[Extended surgery for advanced gastric cancer].
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Clinical Trials as Topic↗
Biomedical subjects
M Tatsuta
Publications and source records attributed to M Tatsuta.
Reduced expression of focal adhesion kinase in liver metastases compared with matched primary human colorectal adenocarcinomas.
The focal adhesion kinase (FAK) is implicated in integrin-mediated signal transduction pathways used in cell adhesion, cell motility, apoptosis, and anchorage-independent growth. Because cancer invasion and metastasis are thought to be associated with alterations in cellular adhesive and motile properties, we studied the expression of four focal adhesion proteins including FAK in matched samples of human normal colorectal mucosa (N), primary colorectal adenocarcinomas (T) and liver metastases (M) from 10 patients by Western blot analysis. This gave us the advantage of directly comparing levels of focal adhesion protein expression within the same genetic background. Average FAK expression level was significantly higher in T than in N and it was significantly lower in M than in T. Average paxillin expression level was also significantly higher in T than in N, but it was not significantly different between T and M. Similar results were obtained by immunohistochemical analyses of FAK and paxillin expression. Average vinculin and talin expression levels showed no significant differences among these three samples (N, T, and M). These data demonstrate that the FAK expression level increases in primary tumors compared with normal mucosa and decreases in liver metastases to the level of normal mucosa in the majority of human colorectal adenocarcinomas. Up- and down-regulation of FAK protein expression observed in this study may have a profound effect on the signal transduction.
Adenocarcinoma↗
[The significance of neoadjuvant intra-arterial chemotherapy for locally advanced breast cancer by different methods].
For neoadjuvant intra-arterial (IA) chemotherapy in locally advanced breast cancer patients, Seldinger's methods were found to be convenient and had the same effect and outcome as conventional methods. The prognosis of the patients in whom IA chemotherapy was locally effective and had fewer than n 1 lymph node metastases was comparatively favorable. However, several patients who underwent IA chemotherapy later experienced local recurrence, and the cause of these patient's death was distant metastases in almost all cases. We recommend neoadjuvant IA and systemic chemotherapy, and systemic adjuvant chemotherapy.
Adult↗
[A case of locally advanced breast cancer successfully treated with wide resection and reconstruction of chest wall with A-O metallic plates].
A 63-year-old female with locally advanced breast cancer was treated with preoperative chemotherapy using docetaxel. The therapeutic regimen was comprised of four cycles at 3-week intervals. One cycle consisted of 80 mg of docetaxel which was administered on day 1. A remarkable response was confirmed. The side effects such as leukopenia, general fatigue and alopecia were moderate and had no influence on the patient's QOL. After preoperative chemotherapy, a full thickness chest wall resection was performed. Chest wall defect was reconstructed with orthopedic A-O metallic plates, Marlex mesh and rectus abdominis myocutaneous flap. These metal plates were very useful because it was easy to bend and twist them manually to fit the defect at the time of operation. Moreover, the curved metal plates preserved the cone form of the chest cage. The postoperative course was favourable without frail chest or wound infection.
Antineoplastic Agents, Phytogenic↗
Hepatoma cell migration through a mesothelial cell monolayer is inhibited by cyclic AMP-elevating agents via a Rho-dependent pathway.
1-Oleoyl lysophosphatidic acid (LPA) induces transmonolayer migration (in vitro invasion) of rat ascites hepatoma MM1 cells and their morphological changes leading to the migration. We have previously shown that an LPA analog, palmitoyl cyclic phosphatidic acid (Pal-cPA), suppresses transmonolayer migration of MM1 cells by rapidly increasing the intracellular cyclic AMP (cAMP) concentration. We report here that various cAMP-elevating agents, including dibutyryl cAMP, forskolin, cholera toxin and 3-isobutyl-1-methylxanthine, consistently inhibited LPA-induced transmonolayer migration of MM1 cells. Moreover, pull-down assays for GTP-bound, active RhoA demonstrated that the blockage by cAMP-elevating agents of morphological changes leading to the migration was probably mediated through inhibiting RhoA activation.
Animals↗
K-ras point mutation is associated with enhancement by deoxycholic acid of colon carcinogenesis induced by azoxymethane, but not with its attenuation by all-trans-retinoic acid.
The effects of deoxycholic acid (DCA) with and without all-trans-retinoic acid (ATRA) on the incidence of colon tumors induced by azoxymethane, the incidence of K-ras point mutation in colon tumors and the labeling index of colon mucosa were investigated in male Wistar rats. Rats received 5 weekly injections of 7.4 mg/kg body weight of azoxymethane. From the start of the experiment, all rats in 3 groups also received chow pellets containing 0.3% DCA with and without s.c. injections of 0.75 or 1.5 mg/kg body weight of ATRA every other day until the end of week 45. Oral administration of DCA significantly increased the incidence of colon tumors in week 45. Concomitant use of DCA and ATRA at either dose significantly attenuated the enhancement by DCA of colon tumorigenesis. Administration of DCA significantly increased the incidence of K-ras point mutation in colon tumors and the labeling index in the colon mucosa. Combined administration of DCA and ATRA significantly reduced the labeling index of colon mucosa, which was increased by DCA, but did not affect the incidence of K-ras point mutation in colon tumors. These findings suggest that DCA enhances development of colon tumors and that this enhancement is attenuated by ATRA. A possible mechanism of this enhancement is induction of K-ras point mutation. However, decreased cell proliferation in the colon mucosa may be closely related to the attenuation of DCA-enhanced colon tumorigenesis, but not suppression of K-ras point mutation.
Administration, Oral↗
Genistein attenuates peritoneal metastasis of azoxymethane-induced intestinal adenocarcinomas in Wistar rats.
The effects of the soybean isoflavonoid genistein on the development of bombesin-enhanced peritoneal metastasis from intestinal adenocarcinomas induced by azoxymethane (AOM) were investigated in male inbred Wistar rats. From the beginning of the experiment, rats were given 10 weekly s.c. injections of AOM (7.4 mg/kg body weight) and s.c. injections of bombesin (40 microg/kg body weight) every other day, and from week 16, s.c. injections of genistein (5 or 10 mg/kg body weight) every other day until the end of the experiment in week 45. Bombesin significantly increased the incidence of intestinal tumors and of cancer metastasis to the peritoneum. Although genistein administered at either dose had little or no effect on the enhancement of intestinal carcinogenesis by bombesin or on the location, histologic type, depth of involvement, labeling index, or growth pattern of intestinal cancers, it significantly decreased the incidence of cancer metastasis. Genistein also significantly decreased the incidence of lymphatic vessel invasion of adenocarcinomas, which was enhanced by bombesin. Our findings indicate that genistein attenuates cancer metastasis by inhibiting cancer cell invasion into lymphatic vessels through activities that do not affect the growth of intestinal cancers.
Animals↗
Suppression by Chai-hu-gui-zhi-tang of the development of liver lesions induced by N-nitrosomorpholine in Sprague-Dawley rats.
The effects of Chai-hu-gui-zhi-tang (TJ-10) on the development of liver lesions induced by N-nitrosomorpholine and on labeling and apoptotic indices were investigated in male Sprague-Dawley rats. Rats were given chow pellets containing 0.5 or 1.0% TJ-10 and, from the beginning of the experiment, were given drinking water containing N-nitrosomorpholine for 8 weeks. Visible white liver nodules, cellular alteration foci, and hepatic foci staining positively for glutathione-S-transferase, placental type, were examined macroscopically or histochemically. In week 16, TJ-10 at both dosages significantly reduced the incidence, and/or number of visible white nodules and hepatic lesions. Quantitative histologic analysis also showed that prolonged feeding of TJ-10 at both dosages significantly reduced the number of hepatic foci positive for glutathione-S-transferase, placental type. Administration of TJ-10 at both dosages also significantly decreased the labeling index of adjacent liver and significantly increased the apoptotic index of adjacent liver but had no significant effect on those of neoplastic lesions. These findings indicate that TJ-10 suppresses the development of liver lesions and suggest that this effect might be related to TJ-10's inhibition of cell proliferation and induction of apoptosis in adjacent hepatocytes.
Animals↗
In vivo electroporetic transfer of bcl-2 antisense oligonucleotide inhibits the development of hepatocellular carcinoma in rats.
To investigate the potential use of a bcl-2 antisense oligonucleotide for therapy against hepatocellular carcinoma, we examined the effects of the electroporetic transfer of a bcl-2 antisense oligonucleotide on rat hepatocarcinogenesis induced by N-nitrosomorpholine (NNM). Sprague-Dawley rats were given water containing 175 mg/l NNM for 8 weeks and received intraperitoneal injections of a bcl-2 antisense phosphorothioate oligonucleotide, a sense oligonucleotide or a scrambled sequence oligonucleotide encapsulated in empty liposomes, at a dose of 150 microg oligonucleotide/kg body weight, every 4 weeks. One hour after injection, in vivo electroporation was performed on the liver to achieve selective transfer of the oligonucleotides. By week 16, the rats that had received the bcl-2 antisense oligonucleotide had significantly fewer and smaller precancerous liver lesions positive for glutathione-S-transferase (placental type), and a significantly lower incidence of hepatocellular carcinoma in the electroporation zone than rats that had received the sense or the scrambled oligonucleotides. Moreover, the bcl-2 antisense oligonucleotide significantly increased the apoptotic indices in foci, neoplastic nodules and in hepatocellular carcinomas. The expression of bcl-2 mRNA also decreased, and 3'-fragments of bcl-2mRNA produced by cleavage at the antisense target site were detected in rat liver. Mean cellular fluorescence in the liver increased with higher doses of fluorescein-isothiocyanate-labeled antisense or sense oligonucleotides. Our results show that the electroporetic transfer of bcl-2 antisense oligonucleotide can inhibit rat hepatocarcinogenesis.
Animals↗
ras p21 Isoprenylation inhibition induces flat colon tumors in Wistar rats.
PURPOSE: The effect of pravastatin, an inhibitor of ras p21 isoprenylation, on the gross type of colon tumors induced by azoxymethane was investigated in Wistar rats. METHODS: Rats received ten weekly subcutaneous injections of 7.4 mg/kg body weight of azoxymethane and intraperitoneal injections of 10 or 20 mg/kg body weight of pravastatin every other day until the end of the experiment at Week 45. RESULTS: Administration of pravastatin at both dosages had no significant effect on the incidence of colon tumors but significantly increased the incidence of rats with adenomas only. In contrast to the elevated adenomas in control rats, flat adenomas were significantly more prevalent in rats given pravastatin. Pravastatin at both doses significantly decreased the labeling index, but not the apoptotic index, of elevated adenomas, whereas it significantly decreased the labeling index but increased the apoptotic index of flat adenomas. Administration of pravastatin at both dosages also significantly decreased the amounts of membrane-associated ras p21 in colon tumors. CONCLUSIONS: These findings suggest that the ras oncogene may be closely related to the development of adenocarcinomas from adenomas and the development of elevated or polypoid tumors of the colon.
Adenocarcinoma↗
A case of breast cancer diagnosed by inguinal lymph node metastasis.
We describe a case of a 58-year-old woman with right inguinal lymph node swelling and a T1 tumor in the right breast. She was referred with an 18-month history of the former complaint and a six-month history of the latter. Excisional biopsy of the inguinal lymph node revealed breast cancer metastasis. Radiographical examination showed no metastases to the lungs, liver or bone. Modified radical mastectomy was performed. Histological examination revealed solid tubular carcinoma, PT2, PM (axillary lymph node metastases 4/16), stage IV. Estrogen and progesterone receptors were negative. Three cycles of postoperative cyclophosphamide, adriamycin and 5-fluorouracil (CAF) chemotherapy were given, and the right inguinal area was irradiated with 40 Gy. The patient complained of swelling in both legs three years after surgery. Computed tomography revealed marked lymph node swellings in the pelvic cavity. She died six months later. Inguinal lymph node metastasis from breast cancer is very rare, although distant lymph node metastasis in the cervix occurs frequently. This case should help clarify how breast cancer metastasizes to distant lymph nodes.
Adenocarcinoma↗
Multiple inflammatory pseudotumors mimicking liver metastasis from colon cancer: report of a case.
A 54-year-old man underwent an operation for colon cancer histologically diagnosed as moderately differentiated adenocarcinoma with clinical staging of Dukes C. He was prescribed carmofur for adjuvant chemotherapy. A follow-up computed tomography scan done 6 months later revealed two new low-density areas in the liver. A diagnosis of metastatic adenocarcinoma from the previous colon cancer was presumed, based on the patient's history and radiological findings, and resection of the affected area of liver was performed. Histological examination of these tumors revealed that they were inflammatory pseudotumors (IPT). The patient had an excellent postoperative course and has shown no further signs of recurrence in the 3 years since his last operation. IPT of the liver is a rare disease, for which no methods of diagnosis and treatment have been established, since it is difficult to distinguish IPT from hepatocellular carcinoma or metastatic carcinoma. We describe this case with a review of the 101 cases of IPT documented in the Japanese literature, in the hope that it will contribute to the diagnosis and treatment of this unusual disease entity.
Adenocarcinoma↗
Total gastrectomy with dissection of lymph nodes along the splenic artery: a pancreas-preserving method.
BACKGROUND: In Japan, the tail and body of the pancreas are generally removed for dissection of lymph nodes along the splenic artery. A new pancreas-preserving method was developed to decrease the postoperative complications due to pancreatic resection. PATIENTS AND METHODS: Between 1981 and 1989, 110 patients were registered in a randomized controlled trial, which included total gastrectomy plus dissection of lymph node along the splenic artery, either with (55 patients: Group A) or without (55: Group B) pancreas tail resection. In Group B, the splenic artery and spleen were removed and the pancreas was preserved. There were no significant differences between the two groups in terms of sex, age, location, microscopic classification, or disease stage. The postoperative complications and survival rates were compared between the two groups. RESULTS: The average number of dissected nodes along the splenic artery was 4.6 and 4.1 for Groups A and B, respectively. The amounts of blood loss during the operation were 994 ml and 904 ml for groups A and B, respectively. Anastomosis failure and/or pancreatic fistula occurred in nine patients in Group A (16%) and seven in Group B (13%). One year after the operation, a glucose tolerance test showed diabetes in 6% and impaired glucose tolerance in 33% of patients in group A, while these findings were normal in group B. The 5-year survival rates were 80% and 76.7% for groups A and B, respectively. CONCLUSIONS: The pancreas-preserving method described here was superior to the more common pancreas resecting method with regard to surgical risk and postoperative glucose tolerance.
Adult↗
Diagnosis of the extent of gastric cancers by a new endoscopic ultrasonic tactile sensor.
BACKGROUND: Because gastrointestinal cancers are generally firm, the presence and extent of a tumor can be assessed by touch during surgery. However, an objective scale for evaluating tissue hardness does not exist. We developed a new instrument, the endoscopic ultrasonic tactile sensor, that allows objective evaluation of hardness. In this study the usefulness of this device for diagnosis of the extent of gastric cancers was evaluated. METHODS: Twenty-three patients with depressed or ulcerated early gastric cancers and 7 patients with active or healed gastric ulcers underwent endoscopic examination with the ultrasonic tactile sensor before gastrectomy. RESULTS: Gastric cancers were significantly harder than normal mucosa or gastric ulcers. The histologic type of gastric cancer and the presence of ulceration did not affect tumor hardness and mucosal cancers could not be differentiated from submucosal or deeper cancers. CONCLUSIONS: This new ultrasonic tactile sensor was useful for endoscopic diagnosis of the extent of gastric cancers.
Endosonography↗
Increased expression of S100A6 at the invading fronts of the primary lesion and liver metastasis in patients with colorectal adenocarcinoma.
Two members of the S100 gene family, S100A6 and S100A4 have been suggested to be associated with cancer invasion and metastasis. To study their involvement in the malignancy of human colorectal adenocarcinoma, we examined the protein expression levels of S100A6 and S100A4 in the primary colorectal adenocarcinoma (T) and paired adjacent normal colorectal mucosa (N) from 12 cases, quantitatively by Western blot analysis. In 11 of 12 and seven of 12 cases, S100A6 and S100A4 expression levels were higher in T than in N, respectively. Average S100A6 level in T was significantly higher than in N (about x 2.3;P = 0.001), whereas average S100A4 level in T was not. When S100A6 expression levels in three sets of matched samples of primary colorectal adenocarcinoma (T) and liver metastasis (M) were examined, S100A6 levels were higher in M than in T in two of three cases. Immunohistochemical analysis using monoclonal anti-S100A6 antibody showed that 23 of 42 (55%) primary colorectal adenocarcinoma and 15 of 16 (94%) liver metastasis specimens were positively stained. S100A6 immunostaining of primary colorectal adenocarcinomas was significantly more intense in the invading fronts with structural atypia than in central portions with glandular structure (P< 0.0001), whereas Ki-67 staining (a growth marker) was similar in these two portions. Interestingly, S100A6 and Ki-67 immunostaining patterns in liver metastases were also the same as in primary lesions. These results suggest that S100A6 is involved in the invasive process of human colorectal adenocarcinomas and that S100A6 expression levels decrease when carcinoma cells form glandular structure again at the central portions of metastatic nodules.
Adenocarcinoma↗
Endoscopic piecemeal resection with submucosal saline injection of large sessile colorectal polyps.
BACKGROUND: Because endoscopic en bloc resection of large, sessile colorectal polyps is technically difficult, they are usually resected piecemeal. However, piecemeal resection makes it difficult to evaluate the completeness of the resection histopathologically. In this study the efficacy of endoscopic piecemeal resection of large, sessile colorectal polyps was investigated after follow-up greater than 1 year. METHODS: We removed 56 sessile colorectal polyps 2 cm or greater in diameter in 56 patients by using an endoscopic submucosal saline injection technique. Endoscopic examinations were repeated at 3, 6, and 12 months and longer after initial endoscopic resection. If no residual tumor was found endoscopically and histologically, the patient was considered to be "cured." RESULTS: Of the 56 polyps, 14 (25%) were resected en bloc, and 42 (75%) were resected piecemeal. Of the 42 patients treated with piecemeal resection, 23 (55%) required additional endoscopic or surgical interventions. In patients followed 1 year or longer after initial treatment, the cure rate by en bloc resection was 100% (14 of 14) and that by piecemeal resection was 83% (35 of 42). Arterial bleeding occurred in 4 patients (7%) during or after endoscopic resection. In 3 of them, bleeding was stopped by endoscopic clipping, but 1 patient required emergent laparotomy. CONCLUSIONS: Endoscopic piecemeal resection after submucosal saline injection with an intensive follow-up program is a safe and effective treatment for large, sessile colorectal polyps.
Adult↗
Effectiveness of endoscopic mucosal resection with submucosal saline injection technique for superficial squamous carcinomas of the esophagus.
BACKGROUND: Intraepithelial cancers (m1 cancer) and cancers that penetrate the basement membrane but do not approach the muscularis mucosae (m2 cancer) do not have lymph node metastasis and thus can be removed completely with mucosal resection. Therefore, in this study, the effectiveness of endoscopic mucosal resection with submucosal saline injection for removal of superficial esophageal cancers was investigated prospectively. METHODS: Twenty-five superficial esophageal cancers in 21 patients were removed with submucosal saline injection. When it was thought that a tumor had not been completely resected en bloc, it was removed completely in piecemeal fashion. Endoscopy was repeated 1, 3, 6, 12 months or more after endoscopic resection. RESULTS: All superficial esophageal cancers were completely removed: 18 (72%) en bloc and 7 (28%) by piecemeal resection. No recurrence was found during a mean observation period of 2.0 years (range 0.8 to 3.6) after resection. Bleeding occurred in 5 cases (24%) during or after resection but was successfully treated with the endoscopic alginate or thrombin spray technique. There was no perforation. CONCLUSION: Endoscopic mucosal resection with submucosal saline injection is effective for removal of superficial cancers of the esophagus.
Aged↗
Effectiveness of the near-infrared electronic endoscope for diagnosis of the depth of involvement of gastric cancers.
BACKGROUND: Near-infrared light penetrates deeply into tissue but is not visible with a conventional endoscope. We developed a new infrared electronic endoscope system and evaluated its usefulness for assessing the depth of involvement of gastric cancers. METHODS: A total of 61 patients with depressed or ulcerated gastric cancers underwent infrared endoscopy after intravenous injection of indocyanine green. RESULTS: Intramucosal cancers were observed as tumors with or without a homogeneous tumor stain, whereas submucosal or deeper cancers were observed as tumors with an inhomogeneous stain or with pooling of the dye. Histologic examination showed staining properties of gastric cancers were significantly correlated with the characteristics of the vascular bed. The accuracy for depth of cancer invasion was 89% for mucosal cancers and 89% for submucosal or deeper cancers. CONCLUSION: Our new infrared electronic endoscope system was useful for distinguishing mucosal cancers from submucosal or deeper cancers either with or without ulcerative changes.
Adult↗