Relationship of EMAST and Microsatellite Instability Among Patients with Rectal Cancer

BackgroundElevated microsatellite instability at selected tetranucleotide repeats (EMAST) is a genetic signature identified in 60% of sporadic colon cancers and may be linked with heterogeneous expression of the DNA mismatch repair (MMR) protein hMSH3. Unlike microsatellite instability-high (MSI-H) in which hypermethylation of hMLH1 occurs followed by multiple susceptible gene mutations, EMAST may be associated with inflammation and subsequent relaxation of MMR function with the biological consequences not known. We evaluated the prevalence of EMAST and MSI in a population-based cohort of rectal cancers, as EMAST has not been previously determined in rectal cancers.MethodsWe analyzed 147 sporadic cases of rectal cancer using five tetranucleotide microsatellite markers and National-Cancer-Institute-recommended MSI (mononucleotide and dinucleotide) markers. EMAST and MSI determinations were made on analysis of DNA sequences of the polymerase chain reaction products and determined positive if at least two loci were found to have frame-shifted repeats upon comparison between normal and cancer samples from the same patient. We correlated EMAST data with race, gender, and tumor stage and examined the samples for lymphocyte infiltration.ResultsAmong this cohort of patients with rectal cancer (mean age 62.2 ± 10.3years, 36% female, 24% African American), 3/147 (2%) showed MSI (three males, two African American) and 49/147 (33%) demonstrated EMAST. Rectal tumors from African Americans were more likely to show EMAST than Caucasians (18/37, 49% vs. 27/104, 26%, p = 0.014) and were associated with advanced stage (18/29, 62% EMAST vs. 18/53, 37%, non-EMAST p = 0.02). There was no association between EMAST and gender. EMAST was more prevalent in rectal tumors that showed peri-tumoral infiltration compared to those without (30/49, 60% EMAST vs. 24/98, 25% non-EMAST, p = 0.0001).ConclusionsEMAST in rectal cancer is common and MSI is rare. EMAST is associated with African-American race and may be more commonly seen with metastatic disease. The etiology and consequences of EMAST are under investigation, but its association with immune cell infiltration suggests that inflammation may play a role for its development

Relationship of EMAST and Microsatellite Instability Among Patients with Rectal Cancer

Elevated microsatellite instability at selected tetranucleotide repeats (EMAST) is a genetic signature identified in 60% of sporadic colon cancers and may be linked with heterogeneous expression of the DNA mismatch repair (MMR) protein hMSH3. Unlike microsatellite instability-high (MSI-H) in which hypermethylation of hMLH1 occurs followed by multiple susceptible gene mutations, EMAST may be associated with inflammation and subsequent relaxation of MMR function with the biological consequences not known. We evaluated the prevalence of EMAST and MSI in a population-based cohort of rectal cancers, as EMAST has not been previously determined in rectal cancers. We analyzed 147 sporadic cases of rectal cancer using five tetranucleotide microsatellite markers and National-Cancer-Institute-recommended MSI (mononucleotide and dinucleotide) markers. EMAST and MSI determinations were made on analysis of DNA sequences of the polymerase chain reaction products and determined positive if at least two loci were found to have frame-shifted repeats upon comparison between normal and cancer samples from the same patient. We correlated EMAST data with race, gender, and tumor stage and examined the samples for lymphocyte infiltration. Among this cohort of patients with rectal cancer (mean age 62.2 ± 10.3 years, 36% female, 24% African American), 3/147 (2%) showed MSI (three males, two African American) and 49/147 (33%) demonstrated EMAST. Rectal tumors from African Americans were more likely to show EMAST than Caucasians (18/37, 49% vs. 27/104, 26%, p = 0.014) and were associated with advanced stage (18/29, 62% EMAST vs. 18/53, 37%, non-EMAST p = 0.02). There was no association between EMAST and gender. EMAST was more prevalent in rectal tumors that showed peri-tumoral infiltration compared to those without (30/49, 60% EMAST vs. 24/98, 25% non-EMAST, p = 0.0001). EMAST in rectal cancer is common and MSI is rare. EMAST is associated with African-American race and may be more commonly seen with metastatic disease. The etiology and consequences of EMAST are under investigation, but its association with immune cell infiltration suggests that inflammation may play a role for its development

Predicting Readmission and Leak Rates Following Colectomy with Red Cell Distribution Width: A Simple but Effective Test

Introduction: Prediction of readmission as a result of either delayed presentation of infection, or worse an anastomotic leak is difficult. Efficient reduction in the length of stay and being able to predict problematic patients who may be readmitted or develop complications would be advantageous. To date, other tests including CRP have proven to be insufficiently sensitive for this task. Materials &amp; Methods: We performed a single center, retrospective review of patients admitted to a large, urban safety net hospital who underwent colectomy over a two year period to determine the predictive value of red cell distribution width (RDW) on the development of anastomotic leak or readmission within 30 days following hospital discharge. Results: A total of 118 patients underwent colectomy during this period. Readmission and/or anastomotic leak occurred in 49 patients. The sensitivity of elevated RDW levels (greater than or equal to 14.0) at detecting future readmission and/or leak was 89.8%. The negative predictive value for a normalized RDW below 14.0 at predicting the non-occurrence of leak or readmission was 87.7%. The specificity of an elevated RDW was 72.4% and the positive predictive value was 76.5%.</p

New Disposable Transanal Endoscopic Surgery Platform: Longer Channel, Longer Reach

Abstract: Background: Transanal endoscopic surgical (TES) resection using rigid transanal platforms (TEM, TEO) is associated with improved outcomes compared to traditional transanal excision (TAE) of rectal lesions. An alternative technique using a disposable single incision surgery platform was developed in 2009, transanal minimally invasive surgery (TAMIS), resulting in a surge in interest and access to transanal access platforms to perform TES. However, compared to rigid transanal access platforms, the disposable platforms do not facilitate internal rectal retraction and have limited proximal reach. A new long channel disposable transanal access platform has been developed (15 cm in length, 4 cm in width) thereby facilitating endoluminal surgical access to the upper rectum and rectosigmoid colon. Methods: This is a retrospective case series report. Patient demographics and peri-operative outcome variables were recorded. The Gelpoint Path Long Channel was utilized in three patients with proximal rectal lesions that were not accessible using a standard disposable transanal access platform.Results: Three patients underwent TES excision of rectal adenomas using a long channel, disposable, transanal access platform. All patients were female, aged 51 – 53, BMI 23-32 kg/m2. The tumor size ranged from 2.4 – 8.5 cm, 15-100% circumference, and proximal location from the dentate line ranged from 9 – 11 cm. Final pathology revealed adenoma with negative margins in all three cases. The hospital length of stay ranged from 1 – 3 days and there were no perioperative complications. None of the patients have developed a local recurrence during the follow up period ranging from 5 – 11 months.Conclusions: The new long channel, disposable, transanal access platform facilitates transanal endoluminal surgical removal of lesions in the mid to upper rectum that may be difficult to reach using the standard disposable transanal access devices. We have successfully achieved 100% margin negative rate using this new device in this small series of patients with proximal rectal adenomas

Transanal Endoscopic Surgical Proctectomy for Proctitis Case Series Report: Diversion, Radiation, Ulcerative Colitis, and Crohn’s Disease

Abstract: Background: With recent trends in natural orifice surgery, there has been a rising interest in the evolution of transanal endoscopic surgery (TES) and transanal access platforms. Transanal endoluminal removal of rectal masses has matured into transanal endoscopic surgical resection of the rectum for benign and malignant disease. The purpose of this study is to evaluate the surgical outcomes of TES completion proctectomy in patients with proctitis in a retained rectum.Methods: This is a retrospective case series report. Patient demographics and peri-operative outcome variables were recorded.Results: TES proctectomy was successfully performed in 6 patients using a disposable transanal access platform. The patient's ages ranged from 22 – 74 years, 4 women and 2 men, BMI ranged from 22 – 51 kg/m2. The indication for surgery was proctitis in a retained rectum: diversion (n=1), radiation (n=1), ulcerative colitis (n=2), and Crohn's disease (n=2). Four applications of TES proctectomy were employed: TES completion proctectomy (n=2), TES assisted single incision abdominal perineal resection (n=1), TES assisted laparoscopic restorative proctectomy with colo-anal anastomosis (n=1), and TES assisted laparoscopic restorative total proctocolectomy with ileal pouch anal anastomosis (n=1). The operative time for TES completion proctectomy ranged from 140 – 238 minutes (n=4). The operative time for TES restorative proctectomy was longer at 446 min and 557 min (n=2). The hospital length of stay for both TES completion and restorative proctectomy ranged from 2 – 5 days (n=5). Complications included 1 urinary tract infection, 1 chronic draining perineal sinus tract, and 1 perineal wound dehiscence requiring re-operation. All six patients are doing well at the time of follow up (range 3 – 19 months).Conclusions: TES completion proctectomy alone or in combination with laparoscopic abdominal surgery is a safe and effective method to perform proctectomy and restorative proctectomy in this small case series of patients with proctitis in a retained rectum due to diversion, radiation, ulcerative colitis, and Crohn's disease