Ioannis Karavokyros

The TNBS-induced colitis animal model: An overview

Background Despite recent advances the pathogenesis of Crohns disease remains incompletely understood. A variety of animal models have been utilized in an effort to provide further insights and develop more therapeutic options. In order to simulate, to an extent, the pathogenesis and the clinical course of the disease, TNBS induced colitis is often used. Various approaches for inducing TNBS -colitis have been described in the literature. Methods/results In this review, we sought to present the animal model of TNBS induced colitis and outline the pathogenesis, pathophysiology, clinical course and pathological characteristics of the model. Furthermore, we describe the differences among those protocols regarding types of animals and colitis induction. Data sources The MEDLINE database was thoroughly searched using the keywords: TNBS, colitis, Crohns disease, animal model. Two investigators independently reviewed the abstracts and appropriate articles were included in this review. Additional articles were gathered and evaluated. Conclusion The aim of this study was to thoroughly present an updated review of the TNBS-induced colitis protocols that are implemented by researchers.

Polycystin-1 and polycystin-2 are involved in the acquisition of aggressive phenotypes in colorectal cancer.

The polycystins PC1 and PC2 are emerging as major players in mechanotransduction, a process that influences all steps of the invasion/metastasis cascade. We hypothesized that PC1 and PC2 facilitate cancer aggressiveness. Immunoblotting, RT‐PCR, semi‐quantitative and quantitative real‐time PCR and FACS analyses were employed to investigate the effect of polycystin overexpression in colorectal cancer (CRC) cells. The impact of PC1 inhibition on cancer‐cell proliferation was evaluated through an MTT assay. In vitro data were analyzed by Students t‐test. HT29 human xenografts were treated with anti‐PC1 (extracellular domain) inhibitory antibody and analyzed via immunohistochemistry to determine the in vivo role of PC1 in CRC. Clinical significance was assessed by examining PC1 and PC2 protein expression in CRC patients (immunohistochemistry). In vivo and clinical data were analyzed by non‐parametric tests, Kaplan‐Meier curves, log‐rank test and Cox model. All statistical tests were two‐sided. PC1 overexpression promotes epithelial‐to‐mesenchymal transition (EMT) in HCT116 cells, while PC2 overexpression results in upregulation of the mTOR pathway in SW480 cells. PC1 inhibition causes reduced cell proliferation in CRC cells inducing tumor necrosis and suppressing EMT in HT29 tumor xenografts. In clinical study, PC1 and PC2 overexpression associates with adverse pathological parameters, including invasiveness and mucinous carcinomas. Moreover, PC1 overexpression appears as an independent prognostic factor of reduced recurrence‐free survival (HR = 1.016, p = 0.03) and lowers overall survival probability, while aberrant PC2 expression predicts poor overall survival (p = 0.0468). These results support, for the first time, a direct link between mechanosensing polycystins (PC1 and PC2) and CRC progression.

Survival in patients with stage IV noncardia gastric cancer - the influence of DNA ploidy and Helicobacter Pylori infection

BackgroundPalliative surgery followed by postoperative chemotherapy is a challenging approach in the treatment of stage IV gastric cancer yet patients must be carefully selected on the basis of likely clinical benefit.MethodsThe records of 218 patients with histological diagnosis of gastric adenocarcinoma who underwent palliative surgery followed by postoperative chemotherapy were retrospectively reviewed. Twelve potential prognostic variables including tumour DNA index and serum IgG anti- Helicobacter pylori (HP) antibodies were evaluated for their influence on overall survival by multivariate analysis.ResultsThe median survival was 13.25 months [95% Confidence Interval (CI) 12.00, 14.50]. Three factors were found to have an independent effect on survival: performance status (PS) [PS 60–70 vs. 90–100 Hazard Ratio (HR) 1.676; CI 1.171-2.398, p = 0.005], liver metastases (HR 1.745; CI 1.318-2.310, p < 0.001), and DNA Index as assessed by Image cytometry (2.2-3.6 vs. >3.6 HR 3.059; CI 2.185-4.283, p < 0.001 and <2.2 vs. >3.6 HR; 4.207 CI 2.751-6.433 <0.001). HP infection had no statistically significant effect on survival by either univariate or multivariate analysis.ConclusionPoor pre-treatment PS, the presence of liver metastasis and high DNA Index were identified factors associated with adverse survival outcome in patients with Stage IV gastric cancer treated with palliative gastrectomy and postoperative chemotherapy. HP infection had no influence on survival of these patients.

Marlex Mesh Prefix Plug Hernioplasty Retrospective Analysis of 865 Operations

For 5 years (January 1998 to November 2002) our department has applied the Marlex Mesh Perfix Plug hernioplasty. This article demonstrates the experience gained in operative and postoperative aspects, costs, and outcome along with the results of a follow-up analysis. Altogether, 801 patients (749 males, 52 females) were operated on Sixty-four males had bilateral groin hernias, so the total number of hernioplasties amounted to 865. A total of 19 hernias were recurrent, 297 were direct, 545 were indirect or scrotal (or both) 21 were femoral, and 2 were Spigelian. Fifty-three operations were performed on an emergency basis. Preoperative routine use of antibiotics was minimized throughout the years. Operating time fluctuated from 20 to 25 min (30-40 minutes for recurrent hernias), and the postoperative hospital stay was 28 hours (6-72) hours. The complication rate was 5% and the recurrence rate less than 1%. Early patient mobilization and return to everyday activities (1-2 weeks) was encouraged. The follow-up of 95% of the patient population lasted 12 to 60 months and was performed at 1 week, 1 month, 1 year, and yearly thereafter. The technique demonstrates less overall postoperative pain, discomfort, and complications combined with a remarkably low recurrence rate. The rapid rehabilitation with great patient comfort and decreased operating room time, resulting in lower financial costs, have led us nowadays to repair all types of inguinal hernias, femoral and recurrent ones, using this technique.

Inflammation, DNA damage, Helicobacter pylori and gastric tumorigenesis.

Helicobacter pylori (H. pylori) is a Gram negative bacterium that colonizes the stomach of almost half human population. It has evolved to escape immune surveillance, establishes lifelong inflammation, predisposing to genomic instability and DNA damage, notably double strand breaks. The epithelial host cell responds by activation of DNA damage repair (DDR) machinery that seems to be compromised by the infection. It is therefore now accepted that genetic damage is a major mechanism operating in cases of H. pylori induced carcinogenesis. Here, we review the data on the molecular pathways involved in DNA damage and DDR activation during H. pylori infection.

Acute Appendicitis: The Reliability of Diagnosis by Clinical Assessment Alone

Background and Aims: This prospective study aimed to review the trustworthiness of the initial clinical assessment in acute appendicitis without employment of imaging modalities, laparoscopy or any other adjunct diagnostic test. Patients and Methods: 717 patients were operated on for appendicitis by six different surgeons. Initial clinical and laboratory examination were evaluated in relation to the intraoperative and the pathological appreciation of the appendiceal inflammation. Results: 598 patients were found to have appendicitis, 34 a different condition, 41 had both appendicitis and an additional condition and 44 no pathology. 6% of the laparotomies and 11 % of the appendectomies were unnecessary. The severity of the inflammation correlated significantly with periumbilical pain, pain migrating to right lower quadrant, loss of appetite, fever, rebound tenderness, local rigidity, polymorphonuclear predominance on deferential, polymorhonucleosis and leukocytosis. Leukocytosis was less frequent in aged patients. All the six surgeons were found to be equally reliable, although they all underestimated the setting compared to the pathologists. Patients with a long duration of symptoms had milder forms of inflammation and increased percentage of unanticipated abdominal conditions. Conclusions: Appendicitis can be reliably diagnosed clinically without employment of adjunct tests. These can be reserved for equivocal cases.

Lymph node, peritoneal and bone marrow micrometastases in gastric cancer: Their clinical significance

The 7th TNM classification clearly states that micrometastases detected by morphological techniques (HE stain and immunohistochemistry) should always be reported and calculated in the staging of the disease (pN1mi or M1), while patients in whom micrometastases are detected by non-morphological techniques (e.g., flow cytometry, reverse-transcriptase polymerase chain reaction) should still be classified as N0 or M0. In gastric cancer patients, micrometastases have been detected in lymph nodes, the peritoneal cavity and bone marrow. However, the clinical implications and/or their prognostic significance are still a matter of debate. Current literature suggests that lymph node micrometastases should be encountered for the loco-regional staging of the disease, while skip lymph node micrometastases should also be encountered in the total number of infiltrated lymph nodes. Peritoneal fluid cytology examination should be obligatorily performed in pT3 or pT4 tumors. A positive cytology classifies gastric cancer patients as stage IV. Although a curative resection is not precluded, these patients face an overall dismal prognosis. Whether patients with a positive cytology should be treated similarly to patients with macroscopic peritoneal recurrence should be evaluated further. Gastric cancer cells are detected with high incidence in the bone marrow. However, the published results make comparison of data between groups almost impossible due to severe methodological problems. If these methodological problems are overcome in the future, specific target therapies may be designed for specific groups of patients.

Anesthetic management of a patient with tuberous sclerosis presenting for renal transplantation.

A 36-year-old woman (160 cm, 56 kg) with tuberous sclerosis, diagnosed 6 years previously, was scheduled for living-donor renal transplantation. The patient had suffered from chronic renal failure for 6 years; the renal parenchyma was replaced by bilateral angiomyolipomas. Four years previously, she underwent unilateral (left) nephrectomy because of massive hematuria and uncontrolled bleeding, but she did not require dialysis. Her blood urea nitrogen was 30mg·dl 1 (21 mmol·l 1) and her serum creatinine was 5.4mg·dl 1 (480 μmol·l 1). Three times during the past 15 years she had had spontaneous pneumothorax; the last time (10 years previously) she underwent right pleurodesis. After both surgical operations, she was admitted to the intensive care unit (ICU) for routine postoperative management. Her recovery after the nephrectomy was uneventful, and she returned to the ward on the second postoperative day. After the pleurodesis, her stay in the ICU was prolonged to 2 weeks because of a pulmonary infection. She suffered from petit mal seizures between the ages of 3 and 6 years but had no mental retardation. She was a regular smoker (10 packet-years). She was not under regular medical treatment and had no history of drug allergy. The nephrologists suggested that she should have one session of hemodialysis 12h before operation. Preoperative physical examination disclosed facial angiofibroma over the cheeks and nose and subungual fibromas and shagreen patch (leathery thickening patch) over the lumbosacral region. Her muscle tone and reflexes in all limbs were normal. Physical examination of the respiratory and cardiovascular system was

Clinical implications of the histologically and immunohistochemically detected solitary lymph node metastases in gastric cancer.

Background: Topographic correlation between the primary gastric tumor and the first peri- and extragastric lymphatic drain basin (solitary lymph node metastasis) on gastrectomy specimens, represents a reliable method to investigate and understand the exact pattern of lymphatic drainage from a gastric tumor. Analyzing that correlation, useful information regarding the extent of the appropriate oncological perigastric lymphadenectomy will be provided. We retrospectively evaluate the usefulness of a modified D2 lymphadenectomy in gastric cancer patients, based on the topographic correlation between the primary tumor and the location of the solitary lymph node metastases, as they were detected by histology and immunohistochemistry. Materials and Method: Between April 2003 and March 2010, 134 gastric cancer patients were submitted to a modified D2 lymphadenectomy. Postoperatively, the standard histological examination by hematoxylin and eosin (HE) staining, disclosed metastatic infiltration of at least two lymph nodes in 90 patients, solitary lymph node metastases were histologically detected in 10 patients, while the remaining 34 patients were classified as pN0. All lymph nodes of the ten patients with histological solitary lymph node metastases, as well as the 34 patients who had been classified as pN0 by histology, were further submitted to immunohistochemistry for micrometastases detection. More than one micrometastases were detected in none of them, while in seven patients solitary micrometastases were detected either in the level I perigastric or in the level II extragastric lymph nodes stations (skip micrometastases). Results: Solitary lymph node metastases were detected by histology in ten patients and by immunohistochemistry in additional seven (nine females and eight males). Solitary metastases were detected in the level I LN stations in seven patients (four by histology and three by immunohistochemistry) and in the level II LN stations in ten patients (six by histology and four by immunohistochemistry). In order of frequency, the solitary lymph node metastases were located in the no 7 (n = 6), no 6 (n = 4), no 9 (n = 2), no 5 (n = 2), no 4 (n = 1), no 8 (n = 1) and no 12 (n = 1) LN stations. Skip metastases encountered the 60% of the histologically detected, 57% of the immunohistochemically detected and 59% of all solitary lymph node metastases. 80% of solitary metastases in the level II LN stations, were mainly located in the nos 7–9 lymph node stations complex. Tumors of the lower and middle-third of the stomach were equally drained both to the level I and level II lymph node stations, while 67% of the tumors towards the lesser curvature, were mainly drained in the level II lymph node stations. Conclusion: D2 lymphadenectomy increases the number of true R0 resections. Thus, a modified D2 lymphadenectomy should be routinely performed in gastric cancer patients.

Spiral computerized tomography : a diagnostic aid in patients with atypical acute appendicitis

Abstract This retrospective study aimed to estimate the value of spiral Computerized Tomography (sCT) in patients with suspected appendicitis who remained undiagnosed after 48 hours of expectant management. We assessed a cohort of 150 patients by focused unenhanced sCT. According to the clinical scenario we occasionally employed contrast media and extended the scanned area. The major radiological signs were appendiceal enlargement and inflammatory changes of periappendiceal tissue and mesenteric fat. Regarding acute appendicitis the examination was 95,8% sensitive, 97,4% specific, had a positive predictive value of 97,18%, a negative predictive value of 96,2% and an accuracy of 96,7%. It also provided alternative diagnoses in 55 patients leading correctly 31 of them to the theatre for a variety of abdominal surgical diseases. For abdominal surgical pathology in general, sCT was 97,1% sensitive, 95,7% specific, had a positive predictive value of 98% and a negative predictive value of 93,8%. The importance of good communication between the clinicians and radiologists was pointed out by the correct alternative diagnoses set by imaging in the 55 patients after modifying the sCT protocol and was highlighted by the unnecessary appendectomy of three patients with negative imaging. Our results verify the accuracy and value of unenhanced sCT in patients with a clinical picture which remains inconclusive after an initial period of expectant management.