Biomedical subjects

M Kayahara

Publications and source records attributed to M Kayahara.

At least 19 recordsLinked to original sources

PubMed1999

Role of nodal involvement and the periductal soft-tissue margin in middle and distal bile duct cancer.

OBJECTIVE: To determine the pattern of middle (Bm) and distal (Bi) bile duct cancers in an attempt to optimize surgical treatment. SUMMARY BACKGROUND DATA: Lymph node involvement and neural plexus invasion are the prognostic factors most amenable to surgery in Bm and Bi disease. However, a detailed analysis of these factors has not been conducted. METHODS: Fifty patients with Bm and Bi disease (Bm 14 patients, Bi 36 patients) were examined histopathologically. A precise determination was made of lymph node involvement and neural plexus invasion. Important prognostic factors were examined by clinicopathologic study to apply these findings to surgical management. RESULTS: Frequencies of nodal involvement for Bm and Bi disease were 57% and 71%, respectively. The inferior periductal and superior pancreaticoduodenal lymph nodes were most commonly involved. Neural plexus invasion occurred in 20% of patients, particularly involving the plexus in the hepatoduodenal ligament and pancreatic head. Tumor was present at the surgical margin in 50% and 14% of patients with Bm and Bi disease, respectively. Five-year survival rates were 65% in the absence of nodal metastasis and 21% with nodal metastasis. A significant correlation existed between absence of tumor at the surgical margin and survival. A Cox proportional hazard model projected absence of tumor at the surgical margin, followed by nodal involvement, as the strongest prognostic variables. CONCLUSIONS: Absence of tumor at the surgical margin and nodal involvement are important independent prognostic factors in Bm and Bi disease. Skeletonization of the hepatoduodenal ligament, including portal vein resection, is necessary for patients with Bm disease, and a wide nodal dissection is essential in all patients.

Adult↗

PubMed1998

Bafilomycin A1 induces apoptosis in the human pancreatic cancer cell line Capan-1.

Bafilomycin A1, a specific inhibitor of vacuolar type H(+)-ATPase, can inhibit the growth of a variety of cultured cells in a dose-dependent manner, but its mechanism is unclear. The aim of this study was to examine whether bafilomycin A1 inhibits the growth of Capan-1 human pancreatic cancer cells through apoptosis. The effect of bafilomycin A1 on tumour growth in vitro and in vivo was examined using an MTT assay and an in vivo tumour model. The presence or absence of apoptosis was determined by morphology and DNA analysis of tumour cells. The concentration of bafilomycin A1 for 50 per cent inhibition of cell viability during 72 h by the MTT assay was 5 nm. In DNA analysis, a ladder of fragmented DNA was detected in Capan-1 cells treated with bafilomycin A1 at concentrations greater than 10 nm for 24 h. Nude mice bearing a xenografted Capan-1 cell line tumour received 4 weeks of bafilomycin A1 (1.0 mg/kg per day). This treatment significantly inhibited tumour growth compared with controls after 21 days (P < 0.05). Histopathological examination of tumour cells in the treated group demonstrated signs of apoptosis with chromatin condensation and cell shrinkage. These observations suggest that bafilomycin A1 inhibits the growth of Capan-1 human pancreatic cancer cells through apoptosis.

Adenocarcinoma↗

PubMed1998

Cationic trypsinogen produced by human pancreatic ductal cancer has the characteristics of spontaneous activation and gelatinolytic activity in the presence of proton.

We examined whether human pancreatic ductal cancer cells express and secrete pancreatic cationic trypsinogen in vitro which can be spontaneously converted into active trypsin at acidic pH (pH 4.5-5. 5), in contrast to anionic trypsinogen. Cationic trypsinogen expression at the mRNA level was observed in differentiated Capan-1 and BxPC-3 cell lines. However, expression was not detected in either poorly-differentiated Panc-1 or undifferentiated MIAPaCa-2 cell line. The gelatinolytic activity of the activated form of trypsinogen in each conditioned medium in the presence of enterokinase (1.0 microg/ml) (a band with a molecular weight of approximately 23 kDa) corresponded well to the level of cationic trypsinogen mRNA. The spontaneous activation of trypsinogen also was observed by gelatin zymography of the acid-loaded conditioned medium (pH 5.5). These findings suggest that trypsinogen produced by human pancreatic ductal cancer has the characteristics of spontaneous activation and gelatinolytic activity in the presence of proton.

Culture Media, Conditioned↗

PubMed1997

Neurotrophin-3 expression in human pancreatic cancers.

Some neurotrophic factors stimulate process outgrowth in peripheral and/or central nerve fibres. There is no published report that has focused on the expression of neurotrophic factors in human pancreatic cancer except basic fibroblast growth factor. This study was therefore designed to examine the mRNA and protein levels of neurotrophin-3 (NT-3), which is one of the representative neurotrophic factors. The mRNA level for NT-3 was first investigated in eight pancreatic cancers and two samples of normal pancreas, using reverse transcription-polymerase chain reaction (RT-PCR). NT-3 protein expression was then studied in 47 human pancreatic cancers, using a monoclonal antibody against human NT-3 protein. There was a notable difference in the level of NT-3 mRNA between normal and pancreatic carcinoma tissues, with no evident difference in the expression of the beta-actin gene. Immunohistochemically, 34 of 47 pancreatic cancers (72 per cent) were mildly to markedly immunoreactive for NT-3 in the cytoplasma. Immunoreactivity was usually more pronounced at the infiltrative margins of the tumours. These observations suggest that pancreatic carcinoma overexpresses NT-3.

Adult↗

PubMed1997

Total resection of the head of the pancreas preserving the duodenum, bile duct, and papilla with end-to-end anastomosis of the pancreatic duct.

Many surgeons have recently attempted operative procedures for limited resection of the head of the pancreas. This site-specific approach has emerged as a result of precise diagnostic radiologic studies that have become available. The author performed a new operative procedure in 2 patients with mucin-producing pancreatic cysts that included total resection of the head of the pancreas with careful regard to its vasculature. The procedure provided a way of resecting the head of the pancreas while preserving the duodenum, bile duct, and papilla. The pancreatic duct was cut 5 mm before the point of confluence with the bile duct, and an end-to-end anastomosis was performed on the pancreatic duct. Both patients were discharged within 1 to 1.5 months after surgery, without complication. The operative procedure requires no processing of the jejunum, only a simple anastomosis of the pancreatic duct.

Anastomosis, Surgical↗

PubMed1997

Surgical strategy for carcinoma of the papilla of Vater on the basis of lymphatic spread and mode of recurrence.

BACKGROUND: Nodal status is one of the most important prognostic factors for carcinoma of the papilla of Vater. The pattern of lymphatic spread and mode of recurrence were analyzed by determining the frequency of nodal involvement and antemortem and postmortem examination of patients with recurrent disease. METHODS: From 1974 to 1994, 36 patients with carcinoma of papilla of Vater underwent pancreatectomy at the Kanazawa University Hospital. A precise evaluation of the nodal involvement was determined by means of careful pathologic review of the extended lymphadenectomy specimen. The mode of recurrence was determined by use of autopsy and radiographic examinations. RESULTS: Fifteen (42%) of 36 patients had nodal involvement. The lymph nodes with the highest metastatic rates were the inferior pancreaticoduodenal lymph nodes (number 13b) and the superior mesenteric lymph nodes (number 14) (13b, 31%; 14, 17%). There were no metastases in the perigastric lymph nodes. A significant relationship existed between the gross appearance of the primary tumor and nodal involvement (protruding, 22%; mixed type, 42%; ulcerative, 100%). The 5-year survival rates were 74% in the absence of nodal metastasis versus 31% with nodal metastasis. The 5-year survival rates for patients with protruding, mixed type, and ulcerative tumors were 75%, 49%, and 17%, respectively. Survival and recurrence were significantly correlated to gross appearance and nodal involvement. Retroperitoneal recurrence and liver metastasis were main modes of recurrence. CONCLUSIONS: Lymph node 13b is important in lymphatic metastasis to the superior mesenteric lymph nodes for carcinoma of papilla of Vater. Nodal dissection around the superior mesenteric artery is needed to improve the prognosis of carcinoma of papilla of Vater except in the nonexposed protruding tumor. Pylorus-preserving pancreatoduodenectomy may be indicated in patients with carcinoma of the papilla of Vater.

Adult↗

PubMed1997

Differential induction of apoptosis in Swiss 3T3 cells by nitric oxide and the nitrosonium cation.

We have investigated the effect of nitric oxide (NO) on apoptosis in Swiss 3T3 fibroblasts and compared it to the effect of the nitrosonium cation (NO+). Both species induced apoptosis, confirmed by electron microscopy, propidium iodide staining, DNA laddering and activation of caspases. The kinetics of triggering apoptosis were different for the two redox species: NO+ required only a 2 hour exposure, whereas NO required 24 hours. Three sources of NO were used: aqueous solutions of NO and two NO donors, S-nitrosoglutathione and S-nitroso-N-acetylpenicillamine. The time course of apoptosis induced by these two S-nitrosothiols correlated with their rate of decomposition to NO. The apoptotic effect of NO was reduced in the presence of the NO scavenger oxyhaemoglobin, or the antioxidants N-acetylcysteine and ascorbic acid, whereas in the case of NO+ these antioxidants potentiated apoptosis. Glutathione also had a potentiating effect on the cytotoxicity of NO+. This suggests that cellular antioxidants may play a role in protecting the cell from NO-induced apoptosis while NO+ may trigger apoptosis independently of oxidative stress mechanisms.

3T3 Cells↗

PubMed1997

[Changes in lymph node dissection for pancreatic cancer].

Two step pancreatoduodenectomy for periampullary carcinoma was first reported in 1912 by Kausch. Pancreatoduodenectomy performed for carcinoma of the head of the pancreas was first reported in 1937 by Brunschwig. Before this report, all previous pancreatoduodenectomy had been performed for other periampullary tumors. By the 1960's, pancreatoduodenectomy was performed for pancreatic cancer without lymph node dissection. However, Fortner advocated regional pancreatectomy for pancreatic cancer in 1973. In our institute, also, extended radical pancreatectomy by translateral retroperitoneal approach has been performed during the past 2 decades. Many Japanese surgeons also adopted extend pancreatectomy. In the 1980's, extended radical pancreatectomy consisted of paraaortic lymph node dissection, total pancreatectomy, and complete resection of extrapancreatic nerve plexus. However, based on the many clinicopathologic studies, pancreatoduodenectomy was better operative procedure than total pancreatectomy. Although extended radical pancreatectomy has the advantage of long-time survival, disadvantage of nutritional status and quality of life was produced by this operative procedure. Tarverso and Longmire reported new operative procedure of pylorus preserving pancreatoduodenectomy (PPPD) in 1978. Recently, this operative procedure was indicated for pancreatic cancer. However, there is a question whether PPPD is the best operative procedure for pancreatic cancer or not.

Humans↗

PubMed1996

Lymphatic flow and neural plexus invasion associated with carcinoma of the body and tail of the pancreas.

BACKGROUND: Lymph node status and neural plexus invasion are the most important prognostic factors that may be amenable to surgery for carcinoma of the body and tail of the pancreas. The pattern of lymphatic spread and neural plexus invasion were evaluated by analysis of various clinicopathologic factors. METHODS: Twenty patients with carcinoma of the body and tail of the pancreas underwent pancreatectomy with systemic regional lymph node dissection at Kanazawa University Hospital. A precise evaluation of their lymph node involvement and neural plexus invasion was determined. RESULTS: Sixteen of 20 patients (80%) had lymph node involvement. The lymph nodes with a high metastatic rate were those along the splenic artery (50%), the inferior body lymph nodes (35%), the lymph nodes around the common hepatic artery (25%), and the paraaortic lymph nodes (20%). There was no relationship between tumor size, histologic type, and lymph node involvement. Plexus invasion was observed in 14 patients (70%). The most frequent site was the splenic plexus, but between 15% and 20% of the patients had celiac or superior mesenteric plexus invasion. There was no relationship between tumor size, histologic type, and neural plexus invasion. CONCLUSIONS: Based on these results, extended lymphadenectomy including the paraaortic lymph nodes, celiac lymph nodes, and superior mesenteric lymph nodes may improve the prognosis for patients with carcinoma of the body and tail of the pancreas. Extrapancreatic neural plexus dissection, especially of the celiac plexus and superior mesenteric plexus, also is necessary.

Adenocarcinoma↗

PubMed1996

Results of extensive surgery for pancreatic carcinoma.

BACKGROUND: Since 1973, 210 patients with pancreatic carcinoma have undergone surgery in our clinic, including 144 with carcinoma of the head of the pancreas. Of these 144 patients, macroscopic curative resections were performed on 53 (36.8%). Five patients (9.4%) died within 30 postoperative days, and an additional 3 (5.7%) died within 60 days. The overall median survival was 13 months. Eight of the patients who underwent macroscopic curative resection survived 5 years, giving a 5-year survival rate of 27.4% using the Kaplan-Meier method. The 5-year survival rate was 39.7% after a microscopically curative resection and 0% after a microscopically noncurative resection. METHODS: Outcome was compared based on the extent of pancreatic cancer by constructing survival curves according to the general rules published by the Japan Pancreas Society. RESULTS: There was no statistically significant difference in survival based on tumor size or stage. However, there was a significant difference in the survival of patients with the absence (so) or presence (se) of invasion to the anterior capsule of the pancreas, the absence (rpo) or presence (rpe) of invasion of the retroperitoneal tissue, the absence (ew0) or presence (ew2) of invasion at the surgical margin of resection, and the extent (n0 to n2) of lymph node metastasis. CONCLUSIONS: The results of this study suggest that extended radical pancreatectomy may be indicated for patients with pancreatic carcinoma because standard dissection may fail when the tumor has spread to the retroperitoneum or extrapancreatic nerve plexus.

Adult↗

PubMed1996

Expression of 16 kDa proteolipid of vacuolar-type H(+)-ATPase in human pancreatic cancer.

Recent studies have shown that bafilomycin A1-sensitive vacuolar-type H(+)-ATPase (V-ATPase) plays important roles in cell growth and differentiation. However, there is no published study that has focused on the expression of V-ATPase in human tumour tissues. This study was designed to examine the mRNA and protein levels for the 16 kilodalton (kDa) proteolipid of V-ATPase in human pancreatic carcinoma tissues. We first investigated the mRNA level for V-ATPase in six cases of invasive pancreatic cancers and two normal pancreases, using reverse transcription-polymerase chain reaction technique. Then, we examined immunohistochemically the level of V-ATPase protein in 49 pancreatic cancers and ten benign cystic neoplasms of the pancreas, using antisera raised against the 16 kDa proteolipid. There was a notable difference in the level of V-ATPase mRNA between normal and pancreatic carcinoma tissues, with no evident difference in the expression of the beta-actin gene. Immunohistochemically, 42 out of 46 invasive ductal cancers (92%) displayed a mild to marked immunoreactivity for V-ATPase in the cytoplasm, whereas neither non-invasive ductal cancers nor benign cystic neoplasms expressed detectable immunoreactive proteins. These findings suggest that the overexpression of V-ATPase protein is characteristic of invasive pancreatic tumours. V-ATPase may play some crucial roles in tumour progression.

Adenocarcinoma↗

PubMed1996

Expression of apolipoprotein A-1 mRNA in normal intrahepatic biliary tree.

Our previous study demonstrated that apolipoprotein A-1 (apo A-1) immunoreactive peptides were located diffusely in the cytoplasm, not only of human normal hepatocytes, but also of intrahepatic bile ducts and peribiliary glands. It is important to determine whether the presence of these immunoreactive peptides in intrahepatic biliary tree is caused by pinocytosis from the bile, or by intracellular protein synthesis. Thus, we investigated whether apo A-1 is synthesized by cells that line the biliary tree. Normal human liver samples obtained at surgery were used; and the expression and distribution of apo A-1 mRNA in normal human liver tissues were examined, using in situ hybridization histochemistry with a 35S-labeled oligonucleotide probe specific for apo A-1. On the autoradiogram, many silver grains were found to be distributed uniformly in hepatocytes. In addition, an appreciable apo A-1 mRNA signal was also observed in both the surface epithelial lining of the bile ducts and the epithelial cells of the peribiliary glands. In conclusion, these findings suggest that the apo A-1 found in bile is secreted both by hepatocytes and by intrahepatic bile duct cells and peribiliary glands.

Aged↗

PubMed1996

[A new strategy for the therapy of pancreatic cancer by proton pump inhibitor].

Bafilomycin A1 is a specific inhibitor of vacuolar type proton pump (V-ATPase). This study was designed to examine the effect of bafilomycin A1 on the growth of Capan-1 human pancreatic cells which overexpress V-ATPase. Nude mice bearing a xenografted tumor of Capan-1 cell line were treated for 4 weeks with bafilomycin A1 (1.0 mg/kg/day). This treatment inhibited tumor growth, which was significantly reduced as compared with controls after 21 days (p < 0.05). However, there were no significant differences in body weights between groups. Microscopically, a large number of tumor cells in the treated group showed signs of apoptosis. These findings suggest that apoptosis induced by bafilomycin A1 was the event involved in suppression of tumor growth in vivo.

Animals↗

PubMed1996

[Inhibitory effect of FOY-305 on liver metastasis of the pancreatic cancer].

The potential for hepatic metastasis in nude mice was studied by the intrasplenic implantation method with five human pancreatic cancer cell lines, Capan-1, BxPC-3, AsPC-1, Panc-1, and MIAPaCa-2, especially in relation to serine protease expression, including urokinase-type plasminogen activator and pancreatic trypsinogen 1 (cationic form). The inhibitory effect of a serine protease inhibitor agent, FOY-305, on hepatic metastasis was also a assessed. As a result, the potential for hepatic metastasis was well correlated with expression of pancreatic trypsinogen 1 in these cell lines, and the incidence of metastasis was significantly decreased by FOY-305. These findings suggest that pharmacologic inhibition of serine protease activity may be a new strategy for the therapy of pancreatic cancer metastasis.

Animals↗

PubMed1996

[Early carcinoma of the biliary tract].

Early carcinoma of the biliary tract was defined as cancer cell invasion limited to the mucosal or muscularis propria in the case of the gallbladder, to the mucosal or fibro-muscular layer in the case of carcinoma of the bile duct and to the sphincter of Oddi in the case of the papilla of Vater from a study on the correlation between the depth of cancer invasion and the result of surgery. A few cases, however, have lymph node metastasis, venous invasion, perineural infiltration or involvement of the lymphatic vessels. The surgical procedures should therefore be selected in order to have a good chance for long-term survival. The importance of systematic lymph node dissection to improve survival is emphasize, even in patients with early biliary tract cancer.

Biliary Tract Neoplasms↗

PubMed1995

A new method of performing continuous intraabdominal drainage after pancreaticoduodenectomy.

Dehiscence of the pancreaticoenterostomy is one of the most feared, yet common, postoperative complications following pancreaticoduodenectomy (PD). We report herein a new technique we developed for performing continuous intraabdominal suction drainage (CISD) following PD. This method of CISD involves positioning an 18 Fr sump tube beside the pancreaticoenterostomy, with a continuous suction pressure of about -20cmH2O. The fluid obtained from the sump tube is also useful for monitoring amylase levels and providing bacterial cultures to enable the early detection of dehiscence of pancreaticoenterostomy. A study was conducted on 150 patients who underwent PD for periampullary carcinoma over a 20-year period. The patients were divided into two groups according to whether or not CISD was performed: group 1 comprised 71 patients who had CISD, and group 2 79 patients who did not have CISD. Although the frequency of anastomotic dehiscence did not differ between the two groups (32% in group 1 and 25% in group 2), the mortality rate of the patients with anastomotic leakage in group 1 was lower than that in group 2 (P = 0.07). Thus, we believe that our new technique for performing CISD could improve the surgical outcome of patients following PD.

Abdomen↗

PubMed1995

Surgical strategy for carcinoma of the pancreas head area based on clinicopathologic analysis of nodal involvement and plexus invasion.

BACKGROUND: The pattern of tumor spread, vis-à-vis nodal involvement and invasion of the extrapancreatic plexus (Plx), has not been thoroughly described for carcinoma of the pancreatic head area. METHODS: From 1973 to 1991, 110 patients (49 with carcinoma of the pancreatic head [Ph], 29 with distal bile duct cancer [Bi], and 32 with carcinoma of the papilla of Vater [Pv]) underwent pancreatectomy at Kanazawa University Hospital. Nodal involvement and Plx invasion were precisely evaluated by histopathologic examination. RESULTS: Thirty-seven (76%) of the 49 patients with Ph, 20 (69%) of the 29 with Bi, and 14 (44%) of the 32 with Pv had nodal involvement. The lymph nodes most commonly involved for Ph were the posterior pancreaticoduodenal lymph nodes (numbers 13a [superior] and 13b [inferior]), the superior mesenteric lymph nodes (number 14), the paraaortic lymph nodes (number 16), and the anterior pancreaticoduodenal lymph nodes (number 17) (13a, 51%; 13b, 47%; 14, 36.7%; 16, 18.4%; 17a, 33%; 17b, 22%). In patients with Bi, lymph nodes around the hepatoduodenal ligament (number 12) and lymph nodes numbers 13a and 14 were most commonly involved (12, 27.6%; 13a, 51.7%; 14, 34.5%). In patients with Pv, lymph node numbers 13b and 14 were most frequently involved (13b, 34.4%; 14, 15.6%). No significant correlation was noted between the tumor size and nodal involvement in these three lesions. Nodal involvement was an important prognostic factor for carcinoma of the pancreatic head area. Plx invasion in these three carcinomas was observed in 61% of patients with Ph, 29% of patients with Bi, and 3% of patients with Pv. CONCLUSIONS: Nodal involvement and Plx invasion differed significantly among carcinomas of the pancreatic head area. We believe that nodal dissection of at least group number 14 is needed for Ph, Bi, and Pv cancers. In addition, dissection of lymph nodes of number 16 and the Plx around the superior mesenteric artery and celiac axis are needed in Ph cancer. Plx dissection of the first portion of plexus pancreaticus capitalis is needed in Bi cancer.

Actuarial Analysis↗

PubMed1995

Expression of basic fibroblast growth factor and its receptor in human pancreatic carcinomas.

We examined the expression of basic fibroblast growth factor (FGF) and FGF receptor by immunohistochemistry in 32 human pancreatic ductal adenocarcinomas. Mild to marked basic FGF immunoreactivity was noted in 19 (59.4%) of the 32 tumours examined, and 30 (93.3%) of the tumours exhibited a cytoplasmic staining pattern against FGF receptor. The tumours were divided into two groups according to the proportion of positively stained tumour cells: a low expression group (positive cells < 25%) and a high expression group (positive cells > or = 25%). No statistically significant difference in tumour size, differentiation, metastases or stage was found between the low and high basic FGF expression groups. However, a significant correlation was found between FGF receptor expression level and the presence of retroperitoneal invasion, lymph node metastasis, and tumour stage. In addition, low FGF receptor expression was significantly associated with a longer post-operative survival as compared with high FGF receptor expression, whereas there was no significant difference in post-operative survival between the low and high basic FGF expression groups. Increased expression of FGF receptor is correlated with the extent of malignancy and post-operative survival in human pancreatic ductal adenocarcinomas. Thus, overexpression of FGF receptor may prove to be a more useful prognostic marker than basic FGF expression level in pancreatic cancer patients.

Adult↗