Genetic pathways of 'de novo' colorectal carcinomas with reference to fetal-type glycogen phosphorylase positive foci

'De novo' carcinogenesis has been advocated besides 'adenoma carcinoma sequence' as another dominant pathway leading to the colorectal carcinoma. Our previous study demonstrated that brain (fetal)-type glycogen phosphorylase (BGP) positive foci in the transitional mucosa (BGP foci) have frequent p53 mutations and that the distribution of BGP foci has a close relationship with the location of 'de novo' carcinoma. The aims of the present study were to investigate further genetic alterations in the BGP foci and to clarify the mechanism of 'de novo' carcinogenesis. Twenty-eight colorectal carcinomas with invasion into submucosa or superficial muscularis propria without any adenoma component expressing immunoreactive p53 protein were selected from 168 resected specimens. Investigations of the p53, K-ras and APC mutations was performed in the BGP foci, BGP negative colorectal mucosa and 'de novo' carcinoma using PCR-SSCP and DNA squencing. In all 28 cases, immunoreactive BGP was positive in the carcinomas and the BGP foci were observed sporadically in the mucosa adjacent to the carcinoma. No K-ras mutation was observed in either carcinoma or BGP foci in any of the cases. Mutations of p53 and APC were 14 (50.0%) and 9 (32.1%) in 'de novo' carcinomas, and 11 (39.3%) and 1 (3.6%) in BGP foci, respectively. Both p53 and APC mutations were detected in 8 and 1, p53 mutation alone in 6 and 10, APC mutation alone in 1 and 0 out of 28 carcinomas and BGP positive foci, respectively. These results suggest that the BGP foci may play a very important role in the 'de novo' colorectal carcinogenesis from the frequent genetic alterations of p53, and that there may be two major pathways, i.e., the p53-APC pathway and the p53 alone pathway, from the chain of genetic alterations between BGP foci and 'de novo' carcinoma.     

High serum soluble E-selectin levels are associated with postoperative haematogenic recurrence in esophageal squamous cell carcinoma patients

E-selectin has been reported to be associated with haematogenic metastasis in various cancer patients. In order to evaluate the risk of postoperative haematogenic recurrence of esophageal squamous cell carcinoma (SCC) patients, we examined the preoperative serum levels of soluble E-selectin and clinicopathological data of the patients. Preoperative serum was obtained from 135 esophageal SCC patients who received esophagectomies from 1990 to 1998. Serum soluble E-selectin levels were measured by means of enzyme linked immunoreactive synthesis assay (ELISA). The expression of sialyl Lewis A and X antigens were evaluated in 58 out of 135 patients. Thirty-five patients (25.9%) had haematogenic recurrence in their postoperative course. Serum soluble E-selectin levels of the haematogenic recurrence group (mean 55.6 ng/ml) were significantly higher than those of the non-haematogenic recurrence group (mean 41.1 ng/ml). When the cut-off level of soluble E-selectin was 56 ng/ml, the logistic regression analysis showed that high serum soluble E-selectin levels, lymph node metastasis and intraepithelial spread were associated with postoperative haematogenic recurrence of the esophageal SCC patients (OR 2.99, p=0.047, OR 4.94, p=0.009 and OR 5.0, p=0.019. respectively). Univariate analysis revealed that the patients with a high serum soluble E-selectin level tended to have poor survival (p=0.078) and Cox multivariate analysis revealed that a high serum soluble E-selectin level was a prognostic factor in esophageal SCC patients (RR 1.84, p=0.065). The patients with a high serum soluble E-selectin concomitant with expression of sialyl Lewis antigens had a significant risk of postoperative haematogenic recurrence (p=0.005). These results indicated that preoperative high serum soluble E-selectin was a risk factor in the development of postoperative haematogenic recurrence and was a prognostic factor in esophageal SCC patients.     

Correlation between serum resistin level and adiposity in obese individuals

OBJECTIVE: Resistin is associated with insulin resistance in mice and may play a similar role in humans. The aim of our study was to examine the relationship of serum resistin level to body composition, insulin resistance, and related obesity phenotypes in humans. RESEARCH METHODS AND PROCEDURES: Sixty-four young (age 32 +/- 10 years), obese (BMI 32.9 +/- 5.6), nondiabetic subjects taking no medication, and 15 lean (BMI 21.1 +/- 1.3) volunteers were studied cross-sectionally. Thirty-five of the subjects were also reevaluated after 1.5 years on a weight reduction program entailing dieting and exercise; changes of serum resistin were compared with changes of BMI, body composition, fat distribution, and several indices of insulin sensitivity derived from plasma glucose and serum insulin levels measured during 75-g oral glucose tolerance test. RESULTS: In a cross-sectional analysis, serum resistin was significantly higher in obese subjects than in lean volunteers (24.58 +/- 12.93 ng/mL; n = 64 vs. 12.83 +/- 8.30 ng/mL; n = 15; p < 0.01), and there was a correlation between resistin level and BMI, when the two groups were combined (rho = 0.35, p < 0.01). Although cross-sectional analysis in obese subjects revealed no correlation between serum resistin and parameters related to adiposity or insulin resistance, longitudinal analysis revealed change in serum resistin to be positively correlated with changes in BMI, body fat, fat mass, visceral fat area, and mean glucose and insulin (rho = 0.39, 0.40, 0.44, 0.50, 0.40, and 0.50; p = 0.02, 0.03, 0.02, <0.01, 0.02, and <0.01, respectively). DISCUSSION: Resistin appears to be related to human adiposity and to be a possible candidate factor in human insulin resistance.     

Tissue-specific induction of cytochromes P450 1A1 and 1B1 by polycyclic aromatic hydrocarbons and polychlorinated biphenyls in engineered C57BL/6J mice of arylhydrocarbon receptor gene

Tissue-specific induction of mRNA of cytochrome P450 (P450 or CYP) 1A1 and 1B1 by polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) was investigated in wild and arylhydrocarbon receptor (AhR)-deficient C57BL/6J mice. Ratios of mRNA expression of CYP1A1 or CYP1B1 over beta-actin were determined and used to compare levels of expression and induction of these P450s by PAHs and PCBs in various organs. CYP1A1 mRNA was detected in control mice at very low levels in liver, lung, heart, kidney, intestine, thymus, testis, uterus, ovary, and brain and was highly induced in these organs by benzo[a]pyrene and 3,4,3',4'-tetrachlorobiphenyl in AhR(+/+) mice. In AhR(+/+) and AhR(-/-) mice, CYP1B1 mRNA was found to be constitutively expressed at significant levels in heart (the ratio of mRNAs of CYP1B1 to beta-actin was approximately 0.6), kidney ( approximately 0.8), intestine ( approximately 0.3), testis ( approximately 0.9), thymus ( approximately 0.4), uterus ( approximately 0.3), ovary ( approximately 1.4), and brain ( approximately 0.4), whereas it was low in liver and lung (the mRNA ratio to beta-actin was <0.2 in these cases). CYP1B1 in the latter two organs was highly induced by PAHs and 3,4,3',4'-tetrachlorobiphenyl in AhR(+/+) mice. The induction of CYP1B1 by PAHs and PCBs was more extensive in organs in which the constitutive expression of CYP1B1 was low. For example, CYP1B1 was induced 9-fold and 10-fold by benzo[a]pyrene and 3,4,3',4'-tetrachlorobiphenyl in livers of male and female mice, respectively, whereas in testis and ovary, the fold induction of CYP1B1 by two inducers was only 1.1 and 1.4, respectively. Liver microsomal xenobiotic oxidation activities were induced by these PAHs and PCBs in male and female AhR(+/+) mice. These results suggest that CYP1A1 and CYP1B1 are differentially regulated in their expression in extrahepatic organs of mice and could be induced by PAHs and PCBs with different extents of induction depending on the inducers used and the organs examined in AhR(+/+) mice. The findings of significant levels of constitutive expression of CYP1B1 in AhR(-/-) mice as well as AhR(+/+) mice in several organs including heart, kidney, thymus, testis, ovary, and brain in AhR(-/-) mice as well as AhR(+/+) mice are of importance in understanding the basis of toxicity and carcinogenesis by chemicals that are metabolized by CYP1B1.     

A case of superficial esophageal cancer complicated with idiopathic muscular hypertrophy of the esophagus

We hereby reported a case of 60-year old man with superficial esophageal cancer complicated with idiopathic muscular hypertrophy of the esophagus. Endoscopic ultrasonography and CT showed the thickness of esophageal muscular layer, but the accurate diagnosis could not be entertained before operation. Idiopathic muscular hypertrophy of the esophagus is an entity rarely encountered, and most cases are diagnosed at postmortem examination. Only a few cases have been reported regarding its clinical symptoms and images. The etiology remains to be elucidated, and the pathologic features are characterized by significant thickness of inner circular muscular layer of esophagus without degeneration of plexus and ganglionic cells. This case report deals with superficial esophageal cancer complicated with idiopathic muscular hypertrophy of esophagus. Literature review is also included.     

Disseminated infection due to Scedosporium apiospermum in a patient with acute myelogenous leukemia

A 62-year-old man diagnosed with acute myelogenous leukemia which had developed from myelodysplastic syndrome received cytarabine and idarubicine as an induction therapy. The patient developed pneumonia and bacterial sepsis during profound neutropenia. Fever and sepsis improved by using many anti-bacterials and anti-fungals but he became febrile again and complained of severe lumbar pain. 67Ga scintigram showed abnormal uptake in the lumbar vertebra and left sternoclavicular joint, suggesting a diagnosis of discitis and osteomyelitis in the lumbar vertebra and sternoclavicular arthritis. We biopsied the site several times but culture of the biopsy specimen could not isolate any pathogens, and high fever persisted for about 10 months despite administration of various anti-bacterials and anti-fungals. Finally we inserted a catheter into the abscess at the iliopsoas muscle and Scedosporium apiospermum was isolated in the bloody pus obtained from the catheter. Itraconazole and amphotericin B were restarted, and the high fever and lumbar pain improved rapidly. The findings of S. apiospermum infection in this patient emphasizes the importance of being aware of this pathogen in patients with hematologic malignancy during the neutropenic phase.     

Skin-sparing mastectomy and immediate reconstruction with a deep inferior epigastric perforator flap

BACKGROUND: It is important for breast reconstruction after mastectomy to recreate immediately good breast symmetry with an adequate amount of soft tissue. METHODS: Eight patients with breast cancer underwent skin-sparing mastectomy and immediate reconstruction with a deep inferior epigastric perforator flap. This operative technique, and the results, advantages, and disadvantages of the technique were assessed. RESULTS: Seven patients had stage IIA disease, and one patient had stage I disease. An arc-shaped incision was made just at the lateral border of the breast in all patients. Three patients had a separate periareolar incision, and one had a circumferential nipple incision. There was 100% flap survival, and good breast symmetry was achieved in all patients. No major perioperative complications occurred in this series. A small amount of fat necrosis occurred in one flap. One patient had slight abdominal bulging. Minor wound-healing problems at the lateral breast skin envelope occurred in two patients. CONCLUSION: These data indicate that skin-sparing mastectomy and immediate reconstruction with a DIEP flap is a reliable and safe technique. This method is a potentially useful surgical technique, which has achieved very promising results.     

Tumor cell spillage to the vaginal cavity and vaginal stump during the surgery of endometrial carcinoma

BACKGROUND: Our purpose was to investigate the spillage of the endometrial carcinoma cells to the vaginal cavity and vaginal stump during the surgery. METHODS: Cytologic examination of specimens obtained from the vaginal cavity and vaginal stump during surgery performed on 15 patients with endometrial carcinoma. And the risk factors of carcinoma cell spillage to the vaginal cavity were investigated. RESULTS: Carcinoma cells from the vaginal cavity were negative for nine patients and positive for six patients. Those from the vaginal stump were negative for l4 patients and positive for one patient. In one patient, both were positive. Total abdominal hysterectomy might be one risk of carcinoma cell spillage to the vaginal cavity compared with modified radical hysterectomy and radical hysterectomy. CONCLUSIONS: Endometrial carcinoma cells were spilled into the vaginal cavity in not a few cases and their spillage from there to the vaginal stump could follow during the surgery.