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ABSTRACT: BACKGROUND: Anastomosis performed during esophagectomy for esophageal cancer is usually involves hand-sewn or circular stapled methods. However, these techniques have been reported to be associated with a high frequency of anastomotic complications, including leakage and benign stenosis. Here a novel triangulating stapling technique for esophagogastrostomy after esophagectomy for esophageal cancer and its retrospective investigation are described. METHODS: Forty-eight patients were underwent esophagectomy for esophageal cancer from January 2006 to December 2009 by the same surgeon using the triangulating stapling technique. The short-term outcomes were evaluated retrospectively. This end-to-end anastomosis used three linear staplers in an everted fashion. RESULTS: Patients comprised 36 men and 12 women with a mean age of 59.4 years. Anastomotic leakage occurred in 4 patients (8.3 %), while anastomotic stenosis was observed in 6 (12.5 %). The average number of endoscopic pneumatic dilatations in patients with anastomotic stenosis was 2.4. The median (range) duration of hospital stay was 40.8 (19-154) days. CONCLUSIONS: Our modified triangulating stapling technique for esophagogastrostomy may be a feasible alternative, resulting in a lower frequency of postoperative anastomotic complications.
Surgical Endoscopy 10/2012; · 4.01 Impact Factor
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ABSTRACT: We retrospectively reviewed the prognosis and clinical outcome of 25 patients who developed metachronous pulmonary metastasis after esophagectomy for esophageal cancer. The site of recurrence was pulmonary without extrapulmonary metastasis in 14 patients and extrapulmonary metastasis was observed in 11. Nineteen patients had multiple pulmonary metastasis and 6 had solitary pulmonary metastasis. Twenty-four of patients underwent systemic chemotherapy during initial treatment for metastatic lesions. Pulmonary metastasectomy was indicated in 5 patients with solitary metastasis. The actual 1-, 2- and 4-year survival rates were 60%, 36% and 27%, respectively. Gender, operative procedure, and postoperative morbidity were not significant prognostic factors. However, pathological staging of primary esophageal cancer was a significant prognostic factor. Survival was significantly worse in patients who did not undergo resection than in those who did. The number of pulmonary metastasis, complicated extrapulmonary metastasis and the time of recurrence were also significant prognostic factors. In conclusions, multiple pulmonary metastases or complicated extrapulmonary metastasis were unfavorable prognostic factors for patients with pulmonary metastasis arising from esophageal cancer. Although, surgical intervention is not recommended in such cases, metastasectomy is an acceptable choice of treatment for solitary pulmonary metastasis.
Journal of Cardiothoracic Surgery 10/2012; 7(1):103. · 1.19 Impact Factor
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ABSTRACT: Basaloid squamous cell carcinoma of the esophagus (BSCE) is a rare malignancy among esophageal cancers. We reported a case of 63-year-old woman with metachronous pulmonary metastasis of BSCE, successfully treated by metastasectomy of the left lung.
Biopsy specimens of upper gastrointestinal fiberscopy led to diagnosis of poorly differentiated squamous cell carcinoma of the esophagus. Computed tomography revealed metastatic lymph nodes surrounding the bilateral recurrent laryngeal nerve and no evidence of metastasis to distant organs. Curative esophagectomy with three-field lymph node dissection was performed through thoracoscopic approach. Pathological examination of the resected specimens led to diagnosis of BSCE with invasion into the submucosal layer of the esophageal wall. Two years later, a solitary oval-shaped pulmonary lesion of approximately 10mm was detected in the left lung. Wedge resection of the left upper lobe was performed via thoracoscopic approach. The postoperative course was uneventful. Histologically, the pulmonary lesion was diagnosed as metastatic BSCE. Follow-up indicated no recurrence 9 years after the initial surgery.
Surgical intervention was acceptable on this case of solitary pulmonary metastasis. However, data are lacking about the efficacy of pulmonary resection for metachronous pulmonary metastasis of BSCE because the postoperative outcome is usually poor. The efficacy of surgical intervention for metastatic lesions of BSCE is debatable and requires further examination.
Although the usefulness of surgical intervention for metastatic lesions from BSCE is controversial, the patients with metachronous solitary metastasis to the lung and without extrapulmonary metastasis would be good candidate for pulmonary resection.
International journal of surgery case reports. 06/2012; 3(9):451-4.
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ABSTRACT: We report a case of gastric malignant schwannoma presenting with gastrointestinal bleeding.
A 70-year-old Japanese man presented with gastrointestinal bleeding to our hospital. Gastrointestinal endoscopy revealed a protruding lesion in the gastric body. Hematoxylin and eosin staining of biopsy specimens from this lesion revealed sheets of spindle cells. Immunohistochemistry revealed that these cells were positive for S-100 protein and negative for c-Kit and smooth muscle actin. Because mitosis was diffusely visible, this tumor was diagnosed as a gastric malignant schwannoma. Distal gastrectomy with lymph node dissection was performed and the patient's postoperative course was uneventful. However, five months after the surgery, he died from multiple liver metastases.
Cases of gastric malignant schwannoma have rarely been reported. The efficacy of surgical resection and postoperative prognosis continues to remain unclear and should be investigated further.
Journal of Medical Case Reports 01/2012; 6(1):37.
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ABSTRACT: Esophageal duplication cyst is a rare congenital anomaly. They can be associated with other congenital anomalies, such as spinal abnormalities, and tracheoesophageal fistulas. In adults, almost of the patients with esophageal duplication cyst is asymptomatic and accidentally diagnosed by chest X-ray or computed tomography. However, cysts may become symptomatic owing to complications such as esophageal stenosis, respiratory system compression, rupture, infarction, or malignancy. Complete surgical resection is the standard treatment even in patients with asymptomatic cysts. Traditional approach for resection is via thoracotomy. But, the thoracoscopic approach makes more indicate for mediastinal diseases, because of minimally invasive for patients. We describe a case with esophageal duplication cyst, which contained the ectopic pancreatic tissue in the solid portion, resected under the thoracoscopic approach in adult.
Journal of Cardiothoracic Surgery 09/2011; 6:118. · 1.19 Impact Factor
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Le Thi Thanh Thuy,
Takashi Morita, Kayo Yoshida,
Kenichi Wakasa,
Masashi Iizuka,
Tomohiro Ogawa,
Mami Mori,
Yumiko Sekiya,
Shinobu Momen,
Hiroyuki Motoyama,
Kazuo Ikeda,
Katsutoshi Yoshizato,
Norifumi Kawada
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ABSTRACT: Cytoglobin (Cygb) is a recently discovered vertebrate globin with molecular characteristics that are similar to myoglobin. To study the biological function of Cygb in vivo, we generated Cygb knockout mice and investigated their susceptibility to N,N-diethylnitrosamine (DEN)-induced tumorigenesis. Four-week-old male mice were administered DEN in drinking water at a dose of 25 ppm for 25 weeks or 0.05 ppm for 36 weeks. Cygb deficiency promoted the DEN-induced development of liver and lung tumors. All Cygb(+/-) and Cygb(-/-) mice treated with 25-ppm DEN exhibited liver tumors, compared with 44.4% of their wild-type counterparts. Lung tumors were present only in Cygb-deficient mice. More than 40% of Cygb(-/-) mice developed liver and lung tumors at the nontoxic dose of DEN (0.05 ppm), which did not induce tumors in wild-type mice. Cygb loss was associated with increased cancer cell proliferation, elevated extracellular signal-regulated kinase and Akt activation, overexpression of IL-1β, IL-6, Tnfα, and Tgfβ3 mRNAs, and hepatic collagen accumulation. Cygb-deficient mice also exhibited increased nitrotyrosine formation and dysregulated expression of cancer-related genes (cyclin D2, p53, Pak1, Src, Cdkn2a, and Cebpa). These results suggest that Cygb deficiency induces susceptibility to cancer development in the liver and lungs of mice exposed to DEN. Thus, globins such as Cygb will shed new light on the biological features of organ carcinogenesis.
American Journal Of Pathology 06/2011; 179(2):1050-60. · 4.89 Impact Factor
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ABSTRACT: Aneurysm of the middle colic artery is very uncommon. In this report, we describe a case of a ruptured aneurysm of the middle colic artery caused by segmental arterial mediolysis and its successful management by surgical resection. A 60-year-old Japanese man was admitted to our institution for the treatment of a ruptured aneurysm of the branch of the superior mesenteric artery suspected by computed tomography. Angiography revealed multiple wide and narrow mural irregularities and some aneurysms in the middle colic artery without extravasation. Transcatheter arterial embolization could not be accomplished because of difficulty in catheterization. Since radiological findings of the patient indicated worsening of the aneurysm, surgical resection was performed. Histopathological findings of the resected specimen were consistent with those of segmental arterial mediolysis. In cases where curative embolization cannot be accomplished, surgical resection is required. However, in a non-ruptured aneurysm, healing occurs gradually. Therefore, if the vital parameters of the patient are stable, conservative observation can be recommended.
Osaka city medical journal 12/2010; 56(2):47-52.
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ABSTRACT: We reported herein four resected cases with basaloid carcinoma of the esophagus and measured the activity of 5-FU related enzymes (TS, DPD, OPRT) in cancer tissue. These activities compared with those in squamous cell carcinoma. Only one case was diagnosed as basaloid carcinoma by preoperative biopsy specimen at endoscopic examination. The esophagectomy was performed thoracoscopically in all cases, and the abdominal procedure was done with the laparoscopic approach in two cases. Anastomotic leakage occurred in one case. No case had lymph node metastasis. On the other hand, a lymphatic invasion was detected in one case, and venous invasion in two, respectively. Two cases had mediastinal lymph node recurrence. DPD activity and OPRT activity showed no difference between squamous cell carcinoma and basaloid carcinoma. On the other hand, the TS activity was significantly higher in basaloid carcinoma. From the standpoint of 5-FU-related enzyme activities, basaloid carcinoma possibly has more resistance to 5-FU than squamous cell carcinoma.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2010; 37(11):2143-6.
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ABSTRACT: We investigated the relationship between DPD, OPRT activities and clinicopathological characteristics in 76 patients with colorectal cancer. There was no significant difference between cancer and normal tissue in DPD activity. OPRT activity was significantly higher in cancer tissue than in normal tissue. In poorly-differentiated adenocarcinoma, DPD activity was significantly higher, and OPRT activity was significantly lower than the other type of cancer. Furthermore, OPRT activity was significantly lower in patients with lymph node metastasis. These results suggested that poorly-differentiated adenocarcinoma of the colorectum shows lower efficacy with treatment by 5-fluorouracil than other types of colorectal cancer. Hence, DPD inhibitory fluorouracil, such as S-1, may have potent therapeutic efficacy for poorly-differentiated adenocarcinoma of the colorectum.
Gan to kagaku ryoho. Cancer & chemotherapy 07/2010; 37(7):1297-301.
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ABSTRACT: We investigated the relationship between orotate phosphoribosyl transferase (OPRT), dihydropyrimidine dehydrogenase (DPD) and clinicopathological characteristics in 48 patients with esophageal cancer. DPD activity resulted in no significant differences between cancer tissue and normal tissue, and no relationship with clinicopathological factors. OPRT activity was significantly increased in cancer tissue; its activity was significantly lower in patients with lymph node metastasis and lymph vessel invasion, and significantly higher in Stage I and II than in Stage III and IV. The OPRT/DPD ratio has a relation to cancer staging and survival rate. These results suggested that OPRT levels were related to the clinic pathological characteristics and survival of esophageal cancer.
Gan to kagaku ryoho. Cancer & chemotherapy 07/2010; 37(7):1283-6.
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ABSTRACT: A liaison-clinical pathway for patients with stageI to III gastric cancer after curative operation has been introduced and managed in our hospital from July 2009. We made two kinds of liaison-clinical pathway in the presence or absence of postoperative adjuvant therapy. The duration of follow-up was 5 years in proportion to the Guidelines for Diagnosis and Treatment of Carcinoma of the Stomach. We held a briefing session for practicing physicians involved after liaison-clinical pathway making, conducted a questionnaire, and judged whether induction was possible. The liaison-clinical pathway consists of a chart for practicing physicians, leaflets with checklists for the patients, and other documents. We began to use them in July, 2009, and involved patients are 11 to date. Because postoperative treatment planning became clear by using the liaison-clinical pathway, we were able to relieve the anxiety of patients with cancer, and it seemed that it was easy to facilitate to perform cancer cooperation by the practicing physicians. For the introduction and management of this pathway, a thorough explanation to the patients with gastric cancer and good communication is required with the practicing physicians in cooperation with the coordinator.
Gan to kagaku ryoho. Cancer & chemotherapy 06/2010; 37(6):1081-5.
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ABSTRACT: Damage-induced neuronal endopeptidase (DINE) is a metalloprotease belonging to the neprilysin family. Expression of DINE mRNA is observed predominantly in subsets of neurons in the CNS and peripheral nervous system during embryonic development, as well as after axonal injury. However, the physiological function of DINE and its substrate remain unknown. We generated DINE-deficient mice to examine the physiological role of DINE. Shortly after birth, these mice died of respiratory failure resulting from a dysfunction of the diaphragm, which showed severe atrophy. As DINE was abundantly expressed in motor neurons and there was atrophy of the diaphragm, we analyzed the interaction between motor nerves and skeletal muscles in the DINE-deficient mice. Although there were no obvious deficiencies in numbers of motor neurons in the spinal cord or in the nerve trajectories from the spinal cord to the skeletal muscle in DINE-deficient mice, detailed histochemical analysis demonstrated a significant decrease of nerve terminal arborization in the diaphragm from embryonic day 12.5. In accordance with the decrease of final branching, the diaphragms from DINE-deficient mice exhibited only a few neuromuscular junctions. Similar changes in nerve terminal morphology were also apparent in other skeletal muscles, including the latissimus dorsi and the intercostal muscles. These data suggest that DINE is a crucial molecule in distal axonal arborization into muscle to establish neuromuscular junctions.
Journal of Neuroscience 05/2010; 30(20):6954-62. · 7.11 Impact Factor
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Katsunobu Sakurai,
Yoshito Yamashita,
Sadatoshi Shimizu, Kayo Yoshida,
Tatsunari Fukuoka,
Zhang Xiang,
Satoshi Yamamoto,
Atsushi Yamamoto,
Akishige Kanazawa,
Masashi Takemura,
Tadashi Tsukamoto,
Yukio Nishiguchi,
Teruyuki Ikehara
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ABSTRACT: We reported a patient with advanced gastric cancer successfully treated with S-1 chemotherapy for three weeks. The patient was a 67-year-old man who had gastric cancer clinically diagnosed as cT3N1H0P0M0, stage IIIA. His treatment was supposed to be daily oral administration of 120 mg S-1 for 28 days. At 21 days, this treatment was stopped due to severe appetite loss. The histological diagnosis of the resected stomach revealed complete disappearance of cancer cells in the stomach and the regional lymph nodes. Our report suggested that S-1 may have a potent therapeutic effect in neoadjuvant chemotherapy for advanced gastric cancer.
Gan to kagaku ryoho. Cancer & chemotherapy 02/2010; 37(2):315-8.
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ABSTRACT: Maintaining the integrity of spermatogenic stem cells is essential to transfer genetic information to a descendant. However, knowledge of maintenance of genetic stability in stem cells is still limited. RAD18 is critical for postreplication repair through mono- and multi-ubiquitination of proliferating cell nuclear antigen (PCNA) to maintain genomic stability. Mammalian RAD18 is highly expressed in the spermatocytes and the nuclei of a few spermatogonia in adult mice. To elucidate the physiological function of RAD18, we analyzed a phenotype of Rad18-/- mice. The mice were born and appeared to grow normally. Although the mice were fertile, fertility and testis weight decreased with age. Histological examination revealed normal spermatogenesis in almost all seminiferous tubules in Rad18-/- testes at 2 months old, and abnormal sperm could not be detected in the epididymis. However, 25% of the tubules lost almost all germ cells at 12 months. The seminiferous tubules frequently retained only late differentiated phase germ cells, suggesting that the exhaustion of spermatogonial stem cells leads to the loss of all germ cells in the seminiferous tubules. Wild-type germ cells were successfully transplanted into and colonized in the seminiferous tubules of aged Rad18-/- mice, indicating that Sertoli cells have a normal supportive function even in aged testes. We conclude that RAD18 is intrinsically required for the long-term maintenance of spermatogenesis.
Mechanisms of development 12/2008; 126(3-4):173-83. · 2.83 Impact Factor
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ABSTRACT: Reductional chromosome segregation in germ cells, where sister chromatids are pulled to the same pole, accompanies the protection of cohesin at centromeres from separase cleavage. Here, we show that mammalian shugoshin Sgo2 is expressed in germ cells and is solely responsible for the centromeric localization of PP2A and the protection of cohesin Rec8 in oocytes, proving conservation of the mechanism from yeast to mammals. However, this role of Sgo2 contrasts with its mitotic role in protecting centromeric cohesin only from prophase dissociation, but never from anaphase cleavage. We demonstrate that, in somatic cells, shugoshin colocalizes with cohesin in prophase or prometaphase, but their localizations become separate when centromeres are pulled oppositely at metaphase. Remarkably, if tension is artificially removed from the centromeres at the metaphase-anaphase transition, cohesin at the centromeres can be protected from separase cleavage even in somatic cells, as in germ cells. These results argue for a unified view of centromeric protection by shugoshin in mitosis and meiosis.
Nature Cell Biology 02/2008; 10(1):42-52. · 19.49 Impact Factor
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ABSTRACT: Approximately 15% of human couples are affected by infertility, and about half of these cases of infertility can be attributed to men, through low sperm motility (asthenozoospermia) or/and numbers (oligospermia). Because mitochondrial genome (mtDNA) mutations are identified in patients with fertility problems, there is a possibility that mitochondrial respiration defects contribute to male infertility. To address this possibility, we used a transmitochondrial mouse model (mito-mice) carrying wild-type mtDNA and mutant mtDNA with a pathogenic 4,696-bp deletion (DeltamtDNA). Here we show that mitochondrial respiration defects caused by the accumulation of DeltamtDNA induced oligospermia and asthenozoospermia in the mito-mice. Most sperm from the infertile mito-mice had abnormalities in the middle piece and nucleus. Testes of the infertile mito-mice showed meiotic arrest at the zygotene stage as well as enhanced apoptosis. Thus, our in vivo study using mito-mice directly demonstrates that normal mitochondrial respiration is required for mammalian spermatogenesis, and its defects resulting from accumulated mutant mtDNAs cause male infertility.
Proceedings of the National Academy of Sciences 11/2006; 103(41):15148-53. · 9.68 Impact Factor
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ABSTRACT: Spermatogenesis consists of complex cellular and developmental processes, such as the mitotic proliferation of spermatogonial stem cells, meiotic division of spermatocytes, and morphogenesis of haploid spermatids. In this study, we show that RNA interference (RNAi) functions throughout spermatogenesis in mice. We first carried out in vivo DNA electroporation of the testis during the first wave of spermatogenesis to enable foreign gene expression in spermatogenic cells at different stages of differentiation. Using prepubertal testes at different ages and differentiation stage-specific promoters, reporter gene expression was predominantly observed in spermatogonia, spermatocytes, and round spermatids. This method was next applied to introduce DNA vectors that express small hairpin RNAs, and the sequence-specific reduction in the reporter gene products was confirmed at each stage of spermatogenesis. RNAi against endogenous Dmc1, which encodes a DNA recombinase that is expressed and functionally required in spermatocytes, led to the same phenotypes observed in null mutant mice. Thus, RNAi is effective in male germ cells during mitosis and meiosis as well as in haploid cells. This experimental system provides a novel tool for the rapid, first-pass assessment of the physiological functions of spermatogenic genes in vivo.
Developmental Biology 07/2005; 282(2):524-34. · 4.07 Impact Factor
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ABSTRACT: The mouse histone H2AX has unique COOH-terminal serine residues that are phosphorylated in response to double-strand DNA breaks introduced by ionizing radiation. This suggests that H2AX acts to maintain genomic stability. We constructed a tetracycline (tet)-directed turn-off vector and integrated it into F9 mouse teratocarcinoma cells by homologous recombination. In homozygously recombined cells, expression of the histone H2AX gene was repressed to 0.02% of the expression observed in wild-type cells by the addition of doxycycline, an analog of tet. Sensitivity of cells with repressed H2AX expression to X-irradiation was increased 1.95x, indicating that DNA repair was impaired by repression of H2AX. When we s.c. injected tet-regulated F9 cells into the flanks of mice, tumor growth was slightly suppressed by X-irradiation in H2AX-repressed tumors, whereas without X-irradiation, tumor growth did not differ by H2AX status. Thus, H2AX might be a potential molecular target for sensitizing cancer cells to radiotherapy to minimize required irradiation doses.
Cancer Research 07/2004; 64(12):4131-6. · 7.86 Impact Factor
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ABSTRACT: The tumor suppressor protein p53 is specifically expressed during meiosis in spermatocytes. Subsets of p53 knockout mice exhibit testicular giant cell degenerative syndrome, which suggests p53 may be associated with meiotic cell cycle and/or DNA metabolism. Here, we show that p53 binds to the mouse meiosis-specific RecA-like protein Mus musculus DMC1 (MmDMC1). The C-terminal domain (amino acid 234-340) of MmDMC1 binds to DNA-binding domain of p53 protein. p53 might be involved in homologous recombination and/or checkpoint function by directly binding to DMC1 protein to repress genomic instability in meiotic germ cells.
Carcinogenesis 07/2004; 25(6):889-93. · 5.70 Impact Factor
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ABSTRACT: The mouse histone H2AX (H2AX) has unique C-terminal Ser residues, which are phosphorylated in response to DNA double-strand breaks (DSBs) by ionizing radiation, suggesting that it plays a role in the maintenance of genomic stability. Here, we show that the H2AX protein was detected in most cells in various tissues, and was abundant in the S phase of the cell cycle. Following X-ray irradiation, H2AX was phosphorylated (gamma-H2AX) in the thymus, small intestine and testis. However, H2AX in epithelial cells in the villi of the small intestine were not strongly phosphorylated, even after X-irradiation. Thus, H2AX was expressed in almost all cells. However, the cells that expressed H2AX were not always phosphorylated by X-irradiation, suggesting a different mechanism of kination in those cells.
Journal of Radiation Research 04/2003; 44(1):47-51. · 1.68 Impact Factor
