Development and internal validation of a clinical prediction model for serious complications after emergency laparotomy.

PURPOSE: Emergency laparotomy (EL) is a common operation with high risk for postoperative complications, thereby requiring accurate risk stratification to manage vulnerable patients optimally. We developed and internally validated a predictive model of serious complications after EL. METHODS: Data for eleven carefully selected candidate predictors of 30-day postoperative complications (Clavien-Dindo grade > = 3) were extracted from the HELAS cohort of EL patients in 11 centres in Greece and Cyprus. Logistic regression with Least Absolute Shrinkage and Selection Operator (LASSO) was applied for model development. Discrimination and calibration measures were estimated and clinical utility was explored with decision curve analysis (DCA). Reproducibility and heterogeneity were examined with Bootstrap-based internal validation and Internal-External Cross-Validation. The American College of Surgeons National Surgical Quality Improvement Program's (ACS-NSQIP) model was applied to the same cohort to establish a benchmark for the new model. RESULTS: From data on 633 eligible patients (175 complication events), the SErious complications After Laparotomy (SEAL) model was developed with 6 predictors (preoperative albumin, blood urea nitrogen, American Society of Anaesthesiology score, sepsis or septic shock, dependent functional status, and ascites). SEAL had good discriminative ability (optimism-corrected c-statistic: 0.80, 95% confidence interval [CI] 0.79-0.81), calibration (optimism-corrected calibration slope: 1.01, 95% CI 0.99-1.03) and overall fit (scaled Brier score: 25.1%, 95% CI 24.1-26.1%). SEAL compared favourably with ACS-NSQIP in all metrics, including DCA across multiple risk thresholds. CONCLUSION: SEAL is a simple and promising model for individualized risk predictions of serious complications after EL. Future external validations should appraise SEAL's transportability across diverse settings.

Eversion Carotid Endarterectomy: Cardiac Troponin Assessment.

Myocardial infarction (MI) is an eversion carotid endarterectomy (eCEA) complication, but most events are unknown, and true incidence and correlation remain controversial. Routine cardiac troponin measurement is a commonly used method for assessing early identification and treatment of MI and stratifying high-risk patients. The aim of the present study is to evaluate the effect of troponin elevation levels following eCEA and to investigate a possible correlation between adverse cardiovascular events and the incidence of postoperative myocardial infarction following emergent vascular surgery. The study included 54 patients who underwent eCEA. High-sensitive troponin I (hsTnI) levels were routinely monitored pre- and postoperatively, with an upper reference range of 34.5 pg/mL for men and 15.6 pg/mL for women. Increases were correlated with demographic and clinical risk factors, as well as clinical or subclinical cardiovascular events. hsTnI was increased in percentage (13%) postoperatively, and non-ST segment elevation MI was diagnosed in eight patients. No patient had clinical symptoms of MI and only two of them presented with simultaneous electrocardiographic changes. Increased levels did not correlate with comorbidities or other surgical risk factors. hsTnI elevation may occur in patients after eCEA and mostly correlates with silent non-ST segment elevation MI that occurred in the early postoperative phase, indicating a possible value as a tool for cardiovascular event diagnosis during the patient's hospitalization.

Surgery of Simple and Complex Anal Fistulae in Adults: A Review of the Literature for Optimal Surgical Outcomes.

Anal fistulas are common anorectal conditions, and surgery is the primary treatment option. In the last 20 years of literature, there exist a large number of surgical procedures, especially for the treatment of complex anal fistulas, as they present more recurrences and continence problems than simple anal fistulas. To date, there are no guidelines for choosing the best technique. We conducted a recent literature review, mainly the last 20 years, based on the PubMed and Google Scholar medical databases, with the goal of identifying the surgical procedures with the highest success rates, lowest recurrence rates, and best safety profiles. Clinical trials, retrospective studies, review articles, comparative studies, recent systematic reviews, and meta-analyses for various surgical techniques, as well as the latest guidelines of the American Society of Colon and Rectal Surgeons, the Association of Coloproctology of Great Britain and Ireland, and the German S3 guidelines on simple and complex fistulas were reviewed. According to the literature, there is no recommendation for the optimal surgical technique. The etiology, complexity, and many other factors affect the outcome. In simple intersphincteric anal fistulas, fistulotomy is the procedure of choice. In simple low transsphincteric fistulas, the patient's selection is crucial in order to perform a safe fistulotomy or another sphincter-saving technique. The healing rate in simple anal fistulas is higher than 95% with low recurrence and without significant postoperative complications. In complex anal fistulas, only sphincter-saving techniques should be used; the optimal outcomes are obtained by the ligation of the intersphincteric fistulous tract (LIFT) and rectal advancement flaps. Those techniques assure high healing rates of 60-90%. The novel technique of the transanal opening of the intersphincteric space (TROPIS) is under evaluation. The novel sphincter-saving techniques of fistula laser closure (FiLac) and video-assisted anal fistula treatment (VAAFT) are safe, with reported healing rates ranging from 65% to 90%. Surgeons should be familiar with all sphincter-saving techniques in order to face the variability of the fistulas-in-ano. Currently, there is no universally superior technique that can treat all fistulas.

Prospective multicenter external validation of postoperative mortality prediction tools in patients undergoing emergency laparotomy.

BACKGROUND: Accurate preoperative risk assessment in emergency laparotomy (EL) is valuable for informed decision making and rational use of resources. Available risk prediction tools have not been validated adequately across diverse health care settings. Herein, we report a comparative external validation of four widely cited prognostic models. METHODS: A multicenter cohort was prospectively composed of consecutive patients undergoing EL in 11 Greek hospitals from January 2020 to May 2021 using the National Emergency Laparotomy Audit (NELA) inclusion criteria. Thirty-day mortality risk predictions were calculated using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP), NELA, Portsmouth Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity (P-POSSUM), and Predictive Optimal Trees in Emergency Surgery Risk tools. Surgeons' assessment of postoperative mortality using predefined cutoffs was recorded, and a surgeon-adjusted ACS-NSQIP prediction was calculated when the original model's prediction was relatively low. Predictive performances were compared using scaled Brier scores, discrimination and calibration measures and plots, and decision curve analysis. Heterogeneity across hospitals was assessed by random-effects meta-analysis. RESULTS: A total of 631 patients were included, and 30-day mortality was 16.3%. The ACS-NSQIP and its surgeon-adjusted version had the highest scaled Brier scores. All models presented high discriminative ability, with concordance statistics ranging from 0.79 for P-POSSUM to 0.85 for NELA. However, except the surgeon-adjusted ACS-NSQIP (Hosmer-Lemeshow test, p = 0.742), all other models were poorly calibrated ( p < 0.001). Decision curve analysis revealed superior clinical utility of the ACS-NSQIP. Following recalibrations, predictive accuracy improved for all models, but ACS-NSQIP retained the lead. Between-hospital heterogeneity was minimum for the ACS-NSQIP model and maximum for P-POSSUM. CONCLUSION: The ACS-NSQIP tool was most accurate for mortality predictions after EL in a broad external validation cohort, demonstrating utility for facilitating preoperative risk management in the Greek health care system. Subjective surgeon assessments of patient prognosis may optimize ACS-NSQIP predictions. LEVEL OF EVIDENCE: Diagnostic Test/Criteria; Level II.

The Hellenic Emergency Laparotomy Study (HELAS): A Prospective Multicentre Study on the Outcomes of Emergency Laparotomy in Greece.

BACKGROUND: Emergency laparotomy (EL) is accompanied by high post-operative morbidity and mortality which varies significantly between countries and populations. The aim of this study is to report outcomes of emergency laparotomy in Greece and to compare them with the results of the National Emergency Laparotomy Audit (NELA). METHODS: This is a multicentre prospective cohort study undertaken between 01.2019 and 05.2020 including consecutive patients subjected to EL in 11 Greek hospitals. EL was defined according to NELA criteria. Demographics, clinical variables, and post-operative outcomes were prospectively registered in an online database. Multivariable logistic regression analysis was used to identify independent predictors of post-operative mortality. RESULTS: There were 633 patients, 53.9% males, ASA class III/IV 43.6%, older than 65 years 58.6%. The most common operations were small bowel resection (20.5%), peptic ulcer repair (12.0%), adhesiolysis (11.8%) and Hartmann's procedure (11.5%). 30-day post-operative mortality reached 16.3% and serious complications occurred in 10.9%. Factors associated with post-operative mortality were increasing age and ASA class, dependent functional status, ascites, severe sepsis, septic shock, and diabetes. HELAS cohort showed similarities with NELA patients in terms of demographics and preoperative risk. Post-operative utilisation of ICU was significantly lower in the Greek cohort (25.8% vs 56.8%) whereas 30-day post-operative mortality was significantly higher (16.3% vs 8.7%). CONCLUSION: In this study, Greek patients experienced markedly worse mortality after emergency laparotomy compared with their British counterparts. This can be at least partly explained by underutilisation of critical care by surgical patients who are at high risk for death.

Primary non-Hodgkin lymphoma of the extra-hepatic bile duct: A case report.

Lymphoma is known to be a systemic lymphoproliferative malignancy, which is divided into two subtypes: Hodgkin lymphoma and non-Hodgkin lymphoma. Non-Hodgkin lymphoma originates from nodal and extranodal sites. In the staging of non-Hodgkin lymphoma, the liver is implicated in 40% of cases; however, primary liver non-Hodgkin lymphoma represents <1% of all non-Hodgkin lymphoma cases. Because of its rarity, it is not usually considered in the differential diagnosis of patients that present with jaundice. Since the first case of primary non-Hodgkin lymphoma of the extra-hepatic bile ducts was presented, only 42 similar cases have been reported in the English literature. The present case report describes a rare case of non-Hodgkin lymphoma of the common hepatic duct, which presented with obstructive jaundice and represented a complex differential diagnostic issue.

Gallstone Ileus in Octogenarians: Is Cholecystectomy Really Needed?

Gallstone ileus is an uncommon complication of cholelithiasis and occurs when a gallstone migrates through a cholecystoenteric fistula and impacts within the gastrointestinal tract. Surgical intervention remains the treatment of choice, which consists of a full-thickness incision of the visceral wall and removal of the impacted gallstone. In this paper we present the treatment approach of 6 cases of gallstone ileus in octogenarians. In our cohort, intestinal obstruction was resolved through an enterotomy or gastrotomy and lithotomy/stone extraction in every patient. No cholecystectomies were undertaken. Despite the fact that gallstone ileus is diagnosed in small percent of patients suffering from gallstone disease, it accounts for a large proportion of intestine obstruction in patients older than 65 years old. Since accurate diagnosis and timely intervention are vital, providers should be familiar with the diagnostic approach and the treatment of this clinical entity.

p53 protein expression in synchronously occurring dedifferentiating stages of thyroid cancer in a patient with neurofibromas: A case report.

Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) have been hypothesized to arise from well-differentiated thyroid carcinoma (WDTC) due to frequently reported synchronous and metachronous occurrence. Loss of normal p53 function has been implicated in this dedifferentiation process. The current case report presents a 60-year-old male with multiple neurofibromas who underwent total thyroidectomy due to multiple palpable thyroid nodules. Histopathological examination revealed three foci of predominantly papillary, but also follicular carcinoma growth pattern, and two lesions with histological features of insular and trabecular variant, with the larger one showing foci of anaplastic transition. Nuclear p53 protein accumulation, corresponding to mutant abnormally stabilized p53, was higher in more aggressive variants compared with WDTC. The somatic molecular events and downstream pathways of this dedifferentiation course have not been unraveled yet. The present case report demonstrated the simultaneous presence of three divergent histological subtypes in a single thyroid gland, with progressive enhancement of nuclear p53 protein expression, associated with mutant p53 protein, in the more aggressive variants. This is a rare case of progressive enhancement of mutant nuclear p53 protein expression in multifocal thyroid tumor areas consisting of WDTC, PDTC and ATC histological types, highlighting the possibility that WDTC can progress to PDTC and then ATC through an intricate procedure, involving loss of normal p53 function.

Radial Basis Function Artificial Neural Network for the Investigation of Thyroid Cytological Lesions.

OBJECTIVE: This study investigates the potential of an artificial intelligence (AI) methodology, the radial basis function (RBF) artificial neural network (ANN), in the evaluation of thyroid lesions. Study Design. The study was performed on 447 patients who had both cytological and histological evaluation in agreement. Cytological specimens were prepared using liquid-based cytology, and the histological result was based on subsequent surgical samples. Each specimen was digitized; on these images, nuclear morphology features were measured by the use of an image analysis system. The extracted measurements (41,324 nuclei) were separated into two sets: the training set that was used to create the RBF ANN and the test set that was used to evaluate the RBF performance. The system aimed to predict the histological status as benign or malignant. RESULTS: The RBF ANN obtained in the training set has sensitivity 82.5%, specificity 94.6%, and overall accuracy 90.3%, while in the test set, these indices were 81.4%, 90.0%, and 86.9%, respectively. Algorithm was used to classify patients on the basis of the RBF ANN, the overall sensitivity was 95.0%, the specificity was 95.5%, and no statistically significant difference was observed. CONCLUSION: AI techniques and especially ANNs, only in the recent years, have been studied extensively. The proposed approach is promising to avoid misdiagnoses and assists the everyday practice of the cytopathology. The major drawback in this approach is the automation of a procedure to accurately detect and measure cell nuclei from the digitized images.

Review of the Literature on Leiomyoma and Leiomyosarcoma of the Adrenal Gland: A Systematic Analysis of Case Reports.

BACKGROUND/AIM: To date few cases of smooth muscle-derived tumors of the adrenal gland have been reported and their treatment remains a medical challenge. The aim of this manuscript was to systematically review the literature and present the tumor characteristics and their management in order to provide a standardized approach to their diagnosis and management. MATERIALS AND METHODS: We searched five databases (PubMed, Scopus, Elsevier, ResearchGate, Google scholar) for relevant articles published until March 2020. RESULTS: Twenty-two cases of adrenal leiomyoma, four cases of adrenal smooth muscle tumor and forty-five cases of adrenal leiomyosarcoma were included. CONCLUSION: We present the demographic, clinical, radiological, pathological and oncological characteristics and prognosis of tumors of the adrenal gland arising from smooth muscle cells, as well as describe the common clinical investigations and therapeutic modalities that have been reported as part of their management.

Carotid Body Baroreceptor Preservation and Control of Arterial Pressure in Eversion Carotid Endarterectomy.

The technique of the eversion carotid endarterectomy (ECEA), as an alternative to the conventional endarterectomy with primary or patch angioplasty, is an established technique for managing internal carotid artery stenoses and recently its application has been upgraded through the European Society for Vascular Surgery guidelines (Recommendation 55: Class 1, Level A). However, the typical eversion method has been associated with postoperative hypertension due to loss of the baroreceptor reflex; the standard oblique transection at the bulb performed in the eversion endarterectomy interrupts either the baroreceptor sensoring tissue, which is mostly located in the adventitia at the medial portion of the proximal internal carotid artery, or even the proper Hering nerve, a branch of the glossopharyngeal nerve. These actions deregulate the natural negative feedback of the carotid baroreceptor. Guided by the anatomical location of the baroreceptor sensor we have elaborated a slight modification of the classical ECEA to maintain as much as possible of the viable carotid baroreceptor sensoring surface. By extending the oblique incision distal to the carotid bifurcation in the medial part of the internal carotid artery stem, an eyebrow-like part of the proximal internal carotid artery is maintained and the axis from the sensoring tissue to the nerve of Hering is protected and following the endarterectomy, postoperative arterial blood pressure levels are lower than in the classical ECEA due to the maintenance of the efficiency of the baroreceptor reflex. During the period from September 2016 to November 2018, carotid endarterectomy was performed in 57 patients. Twenty-eight of them underwent the typical ECEA and 29 patients had the modified eyebrow eversion carotid endarterectomy (me-ECEA). The changes of blood pressure baseline during the postoperative course in ECEA and me-ECEA group were analyzed and compared. Postoperative hypertension was defined as an elevation of systolic blood pressure (SBP) greater than 140 mm Hg. Patients who underwent typical ECEA had significantly higher postoperative blood pressure values compared with those who underwent me-ECEA. Actually, the mean postoperative SBP was 172.67 ± 24.59 mm Hg in the typical ECEA group compared with 160.86 ± 12.83 mm Hg in the me-ECEA group ( p = 0.023). The mean diastolic blood pressure in the ECEA group was 65.42 ± 11.39 mm Hg compared with 58.06 ± 9.06 mm Hg in the me-ECEA group ( p = 0.009). Our proposed me-ECEA technique seems to be related to lower rates of postoperative hypertension compared with the typical ECEA, probably due to the sparing of the main mass of the baroreceptor apparatus; this improved modification (me-ECEA) of the typical eversion procedure could represent an alternative ECEA technique with its inherent advantages.

Survivin expression in hepatocellular carcinoma. Correlation with clinicopathological characteristics and overall survival.

PURPOSE: Survivin expression is a potential prognostic indicator in various carcinomas. The prognostic value of Survivin for survival in hepatocellular carcinoma, (HCC) however, remains controversial. The aim of the study is to examine the expression of the inhibitor of apoptosis Survivin in HCC and investigate the correlation with the clinic-pathologic characteristics and overall survival (OS) following surgical resection. METHODS: Specimens from patients with resected HCC were examined by Immunohistochemical staining for Survivin and BCL-2expression. Clinical and histopathological data were retrieved from medical and pathology records, while OS was determined by reviewing records from the department of Oncology and personal communication with survivors. Bivariate analysis was performed using the Chi-square and Mann-Whitney U tests, while survival was estimated by Kaplan Meier method and compared with log-rank test. RESULTS: Sixty patients were included in the study. Survivin was expressed in 26 patients (43.3%). Survivin expression was significantly correlated to OS (p=0.014). A statistically significant negative correlation between Survivin and BCL-2 was also noted (p<0.001). CONCLUSIONS: Survivin expression reflects aggressive histological and clinical behavior of HCC and correlates with poorer OS. Further studies are required to confirm if Survivin can be used as a predictive biomarker to evaluate prognosis and target treatments for HCC.

Association Between hsa-miR-30e Polymorphisms and Sporadic Primary Hyperparathyroidism Risk.

BACKGROUND/AIM: Almost 15% of patients with sporadic primary hyperparathyroidism (sPHPT) present with multiple gland disease (MGD). The aim of this study was to investigate the potential role of two polymorphisms of the hsa-miR-30e, in sPHPT tumorigenesis. PATIENTS AND METHODS: One-hundred twenty sPHPT patients, 77 presenting a single adenoma and 43 with MGD, and 54 healthy controls were genotyped. The SNPs were identified using the allele-specific PCR methodology, while the hsa-miR-30e expression was analyzed by real-time quantitative reverse transcriptase PCR. RESULTS: Hsa-miR-30e expression was found to be significantly higher in patients with MGD compared to patients with single adenomas (p=0.0019), but no differences were found regarding specific genotype carriers. The genotype frequencies for ss178077483 and rs7556088 were significantly different between patients and healthy controls. CONCLUSION: Although the polymorphisms cannot be used as biomarkers for the differential diagnosis of MGD, hsa-miR-30e expression could potentially serve as a biomarker for this purpose.

The Impact of Technique Standardization on Total Operating and Fluoroscopy Times in Simple Endourological Procedures: A Prospective Study.

PURPOSE: To present the positive impact of technique standardization on successful outcome, fluoroscopy, and total operating time (TOT) shortening in a prospective study. METHODS: Six experienced endourologists participated. To assess whether the adaptation of standardized surgical steps improved their methodology with time, 253 patients were prospectively divided in three consecutive 1-month groups. Patients underwent stent placement and exchange and total operating and fluoroscopy times (FTs) were recorded. All surgeons were unaware of their mean recorded results until the end of the study. At the end of the third month, we evaluated if the suggested technique standardization established a decrease for both FT and TOT. Statistical significance was set to p < 0.05. RESULTS: Total operating and FTs were significantly reduced with time between all groups of patients. For stent placement, TOT showed significant reduction between Groups A and C (p < 0.001), while between other group comparisons did not reach significance. FT showed a significant reduction (p < 0.001) in all group comparisons. For stent exchange, TOT reached significant improvement (p = 0.003) between Groups A and C, whereas between other groups was insignificant. FT improvement was significant between Groups A and C (p < 0.001) and Groups B and C (p < 0.001), but insignificant between Groups A and B. CONCLUSIONS: Even in experienced hands, the adaptation of technique standardization results in significant decrease of total operating and FTs and it is independent from feedback regarding their time performance.

Minimal surgical management of penile paraffinoma after subcutaneous penile paraffin injection.

OBJECTIVES: To describe our reconstructive technique, without flap or graft use, after penile self-augmentation with injected substances, such as paraffin, which are still performed with unfortunate consequences. PATIENT AND METHODS: Successful single-stage minimal surgical management of an already twice unsuccessfully managed ulcerative penile paraffinoma in a 38-year-old Greek man. RESULTS: The patient was discharged with no postoperative complications, with a five-item version of the International Index of Erectile Function score of 23/25 (i.e. normal erectile function) and flaccid penile length of 5 cm. CONCLUSIONS: Penile paraffinoma is a serious complication that can be successfully managed with a single-stage minimal surgical procedure, with normal aesthetic and functional results.

Peptide Receptor Radionuclide Treatment and (131)I-MIBG in the management of patients with metastatic/progressive phaeochromocytomas and paragangliomas.

BACKGROUND AND OBJECTIVES: Radionuclide therapy has been used to treat patients with progressive/metastatic paragangliomas (PGLs) and phaeochromocytomas (PCCs). The aim of the present study is to retrospectively compare the therapeutic outcomes of these modalities in patients with progressive/metastatic PCCs and PGLs. METHODS: Patients with progressive/metastatic PGLs and PCCs that were subjected to radionuclide treatment in our department were retrieved from our department's database for the period 1998-2013. Overall survival (OS), progression free survival (PFS), event free survival (EFS), and response to treatment were calculated. Treatment toxicity was documented. RESULTS: Twenty-two patients with progressive/metastatic PGLs or PCCs were treated with either (131)I-MIBG, (90)Y-DOTATATE or (177)Lu-DOTATATE. A total of 30 treatments were administered (16 treatments with (131)I-MIBG, 2 with (177)Lu-DOTATATE, and 12 with (90)Y-DOTATATE. Patients treated with PRRT had increased PFS and response to treatment compared to (131)I-MIBG treated patients (P < 0.05). However, difference in OS was non significant (P = 0.09). There was no difference in major toxicities between groups. When comparing only patients with PGLs, OS, PFS, EFS, and response to treatment were significantly higher in the PRRT treatment group. CONCLUSION: PRRT treatment offers increased OS, PFS, EFS, and response to treatment compared to (131)I-MIBG therapy in patients with progressive/malignant PGLs.

Molecular studies of the immunological effects of the sevoflurane preconditioning in the liver and lung in a rat model of liver ischemia/reperfusion injury.

Sevoflurane has been shown to improve ischemia/reperfusion injury (IRI) through several mechanisms, including amelioration of inflammatory response. However, there haven't been any studies considering the potential role of the complement system in sevoflurane-mediated amelioration of ischemia/reperfusion injury. Our purpose was to investigate the molecular mechanisms involved in sevoflurane preconditioning in liver and lung injury induced by liver ischemia-reperfusion (LIR), giving emphasis to the immunological mechanisms. In order to do that, fifty male Wistar rats were randomly allocated in five groups (n=10 each): Animals in group LIR received ketamine and xylazine and were then subjected to ischemia of the right and median hepatic lobe for 45 min and reperfusion for 6h. Group SEVO/LIR received sevoflurane and then LIR was induced, as in group LIR. Animals in group SHAM/LIR were anesthetized with ketamine and xylazine and then laparotomy followed. Group SHAM/SEVO received sevoflurane for 30 min and then laparotomy followed. Finally, in group VEN, animals only received ketamine and xylazine. Our results showed that sevoflurane preconditioning significantly improved liver-biochemical tests (decreased Alanine transaminase (ALT), Alkaline phosphatase (ALP), Aspartate transaminase (AST) and Alkaline phosphatase (ALP) levels) and limited inflammatory cell infiltration in BALF. Additionally, compared with the LIR group, the reduction in plasma C3 was significantly reduced in the SEVO/LIR group. No significant differences were observed in histological examination in the liver and lung. Immunostaining of the liver for Intracellular Adhesion Molecule 1 (ICAM1) however, showed a decrease in ICAM1 levels in the SEVO/LIR group. In the lung, sevoflurane seemed to exert no effect in ICAM1 levels. Caspase 3 (CASP3) levels in the liver and the lung also appeared unaffected by sevoflurane preconditioning. In the SEVO/LIR group, ICAM1 mRNA expression was significantly reduced in the liver. No statistical significantly differences were observed in Complement component 3 (C3), Complement component 5 (C5) and Clusterin (CLU) mRNA levels in the liver or the lung tissue. Summarizing, sevoflurane preconditioning seems to ameliorate LIR-induced injury in the rats, mediated by mechanisms that include ICAM1 and complement C3 down regulation.

Association of FokI and PvuII polymorphisms with breast cancer staging and survival among Caucasian women: a prospective study.

PURPOSE: Both vitamin D and estrogens play an important role in breast cell growth and differentiation. Therefore, we hypothesized that FokI polymorphism in the Vitamin D Receptor (VDR) gene, as well as PvuII polymorphism in the Estrogen Receptor (ESR) gene might be associated with progression of breast cancer. The aim of this study was to prospectively examine the association of these polymorphisms with histopathological features and prognosis among women with histologically proven breast cancer. METHODS: Patient characteristics, tumor histopathology, and genotyping of one VDR polymorphism variant (FokI) and one ER polymorphism variant (PvuII) were recorded. Patients were also routinely followed up. RESULTS: There was a significant difference regarding nodal stage (p<0.001) between the different genotypes of FokI polymorphisms (FF, Ff, ff), even though a trend was also detected in the frequency between ductal and lobular type, as well as tumor size (p=0.077). When further analysis was performed regarding patients whose polymorphism included the f allele, we found statistically significant differences in tumor size (p<0.001), nodal stage (p=0.03), tumor grade (p=0.04) and lymphovascular invasion (p<0.001), while no differences in nodal status, distant metastases and tumor stage were noticed. No significant associations were found between any of the PvuII polymorphism variants and tumor histopathology and stage. No statistical significance was proven between FokI polymorphism's variants or f allele and overall or progression-free survival. Statistically significant associations between overall and progression- free survival and PvuII polymorphism's variants was demonstrated (p<0.001). CONCLUSION: The f allele was associated with the presence of lymphovascular invasion and poorly differentiated tumors, whereas the PP genotype was associated with increased overall and progression-free survival, suggesting that this variant is related to a more favorable prognosis.

Effect of infliximab on the healing of intestinal anastomosis. An experimental study in rats.

BACKGROUND AND AIM: Infliximab is effective in the induction and maintenance of remission in Crohn's disease. Whether, the perioperative administration of anti-TNF-a compromises intestinal healing leading to anastomotic failure and increased risk of postoperative complications, remains controversial. The aim of the study was to evaluate the effect of Infliximab on intestinal anastomosis healing. METHODS: Fifty six wistar rats were divided into 4 groups: (a) 20 rats were subjected to excision of part of the terminal ileum followed by anastomosis which was evaluated on the 3rd or 7th postoperative day; (b) 20 rats received Infliximab and thereafter, the same surgical protocol as group (a) was followed; (c) 8 rats received Infliximab and served as relative control group; and (d) 8 served as absolute control group. Bursting pressure was used for testing intestinal healing. Additionally, the anastomoses were examined macroscopically, histologically and immunohistochemically for TGFb1, MMP1, MMP2 and Collagen V. The results were confirmed by Western blot analysis. RESULTS: There were no significant differences in bursting pressures and septic intra-abdominal events among non-Infliximab (a) and Infliximab-treated (b) groups. Infliximab-treated (b) group showed mild to moderate inflammation, whereas the non-Infliximab (a) group exhibited severe inflammation. Expression of TGFb1, MMP2 and collagen V was significantly higher in the Infliximab-treated (b) group. CONCLUSION: Infliximab seems to influence intestinal healing in terms of less inflammatory activity and higher tissue remodeling activity.

The impact of peri-operative anti-TNF treatment on anastomosis-related complications in Crohn's disease patients. A critical review.

INTRODUCTION: Tumor necrosis factor (TNF)α is a cytokine exerting pleiotropic effects on critical cell functions and, most importantly, is the main regulator of pro-inflammatory cytokine production and a key player in the pathophysiology of numerous autoimmune diseases, including Crohn's disease. METHODS: TNFα became a therapeutic target and TNFα blocking agents are currently used in the treatment of inflammatory diseases. Beyond the therapeutic benefits deriving from TNFα neutralization, amendments in the cellular functions of the immune system may as well induce potent immunosuppressive effects. An attenuated immune response may compromise the intestinal healing ability, thus leading to weaker anastomosis and increased risk of anastomotic leak and septic complications. RESULTS: This hypothesis raises great concerns about the safety of perioperative administration of anti-TNF and has been the endpoint of numerous studies. CONCLUSION: The aim of this review is to critically evaluate the evidence regarding the role of TNFα in anastomosis related complications after abdominal surgery in Crohn's disease patients.