Biomedical subjects

W Kimura

Publications and source records attributed to W Kimura.

At least 19 recordsLinked to original sources

PubMed2001

Frequent loss of expression without sequence mutations of the DCC gene in primary gastric cancer.

Loss of heterozygosity (LOH) on chromosome 18q21 is frequently found in various human cancers, suggesting the presence of tumour suppressor gene(s) in this chromosomal region. DCC is the most likely target of LOH because loss or reduction of DCC expression has been found in many types of cancers. However, few reports have focused on sequence mutations of this gene. We investigated sequence mutations and expression of DCC in primary gastric cancers. We studied mutations in 25 of the 29 DCC exons by PCR-SSCP in 17 primary gastric cancers exhibiting LOH on 18q21. No mutations of DCC were found in any of the tumours, although 78% (47/60) of the primary tumours showed apparent loss or reduction of DCC expression by immunohistochemistry. Analysis of methylation status of DCC revealed that methylation frequently occurred in both primary tumours (75%; 45/60) and corresponding non-cancerous gastric mucosae (72%; 43/60). Methylated status of DCC was significantly correlated with the loss of DCC expression in primary tumours (P< 0.01). These results indicate that DCC is frequently silenced, probably by epigenetic mechanisms instead of sequence mutations in gastric cancer.

Base Sequence↗

PubMed2001

Primary sclerosing cholangitis successfully treated by resection of the confluence of the hepatic duct.

Primary sclerosing cholangitis (PSC) is a cholestatic disease characterized by chronic inflammatory fibrosis of the extra- and intrahepatic bile ducts. Although the prognosis of patients with PSC was believed to be poor, some patients have not experienced the expected rapid clinical progression. A 51-year-old man with PSC was initially hospitalized for jaundice. Laboratory data showed low levels of the complement components C3, C4, and CH50. Percutaneous transhepatic biliary drainage was performed. Cholangiography revealed complete obstruction of the common bile duct below the confluence of the cystic duct. The confluence of the hepatic duct was resected and it was reconstructed by hepaticojejunostomy for palliation of the obstructive jaundice. Increased thickness of the walls of the common bile duct, right hepatic bile duct, and gallbladder was observed. Histopathological examination of the resected specimen revealed periductal fibrosis, with an onion-skin-like appearance. The patient is currently doing well, approximately 7 years after the surgery, without any signs of PSC recurrence. In this extraordinary patient, the laboratory data for C3, C4, and CH50 showed a complete return to normal levels. The positive results in this patient suggest that resection of the confluence of the hepatic duct may be an effective surgical treatment for noncirrhotic PSC patients who have dominant extrahepatic strictures.

Cholangiography↗

PubMed2001

Molecular characterization of undifferentiated-type gastric carcinoma.

As the great majority of gastric cancers develop histologically differentiated, and a significant proportion of differentiated-type carcinomas progress to become undifferentiated, both histological types are likely to share several common genetic abnormalities, such as p53 mutations at advanced stages. However, a subset of gastric cancers develop as undifferentiated carcinomas, including signet-ring cell carcinoma and poorly differentiated adenocarcinoma, and the molecular pathogenesis of this tumor type remains largely unknown. To characterize the molecular features of undifferentiated-type gastric carcinomas that developed as undifferentiated-type, we examined for p53, APC, and epithelial (E)-cadherin gene mutations, microsatellite alterations including loss of heterozygosity (LOH) and microsatellite instability (MSI), and hypermethylation of the E-cadherin gene promoter in 26 early undifferentiated gastric carcinomas, consisting of 14 signet-ring cell carcinomas and 12 poorly differentiated adenocarcinomas. E-cadherin expression was evaluated immunohistochemically. p53 mutations were detected in only one poorly differentiated adenocarcinoma sample (3.8%; 1/26), whereas no APC or E-cadherin mutations were found. LOH was present only at D8S261 on the short arm of chromosome 8 in 2 of 14 (14%) informative tumors, both of which were poorly differentiated adenocarcinomas, and MSI was not observed in any of the tumors. No signet-ring cell carcinomas have been found to carry gene mutations or microsatellite alterations. In contrast, hypermethylation of the E-cadherin promoter occurred in 69% (18/26) of the tumors; 57% (8/14) of signet-ring cell carcinomas, and 83% (10/12) of poorly differentiated adenocarcinomas, and was significantly associated with loss or reduced expression of E-cadherin. Thus, whereas tumor suppressor gene mutation, LOH, and MSI were less common in undifferentiated-type early gastric carcinomas, epigenetic inactivation of E-cadherin via promoter hypermethylation may be an early critical event in the development of undifferentiated tumors.

Cadherins↗

PubMed2001

Long descending lymphatic pathway from the pancreaticoduodenal region to the para-aortic nodes: its laterality and topographical relationship with the celiac plexus.

In 6 of 15 postmortem-treated cadaveric specimens, we found macroscopically thick lymphatic collecting vessels that originated from not only the nodes along the common hepatic artery (No. 8 nodes) but also from the pancreaticoduodenal region, and which drained directly into the para-aortic nodes immediately below the left renal vein (No. 16b1-inter or -latero nodes). The collecting vessels, if they originated from the ventral (dorsal) visceral side, passed to the left (right) of the superior mesenteric and celiac arteries. Moreover, the right-side vessels (5 specimens) were classified into superficial and deep courses to the celiac plexus, whereas they were superficial in the left side (2 specimens). One of the deep (right) courses continued to the thoracic duct without any intercalated nodes. In addition, another deep route drained into the para-aortic node immediately above the left renal vein (No. 16a2-inter node). We consider that these collecting vessels form "direct descending pathways" from the relatively peripheral lymphatics in the upper abdomen toward the thoracic duct origin. The pathway seems to be a collateral, or even major drainage route, and it appears responsible for skipped metastasis of primary cancer. Since the classical, limited entity of the intestinal lymph trunk does not coincide with our pathway, it should be reconsidered. The proposed entity of the direct, long descending pathway will influence the selection and modification of lymphadenectomy methods in cancer surgery in the pancreaticoduodenal region.

Aged↗

PubMed2000

Distinct methylation patterns of two APC gene promoters in normal and cancerous gastric epithelia.

The adenomatous polyposis coli (APC) tumor suppressor gene is mutationally inactivated in both familial and sporadic forms of colorectal cancers. In addition, hypermethylation of CpG islands in the upstream portion of APC, a potential alternative mechanism of tumor suppressor gene inactivation, has been described in colorectal cancer. Because a subset of both gastric and colorectal cancers display the CpG island methylator phenotype, we hypothesized that epigenetic inactivation of APC was likely to occur in at least some gastric cancers. APC exhibits two forms of transcripts from exons 1A and 1B in the stomach. Therefore, we investigated CpG island methylation in the sequences upstream of exons 1A and 1B, i.e., promoters 1A and 1B, respectively. We evaluated DNAs from 10 gastric cancer cell lines, 40 primary gastric cancers, and 40 matching non-cancerous gastric mucosae. Methylated alleles of promoter 1A were present in 10 (100%) of 10 gastric cancer cell lines, 33 (82.5%) of 40 primary gastric cancers, and 39 (97.5%) of 40 noncancerous gastric mucosae. In contrast, promoter 1B was unmethylated in all of these same samples. APC transcripts from exon 1A were not expressed in nine of the 10 methylated gastric cancer cell lines, whereas APC transcripts were expressed from exon 1B. Thus, expression from a given promoter correlated well with its methylation status. We conclude that in contrast to the colon, methylation of promoter 1A is a normal event in the stomach; moreover, promoter 1B is protected from methylation in the stomach and thus probably does not participate in this form of epigenetic APC inactivation.

Adolescent↗

PubMed2000

Significance of K-ras mutation and CEA level in pancreatic juice in the diagnosis of pancreatic cancer.

The early diagnosis of pancreatic carcinoma is essential for increasing patient survival rates. In this study, 52 patients with suspected pancreatic diseases were examined to investigate the value of K-ras codon 12 point mutation, levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19-9), and cytology of pancreatic juice in the diagnosis of pancreatic carcinoma. Pancreatic juice was taken without secretin stimulation. K-ras mutation was detected by enriched polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP). K-ras mutation in pancreatic juice was more frequent in carcinoma than in benign diseases (P = 0.0448). The positive predictive value of K-ras mutation for the diagnosis of neoplastic disease was 83%. The CEA level in pancreatic juice in carcinoma was significantly greater than that in benign disease (P< 0.0001). When the cutoff level of CEA was set at 50 ng/ml, its accuracy for the diagnosis of carcinoma was 85%. A multivariate analysis showed that K-ras mutation and CEA level in pancreatic juice, as well as serum CA19-9 level and age of the patient were independent variables for the diagnosis of carcinoma, and the accuracy of diagnosis by this analysis was increased to 90%. In conclusion, both K-ras mutation and CEA level in pancreatic juice may be valuable for the diagnosis of carcinoma. Better discrimination was possible with a multivariate analysis.

Adult↗

PubMed2000

Surgical anatomy of the pancreas for limited resection.

The fusion fascia of the head of the pancreas is called the "fusion fascia of Treitz" and that of the body and tail of the pancreas is termed the "fusion fascia of Toldt". The fusion fascia is histologically composed of a loose connective tissue membrane. All of the important pancreaticoduodenal arcades of arteries and veins are situated on this membrane, i.e., between this membrane and the pancreatic parenchyma. The topography of the head of the pancreas shows that, after departing from the gastroducodenal artery, the anterior superior pancreaticoduodenal artery runs toward a point 1.5 cm below the papilla of Vater, then turns to the posterior aspect of the pancreas to join the anterior inferior pancreaticoduodenal artery. For preserving the duodenum, the artery toward the papilla is very important. The artery toward the papilla of Vater runs along the right side of the common bile duct after departing from the posterior superior pancreaticoduodenal artery. The gastrocolic trunk of Henle has been reported to be found in about 60% of individuals. It is possible that the gastroepiploic vein and anterior superior pancreaticoduodenal vein (ASPDV) can be divided at pancreaticoduodenectomy, with preservation of the superior right colic vein, if this area is free of carcinoma. The ASPDV and anterior inferior pancreaticoduodenal vein form an arcade on the anterior surface of the pancreas. However, arcade formation was not found between the posterior superior pancreaticoduodenal vein and posterior inferior pancreaticoduodenal vein in many of the individuals examined. The vein joined by the inferior mesenteric vein was also investigated.

Humans↗

PubMed2000

Successful resection of a liver metastasis from gastric leiomyoblastoma: report of a case.

A 20-year-old woman was referred to our hospital for detailed investigation of a gastric submucosal tumor. A leiomyoma was preoperatively diagnosed and laparoscopic-assisted enucleation was performed. The resected tumor was 4 x 3 x 1.5 cm in size and postoperative histological examination identified it as a gastric leiomyoblastoma. Therefore, a secondary resection in the form of a distal gastrectomy was carried out. No tumor cells were found in the gastric specimen or in the lymph nodes; however, 5 months after the operation, an abdominal computed tomography scan revealed a recurrence in the liver, and she was readmitted for further examinations. The lesion was diagnosed as a single liver metastasis from the gastric leiomyoblastoma and successfully resected. The histopathological findings of the liver tumor resembled those of the primary gastric tumor. Her postoperative course was uneventful and she has been well, without any evidence of recurrence, to date. Only 12 other cases of leiomyoblastoma of the stomach with liver metastasis have been reported in Japan, all of which were associated with a very poor prognosis. Therefore, patients with this unusual disease entity should be carefully followed up after resection of the primary tumor.

Adult↗

PubMed2000

Significance of thymidine phosphorylase/platelet-derived endothelial cell growth factor in carcinoma of the papilla of Vater.

The expression of thymidine phosphorylase (TP) in carcinoma of the papilla of Vater was studied to clarify its significance in tumor progression and in determining prognosis. Fifty-nine cases of surgically resected carcinoma of the papilla of Vater were studied. Immunohistochemical staining was performed to evaluate the expression of TP, microvessel count and p53 overexpression. TP expression was demonstrated in tumor cells in 62.7% (37/59) of the cases. A higher frequency of regional lymph node metastasis was found in TP-positive tumors than in TP-negative tumors (P = 0.006). TP-positive tumors were more advanced than TP-negative tumors with regard to clinical stage (P = 0.035). TP-positive tumors had significantly higher microvessel density (27.6 +/- 10.1) than TP-negative tumors (20.4 +/- 10.0, P = 0.01). Moreover, TP expression was significantly correlated with a poor prognosis (P = 0. 02). These suggest that in carcinoma of the papilla of Vater, TP production by tumor cells is correlated with tumor progression through its regulatory effect on neovascularization.

Adult↗

PubMed2000

A case of pancreatic carcinoma with marked ductal dilatation: what contributed to the dilatation?

BACKGROUND: We report the case of an 82-yr-old man with invasive ductal carcinoma of the pancreatic head, in which the main pancreatic duct and duct of Santorini were markedly dilated, measuring 1.6 and 1.1 cm, respectively, in diameter on computed tomography. METHODS: A preoperative diagnosis of ductal carcinoma of the pancreatic head was made, and Whipple's procedure was carried out. RESULTS: Histopathologically, the tumor was diagnosed as moderately differentiated tubular adenocarcinoma, and the resected pancreatic parenchyma showed low papillary mucous cell hyperplasia and atypical hyperplasia in dilated ductular branches. Conclusion. Even among patients with tubular adenocarcinoma, the most common type of pancreatic ductal carcinoma, if the patient is aged and has chronic pancreatitis, the main pancreatic duct and duct of Santorini may dilate to the same degree as in mucin-hypersecreting neoplasm.

Adenocarcinoma↗

PubMed2000

[Diseases of the biliary tract and pancreas in the aged--results obtained by investigation of the autopsy cases].

Gross and histological examination of the autopsy cases in the aged revealed that: 1. Acute interstitial pancreatitis, which was characterized by rupture of the ducts and ductules associated with profuse intraluminal exudation of polymorphonuclear leucocytes and protein plugs formation, was found in nine cases (0.62%) out of 1457 autopsies. There was scarce parenchymal or fat necrosis which might be caused by impaired secretion by atrophic parenchyma. The interstitial type may represent characteristics of acute pancreatitis in the aged. 2. Pancreatic lithiasis was found in six of 85 cases, or 7.1%. 3. Sites of isolated islets of Langerhans were found in an incidence of 26.5% (53/200), which increased with age. 4. Incidence of endocrine tumors was 10% (6/60) in individuals having histological studies of all sections and 1.6% (12/738) in individuals having histological studies of three random sections of the pancreas. The facts that multiple hormone production was found in as much as 70% and glucagon cells in as much as 85% were characteristics. 5. The atypical epithelia were observed with the highest incidence in the common pancreaticobiliary channel of the papilla of Vater, where carcinoma may arise most frequently. 6. The incidence of cystic lesions increased with age. Small cystic lesions appear to have the potential to progress to malignancy. 7. it may be possible to remove the head of the pancreas while preserving of the vascular arcades and their branches to the duodenum, the bile duct and the papilla of Vater. The artery toward the papilla of Vater is very important for the blood supply of both the papilla and second portion of the duodenum, and should be preserved in duodenum-preserving subtotal resection of the head of the pancreas. Gallbladder carcinoma was found in 94 cases, or 2.1% and gallbladder stone was found in 957 cases, or 21.4% among 4482 cases. Incidence of gallbladder carcinoma was six times higher in the cases with cholecystolithiasis than those without stone.

Acute Disease↗

PubMed1999

Giant solid cystic tumor of the pancreas with a fibrous septum caused by extracapsular growth in middle-aged woman: report of a case.

We report herein the case of a 57-year-old female who was admitted to our hospital for treatment of rectal carcinoma and incidentally found to have a giant cystic tumor, 20 cm in diameter, in the body and tail of the pancreas. Several imaging procedures, including ultrasonography, computed tomography, and magnetic resonance imaging, showed that this tumor was round and hypovascular, and had a septum with protuberant lesions. The capsule was 3-4 mm thick with partial calcification. A preoperative diagnosis of a solid cystic tumor (SCT) of the pancreas was made, even though these tumors are rarely found in females in their fifties. Moreover, few reports of SCT with a septum have been described. Distal pancreatectomy and splenectomy were performed, and the tumor was found to be filled with massive necrotic tissue. Microscopically, the tumor was confirmed to be a SCT with a fibrous septum. We present this case due to the atypical findings, including the age of the patient and the existence of a septum caused by extracapsular growth.

Biopsy, Needle↗

PubMed1999

Management of severe acute pancreatitis with a somatostatin analog in a patient undergoing surgery for dissecting thoracic aneurysm: report of a case.

A patient who was admitted to our hospital to undergo surgery for a dissecting thoracic aneurysm suffered preoperatively from severe acute pancreatitis with pancreatic pseudocysts. Computerized tomography (CT) demonstrated the presence of new fluid collection around the cyst with the absence of pancreatic necrosis. He was given a somatostatin analog (sandostatin), which was effective in decreasing the abdominal symptoms, leukocyte counts, and the serum C-reactive/protein level. A CT scan revealed that the pancreatic pseudocyst and peripancreatic fluid collection had disappeared. Although somatostatin has been reported to be ineffective for acute pancreatitis with necrosis, pancreatitis without necrosis may regress after treatment with sandostatin. This is probably due to its suppressive effect on the exocrine function, thus resulting in a decrease of pancreatic juice infiltration.

Acute Disease↗

PubMed1999

The development of a pancreatic abscess, suppurative pylethrombosis, and multiple hepatic abscesses after a pancreatojejunostomy for chronic pancreatitis: report of a case.

We present herein an autopsy case of 63-year-old Japanese man who died as a result of pancreatic abscess, suppurative pylethrombosis, and multiple liver abscesses that had developed 10 years after a pancreato- and cystojejunostomy with side-to-side anastomosis for chronic pancreatitis. Even after this operation, the patient had continued to consume excessive amounts of alcohol. He had first experienced back pain with leukocytosis 9 years after the operation, which relapsed the following year. Despite percutaneous transhepatic gallbladder drainage, his icterus had deteriorated into hepatic insufficiency. Computed tomographic scans of the abdomen had disclosed multiple liver abscesses. At autopsy, a pancreatic abscess and suppurative pylethrombosis as well as multiple liver abscesses were found. There have been few reported cases of such lethal complications developing after a pancreato- and cystojejunostomy for chronic pancreatitis. As the consumption of alcohol would have exacerbated the chronic pancreatitis, such patients should be strongly advised to abstain from drinking alcohol.

Alcohol Drinking↗

PubMed1999

Enteral administration of glutamine in purulent peritonitis.

The intestinal hypomotility associated with purulent peritonitis is generally regarded as a contraindication to enteral nutrition. However, enteral nutrition may be feasible in suppurative peritonitis if administered with great caution, i.e., assuring the appropriate amount, delivery speed, and osmolality of the enteral formulation. Glutamine (Gln) increases muscle protein synthesis and decreases muscle protein degradation in sepsis, regardless of the route of administration. Therefore, administering small amounts of supplemental Gln via the enteral route to peritonitis patients may be beneficial. Two purulent peritonitis patients received L-Gln through a jejunostomy tube. The average amount of supplemental Gln was 16 g/d. Systemic inflammatory responses, i.e., high temperature and a high serum C-reactive protein level, persisted throughout the treatment period. Femoral arterial and venous blood samples were drawn simultaneously for determination of amino acid levels before and after 7 d of Gln supplementation. Enterally administered Gln was well-tolerated by both patients. There was an increase in plasma Gln levels after Gln supplementation. Moreover, the release of Gln, alanine, and phenylalanine from the lower extremities was lower after as compared to before Gln supplementation. Enteral administration of Gln may be feasible even in purulent peritonitis.

Amino Acids↗

PubMed1999

Rescue of liver grafts from hepatic artery occlusion in living-related liver transplantation.

BACKGROUND: Hepatic artery thrombosis after liver transplantation remains a significant cause of graft loss and death. Retransplantation is a difficult option after living-related liver transplantation in Japan. METHODS: Twenty-seven patients underwent living-related liver transplantation with left-sided liver grafts donated from their relatives. The hepatic artery was anastomosed end to end under a surgical microscope. Anticoagulant therapy was maintained for 2 weeks after operation. Routine post-transplant Doppler ultrasonography together with serum blood tests were performed twice a day during the first 2 weeks. RESULTS: Three patients developed hepatic artery occlusion, which was identified by routine Doppler ultrasonography before the serum transaminase values increased on days 7, 7 and 3 after surgery respectively. In two of the three patients, no apparent arterial thrombosis was recognized and vasospasm was therefore considered to be the cause of the occlusion. Arterial patency was restored by urgent revascularization with reanastomosis in all patients, but one patient with a functional graft died from a cerebral haemorrhage on day 47. CONCLUSION: Early diagnosis of hepatic artery occlusion by routine Doppler ultrasonography and revascularization of the graft is an indispensable strategy for preventing graft loss after living-related liver transplantation.

Adolescent↗

PubMed1999

A rare combination consisting of primary hyperaldosteronism and glucagonoma.

A 59-yr-old man with multiple pancreatic tumors is presented. Previously, he had undergone left adrenalectomy for primary hyperaldosteronism and left nephrectomy for renal cell carcinoma at the ages of 39 and 55 yr, respectively. This time, 3 yr after removal of renal cancer, two solid lesions in the pancreas associated with hyperglucagonemia were detected. Under a diagnosis of pancreatic metastasis from renal cell carcinoma or islet cell tumor of the pancreas, distal pancreatectomy with splenectomy and enucleation of the tumor in the pancreas head were performed. Microscopically, a glucagonoma, measuring 2.3 mm in diameter, was detected among five pancreatic metastases from renal cell carcinoma. Four years after surgery, the patient remains well, without signs of recurrence despite multiple pancreatic metastases. This is the first report of such a rare combination consisting of aldosterone-secreting adrenal adenoma and glucagonoma.

Adrenal Cortex Neoplasms↗

PubMed1999

p53 and p21/Waf1 protein expression and K-ras codon 12 mutation in carcinoma of the papilla of Vater.

OBJECTIVE: There have been few studies on the molecular biological characteristics of carcinoma of the papilla of Vater. In this study, p53 and p21/Waf1 expression and K-ras codon 12 mutation in carcinoma of the papilla of Vater were investigated. METHODS: Thirty-seven cases of carcinoma of the papilla of Vater were studied. Macroscopically, the carcinoma was ulcerative in 15 cases and nonulcerative in 22 cases. Histologically, nine were intestinal type, 27 were pancreaticobiliary type, and one was undifferentiated. Formalin-fixed, paraffin-embedded sections were immunohistochemically stained for p53 and p21. K-ras codon 12 mutation was detected with the two-step polymerase chain reaction-restriction fragment length polymorphism method, followed by direct sequencing. RESULTS: p53 overexpression was found in 17 of 37 cases (46%) and was more frequent in the ulcerative type than in the nonulcerative type (67% vs 32%, p < 0.05). p21/Waf1 protein expression was found in 15 of 37 cases (41%), and was not correlated with that of p53. K-ras codon 12 mutation was found in 14 of 37 cases (38%), and was more frequently detected in the intestinal type than in the pancreaticobiliary type (66% vs 30%, p < 0.05). On direct sequencing, the mutations were mainly GGT to GAT (9/14) and GGT to GTT (4/14). The type of mutation did not correlate with the histological type. CONCLUSIONS: In carcinoma of the papilla of Vater, p53 overexpression may play a role in tumor ulceration. p21/Waf1 expression is induced via a p53-independent pathway. Carcinomas of the intestinal and pancreaticobiliary types may develop via different mechanisms, and K-ras mutation is mainly associated with the intestinal type.

Adult↗