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H Katai

Publications and source records attributed to H Katai.

52 records · Page 3Linked to original sources

Surgical treatment for gastric cancer: the Japanese approach.

Present status of gastric cancer surgery in Japan and several new procedures are reviewed in this article. Japanese treatment results of this disease were significantly better than Western results even when stages were adjusted. Generally speaking, Japanese surgical procedures are more aggressive and meticulous compared with the Western approach, and these attitudes have produced the difference in survival. Particularly, systematic lymph node (LN) dissection is included as a standard procedure, and the adjacent organs are frequently resected when tumor invades them. The latest topics in surgery are the transdiaphragmatic approach for procedures in the mediastinum, para-aortic LN dissection, computer-assisted rational lymphadenectomy, LN imaging for complete dissection, removal of the peritoneum, and hyperthermo-chemotherapy for peritoneal carcinomatosis. Consideration of postoperative quality of life (QOL) is a new trend, and many interesting procedures have been proposed to maintain QOL, such as endoscopic mucosal resection and laparoscopic wedge resection for early cancer, pylorus-preserving gastric resection to reduce dumping syndrome, pancreas-preserving total gastrectomy to reduce fistula and postoperative diabetes.

Endoscopy↗

[Overview of clinical trials on adjuvant chemotherapy for curatively resected gastric cancer].

Reports of the results of clinical trials on adjuvant chemotherapy for curatively resected gastric cancer were reviewed. All but two trials did not show its efficacy. In spite of this, understanding some results of subset analysis as definite proof, a consensus was achieved in Japan on its efficacy due to lack of proper knowledge of medical statistics among surgeons. Recently it has been recognized that this consensus was groundless and that evaluation of adjuvant chemotherapy should be carried out again. The results of the trial of JCOG, comparing adjuvant chemotherapy versus control (surgery alone) are therefore awaited. For the moment, all clinical trials on adjuvant chemotherapy for curatively resected gastric cancer should have an arm of surgery alone as control.

Antineoplastic Combined Chemotherapy Protocols↗

Transforming growth factor beta gene expression is transiently enhanced at a critical stage during liver regeneration after CCl4 treatment.

BACKGROUND: Transforming growth factor beta 1 (TGF beta 1) gene expression is increased in CCl4-injured rat livers. The biologic link of this increase and liver regeneration has not been established. EXPERIMENTAL DESIGN: To explore the identity of the TGF beta 1-producing cells in the CCl4 regenerating liver, we hybridized untreated and CCl4-treated liver sections of TGF beta 1-specific riboprobes and immunolocalized TGF beta 1 protein, simultaneously. To assess the dynamics of cellular proliferation during hepatic regeneration, chronologic changes in the cellular DNA synthesis were also monitored by [3H]thymidine incorporation and autoradiography. In situ hybridization analyses were further extended by subfractionation of nonparenchymal cells into Kupffer cells/macrophages, endothelial and Ito cells, and determining TGF beta 1 mRNA levels in different cell types. Finally, we experimentally tested if the temporal relationship between the transient elevation of expression of TGF beta 1 and hepatic cell proliferation were casually related. RESULTS: We observed that the rate of DNA synthesis was the highest around 36 hours post-treatment and preceded the time of enhanced accumulation of TGF beta 1 transcripts and protein, both of which peaked at approximately 48 hours and declined thereafter. Transient upregulation of TGF beta 1 gene expression was seen in the inflammatory cell infiltrates around the central vein and at less extent, in portal tracts, and in perisinusoidal cells near the zone of necrosis. Like TGF beta 1 transcripts, TGF beta 1 protein was also predominantly co-localized in and around the pericentral and periportal cells. Kupffer cells, that accumulate abundantly in the liver 48 hours after CCl4 administration, were the primary producers of TGF beta 1. The injection of neutralizing anti-TGF beta 1 antibodies into animals prevented both the decline in [3H]thymidine incorporation and cell division in the waning phases of hepatic regeneration at 72 hours. CONCLUSIONS: Based on our observations that (i) TGF beta 1 gene expression is triggered transiently during a crucial phase of liver regeneration, (ii) the exogenously added TGF beta 1 inhibits hepatic DNA synthesis and that (iii) the administration of TGF beta 1 antibodies extends the proliferative response of the regenerating liver, we conclude that TGF beta 1 plays a pivotal role in down regulating liver regeneration.

Animals↗

[Transcatheter arterial chemoembolization to hepatic metastases from colorectal cancer].

Response of transcatheter arterial chemoembolization (TAE) and transcatheter arterial infusion chemotherapy to hepatic metastases was reported in 25 cases of colorectal cancer. The severity of liver metastases was H1 in 12 cases, H2 in 9 cases, and H3 in 4 cases. Liver metastases were found during surgery in 12 of these patients, and 13 showed metastases or recurrence in the liver after resections of primary lesions. Catheters were inserted selectively to the proper hepatic artery by Seldinger's method, followed by injection of embolizing agents (gelfoam particles of Lipiodol) with adriamycin or 5-FU + leucovorin in most cases. Response was assessed by blood CEA levels, diagnostic imaging, and period of survival. In 5 cases in whom liver resections were performed following TAE, response was assessed by histopathological findings of the resected specimens. Two patients showed partial response (PR), 12 no change (NC) and 11 progressive disease (PD) by diagnostic imaging. Blood CEA levels fell to less than 50% of pre-treatment levels in 26% of cases. Histological changes by TAE were confirmed in 4 of 5 cases after liver resections, but viable cancer cells were observed in all cases. A case of mucinous cancer showed no change histologically. As the other case of mucinous cancer showed PD by diagnostic imaging, TAE was not suggested to be suitable to treat cases of mucinous cancer. More improvements in the dosage, drugs and times of treatment were suggested to yield a better response rate in TAE therapy for liver metastases from colorectal cancer.

Adult↗

An AP-1-like motif in the first intron of human Pro alpha 1(I) collagen gene is a critical determinant of its transcriptional activity.

The first intron of the human Pro alpha 1(I) collagen gene contains an orientation-dependent enhancer composed of both positive and negative cis-acting elements involved in the transcriptional regulation of this gene. Deletion of a 360 bp Sau 3A intronic fragment spanning nucleotide +494 to +854 (S360) resulted in dramatic down-regulation of pCOL-KT (Thompson et al., J Biol Chem 266: 2549-2556, 1991). Using a DNaseI protection assay, we demonstrate a single footprint located at +590 to +615 in the S360 fragment; nuclear extracts prepared from mesenchymal and nonmesenchymal cells exhibited similar binding characteristics. A double stranded oligonucleotide representing a consensus Ap-1 binding sequence competed with S360 for binding. In contrast to what occurred in response to S360 deletion which was always accompanied by reduced expression, the deletion of the Ap-1 binding site (+598 to +off) caused either increased or decreased expression of the reporter gene depending on the target cell. Site-directed mutations in the Ap-1-like cis-element of Pro alpha 1(I) were also tested in transient expression assays. Consistent with the paradoxical results of Ap-1 deletion, we observed that the functional consequences of mutations in the Ap-1 site also varied in different cells. In A204 cells, one point mutation, which resulted in the loss of protein binding to S360, led to increased CAT activity while another point mutant, which retained binding of the Ap-1 like trans-acting factor(s), showed decreased CAT expression. The effects of these two mutations in the HFL-1 cells were exactly opposite of what was seen for A204 cells. Based on these observations, we postulate that the Ap-1 site plays a critical role in the transcriptional activity of the human Pro alpha 1(I) gene. The implications of an apparently dual mode of regulation through a single cis-regulatory element are discussed.

Base Sequence↗

Human fibroblasts synthesize elevated levels of extracellular matrix proteins in response to interleukin 4.

Interleukin 4 (also known as "B cell stimulatory factor-1"), a cytokine product of T lymphocytes and mast cells, stimulates synthesis of the extracellular matrix proteins, types I and III collagen and fibronectin, by human dermal fibroblasts in vitro. Stimulation of collagen by human recombinant (hr)IL-4 was also demonstrated in several fibroblastic synovial cell lines obtained from patients with rheumatoid arthritis and osteoarthritis. The stimulatory effect of hrIL-4 on fibroblast collagen synthesis was specifically neutralized by rabbit anti-hrIL-4 Ig. IL-4 specifically increased the steady-state levels of types I and III procollagen and fibronectin mRNAs, with no effect on cytoplasmic beta-actin mRNA. Quantitative analysis of the levels of Pro alpha 1(I) collagen transcripts in IL-4-treated fibroblast cultures was also corroborated by antisense RNA-mRNA hybridization and RNAse resistant hybrids which showed that IL-4-treated fibroblasts expressed higher levels of Pro alpha 1(I) collagen transcripts. Nuclear run-off transcription experiments indicated that IL-4 stimulated the rates of mRNA biogenesis. Based on these observations we conclude that IL-4 exerts its effect on collagen and fibronectin synthesis at the pretranslational level, resulting in synthesis of these extracellular matrix proteins. These and other data suggest that IL-4 may be a "fibrogenic cytokine" that could be important in promoting biogenesis of extracellular matrix proteins in normal wound healing and in pathological fibrosis in which mast cells and T lymphocytes play a central role.

Cells, Cultured↗

[A case of advanced breast cancer responding to low-dose 5'-DFUR].

A 69-year-old female patient with locally advanced breast cancer with multiple bone metastases (T4cN2-M1) was treated with 5'-DFUR after failure of tamoxifen treatment. The 5'-DFUR dose was limited to 600 mg per day, half the usual dose, because of its gastroenterological side effects. The primary tumor and metastatic axillary lymph nodes regressed three months after the start of treatment, and the complete remission of lesions was obtained in 16 months. Reduction of bone metastasis was confirmed by the disappearance of osteolytic lesion in the skull roentgenogram and the decrease of abnormal accumulation on the bone scintigram. Serum levels of CEA and ST-439 markedly reduced during the treatment as the disease regressed.

Aged↗

[Intra-arterial chemotherapy of local recurrence and non-curative case of colorectal cancer].

Twelve colorectal cancer patients, including 9 with local recurrent cancer and 3 with remnant cancer after surgery, were treated with intraarterial chemotherapy. Three cases were treated with MMC injection alone, 1 case with MMC combined with irradiation (MMC-R) and 8 cases with ADM combined with irradiation (ADM-R). In 7 evaluable patients, the response rate was 28.6% with 1 CR case, 1 PR case and 5 NC cases. The 2 cases treated with ADM-R were successful. Six of 8 patients treated with ADM-R survived more than 1 year, while all 4 patients treated with MMC or MMC-R died within 8 months. The cumulative survival rate after ADM-R treatment was 44% at 24 months. It is suggested that the combination of intra-arterial chemotherapy and radiation therapy is an effective treatment for local recurrence and non-curative cases of colorectal cancer.

Chemotherapy, Adjuvant↗

Generation of monoclonal antibodies to the zinc finger domain of the eukaryotic transcription factor Sp1.

Using a synthetic peptide that encompasses the zinc finger domain of the eukaryotic transcription factor Sp1, we produced a number of monoclonal antibodies that specifically reacted with the target antigen. Analysis by competitive inhibition assay of five of the monoclonal antibodies revealed that they all recognized a dominant epitope in the synthetic peptide and reacted strongly to recombinantly synthesized beta-galactosidase-Sp1 fusion polypeptide. To determine cellular distribution of Sp1-like molecules, cytoplasmic and nuclear proteins from human lung fibroblasts (HFL-1) and a human rhabdomyosarcoma cell line (A204) were immunoblotted and reacted with our antibodies. In addition to the well characterized 95 Kd and 105 Kd proteins, considered to be the authentic Sp1 polypeptide, a number of other cellular proteins reacted with these antibodies. Immunofluorescence staining of the cells with mAb to the zinc finger of Sp1 also revealed cell-specific differences in intracellular distribution of Sp1-like molecules. Both cytoplasmic and nuclear staining was readily observed in the rhabdomyosarcoma cells. In contrast, while some HFL-1 cells exhibited staining of only cytoplasm, both cytoplasmic and nuclear immunofluorescence was seen in others.

Animals↗

[Modified operation for early gastric cancer; rationale, technic and results].

During 1964 to 1976, standard operation, which consisted of subtotal or total gastric resection, extended dissection of lymph node and omentobursectomy, was performed for early gastric cancer. The result was satisfactory, i.e., 5 year relative survival rate was 95.2 per cent. But there were very few lymph-node metastases, which localized almost perigastric, no marked infiltration into the esophagus in cases of early cancer in the cardiac region. Macroscopic determination about the margin of the cancer was well compatible with microscopic one. The recurrent cases seemed to be due to hematogenous metastasis. These suggest that an extended lymph-node dissection, omentobursectomy and thoracotomy are not necessary for the early cancer. Proximal gastric resection and pylorus preserving gastric resection were indicated in some cases. In addition, the diagnosis of the early cancer, especially about the depth of invasion into the gastric wall, was accurate except for the early cancers which contained ulcerous lesion. Since 1977 modified operation for the early cancer has been applied. At this operation, lymph-node dissection was limited to perigastric region, omentobursectomy was omitted and the pancreas and spleen preserved. Through this method the operative time and blood unit have been much spared and the 5 year postoperative relative survival rate has improved, i.e., 100 per cent. It is concluded that the modified operation should be performed for the early gastric cancer.

Humans↗

[New operative technic for resecting cardiac cancers with dissection of the lower mediastinal lymph nodes through transabdominal phrenotomy using an improved hook suspender and an autosuture surgical stapling instrument].

To obtain a sufficient operative field at the operation for cardiac cancer, especially with esophageal infiltration, thoracotomy or sternotomy has been added to laparotomy. These procedures are not easy and cause great stress in patients. Through our new technique, left sided thoracotomy and sternotomy can be eliminated in favor of transabdominal phrenotomy, which is able to be performed much easier to obtain a good operative field. In order to perform the phrenotomy, the diaphragm has to be stretched using our modified hook suspender, by which the costal arch is lifted strongly upward and cranially. With these procedures, about a 5cm long esophagus is able to be resected with lymph node dissection in the lower mediastinum without difficulty. No marked influence of the hook suspender as well as the phrenotomy has been recognized on respiratory and circulatory systems. The anastomosis between the esophagus and jejunum or residual stomach seems to be very difficult, because the site of the anastomosis is located quite deep in the mediastinum. This problem, however, can be completely resolved by means of a surgical stapling autosuture instrument.

Cardia↗

Pancreas-preserving total gastrectomy for proximal gastric cancer.

Lymph node (LN) dissection along the upper border of the pancreas is one of the essential parts of curative surgery for gastric cancer, and the distal portion of the pancreas was frequently resected for complete removal of LNs along the splenic artery. However, pancreatic juice leakage, subphrenic abscess, and postoperative diabetes were common complications in patients treated by pancreatic resection. To avoid these problems a new surgical procedure, the pancreas-preserving operation, was developed by Maruyama in 1979. We found that lymphatic channels from the stomach did not flow into the pancreas parenchyma, and that the spleen, splenic artery, and fatty connective tissue including nodes could be removed completely without dissection of the pancreas parenchyma and splenic vein. The preserved pancreas receives its arterial blood supply through the transverse pancreatic artery, and its preservation prevents postoperative diabetes. A total of 299 patients were treated by this procedure. The operative mortality rate was 0.3%, the hospital death rate 1.6%, and the surgical complications rate 19.6%. The cumulative 5-year survival rate for those with stage II was 70.5% and for those with stage III 54.1%. These results were superior to those of the pancreas resection group.

Gastrectomy↗

[The current situation and treatment strategy for gastric cancer at the National Cancer Center of Tokyo, Japan].

At the National Cancer Center of Tokyo Gastric Division, from 13/09/1993 to 12/11/93, 42 gastrectomies, 3 local resections and 1 exploratory laparotomy, for gastric cancer, were carried out. Resection R2 were carried out in 29/42 (69%), resection R2 plus dissection of the station 16 in 5/42 (12%), resection R3 plus dissection of the station 16 in 4/42 (9.5%) and distal pancreas preserving in 11/14 (78.6%) of the total gastrectomies. The most frequently type of reconstruction done after distal gastrectomy was Billroth 1 in 20/28 (71.4%) and the most frequent stage of the disease was la-b in 34/46 (74%). Postoperative severe complications were present in 5/42 (12%) and the most frequently histological type was tubular adenocarcinoma 27/46 (58.7%).

Adult↗