"Watch and wait" approach in rectal cancer patients following complete clinical response to neoadjuvant chemoradiotherapy does not compromise oncologic outcomes.

BACKGROUND/AIMS: Although standart treatment for non-metastatic locally advanced rectal cancer includes neoadjuvant chemoradiation followed by surgical resection, patients who have achieved complete clinical response can be followed up without surgery. MATERIALS AND METHODS: Between 2010 and 2016, 61 patients received neoadjuvant chemoradiotherapy for low rectal cancer. Those patients who achieved clinical complete response were included in the "watch and wait" protocol and did not receive surgery. The remaining patients underwent radical surgery and some of these were diagnosed as having complete response pathologically. This study compared the oncological results of clinically complete responders with those patients defined as pathologically tumor-free. RESULTS: Seven patients who received neoadjuvant chemoradiotherapy were re-staged as having complete clinical response and included in the "watch and wait" approach protocol. The 5-year disease free survival was 100%. Mean follow-up was 63 months and the mean age was 57.3. Fifty-four patients underwent radical surgery and 7 of them were diagnosed as having pathological complete response. The 5-year survival was 100%. Mean follow-up was 56 months and the mean age was 50.6. All patients except one are alive without tumor recurrence in the surgery group. However, those who received surgery experienced significant morbidities due to their surgery. CONCLUSION: The oncological results of the "watch and wait" approach patients were no different from the patients who received radical surgery and were diagnosed as having pathological complete response. Those patients in particular who required abdomino-perineal resection before chemoradiation should be informed about this approach if they have achieved complete response clinically.

Extralevator abdominoperineal excision versus conventional surgery for low rectal cancer: a single surgeon experience.

OBJECTIVE: Extralevator abdominoperineal excision (ELAPE) reduces the risk of positive circumferential resection margin (CRM) and of intraoperative perforation (IOP), both of which are associated with high local recurrence rates and poor survival outcomes for rectal cancer. The aim of this study was to compare the results of ELAPE with conventional abdominoperineal excision (APE) for low rectal cancer. MATERIAL AND METHODS: A total of 25 consecutive patients underwent ELAPE for low rectal cancer between November 2008 and September 2011. Fifty-six patients treated by conventional APE prior to 2008 were selected from our rectal cancer database for comparison as a historical cohort. RESULTS: The mean follow-up was 44.7 months in the ELAPE group, and 70.6 months in the APE group. Patients undergoing ELAPE had a lower CRM positivity and IOP rate than APE (12% vs. 20%, p=0,531; 4% vs. 8,9%, p=0,826; respectively). The ELAPE group was associated with higher perineal wound complications than the APE group (16.0% vs. 1.8%, p=0.030). Local recurrence rates for patients in both groups did not differ significantly (4.0% vs. 3.6%, p=1.0). CONCLUSION: The results of this study suggest that ELAPE technique was associated with less CRM involvement and reduced rates of IOP but markedly higher rates of postoperative perineal complications occurred as compared to conventional surgery. ELAPE must be reserved for advanced low rectal cancers.

Rate and Predictors of Endoscopic Mucosal Healing in Biologic Naive Patients with Inflammatory Bowel Disease by Azathioprine Treatment: A Real World, 10 Years' Experience from a Single Centre in Turkey.

BACKGROUND: There is increasing evidence that endoscopic mucosal healing (EMH) is a key target in inflammatory bowel disease (IBD) therapy. However, there is limited evidence of EMH rates with conventional IBD therapy outside of Western population groups. AIM: To evaluate the role of azathioprine (AZA) in inducing EMH in IBD patients. METHODS: Patients with inflammatory bowel disease were evaluated in terms of endoscopic mucosal healing and the incidence of surgical interventions during the azathioprine treatment between 1995 to 2014. RESULTS: A total of 120 inflammatory bowel disease patients were enrolled. Endoscopic mucosal healing was found in 37% patients with inflammatory bowel disease (42% in chronic ulcerative colitis and 33% in Crohn's disease). Male gender had a negative impact on the efficacy of azathioprine (P<0.05). Responder inflammatory bowel disease patients were older (age at the IBD diagnose) than the nonresponder (P<0.05). Azathioprine therapy reduced the number of the surgical interventions (P<0.05). CONCLUSION: We showed that azathioprine therapy significantly induced endoscopic mucosal healing in biologic naïve patients with active inflammatory bowel disease as well as decreasing the surgical interventions, with negative predictive factors identified by a younger age at IBD presentation and male gender.

Effects of enteral nutritional support on malnourished patients with inflammatory bowel disease by subjective global assessment.

BACKGROUND/AIMS: To investigate the prevalence of malnutrition in patients with inflammatory bowel disease (IBD) by subjective global assessment (SGA) and the effects of oral nutritional support on the clinical parameters, consumption of energy, macronutrients and fiber intake in the Study and Control groups, prospectively. MATERIALS AND METHODS: A total of 38 (28 Male; 10 Female) hospitalized patients with moderate or severe IBD (13 with Crohn's disease (CD); 25 with Ulcerative colitis (UC)) were included. At stage 1, the disease severity, clinical symptoms and, signs, food consumption and nutritional status by using subjective global assessment (SGA) were recorded. At stage 2, the patients were blindly randomized into a Study Group and Controls. In the Study Group, a standard enteral product was added into the regulated hospital diets, but for the Controls, deficits were regulated by only hospital diets for 3 weeks. the independent variables were the group, the disease and its activity, age, Body body mass index (BMI), weight loss history, the hospitalization period; the dependent variables were SGA, bowel movements, change in nutritional status, disease severity, clinical findings, and also consumption of macronutrients. RESULTS: Prevalance of malnutrition (SGA-B or SGA-C) for all the patients was 92.1% at the beginning and 71.1% at the end of study. Improvements in disease activity score for the patients with UC were statistically significant in both the Study Group and the Controls (p=0.006 for the Study Group and p=0.001 for the Controls, respectively). Macronutrients, total and water soluble fiber consumption levels improved, with statistically significant differences for all the groups. CONCLUSION: The prevalence of malnutrition is a major problem in patients with IBD. Not only the regulation of hospital food, but also enteral nutritional support, improved their levels of malnutrition, as well as their energy, macronutrients, and fiber consumption, and SGA is an easy method for nutritional monitoring.

Cytogenetic damage in Turkish coke oven workers exposed to polycyclic aromatic hydrocarbons: Association with CYP1A1, CYP1B1, EPHX1, GSTM1, GSTT1, and GSTP1 gene polymorphisms.

The aim of this study was to determine the frequencies of chromosomal aberrations (CA) and cytochalasin-blocked micronuclei (CBMN) in peripheral blood lymphocytes from Turkish coke oven workers and the influence of CYP1A1, CYP1B1, EPHX1, GSTM1, GSTT1, and GSTP1 gene polymorphisms on these biomarkers. Cytogenetic analysis showed that occupational exposure significantly increased the CA and CBMN frequencies. Gene polymorphisms, on the other hand, did not affect CA or CBMN in either exposed or control subjects. However, due to the limited sample size, our findings need to be verified in future studies with a larger sample.

Antithrombin prevents apoptosis by regulating inflammation in the liver in a model of cold ischemia/warm reperfusion injury.

BACKGROUND/AIMS: Hepatic ischemia-reperfusion injury is a major problem in liver surgery. To modulate the complex process of inflammation, additional drugs to add to well-defined organ preserving solutions have been sought. The aim of the current study was to investigate the additive potential of antithrombin (AT) in liver preservation. METHODOLOGY: Female Wistar rats were randomized into four groups: sham (Group I), experiment model (Group II), and treatment groups with AT (250U/kg) administration systematically (Group III) or locally (Group IV) before hepatectomy. UW solution was used for liver preservation for 24h at 4°C. The livers in group II, III and IV were reperfused 1h and histopathological parameters were evaluated microscopically. Apoptosis was assessed with TUNEL test. RESULTS: Karyorrhexis was lower in the local treatment with AT group. Sinusoidal desquamation and mononuclear cell infiltration was higher in the experimental model group. Sinusoidal enlargement was higher in the systemic AT treatment group and neutrophil infiltration to sinusoids was lowest in the local treatment group. Apoptosis of hepatocytes and sinusoidal cells were significantly suppressed in rats that were treated with AT via portal vein infusion. CONCLUSIONS: AT treatment obviously contributed to liver preservation in our model; the effects on apoptosis and inflammation were prominent. Therefore, AT should be considered as a potent agent although its clinical role has yet to be defined in ex-vivo hepatic preservation.

The effect of exopolysaccharide-producing probiotic strains on gut oxidative damage in experimental colitis.

BACKGROUND: Oxidative stress plays a role in disease initiation and progression in inflammatory bowel disease (IBD) and manipulation of this pathway may attenuate disease progress. In this study, the effect of exopolysaccharide (EPS)-producing probiotic bacteria on gut oxidative damage was evaluated in a rat model of experimental colitis. METHODS: Colitis was induced by intracolonic administration of acetic acid. Rats were treated daily with two probiotic strains, L. delbrueckii subsp. bulgaricus B3 strain (EPS of 211 mg/l; high-EPS group) or L. delbrueckii subsp. bulgaricus A13 strain (EPS of 27 mg/l; low-EPS group), which were given directly into the stomach. Non-colitis-fed control and preventative groups were only treated with the high-EPS producing strain. Antioxidant enzyme activities (superoxide dismutase, catalase, total glutathione, reduced glutathione, glutathione disulfide) and lipid peroxidation were measured in colonic tissue samples after a treatment period of 7 days. RESULTS: Significant oxidative damage was associated with a higher level of malondialdehyde (MDA) activity and reduced antioxidant enzyme activities in the colitis model group. All antioxidant enzyme activities were higher in both probiotic-treated groups compared with those of the colitis model group (P < 0.001). Lipid peroxidation was significantly ameliorated in both probiotic groups. The improvement of oxidative stress parameters was significantly more in the high-EPS group than in the low-EPS group (P < 0.001). CONCLUSIONS: EPS-producing probiotic bacteria significantly attenuate oxidative stress in experimental colitis. Increased EPS production gives rise to a better probiotic function. These results suggest that EPS molecules could revaluate probiotic strains and exert their beneficial effects on the host and this may have a therapeutic potential.

A tumor-like lesion mimicking mucinous (colloid) carcinoma in heterotopic pancreas of the prepyloric antrum: a formidable challenge for frozen examination.

CONTEXT: Heterotopic pancreas is defined as the presence of pancreatic tissue, outside its usual location, which lacks anatomical and vascular continuity with the pancreas proper. Despite the development of modern diagnostic procedures, it is still difficult to differentiate heterotopic pancreas from benign or malignant tumors and other tumor-like lesions. Frozen examination of mucinous lesions arising from heterotopic pancreas may represent a diagnostic problem. A decision may be very difficult and it is sometimes impossible to decide on the basis of the frozen sections whether a lesion is benign or malignant. CASE REPORT: We report a tumor-like lesion mimicking a mucinous (colloid) carcinoma arising in heterotopic pancreatic tissue in the prepyloric antrum of a 56-year-old woman which was found incidentally during an elective laparoscopic cholecystectomy for cholelithiasis. The tumor was treated by wedge resection and, in the frozen section examination, there were pancreatic ducts in the proper muscle layer, pancreatic acini with islets of Langerhans under the serosal surface and mucinous lakes close to the heterotopic pancreatic tissue and to a peripheral nerve. CONCLUSION: The significance of this unusual lesion is its potential confusion with mucinous (colloid) carcinoma or other mucous tumors. Such confusion is more likely to occur if the tissue sample is selective or limited, and the presence of pancreatic tissue cannot be verified. Therefore, we believe that a choice of local excision, wedge resection or more extensive eradication be determined only after intraoperative, pathological confirmation of the complete and accurate diagnosis.

Cytochrome P450 (CYP) and glutathione S-transferases (GST) polymorphisms (CYP1A1, CYP1B1, GSTM1, GSTP1 and GSTT1) and urinary levels of 1-hydroxypyrene in Turkish coke oven workers

Genetic polymorphisms of xenobiotic metabolizing enzymes have been associated with cancer risk. We evaluated the influences of genetic polymorphisms of polycyclic aromatic hydrocarbon (PAH) metabolizing enzymes on urinary 1-hydroxypyrene (1-OHP) excretion in Turkish coke oven workers. Urinary 1-OHP was analyzed by HPLC after enzymatic hydrolysis. Lymphocyte DNA was used for PCR-based genotyping of cytochrome P450 (CYP) polymorphisms (CYP1A1 and CYP1B1) and glutathione S-transferases (GST) polymorphisms (GSTM1, GSTT1 and GSTP1). The mean urinary 1-OHP levels of coke oven workers were significantly higher than that of controls. No significant difference was detected in the mean urinary 1-OHP levels of smokers and non-smokers either for coke oven workers or controls. Genetic polymorphisms of the CYPs and GSTs studied had no significant influence on 1-OHP excretion in coke oven workers, but in the control group the urinary 1-OHP levels of individuals carrying the GSTT1- genotype were significantly higher than those of individuals carrying GSTT1+ genotype. The duration of occupational exposure and metabolic genotype for GSTT1 were the significant predictors of urinary 1-OHP levels. The control individuals carrying combined GSTM1-/GSTT1- genotypes also had significantly higher levels of urinary 1-OHP than those of individuals carrying GSTM1+/GSTTI+, GSTM1-/GSTT1+, and GSTM1+/GSTT1- genotypes. These results indicate that urinary 1-OHP is a sensitive indicator of recent human exposure to PAHs and that genetic polymorphism of GSTT1 may also to some extent reflect the interindividual variation in susceptibility to PAHs only at low PAH exposure.

Biliary complications after hydatid liver surgery: incidence and risk factors.

The aims of this study were to determine the incidence and risk factors of biliary leakage and biliary fistulae after hydatid liver surgery and to suggest preventive precautions. From January 1999 to June 2000, 70 cysts were examined from 54 patients who were operated on for hydatid liver disease. Age, sex, primary or recurrent disease, liver function tests, number, location, content, radiological type, and diameter and cavity management techniques were examined with univariate and multivariate analyses for biliary complications. Biliary leakage occurred in 14 cysts (26%) from the patients. Purulent and/or bilious cyst content (61.9% vs. 2.0%; P = 0.022), male gender (40.9% vs. 10.4%; P = 0.038), and pre-operative raised alkaline phosphatase and gamma glutamyl transferase levels (34.6% vs. 11.4%; P = 0.047) were found as independent risk factors for post-operative biliary leakage. Nine instances of biliary leakage (16.7%) closed spontaneously within seven days. The remaining five instances of biliary leakage (9.3%) persisted for more than 10 days and were accepted as biliary fistulae. Stepwise logistic regression identified cyst content was the only risk factor for biliary fistulae (19% vs. 2%; P = 0.036). Described risk factors for post-operative biliary complications after hydatid liver surgery may be the guidelines for additional pre-operative or intra-operative radiological interventions of the biliary tract and for preventive procedures such as surgical biliary drainage.