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Biomedical subjects

Georgios I Papachristou

Publications and source records attributed to Georgios I Papachristou.

18 recordsLinked to original sources
PubMed2006

Chronic alcohol consumption is a major risk factor for pancreatic necrosis in acute pancreatitis.

BACKGROUND: Much of the late morbidity and mortality of acute pancreatitis (AP) is attributed to complications of pancreatic necrosis (PNEC). Early diagnosis of PNEC in high-risk patients is critical to management. Hemoconcentration is one risk factor for PNEC, but additional risk factors are likely implicated. AIMS: (1) To evaluate a series of preselected clinical factors in a prospectively collected cohort with AP to identify risk factors for PNEC and (2) to verify the relative risk of any newly identified factor(s) by retrospective analysis of a large patient cohort. METHODS: Phase I: 102 AP patients were prospectively ascertained, of which 77 (mean age 49 yr; 35 women, 42 men) underwent contrast-enhanced computerized tomography (CECT) and were studied. Eleven subjects developed PNEC (14%). Binary logistic regression was performed to identify any clinical factors associated with PNEC. Phase II: 1,474 anonymized patients admitted to the hospital with a diagnosis of AP were electronically reviewed to identify 359 subjects (mean age 54 yr; 157 women, 202 men) with AP and CECT. Seventy-six of these patients (21%) exhibited CECT evidence of PNEC. The associations found in the Phase I group were compared with Phase II by logistic regression analysis. RESULTS: In Phase I, only chronic alcohol consumption was identified as a significant new risk factor for the development of PNEC (6/19 vs 5/58, p= 0.02, OR 4.8, CI 1.27-18.2). In Phase II, it was verified that excessive alcohol consumption was a significant risk factor for PNEC (18/52 vs 58/307, p= 0.012, OR 2.27, CI 1.19-4.30). CONCLUSION: Chronic alcohol consumption seems to constitute a strong risk factor for PNEC.

Alcohol Drinking↗
PubMed2006

Obesity increases the severity of acute pancreatitis: performance of APACHE-O score and correlation with the inflammatory response.

BACKGROUND: Obese patients appear to be at risk for complications of acute pancreatitis (AP). APACHE-O score has been suggested to improve APACHE-II accuracy in predicting severe outcome in AP. AIMS: To determine if APACHE-O adds any predictive value to APACHE-II score and to test the hypothesis that obese patients are at increased risk of severe AP (SAP) because of a more intense inflammatory response to pancreatic injury. METHODS: 102 AP patients were prospectively studied. Using a body mass index (BMI) >30, 28% of the subjects were obese. Nineteen patients developed organ dysfunction and were classified as SAP. Receiver-operating curves for prediction of SAP were calculated using admission APACHE-II and APACHE-O scores. Binary logistic regression was performed to assess if obesity is a risk for SAP and to determine the clinical factors associated with severe disease. Serum levels of IL-6, MCP-1 and CRP as well as Ranson's scores were compared between obese and non-obese patients. RESULTS: Admission APACHE-O (area under the curve AUC 0.895) and APACHE-II (AUC 0.893) showed similar accuracy in predicting severe outcome. BMI was identified as a significant risk for SAP (OR 2.8, p = 0.048) and mortality (OR 11.2, p = 0.022). CRP levels were significantly higher in obese AP patients (p = 0.0001) as well as Ranson's score (p = 0.021). IL-6 and MCP-1 levels were higher in obese patients but did not reach statistical significance. CONCLUSIONS: Obesity is an independent risk for SAP. Admission APACHE-O score is not more accurate than APACHE-II. Our study results suggest that obesity increases the severity of AP by amplifying the immune response to injury.

APACHE↗
PubMed2006

The MCP-1 -2518 A/G polymorphism is not a susceptibility factor for chronic pancreatitis.

BACKGROUND AND AIMS: Chronic pancreatitis (CP) is an inflammatory process initiated by recurrent acute pancreatitis and characterized by progressive parenchyma destruction and fibrosis. Genetic factors influence susceptibility and modify progression. The monocyte chemotactic protein-1 (MCP-1) -2518 G allele, which modifies the severity of acute pancreatitis, was investigated as a susceptibility factor for CP. METHODS: A genetic association study was performed on 177 CP patients and 116 healthy controls from the NAPS2 Study. The MCP-1 A/G genotype was determined by RFLP and confirmed by DNA sequencing. RESULTS: Compared to the control group the MCP-1 -2518 genotypes were similar: A/A (57% vs. 50%), A/G (34.5% vs. 40%) and G/G (8.5% vs. 10%). These allele frequencies were not statistically different (p = 0.267). CONCLUSIONS: Although the pro-inflammatory chemokine MCP-1 -2518 G allele is a severity factor for AP, it does not significantly alter susceptibility to CP.

Adolescent↗
PubMed2006

Endoscopic treatment of an impacted pancreatic duct stone using a balloon catheter for electrohydraulic lithotripsy without pancreatoscopy.

Obstructing main pancreatic duct (PD) stones represent a challenge for endoscopic removal because they are frequently impacted within the duct, are hard, and process sharp edges. Multiple series have been published demonstrating that removal of obstructing stones in the main PD can improve symptoms in the majority of patients with chronic pancreatitis. Extracorporeal shock wave lithotripsy (ESWL) has become an accepted technique to facilitate stone clearance when standard endoscopic methods fail. More recently, direct contact lithotripsy with the use of smaller caliber endoscopes has been described as an alternative to ESWL. Limited experience suggests that intraductal electrohydraulic lithotripsy under direct endoscopic visualization with a small caliber pancreatoscope results in successful fragmentation of PD stones that have been refractory to standard endoscopic methods or ESWL. Herein, we report the use of intraductal electrohydraulic lithotripsy to fragment a large obstructing PD stone guided only by fluoroscopy without the utilization of a pancreatoscope.

Adult↗
PubMed2005

PPAR-gamma is expressed and NF-kB pathway is activated and correlates positively with COX-2 expression in stromal myofibroblasts surrounding colon adenocarcinomas.

PURPOSE: Accumulated evidence indicates that carcinogenesis is closely associated with the transformation of normal stroma into a 'reactive' stromal phenotype. The present study investigated the role of PPARgamma, COX-2 and p-IkB-alpha--important molecular targets of colon cancer chemoprevention--in this stromal remodeling by evaluating and comparing the expression of these factors in stromal myofibroblasts, macrophages and endothelial cells that surround normal colonic mucosa and colon cancer. METHODS: Immunohistochemical methodology was employed on archived paraffin-embedded sections prepared from tumors and adjacent normal colon from 45 patients with colon adenocarcinomas. Double immunostaining with the universal marker for myofibroblasts (alpha-smooth muscle actin/alpha-SMA) as second primary antibody was also performed. RESULTS: Stromal macrophages and endothelial cells expressed these factors both in normal colonic mucosa and colon cancer. By contrast, stromal myofibroblasts expressed PPARgamma, COX-2 and p-IkB-alpha only in colon adenocarcinomas (77.7%, 100% and 100% of cases, respectively) and not in normal colon. COX-2 and p-IkB-alpha expressions were strongly correlated in these cells (P < 0.001). PPARgamma, COX-2 and p-IkB-alpha expression did not correlate with the stage or differentiation of the adenocarcinomas. CONCLUSIONS: NF-kB pathway is activated and COX-2 expression is upregulated in stromal myofibroblasts surrounding colon adenocarcinomas compared to normal colon. Induction of COX-2 expression is primarily induced by NF-kB. NSAIDs, selective COX-2 inhibitors and PPARgamma ligands may exert their chemoprophylactic properties through direct actions on these cells.

Adenocarcinoma↗
PubMed2005

Neoadjuvant imatinib in gastrointestinal stromal tumor of the rectum: report of a case.

Gastrointestinal stromal tumors are rare tumors of the gastrointestinal tract. Gastrointestinal stromal tumors involving the rectum are uncommon. We describe a case of a 43-year-old female with a gastrointestinal stromal tumor of the rectum who declined abdominoperineal resection. Neoadjuvant treatment with imatinib decreased her tumor size, permitting sphincter-sparing transanal excision. She had no evidence of disease for 24 months postoperatively until she recurred with lung metastases. Microdissection genotyping of the recurrent lesion revealed a deletion in exon 11. Further mutational analysis showed that her metastatic lesion was concordant with her primary rectal lesion, suggesting that systemic micrometastasis was previously present at initial diagnosis. Deletion in exon 11 predicts for response with imatinib treatment and is associated with a longer event-free and overall survival. Current studies are underway that may help us optimize the treatment for patients with gastrointestinal stromal tumors.

Antineoplastic Agents↗
PubMed2005

Inflammatory markers of disease severity in acute pancreatitis.

To date, CRP remains the single standard biochemical marker for predicting the severity of AP. Because the combination of clinico-physiological scores and CRP provides good information at 48 hours, research has focused on the predictive ability of various markers when applied in the initial 24 hours after admission to the hospital. After detailed review of the literature, the authors conclude that there is no single tool that serves as the optimal predictor of severity. There are, however, data supporting the use of certain tests to improve upon the clinician's early predictive ability on the subsequent course of AP. These include an APACHE II score greater than seven, IL-6 at the time of admission, and urine TAP, urine trypsinogen-2,and serum PMN-elastase at 24 hours (Box 1). These markers will only be able to help the clinician's predictive ability if they can be performed locally and if the results can be available in a timely manner. Future research should focus on markers such as procalcitonin, IL-8, IL-I ra, sTNFR,CAPAP, PLA-2, novel markers, and the combined use of more than one marker. The conventional research approach in predicting severity used in the last15 years has limitations and appears to have reached its maximal potential. Novel conceptions and approaches, such as identification of genetic polymorphisms that predispose to severe course and complications of AP, are needed for a quantum step forward.

Acute Disease↗
PubMed2005

Is the monocyte chemotactic protein-1 -2518 G allele a risk factor for severe acute pancreatitis?

BACKGROUND & AIMS: Acute pancreatitis (AP) reflects the intensity of the inflammatory response and is divided into mild AP (MAP) or severe AP (SAP). Monocyte chemotactic protein-1 (MCP-1) gene expression is altered by an A/G polymorphism (-2518), with the G allele increasing MCP-1 production. Our aim was to determine whether the MCP-1 -2518 A/G polymorphism affects the severity of AP. METHODS: Seventy-seven consecutive patients and 116 controls were evaluated. The A/G genotype was evaluated by polymerase chain reaction amplification, restriction fragment length polymorphism, and DNA sequencing. MCP-1 serum levels were quantified using a fluorescence bead-based immunoassay. RESULTS: Sixty-three of 77 patients had MAP (82%) and 14 of 77 had SAP (18%). Patients with SAP had a significantly greater proportion of the G allele (12 of 14; 86%) than did control subjects (50 of 116; 43%) (odds ratio [OR], 7.9; 95% confidence interval [CI], 1.7-37, P < .003) or MAP patients (29 of 63; 46%) (OR, 7.0; 95% CI, 1.5-34; P < .007). Patients with pancreatitis and AA genotype had a low risk for SAP (OR, .13; 95% CI, .01-.61; P < .003). As predicted by the genotype, the serum MCP-1 levels were significantly higher in the SAP patients when compared with the MAP patients ( P = .002) and they also predicted death. CONCLUSIONS: MCP-1 -2518 G allele is a risk factor for severe AP. MCP-1 serum levels, measured early in the course of AP, appear to be an accurate predictor of severity of acute pancreatitis and death.

Acute Disease↗
PubMed2005

Acute deterioration of a woman following acute pancreatitis with pseudocysts.

BACKGROUND: A 49-year-old white female with a history of acute pancreatitis that was complicated by pseudocysts presented with severe acute-onset abdominal pain of a few hours duration with associated vomiting. Physical examination showed a soft abdomen with mild diffuse tenderness and positive bowel sounds. Initial blood work revealed a drop in her hematocrit, and elevated but stable amylase and lipase levels. A CT scan of the abdomen revealed a splenic artery pseudoaneurysm with extravasation of contrast medium into an adjacent pseudocyst. INVESTIGATIONS: Physical examination, blood analysis and a CT scan of the abdomen with contrast medium. DIAGNOSIS: Splenic artery pseudoaneurysm bleeding into an adjacent pseudocyst. MANAGEMENT: Embolization of the splenic artery across the neck of the pseudoaneurysm.

Acute Disease↗
PubMed2004

Novel biologics in inflammatory bowel disease.

Understanding of immunologic mechanisms involved in the initiation and perpetuation of chronic inflammation has led to new therapeutic opportunities in the inflammatory bowel diseases. The term "biologics" is used to distinguish new biotechnologic therapeutics from the conventional drugs used in the treatment of immune-mediated inflammatory disorders. This article reviews novel biologic therapies that are being investigated for the treatment of Crohn's disease and ulcerative colitis.

Adalimumab↗
PubMed2004

Predictors of severity and necrosis in acute pancreatitis.

C-reactive protein remains the single standard biochemical marker for predicting the severity of AP. Because the combination of clinical-physiological scores and CRP provide good information at 48 hours, research has focused on the predictive ability of various markers when applied in the initial 24 hours after admission to the hospital. After detailed review of the literature, the authors conclude that there is no single tool that serves as the optimal predictor of severity. There are, however, data that support the use of certain tests to improve upon the clinician's early predictive ability on the subsequent course of AP. These include an APACHE II score greater than 7 and IL-6 at the time of admission, and urine TAP, urine trypsinogen-2, and serum PMN elastase at 24 hours (Table 4). These markers only will be able to help the clinician's predictive ability if they can be performed locally and if the results can be available ina timely manner. Future research should focus on promising markers such as procalcitonin, IL-8, IL-I ra, sTNFR, CAPAP, PLA-2, novel markers, and the combined use of more than one marker. The conventional research approach in predicting severity used in the last 15 years has limitations and appears to have reached its maximal potential. Novel conceptions and approaches, such as identification of genetic polymorphisms that predispose to severe course and complications of AP or other approaches are needed for a quantum step forward.

Acute Disease↗
PubMed2004

Cholestatic jaundice and bone lesions in an elderly woman.

BACKGROUND: A 74-year-old Caucasian female presented with jaundice, clay-colored stools, diarrhea, and fatigue of 3 months' duration, accompanied by a weight loss of 6.8 kg. Physical examination demonstrated mild hepatomegaly. Initial blood work revealed abnormal liver biochemistries with a cholestatic pattern. An abdominal CT scan showed intrahepatic bile-duct dilatation without masses but with multiple lytic and blastic bone lesions. A sacral bone biopsy established the diagnosis. INVESTIGATIONS: Endoscopic ultrasound, endoscopic retrograde cholangiopancreatography, CT scan, bone biopsy and liver biopsy. DIAGNOSIS: Systemic mastocytosis affecting the biliary system resulting in a primary-sclerosing-cholangitis-like picture combined with diffuse blastic and lytic bone lesions. MANAGEMENT: Biliary stenting, histamine 1- and 2-receptor blockers, and chemotherapy (cladribine).

Aged↗
PubMed2004

Inflammatory pseudotumor of the liver associated with Crohn's disease.

Inflammatory pseudotumor (IPT) of the liver is a rare, benign lesion that is characterized by proliferating fibrous tissue infiltrated by inflammatory cells. The exact etiology of IPT remains unclear. Although the association of IPT with systemic inflammatory disorders has been established, a specific link with Crohn's disease is rare. We report two cases of IPT associated with Crohn's disease. Both patients were elderly males who presented with abdominal pain and jaundice. At the time of presentation, both had active Crohn's disease that was undiagnosed. Computed tomography demonstrated a liver mass, and endoscopic retrograde cholangiography revealed biliary strictures in both patients. Given their symptomatic jaundice and concern for cholangiocarcinoma, they underwent abdominal surgical exploration and pathology results revealed IPT. They were subsequently diagnosed with Crohn's disease. Following treatment of Crohn's disease, there was significant improvement in their overall clinical status. An underlying diagnosis of inflammatory bowel disease should be considered in patients with IPT.

Abdominal Pain↗
PubMed2003

Screening intervals for colonic neoplasia.

Surveillance examinations after detection of an adenoma are one of the largest contributors to the cost of colorectal cancer screening. Screening colonoscopy, beginning at the age of 50 years, is increasing in frequency and becoming part of the zeitgeist. Given the high rate of adenomatous polyp detection on colonoscopy, the amount of time spent and costs consumed by surveillance are likely to grow to significant levels in the coming years. Guidelines for surveillance examinations vary across specialty organizations. Individuals with advanced adenomas are at increased risk for recurrent advanced adenomas. The impact of multiple nonadvanced adenomas or a single nonadvanced adenoma on subsequent risk of an advanced adenoma or cancer is less clear. Recommended surveillance after colorectal cancer has greater consensus, but concerns remain. Studies that predict the need and the needed timing of surveillance remain an important research priority.

Journal Article↗