Topical erythritol combined with L-ascorbyl-2-phosphate inhibits staphylococcal growth and alleviates staphylococcal overgrowth in skin lesions of canine superficial pyoderma.

Erythritol (ERT) and L-ascorbyl-2-phosphate (APS) are bacteriostatic, but their effects on staphylococcal skin infections remain unknown. We aimed to determine whether ERT combined with APS inhibits the growth of staphylococci that are commonly isolated from pyoderma skin lesions in dogs. We investigated the individual and combined effects of ERT and APS on the growth of Staphylococcus pseudintermedius, S. schleiferi, and S. aureus using turbidity assays in vitro. Skin lesions from 10 dogs with superficial pyoderma were topically treated with 5% ERT and 0.1% APS for 28 days, and swabbed skin samples were then analyzed using 16S rRNA amplicon sequencing and quantitative real-time PCR (qPCR). Results showed that ERT inhibited S. pseudintermedius growth regardless of harboring the mecA gene, and APS increased the inhibitory effects of ERT against S. pseudintermedius, S. schleiferi, and S. aureus in vitro. Moreover, combined ERT and APS decreased the prevalence of staphylococci on canine skin lesions at the genus level. The combination slightly increased the α-diversity but did not affect the ß-diversity of the microbiota. The qPCR results revealed that the combination significantly decreased S. pseudintermedius and S. schleiferi in skin lesions. Topical administration of EPS combined with APS can prevent staphylococcal colonization on the surface of mammalian skin. The results of this study may provide an alternative to systemic antibiotics for treating superficial pyoderma on mammalian skin surfaces.

The pharmacokinetics and pharmacodynamics of tolvaptan in patients with liver cirrhosis with insufficient response to conventional diuretics: a multicentre, double-blind, parallel-group, phase III study.

OBJECTIVES: This study investigated the pharmacokinetic and pharmacodynamic profile of tolvaptan, and verified its efficacy and safety in patients with liver cirrhosis-associated ascites, with insufficient response to conventional diuretic treatment. METHODS: This multicentre, double-blind, parallel-group study allocated patients with cirrhosis to receive either 3.75 or 7.5 mg/day tolvaptan orally, once daily, for 7 days. Pharmacokinetic, pharmacodynamic and efficacy variables were measured. RESULTS: Tolvaptan was shown to have high plasma concentrations, and prolonged duration of maximum concentration and half life, in these patients with impaired hepatic function. Tolvaptan resulted in dose-dependent decreases in body weight and ascites volume, and increases in urine output. There were no effects on urinary or serum electrolytes. Tolvaptan was well tolerated, with a good safety profile. CONCLUSIONS: Tolvaptan at 3.75 mg/day exerts some effects due to the pharmacokinetic profile in patients with liver cirrhosis. Tolvaptan at 7.5 mg/day is a clinically useful option for treating patients who do not respond well to conventional diuretics.

Risk factors for bacteraemia attributable to Pseudomonas aeruginosa resistant to imipenem, levofloxacin, or gentamicin.

We studied the risk factors associated with resistance to imipenem, levofloxacin and gentamicin in Pseudomonas aeruginosa isolated from blood cultures of 175 patients in a hospital in Japan. Imipenem resistance was associated with transfer from another hospital, and receiving antifungal medication. Gentamicin resistance was associated with previous administration of a penicillin. No specific risk factors were associated with levofloxacin resistance.

Trisectionectomy for large hepatocellular carcinoma using the liver hanging maneuver.

BACKGROUND/PURPOSE: Large liver tumors often expand and severely compress intrahepatic vessels. In cases of the trisectionectomy for such tumors, however, it is difficult to adequately expose the transection planes. The liver hanging maneuver (LHM) is a useful technique for hemihepatectomy and an adequate transection plane might be also required in trisectionectomy. METHODS: LHM procedure is basically followed by the Belghiti's method. A nasogastric tube was used for hanging. At the hepatic hilum, the tube was placed between the liver and Glisson's pedicle. RESULTS: We report here the application of LHM for right and left trisectionectomy in patients with a large hepatoma in two cases. In case of a right trisectionectomy for a large tumor compressing the umbilical Glisson's pedicle, an adequate transection plane was obtained using the LHM because the resected and remnant livers rotated to the other side upon lifting the tube during transection. In case of a left trisectionectomy for a large hepatic tumor compressing the right hepatic vein, an adequate transection plane along the right hepatic vein was obtained using LHM as well. CONCLUSIONS: LHM is a useful surgical application for right and left trisectionectomy in patients with large liver tumors compressing the cut plane.

Comparison of survival between anatomic and non-anatomic liver resection in patients with hepatocellular carcinoma: significance of surgical margin in non-anatomic resection.

AIMS: Anatomic resection, i.e., systematic removal of a liver segment confined by portal branches, is theoretically effective in eradicating intrahepatic metastasis of hepatocellular carcinoma (HCC). The procedure may reduce tumour recurrence and enhance survival of HCC patients. To determine the significance of anatomic resection for HCC patients, we retrospectively conducted a comparative analysis between anatomic (AR) and non-anatomic liver resection (NAR) in 113 Japanese HCC patients with a solitary tumour, a tumour located within one segment, absence or invasion of distal to second order branches of the portal vein, and absence or invasion of peripheral branches of the hepatic vein. METHODS: Patients were divided into two groups, AR group (n = 49) and NAR group (n = 64). RESULTS: The prevalence of liver damage Grade B in the NAR group was significantly greater than in the AR group (p < 0.05). Tumour-free and overall survival following liver resection was not significantly different between AR and NAR groups. In the NAR group, tumour-free and overall survival in patients with tumour exposure at the surgical margin was significantly lower than with a surgical margin greater than 0 mm (not exposed) (p < 0.05). Survival between the AR and NAR groups without tumour exposure at the surgical margin was similar. CONCLUSIONS: Anatomic resection is the theoretical aim. In HCC patients with impaired liver functions, limited liver resection without tumour exposure may provide longer tumour-free and overall survival.

Pathological evidence of rhabdomyolysis-induced acute tubulointerstitial nephritis accompanying Legionella pneumophila pneumonia.

A case of Legionella pneumophila pneumonia with rhabdomyolysis-induced acute tubulointerstitial nephritis (ATIN) and prolonged renal dysfunction is presented. The patient was a 54-year-old man, admitted with high-grade fever, ataxia and muscle dysfunction; chest roentgenogram showed multilobular infiltrations. L pneumophila was detected in his sputum and urine, by PCR and by culture, and L pneumophila pneumonia was diagnosed. Despite antimicrobial treatment, he developed renal failure and rhabdomyolysis. Renal biopsy showed the presence of myoglobin casts that occluded the distal tubuli and tubulointerstitial nephritis, leading to the diagnosis of rhabdomyolysis-induced ATIN. Renal function subsequently normalised, and he was discharged. This is believed to be the first pathological evidence of involvement of rhabdomyolysis in legionellosis-associated ATIN.

Clinical evaluation of magnetic resonance imaging flowmetry of portal and hepatic veins in patients following hepatectomy.

BACKGROUND: Hepatic blood flow was associated with degree of hepatic damage. Measurements of blood flow using ultrasonography (US) may vary due to any observer's and patient's conditions. The utility of magnetic resonance imaging (MRI) flowmetry in portal and hepatic veins was assessed. PATIENTS AND METHODS: Using the phase-contrast method, the mean flow velocity of portal (PVF) and hepatic vein (HVF) were determined by MRI and US in 75 consecutive patients with liver diseases, including 58 patients undergoing hepatectomy. The correlations between these parameters and clinicopathological findings were examined. RESULTS: PVF and HVF measured by MRI flowmetry were 12.8+/-4.5 and 14.7+/-5.3 cm/s, respectively. There was no significant correlation of both flows between MRI and US. PVF correlated significantly with portal pressure (r = -0.722; P < 0.05). There was a negative correlation between HVF and histological activity index score (r = -0.366; P < 0.05). PVF and HVF were lower in patients with cirrhosis and higher staging score (2-4) and PVF was lower in patients with higher grading score (2-3; P < 0.05). PVF and HVF were not significantly associated with postoperative complications. CONCLUSIONS: Our results suggest that MRI flowmetry is a potentially useful tool for measurement of hepatic blood flow and recommend its use for estimation of liver cirrhosis-associated impairment.

Involvement of programmed cell death 4 in transforming growth factor-beta1-induced apoptosis in human hepatocellular carcinoma.

The programmed cell death 4 (PDCD4) gene was originally identified as a tumor-related gene in humans and acts as a tumor-suppressor in mouse epidermal carcinoma cells. However, its function and regulatory mechanisms of expression in human cancer remain to be elucidated. We therefore investigated the expression of PDCD4 in human hepatocellular carcinoma (HCC) and the role of PDCD4 in human HCC cells. Downregulation of PDCD4 protein was observed in all HCC tissues tested compared with corresponding noncancerous liver, as revealed by Western blotting or immunohistochemical staining. Human HCC cell line, Huh7, transfected with PDCD4 cDNA showed nuclear fragmentation and DNA laddering characteristic of apoptotic cells associated with mitochondrial changes and caspase activation. Transforming growth factor-beta1 (TGF-beta1) treatment of Huh7 cells resulted in increased PDCD4 expression and occurrence of apoptosis, also concomitant with mitochondrial events and caspase activation. Transfection of Smad7, a known antagonist to TGF-beta1 signaling, protected cells from TGF-beta1-mediated apoptosis and suppressed TGF-beta1-induced PDCD4 expression. Moreover, antisense PDCD4 transfectants were resistant to apoptosis induced by TGF-beta1. In conclusion, these data suggest that PDCD4 is a proapoptotic molecule involved in TGF-beta1-induced apoptosis in human HCC cells, and a possible tumor suppressor in hepatocarcinogenesis.

The Japanese integrated staging score using liver damage grade for hepatocellular carcinoma in patients after hepatectomy.

AIMS: The new Japanese staging system for hepatocellular carcinoma (HCC), the Japan integrated staging (JIS) score, accounts for both Child-Pugh classification and Japan tumour node metastasis (TNM) staging. However, in HCC patients who undergo hepatectomy, liver function is relatively good and a better prognostic classification of hepatic function is necessary. METHODS: The present study was designed to analyse the modified JIS score using liver damage grade by the Liver Cancer Study Group of Japan instead of the Child-Pugh classification (using the category indocyanine green retention rate at 15 min [ICG(R15)] instead of encephalopathy), and to compare the Japan TNM stage in 101 patients who underwent resection of HCC. RESULTS: The liver damage grade showed significantly better discrimination of disease-free and overall survival than did the Child-Pugh classification. The modified JIS score system showed significant differences of disease-free and overall survivals in each score and this system was superior for discriminating survivals compared with the TNM staging. CONCLUSIONS: The combined staging system of hepatic function, particularly ICG(R15), and tumour stage provides a better prediction of prognosis. The JIS score using the liver damage grade was a useful predictor of prognosis of HCC patients who underwent hepatic resection.

Platelet-derived endothelial cell growth factor expression is an independent prognostic factor in colorectal cancer patients after curative surgery.

AIMS: Platelet-derived endothelial cell growth factor (PD-ECGF) is an angiogenic factor that undergoes increased expression in colorectal carcinomas, but its prognostic value is a topic of debate. The aim of this study is to clarify the prognostic value of PD-ECGF expression in colorectal carcinomas. METHODS: PD-ECGF expression was measured by enzyme-linked immunosorbent assay in frozen materials from 134 colorectal cancer patients who had received curative resections. Patients were divided into high expression and low expression groups based upon selected cut-off value. Correlations among PD-ECGF expression, clinicopathologic features, and disease-free interval were studied by univariate and multivariate analysis. To evaluate the origin of PD-ECGF, serial sections of the 134 tumours were stained for PD-ECGF and CD68. RESULTS: PD-ECGF expression in the normal mucosa was 34.4+/-15.5 (Units/mg protein) and the cut-off value was 65.4 (mean+2SD). There were no significant correlations between clinicopathological features and PD-ECGF expression. The disease-free interval for the high PD-ECGF expression group was significantly longer than that of the low expression group (P=0.05). A multivariate Cox's regression analysis revealed that high PD-ECGF expression is an independent factor for better outcome. In immunohistochemical study, almost all tumour cells were negative for PD-ECGF, but stromal macrophages were predominantly positive for PD-ECGF. CONCLUSIONS: The PD-ECGF expression originated from stromal macrophages was a predictor for favorable outcome after curative resections for colorectal cancer.

Modified CLIP using PIVKA-II for evaluating prognosis after hepatectomy for hepatocellular carcinoma.

AIMS: The new staging system proposed by the Cancer of the Liver Italian Program (CLIP) for hepatocellular carcinoma (HCC) accounts for both liver dysfunction and tumour characteristics. The present study was designed to analyze UICC TNM stage, CLIP and modified CLIP in 91 patients who underwent hepatic resection for HCC. METHODS: In the modified CLIP, scoring of AFP was replaced by that of protein induced by vitamin K absence or antagonist II (PIVKA-II; predictive value, > or = 400 mAU/ml). RESULTS: After hepatic resection, 54 patients developed recurrent tumours. High PIVKA-II was a significant determinant of recurrence (p<0.05). However, a high score of the modified CLIP as well as those other staging systems did not correlate with tumour-recurrence rate. Univariate analysis showed that high TNM score, CLIP score and our modified CLIP score were significant predictors of poor prognosis. Multivariate Cox's analysis revealed that high PIVKA-II and high modified CLIP score were associated with higher risk for disease-free and overall survival as well as high TNM stage. CONCLUSIONS: Compared with the original CLIP, our modified CLIP was a better predictor of prognosis of HCC patients who underwent hepatic resection.

Gasless, video endoscopic transanal excision for carcinoid and laterally spreading tumors of the rectum.

BACKGROUND: The aim of this study is to determine whether gasless, video endoscopic transanal-rectal tumor excision (gasless VTEM) is a valid treatment for rectal carcinoid and laterally spreading tumors (LST). METHODS: Eighty-four patients with an adenoma, adenocarcinoma (Tis/T1), or carcinoid tumor of the rectum were divided into three groups: (i) LST ( n = 17 patients), (ii) carcinoid ( n = 11), and (iii) control with other types of tumors ( n = 56). RESULTS: The LST group had a longer median operating time than in the control group, whereas the carcinoid group had a shorter operating time. Two patients (11.7%) in LST group developed peritoneal entry during the operation, while 2 patients (3.6%) in the control group experienced postoperative complications. During a median follow-up length of 55.2 months, one patient in the LST group developed a recurrence. CONCLUSIONS: Gasless VTEM is a simple, minimally invasive procedure used to treat LST and carcinoid tumors of the rectum. However, resection for the LST group had a high risk of peritoneal entry during operation.

Long-term outcomes of intragastric endoscopic mucosal resection using a modified buess technique for early gastric cancer.

BACKGROUND/AIMS: The aim of this study was to clarify long-term outcomes of endoscopic mucosal resection (EMR) using a modified Buess technique for mucosal gastric cancer. METHODS: The procedure included en bloc mucosal resection using a Buess-type rectoscope into the gastric lumen via a temporary gastrostomy under video camera guidance. We reviewed 5 patients who underwent this procedure between 1995 and 1997 with a single mucosal cancer of the stomach that was unsuitable for en bloc excision by endoscopic snare diathermy. RESULTS: All tumors were superficial elevated types (type 0-IIa) located in the middle third and posterior wall of the stomach. Median maximum tumor diameter was 2.2 (range 1.1-3.5) cm. There was no operative mortality. One patient developed a hemorrhagic gastric ulcer postoperatively. All tumors histologically showed curative potential of the mucosal resection without margin involvement. During a median follow-up period of 64 (50-77) months, none of the patients developed local recurrence. One patient had an early gastric cancer that metachronously developed at another stomach site. CONCLUSION: Intragastric EMR using a modified Buess technique appears to be a useful treatment for cure of mucosal gastric cancer for a limited group of patients unsuitable for complete en bloc excision by endoscopic snare diathermy.

Chromosomal imbalances associated with acquired resistance to fluoropyrimidines in human colorectal cancer cells.

The chromosomal aberrations underlying the development of resistance to fluoropyrimidines have not yet been identified. To characterise the genomic changes that induce the development of resistance to fluoropyrimidines, we used comparative genomic hybridisation (CGH) to analyse and compare the parent DLD-1 human colorectal cancer cell line and two cell lines, DLD-1/5-FU and DLD-1/FdUrd, which were resistant to 5-fluorouracil (5-FU) and 5-fluoro-2'-deoxyuridine (FdUrd), respectively. Both resistant cell lines showed a genetic aberration derived from the parental cell line DLD-1. Losses of 3p and 3q were also detected as additional genetic changes in the two resistant cell lines. Both resistant cell lines showed decreased orotate phosphoribosyltransferase (OPRT) activity, which is associated with the activity of the uridine monophosphate (UMP) synthase gene (3q13). These results suggested that the loss of 3q might be a genetic change responsible for the decreased OPRT activity and fluoropyrimidine cytotoxic response in cancer cells. Amplification of 18p11.2-p11.3 containing the thymidine synthase (TS) gene (18p11.32) was observed only in the DLD-1/FdUrd-resistant cell line, which overexpresses TS. These findings suggested that 18p amplification represents a genetic change associated with the overexpression of the TS protein. Our results indicate that chromosomal aberrations identified by CGH could explain, at least in part, acquired fluoropyrimidine resistance.

Increased expression of sialyl Lewis(x) antigen in penetrating growth type A early gastric cancer.

Early gastric cancer can be divided morphologically into two categories, penetrating growth type-A (Pen-A type) and other growth types (non-Pen-A types). Sialyl Lewis(x) antigen has been demonstrated to play an important role in tumor metastasis by serving as a functional ligand in the cell adhesion system. The aim of this study is to ascertain whether or not sialyl Le(x) antigen expression correlates with tumor growth patterns of early gastric carcinoma. An immunohistochemical assay was performed using monoclonal antibody CSLEX1 in 12 Pen-A type and 79 non-Pen-A type cancers. Scoring was based on the percentage of immunoreactive cells: negative, low expression (< or = 25%), and high expression (> 25%). Lymph node metastasis was found more frequently in Pen-A type than non-Pen-A type cancers (P=0.0004). Furthermore, sialyl Le(x) antigen high expression was detected more often in Pen-A type cancers (7 out of 12; 58.3%) than non-Pen-A type cancers (13 out of 79; 16.5%) (P=0.0036). Multivariate logistic regression analysis showed that these variables are related independently to the Pen-A type and the non-Pen-A type tumor growth patterns. These data suggest that the difference in sialyl Le(x) antigen expression between the Pen-A type and non-Pen-A type tumor growth patterns of early gastric cancer may, at least partially, reflect different biological behavior during tumor progression.

Evaluation of sialyl Lewis(a), sialyl Lewis(x), and sialyl Tn antigens expression levels as predictors of recurrence after curative surgery in node-negative colorectal cancer patients.

This study aimed to determine whether sialyl Lewis(a) (Le(a)), sialyl Lewis(x )(Le(x)), or sialyl Tn antigen expression could identify a subset of node-negative colorectal cancer patients that are at high risk for recurrence after curative surgery. Tumor tissue samples from 90 patients with node-negative colorectal cancer, who had undergone surgical resection, were analyzed immunohistochemically for the expression of each antigen. Patients were classified as having low or high antigen expression depending on whether more or less than 40% of the field showed positive staining. The main outcome measure for each variable was disease-free interval. Sialyl Le(a), sialyl Le(x), and sialyl Tn antigens were expressed in 53 (58.9%), 41 (45.6%), and 34 (37.8%) carcinomas, respectively. The median follow-up was 83.5 months. Patients with high sialyl Le(x) expression had shorter disease-free intervals than those with low sialyl Le(x) expression (P = 0.0041); the expression of sialyl Le(a) or sialyl Tn antigens did not show a significant relationship with disease-free survival. Cox's regression analysis revealed that sialyl Le(x) expression was an independent predictor for disease-free survival, separate from T factor or tumor location. High sialyl Le(x) expression may be useful in identifying a subset of node-negative colorectal cancer patients who are at high risk for recurrence.

Pre-operative serum levels of sialyl Tn antigen predict liver metastasis and poor prognosis in patients with gastric cancer.

AIMS: To clarify the prognostic value of preoperative serum levels of sialyl Tn antigen (STN) for survival of gastric cancer patients. METHODS: Pre-operative serum levels of STN, sialyl Lewis(a)antigen (CA19-9) and carcinoembryonic antigen (CEA) were examined in 180 patients who underwent resection of gastric cancer. Patients were divided into high and low antigen groups on the basis of a selected diagnostic-based cut-off value. Correlation between high antigen serum levels, established clinicopathologic factors and prognosis was examined by univariate and multivariate analysis. RESULTS: Twenty-eight patients (15.6%) were classified as high STN; 37 (20.6%) as high CA19-9; and 33 (18.3%) as high CEA. The survival time of the high STN, CA19-9 or CEA group was shorter than that of the respective low-antigen group (P<0.0001, P=0.0008 or P=0.0002, respectively). Patients with stage III/IV tumours with high STN had a shorter survival time that those with low STN (P=0.0004). Cox's regression with multiple covariates showed that high serum STN is an independent factor predicting a worse outcome in gastric cancer patients. Multiple logistic regression analysis revealed that high serum STN is an independent predictor for the development of liver metastasis. CONCLUSIONS: Pre-operative high serum levels of STN predict both liver metastasis and poor prognosis after resection for gastric cancer.

Minilaparotomy wound edge protector (Lap-Protector): a new device.

Laparoscopic-assisted or minimally invasive surgery involving minilaparotomy is occasionally complicated by infection of the minilaparotomy wound caused by intestinal bacteria. Furthermore, when this procedure is performed to excise colorectal or gastric cancer, tumor recurrence may develop in the minilaparotomy wound. In an attempt to minimize the risk of these complications, we developed a new, easy-to-use device which we named the "Lap-Protector." Minilaparotomy was performed using the Lap-Protector in 28 patients with colon cancer and eight patients with early gastric cancer who underwent minimally invasive surgery between January and September, 1999. During a median follow-up period of 15.9 (range 12.4-21.0) months, none of the 36 patients showed any sign of wound infection or tumor recurrence in the minilaparotomy wound. These results indicated that the Lap-Protector is a safe and useful device that may help to prevent infections and cancer cell contamination of the minilaparotomy wound.

Measurement of serum hyaluronic acid level during the perioperative period of liver resection for evaluation of functional liver reserve.

BACKGROUND AND AIM: The serum hyaluronic acid (HA) concentrations reflect the degree of hepatic fibrosis and sinusoidal endothelial cell damage. The HA concentrations were examined to evaluate liver damage during the perioperative period of hepatectomy. METHODS: The HA level of serum samples from 79 patients who underwent a hepatectomy was measured, and the results were compared to conventional liver function tests, the degree of fibrosis, liver regeneration and complications. RESULTS: Hyaluronic acid concentrations correlated with the severe fibrosis or histological activity index, and also correlated with liver function tests including transaminase level, platelet counts, prothrombin time activity, indocyanine green retention rate at 15 min (ICG R15), liver activity at 15 min by technetium-99m galactosyl human serum albumin scintigraphy (LHL 15), and portal pressure. The HA level postoperatively correlated with liver function, especially with total bilirubin. Hyaluronic acid levels at day 28 postoperatively correlated with ICG R15 and LHL 15. The hyaluronic acid level before surgery and at day 28 postoperatively correlated with the regeneration of remnant liver in major hepatectomy. The HA levels were significantly higher in patients with hepatic failure or prolonged ascites. CONCLUSION: Our results indicate that the measurement of the HA level is useful for monitoring liver damage or predicting complications associated with liver surgery.

Instability of chromosome 17 and the p53 locus in non-familial colorectal cancer with multiple primary malignancies.

Recently, two different mechanisms of genetic instability have been demonstrated in the carcinogenesis of colorectal cancer. Microsatellite instability is an important genetic event for carcinogenesis in hereditary non-polyposis colorectal cancer, proximal colon cancer, and multiple colorectal carcinoma. To examine the association among chromosomal instability and multiple primary malignancies (MPM) in colorectal cancer, fluorescence in situ hybridization using a chromosome 17-specific probe, p53 cosmid probe, and/or an alpha satellite DNA probe was performed in 184 patients with colorectal cancer. The proportion of aneusomy 17 in MPM was significantly higher than that of single cancers (SC) (46.1+/-8.0% and 39.0+/-10.3%, respectively; p<0.01). Multiple numerical aberrations of chromosome 17 in MPM occurred more often than those of SC (64.3% and 22.9%, respectively; p<0.01). The mean frequency of p53 deletion was also higher in MPM (70.4+/-16.7%) compared with SC (53.4+/-18.1%, p<0.05). The frequency of chromosome 17 translocation was significantly greater in tumors with MPM (4/6; 67%) than in SC (3/23; 13%, p<0.05). The frequency of p53 locus translocation was also significantly greater in tumors with MPM (4/6; 67%) than in SC (0/23; 0%, p<0.01). These results suggested that numerical and structural aberrations of chromosome 17 and the p53 locus are important genetic events associated with carcinogenesis in non-familial colorectal cancer with MPM.