Prognostic implication of the CpG island methylator phenotype in colorectal cancers depends on tumour location.

BACKGROUND: Colorectal cancer (CRC) is usually categorised as proximal or distal CRC. Recently, many researchers have tried to determine the molecular heterogeneity of CRCs along bowel subsites. However, the differential effects of the CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) on the clinical outcome according to tumour location are not well-known. METHODS: We analysed clinicopathologic and molecular characteristics, including CIMP, MSI, KRAS and BRAF mutations, in 734 CRCs according to bowel subsites. And the prognostic value of CIMP and MSI was analysed according to tumour location. RESULTS: We found a linear increase of female predominance, T, N category, stage, differentiation, absence of luminal necrosis, tumour -infiltrating lymphocytes, Crohn's-like lymphoid reaction, serration and mucin production from the rectum to caecum. CpG island methylator phenotype -high and MSI-high gradually increased from the rectum to caecum. CpG island methylator phenotype is a poor prognostic factor of overall survival (hazard ratio (HR): 4.13, 95% confidence interval (CI): 1.27-13.46) and disease-free survival (HR: 2.90, 95% CI: 1.04-8.08) in rectal cancers. CONCLUSION: Clinicopathologic and molecular profiles of CRCs gradually change along bowel subsites, and the prognostic implication of CIMP is different according to tumour location.

Prognostic implication of mucinous histology in colorectal cancer patients treated with adjuvant FOLFOX chemotherapy.

BACKGROUND: There have been controversies in prognostic impact of mucinous histology on colorectal cancer, and its implication in patients treated with adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) is unclear. METHODS: Stage II and III colorectal cancer patients who underwent curative resection followed by adjuvant FOLFOX were included. Patients were grouped according to the mucinous content: >50%, mucinous adenocarcinoma (MAC); <50%, adenocarcinoma with intermediated mucinous component (AIM); and without any mucinous component, non-MAC (NMA). Clinicopathological features and disease-free survival (DFS) were compared. RESULTS: Among a total of 521 patients, 27 patients (5.2%) had MAC, 41 patients (7.9%) had AIM, and 453 patients (86.9%) had NMA. Mucinous adenocarcinoma and AIM had higher frequency of proximal location and microsatellite instability, but lower frequency of angiolymphatic invasion. Disease-free survival was significantly worse in the MAC compared with NMA (3-year DFS 57% and 86%, respectively; P<0.001) and AIM (3-year DFS 87%, P=0.01 vs MAC). Multivariate analysis revealed MAC as an independent negative prognostic factor of DFS (adjusted hazard ratio 7.96, 95% confidence interval 3.76-16.8). CONCLUSION: Adenocarcinoma with intermediated mucinous component and MAC have distinct clinicopathological features compared with NMA. Mucinous adenocarcinoma has an adverse prognostic impact on stage II or III colorectal cancer treated with adjuvant FOLFOX.

The beneficial effect of palliative resection in metastatic colorectal cancer.

BACKGROUND: We aimed to determine the role of palliative resection in metastatic colorectal cancer (mCRC) and ascertain which patient populations would benefit most from this treatment. METHODS: A total of 1015 patients diagnosed with mCRC at Seoul National University Hospital between 2000 and 2009 were retrospectively studied. RESULTS: Of the 1015 patients, 168 patients with only liver and/or lung metastasis received curative resection. The remaining 847 patients were treated with palliative chemotherapy and/or palliative resection combined with best supportive care. Palliative resection was performed in 527 (62.2%) cases (complete resection with negative margin (R0) in 93, R1/2 in 434). Resected patients had a more prolonged median overall survival (OS) than unresected patients (21.3 vs 14.1 months; P<0.001). In multivariate analysis, R0 resection was found to be associated with a superior OS compared with R1/2 resection (51.3 vs 19.1 months; P<0.001) and no resection (51.3 vs 14.1 months; P<0.001). When we performed propensity score matching, palliative resection was found to be related to prolonged OS (hazard ratio=0.72, 95% confidence interval=0.59-0.89; P=0.003). CONCLUSION: Palliative resection without residual disease and chemotherapy confers a longer-term survival outcome than palliative chemotherapy alone in mCRC patient subset.

Effect of Flammulina velutipes on spent-hen breast meat tenderization.

An experiment was carried out to investigate the effects of powdered vegetable dip sauces to improve the tenderness of spent-hen breast meat. Our overall purpose was to find lower-priced materials for the tenderization of spent-hen breast meat. The spent-hen breast meat was dipped into vegetable powder for 24 h at 4°C, and then the samples were analyzed. In the results for vegetable-powder treated samples, those treated with papain and pineapple had higher (P ≤ 0.05) myofibrillar fragmentation indices compared with those of the other samples. The kiwi-, pineapple-, and Flammulina velutipes-powder (winter mushroom) treated samples had new peptides of about 32 kDa and degradation to 30 kDa. Also, the Flammulina velutipes-powder treated samples showed new peptides of 15 kDa. These data imply that Flammulina velutipes is superior for common use than papain or pineapple for the tenderization of spent-hen meat.

Comparison of four manikins and fresh frozen cadaver models for direct laryngoscopic orotracheal intubation training.

OBJECTIVE: To compare the acceptability and preference between manikin models and fresh frozen cadaver (FFC) for direct laryngoscopic orotracheal intubation training. METHODS: In this prospective crossover trial, participants in the airway workshop performed direct laryngoscopic orotracheal intubation on four airway training manikins: Airway Management Trainer (Ambu, St Ives, UK), Airway Trainer (Laerdal, Medical, Stavanger, Norway), Airsim (Trucorp, Belfast, Northern Ireland) and "Bill 1" (VBM, Sulz, Germany), and FFC. Participants were asked to access the following: reality of jaw mobility, difficulty with mouth opening, reality of neck flexibility, difficulty with intubation, overall model reality and model preference for each model using a visual analogue scale (VAS) of 0-10 cm. The VAS scores for each model were compared. RESULTS: Fifty-six participants were included in the study. The FFC had a highest VAS score for reality of jaw mobility, overall reality and preference of model. Trucorp manikin and Laerdal manikin followed cadaver. There were no significant statistical differences between Trucorp manikin and Laerdal manikin. In difficulty with mouth opening and difficulty with intubation, Trucorp manikin had the lowest VAS score. CONCLUSION: The FFC is a more realistic and preferred model for direct laryngoscopic orotracheal intubation training. Trucorp and Laerdal manikin can be used as alternative models.

Effects of washing methods on gel properties of chicken surimi prepared from spent hen breast muscle.

In this study, 2 myofibrillar protein extraction methods were compared for the preparation of chicken surimi using spent hen breast muscle. One method involved 1 washing with 0.1, 0.5, or 1% sodium chloride solution followed by 2 washings with distilled water, with homogenization and centrifugation of the breast muscle after each washing (new method; NM). The other method used only distilled water for the extraction, and washing was repeated 3 times followed by homogenization and centrifugation of the breast muscle after each washing (conventional method; CM). The redness values of the batter as well as the cooked gel were significantly lower (P < or = 0.05) by NM as compared with CM. In addition, the SDS-PAGE of NM sarcoplasmic protein fractions showed phosphorylase bands with increased staining intensity as compared with CM, indicating that brightness was related to the sarcoplasmic protein fractions. Overall, the data implied that sodium chloride solution was more appropriate for the myofibrillar protein extraction of spent hen breast muscle than the commonly used distilled water method.

Comparison of manikin versus porcine models in cricothyrotomy procedure training.

OBJECTIVE: To compare the usefulness for training of a porcine model (larynx, trachea, and pig skin) and a manikin model using a Portex cricothyrotomy kit (PCK). METHODS: In a prospective randomised crossover trial, participants in the airway workshop performed crico-thyrotomy using a PCK on the porcine and manikin models (Tracheostomy Trainer and Case). The porcine model was made with larynxes and trachea from freshly slaughtered pigs and covered with a piece of thinned pigskin stapled to a wooden board. Participants were asked to assess the following: reality of skin turgor; difficulty with skin penetration, landmark recognition and procedure; reality of the model; and preference for each model using a visual analogue scale (VAS) of 0-10 cm. The VAS scores for each model were compared. RESULTS: 49 participants were included in the study. Mean (SD) VAS scores for the reality of skin turgor, degree of difficulty with skin penetration and landmark recognition were higher with the porcine model than with the manikin model (7.0 (2.1) vs 4.7 (2.0), 6.4 (2.4) vs 3.6 (2.2), 5.1 (2.2) vs 4.2 (2.5), respectively). There was no difference between the models in the difficulty of the procedure (5.0 (2.4) vs 4.7 (3.2)). The porcine model had a higher VAS score for overall reality and preference of the model (7.1 (2.0) vs 4.8 (2.3) and 7.1 (2.0) vs 4.8 (2.2), respectively). CONCLUSION: The porcine model is a more useful training tool than the manikin model for cricothyrotomy with PCK because of its reality and similarity to human anatomy.

Aberrant GATA2 epigenetic dysregulation induces a GATA2/GATA6 switch in human gastric cancer.

Six GATA transcription factors play important roles in eukaryotic development. Among these, GATA2, an essential factor for the hematopoietic cell lineage, exhibits low expression in human gastric tissues, whereas GATA6, which is crucial for gastrointestinal development and differentiation, is frequently amplified and/or overexpressed in human gastric cancer. Interestingly, we found that GATA6 was overexpressed in human gastric cancer cells only when GATA2 expression was completely absent, thereby showing an inverse correlation between GATA2 and GATA6. In gastric cancer cells that express high GATA6 levels, a GATA2 CpG island is hypermethylated, repressing expression in these cells. In contrast, GATA6 expression is undetectable in GATA2-overexpressing gastric cancer cells, which lack GATA2 DNA methylation. Furthermore, PRC2 complex-mediated transcriptional silencing of GATA6 was observed in the GATA2-overexpressing cells. We also show that the GATA2 and PRC2 complexes are enriched within the GATA6 locus, and that the recruitment of the PRC2 complex is impaired by disrupting GATA2 expression, resulting in GATA6 upregulation. In addition, ectopic GATA2 expression significantly downregulates GATA6 expression, suggesting GATA2 directly represses GATA6. Furthermore, GATA6 downregulation showed antitumor activity by inducing growth arrest. Finally, we show that aberrant GATA2 methylation occurs early during the multistep process of gastric carcinogenesis regardless of Helicobacter pylori infection. Taken together, GATA2 dysregulation by epigenetic modification is associated with unfavorable phenotypes in human gastric cancer cells by allowing GATA6 expression.

CpG island methylation in premalignant stages of gastric carcinoma.

There are limited reports on methylation analysis of the premalignant lesions of gastric carcinoma thus far. This is despite the fact that gastric carcinoma is one of the tumors with a high frequency of CpG island hypermethylation. To determine the frequency and timing of hypermethylation during multistep gastric carcinogenesis, non-neoplastic gastric mucosa (n = 118), adenomas (n = 61), and carcinomas (n = 64) were analyzed for their p16, human Mut L homologue 1 (hMLH1), death-associated protein (DAP)-kinase, thromobospondin-1 (THBS1), and tissue inhibitor of metalloproteinase 3 (TIMP-3) methylation status using methylation-specific PCR. Three different classes of methylation behaviors were found in the five tested genes. DAP-kinase was methylated at a similar frequency in all four stages, whereas hMLH1 and p16 were methylated in cancer samples (20.3% and 42.2%, respectively) more frequently than in intestinal metaplasia (6.3% and 2.1%, respectively) or adenomas (9.8% and 11.5%, respectively). However, hMLH1 and p16 were not methylated in chronic gastritis. THBS-1 and TIMP-3 were methylated in all stages but showed a marked increase in hypermethylation frequency from chronic gastritis (10.1% and 14.5%, respectively) to intestinal metaplasia (34.7% and 36.7%, respectively; P < 0.05) and from adenomas (28.3% and 26.7%, respectively) to carcinomas (48.4% and 57.4%, respectively: P < 0.05). The hMLH1, THBS1, and TIMP-3 hypermethylation frequencies were similar in both intestinal metaplasia and adenomas, but the p16 hypermethylation frequency tended to be higher in adenomas (11.5%) than in intestinal metaplasia (2.1%; P = 0.073). The average number of methylated genes was 0.6, 1.1, 1.1, and 2.0 per five genes per sample in chronic gastritis, intestinal metaplasia, adenomas, and carcinomas, respectively. This shows a marked increase in methylated genes from non-metaplastic mucosa to intestinal metaplasia (P = 0.001) as well as from premalignant lesions to carcinomas (P = 0.002). These results suggest that CpG island hypermethylation occur early in multistep gastric carcinogenesis and tend to accumulate along the multistep carcinogenesis.

Applicability of carcinoembryonic antigen-specific monoclonal antibodies to radioimmunoguided surgery for human colorectal carcinoma.

Two carcinoembryonic antigen (CEA)-specific monoclonal antibodies (MAbs), PR1A3 and T84.66, were tested to determine whether they could accurately localize colorectal carcinoma and therefore be applicable in radioimmunoguided surgery (RIGS). Twenty-one tumors by three human colorectal carcinoma cell lines with various levels of CEA expression (KM-12c, C75, and Clone A) were successfully implanted in the intra-abdominal organs of 15 nude mice. The tumors was localized using a portable radioisotope detector (Neoprobe 1000) 48 h after injection of radiolabeled MAbs (10 mCi/mouse) when the precordial counts were <20 per 2 s. Histopathological identification of radiolabeled MAbs were also performed using immunohistochemistry and microautoradiography. Radioactivity counted on a portable radioisotope detector correlated well with that on a gamma counter. The distribution in the blood was significantly greater than in other organs (P < 0.001). Localization indices of the tumor in various organs was from 1.1 to 8.5 in the PR1A3-pretreated mice and 3.0 to 8.6 in the T84.66-pretreated mice. Silver grains and immune staining were distributed in the tumor cells of the PR1A3-pretreated mice, whereas they were in the necrotic debris as well as the tumor cells of the T84.66-pretreated mice. There were significantly more silver grains in the liver in the T84.66-pretreated mice than in the PR1A3-pretreated mice (P = 0.004). The sensitivity and specificity of tumor localization by RIGS were 71.4 and 91.4% in the PR1A3-pretreated mice, whereas they were 60 and 76% in the T84.66-pretreated mice. A study using specific anti-CEA MAbs suggested PR1A3 as an efficient immune probe for RIGS in colorectal carcinoma with a low rate of false-positive detection.

Protein C and/or S deficiency presenting as peripheral arterial insufficiency.

Although protein C and/or S deficiency has frequently been associated with venous thromboembolic events, instances of arterial thromboses have been reported. However, the exact incidence of protein C and/or S deficiency in patients with peripheral arterial insufficiency has not been established. Furthermore, given the lack of adequate studies to define the natural history and angiographic findings of these patients, the treatment has not been well delineated. Therefore, we conducted a prospective study to investigate the prevalence, characteristic angiographic findings and optimal treatments in patients with peripheral arterial insufficiency associated with protein C and/or S deficiency. Between September 2000 and August 2004, 133 patients who presented with peripheral arterial insufficiency underwent hypercoagulability tests before the initiation of any treatments. Of these, 11 patients (8.3%) with protein C and/or S deficiency were included in this study. There were nine males and two females. The ages ranged from 38 years to 72 years (mean 57 years). All patients showed characteristic angiographic findings: long segment thrombotic occlusion of a main peripheral artery without evidence of atherosclerosis or with mild atherosclerotic changes in the aorta and other major arterial trees. Surgical or endovascular procedures were performed in nine patients: bypass graft in four, thrombectomy in four and catheter-directed thrombolysis in one. Conservative treatment with full anticoagulation was performed in two patients. All patients received pre- and post-operative anticoagulation. Except for one amputated case, clinical and vascular laboratory improvements were achieved in 10 patients. Mean follow-up period was 21 months (range 4-45 months). However, one patient, in whom re-vascularization surgery was performed successfully, discontinued warfarin therapy himself at 10 months after surgery, graft occlusion and limb loss occurred at 30 months after surgery. This initial experience suggests that protein C and/or S deficiency may be an independent risk factor for peripheral arterial insufficiency. Patients who present with peripheral arterial insufficiency and protein C and/or S deficiency demonstrate characteristic angiographic findings. Once the diagnosis of protein C and/or S deficiency is made, patients should be treated with life-long anticoagulation.

Somatic mutations of the first 14 exons of APC in hamartomatous polyps of the colon.

Although hamartomatous or hyperplastic polyps are rarely accompanied by adenomatous or carcinomatous foci, the role of APC (MIM# 175100) mutations in these polyps is not clear. The neoplastic potential of these polyps was assessed with regard to somatic mutation of the first 14 exons of APC. DNA from 14 hamartomatous polyps (12 patients with juvenile polyp, JP; two patients with Peutz-Jeghers syndrome, PJS) and 27 hyperplastic polyps was used. Exons 1-14 of APC were amplified using verified oligonucleotide primers, and PCR-SSCP analysis was performed. Translation-terminating mutation in exon 15 was also screened using the protein truncation test. All mutations found were transitions or transversions with heterozygous alleles of both wild-type and mutant APC in exons 2, 9, 10, and 11. Four hamartomatous polyps (three from JP and one from PJS) showed seven, new mutations and one common APC variant (codon 486), whereas no hyperplastic polyps demonstrated mutation. APC mutation was not correlated with previous history of colorectal carcinoma or number of polyps. Since all mutations were missense or silent mutations occurred in exons not previously known to have functionally relevant area, their phenotypic implication appeared to be limited.

Smooth muscle distribution in the extrahepatic bile duct: histologic and immunohistochemical studies of 122 cases.

The distribution of smooth muscle fibers in the extrahepatic bile duct (EBD) wall is not well characterized. We analyzed 101 consecutive Whipple's operation specimens and 21 autopsy specimens for the pattern of smooth muscle distribution in EBD using the Masson-trichrome stain and the desmin immunohistochemical stain. The patterns were categorized as continuous, interrupted, scattered, and no muscle layer. EBDs were divided into lower, middle, and upper portions, and the distribution pattern of smooth muscle fibers was analyzed separately in each portion. Because most surgically resected specimens contained the middle and lower EBDs with only a portion of the upper EBD, only the length of the middle and lower EBDs (common bile duct, CBD) was measured. The mean length of CBD in surgically resected specimens was 6.4 +/- 1.4 cm (men, 6.6 +/- 1.3 cm; women, 6.1 +/- 1.5 cm). The mean length of CBD in autopsy specimens was 6.8 +/- 1.0 cm. The predominant patterns of the lower third of the EBD were interrupted (49%) and continuous (43%). The predominant patterns of the middle third of the EBD were scattered (63%) and interrupted (23%). Those of the upper third of the EBD were no muscle fiber (58%) and scattered (39%). In conclusion, different patterns of smooth muscle distribution were observed in different portions of the EBD. Because scattered muscle fibers or no muscle fibers were the main features of the upper third of the EBD, understanding of this pattern may be helpful for assessment of the depth of invasion or staging of carcinoma of the upper third of the EBD.

DNA hypermethylation in gastric cancer.

BACKGROUND: Transcriptional silencing of tumour suppressor genes by DNA hypermethylation plays a crucial role in the progression of gastric cancer. Many genes involved in the regulation of cell cycle, tissue invasion, DNA repair and apoptosis have been shown to be inactivated by this type of epigenetic mechanism. RESULTS: Recent studies have demonstrated that DNA hypermethylation begins early in cancer progression, and in some cases, may precede the neoplastic process. Ageing is associated with DNA hypermethylation, and may provide a mechanistic link between ageing and cancer. Several reports have indicated that Epstein-Barr virus-related gastric cancer is associated with a high frequency of DNA hypermethylation, suggesting that viral oncogenesis might involve DNA hypermethylation with inactivation of tumour suppressor genes. Hypermethylation of hMLH1 with the resulting loss of its expression is known to cause microsatellite instability, which reflects genomic instability associated with defective DNA mismatch repair genes in the tumour. CONCLUSIONS: In conclusion, recent studies demonstrate that DNA hypermethylation is a crucial mechanism of inactivation of tumour suppressor genes in gastric cancer. A better understanding of DNA hypermethylation will provide us with new opportunities in the diagnosis and therapy of gastric cancer.

Kaposi's sarcoma-associated herpesvirus in Kikuchi's disease.

Kikuchi's disease is a fairly common self-limited disorder among Orientals that usually involves the cervical lymph nodes of young individuals and occurs predominantly in females. Frequently, the disease is associated with fever or flu-like symptoms, an elevated erythrocyte sedimentation rate (ESR), neutropenia, and lymphocytosis with atypical lymphocytes in the peripheral blood, suggesting a viral origin. However, no infectious agent has been identified. The presence of Kaposi sarcoma-associated herpesvirus, known as human herpesvirus 8 (KSHV/HHV 8), was investigated by polymerase chain reaction (PCR) in archival tissue from 26 cases of Kikuchi's disease using published sequences of KSHV/HHV 8 as primers. PCR products were further characterized by Southern blot analysis. Forty reactive lymph nodes and a case of Kaposi sarcoma (KS) were included as negative and positive controls, respectively. Patients consisted of 10 men and 16 women with a mean age of 27 years. All patients were previously healthy and presented with cervical or axillary lymphadenopathy. None were positive for human immunodeficiency virus (HIV) or otherwise immunocompromised. Viral DNA was amplified by PCR in six cases of Kikuchi's disease (23%) and the control KS tissue. Southern blot analysis confirmed that the amplified products were KSHV/HHV 8. In the reactive lymph nodes, no viral genome was amplified by PCR. The presence of DNA sequences of KSHV/HHV 8 in a substantial portion of Kikuchi's disease suggests that KSHV/HHV 8 might play an important role in the pathogenesis of a subset of Kikuchi's disease.

An experimental study of embolic effect according to infusion rate and concentration of suspension in transarterial particulate embolization.

RATIONALE AND OBJECTIVES: The authors evaluate the embolic effect according to infusion rate and concentration of particulate suspension, focusing on arterial occlusion level. METHODS: The renal arteries of 14 rabbits were embolized with 150 to 250 microns polyvinyl alcohol (PVA) particles, divided into four groups according to two different infusion rates (1 mg/second and 0.1 mg/second) and two different concentrations of suspension (10 mg/mL and 2.5 mg/mL). Arteriograms obtained immediately and a week after embolization were assessed for occlusion level. For the nephrograms obtained a week after embolization, the opacifying areas were graded from 0 to 4. Median coronal sections of each kidney specimen were investigated for the presence of peripheral infarct grossly and for the presence of PVA particles in the small artery microscopically. RESULTS: Arteriograms showed various occlusion levels. Using a 0 to 4 grading system, the opacifying area of the nephrogram obtained 1 week after embolization was noted to be smaller in the low infusion rate group (P < 0.05). In gross and microscopic pathologic examination, the number of cases with peripheral infarct or PVA particles in the small artery (< 300 microns) was greater in the group with the low infusion rate and low concentration (P < 0.05). CONCLUSIONS: In transarterial particulate embolization, slower infusion of more diluted suspension provides for a more distal arterial occlusion.

Alpha-fetoprotein-producing gastric carcinoma presenting focal hepatoid differentiation in metastatic lymph nodes.

Hepatoid adenocarcinoma (HA) is a rare variant of adenocarcinoma of the stomach, which is clinically characterized by increased level of serum alpha-fetoprotein (AFP) and poor prognosis. Microscopic findings include both adenocarcinomatous and hepatoid elements. A case of gastric adenocarcinoma with focal hepatoid differentiation confined within the metastatic lymph nodes occurred in a 55-year-old woman, who developed an advanced gastric carcinoma composed entirely of a typical papillo-tubular adenocarcinoma. Metastatic tumors were present in 8 of 13 perigastric lymph nodes, and 3 of these showed medullary and trabecular tumour growth reminiscent of hepatocellular carcinoma with immunohistochemical positivity for AFP. Preoperative serum AFP was 630 ng/ml and dropped to 76 ng/ml 2 weeks after the operation. Microscopic and immunohistochemical studies on the entire primary tumour tissue failed to demonstrate a focus of hepatoid or an AFP-positive area. This suggests that elevation of serum AFP may be reflected by focal hepatoid differentiation only in the metastatic lymph nodes, requiring extensive evaluation of the metastatic tumour in regional lymph nodes in the case of AFP-producing gastric carcinoma.

p53 mutation and overexpression in hepatocellular carcinoma and dysplastic nodules in the liver.

In hepatocarcinogenesis, both de novo and multistep pathways have been suggested and in the latter a dysplastic nodule is the proposed precancerous lesion. In this study, we tried to ascertain whether or not the p53 gene is altered in low-grade/high-grade dysplastic nodules (LDN/HDN) and to determine the role of p53 alteration in multistep hepatocarcinogenesis. Eight hepatocellular carcinomas (HCCs), 9 HDNs, 17 LDNs and 25 cirrhotic nodules (LCs) were examined by polymerase chain reaction-single strand conformation polymorphism/direct sequencing and immunohistochemical staining for p53. Four of the 8 HCCs (50%) revealed p53 overexpression and 2 (25%) had missense mutations. Four of the 9 HDNs (44%) showed weak and/or focal p53 overexpression but none had mutation in the exons examined. Neither p53 overexpression nor mutation was found in 17 LDNs and 25 LCs. These results suggest that p53 mutation might be an unusual event in precancerous lesions of multistep hepatocarcinogenesis (DN-HCC sequence) and may play a less crucial part than in colorectal carcinogenesis.

Multifocal meningioangiomatosis: a report of two cases.

We report the CT and MR findings in two patients with multifocal meningioangiomatosis, neither of whom had a family history or stigmata of neurofibromatosis. All lesions were located in the cortical and subcortical areas and had round dense calcifications with eccentric cysts. The masses were associated with surrounding edema and gliosis.

Zinc deficiency manifested by dermatitis and visual dysfunction in a patient with Crohn's disease.

We report a case of Crohn's disease with low serum zinc concentration in a 26-year-old woman. She demonstrated acrodermatitis enteropathica and decreased visual acuity during total parenteral nutrition. Subsequent intravenous zinc supplementation resulted in alleviation of the skin lesions and improvement of visual acuity. This case supports the notion that depressed serum zinc in Crohn's disease may cause clinical manifestations, such as acrodermatitis enteropathica and retinal dysfunction, which may be correctable with zinc supplementation.