Yield of esophagogastroduodenoscopy and colonoscopy in cancer of unknown primary

Objectives: Carcinoma of unknown primary origin (CUP) is heterogeneous group of cancers. Role of gastrointestinal (GI) endoscopy in this entity is under investigated. Aim of this study was to evaluate yield of Colonoscopy and Esophagogastroduodenoscopy (EGD) in localizing primary tumor in patients with CUP. METHODOLOGY: Patients with histopathologically proven CUP who underwent colonoscopy / EGD to find the primary tumor from December 2009 to December 2011 were included in the study. Abdominal symptoms and cytokeratin (CK) 7 and 20 markers were correlated with presence of primary in GI tract. Results: After giving informed consent 86 patients were included in final analysis. All patients underwent colonoscopy while 60(70%) got EGD along with colonoscopy. Mean age was 55.10 +/-11.94 years with 52(60%) male. Abdominal symptoms were present in 50%. CK7+/CK20- in 34(40%); CK7-/CK20+ in 2(2%) while CK7+/20+ in 7(8%) of metastatic tumor samples. Liver was metastatic site in 47(55%), Lymph node 12(14%) and Ascites in 8(9%). Endoscopy detected primary in 6 (7%) patients with 3 each in stomach and colon. No association of abdominal symptoms and cytokeratin markers was found with presence of GI primary site. CONCLUSION: Yield of localizing primary lesion in the GI tract by pan-endoscopy was limited. Abdominal symptoms and cytokeratin markers do not predict presence of gastrointestinal malignancies

Modulations of cell cycle checkpoints during HCV associated disease

Background Impaired proliferation of hepatocytes has been reported in chronic Hepatitis C virus infection. Considering the fundamental role played by cell cycle proteins in controlling cell proliferation, altered regulation of these proteins could significantly contribute to HCV disease progression and subsequent hepatocellular carcinoma (HCC). This study aimed to identify the alterations in cell cycle genes expression with respect to early and advanced disease of chronic HCV infection. Methods Using freshly frozen liver biopsies, mRNA levels of 84 cell cycle genes in pooled RNA samples from patients with early or advanced fibrosis of chronic HCV infection were studied. To associate mRNA levels with respective protein levels, four genes (p27, p15, KNTC1 and MAD2L1) with significant changes in mRNA levels (\u3e 2-fold, p-value \u3c 0.05) were selected, and their protein expressions were examined in the liver biopsies of 38 chronic hepatitis C patients. Results In the early fibrosis group, increased mRNA levels of cell proliferation genes as well as cell cycle inhibitor genes were observed. In the advanced fibrosis group, DNA damage response genes were up-regulated while those associated with chromosomal stability were down-regulated. Increased expression of CDK inhibitor protein p27 was consistent with its mRNA level detected in early group while the same was found to be negatively associated with liver fibrosis. CDK inhibitor protein p15 was highly expressed in both early and advanced group, but showed no correlation with fibrosis. Among the mitotic checkpoint regulators, expression of KNTC1 was significantly reduced in advanced group while MAD2L1 showed a non-significant decrease. Conclusion Collectively these results are suggestive of a disrupted cell cycle regulation in HCV-infected liver. The information presented here highlights the potential of identified proteins as predictive factors to identify patients with high risk of cell transformation and HCC development

Designing a balanced scorecard for a tertiary care hospital in Pakistan: a modified Delphi group exercise.

Balanced Scorecards (BSC) are being implemented in high income health settings linking organizational strategies with performance data. At this private university hospital in Pakistan an elaborate information system exists. This study aimed to make best use of available data for better performance management. Applying the modified Delphi technique an expert panel of clinicians and hospital managers reduced a long list of indicators to a manageable size. Indicators from existing documents were evaluated for their importance, scientific soundness, appropriateness to hospital\u27s strategic plan, feasibility and modifiability. Panel members individually rated each indicator on a scale of 1-9 for the above criteria. Median scores were assigned. Of an initial set of 50 indicators, 20 were finally selected to be assigned to the four BSC quadrants. These were financial (n = 4), customer or patient (n = 4), internal business or quality of care (n = 7) and innovation/learning or employee perspectives (n = 5). A need for stringent definitions, international benchmarking and standardized measurement methods was identified. BSC compels individual clinicians and managers to jointly work towards improving performance. This scorecard is now ready to be implemented by this hospital as a performance management tool for monitoring indicators, addressing measurement issues and enabling comparisons with hospitals in other settings