONS: PIK3CA and TFRC mRNA represent prognostic factors in patients with ESCC. TFRC mRNA offers an independent prognostic factor, and expression may have clinically important implications.

Aged↗

Consecutive left lower sleeve lobectomy and left S3 segmentectomy for a patient with node-negative double lung cancer.

A 74-year-old-man visited our hospital because of a dry cough. A chest radiograph showed a nodular shadow measuring 2.0 cm diameter in the left S3 segment and a tumor shadow measuring 3.5 cm diameter in the left S6 segment; no mediastinal lymph node enlargement was observed. The bronchoscopic findings revealed direct invasion of the tumor into the spur of the left B6 branch, but no abnormal findings were found in the upper bronchus. An endobronchial biopsy revealed squamous cell carcinoma in a left B6 biopsy specimen and adenocarcinoma in the left S3 lung biopsy specimen. The patient's lung function was not good, and an arterial blood gas analysis was Po2 69.3mmHg and PCO2 48.5 mmHg. We performed left lower sleeve lobectomy and left S3 segmentectomy simultaneously. He was discharged uneventfully on the 14th day after the operation, and he has since been doing fine without lung caner recurrence for 3 years after surgery.

Adenocarcinoma↗

Comparison of surgical outcome using the prediction scoring system of E-PASS for thoracic surgery.

OBJECTIVE: The purpose of this study was to determine if our predictive scoring system, E-PASS, can estimate the surgical outcome. METHODS: We conducted a multicenter cohort study for 3 years in four national hospitals. A consecutive series of 731 patients who underwent elective thoracic operations were analyzed. The preoperative risk score (PRS) and the comprehensive risk score (CRS) of the E-PASS were determined preoperatively and immediately after the operation, respectively. The cost of the surgical admission and the severity of the postoperative complications were recorded at the time of discharge. RESULTS: The CRS significantly correlated with the severity of the postoperative complications (rs = 0.728, P < 0.0001) and the charge (rs = 0.530, P< 0.0001). When the estimated/real morbidity ratio (MR) among the hospitals was compared, it varied from 0.16 to 0.59. A significant increase in the cost was observed according to the CRS. CONCLUSION: The E-PASS scoring system may be useful for standardizing the patient population and surgical severity to compare the surgical outcome.

Adolescent↗

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↗

Reduced expression of p63 has prognostic implications for patients with esophageal squamous cell carcinoma.

The p63 gene is a member of the p53 family that plays a role in cell differentiation, development and carcinogenesis. The relationship between p63 expression and the prognosis of esophageal squamous cell carcinoma (ESCC) remains unknown. The present study examines the clinical impact of p63 in patients with ESCC. Resected specimens from 180 patients with ESCC were immunostained for p63 and p53. After establishing a cut-off value for p63 expression, we statistically examined its clinical impact and relationship to p53 expression. At a 50% cut-off value for p63 expression, the 5-year overall survival was significantly longer in p63-positive (46.4%) than -negative patients (11.1%, p=0.05). Among the 180 ESCC patients, 171 (95.0%) were p63 immunoreactive and only 9 (5.0%) were negative. The correlation between p63 status and clinicopathological parameters was not significant, although p63-negativity tended to correlate with distant metastasis (p=0.06) and clinical stage (p=0.08). Univariate analysis demonstrated significant correlations between patient survival and tumor diameter, depth of invasion, lymphatic invasion, vascular invasion, lymph node metastasis and distant metastasis. The survival of patients who did not express p63 and p53 was obviously unfavorable (p=0.03). Multivariate analysis revealed that only lymph node metastasis was a critical independent prognostic marker for overall survival (p=0.0015). Expression of p63 was not an independent prognostic factor for overall survival in this study (p=0.69). These data suggest that, although a reduced expression of p63 is infrequent, it has a prognostic impact upon patients with ESCC.

Aged↗

Chemosensitivity prediction in esophageal squamous cell carcinoma: novel marker genes and efficacy-prediction formulae using their expression data.

Esophageal cancer is a highly lethal disease and the optimal therapy remains unclear. Since adjuvant chemotherapy gives a better chance of survival, we attempted to develop a chemosensitivity prediction model to improve individual responses to therapy. Comprehensive gene expression analyses (cDNA and oligonucleotide microarrays) and MTT assay of 8 drugs in 20 KYSE squamous cell carcinoma cell lines were performed to distinguish candidate marker genes whose expression levels reproducibly correlated with cellular drug sensitivities. After confirmation with real-time RT-PCR, we performed multiple regression analyses to develop drug-sensitivity prediction formulae using the quantified expression data of selected marker genes. Using the same sets of genes, we also constructed prediction models for individual clinical responses to 5-FU-based chemotherapy using 18 cases. We selected 5 better marker genes, known as drug sensitivity determinants, identified 9 novel predictive genes for 4 of 8 anticancer drugs [5-FU, CDDP, DOX, and CPT-11 (SN-38)], and developed highly predictive formulae of in vitro sensitivities to the 4 drugs and clinical responses to 5-FU-based adjuvant chemotherapies in terms of overall and disease-free survivals. Our selected genes are likely to be effective drug-sensitivity markers and formulae using the 9 novel genes would provide advantages in prediction.

Antineoplastic Agents↗

[High-dose chemotherapy with peripheral blood stem cell auto transplantation for an intractable case of mediastinal seminoma].

HDC with PBSCT is effective for some intractable cases with malignant neoplasma. We encountered an intractable case of mediastinal seminoma treated by HDC with PBSCT. The patient was a 25-year-old man with mediastinal seminoma. He had undergone chemo-radiotherapy several times and salvage surgery for the mediastinal tumor and chest wall recurrence since September 2001. He was referred to our clinic for management of recurrent seminoma in the chest wall in January 2004. In our clinic, chemo-radiotherapy consisting of cisplatin and etoposide was performed. The tumor size decreased transiently, but re-growth was observed 2 months after chemo-radiotherapy. We then performed HDC with PBSCT twice without any lethal complication. Now, the patient is well and disease-free 1 year after HDC with PBSCT.

Adult↗

Thymidine phosphorylase levels and dihydropyrimidine dehydrogenase levels in non-small cell lung cancer tissues.

Thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) are the major catabolic enzymes of 5-FU. In this study, we analyzed the concentration of TP and DPD in non-small cell lung cancer tissue by enzyme-linked immunosorbent assay. We measured the TP and DPD levels in 25 adenocarcinoma tissues and 25 squamous cell carcinoma tissues. The mean TP concentration in non-small cell lung cancer tissue was statistically higher than that of normal lung tissue as was the mean DPD concentration. The ratio of the TP level to DPD level in tumor tissue was higher in squamous cell carcinoma than in adenocarcinoma. No significant difference could be detected between the TP level, DPD level, or TP/DPD level and the tumor size or lymph node metastasis. In conclusion, chemotherapy with 5-FU may be more effective in squamous cell lung cancer patients than lung adenocarcinoma patients from the result of the ratio of TP to DPD.

Adenocarcinoma↗

A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation.

MicroRNAs (miRNAs) are small noncoding RNAs, thought to be involved in physiologic and developmental processes by negatively regulating expression of target genes. We have previously reported frequent down-regulation of the let-7 miRNA family in lung cancers and, in the present study, assessed alteration in a panel of 19 lung cancer cell lines. As a result, we found for the first time that the miR-17-92 cluster, which comprises seven miRNAs and resides in intron 3 of the C13orf25 gene at 13q31.3, is markedly overexpressed in lung cancers, especially with small-cell lung cancer histology. Southern blot analysis revealed the presence of increased gene copy numbers of the miRNA cluster in a fraction of lung cancer cell lines with overexpression. In addition, we were able to show predominant localization of C13orf25 transcripts within the nucleus and introduction of the expression construct of the miR-17-92 cluster, but not the putative open reading frame of C13orf25, enhancing lung cancer cell growth. These findings clearly suggest that marked overexpression of the miR-17-92 cluster with occasional gene amplification may play a role in the development of lung cancers, especially in their most aggressive form, small-cell lung cancer, and that the C13orf25 gene may well be serving as a vehicle in this regard.

Base Sequence↗

DNA methylation of genes linked with retinoid signaling in gastric carcinoma: expression of the retinoid acid receptor beta, cellular retinol-binding protein 1, and tazarotene-induced gene 1 genes is associated with DNA methylation.

BACKGROUND: Hypermethylation of CpG islands has been associated with silencing of various tumor suppressor genes, and the retinoid acid receptor beta (RARbeta), cellular retinol-binding protein 1 (CRBP1), and tazarotene-induced gene 1 (TIG1) genes have been associated with retinoic acid signaling. To the authors' knowledge, little is known regarding the involvement of these three genes in gastric carcinoma (GC). In this study, the authors investigated the methylation status of these genes and analyzed the role of their DNA methylation in GC. METHODS: DNA methylation of 3 retinoic acid-associated genes was analyzed in 42 samples of GC from 42 patients and in 8 GC cell lines by methylation-specific polymerase chain reaction (PCR) analysis. The mRNA expression levels for these three genes were measured by quantitative reverse transcription-PCR. RESULTS: In 7 of 8 GC cell lines, the CRBP1 gene was hypermethylated, and CRBP1 transcription was inactive. In 6 of 8 GC cell lines, the TIG1 gene was hypermethylated, and TIG1 transcription was inactive. Treatment with demethylating agent 5-aza-2'-deoxycytidine restored both CRBP1 and TIG1 transcription. DNA methylation of the RARbeta, CRBP1, and TIG1 genes was detected in 15 of 42 GC samples (36%), 14 of 42 GC samples (33%), and 4 of 42 GC samples (10%), respectively, and in 6 of 30 samples (20%), 0 of 30 samples (0%), and 1 of 30 samples (3%) of corresponding nonneoplastic mucosa. None of the 10 normal gastric mucosa samples from young, healthy individuals demonstrated hypermethylation of any of these genes. DNA methylation of each gene was associated significantly with low mRNA expression of the respective gene. Twenty-four of 42 GC samples (57%) demonstrated hypermethylation of at least 1 of the 3 genes. However, no significant, concordant hypermethylation of these genes was observed. CONCLUSIONS: The results suggested that gastric carcinogenesis involves transcriptional inactivation by aberrant DNA methylation of genes related to retinoid signaling.

Adenocarcinoma↗

Spontaneous hemothorax in patients with von Recklinghausen's disease.

Spontaneous massive intrathoracic bleeding is rare except for the rupture of aortic aneurysm or pleural adhesions in association with pneumothorax. We encountered two cases of critical massive hemothorax in patients with von Recklinghausen's disease (type I neurofibromatosis). Case 1; a 59-year-old female suddenly experienced severe back pain followed by syncope and shock. The hemothorax was caused by a bleeding of diffuse type neurofibroma of the parietal pleura and she underwent thoracotomy and surgical ligation of the bleeding vessels. Case 2; a 46-year-old male suddenly suffered back pain and fainted while driving. An intercostal aneurysmal rupture caused a spontaneous hemothorax and he underwent chest tube drainage followed by endovascular coil embolization. We reviewed 23 cases reported in the literature, including our two cases. Spontaneous hemothorax in patients with von Recklinghausen's disease is a life-threatening syndrome and may require emergency surgical or endovascular embolization.

Acute Disease↗

Successful treatment of an adult patient with pulmonary abscess secondary to congenital cystic adenomatoid malformation.

We report a case of a 29 year old male who at age 25, developed a pulmonary abscess in the left lower lobe. A left lower lobectomy was performed following two recurrences on antibiotic treatment. The result of histopathological examination confirmed congenital cystic adenomatoid malformation (CCAM), a congenital disease characterized by multiple cysts resulting from adenomatous hyperplasia of the bronchial epithelia. In many cases, respiratory distress occurs during the neonatal period, and in about 80-85% of patients, CCAM is diagnosed before the age of two years due to respiratory infection. CCAM which was diagnosed in adulthood is very rare.

Adolescent↗

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↗

Impact of nuclear galectin-3 expression on histological differentiation and vascular invasion in patients with esophageal squamous cell carcinoma.

Expression of galectin-3, a member of the beta-galactosidase binding lectin family, is reported to correlate with cell adhesion. The present immunohistochemical study was performed to clarify the impact of galectin-3 expression on patients with esophageal squamous cell carcinoma. Galectin-3 expression was examined immunohistochemically in 154 patients with esophageal squamous carcinoma, who had undergone surgery without preoperative supplemental therapy at the Department of Surgery II in the Hospital of the Faculty of Medicine, Oita University, between 1990 and 2000. The cases with > or =30% nuclear-stained cancer cells were considered high nuclear expression cases. In contrast, the cases with > or =45% cytoplasm-stained cancer cells were considered high cytoplasm expression cases. Twenty-three of 154 ESCC cases were regarded as high nuclear expression (14.9%) and 72 of 154 cases were regarded as high cytoplasm-expression (46.5%). High expression of galectin-3 in the nuclei inversely correlated with vascular invasion (p=0.030) and histological differentiation (p=0.0064). In contrast, cytoplasmic expression of galectin-3 revealed no significant impact on clinicopathological factors. Neither nuclear nor cytoplasmic expression of galectin-3 was a prognostic indicator in ESCC. Elevated expression of galectin-3 in the nuclei but not the cytoplasm may be an important biological parameter related to histological differentiation and vascular invasion in patients with ESCC.

Adult↗

[Surgical procedure of thoracoscopic and video-assisted anatomical segmentectomy for small peripheral lung cancer].

Recently, small peripheral lung cancers which is indicated limited resection are frequently found by HRCT or PET. The limited resection for lung cancer includes thoracic and video-assisted anatomical segmentectomy (VATS segmentectomy) and wedge resection of the lung parenchyma. In anatomical segmentectomy, intra-plumonary lymph nodes are dissected, on the other hand, those lymph nodes can not be dissected in wedge resection. Consequently, segmentectomy will be radical procedure for lung cancer compared with wedge resection. Thoracic surgeons are required to perform anatomical segmentectomy for small peripheral lung cancer. The anatomical segmentectomy is not familiar procedure for recent thoracic surgeons. Thoracic surgeons should be skilled in that procedures. This is a review of basic procedures of VATS segmentectomy for lung cancer for young thoracic surgeones.

Humans↗

[Thoracic trauma in elderly patients].

UNLABELLED: We investigated clinical character of thoracic trauma in the octogenarians in local city. Between Jan 2000 and Dec 2004, 369 patients with thoracic trauma were managed in our clinic and 3 local city hospitals in Oita. Ninety patients (23%) were aged 80 or above, 177 patients (46.7%), 64 or below, and 102 patients (26.9%), from 65 to 79. Blunt trauma occurred in the elderly. Penetrating trauma occurred in only 3 younger patients. In the octogenarians, causes of trauma were falls in 54 (60%) of the patients, traffic accidents in 15 (16.7%), and strained back in 14 (15.6%). Falls occurred on steps, most commonly, from flat surface as the elder fails to navigate environmental hazards or simply drops owing to a syncopal episode or loss of balance. Fractures of the thoracic vertebrae with or without rib fractures were observed in 29 (32.2%) of the octogenarians. Overall mortality was 2.3%. Three octogenarians (3.3%) died of pneumonia. Twenty-two (24.4%) of the octogenarians could discharge to their home, but the other 67 patients (74.4%) were referred to nursing home. CONCLUSION: Falls most commonly occur in the octogenarians. Occasionally, the patients require to discharge to nursing home, because of fracture of thoracic vertebrae or debilitated disorder.

Accidental Falls↗

Successful treatment of a patient with penetrating injury of the esophagus and brachiocephalic artery due to migration of Kirschner wires.

Pins and wires offer the simplest and most effective tools for managing bone fractures and dislocations. Migration of these devices within the chest is rare, but can cause serious problems. The spontaneous migration of Kirschner wires from the right clavicle to the mediastinum resulted in penetrating injury of the esophagus and pseudo-aneurysm of the brachiocephalic artery in an 84-year-old patient. Two Kirschner wires were removed via a vertical incision on the right shoulder without thoracotomy and the brachiocephalic artery was replaced with a Dacron graft.

Aged↗

Multiple calcifying fibrous tumors of the pleura.

Calcifying fibrous tumor (CFT) is a rare lesion characterized histologically by hypocellular hyalinized collagenous tissue with psammomatous and/or dystrophic calcifications and patchy lymphoplasmacytic infiltrates. CFT usually occurs in the somatic soft tissue of children and young adults but is rarely found in the pleura. We describe here an unusual case of multiple small CFTs in the right mediastinal pleura of a 54-year-old man who had a history of renal cell carcinoma. Suspecting pulmonary and pleural metastases, we performed wedge resection of the right middle lobe and local excision of two nodules in the right pleura. Light microscopy revealed metastatic lesions of renal cell carcinoma in the resected wedge. The pleural nodules were well circumscribed and composed of hypocellular, dense, hyalinized, collagenous tissue with scant lymphoplasmacytic infiltration and characteristic psammoma bodies. Immunohistochemical staining revealed that most spindle cells were positive for vimentin, CD34 and factor XIIIa, and negative for epithelial membrane antigen, keratin, smooth-muscle actin, desmin, S-100 protein and anaplastic lymphoma kinase. We made a histological diagnosis of CFT of the pleura, and the patient remains well 6 months after the wedge resection.

Calcinosis↗