[Cholesterol embolism after percutaneous transluminal coronary angioplasty procedure: a case report].

A 68-year-old man with chest pain was treated under a diagnosis of angina pectoris based on coronary angiography by percutaneous transluminal coronary angioplasty including stent implantation performed by the femoral approach. About 1 month after intervention, his renal function deteriorated and purpura appeared on both feet, especially at the toe tips. He was treated under a tentative diagnosis of cholesterol embolism conservatively at the out-patient clinic. However, he was admitted by ambulance due to worsening renal failure 2 months later and died from multiple organ failure 2 weeks after admission. Autopsy examination identified cholesterol embolism due to crystal emboli in several organs. Cholesterol embolism rarely occurs after angiographic or interventional procedures, but is difficult to diagnose clinically and there is no established therapy. The number of intervention and angiography procedures is increasing, so the occurrence of embolism as a complication of these procedures might also increase.

[Study on the intensity of MMC and UFT in postoperative adjuvant chemotherapy for gastric cancer--study report of JFMTC Study No. 10].

The purpose of this study was to investigate the correlation between efficacy and dose intensity of postoperative adjuvant chemotherapy with MMC and UFT. A total of 1,410 patients from 180 institutions were allocated into a low-dose group and a high-dose group. The patients in the low-dose group received MMC at 8 mg/m2 on the day of surgery and 3 capsules of UFT (300 mg in tegafur) daily for 6 months. The patients in the high-dose group received MMC at 8 mg/m2 on the day of surgery, and in weeks 4, 10, 16, and 22 after surgery and 6 capsules of UFT (600 mg in tegafur) daily for 6 months. The patients in the high-dose group tended to exhibit higher survival rates than those in the low-dose group, although the difference was not significant. For the n(+)ps(-) patients, however, the survival rates were significantly higher in the high-dose group (p = 0.043). The recurrence-free rates showed a similar tendency. The incidence rates of adverse events were significantly higher in the high-dose group than in the low-dose group. Compliance was poorer in the high-dose group. Although the number of adverse events increases, a better prognosis can be expected with a high dose. These results confirmed a dose-dependency in adjuvant chemotherapy with MMC and UFT.

A novel PTEN mutation in a Japanese patient with Cowden disease.

Cowden disease (CD) is an autosomal dominant syndrome characterized by multiple hamartomatous lesions and an increased risk for malignancies. Recent evidence has indicated that the PTEN gene, encoding a protein tyrosine phosphatase, is the CD susceptibility gene. However, another line of evidence has suggested that CD might be genetically heterogeneous. Clinical features of CD are variable, and there are interfamilial differences in the expression of skin lesions. Therefore, information on PTEN mutations in CD patients should be accumulated to clarify the genotype-phenotype correlation. In the present study, we found heterozygous germline mutations of PTEN in all of three Japanese patients with CD examined, indicating no genetic heterogeneity among our patients. The mutations included two non-sense mutations of R335X and R130X, and a mis-sense mutation of C136R. To the best of our knowledge, the C136R mutation has not previously been reported in CD patients. This novel mutation was located outside the core motif of the phosphatase domain of PTEN protein, where most of the missense mutations previously reported in CD patients were clustered. Mucocutaneous manifestations were far fewer in the patient with this mutation than in the patients with nonsense mutations. Whether the phenotypic difference in mucocutaneous features was due to the different mutations remains unclear.

Creation and use of a composite polyurethane-expanded polytetrafluoroethylene graft for hemodialysis access.

The Thoratec (Vectra) polyurethane vascular access graft (TPVA) is among the most recent additions to the list of materials used to construct prosthetic grafts for vascular access during hemodialysis. We give the TPVA very high marks, and recognize the utility of such a graft for use in hemodialysis. However, the strong elasticity of this graft can lead to unexpected complications after suturing. We devised a new surgical method using a TPVA-ePTFE (expanded polytetrafluoroethylene) composite graft, substituting the anastomosis section of the TPVA with a portion of ePTFE graft material, and have been able to overcome most of the TPVA's potential problems. We herein describe the technique.

Epithelial cell proliferation activity of the biliary ductal system with congenital biliary malformations.

Congenital biliary malformations such as anomalous arrangement of the pancreaticobiliary ductal system (AAPB), congenital cystic dilatation of the common bile duct (CCDB), and congenital biliary strictures at the hepatic hilum (CBSH) are newly designated disease entities and are frequently found in adult patients with biliary malignancy such as gallbladder carcinoma, common bile duct carcinoma, and intrahepatic bile duct carcinoma. In the present study, the relationship of these malformations and biliary malignancy was investigated. We studied 61 gallbladders of patients with AAPB and 56 gallbladders of patients without AAPB; 16 common bile ducts of patients with CCDB (12 with AAPB and 4 without AAPB) and 11 gallbladders of patients without CCDB; and 17 intrahepatic bile ducts of patients with CBSH and 6 intrahepatic bile ducts of patients without CBSH. Tissue sections from the mucosa of the gallbladder, common bile duct, and intrahepatic bile duct were stained for proliferating cell nuclear antigen (PCNA). The PCNA labeling indexes of patients with these malformations were significantly higher than those of patients without these malformations (P < 0.05). Cell proliferation of the epithelia in the biliary ductal system in patients with these congenital biliary malformations was accelerated. Consequently, these congenital malformations appear to be an important risk factor for the occurrence of biliary malignancy.

A Case of Sclerosing Lymphocytic Lobulitis of the Breast Associated with Diabetes Mellitus.

BACKGROUND: The benign breast disease sclerosing lymphocytic lobulitis is thought to result from autoimmune diseases causing insulin-dependent diabetes mellitus (IDDM) due to insulinitis. In cases of sclerosing lymphocytic lobulitis accompanied by IDDM, the clinical term gdiabetic fibrous breast disease hhas been proposed. METHODS: A case of sclerosing lymphocytic lobulitis of the breast is described RESULTS: The patient was a 43-year-old woman diagnosed with non insulin-dependent diabetes mellitus (NIDDM) 8 years previously. Insulin therapy was thought to be necessary because treatment with glibenclamide was not effective. She visited our facility complaining of a lump in her right breast that was 5 cm in diameter, painless, rock-hard, discrete, and irregularly outlined. Biopsy was performed because breast cancer was strongly suggested by its hardness and its irregular internal echo on ultrasonography. Histopathological findings demonstrated marked stromal sclerosis and lymphocyte infiltration in the perivascular and perilobular areas. Sclerosing lymphocytic lobulitis was diagnosed. CONCLUSION: Referring physicians should avoid performing unnecessary repeated biopsies by recognizing this disease entity, which often occurs bilaterally.

Bile-induced DNA strand breaks and biochemical analysis of bile acids in an experimental model of anomalous arrangement of the pancreaticobiliary ducts.

A canine experimental model for the anomalous arrangement of the pancreaticobiliary ducts (APBD) was made to investigate the effects of bile acids on carcinogenesis. Seven adult mongrel dogs underwent dorsal pancreatico-cholecystostomy to serve as a functional model for APBD, and six dogs underwent the same procedure with the pancreatic duct ligated as a control group. Bile from the gallbladder was taken 14 months after surgery for bile acid analysis by HPLC. DNA strand breaks in HeLa cells induced by the bile were also investigated in situ by nick translation method. As a result, the fraction of cholic acid tended to be lower, and that of deoxycholic acid slightly higher in APBD-dogs (N.S.). The ursodeoxycholic acid percentage in APBD-dogs significantly decreased compared with that in the control and normal dogs (p < 0.05). Extremely high frequency of DNA strand breaks was shown in only two out of seven APBD-dogs. In those two dogs, the cholic acid percentage decreased and that of deoxycholic acid increased extremely. These findings suggest that the alteration of the bile composition in APBD caused frequent DNA strand breaks and repair which might lead to gene mutation and biliary tract carcinoma.

Rectal cancer risk in hereditary nonpolyposis colorectal cancer after abdominal colectomy. International Collaborative Group on HNPCC.

OBJECTIVE: The authors analyzed the incidence of rectal cancer in patients with hereditary nonpolyposis colorectal cancer (HNPCC) after an abdominal colectomy. SUMMARY BACKGROUND DATA: The treatment of choice for a newly diagnosed patient with HNPCC with colon cancer is an abdominal colectomy. The incidence of rectal cancer after abdominal colectomy in HNPCC is not known. MATERIALS AND METHODS: A questionnaire was mailed to all International Collaborative Group on HNPCC members to identify patients in whom rectal cancer developed after total, subtotal or completion colectomy. Statistics were performed using the log-rank test, Kaplan-Meier method, and Cox's proportional hazards model. RESULTS: Rectal cancer developed in 8 (11%) of 71 patients a median of 158 months (range, 38-282 months) from their primary procedure. Of these eight patients, adenomas in the rectal mucosa developed in five at risk either before (4) or synchronous (1) with the diagnosis of rectal cancer. At the time of diagnosis of rectal cancer, six of eight patients were being observed. Age at first procedure and whether the patient was under surveillance were the only significant variables (p < 0.05) in the multivariate analysis in terms of rectal cancer risk. The risk of developing rectal cancer was estimated to be 3% every 3 years after abdominal colectomy for the first 12 years. CONCLUSIONS: The risk of rectal cancer in patients with HNPCC after an abdominal colectomy is approximately 12% at 12 years. Age at first surgical procedure and surveillance correlated with rectal cancer risk. Aggressive endoscopic surveillance of the rectum should be performed after abdominal colectomy.

Analysis of c-Ki-ras oncogene and p53 immunocytochemistry in the gallbladder mucosa of an experimental dog model of anomalous arrangement of the pancreaticobiliary ducts.

Anomalous arrangement of the pancreaticobiliary ducts is a congenital condition which predisposes the affected person to biliary tract carcinoma. We developed an experimental dog model of anomalous arrangement of the pancreaticobiliary ducts to investigate the mechanism of carcinogenesis in this condition. We used this model to analyze point mutations in the c-Ki-ras gene, and to assess the expression of mutant p53 protein in the gallbladder mucosa. The histopathological appearance of the gallbladder mucosa was also examined. Glandular structures were seen in four of seven (57%) gallbladders examined 14 months after the surgical creation of an anastomosis between the gallbladder and the pancreatic duct. Goblet cells were seen in two of seven gallbladders (29%). However, dot-blot hybridization and immunohistochemical study did not reveal any mutations in the c-Ki-ras gene, or any over-expression of the p53 protein in the specimens. These results show that the gallbladder mucosa is damaged by refluxing pancreatic juice in this dog model of anomalous arrangement of the pancreaticobiliary ducts, but that severe damage may be necessary to induce mutations in the c-Ki-ras proto-oncogene, or in the p53 gene.

Serum hyaluronic acid and interleukin-6 as possible markers of carpal tunnel syndrome in chronic hemodialysis patients.

To elucidate the precise mechanism of carpal tunnel syndrome (CTS), serum hyaluronic acid (HA), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) were measured in 71 chronic hemodialysis patients with or without CTS and/or shoulder pain. Patients were divided into two groups: Group 1 (n = 40) was the control group, and Group 2 (n = 31) patients had carpal tunnel syndrome, shoulder pain, or both. None of the patients had liver disease, rheumatoid arthritis, other inflammatory disease, or cancer. Serum HA concentrations in Groups 1 and 2 were 106.0 +/- 77.5 and 442.6 +/- 564.7 ng/dl (mean +/- SD), respectively. The difference between the groups was significant (p < 0.01). The serum concentrations of IL-6 in Group 1 were significantly lower than in Group 2 (p < 0.05); however, there was no significant difference in serum IL-1 beta and TNF-alpha levels. The mechanisms regulating in vivo synthesis of HA was obscure; however, in vitro studies suggest that inflammatory cytokines may stimulate an increased production of HA. In this study, CTS might be associated with increased serum concentrations of HA, and HA production might be mediated by IL-6.

Mutagenicity of the bile of dogs with an experimental model of an anomalous arrangement of the pancreaticobiliary duct.

To learn the reasons for the high incidence of biliary carcinoma in patients with anomalous arrangement of the pancreaticobiliary duct (APBD) mutagenicity of the bile of APBD-modeled dogs that had received a dorsal pancreatico-cholecystostomy was assayed by the Ames Salmonella mutation test. The bile from two out of 18 APBD dogs was mutagenic for Salmonella typhimurium strain TA98 under the condition of metabolic activation by rat liver S9 fraction, while the bile from 17 normal dogs was not mutagenic. Furthermore, the bile from five APBD dogs i.p. administered 1-nitropyrene (1-NP), which is a typical environmental mutagen, was more mutagenic for strain TA98 than that from 1-NP-treated normal dogs. The bile from the APBD dogs had very high amylase activity, indicating that the bile contained pancreatic juice as a result of the pancreatico-cholecystostomy. When pancreatic juice from a normal dog was added to the bile from 1-NP-treated normal dogs, mutagenicity of the bile increased 1.6- to 2.0-fold. Furthermore, sulfatase increased the mutagenic activity of the bile in the presence of the pancreatic juice. HPLC revealed that the bile from a 1-NP-treated APBD dog contained mutagenic 1-nitro-6/8-hydroxypyrene and 1-nitro-3-hydroxypyrene, while bile from a 1-NP-treated normal dog did not contain these deconjugated products. The pancreatic juice from a normal dog had very high gamma-glutamyltransferase (GGT) and aminopeptidase activities and low sulfatase activity, but it had no beta-glucuronidase activity. In addition, the bacteria that easily infect the biliary duct of APBD dogs, Escherichia coli, Klebsiella, Enterobacter and Proteus, had high beta-glucuronidase activity. In particular, Klebsiella showed a very high sulfatase activity. These results suggest that pancreatic juice enzymes and bacteria infecting the biliary duct deconjugate the detoxified mutagens in the bile and induce mutagenicity of the bile from APBD dogs or APBD patients.

Case report of an anomalous arrangement of the pancreaticobiliary ducts and nuclear DNA ploidy analysis.

Two cases with an anomalous arrangement of the pancreaticobiliary ducts (APBD) are reported in order to investigate the mechanism of carcinogenesis of the extrahepatic biliary tract from the aspect of DNA ploidy analysis. Highly elevated biliary enzymes were found in both cases. Although inflammatory changes without any metaplasia or neoplasia were observed histologically, a cytofluorometric nuclear DNA ploidy analysis showed an aneuploid low ploidy pattern in a histogram of the gall bladder, an aneuploid high ploidy pattern in a histogram of the common bile duct in one patient, and a diploidy pattern in the gall bladder, an aneuploid low pattern in the common bile duct in another case. These results may show that APBD may play a role in the development in DNA ploidy abnormality with refluxed pancreatic juice which may induce repeated irritation and inflammation. Radical surgery including a complete excision of the extrahepatic biliary tract followed by reconstruction may achieve better results with regard to undesirable consequences with an abnormal nuclear DNA ploidy pattern and decrease the likelihood of developing carcinoma.

Does the type of anomalous arrangement of pancreaticobiliary ducts influence the surgery and prognosis of choledochal cyst?

A new classification of the anomalous arrangement of pancreaticobiliary ducts (APBD) has been proposed following amendments and modificiations of the previous one. Fifty-one cases of choledochal cyst complicated with APBD were extensively examined and analyzed for clear visualization of the APBD system to make a standard classification. APBD were classified broadly into three types: type I, type II, and type III with their subtypes. Type I of APBD was seen in 18 (35.3%), type II in 11 (21.6%) and type III in 22 (43.1%) cases, respectively. A radical operation, including complete excision of the dilated biliary duct followed by reconstruction of the biliary tract was the surgical treatment of choice, because the reflux of the pancreatic juice into the biliary tract is prevented. However, a dilated common channel or accessory pancreatic duct, according to the new Komi type Ib, IIb, and IIIc3 of APBD, could be the cause of relapsing pancreatitis leading to chronic pancreatitis, due to the formation of a protein plug or pancreatic calculus in the dilated duct, even after this radical operation. In two complicated cases of type IIIc3 of APBD in choledochal cyst, we performed a pylorus-preserving pancreatoduodenectomy as one of the operative methods of choice. Long-term follow-up, more than decades, is essential to evaluate the results of surgical procedure for choledochal cyst, especially in those complicated cases with type Ib, IIb, and IIIc3 of APBD according to the new Komi's classification.

Experimental studies on carcinogenesis in anomalous arrangement of the pancreaticobiliary ducts.

An experimental model of anomalous arrangement of the pancreaticobiliary ducts (APBD) was produced by pancreaticocholecystostomy performed in 29 mongrel dogs. Our purpose was to study carcinogenesis of the extrahepatic biliary tract by DNA ploidy analysis with cytofluorometry. The amylase level in the bile was elevated in all 25 dogs tested except the controls. The phospholipase A2 level in the bile was elevated in all selected dogs except the controls. Common bile duct (CBD) dilatation was found in 23/29 (79%) of the dogs, and biliary stones were found in 3/29 (10%) dogs. Inflammatory changes were observed microscopically in all specimens except those from the controls. Intramural glandular structures were found in 17/25 (68%) of gallbladder (GB) specimens and 10/25 (40%) of CBD specimens; goblet cells were found in 7/25 (28%) of GB specimens and 2/25 (8%) of CBD specimens. In the controls neither glandular structures nor goblet cells were observed except for two GB specimens showing mild cholecystitis. Cytofluorometry showed 21% GB and 7% CBD diploidy, 69% GB and 65% CBD low ploidy, 10% GB and 28% CBD high ploidy patterns of histograms. These results show that, APBD may be central to high risk condition or play a key role to develop atypical biliary tract epithelium and DNA ploidy abnormality with or without biliary duct dilatation.

Comparison of cytofluorometric nuclear DNA ploidy analysis on fresh and paraffin embedded specimen.

The cytofluorometric nuclear DNA ploidy analysis was performed in gallbladder (GB) epithelium of eight patients of chronic cholecystitis to make a comparison between fresh and paraffin embedded tissue analysis, to make an ideal single cellular suspension, to evaluate the ploidy pattern affected by inflammation and to assess the histological correlations. Six (75%) fresh specimens and eight (100%) paraffin embedded specimens showed diploidy pattern of histogram. Two (25%) fresh specimens showed low ploidy pattern of histogram. There was a good correlation between histological findings and the ploidy patterns of 100% paraffin embedded specimens and 75% fresh specimens. The relative fluorescence intensity was found higher and more stable in paraffin embedded tissues than fresh tissues. Inflammation did not affect the ploidy patterns of paraffin embedded specimens whereas the ploidy patterns of fresh specimens were affected. It can be concluded that the DNA ploidy patterns and histological findings have a good correlation and inflammation does not affect the cytofluorometric DNA ploidy pattern when using the paraffin embedded specimens. Paraffin embedded specimens are superior to fresh specimens for making an ideal single cellular suspension to obtain stable, high, and accurate fluorescence intensity with less background fluorescence which makes the ploidy pattern behave like exact behavior of tissues.

Case report of hepatocellular carcinoma and cytofluorometric nuclear DNA ploidy.

Cytofluorometric nuclear DNA ploidy analysis was performed in two cases of primary hepatocellular carcinoma (HCC). This study was done to get the information about clinical behavior of tissues and to assess the prognosis. In both cases, almost all the liver function tests were abnormal, the tumors were thickly encapsulated, and the size of the tumors were below 5 cm in diameter. The DNA distribution pattern was categorized in two types, diploid and aneuploid with low and high ploidy, according to the mode and degree of dispersion of cells on the DNA histogram. Low ploidy pattern of histogram was found in one and diploidy pattern in another case. The serum alpha FP level was found high in case of diploidy pattern of histogram. The case of diploidy pattern of histogram died earlier than the case of aneuploid low ploidy pattern of histogram. The DNA ploidy patterns did not relate to the survival rates of patients. A preoperative cytofluorometric nuclear DNA ploidy analysis on biopsy specimens may be potentially useful to get the information about clinical behavior of tissues, to do the selective surgical procedures, and to assess the prognosis.