Remote Ischemic Preconditioning Decreases the Magnitude of Hepatic Ischemia-Reperfusion Injury on a Swine Model of Supraceliac Aortic Cross-Clamping.

BACKGROUND: Temporary hepatic ischemia is inevitable during open aortic surgery when supraceliac clamping is necessary, as in thoracoabdominal or pararenal aneurysms. Remote ischemic preconditioning (RIPC) has been described as a potential protective means against ischemia-reperfusion injury (IRI) in various tissues including the liver. The aim of this experimental study was to detect the effect of RIPC on liver IRI in a model of supraceliac aortic cross-clamping. METHODS: An animal study was performed. Four groups of 6 swines each were examined: the control (sham) group, the ischemia-reperfusion (IR) group, and 2 remote ischemic preconditioning groups (RIPC I and RIPC II group). In the IR group, the animals underwent a complete cessation of the splanchnic arterial circulation for 30 min by a concomitant occlusion of the supraceliac and the infrarenal aorta. In the RIPC groups, a remote preconditioning was applied before the splanchnic ischemia. This consisted of a temporary occlusion of the infrarenal aorta for 15 min followed by 15 min of reperfusion (RIPC I group), and 3 cycles of 5 min similar ischemia, followed by 5 min of reperfusion each (RIPC II group). All animals were followed for 24 hr after the ischemia (reperfusion period). The liver ischemia-reperfusion injury was assessed by examining specific serum biomarkers indicating the magnitude of metabolic injury from selective blood samples of the hepatic circulation. In particular, the following parameters were examined: C-reactive protein, interleukin 6, tumor necrosis factor a, ferritin, and L-arginine. RESULTS: All parameters were affected in the IR group as compared to the sham group. Both RIPC groups developed a less serious change as compared to the IR group, in all examined parameters. CONCLUSIONS: In an animal study of splanchnic ischemia produced in a way to this produced during a supraceliac aortic aneurysm open repair, the remote ischemic preconditioning seemed to attenuate the effect of hepatic ischemia-reperfusion injury. CLINICAL RELEVANCE: Remote ischemic preconditioning produced with short bouts of ischemia of the lower body by temporary clamping of the infrarenal aorta might be used as a means of decreasing the detrimental effects of hepatic ischemia-reperfusion injury after supraceliac aortic cross-clamping. This was found in a swine model of suprarenal AAA open repair by studying the variance of certain biological biomarkers in selective blood samples retrieved from the hepatic vein.

From Clinical Standards to Translating Next-Generation Sequencing Research into Patient Care Improvement for Hepatobiliary and Pancreatic Cancers.

Hepatobiliary and pancreatic (HBP) cancers are associated with high cancer-related death rates. Surgery aiming for complete tumor resection (R0) remains the cornerstone of the treatment for HBP cancers. The current progress in the adjuvant treatment is quite slow, with gemcitabine chemotherapy available only for pancreatic ductal adenocarcinoma (PDA). In the advanced and metastatic setting, only two targeted drugs have been approved by the Food & Drug Administration (FDA), which are sorafenib for hepatocellular carcinoma and erlotinib for PDA. It is a pity that multiple Phase III randomized control trials testing the efficacy of targeted agents have negative results. Failure in the development of effective drugs probably reflects the poor understanding of genome-wide alterations and molecular mechanisms orchestrating therapeutic resistance and recurrence. In the post-ENCODE (Encyclopedia of DNA Elements) era, cancer is referred to as a highly heterogeneous and systemic disease of the genome. The unprecedented potential of next-generation sequencing (NGS) technologies to accurately identify genetic and genomic variations has attracted major research and clinical interest. The applications of NGS include targeted NGS with potential clinical implications, while whole-exome and whole-genome sequencing focus on the discovery of both novel cancer driver genes and therapeutic targets. These advances dictate new designs for clinical trials to validate biomarkers and drugs. This review discusses the findings of available NGS studies on HBP cancers and the limitations of genome sequencing analysis to translate genome-based biomarkers and drugs into patient care in the clinic.

E-cadherin in gastric carcinomas: Relations with histological parameters and its prognostic value.

PURPOSE: Gastric cancer (GC) is still one of the most common malignancies with the majority of the tumors being diagnosed at advanced stage. The need for identification of prognostic and early detection biomarkers is thus compulsory. E-cadherin is one of the emerging biomarkers that is currently evaluated in the literature in the frame of epithelial-mesenchymal transition (EMT). Our aim was to study the expression of E-cadherin in the various histological subtypes of GC and to evaluate its prognostic value. METHODS: This historical cohort survey was performed on gastric tumors obtained from 66 (46 men and 20 women) patients with documented gastric adenocarcinoma who underwent total or partial gastrectomy and regional lymphadenectomy from 2003 till 2011. Features such as tumor size, depth of invasion, grade and histological subtype, lymphovascular space invasion and regional lymph nodes involvement were also evaluated. Immunohistochemistry (IHC) was used for assessing the expression of E-cadherin with a semi-quantitative model. RESULTS: The correlation of E-cadherin tissue expression with patient overall survival (OS) or disease-free survival (DFS) was not statistically significant, as well as with gender, T stage, N stage, TNM stage, grade, positive lymph nodes ratio or lymphovascular invasion. CONCLUSIONS: 73.0% of the evaluated tumors showed abnormal E-cadherin expression in IHC, but the correlation of E-cadherin tissue expression with patient OS or DFS was not statistically significant. Literature stands equivocal about the association between E-cadherin gene mutation, and histopathology and tumor invasiveness. Our results further strengthen the need of larger studies to fully elucidate the predictive role of E-cadherin in the natural history of GC.

Improvement of gastric emptying by enhanced recovery after pancreaticoduodenectomy.

BACKGROUND: Enhanced recovery after surgery (ERAS) has improved postoperative outcomes particularly in colorectal surgery. This study aimed to assess compliance with an ERAS protocol and evaluate its effect on postoperative outcomes in patients undergoing pancreaticoduodenectomy. METHODS: Fifty patients who had received conventional perioperative management from 2005 to 2009 (conventional group) were compared with 75 patients who had received perioperative care with an ERAS protocol (fast-track group) from 2010 to 2014. Mortality, complications, readmissions and length of hospital stay were evaluated and compared in the groups. RESULTS: Compliance with each element of the ERAS protocol ranged from 74.7% to 100%. Uneventful patients had a significant higher adherence to the ERAS protocol (87.5% vs 40.7%; P<0.001). There were no significant differences in demographics and perioperative characteristics between the two groups. Patients in the fast-track group had a shorter time to remove the nasogastric tube, start liquid diet and solid food, pass flatus and stools, and remove drains. No difference was found in mortality, relaparotomy, readmission rates and overall morbidity. However, delayed gastric emptying and length of hospital stay were significantly reduced in the fast-track group. The independent effect of the ERAS protocol in reducing delayed gastric emptying and length of hospital stay was confirmed by multivariate analysis. CONCLUSION: ERAS pathway was feasible and safe in improving gastric emptying, yielding an earlier postoperative recovery, and reducing the length of hospital stay.

Adhesions and Healing of Intestinal Anastomoses: The Effect of Anti-Adhesion Barriers.

Background Postoperative adhesions are the result of aberrant peritoneal healing. As they are the leading cause of postoperative bowel obstruction, anti-adherence barriers are advocated for their prevention. This study looks into the effect of these biomaterials on the healing of intestinal anastomoses. Materials and Methods Thirty-three New Zealand White rabbits underwent laparotomy, transection of the terminal ileum, and creation of an end-to-end anastomosis. Animals were randomized into 3 groups: the Control group (n = 11); the Icodextrin group, receiving icodextrin 4% intraperitonealy (n = 11); and the HA/CMC group, having the anastomosis wrapped with a hyaluronic acid/carboxymethylcellulose film (n = 11). All animals were sacrificed on the seventh postoperative day. Macroscopic adhesions were graded and anastomotic strength was tested by the burst pressure. Histological healing was assessed in a semiquantitative way for the presence of ulceration, reepithelization, granulation tissue, inflammation, eosinophilic infiltration, serosal inflammation, and microscopic adhesions. Univariate and multivariate analysis was used. Results are given as medians with interquartile range. Results The median adhesion scores were the following: Control 1 (0-3), Icodextrin 0 (0-1), HA/CMC 0 (0-0), P = .017. The burst pressure did not differ between the groups; however, all except one bowel segments tested burst away from the anastomosis. The macroscopic and histological anastomotic healing was comparable in all 3 groups. A poor histological anastomotic healing score was associated with a higher adhesion grade (odds ratio = 1.92; 95% confidence interval = 1.06-3.47; P = .032). Conclusion Adhesion formation was inhibited by the materials tested without direct detrimental effects on anastomotic healing. Poor anastomotic healing provokes adhesions even in the presence of anti-adhesion barriers.

Idiopathic Double Perforation of the Gastrointestinal Tract.

A 73-year old woman was operated on with diffuse peritonitis and multiple abscesses throughout the mesentery which were drained. After the operation the patient could not recover. After an indicative computerized tomography the patient was re-explored. Perforation of the ileum and gastric perforation at the pylorus were found. There was no history of underline disease. The double perforation of the GI tract was surgically managed but the patient's course was fatal.

Predictors affecting in-hospital mortality of ruptured abdominal aortic aneurysms: a Greek multicenter study.

BACKGROUND: Endovascular aortic repair (EVAR) is being used with increasing frequency for the treatment of ruptured abdominal aortic aneurysms (rAAAs), although conflicting results have been reported concerning perioperative mortality. The aim of our study was to evaluate potential difference in mortality rates between EVAR and open surgical repair (OSR) and identify independent risk factors for in-hospital mortality in rAAAs. This study also aimed to evaluate the Glasgow Aneurysm Score (GAS) in predicting in-hospital mortality. A time-trend analysis of EVAR for ruptured AAAs was also performed. METHODS: Prospectively collected data from 7 public hospitals in Greece concerning rAAA repairs between January 2006 and April 2012 were analyzed. Primary outcome was in-hospital mortality. Multivariate logistic regression analysis was used to identify independent risk factors. The receiver-operator characteristic curve was used to determine the value of the GAS in predicting in-hospital death. Time-trend analysis, depicting annual changes (%), concerning EVAR for ruptured AAAs was also conducted. RESULTS: A total of 418 patients (92.3% men, mean age = 74.3 ± 8.8) with rAAAs were recorded during the study period. Among them, 113 patients (27%) underwent EVAR. Overall in-hospital mortality was 45.2%, whereas in-hospital mortality after EVAR and OSR was 20.4% and 54.3%, respectively (P < 0.001). Multivariate analysis evidenced that hemodynamic instability (P < 0.001), OSR (P < 0.001), age ≥80 years (P < 0.001), coronary artery disease (P < 0.001), and renal insufficiency (P = 0.02) independently increased in-hospital mortality. Area under the curve of GAS was 0.80 (95% confidence interval [CI] = 0.75-0.85, P < 0.001) for OSR and 0.64 (95% CI = 0.51-0.77, P = 0.04) for EVAR. Annual increase of proportion (%) of EVAR for rupture was 5% (P = 0.004). CONCLUSIONS: EVAR is being used with increasing frequency for the treatment of rAAAs and it appears to be associated with lower in-hospital mortality compared with OSR, after adjustment for hemodynamic instability and known atherosclerotic risk factors. Preoperative predictors of in-hospital mortality such as GAS should be probably modified in these patients.

Are females predisposed to complications in head and neck cancer free flap reconstruction?

PURPOSE: To investigate gender and other possible factors affecting the frequency and severity of postoperative complications in head and neck cancer free flap reconstruction. MATERIALS AND METHODS: A prospective longitudinal cohort study was conducted at the Greek Anticancer Institute, St. Savvas Hospital in head and neck cancer free flap reconstruction concerning postoperative complications. We documented the patients' demographic characteristics, social habits, and perioperative factors (ie, duration of general anesthesia), reconstructive techniques, neoadjuvant radiotherapy, and physical status. Initially, univariate statistical analysis was performed to confirm which predictor variables might influence the presence and severity of complications. Next, multivariate statistical analysis was performed using logistical regression and including the factors that were statistically significant on univariate analysis. RESULTS: From 1999 to 2009, we assessed 95 patients who had undergone surgery for head and neck cancer. Of the 95 patients, 24 were women and 71 were men. The patient age range was 20 to 87 years (mean 52, median 55). A total of 55 complications occurred in 49 patients (51.57%). Of the 55 complications, 12 (12.63%) were of major severity, 21 (22.10%) of median severity, and 22 (23.15%) of low severity. The statistical analysis revealed that the factors associated with complications were preoperative radiotherapy, female gender, and operation time. The factors associated with severe complications were female gender and alcohol use. CONCLUSIONS: Multivariate analysis of the data revealed that the factor associated with an increased incidence of postoperative complications was preoperative radiotherapy. Moreover, the variable that remained statistically significant and correlated with an increased incidence and severity of free flap reconstruction complications was female gender. Identifying the etiology of these findings is an intriguing field for additional research.

Epidermoid cyst of an intrapancreatic accessory spleen: a case report and literature review.

BACKGROUND: An epidermoid cyst in an intrapancreatic accessory spleen is a rare lesion. Despite advances in radiologic techniques, in most cases it has been diagnosed preoperatively as a possible pancreatic neoplasm. CASE PRESENTATION: Herein, we present a 63-year-old Caucasian woman, diagnosed preoperatively with enhanced-contrast abdominal computed tomography, as having a potential cystic tumor in the tail of the pancreas. The patient underwent a distal pancreatectomy and splenectomy, and the histological examination revealed the presence of an epidermoid cyst of an accessory intrapancreatic spleen. CONCLUSIONS: Familiarity with the imaging features, the clinical presentation and the location of the cyst are important to consider if this rare entity is to be included in the differential diagnosis of cystic neoplasms of the pancreas.

Kallikrein-related peptidases in cancers of gastrointestinal tract: an inside view of their role and clinical significance.

Human tissue kallikrein (KLK1) and is related peptidases (KLK2-KLK15) are a family of 15 homologous serine proteases, participating in numerous processes of normal physiology. Considering the irreversible impact of proteases on substrates, the tissue-dependent regulation of KLKs activity becomes crucial for their beneficial role in normal homeostasis. Moreover, KLKs expression is strongly regulated at the transcriptional and post-transcriptional level by steroid hormones and miRNAs, respectively. Deregulation of KLKs expression, secretion and/or activation has been observed in most human malignancies and there is a trend to identify their role in the multi-complex process of cancer development. The identification of extracellular matrix (ECM) proteins, cell-surface receptors, cell-surface adhesion molecules and growth factors among substrates, clearly support the driving role of KLK abnormal expression and function during tumorigenesis and cancer progression. KLKs have also clinical utility in cancer diagnosis and monitoring like KLK 3 (PSA) in prostate cancer. In this review, we tried to summarize the existing literature about the role of KLKs in gastrointestinal cancers as well as to emphasize their clinical significance for patients' prognosis.

Pre-treatment with low-dose endotoxin prolongs survival from experimental lethal endotoxic shock: Benefit for lethal peritonitis by Escherichia coli.

Although LPS tolerance is well-characterized, it remains unknown if it is achieved even with single doses of lipopolysaccharide (LPS) and if it offers protection against lethal bacterial infections. To this end, C57B6 mice were assigned to groups A (sham); B (saline i.p followed after 24h by i.p 30mg/kg LPS); and C (3mg/kg LPS i.p followed after 24h by i.p 30mg/kg LPS). Survival was monitored and animals were sacrificed early after lethal challenge for measurement of tumour necrosis factor-alpha (TNFα) in serum; isolation of splenocytes and cytokine stimulation; and flow-cytometry for apoptosis and TREM-1. Experiments were repeated with mice infected i.p by Escherichia coli after challenging with saline or LPS. Mortality of group B was 72.2% compared with 38.9% of group C (p: 0.020). Serum TNFα of group C was lower than group B. Expression of TREM-1 of group C on monocytes/neutrophils was greater than group B. Release of TNFα, of IFNγ and of IL-17 from splenocytes of group C was lower than group B and the opposite happened for IL-10 showing evidence of cellular reprogramming. In parallel, apoptosis of circulating lymphocytes and of splenocytes of group C was greater compared with group B. Pre-treatment of mice challenged by E. coli with low dose LPS led to 0% mortality compared with 90% of saline pre-treated mice; in these mice, splenocytes improved over-time their capacity for release of IFNγ. It is concluded that single low doses of LPS lead to early reprogramming of the innate immune response and prolong survival after lethal E. coli challenge.

The effect of synbiotics on acute radiation-induced diarrhea and its association with mucosal inflammatory and adaptive responses in rats.

BACKGROUND: Previous clinical studies advocated that probiotics beneficially affect acute radiation-induced diarrhea. These encouraging results were attributed to the restoration of the intestinal flora; however, there is lack of evidence if and how probiotics influence the underlying pathophysiological mechanisms. AIMS: The present study was conducted to investigate the potential supporting role of a synbiotic preparation (combination of pro- and pre-biotics) on experimentally-induced acute radiation diarrhea from the perspective of mucosal inflammation and histological injury. METHODS: Ninety adult Wistar rats were randomly assigned into six groups. Group A (non-irradiated), group B (non-irradiated/synbiotic supplemented), group C (irradiated), and group D (irradiated/synbiotic supplemented) were followed up to a week after the beginning of the experiment. Group E (irradiated) and group F (irradiated/synbiotic supplemented) were followed up for four days. On the last day of the experiments tissues were harvested for structural and molecular assessments. RESULTS: Synbiotic administration could not avert the occurrence of diarrhea, but significantly attenuated its severity. This effect was associated with the significant downregulation of neutrophil accumulation and lipid peroxidation during the acute phase. During the subacute phase, synbiotic treatment significantly improved both the histological profile and radiation mucositis. These mechanisms significantly contributed to the rehabilitation of the intestinal absorptive function as further indicated from the significantly reduced weight loss. CONCLUSIONS: Given the optimization of the intestinal flora exerted by synbiotics, the resolution of diarrhea relies on the suppression of the "reactive" and the augmentation of "regenerative" components of acute radiation-induced intestinal response.

Risk and predictive factors of hypoalbuminemia in cancer patients following extensive abdominal surgery despite total parenteral nutritional support.

Postoperative hypoalbuminemia is associated with adverse outcomes, particularly in cancer patients. The risk and predictors of hypoalbuminemia in cancer patients following extensive abdominal surgery (EAS), despite total parenteral nutrition (TPN) support, were evaluated. A prospective cohort study (n = 115) was conducted in patients with gastrointestinal and/or urogenital malignancies following extensive (n = 81) or moderate (n = 34) abdominal surgery (mean age ± standard deviation: 66.0 ± 11.7 years). EAS patients received daily TPN, including 200 mL of 5% human albumin solution. Serum albumin (SA) levels and hypoalbuminemia (SA < 3.5 g/dL) were assessed daily. EAS patients had an elevated risk of hypoalbuminemia during the first postoperative week [relative risk (RR): 3.12; 95% confidence interval (95% CI): 1.64-5.91]. Postoperative hypoalbuminemia was associated with surgery duration (RR: 1.76; 95% CI: 1.32-2.36), preoperative SA (RR: 0.24; 95% CI: 0.11-0.55), blood (RR: 1.46; 95% CI: 1.04-2.04) and Ringer's lactated solution (RR: 1.52; 95% CI: 1.12-2.07) volumes transfused intra-operatively. Therefore, despite TPN, cancer patients who underwent EAS had an elevated risk of postoperative hypoalbuminemia. Additional tailored nutritional support among this group is necessary to deter adverse clinical outcomes.

Postoperative hypoproteinemia in cancer patients following extensive abdominal surgery despite parenteral nutritional support.

Determination of the predictors of hypoproteinemia among cancer patients following extensive surgery may enhance their nutritional management and clinical outcome. This study evaluated the predictive factors of postoperative hypoproteinemia among cancer patients following extensive abdominal surgery. An age- and gender-matched case-control study (n = 115) was conducted among cancer patients undergoing extensive (cases; n = 81) and moderate (controls; n = 34) abdominal surgery. Case patients received total parenteral nutrition (TPN), including 3 units of fresh frozen plasma and 200 mL 5% human albumin solution, for 8 postoperative days (POD). Case patients had lower mean total serum protein (TSP) levels throughout POD 8 (F value = 13.81; P = 0.001). Despite TPN, cases had greatest mean (±SD) TSP percent change on POD 1 (-24.6% ± 13.0, vs. -12.6% ± 9.2; P < 0.0001) and did not regain preoperative levels (POD 8: -14.3% ± 12.5 vs. 6.9% ± 13.4; P = 0.006). The likelihood of hypoproteinemia in this group was greatest on POD 3 (OR = 30.57; 95% CI 5.44-171.83). Multivariate regression analyses indicated that the determinants of postoperative hypoproteinemia were age [Adjusted OR (AOR) = 1.04; 95% CI 1.00-1.08), preoperative TSP (AOR = 0.46; 95% CI 0.23-0.92), and extensive surgery (AOR = 2.65; 95% CI 1.01-6.95). Tailored nutritional support, regarding extent of surgery, preoperative TSP, and patient age are needed to deter the occurrence of postoperative hypoproteinemia and consequent adverse surgical outcome among cancer patients.

Synchronous well differentiated neuroendocrine tumour and gastrointestinal stromal tumour of the stomach: a case report.

BACKGROUND: Well differentiated neuroendocrine tumours (carcinoids), arising from cells of the diffuse neuroendocrine system, represent the most commonly encountered gastric endocrine tumours. Gastrointestinal stromal tumours (GISTs), which stem from interstitial Cajal cells located within the wall of the gastrointestinal tract and have a characteristic immunoreactivity for CD117 (c-kit protein), account for the majority of gastrointestinal mesenchymal neoplasms. Simultaneous occurrence of a GIST with a well differentiated neuroendocrine tumour in the stomach is very rare. METHODS: Clinical history, endoscopy and histopathological findings were utilized for our diagnostic considerations. RESULTS: We report the coexistence of a high risk GIST with a well differentiated neuroendocrine tumour of benign clinical behavior, both located in the stomach, in a 62-year-old man previously operated for a gastric well differentiated neuroendocrine tumour with uncertain malignant behaviour. CONCLUSIONS: Even single well differentiated, sporadic, NETs of small size may coexist with GISTs. An appropriate initial therapeutic approach combined with a scrupulous follow-up seems to play a significant role in terms of preventing a metastatic disease.

A rare case of extrahepatic biliary mucinous cystic neoplasm in a middle-aged woman: A case report.

Biliary mucinous cystic neoplasms are very rare tumors of the biliary tract with malignant potential. Preoperative diagnosis is challenging, as clinical, biochemical and radiological features are not specific. Surgical resection with negative margins is the gold standard treatment for these uncommon lesions. A 55-year-old woman presented at the Third Department of Surgery (Attikon University Hospital, Athens, Greece) with a history of mild right upper quadrant (RUQ) abdominal pain and jaundice. A 2-cm lesion in the distal common bile was identified by imaging. Following discussion in our multidisciplinary board meeting the patient underwent a pylorus preserving pancreatoduodenectomy, and histopathological examination revealed an ovarian-stromal type intraductal mucinous cystic neoplasm of the extra hepatic biliary. Since biliary mucinous cystic neoplasms are characterized by malignant transformation and high rates of recurrence, surgical resection with negative margins is the treatment of choice for both non-invasive and invasive biliary mucinous cystic neoplasms.

The Modulating Effect of Ursodeoxycholic Acid on Liver Tissue Cyclooxygenase-2 Expression Following Extended Hepatectomy.

INTRODUCTION: Hepatic regeneration is a complex process involving a multitude of well-timed molecular operations. Ursodeoxycholic acid (UDCA) is postulated to exert a protective effect against oxidative stress and enzymatic degradation of the extracellular matrix, in turn potentiating the regenerative response. The aim of the present animal study is to evaluate the impact of UDCA administration in liver tissue expression of cyclooxygenase-2 (COX-2) in a setting of acute liver failure achieved by 80% hepatectomy. MATERIALS AND METHODS: Twenty-four adult male Sprague-Dawley rats were randomly assigned to an experimental (UDCA) and a control group. Animals in the UDCA received oral pretreatment with UDCA for 14 days via feeding tube, while animals in the control group received saline. All animals underwent resection of approximately 80% of the liver parenchyma. Tissue and blood sample collection were performed 48 hours postoperatively. RESULTS: The postoperative mitotic index and Ki-67 levels were found to be elevated in the UDCA group (43±11.4 and 13.7±24.7 versus 31±16.7 and 7.6±5.7), albeit without any statistical significance. Pretreatment with UDCA significantly decreased COX-2 expression levels (p=0.28) as well as serum tumor necrosis factor α (TNFα) levels (37.3±10.9 pg/mL versus 75.4±14.4 pg/mL, p=0.004). COX-2 expression score was observed to be weakly correlated to Ki-67 levels in both groups. Although COX-2 expression score was not correlated with serum TNFα levels in the control group, animals pretreated with UDCA exhibited moderate correlation (r=0.45). CONCLUSION: Preoperative administration of UDCA exerts a suppressive effect on tissue expression of COX-2 following 80% hepatectomy and enforces a positive correlation between COX-2 and serum TNFα levels, suggesting that UDCA preconditions liver tissue to display an enhanced regenerative response to circulating cytokines, most notably TNFα. The weak association of COX-2 with Ki-67 expression levels suggests that COX-2 may be of secondary importance during the early phases of liver regeneration.

Gastrointestinal stromal tumors (GISTs): an updated experience.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are relatively common mesenchymal tumors of the digestive tract characterized by c-KIT mutations. This is a comprehensive review of the current data of the literature on the various aspects of the diagnosis and treatment of these tumors. METHODS: The stomach is the most commonly involved site for these tumors in the digestive tract. Computed tomography and endoscopy can usually establish the diagnosis. The study of certain specific immunohistochemical markers may contribute to better characterization of these tumors. RESULTS: Surgical resection of GISTs has been the most effective therapy. In addition, targeted therapy with tyrosine kinase inhibitors may reduce the development of recurrence or decrease the disease progression in patients with metastatic disease. CONCLUSIONS: The introduction of tyrosine kinase inhibitors has resulted in significant improvement in the overall prognosis of these patients. Furthermore, preoperative imatinib can decrease tumor volume and is associated with complete surgical resection in locally advanced primary GISTs.

The Effects of Ursodeoxycholic Acid Pretreatment in an Experimental Setting of Extended Hepatectomy: A Feasibility Study.

Introduction Liver regeneration is an exceptionally complex process, orchestrated by a multitude of growth factors and cytokines. Tumor necrosis factor-alpha (TNF-a) and interleukin-6 (Il-6) have a pivotal role in the initiation of the regenerative response. Ursodeoxycholic acid (UDCA) exhibits a liver protective effect that enhances liver growth after injury. The aim of the present study is to evaluate the effect of UDCA in the circulating levels of TNF-a and Il-6 in rats undergoing extended 80% hepatectomy. Materials and methods Twenty-two male Sprague Dawley rats were randomly assigned in an experimental (UDCA group) and a control group. Mice in the UDCA-group received oral pretreatment of UDCA for two weeks preoperatively at a dosage of 25 mg/kg/day. An 80% hepatic resection was performed in both groups by resecting the middle, inferior right, and left lateral liver lobes. The experiment ended 48 hours postoperatively. Results UDCA pretreatment significantly depressed circulating levels of both TNF-a and Il-6 after the conclusion of the experiment as compared to the control group (p=0.001 and p=0.01, respectively). Furthermore, TNF-a levels were significantly reduced before the institution of liver injury (p=0.02). Mice in the UDCA-group exhibited better liver growth as demonstrated by significantly increased Ki-67 and mitotic rate (p=0.04 and p=0.02, respectively). Finally, the liver regeneration rate (LRR) was significantly elevated in the experimental group (UDCA group, 54.5% vs control group, 35.8%; p=0.002) signifying enhanced liver growth kinetics. Conclusion UDCA reduces the expression of TNF-a and Il-6 during the priming phase of liver regeneration. An 80% hepatectomy model of acute liver failure exhibited enhanced liver regeneration in the experimental group, plausibly due to the immunomodulatory effects of UDCA.