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Hepatocellular Carcinoma Microvessel Density Quantitation with Image Analysis: Correlation with Prognosis
Pages 135-141
Amr Mohamed, Shelley A. Caltharp, Jason Wang, Cynthia Cohen and Alton B. Farris
DOI: http://dx.doi.org/10.6000/1927-7229.2013.02.03.2

Published: 31 July 2013


Abstract: Hepatocellular carcinoma (HCC) has a progression considered to be dependent on angiogenesis. Intratumoral microvessel density (MVD) has been associated with metastasis and recurrence risk; however, selection bias, counting errors, and lack of standardized assessment criteria have limited the clinical utility of angiogenesis quantitation. Therefore, we analyzed HCC angiogenesis with image cytometry using different methods and determined the correlation to prognosis. Tissue microarrays with 135 HCCs were CD31 and CD34 immunostained and quantitated with the Dako ACIS III Image Cytometer labeling index (LI) and Aperio Scanscope XT and MVD algorithm. LI and MVD were compared to each other and to pathologic features and prognosis (recurrence free survival). Using median cutoffs of microvesselquantitation, survival curve analysis showed a statistically significant difference between CD31 MVD algorithm measurement and prognosis (low MVD mean survival = 56.6 months and high MVD mean = 26.5 months; Log-Rank P = 0.0076). Survival was not significantly related to CD31 LI, CD34 LI or CD34 MVD. By linear regression, a direct correlation was observed between CD31 and CD34 using MVD (r = 0.45, P <0.0001), between CD31 MVD and CD31 LI (r = 0.55, P < 0.0001), and between CD31 LI and CD34 LI (r = 0.51, P < 0.0001). In addition, there was a weak but statistically significant relationship between CD31 MVD and CD34 LI (r = 0.25, P = 0.0050). Together, this data confirms previous studies linking angiogenesis to disease prognosis and suggests the utility of MVD image analysis algorithms.

Keywords: Hepatocellular carcinoma, microvessel density, immunohistochemistry, prognosis.
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A Review of the Expression of Genes Involved in Sex Steroid Hormone Metabolism in Prostate Tissue: A Need for Epigenetic Information
Pages 142-150
Jamie Ritchey, Wilfried Karmaus, Tara Sabo-Attwood, Susan E. Steck and Hongmei Zhang
DOI: http://dx.doi.org/10.6000/1927-7229.2013.02.03.3

Published: 31 July 2013


Abstract: There is strong clinical and laboratory evidence indicating that sex steroid hormones are important to the development and progression of prostate cancer, yet results from epidemiologic research conflicts. Examining gene expression in the sex steroid hormone pathway may uncover differences between cancerous and non-cancerous prostate tissues, yet our review using a pathway-oriented approach indicates that there is limited consistency across results, with the exception of GSTP1 found in the estrogen pathway, which was under-expressed in cancerous prostate tissue. This agrees with past studies that reported GSTP1 is methylated in prostate cancer. With new cost-effective technology, we can screen for epigenetic markers, like methylation, which can be applied in epidemiological studies. A clearer understanding of gene expression and epigenetic mechanisms in prostate cancer may contribute to improving prevention, diagnosis, and treatment.

Keywords: Prostate tissue, cancer, sex steroid hormones, methylation, GSTP1.
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Phase II Study of Irinotecan in Combination with Capecitabine on a 3-Weekly Schedule as First-Line Chemotherapy for Patients with Metastatic or Locally Advanced Colorectal Cancer
Pages 151-159
Antonieta Salud, Vicente Alonso, Pilar Escudero, Miguel Burillo, Cristina Martín, Fernando Rivera, Alfonso Yubero, Carlos García-Girón and Alberto Muñoz
DOI: http://dx.doi.org/10.6000/1927-7229.2013.02.03.4

Published: 31 July 2013


Abstract: Background: Capecitabine has demonstrated non inferiority efficacy and improved safety compared with 5-fluorouracil (5-FU)/leucovorin (LV) in metastatic colorectal cancer (mCRC) without the inconvenience of an infusional therapy. The aim of the present study was to evaluate the efficacy and safety of capecitabine plus irinotecan (CPT-11) given every 3 weeks (XELIRI regimen) as first-line treatment in locally advanced (LA) or mCRC, in order to improve patient tolerability and quality of life. Patients and methods: Patients with LA or mCRC received CPT-11 225 mg/m2 (180 mg/m2 if > 65 years old) on day 1 and capecitabine 1000 mg/m2 (750 mg/m2 if > 65 years old) twice daily on days 2-15 every 3 week. Primary endpoints were objective response rate (ORR) and toxicity of the chemotherapeutic regimen. Secondary endpoints of overall survival (OS), progression-free survival (PFS), response duration and quality of life were also evaluated.

Results: Ninety-one patients were included. In an intention-to-treat analysis, complete response was achieved in 3 patients and partial response in 27, for an ORR of 33%. The disease control rate (ORR + stable disease) was 72.5%. Median time to progression and OS were 9.3 and 17.1 months respectively. Grade 3/4 neutropenia and diarrhea were the most commonly reported adverse vents.

Conclusion: The XELIRI regimen given every 3 weeks, as first-line therapy of LA or mCRC was effective and well tolerated, including elderly patients. Severe gastrointestinal toxicities and hematological events were manageable.

Keywords: CPT-11, Capecitabine, Irinotecan, XELIRI regimen, Colorectal cancer.
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Urolithiasis in Children with Acute Lymphoblastic Leukemia
Pages 160-164
Mariane Gouvêa Monteiro de Camargo, Ricardo Jordão Duarte, Lilian Maria Cristofani, Vicente Odone Filho and Miguel Srougi
DOI: http://dx.doi.org/10.6000/1927-7229.2013.02.03.5

Published: 31 July 2013Open Access


Abstract: Background: Urinary tract lithiasis(UTL) requires careful intervention, especially when associated with other diseases. The purpose of this study was to assess the outcome of symptomatic UTL in children with acute lymphoblastic leukemia (ALL) and to evaluate its correlation with the anti-neoplastic treatment phase and drugs, and to assess the need for intervention, results, complications and follow-up.

Procedure: The charts of 350 patients with ALL (1990-2008) were retrospectively evaluated. Signs and symptoms, methods of diagnosis, complications, treatment approach, resolution, anti-leukemic treatment phase when the UTL was diagnosed, drugs used and interference on ALL treatment were recorded.

Results: A total of 12/350 patients (3.4%) had UTL (14 stones). The median age was 7.6 years. Pain was present in 60%, hematuria in 20% and both in 20%. The median stone size was 4mm (3- 13.8mm). Three patients required hospitalization (pain) and one had chemotherapy discontinued due to severe hematuria and blood support. At the time of diagnosis of UTL, four patients were in the induction phase with corticosteroids, four were in the maintenance phase with corticosteroids, two were in the maintenance phase without corticosteroids, and one had a recurrence after therapy, and two were off-therapy. 11/13 episodes of UTL had spontaneous resolution, two underwent successful extracorporeal shockwave lithotripsy, and one patient remains with an asymptomatic stone.

Conclusions: 3.4% of children with ALL presented symptomatic UTL. While the majority of cases have been resolved spontaneously, hospitalization and delay in chemotherapy have increased morbidity in these children.

Keywords: Urothelial carcinoma, cisplatin, gemcitabine, pathological complete response.
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