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Biomedical subjects

Emmanuel E Zervos

Publications and source records attributed to Emmanuel E Zervos.

At least 19 recordsLinked to original sources
PubMed2006

Differential gene expression in patients genetically predisposed to pancreatic cancer.

BACKGROUND: Nearly 10% of all pancreatic cancer (PCA) results from genetic predisposition. Although abnormalities in sporadic PCA have been described, little is known about the genetics of heritable PCA. The purpose of this study was to identify novel genes expressed in patients with a presumed genetic predisposition or "familial" PCA. PATIENTS AND METHODS: We defined "familial" PCA as patients having one or more first-degree relatives with biopsy-proven adenocarcinoma of the pancreas. Using a PCR-based subtractive and enrichment procedure, representational difference analysis (RDA), pancreatic tumor cDNA was reverse-transcribed from pooled poly(A)+ mRNA from six such patients (tester) and compared to pooled cDNA from five normal pancreata (driver). Tumor-specific gene fragments were identified and confirmed to be overexpressed in familial PCA by comparative RT-PCR. Six PCA cell lines, 11 sporadic tumors, 5 neuroendocrine tumors, and 3 chronic pancreatitis tissues were screened to determine the specificity of these genes. RESULTS: Sequence analysis revealed several sequences of unknown significance and six genes previously described in neoplasia/carcinogenesis: Apolipoprotein A4, CEA, Keratin 19, Stratifin (14-3-3 sigma), Trefoil Factor, and Calcium Binding Protein S100 A6. Screening of cell lines and pancreatic tissue types showed varying degrees of specificity for familial and sporadic PCA. The APO-A4 gene was up-regulated in familial PCA. CONCLUSIONS: The pattern of frequency in all screened tissue suggests that these genes are associated with conditions that produce significant desmoplastic responses and are difficult to differentiate from chronic inflammatory processes. Apolipoprotein A4 is preferentially expressed in familial patients, suggesting that the importance of fatty acid synthesis in carcinogenesis be investigated further.

Adenocarcinoma↗
PubMed2006

EGF receptor antagonism improves survival in a murine model of pancreatic adenocarcinoma.

INTRODUCTION: The purpose of this study was to determine whether inhibition of the epidermal growth factor receptor (EGFR) is a plausible therapeutic strategy in pancreatic cancer. METHODS: A human pancreatic cancer cell line (HPAC) was evaluated for the presence of EGFR with rtPCR and immunohistochemistry. Cells were grown in the presence of either 50 or 100 microM of erlotinib (EGFRI) for 72 hours and evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Eighty-six athymic nude/nude mice underwent orthotopic implantation of 10(7) HPAC cells and were blindly randomized into four groups: (1) Control; (2) Batimastat, a matrix metalloproteinase inhibitor (MMPI) at 400 ng/ml qod; (3) EGFRI at 100 mg/kg qd; and (4) MMPI and EGRRI (both). In vitro and in vivo effects of EGFRI with and without MMPI were compared. RESULTS: HPAC demonstrated high levels of expression of both the EGFR gene and the gene product. In vitro, both doses of EGFRI significantly reduced proliferation of HPAC at 48 (50 microM: 1.15 + 0.05 [st dev] versus 0.63 + 0.09 abs, P < 0.001) and 72 h (50 microM: 1.48 +/- 0.09 versus 0.73 +/- 0.05 abs, P < 0.001, paired Student's t-test). In vivo, each treatment group demonstrated a significant survival advantage (P = 0.0002 group 2, P = 0.0001 group 3, P = 0.012 group 4, log rank test) over controls. Mice treated with EGFRI showed reduced tumor implantation, size, weight, metastatic potential, and jaundice as compared to controls and MMPI-treated mice (all P < 0.05, Fisher's exact test). CONCLUSION: EGF receptor antagonism is not only a plausible therapy for treatment of ductal adenocarcinoma of the pancreas, but is also superior to matrix metalloproteinase inhibition alone or in combination.

Adenocarcinoma↗
PubMed2006

Prognostic significance of new onset ascites in patients with pancreatic cancer.

BACKGROUND: The purpose of this study was to determine risk factors for development of malignant ascites and its prognostic significance in patients with pancreatic cancer. METHODS: A prospective database was queried to identify patients with pancreatic cancer who develop ascites. Stage at presentation, size, and location of primary tumor, treatment received and length of survival after onset of ascites were determined. RESULTS: A total of 15 patients were identified. Of which 4 patients (1 stage II, 3 stage III) underwent pancreaticoduodenectomy and manifested with ascites 2, 3, 24 and 47 months after surgery (tumor size 2.9 +/- 1.32 cm). All but one of the remaining 11 patients (tumor size 4.4 +/- 3.38 cm) presented with metastatic disease, and all developed malignant ascites 9 months after diagnosis, dying 2 months later. Resected patients lived longer before the onset of ascites, but not after. CONCLUSION: Once diagnosed, ascites in pancreatic cancer patients heralds imminent death. Limited survival should be considered when determining the aggressiveness of further intervention.

Journal Article↗
PubMed2006

Improved outcome with cytoreduction versus embolization for symptomatic hepatic metastases of carcinoid and neuroendocrine tumors.

BACKGROUND: Few data exist regarding outcomes after resection versus embolic treatment of symptomatic metastatic carcinoid and neuroendocrine tumors. The purpose of this study was to determine whether cytoreduction provides any benefit over embolic management of diffuse neuroendocrine tumors. METHODS: A prospective database of 734 patients treated at our institution was retrospectively queried for symptomatic metastatic tumors treated with embolization or cytoreduction. Patients were compared with regard to pretreatment performance status, relief of symptoms, and survival. RESULTS: A total of 120 patients were identified: 59 undergoing embolization and 61 undergoing cytoreduction. Twenty-three patients had palliative cytoreduction (gross residual disease). Pretreatment performance status (Eastern Cooperative Oncology Group) was similar for both groups: .7+/-.70 (embolization) versus .8+/-.72 (cytoreduction; P=.27). Complete symptomatic relief was observed in 59% and partial relief in 32% of patients who underwent embolization, with a mean symptom-free interval of 22+/-13.6 months. A total of 69% of patients who underwent cytoreduction had complete symptomatic relief, and 23% had partial relief (P=.08 vs. embolization). The mean duration of relief was 35+/-22.0 months (P<.001 vs. embolization). The mean survival for the patients who underwent embolization was 24+/-15.8 months versus 43+/-26.1 months for those who underwent cytoreduction (P<.001). Survival in patients who underwent palliative cytoreduction was 32+/-18.9 months (P<.001 vs. embolization), whereas it was 50+/-27.6 months in patients who underwent curative resection (P<.001 vs. embolization; P<.001 vs. palliative). CONCLUSIONS: Cytoreduction for metastatic neuroendocrine tumors resulted in improved symptomatic relief and survival when compared with embolic therapy in this nonrandomized study. Cytoreduction should be pursued whenever possible even if complete resection may not be achievable.

Carcinoid Tumor↗
PubMed2006

Preshunt liver function remains the prominent determinant of survival after portasystemic shunting.

BACKGROUND: Forty-five years after the development of the Child classification, we sought to determine if hepatic function is still a primary determinant between short-term and long-term survival after portasystemic shunting. METHODS: One hundred forty-six patients underwent small-diameter prosthetic H-graft portacaval shunting (HGPCS). The patients were stratified into 2 groups: those surviving less than 5 years and those surviving more than 5 years. Preoperative data determined Child class and model for end-stage liver disease (MELD) score. RESULTS: Ninety-four (64%) patients were short-term and 52 (36%) patients were long-term survivors. No significant differences in the cause of cirrhosis, presence of ascites, encephalopathy, or emergency operations were noted between short- and long-term survivors. Preshunt MELD scores were significantly greater with short-term survivors, although actual survival was superior to predicted survival by MELD. Child class was inferior for short-term survivors. Child class and MELD score significantly correlated with survival after portasystemic shunting. CONCLUSIONS: Long-term survival after HGPCS is possible even with severe hepatic dysfunction; however, actual survival is superior to predicted survival. Hepatic dysfunction, as denoted by Child class and MELD, still remains a primary determinant of survival after portasystemic shunting.

Aged↗
PubMed2006

Does Barrett's esophagus impact outcome after laparoscopic Nissen fundoplication?

BACKGROUND: This study was undertaken to compare patients with gastroesophageal reflux disease (GERD) with or without Barrett's esophagus for severity and frequency of symptoms and their response to antireflux surgery. METHODS: Eighty patients with GERD and Barrett's esophagus and 93 concurrent patients with GERD alone, all of whom underwent laparoscopic Nissen fundoplication, were compared by using symptom scores graded by a Likert scale. RESULTS: Before fundoplication, patients with Barrett's esophagus had higher DeMeester scores. Symptom scores were not different for patients with versus without Barrett's esophagus before or after laparoscopic Nissen fundoplication. CONCLUSIONS: Before and after fundoplication, patients with Barrett's esophagus, despite more severe reflux, have symptoms nearly identical in frequency and severity when compared with patients with GERD alone. Regardless of presence of Barrett's, all improve dramatically with laparoscopic Nissen fundoplication. Barrett's esophagus does not impact presentation before or outcome after laparoscopic Nissen fundoplication.

Adult↗
PubMed2006

Laparoscopic cholecystectomy: past, present, and future.

Laparoscopic cholecystectomy is one of the most commonly undertaken procedures in General Surgery with more than 500,000 performed annually. Overall, the complication rate is less than 1.5%, and the mortality rate is less than 0.1%. As such, laparoscopic cholecystectomy was considered by most to be at its zenith since its inception in the early 1990 s. Advancements in technology and equipment have opened new doors to physicians and allowed the laparoscopic cholecystectomy to once again evolve. Traditional four-port cholecystectomy has given way to three- and even two-port techniques. Standard 12-mm ports have been replaced by 2-mm ports, and experiments have now been implemented to achieve cholecystectomy with no ports-known as the transgastric technique. The authors reviewed evolution of these techniques that included a synopsis of our experience with the three-port cholecystectomy, as well as the future direction of laparoscopic surgery.

Cholecystectomy, Laparoscopic↗
PubMed2005

Full-term gestation and transvaginal delivery after wide resection of an abdominal desmoid tumor during pregnancy.

A 29-year-old female was diagnosed with a symptomatic, extra-abdominal desmoid tumor during the first trimester of pregnancy. Computerized tomography (CT) and transabdominal ultrasound (US) noted a mass within the left rectus sheath measuring up to 15 cm in greatest diameter, with mild compression of the uterus. Preoperative diagnosis was confirmed by core-needle biopsy of the lesion. At 20-weeks gestation, wide local resection of the tumor with disease-free margins, as well as abdominal wall reconstruction with polytetrafluoroethylene (PTFE) mesh was successfully undertaken. Histological examination of the tumor ex vivo confirmed that the lesion was a desmoid tumor consisting of spindle cells with dense infiltrating collagenous fibers. Subsequent to her resection, the patient completed a full-term pregnancy without complication, and proceeded with a complication-free transvaginal delivery at 39 weeks. This case illustrates the probable contribution of estrogens towards desmoid tumor development, the durability of abdominal wall reconstruction when subjected to the extraordinary strain of both a gravid uterus and labor, as well as the safety and efficacy of aggressive surgical therapy during pregnancy.

Abdominal Wall↗
PubMed2005

Stage does not predict survival after resection of hilar cholangiocarcinomas promoting an aggressive operative approach.

INTRODUCTION: Staging systems have been developed to predict survival after resection of hilar cholangiocarcinoma. Notably, they have not been validated nor compared for relative predictive ability. METHODS: Forty-two patients underwent resection of hilar cholangiocarcinoma and have been followed through a prospectively collected database. The tumors were staged using the Bismuth-Corlette, Blumgart, and American Joint Committee on Cancer (AJCC) systems, and a significant relationship with survival was sought. RESULTS: Eleven patients were treated by extrahepatic biliary resection alone, while 31 required extrahepatic biliary resections with in-continuity hepatic resections. All patients underwent adjuvant therapy. To date, 30 patients have died with a mean survival time of 30 months +/- 35.0 (SD). Twelve patients are alive with a mean survival of 90 months +/- 61.8. By regression analysis, none of the staging systems had a significant relationship with survival (Bismuth: P = .64; Blumgart: P = .66; AJCC: P = .31). CONCLUSIONS: Most patients with hilar cholangiocarcinoma require in-continuity hepatic resections. Survival after resection promotes an aggressive approach, with cure in as many as 30%. Staging systems should not impact the decision to operate or postoperative management, as all tumors should be aggressively resected and all patients should receive adjuvant treatment.

Aged↗
PubMed2005

Esophagography predicts favorable outcomes after laparoscopic Nissen fundoplication for patients with esophageal dysmotility.

BACKGROUND: We undertook this study to determine if clearance of a food bolus at preoperative esophagography predicts acceptable outcomes after laparoscopic Nissen fundoplication for patients with manometrically abnormal esophageal motility. STUDY DESIGN: Patients with gastroesophageal reflux disease (GERD) or symptomatic hiatal hernia with evidence of esophageal dysmotility by stationary manometry underwent videoesophagography to document the ability of their esophagus to clear food boluses of varying consistencies. Sixty-six patients were identified who had manometric dysmotility yet were able to clear a food bolus at esophagography, and subsequently underwent laparoscopic Nissen fundoplication. These patients were compared with 100 randomly selected patients with normal motility who underwent laparoscopic Nissen fundoplication. Symptom reduction and satisfaction were assessed through followup. Patients with normal motility were compared with those with manometrically moderate and severe dysmotility. RESULTS: Preoperative patient demographic data, symptoms, and symptom scores were similar among patients with normal motility and moderate or severe dysmotility. After fundoplication, symptom reduction was notable for all patients regardless of preoperative motility (p < 0.01, paired Student's t-test). There was no notable difference in postoperative symptom scores (p = NS, Kruskal-Wallis ANOVA) or in patient satisfaction (p = NS, chi-square analysis) among patients stratified by esophageal motility. CONCLUSIONS: Patients with esophageal dysmotility documented by manometry who are able to clear a food bolus at contrast esophagography, have functional results after laparoscopic Nissen fundoplication similar to patients with normal motility. Preoperative esophagography predicts successful outcomes after laparoscopic Nissen fundoplication for patients with manometric esophageal dysmotility.

Barium Sulfate↗
PubMed2005

H-graft portacaval shunts versus TIPS: ten-year follow-up of a randomized trial with comparison to predicted survivals.

OBJECTIVE: To report long-term outcome of patients undergoing prosthetic 8-mm H-graft portacaval shunts (HGPCS) or TIPS and to compare actual with predicted survival data. METHODS: A randomized trial comparing TIPS to HGPCS for bleeding varices began in 1993. Predicted survival was determined using MELD (Model for End-stage Liver Disease). RESULTS: Patients undergoing TIPS (N = 66) or HGPCS (N = 66) were very similar by Child's class and MELD scores and predicted survival. After TIPS (P = 0.01) and HGPCS (P = 0.001), actual survival was superior to predicted survival. Through 24 months, actual survival after HGPCS was superior to actual survival after TIPS (P = 0.04). Compared with TIPS, survival was superior after HGPCS for patients of Child's class A and B (P = 0.07) and with MELD scores less than 13 (P = 0.04) with follow-up at 5 to 10 years. Shunt failure was less following HGPCS (P < 0.01). CONCLUSIONS: Predicted survival data for patients undergoing TIPS or HGPCS confirms an unbiased randomization. Actual survival following TIPS or HGPCS was superior to predicted survival. Shunt failure favored HGPCS, as did survival after shunting, particularly for the first few years after shunting and for patients of Child's class A or B or with MELD scores less than 13. This trial irrefutably establishes a role for surgical shunting, particularly HGPCS.

Adult↗
PubMed2005

Twenty-millimeter laparoscopic cholecystectomy: fewer ports results in less pain, shorter hospitalization, and faster recovery.

Improvements in technology offer the ability to refine operations without compromising safety. In this study, we determine whether a modified method of laparoscopic cholecystectomy using three ports and an aggregate incision length of 20 mm offers any advantage or poses increased risk. Using a 5-mm, 30 degree laparoscope, clip applier, and dissector, the gall bladder is removed through an extended umbilical incision. Standard safety principles were followed: achieving the "critical view," lateral retraction of the fundus, double ligation of the proximal structures, and maintaining sterility for specimen removal. Forty-one consecutive standard laparoscopic cholecystectomies were used as a control group to compare complications, length of stay and surgery, pain scores, and return to work. Sixty patients have undergone the modified technique. There were no differences between the modified and standard technique with regard to cost or complications. Length of surgery was significantly shorter, as was length of stay, narcotics use, and return to work for the modified group versus the control. A modified technique for laparoscopic cholecystectomy poses no increased risk to patients but offers potential for shorter surgery and hospital stays, less need for narcotic analgesia, and faster recovery.

Adult↗
PubMed2004

In-continuity hepatic resection for advanced hilar cholangiocarcinoma.

BACKGROUND: The purpose of this study was to examine outcomes of patients undergoing concomitant hepatectomy and bile duct excision for advanced Klatskin tumors. METHODS: Thirty-one patients, 16 men and 15 women, with an average age of 64 years, underwent concomitant biliary and hepatic resections for Klatskin tumors. Outcomes, including complications and survival, are reported. RESULTS: Fifteen patients had postoperative courses free of complications. Sixteen patients experienced a total of 50 complications; 13 patients experienced 1 or more major complications (including hemorrhage [n = 1], pneumonia [n = 5], intra-abdominal abscess [n = 8], hepatic failure [n = 3], and myocardial infarction [n = 2]). Five patients died perioperatively, 1 from adult respiratory distress syndrome and 4 from multisystem organ failure precipitated by hepatic failure. One-, 3-, and 5-year survival after resection was 69%, 33%, and 26%, respectively. American Joint Committee on Cancer stage and margin status did not impact long-term survival after resection. CONCLUSIONS: Concomitant hepatic and biliary resections for Klatskin tumors carry relatively high risk but offer hope for long-term survival. This study supports in-continuity hepatectomy and extrahepatic biliary resection for advanced Klatskin tumors even when microscopically negative margins cannot be obtained.

Adult↗
PubMed2004

Differential expression of the Tie-2 receptor and its ligands in human pancreatic tumors.

BACKGROUND: Derangements in the balance of the Tie-2 receptor ligands, angiopoietin-1 and angiopoietin-2 (Ang-1 and Ang-2), have been implicated in the growth and differentiation of several human tumors. To assess the potential role of angiogenesis factors in pancreatic tumorigenesis, we confirmed previously observed oligonucleotide-based microarray data by analyzing their expression in pancreatic tumors using semiquantitative reverse transcription polymerase chain reaction and immunohistochemistry. STUDY DESIGN: RNA harvested from tissue samples obtained from patients with normal pancreata, adenocarcinoma of the pancreas, and neuroendocrine tumors of the pancreas (nine each) was grouped by tissue type, pooled, and hybridized to a cDNA microarray and global gene expression patterns were determined. Semiquantitative reverse transcription polymerase chain reaction was applied to individual pool components to specifically determine expression of Tie-2, Ang-1, and Ang-2. A separate set of tumors and matched normal pancreas were then stained for expression of Ang-2 protein using immunohistochemistry. RESULTS: Microarray data showed that Ang-2 was upregulated in neuroendocrine tumors ( approximately 8 times more than normal) and adenocarcinoma of the pancreas ( approximately 5 times more than normal) although Ang-1 and Tie-2 were not differentially expressed. Reverse transcription polymerase chain reaction confirmed these findings showing strong Ang-2 expression in nine of nine neuroendocrine tumors, eight of nine adenocarcinoma of the pancreas, and weak expression in two of nine normal pancreata. Immunohistochemistry showed tumor-specific staining of Ang-2 in 10 of 15 matched adenocarcinoma of the pancreas (67%) and 6 of 8 neuroendocrine tumors (75%). CONCLUSIONS: Although Tie-2 and Ang-1 are not differentially expressed in pancreatic tumors, Ang-2 gene and gene product are overexpressed, suggesting a significant role for Ang-2 in pancreatic tumorigenesis. Differential expression of Ang-2 in human tumors may be useful as a diagnostic and therapeutic target.

Adenocarcinoma↗
PubMed2004

TIPS versus peritoneovenous shunt in the treatment of medically intractable ascites: a prospective randomized trial.

OBJECTIVE: We undertook a prospective randomized clinical trial comparing TIPS to peritoneovenous (PV) shunts in the treatment of medically intractable ascites to establish relative efficacy and morbidity, and thereby superiority, between these shunts. METHODS: Thirty-two patients were prospectively randomized to undergo TIPS or peritoneovenous (Denver) shunts. All patients had failed medical therapy. RESULTS: After TIPS versus peritoneovenous shunts, median (mean +/- SD) duration of shunt patency was similar: 4.4 months (6 +/- 6.6 months) versus 4.0 months (5 +/- 4.6 months). Assisted shunt patency was longer after TIPS: 31.1 months (41 +/- 25.9 months) versus 13.1 months (19 +/- 17.3 months) (P < 0.01, Wilcoxon test). Ultimately, after TIPS 19% of patients had irreversible shunt occlusion versus 38% of patients after peritoneovenous shunts. Survival after TIPS was 28.7 months (41 +/- 28.7 months) versus 16.1 months (28 +/- 29.7 months) after peritoneovenous shunts. Control of ascites was achieved sooner after peritoneovenous shunts than after TIPS (73% vs. 46% after 1 month), but longer-term efficacy favored TIPS (eg, 85% vs. 40% at 3 years). CONCLUSION: TIPS and peritoneovenous shunts treat medically intractable ascites. Absence of ascites after either is uncommon. PV shunts control ascites sooner, although TIPS provides better long-term efficacy. After either shunt, numerous interventions are required to assist patency. Assisted shunt patency is better after TIPS. Treating medically refractory ascites with TIPS risks early shunt-related mortality for prospects of longer survival with ascites control. This study promotes the application of TIPS for medically intractable ascites if patients undergoing TIPS have prospects beyond short-term survival.

Aged↗
PubMed2004

Identification of molecular markers specific for pancreatic neuroendocrine tumors by genetic profiling of core biopsies.

BACKGROUND: There is a paucity of known molecular markers that distinguish pancreatic neuroendocrine tumors from other pancreatic tumor types. We hypothesized that novel markers for pancreatic neuroendocrine tumors could be identified with molecular fingerprinting of pooled RNA samples from core biopsies. METHODS: Total RNA was harvested from nine core biopsies of normal pancreas, pancreatitis, pancreatic adenocarcinoma, pancreatic adenocarcinoma metastases, and pancreatic neuroendocrine tumors. RNA from each group of samples was pooled and hybridized to an oligonucleotide-based microarray. Four genes (ANG2, NPDC1, ELOVL4, and CALCR) were selected for further investigation by reverse transcriptase polymerase chain reaction from the top 20 highest expressed genes, on the basis of potential as novel markers. RESULTS: Neuroendocrine tumors were most unique from normal pancreas. Pancreatitis, pancreatic adenocarcinoma, and metastases are more closely related to each other and to normal pancreas. ANG2 was overexpressed in 89% of neuroendocrine tumors, compared with 22% of normal pancreas, making it the best potential molecular marker or therapeutic target of the four genes selected for analysis. CONCLUSION: We have identified a specific set of molecular markers for pancreatic neuroendocrine tumors distinct from pancreatitis and pancreatic adenocarcinoma. These novel markers may prove useful as molecular markers or therapeutic targets unique to pancreatic neuroendocrine tumors.

Adenocarcinoma↗
PubMed2003

Defining the role of the epidermal growth factor receptor in pancreatic cancer grown in vitro.

BACKGROUND: The purpose of this study was to determine the effect of a novel epidermal growth factor (EGF) receptor tyrosine kinase inhibitor, Erlotinib, on pancreatic cancer cell lines of varying differentiation in vitro. METHODS: Six pancreatic cancer cell lines (AsPc-1, CAPAN-1, HPAC, HPAF-II, Mia PaCa-2, PANC-1) were grown in the presence of 50 microM or 100 microM of Erlotinib or recombinant EGF. Cell proliferation was determined using the MTT assay over 72 hours. The EGF receptor gene and protein expression were determined by polymerase chain reaction and immunohistochemistry respectively. RESULTS: All cell lines demonstrated the presence of the EGF receptor gene and its gene product. Five of six cell lines showed significant growth inhibition at 72 hours compared with controls (P <0.05). The EGF augmentation increased proliferation of each cell line but this increase was only significant in AsPc-1. CONCLUSIONS: Inhibition of EGF receptor is a valid therapeutic strategy in pancreatic cancer.

Cell Line↗