Recurrent umbilical varix rupture with hemoperitoneum: a case report and review of literature.

BACKGROUND: Non-traumatic hemoperitoneum was a rare event with the risk of sudden death. Spontaneous rupture of hepatocellular carcinoma is the most intuitive diagnosis when hemoperitoneum occurs in cirrhotic patients who are not regularly followed up. However, other etiologies of hemoperitoneum, such as intra-abdominal varix rupture, should be kept in mind. CASE PRESENTATION: A 44-year-old man with alcoholic liver cirrhosis, Child-Pugh B was sent to our emergency department (ED) because of recurrent abdominal pain and hypovolemic shock. He had similar symptoms one month ago and was diagnosed as hepatocellular carcinoma (HCC) rupture with hemoperitoneum, therefore he underwent trans-arterial embolization (TAE). However, the follow-up magnetic resonance imaging (MRI) showed less possibility of hepatocellular carcinoma. Contrast enhanced abdominal computed tomography (CT) showed possible umbilical vein contrast agent extravasation. Exploratory laparotomy confirmed the diagnosis of rupture umbilical varix with hemoperitoneum. CONCLUSION: Although umbilical varix rupture is a rare cause of hemoperitoneum, it should be kept in mind in cirrhotic patients with unexplained hemoperitoneum.

Surgical treatment of pelvic organ prolapse in women aged ≥75 years in Hong Kong: a multicentre retrospective study.

INTRODUCTION: Pelvic organ prolapse (POP) is common among older women. With the increasing lifespan and emphasis on quality of life worldwide, older women increasingly prefer surgical treatment for POP. We reviewed the surgical treatment of POP in older women to characterise its safety, effectiveness, and the type most often selected. METHODS: This multicentre, retrospective study was conducted at four hospitals between 2013 and 2018. Included patients were aged ≥75 years and had undergone POP surgery. We compared patient demographic characteristics, POP severity, and surgical outcomes between reconstructive and obliterative surgeries; these comparisons were also made among vaginal hysterectomy plus pelvic floor repair (VHPFR), transvaginal mesh surgery (TVM), vaginal hysterectomy (VH) plus colpocleisis, and colpocleisis alone. RESULTS: In total, 343 patients were included; 84.3% and 15.7% underwent reconstructive and obliterative surgeries, respectively. Overall, 246 (71.7%), 43 (12.5%), 20 (5.8%), and 34 (9.9%) patients underwent VHPFR, TVM, VH plus colpocleisis, and colpocleisis alone, respectively. Patients who were older (81.9 vs 79.6 y; P=0.001), had vault prolapse (38.9% vs 3.5%; P<0.001), and had medical co-morbidities (37% vs 4.8%; P<0.001) chose obliterative surgery more frequently than reconstructive surgery. Obliterative surgeries had shorter operative time (73.5 min vs 107 min; P<0.001) and fewer surgical complications (9.3% vs 28.0%; P=0.003). Vaginal hysterectomy plus pelvic floor repair had the highest rate of surgical complications (most were minor), while colpocleisis alone had the lowest rate (30.1% vs 8.8%; P=0.01). CONCLUSIONS: Pelvic organ prolapse surgeries were safe and effective for older women. Colpocleisis may be appropriate as primary surgery for fragile older women.

A simple and efficient method of generating HCMV pp65-specific T cells using overlapping peptides.

The methods for expansion of human cytomegalovirus (HCMV)-specific T lymphocytes are limited due to the complex culture process, long culture duration, and human leukocyte antigen (HLA) restriction. Here, we report that in vitro stimulation with pp65 kDa phosphoprotein (pp65)-derived overlapping synthetic peptides rapidly generates large numbers of HCMV-specific cytotoxic T lymphocytes from peripheral blood mononuclear cells (PBMCs) regardless of HLA type. Treatment of PBMCs from healthy volunteers expressing HLA-A*02:01 or HLA-A*24:02 with 138 pp65 overlapping peptides (OLP) resulted in an expansion of HCMV pp65 NLVPMVATV (NLV) pentamer-specific CD8+ T lymphocytes that expressed interferon (IFN)-γ, but the pp65 NLV peptide did not generate HCMV-specific CD8+ T lymphocytes in PBMCs obtained from an HLA-A*24:02 donor due to HLA restriction. The OLP-induced T lymphocytes specific for HCMV derived from PBMCs of HLA-A*02:01- and HLA-A*24:02-expressing donors showed effective cytolytic responses against target cells loaded with OLP or the NLV epitope, but pp65 NLV peptide-induced T lymphocytes did not. Phenotypic analyses demonstrated that OLP increased the frequency of CD3+ CD8+ cells, but not CD3+ CD4+, CD14+, or CD56+ cells, in donor PBMCs. Thus, this study provides evidence that in vitro stimulation with OLP efficiently generates sufficient numbers of HCMV pp65-specific cytotoxic T lymphocytes for adoptive cell therapy. Keywords: human cytomegalovirus; cytotoxic T lymphocyte; overlapping peptides; pp65; cytotoxicity.

Untangling the Complexity of Liver Fluke Infection and Cholangiocarcinoma in NE Thailand Through Transdisciplinary Learning.

This study demonstrates how a transdisciplinary learning approach provided new insights for explaining persistent Opisthorchis viverrini infection in northern Thailand, as well as elucidating problems of focusing solely on the parasite as a means of addressing high prevalence of cholangiocarcinoma. Researchers from diverse backgrounds collaborated to design an investigative homestay program for 72 Singaporean and Thai university students in five northeast Thai villages. The students explored how liver fluke infection and potential cholangiocarcinoma development are influenced by local landscape dynamics, aquatic ecology, livelihoods, food culture and health education. Qualitative fieldwork was guided daily by the researchers in a collaborative, co-learning process that led to viewing this health issue as a complex system, influenced by interlinked multidimensional factors. Our transdisciplinary experience has led us to believe that an incomplete understanding of these linkages may reduce the efficacy of interventions. Further, viewing liver fluke infection and cholangiocarcinoma as the same issue is inadvisable. Although O. viverrini infection is an established risk factor for the development of cholangiocarcinoma, multiple factors are known to influence the likelihood of acquiring either. Understanding the importance of the current livelihood transition, landscape modification and the resulting mismatch between local cultures and new socio-ecological settings on cholangiocarcinoma initiation and liver fluke transmission is of critical importance as it may help readjust our view of the respective role of O. viverrini and other socioeconomic risk factors in cholangiocarcinoma etiology and refine intervention strategies. As demonstrated in this study, transdisciplinary approaches have the potential to yield more nuanced perspectives to complex diseases than research that focuses on specific aspects of their epidemiology. They may therefore be valuable when designing effective solutions to context-sensitive diseases such as liver fluke infection and cholangiocarcinoma.

Cardiac transplantation and concomitant coronary artery bypass grafting: our experiences in 11 cases.

INTRODUCTION: The shortage of donor hearts for transplantation could be alleviated by including the hearts of older donors. Previous literature revealed similar early and medium-term survival outcomes compared with those of younger donors. This study presents our experience with patients who underwent orthotopic heart transplantation and concomitant coronary artery bypass grafting at our institution. METHODS: We present our experience with 11 patients with end-stage cardiomyopathy (8 men and 3 women) undergoing orthotopic heart transplantation and concomitant coronary artery bypass grafting from September 2002 to November 2011 at our institute. RESULTS: All 11 donor organs would otherwise have been rejected, depriving potential recipients of organ transplantation. Two patients received concurrent 2-coronary-artery bypass, and the other 9 patients received concurrent single-coronary-artery bypass during orthotopic heart transplantation. All patients had an uneventful postoperative course, with follow-up completed 3 to 128 months after cardiac transplantation and concomitant coronary artery bypass grafting surgery. CONCLUSIONS: Our experiences suggest that donor hearts requiring coronary artery bypass grafting, which form a small but significant donor subgroup, can be used effectively and safely when matched to the recipients' age and medical condition.

The impact of number of drugs prescribed on the risk of potentially inappropriate medication among outpatient older adults with chronic diseases.

BACKGROUND: Older patients with chronic diseases often take multiple prescription drugs, increasing their risk of adverse health events. However, polypharmacy remains ill-defined. AIM: To investigate the impact of number of drugs prescribed on potentially inappropriate medication (PIM) and the associated risk factors in older outpatients with chronic diseases. DESIGN: Retrospective cross-sectional study. METHODS: We retrospectively assessed 780 older patients (mean, 75.5 ± 7.1 years) with long-term (≥ 28 days) prescriptions for chronic diseases at the geriatric clinics of a university hospital from January to June 2012 using the Screening Tool of Older Person's potentially inappropriate Prescriptions (STOPP). Clinical information for each patient was analyzed. Logistic regression and receiver operating characteristic curve (ROC) analyses were performed; number needed to harm (NNH) was also estimated. RESULTS: According to STOPP criteria, 302 patients (39%) had at least one PIM. Multivariate analysis revealed that PIM risk was associated with the number of medications prescribed (P < 0.001) and the presence of cardiovascular (P < 0.001) or gastrointestinal disease (P = 0.003). The estimated area under the ROC for the number of medications needed to predict PIM risk was 0.680 (P < 0.001) with the optimal cut-off value of five medications. After adjusting covariates, patients prescribed ≥ 5 drugs [adjusted odds ratio (OR) = 5.4; adjusted NNH = 4.25; P < 0.001] and those prescribed 4 drugs (adjusted OR = 3.5; adjusted NNH = 6.88; P = 0.003) had significantly higher PIM risk than those prescribed ≤ 2 drugs. CONCLUSIONS: The number of prescribed medications can be an index of PIM risk in older patients with chronic diseases. Clinicians should suspect high PIM risk in older outpatients with ≥ 5 prescriptions.

Association between tuberculosis infections and non-pulmonary malignancies: a nationwide population-based study.

BACKGROUND: In addition to lung cancers, tuberculosis infections have been associated with increased risk of non-pulmonary malignancies in case reports. Our population-based study employed standardized incidence ratios (SIRs) to systemically survey non-pulmonary cancer risks after tuberculosis infections. METHODS: Data of patients who had newly diagnosed tuberculosis, were aged 20 years or older, and had no prior cancer or tuberculosis were sampled from the Taiwan National Health Insurance database between 2000 and 2010. SIRs compared cancer incidence in patients with tuberculosis infections to the general population. SIRs of specific cancers were further analyzed with respect to gender and time after tuberculosis infections. RESULTS: After a follow-up period of 28 866 person-years, 530 tuberculosis cases developed cancers compared with 256 cases in the general populations (2.07, 95% confidence interval (CI), 1.90-2.26). The SIR of non-pulmonary malignancies was also increased (1.71, 95% CI, 1.54-1.90). For males, SIRs were increased within 1 year after tuberculosis diagnosis for the following cancers: head and neck, esophageal, colorectal, liver, lung, melanomas, and Hodgkin's disease. SIRs were increased for liver, biliary, lung, and bladder cancers beyond the first year after tuberculosis diagnosis. For females, SIRs were increased for leukemia, esophageal, and lung cancers within the first year, and only for leukemia beyond 1 year post diagnosis. CONCLUSION: Having found increased risks of several cancers that differ with gender and time after tuberculosis diagnosis, physicians may consider these factors in patients following tuberculosis diagnosis.

Combined St. Thomas and histidine-tryptophan-ketoglutarat solutions for myocardial preservation in heart transplantation patients.

BACKGROUND: To establish quicker cardiac arrest and less myocardial distension injury during heart procurement, we combined St. Thomas and histidine-tryptophan-ketoglutarate (HTK) solutions for donor heart preservation since June 2008. METHODS: From June 2008 to March 2010, we enrolled 31 heart transplantation (HT) patients in this study. During heart procurement we initially infused 1,000 mL cold St Thomas cardioplegic solution to achieve cardiac arrest. After procurement, a further 2,000 mL of cold HTK solution was infused at low perfusion pressure. Another 1,000 mL cold HTK solution was perfused before donor heart implantation. We examined donor age, recipient preoperative characteristics, ischemia time, hospital stay, postoperative graft function, major cardiac events, and transplant vasculopathy (TCAD). RESULTS: Twenty-two patients (71.0%) presented with dilated cardiomyopathy and 7 (23.3%) with ischemia cardiomyopathy. There were 23 (76.7%) male donors, and the mean donor age was 38.4 ± 13.8 years. Six patients underwent a redo sternotomy, 1 patient needed a third-do sternotomy, and 1 a seventh sternotomy (third HT) for repeated endocarditis and graft failure. The average ischemia time was 224.9 ± 71.0 minutes and the postoperative hospital stay was 57.7 ± 47.7 days. The surgical mortality (3.2%) was not accompanied by hospital or follow-up mortality. Patient left ventricular ejection fraction postoperative was 59.6 ± 2.3% with good functional status. Major cardiac events occurred in 8 patients (26.7%) without major complications. There were two subjects with TCAD but normal graft function. The correlation between ischemia time and hospital stay was insignificant (r = 0.21; P = .26). CONCLUSIONS: Donor heart preservation combining St Thomas cardioplegic arest and low-pressure perfusion with HTK solution seemed to be safe with. short-term survival similar to other approaches.

Combined heart transplantation and total replacement of thoracic aorta in Marfan's syndrome with recurrent aortic dissection: a case report.

It is extremely rare for a patient to need simultaneous heart transplantation (HTx) and replacement of the thoracic aorta. A 23-year-old woman with Marfan's syndrome underwent Bentall's operation and replacement of the ascending aorta (AsA) due to a type A aortic dissection (AD) in August 2001. In March 2005, she began to experience dyspnea on exertion and was found to have a huge pseudoaneurysm at the aortic root, which had caused dehiscence of the aortic conduit. In July 2009, she suffered acute chest pain followed by hypotension and cold sweating. The computed tomography (CT) scan showed a recurrent dissection with a long intimal tear extending from the arch to the mid-portion of the descending thoracic aorta (DTA). Due to technical difficulties in the repair of the aortic root, she was placed on the HTx waiting list. The next day, she received a donor heart and underwent combined HTx and total replacement of the thoracic aorta. Explantation of the heart improved the exposure of the DTA. With the use of a vascular ring connector (Vasoring), the operation was successfully performed without need for a blood transfusion. The patient was still well at 2 years after the operation. Simultaneous replacement of the heart and the whole segment of the thoracic aorta is technically possible in Marfan patients who are complicated with aortic dissection.

Clinical characteristics and outcomes of bacteremia due to different genomic species of Acinetobacter baumannii complex in patients with solid tumors.

PURPOSE: Acinetobacter baumannii, Acinetobacter genomic species 3 (AGS 3), and Acinetobacter genomic species sensu Tjernberg and Ursing (AGS 13TU) are phenotypically indistinguishable and are often reported together as the A. baumannii complex (ABC). Few studies have investigated the difference in outcome caused by these different species, and all involved heterogeneous groups of patients. This study aimed to delineate whether there are differences in the clinical characteristics and outcome among patients with solid tumors and bacteremia caused by A. baumannii or two other non-baumannii ABC species (AGS 3 plus AGS 13TU). METHODS: Patients with solid tumors and ABC bacteremia over a period of 5 years in a medical center were identified. The patient data were retrospectively reviewed and analyzed. RESULTS: We identified 103 patients with ABC bacteremia during the study period. Bacteremia was due to A. baumannii in 30 patients, AGS 3 in 24 patients, and AGS 13TU in 49 patients. Among the 103 patients with ABC bacteremia, recent stay in the intensive care unit (ICU) (p = 0.008) was independently associated with the acquisition of A. baumannii bacteremia. Multivariate analysis revealed that bacteremia caused by A. baumannii (hazard ratio [HR] 2.990, 95% confidence interval [CI], 1.021-8.752, p = 0.046) and Acute Physiology and Chronic Health Evaluation (APACHE) II score ≥21 (HR 4.623, 95% CI 1.348-15.859, p = 0.015) were independent factors associated with 14-day mortality. CONCLUSIONS: Infection with A. baumannii and a high APACHE II score (≥21) might be associated with poor outcome in patients with solid tumors and ABC bacteremia.

Effects of the surface characteristics of nano-crystalline and micro-particle calcium phosphate/chitosan composite films on the behavior of human mesenchymal stem cells in vitro.

Calcium phosphate (CaP) compounds, the main inorganic constituent of mammalian bone tissues, are believed to support bone precursor cell growth and osteogenic differentiation. Chitosan, a deacetylated derivative of chitin, is a versatile biopolymer to offer broad possibilities for cell-based tissue engineering. In the present study, different scales of CaP crystals on chitosan membranes were prepared for culture of human mesenchymal stem cells (hMSCs) in vitro. A series of aqueous CaP suspensions with different concentrations were mixed with chitosan solution and chitosan/calcium phosphate (C/CaP) films were fabricated by the solvent-casting method. With different weight ratios of CaP in chitosan solution, the various surface characteristics of nano-amorphous (C/CaP 0.1), nano-crystalline (C/CaP 0.5) and micro-particle (C/CaP 2) CaP compounds were examined by scanning electron microscopy and electron dispersion spectroscopy. X-ray diffraction on micro-particles of CaP indicated the formation of crystalline hydroxyapatite. The behavior of hMSCs, including proliferation, cell spreading and osteogenic differentiation, was studied on the C/CaP films. In basal culture medium, the incorporation of CaP into chitosan films could promote the proliferation of hMSCs. The C/CaP 0.5 film with connected CaP nano-crystals had better cellular viability. The fluorescence microscope images at 14 days of culture revealed extensive networks of F-actin filaments of hMSCs on chitosan, C/CaP 0.1 and C/CaP 0.5 films. The cellular morphology on C/CaP 2 film with discrete CaP micro-particles was partly restrained. In osteogenic medium, the alkaline phosphatase (ALP) activity of hMSCs increased and showed the process of osteogenic differentiation. The ALP levels on C/CaP 2 film were higher than those on C/CaP 0.1 and C/CaP 0.5 films. These results demonstrated that the crystallinity and topography of CaP on chitosan membranes could modulate the behaviors of cultured hMSCs in vitro.

Catechin stimulates osteogenesis by enhancing PP2A activity in human mesenchymal stem cells.

SUMMARY: Using human mesenchymal stem cells, we identified catechin from a panel of herbal ingredients and Chinese traditional compounds with the strongest osteogenic effects. Catechin increased alkaline phosphatase activity, calcium deposition, and mRNA expression of Runx2 and osteocalcin. We further clarified the signaling pathway that catechin mediated to stimulate osteogenesis. INTRODUCTION: Human mesenchymal stem cells (hMSCs), useful as a species specific cell culture system for studying cell lineage differentiation, were examined as a tool to identify novel herbal ingredients and Chinese traditional compounds for enhancing osteogenesis. METHODS: Immortalized and primary hMSCs were induced in osteogenic induction medium in the presence of a variety of herbal ingredients and Chinese traditional compounds and osteogenic differentiation was evaluated by histochemical assays and quantitative RT-PCR. RESULTS: Using immortalized hMSCs, we first identified catechin, 18ß-glycyrrhetinic acid, baishao, and danggui with osteogenic properties, which enhanced calcium deposition at the dose without significant cytotoxic effects. Primary hMSCs were then applied for confirming the osteogenic effects of catechin, which increased alkaline phosphatase activity, calcium deposition, and mRNA expression of Runx2 and osteocalcin. We further found the extracellular signal-regulated kinase (ERK) pathway was downregulated upon stimulation with catechin. Catechin increased the level and activity of protein phosphatases 2A (PP2A) that dephosphorylates ERK kinase (MEK) and ERK. Further, PP2A inhibitor, okadaic acid, abolished the effect of catechin-mediated inactivation of ERK and stimulation of osteogenesis. The blocking effect of okadaic acid on osteogenesis was further reversed by PD98059, a specific inhibitor of MEK. Co-immunoprecipitation revealed the association of PP2A to both MEK and ERK. CONCLUSIONS: These studies propose catechin enhanced osteogenesis by increasing the PP2A level that inhibits the MEK and ERK signaling in hMSCs. These results prove the concept of using hMSCs as a convenient tool for rapid and consistent screening of the osteogenic herbal ingredients and traditional Chinese compounds.

Endoscopic ultrasonography-guided fine-needle aspiration in the management of mediastinal diseases: local experience of a novel investigation.

OBJECTIVE: To study the efficacy and safety of endoscopic ultrasonography-guided fine-needle aspiration in the management of mediastinal diseases in Hong Kong. DESIGN: Retrospective review of prospectively collected data. SETTING: University teaching hospital, Hong Kong. PATIENTS: A total of 125 consecutive patients with various mediastinal and pulmonary lesions that underwent trans-oesophageal endoscopic ultrasonography-guided fine-needle aspiration from July 1998 to June 2007. MAIN OUTCOME MEASURES: The diagnostic accuracy and safety of the procedure and its influence in patient management. RESULTS: Malignancy was confirmed in 62 (50%) of the patients and excluded in 42 (34%). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of endoscopic ultrasonography-guided fine-needle aspiration in diagnosing mediastinal malignancies were 75% (95% confidence interval, 64-83%), 100% (90-100%), 100% (93-100%), 67% (54-78%), and 83%, respectively. Eighty-six (69%) of the patients had their initial plan of invasive investigations changed. Only one (0.8%) patient developed a septic complication in a mediastinal cyst after puncturing, and was treated surgically. CONCLUSIONS: Trans-oesophageal endoscopic ultrasonography-guided fine-needle aspiration is a minimally invasive, effective, and safe method of diagnosing malignant mediastinal disease. It may reduce the need for other invasive investigations.

Adaptive correction technique for 3D reconstruction of fluorescence microscopy images.

Recent advances in high-resolution imaging have provided valuable novel insights into structural relationships within cells and tissues both in vitro and in vivo. An analysis of this kind is regularly done by optical sectioning using either confocal or deconvolution microscopy. However, the reconstruction of 3D images suffers from light scattering and absorption with increasing depth by finite transparency of the used media. Photobleaching of fluorochromes has been especially troublesome and often the only remedy for loss of signal during optical sectioning is to reduce the number of sections. This causes disparities in the x-y and z dimensions of voxels, which lead to vertical distortion of the original stack of images and necessitates interpolation. Interpolation is necessary to fill up the gaps between consecutive sections in the original image stack to obtain cubic voxels. The present manuscript describes a novel method for adaptive compensation of attenuation of light intensity in stacks of fluorescence microscopy images that is based on a physical model of light attenuation. First, we use a fast interpolation technique to generate a cubic voxel-based volume stack with the aid of a contribution look up table. With the contribution look up table, multiple calculations are avoided, which substantially reduces the computational time without compromising the accuracy of the restoration procedure. Second, each section within the resulting volume is processed to rectify its intensity values that have been altered due to photobleaching and scattering and absorption. The method allows to define the last good section in the stack and the correction is then done automatically.

Endoscopic submucosal dissection used for treating early neoplasia of the foregut using a combination of knives.

BACKGROUND: Endoscopic submucosal dissection (ESD) has emerged as a novel technique for achieving en bloc resection for early esophageal or gastric carcinoma limited to the mucosa. The authors report their experience with a combination of various devices to treat early neoplasia of the foregut using the ESD technique. METHODS: In this prospective case series, ESD was performed for early esophageal or gastric carcinoma limited to the mucosa. These lesions were staged by endoscopic ultrasonography before resection. Magnifying endoscopy and chromoendoscopy were used to locate the tumor and define the margin. The resection was accomplished with submucosal dissection using the insulated tip knife, the hook knife, and the triangular tip knife. The resected specimen was examined systematically for the lateral and deep margins. RESULTS: From January 2004 to March 2006, ESD was performed to manage 30 cases of early gastric or esophageal carcinoma. For 29 of these patients, R0 resection was successfully achieved. The mean operating time was 84.6 min. One patient experienced reactionary hemorrhage 12 h after resection, which was controlled endoscopically. There was no perforation. Most of the circumferential mucosal incisions were performed using the insulated tip knife (76.6%), whereas submucosal dissection was accomplished with a combination of various knives. One of the specimens showed involvement of the lateral margin, whereas another patient had two areas of new early gastric cancer 6 months after the initial procedure. These patients received salvage laparoscopically assisted gastrectomy. CONCLUSIONS: Endoscopic submucosal dissection to manage early neoplasia of the foregut can be achieved safely and effectively with a combination of knives.

Constitutively active CCK2 receptor splice variant increases Src-dependent HIF-1 alpha expression and tumor growth.

Gastrointestinal (GI) cancers ectopically express multiple splice variants of the cholecystokinin-2 (CCK(2))/gastrin receptor; however, their relative contributions to the cancer phenotype are unknown. The aim of this study was to compare the effects of CCK(2) receptor (CCK(2)R) and CCK(2i4sv)R expression on cell growth both in vitro and in vivo using a human epithelial cell model, HEK239. In vitro, receptor variant expression did not affect cell proliferation either in the absence or presence of agonist. However, in vivo, the expression of CCK(2i4sv)R, but not CCK(2)R, increases HEK293 tumor growth in a constitutive, Src-dependent manner. Enhanced tumorigenicity of CCK(2i4sv)R is associated with an Src-dependent increase in the transcription factor, hypoxia-inducible factor-1alpha, its downstream target, vascular endothelial growth factor and tumor micro-vessel density, suggesting that CCK(2i4sv)R may contribute to the growth and spread of GI cancers through agonist-independent mechanisms that enhance tumor angiogenesis.