Flow cytometric DNA ploidy analysis has been reported to be more objective and sensitive than morphologic evaluation as a surveillance method in patients with Barrett esophagus (BE) for the ...development and progression of precancerous lesions. Such analyses are typically performed using fresh samples that require a separate or "jumbo" biopsy, are prone to false DNA aneuploidy if not promptly processed, and do not allow for retrospective studies. The feasibility of performing flow cytometric DNA analysis on paraffin-embedded biopsies was studied to circumvent some of these problems using 12 squamous esophageal mucosa with inflammation and 58 BE cases showing varying degrees of dysplasia. Among the BE cases, 12 had no dysplasia, 20 were indefinite for dysplasia, 14 had low grade dysplasia, and 12 had high grade dysplasia. Satisfactory histograms were obtained in 86% of the analyzed samples. Among cases with adequate histograms, DNA aneuploidy was identified in 77% with high grade dysplasia, 16% with low grade dysplasia, 23% of indefinite for dysplasia, and 0% without dysplasia. One of the esophagitis samples was also DNA aneuploid. Correlation of DNA aneuploidy and degree of dysplasia is highly significant (P = .001). The authors have demonstrated that routinely processed paraffin-embedded biopsies can be used for flow cytometric ploidy analysis. DNA aneuploidy was highly correlated with degree of dysplasia and serves as a quantitative prognostic indicator for prospective as well as retrospective studies of the evolution of BE to carcinoma.
Pediatric obesity Holterman, Mark J; Le Holterman, Ai-Xuan; Browne, Allen F
The Surgical clinics of North America,
06/2012, Volume:
92, Issue:
3
Journal Article
Peer reviewed
Childhood obesity is a tremendous burden for children, their families, and society. Obesity prevention remains the ultimate goal but rapid development and deployment of effective nonsurgical ...treatment options is not currently achievable given the complexity of this disease. Surgical options for adolescent obesity have been proven to be safe and effective and should be offered. The development of stratified protocols of increasing intensity should be individualized for patients based on their disease severity and risk factors. These protocols should be offered in multidisciplinary, cooperative clinical trials to critically evaluate and develop optimal treatment strategies for morbid obesity.
Surveillance methods in Barrett esophagus (BE) using light microscopic examination of random biopsy specimens may miss focal dysplasia. In addition, dysplastic foci identified initially may not be ...relocated subsequently, making chemoprevention studies difficult. By using a special gastroscope, systematic mapping (4-quadrant biopsy specimens at 1-cm intervals) was performed in 22 patients (33 total mappings yielding 700 biopsy specimens). H&E, immunohistochemistry, and DNA ploidy analysis were performed. c-erbB-2 and positive Ki-67 were detected only in dysplastic sites; thus, their detection did not precede morphologically identifiable dysplasia. On the other hand, aneuploidy and p53 were detected in dysplastic and nondysplastic areas. p53 was correlated with dysplasia, and S-phase narrowly missed correlation, while aneuploidy was not correlated. PCNA and bcl-2 were ubiquitous, limiting their usefulness. On second maps, epithelial type was reidentified with 81% accuracy. A significant correlation was found between p53 and dysplasia. Sites of dysplasia and abnormal biomarkers could be relocated accurately by using endoscopic mapping. Therefore, mapping combined with biomarker studies may provide better surveillance and serve as a useful technique in chemoprevention studies.
Background Biliary atresia is an idiopathic, neonatal liver disease of the bile ducts. The natural evolution of biliary atresia is known in developed countries. This study describes the clinical ...course of biliary atresia in Vietnam, a developing country. Methods Chart reviews were undertaken of patients treated with or without the Kasai procedure between January 2010 and July 2013 at a children's hospital in Vietnam. Results Of 287 children with biliary atresia, 149 (52%) were treated without the Kasai procedure and 138 (48%) were treated with the Kasai procedure. Median age at diagnosis was 2.4 months for children treated without the Kasai procedure vs 2.3 months for those treated with the procedure. The percentages of patients in the group treated without the Kasai procedure presenting at <2 months, 2 to <3 months, 3 to <4 months, 4–6 months, and >6 months of age were 31%, 35%, 15%, 10%, and 9%, respectively, compared to those treated with the Kasai procedure at 36% ( P = .38), 44% ( P = .12), 16% ( P = 1.0), 4% ( P = .037), and 0% ( P < .001), respectively. The group treated without the Kasai procedure had 1- and 2-year survivals of 52% and 28%, respectively (median survival 6.6 months); in contrast, the group treated with the Kasai procedure had 1- and 2-year transplant-free survivals of 84% and 71%. No patients were treated by liver transplantation because of lack of a liver transplantation program in Vietnam. Conclusion The majority of biliary atresia in Vietnam remains untreated despite early presentation and reasonable outcomes after a Kasai procedure relative to Western countries. These data illustrate the high health care burden for biliary atresia in Vietnam and the need to improve education about biliary atresia and its treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Obesity is a multi-organ system disease with underlying insulin resistance and systemic chronic inflammation. Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of the ...underlying metabolic dysfunction. This review provides a highlight of the current understanding of NAFLD pathogenesis and disease characteristics, with updates on the challenges of NAFLD management in obese and severely obese (SO) patients and recommendations for the pediatric surgeons' role in the care of SO adolescents.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Alpha-defensin (α-defensin) has been identified as a potential marker for bladder cancer in urine by surface enhanced laser desorption ionization studies, and confirmed using both immunoabsorption ...and immunodepletion studies. The objective of this study was to investigate the role of α-defensin in bladder cancer. Immunohistochemical analysis of tissue sections showed that α-defensin peptides are frequently expressed in bladder cancer cells. It is noteworthy that expression of α-defensins increased with tumor invasiveness. Surface enhanced laser desorption ionization analysis showed the presence of α-defensin in the T24 and A498 cancer cell lines. These cell lines show higher classically aggressive
in vitro characteristics compared with the J82 cells that did not express α-defensin. Exogenously added α-defensin increased the proliferation and motility/invasiveness of these cell lines using respective assays. It is interesting that α-defensin peptides increased intracellular calcium ions (Ca
2+). These data are consistent with a role for α-defensin in bladder cancer via modulation of cell motility and invasiveness using common intracellular signals, such as Ca
2+. We propose that autocrine tumor expression of α-defensins may play an important role in facilitating the invasive phenotype of bladder cancer in patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
We have previously reported that Fms-like tyrosine kinase-3 ligand (flt3-L) induced tumor stabilization and regression of palpable ectopic prostate tumors (TRAMP-C1). Although some mice remained ..."tumor free" for several months following termination of therapy, tumors invariably reappeared and grew progressively in all animals. The lack of a curative response suggests that TRAMP-C1 tumors may inhibit the development of a flt3-L-induced anti-tumor immune response. Consistent with this view, we demonstrate herein that TRAMP-C1 tumors isolated from flt3-L treated animals contained a marked dendritic cell (DC) infiltrate that was temporally correlated with tumor regression. However, tumor-associated DCs, especially in a flt3-L setting, progressively lost MHC class II antigen expression during tumor growth. Treatment with the DC maturation factor trimeric CD40 ligand (CD40-L) either alone or in combination with fl3-L neither prevented loss of DC class II antigens nor disease relapse. Because loss of class II antigens would prevent CD4+ helper T (Th) cell development, we treated tumor-bearing mice with agonistic anti-4-1BB antibody (Ab), which can promote cytotoxic T lymphocyte (CTL) development independent of Th cell function. However, anti-4-1BB Ab alone did not alter TRAMP-C1 growth kinetics, and, when used in combination, was no more effective than flt3-L alone. The inability of the 4-1BB co-stimulatory signal to promote tumor regression may have been related to two additional features of TRAMP-C1 tumors. First, tumor-associated T cells, but not splenic T cells from tumor-bearing animals, were profoundly deficient in expression of CD3-epsilon (CD3epsilon) and T cell receptor-beta chain (TCRbeta). Second, CTLs required 24 h to efficiently kill TRAMP-C1 target cells even after up-regulation of MHC class I antigens by interferon-gamma. This rate of tumor cell destruction by CTLs may not be sufficient to prevent tumor progression. Taken together, these data reveal several important immunosuppressive characteristics of the prostate tumor microenvironment (TME) that immunotherapeutic interventions must first overcome to achieve longterm cures. These data also highlight the importance of utilizing treatment versus vaccination models in the evaluation of immunotherapeutic modalities.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Alpha-interferon (IFN-α) is thought to be important in the pathogenesis of insulin dependent diabetes mellitus (IDDM). However, since potent inducers of IFN-α, viruses, have been shown to modulate ...immune function and autoimmunity, we investigated whether administration of recombinant IFN-α (rIFN-α) would inhibit the diabetic process in BB rats. The development of diabetes was significantly inhibited by injections of either 10
5 units or 4 × 10
5 units rIFN-α. rIFN-α was more effective in preventing disease when injections were initiated at an earlier age (28–30 days vs 35–40 days). Histologic examination revealed a markedly lower degree of insulitis in rIFN-α treated rats. The mean total peripheral WBC and differential count, T-cell subsets, peripheral blood NK cell number, splenic NK cell activity, and serum cytotoxic beta cell surface antibody levels were unaltered by rIFN-α administration.
In vitro incubation with rIFN-α inhibited the Con A proliferative response of mononuclear splenocytes of BB rats but not of Sprague Dawley rats. These results document that rIFN-α treatment potently prevents diabetes by inhibiting the development of insulitis. This paradoxical diabetes sparing effect may have significant implications for the treatment and prevention of IDDM and towards the understanding the autoimmune process.
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IJS, IMTLJ, KILJ, KISLJ, NUK, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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