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Introduction: Surgery is recommended following endoscopic polypectomy for malignant adenoma (MA) in the large bowel in patients with risk factors for tumor recurrence or distant metastasis are present., Objectives: We present long‑term outcomes of a prospective study in patients with endoscopically removed MAs., Patients and Methods: A total of 128 patients who underwent endoscopic polypectomy were followed up for a median of 70.4 months. The criteria for adequate polypectomy included endoscopically and histologically (margin ≥2 mm) complete excision, lack of angioinvasion, and good tumor differentiation (G1 or G2). Sixty‑seven patients did not meet 1 or more of the criteria (high‑risk group) and 61 met all of the criteria (low‑risk group). Unfavorable outcomes were residual disease, lymph node metastasis, recurrent disease, distant metastasis, or death due to colorectal cancer. Histological samples from 85 patients were reassessed to determine the effect of a margin width of 1 mm or more and tumor budding on the outcomes., Results: Surgery was performed in 36 patients (28.1%), of whom 32 (47.7%) were high‑risk and 4 (6.5%) were low‑risk. Unfavorable outcome was observed in 10 patients (7.8%; all high‑risk; 10 of 67 patients, 14.9%). Favorable outcome was observed in 61 of 128 patients who had a 2‑mm free margin, and in 44 of 85 patients who fulfilled the modified criterion of 1‑mm free margin. Tumor budding was detected in 17 of 85 patients (20.9%). Unfavorable outcome was observed in 2 of these patients (11.7%) and in 5 patients (7.3%) without tumor budding (P >0.05)., Discussion: Long‑term outcomes of an endoscopic resection of MAs are good. Bowel resection does not prevent unfavorable outcomes, while a reduction of the tumor‑free margin would not deteriorate the results (STROBE 1B).

Up to date several authors discussed interactions between cells forming inflammatory infiltrates in the course of inflammatory bowel disease (IBD), mainly dealing with endoscopic biopsy specimens. These usually contain only mucosa. We have evaluated full bowel wall sections, which seems to be especially important in patients with Crohn's disease (CD). The purpose of our study was to evaluate the relationship between vascular density and expression of thrombospondin-1 (TSP-1) and vascular endothelial growth factor receptor 1 (VEGFR-1) in full-thickness tissue fragments of intestinal wall taken from patients after colectomy, comparing those with IBD to non-IBD control group. Histological sections were immunostained with antibodies against CD-31, TSP-1, and VEGFR-1 and analyzed by pathologists with the use of computer-assisted morphometrics. Our research showed significantly higher vascular density and vascular area percentage in all layers of bowel wall in patients with CD when compared to control. We have also demonstrated differences in vascular density distribution between ulcerative colitis (CU) and CD and between CU and control. However we have not found statistically significant correlation between those findings and VEGFR-1 or TSP-1 expression. Our results might suggest existence of different, TSP-1 independent pathways of antiangiogenesis in IBD.

Colon anastomosis is therapeutically challenging because multiple, usually undetectable factors influence a spectrum of repair mechanisms. We hypothesized that low molecular weight heparins, routinely administered perioperatively, may differentially affect gene expression related to colon healing. Twenty pairs of untreated and enoxaparin-treated rats underwent left-side hemicolectomy with a primary end-to-end anastomosis. Normal colon and anastomotic bowel segments were resected on day 0 and on days 1, 3, 5, and 7 after surgery, respectively. Serial anastomosis transverse cross-sections were evaluated microscopically and by microarray (Rat Genome 230 2.0, Affymetrix). Differentially expressed probe sets were annotated with Gene Ontology. We also examined the influence of enoxaparin on fibroblast proliferation and viability in vitro. Among the 5476 probe sets, we identified differential expression at each healing time point, yielding 79 subcategories. Most indicated genes were involved in wound healing, including multicellular organismal development, locomotory behavior, immune response, cell adhesion, inflammatory response, cell-cell signaling, blood vessel development, and tissue remodeling. Although we found no intensity differences in histological features of healing between enoxaparin-treated and control rats, treatment did induce significant expression changes during early healing. Of these changes, 83 probe sets exhibited at least twofold changes and represented different functional annotations, including inflammatory response, regulation of transcription, regulation of apoptosis, and angiogenesis. Fibroblast culture confirmed an anti-viability effect of enoxaparin. Enoxaparin affects colon wound-related gene expression profiles, but further studies will resolve whether heparin treatment is a risk factor after intestinal surgery, at least in some patients.

Background: Clinical progression of colorectal cancers (CRC) may occur in parallel with distinctive signaling alterations. We designed multidirectional analyses integrating microarray-based data with biostatistics and bioinformatics to elucidate the signaling and metabolic alterations underlying CRC development in the adenoma-carcinoma sequence., Methodology/principal Findings: Studies were performed on normal mucosa, adenoma, and carcinoma samples obtained during surgery or colonoscopy. Collections of cryostat sections prepared from the tissue samples were evaluated by a pathologist to control the relative cell type content. The measurements were done using Affymetrix GeneChip HG-U133plus2, and probe set data was generated using two normalization algorithms: MAS5.0 and GCRMA with least-variant set (LVS). The data was evaluated using pair-wise comparisons and data decomposition into singular value decomposition (SVD) modes. The method selected for the functional analysis used the Kolmogorov-Smirnov test. Expressional profiles obtained in 105 samples of whole tissue sections were used to establish oncogenic signaling alterations in progression of CRC, while those representing 40 microdissected specimens were used to select differences in KEGG pathways between epithelium and mucosa. Based on a consensus of the results obtained by two normalization algorithms, and two probe set sorting criteria, we identified 14 and 17 KEGG signaling and metabolic pathways that are significantly altered between normal and tumor samples and between benign and malignant tumors, respectively. Several of them were also selected from the raw microarray data of 2 recently published studies (GSE4183 and GSE8671)., Conclusion/significance: Although the proposed strategy is computationally complex and labor-intensive, it may reduce the number of false results.

Barrett's esophagus represents a well-defined precursor lesion of esophageal adenocarcinoma, although only a subset of patients with these lesions advances to invasive cancer. Currently, reliable markers predicting neoplastic progression in Barrett's esophagus are lacking. The only clinically useful risk factor is the presence of dysplasia in Barrett's epithelium, but its use as a prognostic marker of disease progression has several significant limitations. Thus, identification of biomarkers of potential prognostic value in dysplasia development in Barrett's esophagus is highly important. The aim of the study was to determine if expression levels of selected genes support histologic diagnosis of dysplastic changes in Barrett's esophagus. Upon rigorous sampling and independent histopathologic examination of endoscopic specimens by two experienced gastrointestinal pathologists, 56 patients with Barrett's esophagus (16 negative for dysplasia, 15 with indefinite, 21 with low-grade, and 4 with high-grade dysplasia) were selected for molecular analysis. The relative mRNA levels of ten selected genes were estimated by quantitative real-time polymerase chain reaction (PCR) analysis. Although expression of nine genes showed trends toward down- or upregulation during progression from Barrett's esophagus without dysplasia to Barrett's esophagus with high-grade dysplasia, only a decrease in S100A2 mRNA levels was statistically significant (P<0.05). However, there was considerable variation among individuals and significant overlapping of ranges. Furthermore, detailed, comparative analysis of serial samples from Barrett's mucosa and normal squamous epithelium shows large intra-individual variability of gene expression levels. In conclusion, expression of this set of ten genes cannot be used as a molecular marker aiding histological examination of dysplasia in Barrett's esophagus. Significant inter- and intra-patient variations of gene expression levels makes use of the selected genes impractical.

Background: Based on recommendations of the Fifth and Sixth Reports of the Joint National Committee (JNC) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, Health Care Plan (now Univera Healthcare) Buffalo, NY, developed a clinical guideline to improve the management of patients with hypertension. To increase awareness and utilization, the guideline was distributed as hard copy reports and made available through our electronic information system., Objective: To determine blood pressure (BP) control rates and adherence to guideline recommendations., Study Design: Retrospective chart review., Patients and Methods: We randomly sampled hypertensive patients seen during 1998 to evaluate hypertension management. Computerized medical and pharmacy records were reviewed for patient demographics, antihypertensive medications, comorbid conditions, and BP readings. Patient assessment was based on antihypertensive regimen and achievement of target BP according to the recommendations of the guidelines (< 140/90 mm Hg for the general population and < 130/85 mm Hg for special populations). In addition, we assessed control rates using traditional Health Plan Employer Data and Information Set (HEDIS) measures (< 140/90 mm Hg)., Results: Overall, 35% of patients achieved target BP and 68% were treated with agents recommended by our JNC-based guideline. In contrast, using traditional HEDIS measures, 41% of patients achieved BP control. Of 39 patients with compelling indications (primarily diabetic patients), 13% achieved BP target and 67% were treated with recommended agents., Conclusions: The impact of our clinical guideline is reflected through the relatively high utilization of recommended drugs. However, optimal BP control continues to be problematic. In particular, patients with diabetes warrant focused attention.

Background: The complex between urokinase (uPA) and its type-1 inhibitor (PAI-1) is formed exclusively from the active forms of these components; thus, the complex concentration in a biological sample may reflect the ongoing degree of plasminogen activation. Our aim was to establish an ELISA for specific quantification of the uPA:PAI-1 complex in plasma of healthy donors and breast cancer patients., Methods: A kinetic sandwich format immunoassay was developed, validated, and applied to plasma from 19 advanced-stage breast cancer patients, 39 age-matched healthy women, and 31 men., Results: The assay detection limit was <2 ng/L, and the detection of complex in plasma was validated using immunoabsorption, competition, and recovery tests. Eighteen cancer patients had a measurable complex concentration (median, 68 ng/L; range, <16 to 8700 ng/L), whereas for healthy females and males the median signal values were below the detection limit (median, <16 ng/L; range, <16 to 200 ng/L; P <0.0001). For patient plasma, a comparison with total uPA and PAI-1 showed that the complex represented a variable, minor fraction of the uPA and PAI-1 concentrations of each sample., Conclusion: The reported ELISA enables detection of the uPA:PAI-1 complex in blood and, therefore, the evaluation of the complex as a prognostic marker in cancer.

Spinal cord injuries (SCIs) in the pediatric population present a unique challenge to the caregiver in that both the physical injury and the growth and development issues need to be addressed simultaneously. Different types of injuries are anticipated than those seen in adults because of the developmental phases of the pediatric spinal cord. This article will review the differences between the pediatric and adult spinal cords, growth and development, and the types of injuries incurred by this population, followed by a case presentation.

Mammalian bites account for 1% of all emergency department visits and dogs are common perpetrators. School-aged children are the most vulnerable and experience the majority of this type of trauma. Most of the cases involve a known dog and many of the attacks involve the family pet. When a child presents with a severe dog bite, the injury should be managed using appropriate assessment and intervention techniques. In some cases, conscious sedation can be used to provide amnesia, analgesia and sedation during the surgical repair. Proper preparation of the wound prior to repair will decrease infection rates. The need for tetanus and rabies prophylaxis must be evaluated in all dog bites. Facial injuries may require complex repair and reconstruction with appropriate surgical referral. Thorough discharge instructions are an important aspect of the nursing role.

A case of giant diffuse filiform polyposis of the entire colon with pathological features of Crohn's disease in a 30-year-old man is presented. The most important aspects and difficulties with differential diagnosis of filiform polyposis are discussed.

Objectives: To compare the malignant potential of hyperplastic polyps and adenomas in relation to different histological classifications and to try to follow the natural history of the BEGP-carcinoma sequence., Methods: During a 13-yr period (1981-1993), 811 BEGP were discovered in 432 patients in consecutive esophagogastroscopic examinations in our department. Adequate endoscopic biopsies or polypectomy specimens were histologically diagnosed as hyperplastic polyp in 751 (92.6%) and adenoma in 60 (7.4%) of the lesions, according to WHO classification. Hyperplastic lesions were further divided into two subgroups: 268 were polypoid foveolar hyperplasia (FH) and 483 were typical hyperplastic polyps (HP), according to Elster's classification. Special attention was paid to focal malignancy at the first examination or malignant transformation of BEGP during follow-up. Ninety-six patients with 220 BEGP were followed for 1-11 yr, with an average of 2 yr and 8 months., Results: According to Elster's classification, there were 10/483 (2.1%) HP and 6/60 (10.0%) adenomas with focal carcinoma. Moreover, in 19/265 patients (7.1%) with HP and in 4/30 patients (13.3%) with adenomas, carcinoma was found elsewhere in the stomach. During our follow-up, 5/131 HP showed different steps of histological transformation: focal intestinal metaplasia in two, focal dysplasia in one, and focal carcinoma in two of them, which is 1.6%, 0.8%, and 1.6%, respectively. In 1/23 adenomas, focal carcinoma developed after 1 yr of observation (4.3%). Separate gastric carcinomas developed outside polyps during follow-up in 2/58 (3.5%) patients with hyperplastic polyps only. None of those with FH had focal carcinoma either at primary biopsy or during long-term observation. All proportions concerning gradual transformation of hyperplastic polyps classified as only one group according to WHO were lower., Conclusions: In contrast to hitherto existing opinions, our results give support to the idea that gastric HP, like adenomas, are susceptible to malignant transformation. It seems sensible to separate a subgroup of FH from HP, since FH have no malignant potential until they change their histology to HP. The treatment of FH and HP as one group is the main reason why the malignant potential of hyperplastic polyps is still underestimated.

An increased expression of lysosomal enzymes, cathepsin (Cat) D, Cat B and Cat L, was observed in various human tumours and after in vitro cell transformation. To establish possible co-ordination in their expression, all three cathepsins were determined in human breast tumours and in transformed human breast epithelial cells (HBEC). In breast carcinoma (n = 120) all three cathepsins, determined immunochemically and by enzymatic activity, were increased compared to normal breast tissues. The activities, correlated with the corresponding protein masses for Cat D (r = 0.77, p < 0.01), but not for Cat B and Cat L. Significant increase in Cat B activity was observed in stage II compared to stage I tumours, and Cat L activity in stage III compared to stage II tumours, but no significant correlation of cathepsin protein with tumour stage (TNM) was established. No significant correlation between Cat D and the cysteine cathepsins B and L was observed. Similarly, Cat D, Cat B and Cat L levels did not correlate in the in vitro system, e.g. in the five transformed HBEC, such as evolved after dimethylbenz(a)anthracene treatment and c-Has-ras oncogene transfection of diploid MCF-10F cell line (Calaf et al., 1993). Transformed cells showed increased anchorage-independent growth and invasive capability (MCF-10 < MCF-10FTras < D3 < D3-1 < D3-1Tras). The intracellular level of Cat D was not related to cell invasiveness, while total cellular Cat B and Cat L increased 13 fold and 4 fold, respectively, in the most invasive cell line, D3-1Tras compared to MCF-10F.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in the expression and processing of cathepsin D (CD) have been shown to be associated with cancer invasion and metastasis. However, the value of CD as a prognostic marker remains controversial. Most studies have used immunological methods to measure the mature form of CD, although it is the precursor (pro-CD) that appears to be abnormally secreted by breast cancer cells. A sandwich-type ELISA has been developed that is specific for pro-CD. The assay employs a monoclonal antibody to mature CD as the capture reagent and a rabbit polyclonal to the pro fragment as the detector. The assay is specific for pro-CD and capable of quantitating this antigen in biological samples. Pro-CD levels were measured in plasma samples from 76 breast cancer patients and compared with 36 samples from normal control individuals. The plasmas of breast cancer patients showed elevated levels of pro-CD; 12% were more than two standard deviations above the mean for the normal samples. Immunoblots of the plasma samples using a CD monoclonal antibody revealed a band at the appropriate size for pro-CD that corresponded in intensity with the ELISA results. Affinity adsorption of breast cancer plasmas with pepstatin agarose followed by immunoblot analysis revealed a single protein band that correlated with pro-CD. Only trace amounts were detected in the normal control plasmas. These results demonstrate that cathepsin D is present in the plasma of breast cancer patients primarily in its precursor form and that it may be a useful prognostic indicator.

The present experiments were undertaken to extent our earlier observations (J Physiol Pharmacol 1991, 42, 367-79) relating membrane potential with membrane recycling of parietal cells. Studies were performed in vitro using gastric glands that were isolated through the use of rat stomachs transformed into "everted sacs" and filled with hyperosmolar NaCl-EDTA solution. Acid production was indirectly determined by accumulation of 14C-aminopyrine (AP) and its translocation by measurement of acridine orange fluorescence. H+/K(+)-ATPase activity was assayed by measurement of K(+)-stimulated p-nitrophenylphosphatase (pNPPase) of the proton pump. Morphologic state of parietal cells in relation to their functional activity was observed using electron microscopy. Changes in the membrane potential were obtained by the treatment of gastric glands with protonophore carbonyl cyanide m-chlorophenylhydrazone (CCCP) in the incubation media of different pH. CCCP caused time-dependent decrease in AP accumulation by parietal cells from the medium of pH 6.6 but not that of pH 7.8. pNPPase activity increased in aplical and decreased in tubulovesical membrances prepared from CCCP treated glands which were incubated in the medium being more acidic than cell cytoplasm. Electron microscopic assessment showed morphological transformation of resting parietal cells treated with CCCP in pH 6.6 from nonsecreting to secreting state. CCCP acting in acidic incubation medium also caused the decrease in acridine orange fluorescence in the cytoplasm of parietal cells with some temporary increase of its fluorescence in the lumen o gastric glands. These findings support our hypothesis that changes in parietal cell membrane potential by protonophore CCCP may translocate HCl from tubulovesicles to secretory canaliculi. While the above explanation is suggestive, the exact mechanisms controlling a membrane recycling during the secretory response of parietal cells in vitro remain to be elucidated.

During a 5-year period from January 1987 through January 1992, 58 patients were admitted to the Allegheny General Hospital trauma center for non-scuba, non-suicidal diving injuries. There were 46 men and 12 women (mean age, 23 years). Forty-five patients were injured in swimming pools. Twenty-two patients had blood alcohol levels > 100 mg/dL. Cervical spine injury was the most common pathologic entity encountered in this group of patients. Closed head injury, pelvic fracture, thoracic vertebral fracture, and rib fractures were other injuries identified. Some patients had multiple organ failure syndrome. Aquatic recreational activities carry a risk for injury that is preventable. The mechanism, clinical data, and complications of 58 patients are presented and the importance of prevention is discussed.

The tumor-suppressor gene p53 is altered by missense mutation in numerous human malignancies. However, the biochemical properties of p53 and the effect of mutation on these properties are unclear. A human DNA sequence was identified that binds specifically to wild-type human p53 protein in vitro. As few as 33 base pairs were sufficient to confer specific binding. Certain guanines within this 33-base pair region were critical, as methylation of these guanines or their substitution with thymine-abrogated binding. Human p53 proteins containing either of two missense mutations commonly found in human tumors were unable to bind significantly to this sequence. These data suggest that a function of p53 may be mediated by its ability to bind to specific DNA sequences in the human genome, and that this activity is altered by mutations that occur in human tumors.

Four hundred fifty three percutaneous fine-needle biopsies (FNB) guided ultrasonically of the focal lesions to the liver and 418 to the pancreas were subjected to retrospective analysis. Biopsies were performed with the aid of real time ultrasound equipment ALOKA SSD-280. The needles of 0.7 and 0.8 mm in outer diameter were used for the aspiration. Smears were fixed with alcohol and stained with hematoxylin and eosin, and examined under light microscope. Specimens suitable for the examination were obtained in 97% of liver biopsies and 90% of pancreatic biopsies. Sensitivity of FNB in the diagnosis of hepatic and pancreatic carcinoma was 97% and 91%, respectively. Its specificity was 100%. ENB efficiency in the diagnosis of the focal lesions to the liver was 98% and in case of the focal lesions to pancreas -95%.

The concentrations of vitamin A in liver samples obtained at autopsy of patients who died of cancer was investigated. It was found that liver vitamin A levels in cancer patients were significantly lower than in controls. Although our recent results have suggested that the decreased serum retinol level in cancer patients reflects rather a functional impairment of vitamin A release from the liver, the results of this study suggest that this phenomenon can also indicate a true vitamin A deficiency in patients with neoplastic process.

A series of 2,772 accidents has been analyzed in two plants. The following aspects were considered: 1) environmental circumstances, 2) accident causes as given by witnesses or victims, and 3) time of day. Activity of the plants or particular groups of workers was assessed by supervisors on a 10-point scale. A circadian rhythm of accidents has been shown. It was determined to be governed by the interrelationships between the following endogenous and exogenous rhythmic factors: human factors, such as fatigue and circadian fluctuation of biological functions; and multiple hygienic and social components, which either promote human performance or suppress it, e.g., high environmental temperature, overcrowding, and noise. The rate of accidents depends on the particular combinations of these factors, all of which change around the clock. In both plants, the circadian rhythm of accidents was approximately parallel to the circadian rhythm of activity of the plant as a whole rather than to the activity of shift workers only, with a peak around 1100 hr. The lowest number of accidents was noted during night shifts; some increase was observed after midnight, however, in spite of the lowest level of plant activity at that time.