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Histone Methylation Marks on Circulating Nucleosomes as Novel Blood-Based Biomarker in Colorectal Cancer

Circulating nucleic acids (CNAs) are under investigation as a liquid biopsy in cancer as potential non-invasive biomarkers, as stable structure in circulation nucleosomes could be valuable sources for detection of cancer-specific alterations in histone modifications. Our interest is in histone methylation marks with a focus on colorectal cancer, one of the leading cancers respective the incidence and mortality. Our previous work included the analysis of trimethylations of lysine 9 on histone 3 (H3K9me3) and of lysine 20 on histone 4 (H4K20me3) by chromatin immuno- precipitation-related PCR in circulating nucleosomes. Here we asked whether global immunologic measurement of histone marks in circulation could be a suitable approach to show their potential as biomarkers. In addition to H3K9me3 and H4K20me3 we also measured H3K27me3 in plasma samples from CRC patients (n = 63) and cancer free individuals (n = 40) by ELISA-based methylation assays. Our results show that of three marks, the amounts of H3K27me3 (p = 0.04) and H4K20me3 (p < 0.001) were significantly lower in CRC patients than in healthy controls. For H3K9me3 similar amounts were measured in both groups. Areas under the curve (AUC) in receiver operating characteristic (ROC) curves indicating the power of CRC detection were 0.620 for H3K27me3, 0.715 for H4K20me3 and 0.769 for the combination of both markers. In conclusion, findings of this preliminary study reveal the potential of blood-based detection of CRC by quantification of histone methylation marks and the additive effect of the marker combination.

Iatrogenic major vascular injury during lumbar discectomy: report of three cases.

Iatrogenic vascular injury rarely occurs during lumbar disc surgery and can be fatal if it is not recognized instantly. In this paper we aim to introduce three iatrogenic vascular injuries that occurred during the lumbar disc surgery. The first case was consulted because of the sudden hypotension attack during lumbar disc surgery. The left common iliac artery and bilateral common iliac vein injuries were detected in emergency laparotomy, and repaired primarily. The second case was consulted to our clinic because of the hypotension attack at the first postoperative day. Left common iliac artery and vein injuries were diagnosed by CT angiography. Left common iliac vein was ligated and left common iliac arterial injury was repaired primarily by laparotomy. The third case was referred to our clinic for left lower extremity ischemia. Left common iliac artery injury was diagnosed by simple physical examination. Reconstruction by PTFE graft interposition was performed. The first patient died due to disseminated intravascular coagulation at the early postoperative period. Pulmonary embolus developed in the iliac vein ligated patient but was well treated by anticoagulant therapy. The last patient was discharged without any problem. Two of the patients are well on long-term follow-up.

The role of the laparoscopy on circumferential resection margin positivity in patients with rectal cancer: long-term outcomes at a single high-volume institution.

Background: The aim of this study was to evaluate the influence of laparoscopic rectal cancer surgery on circumferential resection margin (CRM) involvement. Materials and Methods: The data from 579 consecutive patients who underwent laparoscopic or open resection of rectal cancer from October 2002 to August 2008 were analyzed retrospectively. The primary endpoint was CRM status. The secondary endpoints were morbidity, local recurrence rate, overall survival, and disease-free survival. Results: Laparoscopic resections were performed in 266 patients (46%), and the remainder of the patients underwent open resection. The rates of CRM involvement were similar between the laparoscopic and open groups (5.6% vs. 5.4%). The perioperative morbidity rates between the 2 groups were not significantly different (P=0.2). The incidence of local recurrence for the CRM-negative group was 8.4% (8.3% laparoscopic vs. 8.45% open; P=0.99), whereas the local recurrence rate was 34.3% for the CRM-positive group. The local recurrence rate was 20% for the CRM-positive patients in the laparoscopic group and 47% for the CRM-positive patients in the open group (P<0.001). We did not observe any significant differences in local recurrence rates between the Lap R and Open R groups after omitting CRM status. CRM positivity was correlated with both 5-year survival and the 5-year disease-free survival rate (P=0.009 and P=0.001, respectively). We did not observe any significant differences in morbidity, local recurrence, or overall or disease-free survival rates between the overall laparoscopic and open resection groups. Conclusions: Laparoscopic surgery for rectal cancer is associated with similar complication rates, CRM involvement status, and long-term outcomes as those associated with open surgery but with the advantages of minimally invasive surgery. Although laparoscopic surgery might necessitate more advanced technical skills, similar long-term oncological results can be obtained with this technique.

Tumor Budding Is Independently Predictive for Lymph Node Involvement in Early Gastric Cancer.

Background. The most important prognostic factor for early gastric cancer (EGC) is the lymph node status. It is important to predict early lesions without lymph node metastasis (LNM) before proceeding to radical surgery in locally excised lesions. Tumor budding is a feature known to be related to aggressive tumor behavior in several solid tumors. We aimed to assess the predictive value of tumor budding for LNM in pT1a and pT1b gastric cancer. Methods. We retrospectively investigated radical gastrectomy specimens for of 126 EGC patients and assess the possible relation between the clinicopathologic features, including age, gender, tumor location, tumor size, macroscopic tumor type, histologic differentiation, depth and width of submucosal invasion, lymphovascular invasion, and tumor budding with lymph node involvement. Results. Among the 126 EGCs, 38 were stages as pT1a and 88 as pT1b. LNM rate in pT1a tumors was 13% whereas it was 33% in pT1b tumors. Tumor budding was the only factor significantly and independently related to LNM in pT1a patients. Female gender and tumor budding were found to be independent risk factors in pT1b group. Other clinicopathologic features were not related to LNM. Conclusion. Based on these results, we suggest that budding is a promising parameter to assess for prediction of LNM in EGC removed by endoscopic surgery, and to decide on the appropriate surgical approach.

Parameters That May Be Used for Predicting Failure during Endoscopic Retrograde Cholangiopancreatography

Aim. Endoscopic retrograde cholangiopancreatography (ERCP) is frequently used for the diagnosis and treatment of hepatic, biliary tract, and pancreatic disorders. However, failure during cannulation necessitates other interventions. The aim of this study was to establish parameters that can be used to predict failure during ERCP. Methods. A total of 5884 ERCP procedures performed on 5079 patients, between 1991 and 2006, were retrospectively evaluated. Results. Cannulation was possible in 4482 (88.2%) patients. For each one-year increase in age, the cannulation failure rate increased by 1.01-fold (P = 0.002). A history of previous hepatic biliary tract surgery caused the cannulation failure rate to decrease by 0.487-fold (P < 0.001). A tumor infiltrating the ampulla, the presence of pathology obstructing the gastrointestinal passage, and peptic ulcer increased the failure rate by 78-, 28-, and 3.47-fold, respectively (P < 0.001). Conclusions.Patient gender and duodenal diverticula do not influence the success of cannulation during ERCP. Billroth II and Roux-en-Y gastrojejunostomy surgeries, a benign or malignant obstruction of the gastrointestinal system, and duodenal ulcers decrease the cannulation success rate, whereas a history of previous hepatic biliary tract surgery increases it. Although all endoscopists had equal levels of experience, statistically significant differences were detected among them.

Effectiveness of Endoluminal Vacuum-assisted Closure Therapy (Endosponge) for the Treatment of Pelvic Anastomotic Leakage After Colorectal Surgery.

Anastomotic leakage is a serious complication with significant morbidity and mortality. The popularity of endoscopic treatment (Endo-SPONGE) is increasing for distally located colorectal pouch-anal anastomotic leakages. This was a retrospective study of 15 cases involving the application of the Endo-SPONGE for anastomotic leakage following proctectomy between May 2009 and May 2014. Of the 15 cases, lower anterior resection occurred in 12 cases (80%), and pouch-anal anastomosis in 3 cases (18%). In 8 patients (55%), the endosponge was applied during the early term, and in 7 patients (45%) during the late term. The average number of applications was 2.2 (range, 1 to 5). Treatment was discontinued due to the progression of pelvic sepsis in 2 patients and due to bleeding in 1 patient. Lumen integrity was achieved in 12 cases. Lumen integrity after anastomotic leakages can be preserved by endoluminal vacuum therapy, which permits the closure of the stoma without requiring reconstructive surgery.

Open Versus Laparoscopic Surgery for Rectal Cancer: Single-Center Results of 587 Cases.

Purpose: We aimed to compare the short-term and long-term results of laparoscopic and open rectal resections. Methods: A total of 587 rectal cancer patients were included. The main measures were demographic data, duration of surgery, early postoperative results, pathologic data, and long-term follow-up. Results: There were no significant differences in demographic data, morbidity rate, tumor location, and sphincter-preservation rates between the 2 groups. The duration of surgery (155 vs. 173 min, P<0.001), time to gas passage, defecation, and solid food intake and length of hospital stay were significantly shorter in the laparoscopic group than the open group (P<0.05). According to the univariate and multivariate analysis, laparoscopic surgery did not have an effect on local recurrence but had a favorable effect on survival rates. Conclusions: Laparoscopic rectal surgery has advantages over open surgery with respect to short-term and long-term clinical results and when performed in high-volume centers.

Use of Antifibrotics to Prevent Ventriculoperitoneal Shunt Complications Due to Intra-abdominal Fibrosis: Experimental Study in a Rat Model.

BACKGROUND Cerebrospinal fluid shunt operations have reduced the morbidity and mortality of hydrocephalus, but have potential complications. Ventriculoperitoneal (vp) shunt obstruction is one of the common complications of shunt surgery. The obstruction is caused by fibrosis and is usually located on the tip of the ventricular and/or peritoneal catheter. OBJECTIVE In our study, we aimed to demonstrate the known antifibrotic effects of heparin, hyaluronate/carboxymethylcellulose, and icodextrin on peritoneal catheter obstruction in a vp shunt model in rats. METHODS Thirty-two male Sprague-Dawley rats were used in this study. A shunt catheter was placed in the abdominal cavity. In the control group, isotonic solution, in the study groups, heparin, sodium hyaluronate/carboxymethylcellulose (HA/CMC), and icodextrin were intraperitoneally applied. The severity of adhesions and inflammation around the peritoneal catheter was evaluated after the rats were killed on day 30. RESULTS One animal in the heparin group died due to intra-abdominal hemorrhage. We found the most adhesions in the control group. All three drugs (heparin, HA/CMC, icodextrin) were effective for adhesion prevention. HA/CMC was more effective than heparin, and icodextrin was most effective. There was a statistically significant difference between the icodextrin and the control group (p = 0.007). CONCLUSION The intra-abdominal instillation of icodextrin, HA/CMC, and heparin, especially icodextrin, can decrease the rate of vp shunt dysfunction by preventing formation of intraperitoneal fibrosis.

Unexpected colonic perforation in a renal recipient: a case report

Gastrointestinal complications such as gastrointestinal bleeding and perforation due to immunosuppressant use are seen more frequently after solid organ transplantation. A 52-year-old male was admitted on the 7th day of a living donor renal transplantation with serous drainage at the incision site. He had no abdominal complaints. He was on triple immunosuppressant therapy. Abdominal plain X-ray and ultrasonography were normal, but diffuse extraluminal air was detected on the computed tomography scan. There were no pathological laboratory findings regarding the function of the renal allograft. We began the operation laparoscopically and then converted to laparotomy. Sigmoid colonic perforation was detected on the antimesenteric side. Neither diverticulitis nor ischemia was observed, and no evidence of iatrogenic injury was seen. There was no transrectal instrumentation history. Omentoplasty and sigmoid loop colostomy were performed. He was discharged on the 9th day following the operation. His colostomy was closed one year after the operation. Gastrointestinal complications can be fatal, but do not seem to influence the long-term survival or renal allograft function. Most of them are seen after using high doses of immunosuppressants to manage the early postoperative period or episodes of acute rejection. Early diagnosis and aggressive treatment play an important role in survival.

A solution to the negative effects of splenectomy during colorectal trauma and surgery: an experimental study on splenic autotransplantation to the groin area

BackgroundSplenectomy after combined colosplenic trauma or iatrogenic splenic injury during colorectal surgery associates with worse short- and long-term outcomes, including reduced survival in patients with colorectal cancer. Splenic autotransplantation may improve the outcomes of such patients. Omental splenic transplantation is the standard procedure but may be difficult when performing laparoscopic colorectal surgery or when total or subtotal omentectomy is required. This animal model study was performed to evaluate the impact of splenic autotransplantation to the groin area on colonic wound healing.MethodsThirty rats were divided into three groups of ten animals. One group underwent colon anastomosis and sham splenectomy, the second underwent colon anastomosis and splenectomy, and the third underwent colon anastomosis, splenectomy, and intramuscular autotransplantation of the spleen. On postoperative day 7, anastomotic healing was evaluated by measuring bursting pressure and hydroxyproline levels. The third group was subjected to scintigraphy before sacrifice to assess whether the transplant was functional.ResultsThe mortality rates of the sham, splenectomized, and transplanted animals were 0 %, 30 %, and 20 %, respectively: the splenectomized animals had significantly lower mean bursting pressures than the other two groups (p = 0.002). The mean hydroxyproline levels of the three groups were 467.4, 335.3, and 412.7 mg hydroxyproline/g protein, respectively (p = 0.0856). Nine of the ten transplanted animals (90 %) had splenic activity on scintigraphy.ConclusionsSplenectomy impaired the healing of the colonic anastomosis. This effect was largely reversed by splenic autotransplantation. Intramuscular autotransplantation to the groin area appears to be feasible and effective.