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

The inflammatory response in transgastric surgery: gastric content leak leads to localized inflammatory response and higher adhesive disease

Risk of gastric spillage during transgastric surgery is a potential complication of NOTES procedures. The aim of this study was to determine risk outcomes from gastric spillage in a rat survival model by measuring local and systemic inflammatory markers, adhesive disease, and morbidity. We performed a minilaparotomy with needle aspiration of 2 ml of gastric contents mixed with 2 ml of sterile saline (study group, SG) or 4 ml of sterile saline (control group, CG) injected into the peritoneal cavity of 60 male rats. Inflammatory markers (TNFα, IL-6, and IL-10) were analyzed at 1, 3, 6, and 24 h postoperatively by obtaining plasma levels and peritoneal washings. At necropsy, the peritoneal cavity was examined grossly for adhesions. Adhesions were seen more frequently in the SG versus the CG (100% vs. 33.3%, p < 0.014). There was a significant difference in the peritoneal TNFα levels in the SG compared with the CG, which peaked 1 h after surgery (p < 0.02). Both peritoneal IL-6 and IL-10 levels were higher in the SG versus the CG, which peaked 3 h after surgery (p < 0.005 and p < 0.001, respectively). All peritoneal inflammatory markers returned to undetectable levels at 24 h for both groups. Plasma cytokines were undetectable at all time intervals. The inflammatory response was found to be a localized and not systemic event, with plasma cytokine levels remaining normal while peritoneal washings revealed a brisk, short-lived localized inflammatory response. There was a significantly higher rate of adhesive disease in the SG compared with the CG; this, however did not translate into a difference in apparent clinical outcome. We conclude that gastric leakage in this NOTES rodent model induces a localized inflammatory response, followed by mild to moderate adhesive disease. This may be important in human NOTES

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

Natural orifice surgery: initial clinical experience

Natural orifice translumenal endoscopic surgery (NOTES) has moved quickly from preclinical investigation to clinical implementation. However, several major technical problems limit clinical NOTES including safe access, retraction and dissection of the gallbladder, and clipping of key structures. This study aimed to identify challenges and develop solutions for NOTES during the initial clinical experience. Under an Institutional Review Board (IRB)-approved protocol, patients consented to a natural orifice operation for removal of either the gallbladder or the appendix via either the vagina or the stomach using a single umbilical trocar for safety and assistance. Nine transvaginal cholecystectomies, one transgastric appendectomy, and one transvaginal appendectomy have been completed to date. All but one patient were discharged on postoperative day 1 as per protocol. No complications occurred. The limited initial evidence from this study demonstrates that NOTES is feasible and safe. The addition of an umbilical trocar is a bridge allowing safe performance of NOTES procedures until better instruments become available. The addition of a flexible long grasper through the vagina and a flexible operating platform through the stomach has enabled the performance of NOTES in a safe and easily reproducible manner. The use of a uterine manipulator has facilitated visualization of the cul de sac in women with a uterus to allow for safe transvaginal access

Women in surgery: bright, sharp, brave, and temperate.

Women make up an increasing proportion of students entering the medical profession. Before 1970, women represented 6% or less of the medical student population. In drastic contrast, nearly half of first-time applicants to medical schools in 2011 were women. However, the ratio of women to men is less balanced among graduates from surgical residencies and among leadership positions in surgery. Less than 20% of full professor, tenured faculty, and departmental head positions are currently held by women. However, this disparity may resolve with time as more women who entered the field in the 1980s emerge as mature surgeons and leaders. The aim of this article is to review the history of women in surgery and to highlight individual and institutional creative modifications that can promote the advancement of women in surgery. A secondary aim of the article is to add some levity to the discussion with personal anecdotes representing the primary author\u27s (ECM) personal opinions, biases, and reflections

Academic Surgical Oncologists' Productivity Correlates with Gender, Grant Funding, and Institutional NCI Comprehensive Cancer Center Affiliation.

BackgroundA scholar's h-index is defined as the number of h papers published, each of which has been cited at least h times. We hypothesized that the h-index strongly correlates with the academic rank of surgical oncologists.MethodsWe utilized the National Cancer Institute (NCI) website to identify NCI-designated Comprehensive Cancer Centers (CCC) and Doximity to identify the 50 highest-ranked general surgery residency programs with surgical oncology divisions. Demographic data of respective academic surgical oncologists were collected from departmental websites and Grantome. Bibliometric data were obtained from Web of Science.ResultsWe identified 544 surgical oncologists from 64 programs. Increased h-index was associated with academic rank (p < 0.001), male gender (p < 0.001), number of National Institutes of Health (NIH) grants (p < 0.001), and affiliation with an NCI CCC (p = 0.018) but not number of additional degrees (p = 0.661) or Doximity ranking (p = 0.102). H-index was a stronger predictor of academic rank (r = 0.648) than total publications (r = 0.585) or citations (r = 0.450).ConclusionsThis is the first report to assess the h-index within academic surgical oncology. H-index is a bibliometric predictor of academic rank that correlates with NIH grant funding and NCI CCC affiliation. We also highlight a previously unexpected and unappreciated gender disparity in the academic productivity of US surgical oncologists. When academic rank was accounted for, female surgical oncologists had lower h-indices compared with their male colleagues. Evaluation of the etiologies of this gender disparity is needed to address barriers to academic productivity faced by female surgical oncologists as they progress through their careers

Incidence and survival patterns of rare anal canal neoplasms using the surveillance epidemiology and end results registry.

Small cell, neuroendocrine tumors, and melanoma of the anus are rare. Limited data exist on the incidence and management for these rare tumors. A large, prospective, population-based database was used to determine incidence and survival patterns of rare anal neoplasms. The Surveillance, Epidemiology and End Results registry was queried to identify patients diagnosed with anal canal neoplasms. Incidence and survival patterns were evaluated with respect to age, sex, race, histology, stage, and therapy. We identified 7078 cases of anal canal neoplasms: melanoma (n = 149), neuroendocrine (n = 61), and small cell neuroendocrine (n = 26). Squamous cell carcinoma (SCC) (n = 6842) served as the comparison group. Anal melanoma (AM) demonstrated the lowest survival rate at 2.5 per cent. Neuroendocrine tumors (NETs) demonstrated similar survival as SCC (10-year survival for regional disease of 25 and 22.3%, respectively). Ten-year survival of small cell NETs resembled AM (5.3 vs 2.5%). Age 60 years or older, sex, black race, stage, and surgery were independent predictors of survival. This study presents the largest patient series of rare anal neoplasms. NETs of the anal canal demonstrate similar survival patterns to SCC, whereas small cell NETs more closely resemble AM. Accurate histologic diagnosis is vital to determine treatment and surgical management because survival patterns can differ among rare anal neoplasms

Experience with 10 years of a robotic surgery program at an Academic Medical Center.

BackgroundFew studies have examined robotic surgery from a programmatic standpoint, yet this is how hospitals evaluate return on investment clinically and fiscally. This study examines the 10-year experience of a robotic program at a single academic institution.Study designAll robotic operations performed at our institution from August 2005 to December 2016 were reviewed. Data were collected from the robotic system and hospital databases.ResultsA total of 3485 robotic operations were performed. Yearly case volume nearly quadrupled. There have been 37 robotic-trained surgeons in 5 specialties performing 53 different operations. Rate of conversion to open was 4.2%. American Society of Anesthesiologists (ASA) class increased over time, with ASA class 3 increasing from 20% of patients to 45% of patients. Average case time in 2005 was 453 min, but decreased by 46% to 246 min by 2007, then remained relatively stable (range 226-247). Operating efficiency improved, with room time and case time decreasing by 9% in the past 4 years. Average cost for robotic supplies was $1519 per case. Additional costs per case related to equipment and contracts totaled an average of$11,822. Average length of stay (LOS) for robotic cases was 3.3 days, compared to 3.0 days for laparoscopic and 7.0 for open. Cost per day for admission after robotic surgery was 1.7 times greater than the cost of open or laparoscopic surgery. Total admission costs of robotic operations were 1.5 times those of laparoscopic surgery, but less than open operations. Readmissions following robotic cases were lower than open (15% v 26%, p < 0.0001).ConclusionsOver 10 years, the use of robotic technology has grown significantly at our institution, with good fiscal and clinical outcomes. Operating room costs are high; however, efficiency has improved, LOS is shorter, admission costs are lower than open operations, and readmission rates are lower