Clinicopathologic Features and Prognostic Significance of Immunohistochemistry and In Situ Hybridization Based Molecular Classification in Gastric Carcinoma.

BACKGROUND/AIM: Gastric carcinoma (GC) is a highly heterogeneous disease with many subtypes that have different morphologic and molecular characteristics. In the current study, we analyzed immunohistochemical (IHC) and in situ hybridization (ISH) features of GCs and evaluated their association with prognosis and clinicopathological features. MATERIALS AND METHODS: Three hundred cases analyzed by IHC and ISH for microsatellite stability, p53, e-cadherin, HER2, PD-L1 expression, and Epstein-Barr virus (EBV) status. Cases were classified into five subgroups based on expression profile. The relationships between subgroups, clinicopathological features, and survival were determined. RESULTS: Ten (3.3%) cases were classified as EBV-associated, 45 (15%) as microsatellite instable (MSI), 73 (24.3%) as EBV-/microsatellite-stable (MSS)/epithelial-mesenchymal-transformation (EMT)-like, 75 (25%) as EBV-/MSS/ non-EMT-like/p53+, and 97 (32.3%) as EBV-/MSS/non-EMT-like/p53-. The MSI subtype had the best overall survival (OS). In contrast, the EBV-/MSS/EMT-like subtype had the poorest OS. The MSI subtype was also related with old age of the patient and antrum-corpus localized tumors, whereas the EBV-/MSS/EMT-like was associated with young age, larger tumor size, and advanced stage presentation. PD-L1 positivity is highly correlated with MSI and EBV-associated subtypes. CONCLUSION: Our data demonstrated a link between IHC/ISH characteristics of GC and clinical outcomes. IHC/ISH based molecular classification may be helpful in predicting the survival.

Helicobacter Pylori Colonization Density is an Important Risk Factor for Eradication Therapy.

BACKGROUND AND AIMS: Despite the known risk factors, it is not clear why the same treatment protocol for Helicobacter pylori infection (H. pylori) doesnot show a similar effect in patients with common risk factors. We hypothesized that as the severity of H. pylori - induced gastric mucosa inflammation and density increase, the rate of successful treatment decreases. This study aimed to explore the existence of a possible association between gastric H. pylori colonization density and the efficacy of bismuth-containing quadruple eradication therapy. METHODS: A total of 330 patients with H. pylori positive gastritis were initially included; the diagnosis was based on the histopathological examination. H. pylori colonization density was graded according to the Sydney classification: mild (n=101), moderate (104) and severe (98). H. pylori eradication was determined via the 13C-Urea breath test performed eight weeks after therapy. RESULTS: There was no significant difference in terms of the distributions of age, gender, alcohol consumption, and smoking status among the groups (p>0.05). The successful eradication rates of H. pylori were 87.1%, 78.8%, and 75.5%, respectively, for the mild, moderate, and severe H. pylori colonization groups by per-protocol analysis (p=0.038). The eradication rates of H. pylori were 81.5%, 73.2%, and 67.3% respectively, for the mild, moderate, and severe H. pylori colonization groups by intention-to-treat analysis (p=0.017). CONCLUSIONS: Helicobacter pylori colonization severity might predict the usefulness of eradication therapy in pre-treatment assessment. We recommend the use of more effective therapy regimens for H. pylori eradication in patients with severe densities.

Efficacy of a novel sequential treatment regimen containing bismuth for Helicobacter pylori eradication in Turkish children.

BACKGROUND: Eradication rates of Helicobacter pylori (H pylori) with standard triple therapy are gradually decreasing all over the world, including in children, due to the development of strains resistant to antimicrobials. Sequential therapy can be used as an alternative method to increase eradication rates. MATERIALS AND METHODS: A total of 75 patients ≥ 8 years of age with H pylori gastritis were included in the study. According to Rome IV criteria, 38 patients had functional abdominal pain and dyspepsia, and 37 patients had alarm findings suggesting organic disease. Patients were treated with a novel sequential therapy consisting of the proton pump inhibitor (PPI)-lansoprazole (1 mg/kg/day, maximum 30 mg daily), amoxicillin (50 mg/kg/d in two doses, maximum 2 × 1000 mg) for 7 days followed by PPI-lansoprazole (1 mg/kg/d, maximum 30 mg daily), metronidazole (20 mg/kg/day in two doses, maximum 2 x 500 mg), tetracycline (50 mg/kg/d divided into four equal doses, maximum 4 x 500 mg), and bismuth subsalicylate (262 mg QID in patients ≤ 10 years of age, 524 mg QID in patients > 10 years of age in days 8-14). Eradication status was evaluated by H pylori stool antigen test 8 weeks after the completion of treatment. RESULTS: The mean age of the patients was 15.1 ± 2.4 years and 51 (68%) were female. No patient discontinued therapy due to side effects. All patients had antral gastritis (76.0%) or pangastritis (24.0%). The peptic ulcer rate was 6.6%. Eradication therapy was given to all patients with or without peptic ulcer. H pylori eradication was achieved in 69 (92.0%) patients and symptoms improved in 61 of those eradicated. CONCLUSIONS: As a first-line treatment for H pylori eradication in children, administering a novel sequential therapy including bismuth for 14 days provides a high rate of eradication.

Type 4 hypersensitivity development in a case due to mifamurtide.

BACKGROUND: This report aims to discuss the mechanism of pleural and pericardial effusion related to mifamurtide which is an immunological agent used as adjuvant chemotherapy in osteosarcoma. CASE: Mifamurtide (2 mg/m < sup > 2 < /sup > ) and European and American Osteosarcoma Studies (EURAMOS) protocol were used together intravenously after complete surgical resection. No side effects occurred except for fever after the first dose. However, pleural, pericardial effusion, and splenic nodule formation began 11 months after discontinuation of mifamurtide treatment. Pleural biopsy revealed a type 4 hypersensitivity reaction. We treated the patient with 1,5 mg per day colchicine. Pericardial effusion attacks and nodules in the spleen disappeared. The patient had a mild pleural effusion attack which has not yet repeated. CONCLUSION: Mifamurtide, which activates macrophages, can also activate immunity with a stand by effect and cause a hypersensitivity reaction.

In Vivo Comparison of "V-Loc 90 Wound Closure Device" With "Vicryl" and "Monocryl" in Regard to Tissue Reaction in a Rabbit Bladder Model.

OBJECTIVE: To compare the barbed polyglyconate suture (BPS) with 2 commonly used conventional sutures, this prospective randomized trial was designed. The sutures applied in the urinary collecting system, in terms of long-term histopathologic and macroscopic suture material features. MATERIALS AND METHODS: Eight female and 6 male New Zealand rabbits were included in the study. Each animal served as its own control and was subjected to cystotomy. Watertight running cystorrhaphies were performed using 3 different sutures in a randomized fashion, namely Monocryl, Vicryl, and V-Loc 90. Seven animals were sacrificed after the third and 7 after the sixth week. Macroscopic and histopathologic examinations were performed. Tissue reaction, like inflammation and fibrosis, around the sutures were evaluated. Friedman and Wilcoxon signed ranks test was used for the statistical analysis. RESULTS: The BPS demonstrated no adhesion. However, in the six-week group, stone formation was recorded on 4 BPS and 1 Vicryl thread, a difference being statistically significant (P = .039). Additionally, in the third- and in the sixth-week group, 1 (P = .368) and 3 (P = .050) BPS threads migrated, respectively. The histopathologic analysis revealed less inflammation and fibrosis associated with the BPS thread in both the third and the sixth-week groups (P = .010 and P = .002, respectively). CONCLUSION: The BPS appears to be superior to conventional sutures in terms of local inflammation and fibrosis. However, suture migration and stone formation following collecting system closure could be potential predicaments.

A Retrospective Evaluation of the Epithelial Changes/Lesions and Neoplasms of the Gallbladder in Turkey and a Review of the Existing Sampling Methods: A Multicentre Study.

OBJECTIVE: As there is continuing disagreement among the observers on the differential diagnosis between the epithelial changes/lesions and neoplasms of the gallbladder, this multicentre study was planned in order to assess the rate of the epithelial gallbladder lesions in Turkey and to propose microscopy and macroscopy protocols. MATERIAL AND METHOD: With the participation of 22 institutions around Turkey that were included in the Hepato-Pancreato-Biliary Study Group, 89,324 cholecystectomy specimens sampled from 2003 to 2016 were retrospectively evaluated. The numbers of adenocarcinomas, dysplasias, intracholecystic neoplasms/adenomas, intestinal metaplasias and reactive atypia were identified with the review of pathology reports and the regional and countrywide incidence rates were presented in percentages. RESULTS: Epithelial changes/lesions were reported in 6% of cholecystectomy materials. Of these epithelial lesions, 7% were reported as adenocarcinoma, 0.9% as high-grade dysplasia, 4% as low-grade dysplasia, 7.8% as reactive/regenerative atypia, 1.7% as neoplastic polyp, and 15.6% as intestinal metaplasia. The remaining lesions (63%) primarily included non-neoplastic polypoids/hyperplastic lesions and antral/pyloric metaplasia. There were also differences between pathology laboratories. CONCLUSION: The major causes of the difference in reporting these epithelial changes/lesions and neoplasms include the differences related to the institute's oncological surgery frequency, sampling protocols, geographical dissimilarities, and differences in the diagnoses/interpretations of the pathologists. It seems that the diagnosis may change if new sections are taken from the specimen when any epithelial abnormality is seen during microscopic examination of the cholecystectomy materials.

Prevention of Intraabdominal Adhesions: An Experimental Study Using Mitomycin-C and 4% Icodextrin.

BACKGROUND: Intraabdominal adhesions remain a significant cause of morbidity and mortality. Moreover, intraabdominal adhesions can develop in more than 50% of abdominal operations. AIMS: We compared the anti-adhesive effects of two different agents on postoperative adhesion formation in a cecal abrasion model. STUDY DESIGN: Experimental animal study. METHODS: Forty Wistar albino type female rats were anesthetized and underwent laparotomy. Study groups comprised Sham, Control, Mitomycin-C, 4% Icodextrin, and Mitomycin-C +4% Icodextrin groups. Macroscopic and histopathological evaluations of adhesions were performed. RESULTS: The frequencies of moderate and severe adhesions were significantly higher in the control group than the other groups. The mitomycin-C and Mitomycin-C +4% Icodextrin groups were associated with significantly lower adhesion scores compared to the control group and 4% Icodextrin group scores (p=0.002 and p=0.008, respectively). The adhesion scores of the Mitomycin-C group were also significantly lower than those of the 4% Icodextrin group (p=0.008). CONCLUSION: Despite its potential for bone marrow toxicity, Mitomycin-C seems to effectively prevent adhesions. Further studies that prove an acceptable safety profile relating to this promising anti-adhesive agent are required before moving into clinical trials.

Can Human Recombinant Epidermal Growth Factor Improve Ischemia and Induce Healing of Anastomosis in an Experimental Study in a Rabbit Model?

PURPOSE: Anastomotic leaks following intestinal operations may cause devastating effects on patients. Ischemia may also occur at the intestinal walls in the presence of strangulations. In this study, we examined the effects of human recombinant (Hr)-epidermal growth factor (EGF) given at a single intramural dose into the intestinal walls and daily intraperitoneal cavity on ischemia and the healing process of anastomosis. MATERIALS AND METHODS: Sixteen male New Zeland white rabbits were randomly divided into four groups (n = 4 in each group). In Group 1, two different segments of ileum were identified and, then, transected and the free ends were sutured each other. In the other groups, ischemia was induced by ligating the mesenteric vascular arcade. After the ischemic induction, Group 2 received intramural injections of %0.9 saline, Group 3 received intramural injections of a single dose of EGF, and Group 4 received intramural and intraperitoneal injections of EGF. Bursting pressures and tissue hydroxyproline levels were analyzed. Necrosis, fibroblastic activity, collagen deposition and neovascularization were also studied. RESULTS: The mean levels of bursting pressures in Group 4 (148.6 ± 25.3 mmHg) were higher than Group 2 (70 ± 21.5 mmHg) (p = 0.001). The mean level of bursting pressures was not statistically significant between Group 1 (170.1 ± 35 mmHg) and Group 4 (p = 0.073). Hydroxyproline levels in Group 2 were lower than Groups 3 and 4. There was a statistically significant difference in the mucosal ischemia, mucosal healing and degree of adhesion, but not in the mural anastomotic healing among the groups. CONCLUSIONS: Intramural injection with daily intraperitoneal administration of low-dose EGF enhances the bursting pressure and collagen accumulation in ischemic anastomosis, improving many histological variables associated with ischemic intestinal anastomosis.

Sutureless microvascular anastomosis with the aid of heparin loaded poloxamer 407.

BACKGROUND: Anastomosis with tissue adhesives is an alternative method for conventional anastomosis. However, this method has several technical challenges. It requires the use of suture to prevent leakage into lumen and precise application onto all surfaces of the anastomosis site. To solve these problems, poloxamer 407 (P 407) was previously used as a stent. In this study, we made heparinized P 407 (h-P 407) as a new formula. We aimed to successfully use h-P 407 as a stent in sutureless anastomosis in a rat abdominal aorta model. METHODS: Sixty Sprague-Dawley rats were used. In the first group, end-to-end anastomoses were performed with suture; in the second and third groups, sutureless anastomoses were performed with 2-octyl cyanoacrylate. As an intraluminal stent, P 407 was used in the second group, and h-P 407 was used in the third group. Anastomosis time was measured. Lumen width, intimal hyperplasia, and foreign body reaction were assessed histologically. Velocity flow rates and vessel diameters were measured radiologically. Burst strength was measured, and the results were statistically evaluated. RESULTS: Sutureless anastomosis was more rapid than conventional anastomosis. Lumen width was narrower in the suture group. Inflammation and foreign body reaction were more severe in the suture group. There was no radiologic and biomechanical difference between the groups. We found that intimal hyperplasia was less in h-P 407 than in P 407. CONCLUSION: h-P407 can be successfully used as an intraluminal stent for sutureless microvascular anastomosis with tissue adhesives.

Role of alkaline phosphatase intestine-isomerase in acute mesenteric ischemia diagnosis.

BACKGROUND: The aim of the present study was to investigate the diagnostic value of alkaline phosphatase (ALP) intestine-isomerase, plasma lactate dehydrogenase (LDH), and D-dimer levels in acute mesenteric ischemia. METHODS: Thirty Wistar rats were divided into 5 groups of 6 rats each. In Group 1, blood samples were obtained to determine normal parameter levels. In the sham group, Group 2, blood samples were obtained following laparotomy. In Group 3, blood samples were obtained 2 hours after ligation. In Groups 4 and 5, blood samples were obtained at 4 and 6 hours after ligation, respectively. Ischemic damage was assessed using a pathological scoring system. Blood samples were analyzed for hourly changes in parameters. RESULTS: No statistically significant difference in D-dimer levels was found between ischemia groups (p=0.337). A statistically significant difference in LDH levels was found between the control group, Group 1, and Group 4 (p=0.018). ALP intestine-isomerase enzyme levels were not statistically significant in other groups (p=0.077). CONCLUSION: Findings indicate that plasma LDH levels higher than 1900 IU/L may be a useful marker in the early diagnosis of acute mesenteric obstruction. However, ALP intestine-isomerase enzyme and D-dimer plasma levels were not found to contribute to the diagnosis.

Distinctive immunostaining of claudin-4 in spiradenomas.

The intercellular bridges are essential structures in maintaining the histologic organization of the epithelium, while providing a very efficient way to exchange molecules between cells and transduction of the cell-to-cell and matrix-to-cell signals. Derangement in those important structures' physical integrity and/or function, which can be assessed by the presence or absence of several intercellular bridge proteins including claudin-4, E-cadherin, and ß-catenin, was found to be related to several phenomena in the path to the neoplastic transformation. However, these proteins have not been studied in the wide variety of the skin neoplasms, in detail. Herein, we immunohistochemically assessed the expression patterns of these 3 intercellular bridge proteins on a total of 86 epidermal and eccrine adnexal tumors including basal cell carcinoma, squamous cell carcinoma, poroma, spiradenoma, syringoma, and hidradenoma. We observed a selective and distinct claudin-4 expression in the ductal-type cells of all cases of spiradenomas. Similarly, in the poromas, syringomas, and hidradenomas, claudin-4 was only positive in the luminal cells of microcystic structures, although not as conspicuous as in the spiradenomas. On the other hand, E-cadherin and ß-catenin were positive in almost all types of the tumors, in a way which was not contributory to differentiate from each other. In conclusion, we think that claudin-4 can be helpful at least in making a reliable differential diagnosis of spiradenoma when overlapping morphologic features do not allow to further subclassification in the overwhelming variety of the adnexal tumors.

Indications for eye removal surgeries. A 15-year experience at a tertiary military hospital.

OBJECTIVES: To analyze the indications and types of eye removals at a military tertiary care hospital in Turkey. METHODS: The medical records (age, gender, affected eye, type of surgical procedure, indications of surgery) of 123 patients who underwent evisceration and enucleation in the course of a 15-year period (January 2000 to December 2014) at Gulhane Military Medical Academy, Ankara, Turkey were reviewed retrospectively. RESULTS: The mean age was 35.61±18.52 (range 3-80 years). The number of male in the patient group was 92 (74.8%) and female was 31 (25.2%). Patients who underwent evisceration were 95 (77.2%), whereas 28 (22.8%) of them underwent enucleation. The mean age of the eviscerated patients was 30.63±13.08, whereas the mean age of the enucleated patients was 52.50±23.92 (p less than 0.001). The leading indications for eye amputations were trauma (n=62, 50.4%), malignancy (n=20, 16.3%), painful blind eye and absolute glaucoma (n=20, 16.3%), endophthalmitis (n=12, 9.7%), and phthisis bulbi, and cosmetic reasons (n=9, 7.3%). CONCLUSION: Trauma was the most common etiology for evisceration, and malignancy was the most common etiology for enucleation. Using protective eyewear and early detection of intraocular malignancy and glaucoma through routine ophthalmic examinations are essential for providing non-invasive treatment modalities instead of eye removal.

Pituitary macroadenomas (>3 cm) in young adulthood: Pathologic and proliferative characteristics.

BACKGROUND: There are scarce data regarding the significance of the tumor size, hormonal activity and size of the pituitary tumor of the young; therefore, the study was designed to define the relation of the hormonal status of the large pituitary adenomas. OBJECTIVE: We compared those features with tumors of the elderly (>40) with the young patients, and analyzed the clinicopathologic and proliferative features of pituitary macroadenomas in young adulthood (≤40). METHODS: 20-year archives of pituitary tumors in our clinics were reviewed and macroadenomas with diameter≥3 cm were included in the study. We identified 46 pituitary adenomas and immunohistochemically stained them with pituitary hormones, p53 and Ki-67. Twenty-four cases were ≤40-year with an age range of 11-40 years (mean 28.0). Twenty-two cases were >40 with an age range of 44-78 years (mean 58.8). RESULTS: In the young patient group, 15 (62.5%) were functional adenomas (6 prolactinomas, six growth hormone [GH], one adrenocorticotrophic hormone [ACTH] adenoma, two multihormonal [GH+ACTH]) and nine (37.5%) were either gonadotrophic or null cell adenomas. In the elderly group, five (22.7%) were functional adenomas (two adrenocorticotrophic hormone [ACTH] adenoma, one prolactinoma, one growth hormone [GH], one multihormonal [GH+ACTH]) and 17 (77.3%) were either gonadotrophic or null cell adenomas. Ki-67 proliferation index in adenomas of the young was approximately two-folds higher than the elderly (2.7% vs. 1.2%). CONCLUSION: In both groups, rare p53 positivity was identified. In conclusion, pituitary macroadenomas of the young show hormonal expression frequently with relatively high Ki-67 proliferation indices.

An animal model (guinea pig) of ocular siderosis: histopathology, pharmacology, and electrophysiology.

PURPOSE: Ocular siderosis is a rare sight-threatening complication that occurs after a penetrating ocular injury by an iron-containing foreign body. The purposes of this study were to (i) investigate the histopathology, electrophysiology and iron levels/accumulation in ocular siderosis using an animal (Guinea pig) model and (ii) determine the appropriate timing for follow-up foreign body-removal surgery. MATERIALS AND METHODS: Thirty guinea pigs were divided into five groups (n = 6 animals/group). On day-1, an iron body was inserted into the vitreous of the right eye of all animals; the left eyes were left undisturbed and were used as controls. At the end of each week during the 5-week study period, electroretinography (ERG) was performed on all animals in one of the five groups. Each animal in that group was sacrificed, after which both eyes were enucleated for histopathological and pharmacological evaluation of intraocular iron. RESULTS: Accumulated iron levels of study eyes were significantly higher than those of control eyes (135.13 and 13.55 µg/g, respectively, p < 0.01). In addition, there was a significant decrease in electrophysiological responses of study eyes. During the first week, iron levels were higher in study eyes than control eyes, but neither histological iron accumulation nor decreased electrophysiological responses could be detected. By the end of the second week, increased iron accumulation was observed histologically in intraocular tissues, along with signs of retinal toxicity, as verified by decreased electrophysiological responses. CONCLUSIONS: The present study indicates that the 14th day after a penetrating eye injury by an iron-containing intraocular foreign body represents a clinically critical threshold, after which structural damage to and functional alterations in ocular tissues occur.

The effect of combined use of platelet-rich plasma and adipose-derived stem cells on fat graft survival.

BACKGROUND: Free fat grafts have an unpredictable survival rate that limits their successful use. To increase the viability of fat grafts, it is important to minimize the reabsorption rate. OBJECTIVE: Our aim was to investigate whether the combined use of platelet-rich plasma (PRP) and adipose derived stem cells (ADSCs) would contribute an improvement in lower resorption rates of fat grafts. METHODS: Inbred Fischer 344 rats were randomized into 4 groups (n = 10). Fat grafts were mixed with Dulbecco modified Eagle medium in group A, with PRP in group B, with ADSC in group C, and with PRP + ADSC in group D and were injected to the scalp.In vitro growth factor (vascular endothelial growth factor, transforming growth factor-ß, and fibroblast growth factor) levels were compared using enzyme-linked immunoassay method. After 12 weeks weight, volume and histology of the transplants were evaluated. RESULTS: The mean weight and volume of the fat grafts were highest in group D. Histopathological investigations revealed that the number of viable adipocytes and blood vessels were highest in group D. The level of growth factors was significantly higher in stem cell plus PRP group. CONCLUSION: Adipose-derived stem cells combined with PRP can enhance the survival of transplanted fat tissue.

A comparison of intravitreal bevacizumab and steroid activity in an experimental uveitis model.

PURPOSE: To compare intravitreal bevacizumab (IVB) and steroid activity in an experimental uveitis (EU) model. MATERIALS AND METHODS: EU was induced by intravitreal injection of bovine serum albumin (BSA) at baseline. Rabbits were randomly divided into three groups (n = 8) according to treatment with a single dose of IVB, steroid or saline on day 3. Aqueous humor (AH) samples were collected periodically (baseline and days 1, 3, 10 and 33). Rabbits were sacrified and eyes were enucleated for histopathology on day 33. AH vascular endothelial growth factor (VEGF) levels and histopathological changes were subjected to statistical analysis. RESULTS: VEGF levels increased significantly after BSA injection (day 1) when compared with baseline in all three groups. Mean VEGF levels were 794.46 pg/mL, 777.91 pg/mL and 872 pg/mL for IVB, steroid and control groups, respectively (p = 0.002, p = 0.019 and p = 0.014). Seven days after treatment (day 10), VEGF levels decreased significantly in both treatment groups. Mean VEGF levels were 0 pg/mL, 292 pg/mL and 872 pg/mL, repectively (p < 0.001, p = 0.016 and p = 0.12). On day 33, the VEGF levels and inflammation had returned to baseline levels in both treatment groups, whereas no decrease in inflammation was observed in the control group. The histopathological evaluation revealed a mild congestion in ciliary tissue with a normal retina and choroidea in IVB group, a mild congestion in ciliary tissue with moderate inflammation in the posterior vitreus and a normal retina in steroid group and a severe inflammation in ciliary tissue with moderate inflammation in the retina in control group. CONCLUSIONS: These findings suggest that IVB may be used as an alternative to steroid treatment to reduce the acute effects of inflammation in patients with uveitis in whom intraocular steroids are contraindicated.

The Effects of Total Colectomy on Bacterial Translocation in a Model of Acute Pancreatitis.

Prevention of secondary infection is currently the main goal of treatment for acute necrotizing pancreatitis. Colon was considered as the main origin of secondary infection. Our aim was to investigate whether prophylactic total colectomy would reduce the rate of bacterial translocation and infection of pancreatic necrosis. Forty-two Sprague-Dawley rats were used. Pancreatitis was created by ductal infusion of sodium taurocholate. Rats were divided into four groups: group-1, laparotomy + pancreatic ductal infusion of saline; group-2, laparotomy + pancreatic ductal infusion of sodium taurocholate; group-3, total colectomy + pancreatic ductal infusion of saline; and group-4, total colectomy + pancreatic ductal infusion of sodium taurocholate. Forty-eight hours later, tissue and blood samples were collected for microbiological and histopathological analysis. Total colectomy caused small bowel bacterial overgrowth with gram-negative and gram-positive microorganisms. Bacterial count of gram-negative rods in the small intestine and pancreatic tissue in rats with colectomy and acute pancreatitis were significantly higher than in rats with acute pancreatitis only (group-2 versus group-4; small bowel, p = <0.001; pancreas, p = 0.002). Significant correlation was found between proximal small bowel bacterial overgrowth and pancreatic infection (r = 0,836, p = 0.001). In acute pancreatitis, prophylactic total colectomy (which can mimic colonic cleansing and reduction of colonic flora) induces small bowel bacterial overgrowth, which is associated with increased bacterial translocation to the pancreas.

The effect of relaparotomy timing on wound healing in an animal model.

BACKGROUND: The effect of the timing of the second laparotomy on wound healing is not clear. In an experimental study in rats, we aimed to investigate the effect of timing on wound healing after reoperations on the same surgical site. MATERIAL AND METHODS: Forty-eight rats were divided into four groups. The control group (GC) didn't have another laparotomy whereas the relaparotomies on the same surgical site were performed either on the 3rd, 15th or the 30th postoperative days in the three study groups (G3, G15, G30 respectively). The midline tension pressure, collagen types I, III and, histological analysis were performed from the specimens in order to assess the wound healing and strength. RESULTS: The tensile strength was the highest in GC and decreased gradually in G3, G15 and G30, the difference between the groups did not reach statistical significance. Higher collagen levels, increased fibrosis, and large defects were observed in relaparotomy groups than CG. The musculoaponeurotic gap was shortest in GC when compared to other three relaparotomy groups (P < 0.001) and, it was the longest in G30 (P = 0.004 between G3 and G30). CONCLUSIONS: Although non-statistically significant the gradual decrease in the tensile strength and the statistically significant increase in the musculoaponeurotic gap with time point out the importance of the timing of relaparotomy in the healing process. Early relaparotomies do not disrupt the healing process as much as relaparotomy performed later.

Telomere 1 (POT1) gene expression and its association with telomerase activity in colorectal tumor samples with different pathological features.

The ends of chromosoms, telomeres are bound with a number of proteins which protect and stabilize telomeres against degredation, end to end fusion and aberrant recombinations. Telomeric DNA is bound of two groups of proteins, which are double-stranded telomeric DNA bindings proteins, and single stranded telomeric binding proteins. Among telomere binding proteins, protections of telomere 1 protein is a single stranded telomere binding proteins and suggested to be a significant player for telomere elongation and has an association with an enzyme called as telomerase which is an intrinsic reverse transcriptase. Telomerase synthesizes hexameric telomeric repeats onto the chromosomes thereby compansating telomere loss in immortal cells, such as tumor cells, whereas telomeres are shorthened with each division in normal cells. PCR-based TRAP (telomeric repeat amplification protocol) assay is a very sensitive assay for the detection of enzymatic activity of telomerase even if a few numbers of cancerous cells are available. The association between telomerase activity and hPOT1 expression in colorectal cancer is still unclear. Protein extraction was performed from specimens of matched normal and colorectal cancer specimens. Protein concentrations were determined by Bradford assay. Optimized protein concentrations were used for TRAP Assay. TRAP products were seperated by vertical gel electrophoresis on 12.5% polyacrylamide gels and visualized by silver staining. Gene expression of hPOT1 was determined by qPCR analysis. The results demonstrated that all tumor tissues were telomerase positive whereas all corresponding normal tissue was telomerase negative. Among clinicopathological findings, telomerase activity was found to be associated with stage, histology, localization, distant metastasis and lymph node metastasis of tumor in the current study. Although all of the clinicopathological findings differed in the expression of hPOT1 compared to normal tissues, they did not differ from each other significantly, except side of tumor and lymph node metastasis. Telomerase activity and hPOT1 gene expression may serve as a promising tumor marker for colorectal cancer and there is a close association between the enzymatic activty of telomerase and the expression of human protection of telomere 1 gene.

The efficacy of mesenchymal stem cell transplantation in caustic esophagus injury: an experimental study.

Introduction. Ingestion of corrosive substances may lead to stricture formation in esophagus as a late complication. Full thickness injury seems to exterminate tissue stem cells of esophagus. Mesenchymal stem cells (MSCs) can differentiate into specific cell lineages and have the capacity of homing in sites of injury. Aim and Methods. We aimed to investigate the efficacy of MSC transplantation, on prevention of esophageal damage and stricture formation after caustic esophagus injury in rats. 54 rats were allocated into four groups; 4 rats were sacrificed for MSC production. Group 1, untreated controls (n: 10). Group 2, membrane labeled MSCs-treated rats (n: 20). Group 3, biodistribution of fluorodeoxyglucose labeled MSCs via positron emission tomography (PET) imaging (n: 10). Group 4, sham operated (n: 10). Standard caustic esophageal burns were created and MSCs were transplanted 24 hours after. All rats were sacrificed at the 21st days. Results. PET scan images revealed the homing behavior of MSCs to the injury site. The histopathology damage score was not significantly different from controls. However, we demonstrated Dil labeled epithelial and muscle cells which were originating from transplanted MSCs. Conclusion. MSC transplantation after caustic esophageal injury may be a helpful treatment modality; however, probably repeated infusions are needed.