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Biomedical subjects

K Shigemitsu

Publications and source records attributed to K Shigemitsu.

16 recordsLinked to original sources

[Mucinous adenocarcinoma of the anterior mediastinum].

The authors report are a rare case of primary mucinous adenocarcinoma of the anterior mediastinum in a 34-year-old Japanese woman. Routine chest radiography revealed an abnormal mass lesion in the left upper mediastinum. Her serum CA 19-9 level was elevated at 299 (normal < 37) U/ml. The large tumor in the anterior mediastinum, 8 cm in diameter, were made of multicystic part with thick wall and thick spetrum and solid part in chest computed tomography (CT). Teratoma was suggested by percutaneous needle biopsy under CT scanning. When the chest was opened through a median sternotomy, adding a left collar incision, we found a hard tumor occupying the superior anterior mediastinum and then resected the tumor together with the left brachiocephalic vein, the left pleura, the pericardium and the left phrenic nerve because of invaded them. Grossly, the tumor was 13 x 10 x 8 cm and weighted 400 g. Pathologic diagnosis was mucinous adenocarcinoma of the anterior mediastinum. No primary cancer lesions were found in pancreas, ovarium, gastrointestinal tract and mammary gland. Microscopic examination showed minimal atypia site in mucinous adenocarcinoma and normal thymic tissues surrounding this tumor. These findings have led this case to conclude the primary tumor of thymus.

Adenocarcinoma, Mucinous↗

Esophageal cancer associated with right aortic arch: report of two cases.

Esophageal carcinoma associated with a right aortic arch is very rare. In such cases, the dissection of right paratracheal lymph nodes is difficult. Herein, we report two cases of thoracic esophageal carcinoma with right aortic arch, for which the left door open method was used to provide a good surgical view. Postoperative chemotherapy and radiotherapy were used for both cases and no evidence of recurrence or metastasis has been noted in the 24-month postoperative period.

Aged↗

Two cases of superficial basaloid squamous carcinoma of the esophagus.

. Basaloid squamous carcinoma of the esophagus is very rare. We report two cases of basaloid squamous carcinoma of the esophagus. Both tumors histologically consisted of solid cell nests with intervening fibromyxoid stroma. In some tumor nests were comprised of pseudoglandular structures containing myxoid matrix, and displayed focal immunoreactivity for laminin. Thoracic esophagectomy with lymph node dissection was followed by intrathoracic esophagogastrostomy in both patients. The patients had uneventful postoperative courses. Regular periodic follow-up showed no evidence of recurrence or metastasis in the 22-month postoperative period.

Carcinoma, Squamous Cell↗

Genetic alteration of the beta-catenin gene (CTNNB1) in human lung cancer and malignant mesothelioma and identification of a new 3p21.3 homozygous deletion.

The beta-catenin gene (CTNNB1) has been shown to be genetically mutated in various human malignancies. To determine whether the beta-catenin gene is responsible for oncogenesis in thoracic malignancies, we searched for the mutation in 166 lung cancers (90 primary tumors and 76 cell lines), one blastoma and 10 malignant mesotheliomas (two primary tumors and eight cell lines). Among the lung cancers, including 43 small cell lung cancers (SCLCs) and 123 non-small cell lung cancers (NSCLCs), we identified four alterations in exon 3, which is the target region of mutation for stabilizing beta-catenin. One primary adenocarcinoma had a somatic mutation from C to G, leading to an amino acid substitution from Ser to Cys at codon 37. Among the cell lines, SCLC NCI-H1092 had a mutation from A to G, leading to an Asp to Gly substitution at codon 6, NSCLC HCC15 had a mutation from C to T, leading to a Ser to Phe substitution at codon 45, and NSCLC NCI-H358 had a mutation from A to G, leading to a Thr to Ala substitution at codon 75. One blastoma also had a somatic mutation from C to G, leading to a Ser to Cys substitution at codon 37. Among the 10 malignant mesotheliomas, we identified a homozygous deletion in the NCI-H28 cell line. Cloning of the rearranged fragment from NCI-H28 indicated that all the exons except exon 1 of the beta-catenin gene are deleted and that the deletion junction is 13 kb downstream from exon 1. Furthermore, Northern blot analysis of 26 lung cancer and eight mesothelioma cell line RNAs detected ubiquitous expression of the beta-catenin messages except NCI-H28, although Western blot analysis showed that relatively less amounts of protein products were expressed in some of lung cancer cell lines. Our findings suggest that the beta-catenin gene is infrequently mutated in lung cancer and that the NCI-H28 homozygous deletion of the beta-catenin gene might indicate the possibility of a new tumor suppressor gene residing in this region at 3p21.3, where various types of human cancers show frequent allelic loss.

Base Sequence↗

Advanced gastric cancer with multiple lymph node metastasis successfully treated with etoposide, adriamycin and cisplatin.

Gastric cancer usually shows poor sensitivity to chemotherapy, and the presence of lymph node metastases is associated with extremely poor prognosis, especially when the number of such nodes is more than 10. We report here a case of advanced gastric cancer with histopathologically confirmed metastases in 15 regional lymph nodes, in which the recurrent tumor was sensitive to combination chemotherapy. Distal gastrectomy with lymphadenectomy was performed for the primary tumor. A hard (recurrent) tumor was detected in the upper abdomen 5 months postoperatively. Abdominal CT revealed two tumors measuring 3.5 x 1.8 and 3.3 x 2 cm in diameter at the front of the pancreatic head, which suggested recurrence. Etoposide, adriamycin and cisplatin (EAP) chemotherapy (20 mg/kg adriamycin, 100 mg/kg etoposide and 50 mg/kg cisplatin (CDDP)) was administered every 6 weeks. The tumors regressed and became undetectable on CT after four cycles. At that stage, CDDP was replaced with 400 mg/kg carboplatin, which was administered every 1 or 2 months. The patient had no recurrence 8 years after surgery. For treatment of advanced gastric cancer with multiple lymph node metastases, a wide resection of the tumor should be performed followed by treatment of the residual tumor cells with a suitable combination chemotherapy taking into consideration the characteristics of the tumor and the condition of the host. We present a patient with gastric cancer and histopathologically confirmed metastases in 15 regional lymph nodes, who was successfully treated by surgery followed by EAP adjuvant chemotherapy. The patient remains alive and well at 8 years after surgery.

Adult↗

A family of multiple endocrine neoplasia type 2A with the RET proto-oncogene mutation in codon 618 (Cys-->Arg).

Multiple endocrine neoplasia type 2 (MEN-2) is a hereditary syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and hyperplasia or adenoma of the parathyroid gland with hyperparathyroidism. Recent genetic studies have identified the presence of germline missense mutations in the RET proto-oncogene in almost 100% of MEN-2 patients. We report here three generations of one MEN-2 family with rare missense mutation at codon 618 (Cys-->Arg) of the RET proto-oncogene. The first patient was surgically treated at the age of 63 years but died of bone metastasis. His two children (29-year-old daughter and 25-year-old son) were treated surgically for MTC and neck lymph node metastasis. Germline mutations of the RET proto-oncogene of these three MTC patients and two children of the 29-year-old daughter (9-year-old female and 7-year-old male) were examined. Three MTC patients and the 9-year-old female possessed the mutation. The phenotype of the family with this rare point mutation of the RET proto-oncogene is reported.

Adult↗

Leiomyosarcoma arising in a remnant esophagus after esophagectomy: a case report.

We report an extremely rare case of leiomyosarcoma arising from a remnant esophagus. A 52-year-old Japanese man was referred to our hospital for treatment of a tumor arising from the remnant esophagus. Four years earlier, he underwent a subtotal esophagectomy for esophageal squamous cell carcinoma (well differentiated squamous cell carcinoma, T1N0M0 Stage I) located in the lower esophagus. After preoperative studies, partial esophagectomy with laryngeal preservation and reconstruction using a free graft from the jejunum were performed. Histopathological and immunohistochemical examination revealed leiomyosarcoma without metastasis. Immunohistochemical examination showed that most tumor cells were positive for smooth muscle actin and vimentin, but were negative for cytokeratin and S100. The deeply biopsied specimens are helpful for preoperative histological diagnosis. Mitotic activity has been considered an important criterion of malignancy. However, some cases with minimal mitosis in the tumor grow rapidly and were associated with poor prognosis. Therefore, we advocate that the clinical behavior is the only true indication of malignancy. We also provide a review of 64 cases of esophageal leiomyosarcoma reported in the Japanese literature with available data between 1969 and 1999, including the present case, and discuss their clinicopathological features. Asynchronous occurrence of leiomyosarcoma and squamous cell carcinoma in the esophagus is most unusual and has never been reported. Patients with infiltrating type leiomyosarcoma measuring more than 5 cm in diameter tend to have a poor prognosis. Chemotherapy did not exhibit any survival benefits. In the present patient, no recurrence has been noted for 23 months after surgery.

Carcinoma, Squamous Cell↗

Retroperitoneal liposarcoma presenting a indirect inguinal hernia.

A 60-year-old man was admitted to our hospital with a right inguinal swelling that had been growing in size without any pain for 7 months. We diagnosed the growth as a right inguinal hernia and operated on him. The growth, however, was found to be a tumor it situated along the spermatic cord and testicular vessels. We diagnosed it as a lipoma. The tumor was resected near part of the internal inguinal ring. Histopathological diagnosis showed well-differentiated liposarcoma of the sclerosing type. Postoperative computed tomography (CT) revealed a large residual tumor in the retroperitoneum. We believed that the tumor was a retroperitoneal liposarcoma and that it developed in the inguinal region. The residue of the liposarcoma was resected onto the right inguinal tract. A periodic follow up has been performed and no evidence of recurrence or metastasis has been seen in the 4 years and 9 months since the second surgery. No adjuvant therapy was performed. Inguinal liposarcomas are relatively rare and in most cases these tumors are thought to originate in the spermatic cord. The origin of the tumor is believed to be the retroperitoneum.

Hernia, Inguinal↗

[A surgical case of giant mediastinal neurilemmoma].

A 45-year-old male was admitted to Nagoya University Hospital with dyspnea. He was examined by chest X-ray, CT, MRI, and bronchofiberscope. The chest X-ray showed a large abnormal shadow in the right lung field. A large tumor mass pressing the right lung occupied a half of thoracic cavity on a chest CT and MRI. Bronchofiberscopic findings showed a stenosis of the right intermediate bronchus. The clinical diagnosis was posterior mediastinal tumor. He underwent a posterolateral thoracotomy and the tumor was removed smoothly. The size of resected specimen was 15 x 13 x 11 cm. Histopathological examination of the specimen revealed a mediastinal neurilemmoma. He has been well for 4 months postoperatively.

Dyspnea↗

Esophageal hemangioma successfully treated by fulguration using potassium titanyl phosphate/yttrium aluminum garnet (KTP/YAG) laser: a case report.

Esophageal hemangioma is an extremely rare tumor. We report a case of a 39-year-old man who was found to have an hemangioma which extended from the hypopharynx to the upper thoracic esophagus revealed by endoscopic examination. Computed tomography (CT) images, magnetic resonance imaging (MRI) and angiography were useful in the diagnosis. He was successfully treated by fulguration using potassium titanyl phosphate/yttrium aluminum garnet (KTP/YAG laser) four times and no recurrence has been seen. This patient has since been followed up carefully and additional fulguration will be performed if necessary. KTP/YAG laser is useful for the treatment of a large hemangioma as a less invasive method.

Adult↗

A case of thyroid cancer involving the trachea: treatment by partial tracheal resection and repair with a latissimus dorsi musculocutaneous flap.

A 65 year-old man had undergone left thyroidectomy for thyroid cancer. The cancer had directly invaded the cervical esophagus and trachea and the patient was referred to our hospital for radical resection and reconstruction. Cervical computed tomography showed a mass at the left-posterior wall of the trachea. Cervical esophagectomy, resection of the left half of the trachea (6 x 3 cm) including seven rings and cervical lymph node dissection were performed. The tracheal defect was covered by a latissimus dorsi musculocutaneous flap. The patient did not lose vocal function and remains alive and well 3 years after surgery without any evidence of recurrence. Latissimus dorsi muscle flap coverage of tracheal defects seems to be a useful technique in the combined resection of the trachea.

Aged↗

Evaluation of endoscopic mucosal resection for superficial esophageal carcinoma.

Esophageal superficial carcinoma safely can be resected surgically or endoscopically. We evaluated indications for endoscopic mucosal resection (EMR) and optimal treatment modality for superficial carcinoma of the esophagus based on clinical and pathologic analyses. Between January 1, 1984, and September 30, 1999, 113 patients with superficial cancer of the esophagus underwent surgical or endoscopic resection (n = 33 patients, 36 lesions). The two-channel method, esophageal EMR-tube method or EMR cap-fitted panendoscope was used. Mucosal and submucosal cancers were classified to be epithelial layer (m1), proper mucosal layer (m2), muscularis mucosae (m3), upper third of the submucosal level (sm1), middle third of the submucosal layer (sm2), or the lower third of the submucosal level (sm3) cancers, according to criteria of the Japanese Society for Esophageal Disease. Absolute indication for EMR was restricted to m1 or m2 cancers, and relative indications for EMR included m3 or sm1 lesions. In our department, indications for EMR were not related to size or circumference of lesions. Lymph vessel invasion and lymph node metastasis markedly increased in lesions that infiltrated the lamina muscularis mucosa (m3). All lesions resected with use of EMR were 0-II (flat), and the depth of invasion in 10 0-IIa or 0-IIb lesions was m1 or m2. Twenty-one 0-IIc lesions were distributed widely from m1 to sm1. All 0-IIa+IIc lesions were m3 or sm1. Preoperative diagnosis accurately was established preoperatively in 61% of patients. Complications related to EMR were detected in 21% of patients and included perforation, stenosis, and hemorrhage. Ten patients also received radiotherapy, chemotherapy, or esophagectomy with lymph node dissection after use of EMR. No such combination therapy was administered in six patients with m3 lesions, but without lymph vessel invasion. All patients treated with use of EMR, including patients with m3 cancer who did not receive additional treatment, are living without recurrence. Local resection with use of EMR could be regarded to be the preferred treatment of superficial esophageal cancers limited to the lamina propria mucosae. Endoscopic mucosal resection also could be regarded to be the preferred treatment of m3 cancer without lymph vessel invasion. Use of additional therapy, such as radiotherapy, allows the use of EMR for m3 cancer with lymph vessel invasion or sm1 cancers.

Aged↗

Structural requirement of leucine for activation of p70 S6 kinase.

The addition of leucine induced activation of p70S6k in amino acid-depleted H4IIE cells. Whereas the activation of p70S6k by leucine was transient, the complete amino acid stimulated p70S6k more persistently. The effect of leucine on p70S6k was sensitive to rapamycin, but less sensitive to wortmannin. Using various amino acids and derivatives of leucine, we found that the chirality, the structure of the four branched hydrocarbons, and the primary amine are required for the ability of leucine to stimulate p70S6k, indicating that the structural requirement of leucine to induce p70S6k activation is very strict and precise. In addition, some leucine derivatives exhibited the ability to stimulate p70S6k and the other derivatives acted as inhibitors against the leucine-induced activation of p70S6k.

Amino Acids↗

Regulation of translational effectors by amino acid and mammalian target of rapamycin signaling pathways. Possible involvement of autophagy in cultured hepatoma cells.

Amino acid deprivation of Chinese hamster ovary cells overexpressing human insulin receptors results in deactivation of p70 S6 kinase (p70) and dephosphorylation of eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), which become unresponsive to insulin; readdition of amino acids restores these responses in a rapamycin-sensitive manner, suggesting that amino acids and mammalian target of rapamycin signal through common effectors. Contrarily, withdrawal of medium amino acids from the hepatoma cell line H4IIE does not abolish the ability of insulin to stimulate p70 and 4E-BP1. The addition of 3-methyladenine (3MA) to H4IIE cells deprived of amino acids inhibited the increment in protein degradation caused by amino acid withdrawal nearly completely at 10 mM and also strongly inhibited the ability of insulin to stimulate p70 and 4E-BP1 at 10 mM. Treatment of H4IIE cells with 3MA did not alter the ability of insulin to activate tyrosine phosphorylation, phosphoinositide 3-kinase, or mitogen-activated protein kinase. In conclusion, the ability of H4IIE cells to maintain the insulin responsiveness of the mammalian target of rapamycin-dependent signaling pathways impinging on p70 and 4E-BP1 without exogenous amino acids reflects the generation of amino acids endogenously through a 3MA-sensitive process, presumably autophagy, a major mechanism of facultative protein degradation in liver.

Amino Acids↗

Theory of air pollution damage on human populations.

Existing ideas of dose or exposure are discussed and criticized from the view point of the health damage caused by time dependent air pollutant concentrations. The idea of "dosage" is introduced and some of its mathematical properties are shown and illustrated. The problem of whether or not there exists threshold concentration in air pollution, as well as that of the relation between equi-exposure and equi-damage, is then discussed by making use of the ideas of dosage and healing power of the population. The assumption of this discussion is that the statistical distribution of air pollutant concentrations is log-normal, and that its time series is stationary.

Air Pollution↗

Apoptosis in normal tissues induced by anti-cancer drugs.

To investigate the damage mediated by anti-cancer drugs in normal cells, we examined the effect of such drugs on apoptosis of normal cells of the small intestinal epithelium and the bone marrow by in situ DNA end-labelling and transmission electron microscopy. Mice received a single dose of 5-fluorouracil (5-FU) or cisplatin, or repeated daily doses of 5-FU for 7 days. In mice treated with a single dose of 5-FU 50 mg/kg or cisplatin 5 mg/kg, the number of apoptotic cells appearing in the small intestine 12 h after injection was relatively small, but increased steadily reaching a peak after 36 h and then decreasing to close to that in the control group by 48 h. In bone marrow cells, results were similar in mice treated with single doses of 5-FU 50 mg/kg but apoptosis increased much less in those treated with cisplatin 5 mg/kg. The proportion of apoptotic cells reached peak values earlier at higher concentrations of 5-FU or cisplatin both in small intestine and in bone marrow. In the mice treated repeatedly with 5-FU 50 mg/kg, the proportion of apoptotic small intestinal epithelial cells reached a succession of peaks at 48-h intervals. Mice treated repeatedly with 5-FU 50 mg/kg also showed a rapid increase in diarrhoea symptoms and a steady decrease in the height of villi. Our results suggest it may be possible to prevent the side-effects of anti-cancer drugs by inhibiting apoptosis in the gastrointestinal tract.

Animals↗