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ABSTRACT: BACKGROUND: Many studies have described the risk factors of gallstone formation in gastric cancer patients after gastrectomy, but few studies focus on the management of asymptomatic gallstones. Our goal is to examine the rationale of simultaneous cholecystectomy during gastric cancer surgery, and influence of surgical mortality, morbidity and overall survival after combined cholecystectomy and gastrectomy. METHODS: We retrospectively reviewed 445 gastric cancer patients and the gallbladders evaluated by abdominal ultrasound or computed tomography preoperatively and postoperatively. Clinicopathologic factors, including surgical morbidity, mortality and overall survival of combined surgery, were compared between patients receving gastrectomy with simultaneous cholecystectomy and patients receiving gastrectomy only. We also evaluated the risk factors of gallstone formation after gastrectomy and the probability of subsequent cholecystectomy after gastrectomy in gastric cancer patients with or without asymptomatic gallstones. RESULTS: Of 445 gastric cancer patients, 52 (11.7%) patients had asymptomatic gallstones upon diagnosis of gastric cancer. Among patients with healthy gallbladders, 15.2% developed gallstones after gastrectomy. Men and older patients (age over 60) had significantly higher risk of gallstone formation. Rate of subsequent cholecystectomy in patients with and without preoperative asymptomatic gallstones was 30.8% and 4.5%, respectively (p=0.005). The rates of mortality and morbidity were not significantly different between combined surgery (3.4%, 24.2%) and gastrectomy only (3.1%, 22%). There was also no significant difference in 5-year survival between combined surgery (61%) and gastrectomy only (63%) groups. CONCLUSION: Combined cholecystectomy for asymptomatic gallstone in gastric cancer surgery may be considered. It was not associated with increased surgical morbidity or mortality, and had no significant effect on overall survival.
International journal of surgery (London, England) 02/2013;
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ABSTRACT: Traditional open surgery for gastrointestinal stromal tumors (GIST) requires a long incision. Moreover, the gas-filling laparoscopic technique used in GIST surgery still has its limitations. Therefore, we developed a gasless laparoscopic (GL) surgery for GIST and compared it with traditional open surgery.
Between October 2007 and September 2009, 62 GIST patients in the National Taiwan University Hospital received wide excisions. Of these 62 patients, 30 underwent the new procedure (GL group) and 32 had open surgery (OS group). Preoperative and postoperative clinicopathologic characteristics were compared between the groups.
There were no significant differences in preoperative characteristics or blood loss. However, the days to first flatus, postoperative hospital stay, wound length, white blood cell count at postoperative day one, and peak daily body temperature were all significantly improved in the GL group. Usage of postoperative analgesia on postoperative days one to five was also significantly lower in the GL group.
Wide-excision laparoscopy for gastric GIST can be performed more safely, more effectively, and with faster postoperative recovery using the gasless technique as compared with the open method. We, therefore, recommend this new surgical technique, which hybridizes the advantages of both the traditional open method and pure laparoscopic surgery.
World Journal of Surgical Oncology 01/2013; 11:44. · 1.12 Impact Factor
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ABSTRACT: Background. Minimally invasive surgery has proved to be effective and efficient in the management of gastric submucosal tumors (SMT). However, confronting a SMT near the esophagogastric junction (EGJ) is still challenging because of the potentially devastating risks of stenosis or leakage. This study evaluated the safety, feasibility, and oncological efficacy of laparoscopic resection for SMTs located near the EGJ. Methods. From December 2008 to November 2011, we enrolled a total of 19 patients diagnosed with gastric SMTs located near the EGJ who underwent laparoscopic surgery. The clinicopathological characteristics and surgical outcomes of the 19 patients were recorded and reviewed retrospectively. Results. All 19 patients underwent laparoscopic resections of their gastric SMTs without complications during the study period. There were 9 men and 10 women, with a mean age of 63.3 ± 15.1 years (range 33-86 years). The operative duration was 187.8 ± 58.9 minutes (range 90-310 minutes). Intraoperative localization included endoscopy (n = 3), tattooing (n = 2), and combined modalities (n = 1). The exogastric (n = 12) and transgastric methods (n = 7) were used. The histopathology showed 10 gastrointestinal stromal tumors, 7 leiomyomas, 1 hyperplastic polyp, and 1 lipoma. The postoperative courses for all cases were uneventful. The mean follow-up period was 16.7 ± 9.4 months, with no recurrence noted. Conclusions: Laparoscopic resections for gastric SMTs near the EGJ are safe and feasible, with satisfactory oncological outcomes in the short term.
Surgical Innovation 12/2012; · 2.13 Impact Factor
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ABSTRACT: : Older hospitalized patients often experience geriatric syndromes that may be prevented using complex interventions. For example, the Hospital Elder Life Program (HELP) was shown to be successful, but sites with limited resources might find HELP costly. Thus, modifying HELP to include only key components might prove more cost-effective.
: The aim of this study was to develop and evaluate a modified HELP intervention derived from a conceptual model of shared geriatric risk factors for older hospitalized patients undergoing major abdominal surgery.
: The modified HELP intervention was developed and evaluated in Taiwan, based on the UK Medical Research Council evaluation framework. According to this 4-phase framework, HELP (Phase 1) was modified based on a theoretical model of shared risk factors, and HELP's feasibility andefficacy (Phases 2 and 3) were evaluated between August 2007 and April 2009 in a preintervention and postintervention pilot trial. Participants were 179 patients enrolled as the control (n = 77) and intervention (n = 102) groups.
: The modified HELP intervention targeting 3 shared risk factors (cognitive, functional, and nutritional status) was developed and implemented successfully on a surgical ward. By hospital discharge, patients in the intervention group experienced significantly less risk for five geriatric syndromes: functional dependence, malnutrition, in-hospital weight loss >5%, depression, and sleep disturbance (adjusted odds ratio = 0.01-0.39; p < .05). These results were independent of patients' baseline malnutrition, education, periampullary diagnosis, and duration of surgery.
: The positive findings of this pilot trial support continued development of modified HELP. The next logical step in testing its effectiveness and long-term benefit is a randomized controlled trial.
Nursing research 03/2012; 61(2):111-8. · 1.80 Impact Factor
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ABSTRACT: We aimed to find clinically relevant gene activities ruled by the signal transducer and activator of transcription 3 (STAT3) proteins in an ER(-) breast cancer population via network approach. STAT3 is negatively associated with both lymph nodal category and stage. MYC is a component of STAT3 network. MYC and STAT3 may co-regulate gene expressions for Warburg effect, stem cell like phenotype, cell proliferation and angiogenesis. We identified a STAT3 network in silico showing its ability in predicting its target gene expressions primarily for specific tumor subtype, tumor progression, treatment options and prognostic features. The aberrant expressions of MYC and STAT3 are enriched in triple negatives (TN). They promote histological grade, vascularity, metastasis and tumor anti-apoptotic activities. VEGFA, STAT3, FOXM1 and METAP2 are druggable targets. High levels of METAP2, MMP7, IGF2 and IGF2R are unfavorable prognostic factors. STAT3 is an inferred center regulator at early cancer development predominantly in TN.
Cancer informatics 01/2012; 11:87-111.
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ABSTRACT: Helicobacter pylori (H. pylori), the human stomach pathogen, lives on the inner surface of the stomach and causes chronic gastritis, peptic ulcer, and gastric cancer. Plasma membrane repair response is a matter of life and death for human cells against physical and biological damage. We here test the hypothesis that H. pylori also causes plasma membrane disruption injury, and that not only a membrane repair response but also a cell proliferation response are thereby activated. Vacuolating cytotoxin A (VacA) and cytotoxin-associated gene A (CagA) have been considered to be major H. pylori virulence factors. Gastric cancer cells were infected with H. pylori wild type (vacA+/cagA+), single mutant (ΔvacA or ΔcagA) or double mutant (ΔvacA/ΔcagA) strains and plasma membrane disruption events and consequent activation of membrane repair components monitored. H. pylori disrupts the host cell plasma membrane, allowing localized dye and extracellular Ca(2+) influx. Ca(2+)-triggered members of the annexin family, A1 and A4, translocate, in response to injury, to the plasma membrane, and cell surface expression of an exocytotic maker of repair, LAMP-2, increases. Additional forms of plasma membrane disruption, unrelated to H. pylori exposure, also promote host cell proliferation. We propose that H. pylori activation of a plasma membrane repair is pro-proliferative. This study might therefore provide new insight into potential mechanisms of H. pylori-induced gastric carcinogenesis.
International Journal of Molecular Sciences 01/2012; 13(8):10176-92. · 2.60 Impact Factor
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PROTEOMICS - CLINICAL APPLICATIONS 10/2011; 5(9-10):567. · 1.81 Impact Factor
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ABSTRACT: This study explored the feasibility of using the ultrasound Nakagami image to assess the degree of liver fibrosis in rats. The rat has been widely used as a model in investigations of liver fibrosis. Ultrasound grayscale imaging makes it possible to observe fibrotic rat livers in real time. Statistical analysis of the envelopes of signals backscattered from rat livers may provide useful clues about the degree of liver fibrosis. The Nakagami-model-based image has been shown to be useful for characterizing scatterers in tissues by reflecting the echo statistics, and hence the Nakagami image may serve as a functional imaging tool for quantifying rat liver fibrosis. To validate this idea, fibrosis was induced in each rat liver (n=21) by an intraperitoneal injection of 0.5% dimethylnitrosamine. Livers were excised from rats for in vitro ultrasound scanning using a single-element transducer. The backscattered-signal envelopes of the acquired raw ultrasound signals were used for Nakagami imaging. The Metavir score determined by a pathologist was used to histologically quantify the degree of liver fibrosis. It was found that the Nakagami image could be used to distinguish different degrees of liver fibrosis in rats, since the average Nakagami parameter increased from 0.55 to 0.83 as the fibrosis score increased from 0 (i.e., normal) to 4. This correlation may be due to liver fibrosis in rats involving an increase in the concentration of local scatterers and the appearance of the periodic structures or clustering of scatterers that would change the backscattering statistics. The current findings indicate that the ultrasound Nakagami image has great potential as a functional imaging tool to complement the use of the conventional B-scan in animal studies of liver fibrosis.
Ultrasonics 08/2011; 52(2):215-22. · 1.84 Impact Factor
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Pai-Sheng Chen,
Jen-Liang Su,
Shih-Ting Cha,
Woan-Yuh Tarn,
Ming-Yang Wang,
Hsing-Chih Hsu,
Ming-Tsan Lin,
Chia-Yu Chu,
Kuo-Tai Hua, Chiung-Nien Chen,
Tsang-Chih Kuo,
King-Jen Chang,
Michael Hsiao,
Yi-Wen Chang,
Jin-Shing Chen,
Pan-Chyr Yang,
Min-Liang Kuo
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ABSTRACT: MicroRNAs (miRNAs) influence many biological processes, including cancer. They do so by posttranscriptionally repressing target mRNAs to which they have sequence complementarity. Although it has been postulated that miRNAs can regulate other miRNAs, this has never been shown experimentally to our knowledge. Here, we demonstrate that miR-107 negatively regulates the tumor suppressor miRNA let-7 via a direct interaction. miR-107 was found to be highly expressed in malignant tissue from patients with advanced breast cancer, and its expression was inversely correlated with let-7 expression in tumors and in cancer cell lines. Ectopic expression of miR-107 in human cancer cell lines led to destabilization of mature let-7, increased expression of let-7 targets, and increased malignant phenotypes. In contrast, depletion of endogenous miR-107 dramatically increased the stability of mature let-7 and led to downregulation of let-7 targets. Accordingly, miR-107 expression increased the tumorigenic and metastatic potential of a human breast cancer cell line in mice via inhibition of let-7 and upregulation of let-7 targets. By mutating individual sites within miR-107 and let-7, we found that miR-107 directly interacts with let-7 and that the internal loop of the let-7/miR-107 duplex is critical for repression of let-7 expression. Altogether, we have identified an oncogenic role for miR-107 and provide evidence of a transregulational interaction among miRNAs in human cancer development.
The Journal of clinical investigation 08/2011; 121(9):3442-55. · 15.39 Impact Factor
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ABSTRACT: Bladder cancer is a common urothelial cancer. Through proteomic approaches, calreticulin (CRT) was identified and proposed as a urinary marker for bladder cancer. CRT is a multifunctional molecular chaperone that regulates various cellular functions such as Ca(2+) homeostasis and cell adhesion. CRT is overexpressed in various cancers, but its mechanism of action in the development of bladder tumors remains unclear. We generated J82 bladder cancer cells lines that either stably overexpressed or knocked down CRT to investigate the physiological effects of CRT on bladder tumors. Compared with the transfected control vector cells, the knockdown of CRT suppressed cell proliferation, migration, and attachment, whereas overexpression of CRT enhanced cell migration and attachment. We further demonstrated that the phosphorylation status of focal adhesion kinase and paxillin, important regulators of the focal adhesion complex, was also regulated in these cells. In contrast, phosphorylation of Src, a protein tyrosine kinase reported to be affected by CRT, was not significantly different between the control and CRT-RNAi groups. Most importantly, we observed that tumors derived from J82 CRT-RNAi cells were significantly smaller and had fewer metastatic sites in the lung and liver in vivo than did transfected control vector cells. In conclusion, our results suggest that alteration of CRT expression levels might affect bladder cancer progression in vitro and in vivo.
American Journal Of Pathology 06/2011; 179(3):1425-33. · 4.89 Impact Factor
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ABSTRACT: MicroRNAs (miRNAs) are a class of endogenous, small and highly conserved noncoding RNAs that control gene expression either by degradation of target mRNAs or by inhibition of protein translation. They play important roles in cancer progression. A single miRNA can provoke a chain reaction and further affect protein interaction network (PIN). Therefore, we developed a novel integrative approach to identify the functional roles and the regulated PIN of oncomirs.
We integrated the expression profiles of miRNA and mRNA with the human PIN to reveal miRNA-regulated PIN in specific biological conditions. The potential functions of miRNAs were determined by functional enrichment analysis and the activities of miRNA-regulated PINs were evaluated by the co-expression of protein-protein interactions (PPIs). The function of a specific miRNA, miR-148a, was further examined by clinical data analysis and cell-based experiments. We uncovered several miRNA-regulated networks which were enriched with functions related to cancer progression. One miRNA, miR-148a, was identified and its function is to decrease tumor proliferation and metastasis through its regulated PIN. Furthermore, we found that miR-148a could reduce the invasiveness, migratory and adhesive activities of gastric tumor cells. Most importantly, elevated miR-148a level in gastric cancer tissues was strongly correlated with distant metastasis, organ and peritoneal invasion and reduced survival rate.
This study provides a novel method to identify active oncomirs and their potential functions in gastric cancer progression. The present data suggest that miR-148a could be a potential prognostic biomarker of gastric cancer and function as a tumor suppressor through repressing the activity of its regulated PIN.
BMC Systems Biology 06/2011; 5:99. · 3.15 Impact Factor
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ABSTRACT: To improve the ultrasonographic detection rates of thyroid cancers with microcalcifications, we propose to enhance the sensitivity of sonographic calcifications detection and to avoid interobserver variation by a computerized quantification method in a prospective setting. A total of 227 participants with 258 nodules were evaluated. Among them, two nodules were excluded for suspicious aspiration cytology results without pathologic proof. Among the remaining 256 nodules, the diagnosis of 181 nodules was verified by surgical pathology and the diagnosis of 75 was based on fine needle aspiration (FNA) biopsy results. There were 173 benign thyroid nodules and 83 malignant thyroid nodules, which included 74 papillary carcinomas. Patient clinical data were collected and the presence of calcifications on conventional gray-scale ultrasound images was retrospectively reviewed by a thyroid specialist. Quantification of cystic components and calcifications was automatically performed by a proprietary program (AmCAD-UT) implemented with methods proposed in this article. The calcification index (CI) was calculated after the cystic component was excluded. The CI between benign and malignant nodules diagnosed by combined FNA biopsy and surgical pathology results (total number, 256) showed a significant difference (p < 0.0001, AUC = 0.746). Furthermore, we excluded patients without surgical pathology results for further validation and the CI between benign and malignant nodules confirmed by pathology results (total number, 181) showed a significant difference (p < 0.0001, AUC = 0.763). To learn whether our computer program increased our diagnostic capabilities, we analyzed human investigators and their abilities to detect and evaluate. In this study, calcifications were noted in 48.19% (40 of 83) of malignant thyroid nodules and in 10.98% (19 of 173) of benign nodules. This new computer-aided diagnosis method to evaluate the sonographic calcifications of thyroid nodules is a more sensitive and more objective method. It can provide better sensitivity than conventional methods in the diagnosis of thyroid malignancies containing microcalcifications.
Ultrasound in medicine & biology 06/2011; 37(6):870-8. · 2.02 Impact Factor
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ABSTRACT: Gastric cancer is the second most common cause of cancer deaths worldwide and due to its poor prognosis, it is important that specific biomarkers are identified to enable its early detection. Through 2-D gel electrophoresis and MALDI-TOF-TOF-based proteomics approaches, we found that 14-3-3β, which was one of the proteins that were differentially expressed by 5-fluorouracil-treated gastric cancer SC-M1 cells, was upregulated in gastric cancer cells. 14-3-3β levels in tissues and serum were further validated in gastric cancer patients and controls. The results showed that 14-3-3β levels were elevated in tumor tissues (n=40) in comparison to normal tissues (n=40; p<0.01), and serum 14-3-3β levels in cancer patients (n=145) were also significantly higher than those in controls (n=63; p<0.0001). Elevated serum 14-3-3β levels highly correlated with the number of lymph node metastases, tumor size and a reduced survival rate. Moreover, overexpression of 14-3-3β enhanced the growth, invasiveness and migratory activities of tumor cells. Twenty-eight proteins involved in anti-apoptosis and tumor progression were also found to be differentially expressed in 14-3-3β-overexpressing gastric cancer cells. Overall, these results highlight the significance of 14-3-3β in gastric cancer cell progression and suggest that it has the potential to be used as a diagnostic and prognostic biomarker in gastric cancer.
Proteomics 06/2011; 11(12):2423-39. · 4.43 Impact Factor
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ABSTRACT: This report describes a system that utilizes a single high-intensity focused ultrasound (HIFU) transducer for both the localization and ablation of arteries with internal diameters of 0.5 and 1.3 mm. In vitro and in vivo tests were performed to demonstrate both the imaging and ablation functionalities of this system. For imaging mode, pulsed acoustic waves (3 cycles for in vitro and 10 cycles for in vivo tests, 2 MPa peak pressure) were emitted from the 2-MHz HIFU transducer, and the backscattered ultrasonic signal was collected by the same transducer to calculate Doppler shifts in the target region. The maximum signal amplitude of the Doppler shift was used to determine the location of the target vessel. The operation mode was then switched to the therapeutic mode and vessel occlusion was successfully produced by high-intensity continuous HIFU waves (12 MPa) for 60 s. The system was then switched back to imaging mode for residual flow to determine the need for a second ablation treatment. The new system might be used to target and occlude unwanted vessels such as vasculature around tumors, and to help with tumor destruction.
IEEE Transactions on Ultrasonics Ferroelectrics and Frequency Control 05/2011; · 1.69 Impact Factor
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ABSTRACT: We had developed an innovative method of minimally invasive surgery using gasless laparoscopy in resection of the small bowel lesion. This study aimed at evaluating the feasibility and efficacy of this procedure by comparison with traditional open small bowel surgery.
A wedge or segmental resection of the small bowel for removal of the lesion was performed in 25 patients at National Taiwan University Hospital from September 2006 to January 2009. Thirteen patients underwent gasless laparoscopy-assisted surgery (GLAS), and 12 patients underwent open surgery. The perioperative characteristics and clinical results between the two groups were compared.
The demographics, clinical data, lesion size, and operative time were comparable between the GLAS and open surgery groups, but the wound length and blood loss were significantly less in the GLAS group (P < 0.001 and P = 0.021, respectively). The time to first postoperative flatus and first oral intake were significantly less in the GLAS group (P = 0.007 and 0.036, respectively). No major complication occurred in either group. No tumor recurrence was found after a median follow-up period of 14 months (range = 1-30) in the GLAS group.
GLAS for resection of the small bowel may be a feasible and safe procedure for the small bowel lesions. It has the advantages of better cosmetic outcome, less blood loss, and earlier recovery of bowel movement.
Journal of Laparoendoscopic & Advanced Surgical Techniques 10/2010; 20(8):699-703. · 1.40 Impact Factor
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ABSTRACT: Previous studies have demonstrated the usefulness of the Nakagami parameter in characterizing breast tumors by ultrasound. However, physicians or radiologists may need imaging tools in a clinical setting to visually identify the properties of breast tumors. This study proposed the ultrasonic Nakagami image to visualize the scatterer properties of breast tumors and then explored its clinical performance in classifying benign and malignant tumors. Raw data of ultrasonic backscattered signals were collected from 100 patients (50 benign and 50 malignant cases) using a commercial ultrasound scanner with a 7.5 MHz linear array transducer. The backscattered signals were used to form the B-scan and the Nakagami images of breast tumors. For each tumor, the average Nakagami parameter was calculated from the pixel values in the region-of-interest in the Nakagami image. The receiver operating characteristic (ROC) curve was used to evaluate the clinical performance of the Nakagami image. The results showed that the Nakagami image shadings in benign tumors were different from those in malignant cases. The average Nakagami parameters for benign and malignant tumors were 0.69 +/- 0.12 and 0.55 +/- 0.12, respectively. This means that the backscattered signals received from malignant tumors tend to be more pre-Rayleigh distributed than those from benign tumors, corresponding to a more complex scatterer arrangement or composition. The ROC analysis showed that the area under the ROC curve was 0.81 +/- 0.04 and the diagnostic accuracy was 82%, sensitivity was 92% and specificity was 72%. The results showed that the Nakagami image is useful to distinguishing between benign and malignant breast tumors.
Ultrasound in medicine & biology 12/2009; 36(2):209-17. · 2.02 Impact Factor
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ABSTRACT: This study was conducted to evaluate the correlation between color Doppler vascularity index (CDVI), clinical outcomes and five angiogenesis-related molecules including vascular endothelial growth factor (VEGF), placenta growth factor (PlGF), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and calreticulin (CRT) in gastric cancer, and to develop an effective model selected from these five molecules to predict patient survival.
CDVI could be obtained preoperatively by transabdominal ultrasound from 30 patients. Enzyme immunoassay was adopted to determine protein level of VEGF and PlGF, and immunohistochemistry was used to detect COX-2, iNOS and CRT expression. Correlation between CDVI and five individual molecules was assessed. Multiple molecules model was developed using classification and regression tree (CART) analysis from five molecules, and was tested for patient survival in another 45 patients.
CDVI was significantly correlated with patient survival (P = 0.00907) and absolute number of metastatic lymph nodes (P = 0.01). There was no significant association between CDVI and any individual molecule. The model, developed by CART consisting of VEGF and PlGF, could differentiate high and low CDVI and survival in testing group (P = 0.00257).
CDVI was associated with lymph node metastasis, combined VEGF and PlGF expression status and patient survival in gastric cancer.
Journal of Surgical Oncology 07/2009; 99(7):402-8. · 2.10 Impact Factor
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ABSTRACT: Cell-mediated immunity, which includes interferon gamma (IFN-gamma) expression, is activated during the process of liver regeneration; however, the genetic pathway of this activation is still unclear. The present study evaluated variations in the interferon gamma receptor (IFN-gamma R) gene and its mRNA expression during liver regeneration after partial hepatectomy (PH). Male Wistar rats weighing approximately 200 g were subjected to PH (70 or 40%). IFN-gamma R gene expression in the remnant liver was measured by cDNA microarray, and mRNA expression was verified by real-time quantitative reverse transcription-polymerase chain reaction (Q-PCR) preoperatively and at 2, 4, 6, 12, 24, and 72 hours and 7 days postoperatively. The ratio of remnant liver weight to body weight increased markedly after 70 per cent PH and more gradually after 40 per cent PH. It reached near 90 per cent of the preoperative level at 72 hours after PH in both groups. The scanned spots of the genomic survey on the cDNA microarray chips were uneven and increased irregularly in number and density after PH. IFN-gamma R gene expression increased markedly in a single peak pattern, up to more than double the preoperative level, at 6 hours after 70 per cent PH. The curve in the 40 per cent PH group was flat and peaked at only 1.6 times the preoperative level. The variations in IFN-gamma R-related mRNA expression were verified by Q-PCR. Elevations in IFN-gamma R gene and mRNA expression were shown during the early stage of liver regeneration after PH. The genetic pathway of IFN-gamma/IFN-gamma R expression is activated during liver regeneration.
The American surgeon 02/2009; 75(1):49-54. · 1.28 Impact Factor
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ABSTRACT: The small intestine, after the stomach, is the second most common primary site for gastrointestinal stromal tumors (GISTs). This study aimed to identify clinicopathologic prognostic factors of tumor recurrence and survival and to analyze the influence of imatinib and sunitinib for small-intestine GISTs.
We reviewed the surgical experience of patients with small-intestine GISTs at National Taiwan University Hospital from January 1995 to March 2007. We analyzed the perioperative clinicopathologic data and treatment course.
Seventy patients were included. The tumor was local in 43 patients, advanced in 21 patients, and 6 had metastasis. The median size of the tumor was 6.5 cm. Forty-four patients had a mitotic rate of less than 5/50 high-power field. The 1-year and 5-year disease-free survival rates were 85 and 66.7%, respectively, while the 1-year and 5-year overall survival rates were 98.5 and 86.6%, respectively. There were 19 patients with recurrent disease and 6 patients died of intestinal GISTs. The response rate of imatinib and sunitinib were 73.3 and 60%, respectively. According to multivariate analysis for disease recurrence, only invasion status, tumor size, and mitotic rate are significant (P=0.007, 0.035, 0.007 respectively). They are also associated with poor survival (P<or=0.001, 0.006, 0.002, respectively).
The invasion status, size, and mitotic rate of tumor involve higher risk of recurrence and poor survival in small-intestine GISTs. The patients with recurrent small-intestine GISTs may have a lower mortality rate after using imatinib and sunitinib.
World Journal of Surgery 02/2009; 33(4):828-34. · 2.36 Impact Factor
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Chiung-Nien Chen,
Cheng-Chi Chang,
Ting-En Su,
Wen-Ming Hsu,
Yung-Ming Jeng,
Ming-Chih Ho,
Fon-Jou Hsieh,
Po-Huang Lee,
Min-Liang Kuo,
Hsinyu Lee,
King-Jen Chang
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ABSTRACT: The purpose of this study was to identify genes of interest for a subsequent functional and clinical cohort study using complementary (c)DNA microarrays. cDNA microarray hybridization was performed to identify differentially expressed genes between tumor and nontumor specimens in 30 gastric cancer patients. Subsequent functional studies of the selected gene were carried out, including cell cycle analysis, cell migration analysis, analyses of vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF), and oligo-microarray studies using two pairs of stable cell lines of the selected gene. Another independent cohort study of 79 gastric cancer patients was conducted to evaluate the clinical significance of the selected gene in human gastric cancer. Calreticulin (CRT) was selected for further investigation. Two pairs of stable cell lines of CRT overexpression and CRT knockdown were constructed to perform functional studies. CRT enhanced gastric cancer cell proliferation and migration. Overexpressed CRT upregulated the expression and secretion of PlGF and VEGF. CRT had a reciprocal effect on connective tissue growth factor (CTGF) expression. Positive immunohistochemical staining of calreticulin was significantly correlated with high microvessel density (MVD) (p = 0.014), positive serosal invasion (p = 0.013), lymph node metastasis (p = 0.002), perineural invasion (p = 0.008), and poor patient survival (p = 0.0014). Multivariate survival analysis showed that CRT, MVD, and serosal invasion were independent prognosticators. We conclude that CRT overexpression enhances angiogenesis, and facilitates proliferation and migration of gastric cancer cells, which is in line with the association of CRT with MVD, tumor invasion, lymph node metastasis, and survival in gastric cancer patients.
Annals of Surgical Oncology 01/2009; 16(2):524-33. · 4.17 Impact Factor
