ABSTRACT
BACKGROUND: Elderly patients are underrepresented in studies demonstrating the advantages of laparoscopy for the management of colorectal diseases. Moreover, few studies have examined the robotic approach in this population. In this retrospective analysis, we compare outcomes for open, laparoscopic, and robotic approaches in elderly patients with nonmetastatic rectal cancer. METHODS: The U.S. National Cancer Database was queried for patients aged ≥ 65 with nonmetastatic adenocarcinoma of the rectum who underwent surgical resection from 2010 to 2016. Groups were separated based on approach (open, laparoscopic, robotic). One-to-one nearest neighbor propensity score matching (PSM) ± 1% caliper was performed across surgical approach cohorts to balance potential confounding covariates. Kaplan-Meier estimation and Cox-proportional hazards regression were used to analyze the primary outcome of survival. Secondary outcomes were analyzed by way of logistic regression. RESULTS: Inclusion criteria and PSM identified 1891 patients per approach (n = 5673). PSM provided adequate discrimination between cohorts (0.6 < AUC < 0.8), and potential confounding covariates did not significantly differ (respective P > 0.05). After PSM, robotic and laparoscopic approaches were associated with decreased odds of 90 day mortality compared to the open approach (P < 0.05). Compared to laparoscopy, a robotic approach was associated with increased odds of ≥ 12 regional lymph nodes examined and negative circumferential resection margin (P < 0.05). No differences were seen in 30 day or 90 day mortality between robotic and laparoscopic approaches. Cox proportional hazards regression showed that both robotic and laparoscopic approaches were significantly associated with decreased mortality hazards relative to open. CONCLUSION: Our study demonstrates that in elderly patients, minimally invasive surgery for rectal adenocarcinoma was associated with equivalent or improved short- and long-term mortality over open surgery. Compared to laparoscopy, the robotic approach showed no survival disadvantage and greater odds of an appropriate oncological resection. Our study adds evidence to the conclusion that robotic rectal surgery can be safely performed in patients regardless of age.
Subject(s)
Laparoscopy , Rectal Neoplasms , Robotic Surgical Procedures , Aged , Humans , Propensity Score , Rectal Neoplasms/surgery , Rectum/surgery , Retrospective Studies , Treatment OutcomeABSTRACT
AIM: This study aimed to present our experience with robotic colorectal surgery since its establishment at our institution in 2009. By examining the outcomes of over 500 patients, our experience provides a basis for assessing the introduction of a robotic platform in a colorectal practice. Specific measures investigated include intraoperative data and postoperative outcomes for all operations using the robotic platform. In addition, for our most commonly performed operations we wished to analyse the learning curve to improve operative proficiency. This is the largest single-surgeon robotic database analysed to date. METHOD: A prospectively maintained database of patients who underwent robotic colorectal surgery by a single surgeon at the George Washington University Hospital was retrospectively reviewed. Demographic data and perioperative outcomes were assessed. Additionally, an operating time learning curve analysis was performed. RESULTS: Inclusion criteria identified 502 patients who underwent robotic colorectal surgery between October 2009 and December 2018. The most common indications for surgery were diverticulitis (22.9%), colon adenocarcinoma (22.1%) and rectal adenocarcinoma (19.5%). The most common operations were anterior/low anterior resection (33.9%), right hemicolectomy/ileocaecectomy (24.9%) and left hemicolectomy/sigmoidectomy (21.9%). The rate of conversion to open surgery was 4.8%. The most common postoperative complications were wound infection (5.0%), anastomotic leakage (4.0%) and abscess formation (2.8%). The operating time learning curve plateaued at 55-65 cases for anterior and low anterior resection and 35-45 cases for left hemicolectomy and sigmoidectomy. A clear learning curve was not seen in right hemicolectomy. CONCLUSION: Robotic-assisted surgery can be performed in a diverse colorectal practice with low rates of conversion and postoperative complications. Plateau performance was achieved after 65 anterior/low anterior resections and 45 left and sigmoid colectomies.
Subject(s)
Laparoscopy , Rectal Neoplasms , Robotic Surgical Procedures , Colectomy , Humans , Learning Curve , Rectal Neoplasms/surgery , Retrospective Studies , Robotic Surgical Procedures/adverse effectsABSTRACT
BACKGROUND: Crohn's disease has historically been managed medically with sparing use of surgical resection. With the development of strictures or fistulas, surgical management such as an ileocecal resection may become necessary. Minimally invasive options such as laparoscopic and robotic-assisted techniques are alternatives to open surgery. The purpose of this study was to evaluate the safety of minimally invasive surgery for Crohn's disease. METHODS: We performed a retrospective review of the National Surgical Quality Improvement Program (NSQIP) database to select 5158 patients with Crohn's disease who underwent ileocecal resection (open, laparoscopic, or robotic-assisted). Preoperative, perioperative, and 30-day postoperative outcomes were compared between the groups using both univariate and multivariate logistical regression models. SAS was used for data analysis with p < 0.05 considered significant. RESULTS: The three treatment groups (open, laparoscopic, and robotic-assisted ileocecal resection) had 30-day postoperative outcomes reported in NSQIP. The average BMI was 25 kg/m2 and the average age was 41. The rate of anastomotic leaks was significantly higher in the open surgery group compared to the minimally invasive groups (p = 0.001). The open surgery group had a significantly higher reoperation rate (p = 0.0002) and wound infection rate (p < 0.0001). The robotic-assisted group had significantly longer operative times compared to the laparoscopic and open groups (p < 0.0001). CONCLUSIONS: The decision to operate on a patient with Crohn's disease involves selecting an approach based on patient factors, surgeon preference, and availability of equipment. When evaluating the short-term postoperative outcomes in patients that have undergone ileocecal resection for management of Crohn's, minimally invasive techniques have had a lower incidence of wound infections, anastomotic leaks, and re-intervention in carefully selected patients. This retrospective review of a large national database demonstrates the efficacy of minimally invasive techniques in managing Crohn's disease in selected patients.
Subject(s)
Crohn Disease , Laparoscopy , Robotic Surgical Procedures , Adult , Crohn Disease/surgery , Humans , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies , Robotic Surgical Procedures/adverse effects , Treatment OutcomeABSTRACT
BACKGROUND: This study examined utilization and conversion rates for robotic and laparoscopic approaches to non-metastatic rectal cancer. Secondary aims were to examine short- and long-term outcomes of patients who underwent conversion to laparotomy from each approach. METHODS: The National Cancer Database (NCDB) was reviewed for all cases of non-metastatic adenocarcinoma of the rectum or rectosigmoid junction who underwent surgical resection from 2010 to 2016. Utilization rates of robotic, laparoscopic, and open approaches were examined. Patients were split into cohorts by approach. Subgroup analyses were performed by primary tumor site and surgical procedure. Multivariable analysis was performed by multivariable logistic regression for binary outcomes and multivariable general linear models for continuous outcomes. Survival analysis was performed by Kaplan-Meier and multivariable cox-proportional hazards regression. RESULTS: From 2010 to 2016, there was a statistically significant increase in utilization of the robotic and laparoscopic approaches over the study period and a statistically significant decrease in utilization of the open approach. The conversion rates for robotic and laparoscopic cohorts were 7.0% and 15.7%, p < 0.0001. Subgroup analysis revealed statistically lower conversion rates between robotic and laparoscopic approaches for rectosigmoid and rectal tumors and for LAR and APR. Converted cohorts had statistically significant higher odds of short term mortality than the non-converted cohorts (p < 0.05).Laparoscopic conversion had statistically higher odds of positive margins (p < 0.0001) and 30-day unplanned readmission (p < 0.0001) than the laparoscopic non-conversion. Increased adjusted mortality hazard was seen for converted laparoscopy relative to non-converted laparoscopy (p = 0.0019). CONCLUSION: From 2010 to 2016, there was a significant increase in utilization of minimally invasive approaches to surgical management of non-metastatic rectal cancer. A robotic approach demonstrated decreased conversion rates than a laparoscopic approach at the rectosigmoid junction and rectum and for LAR and APR. Improved outcomes were seen in the minimally invasive cohorts compared to those that converted to laparotomy.
Subject(s)
Laparoscopy , Rectal Neoplasms , Robotic Surgical Procedures , Humans , Rectal Neoplasms/surgery , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Traditional trocar systems suffer from several innate flaws due to their silicone seal design. The AirSeal® is a valve-less trocar system that overcomes these flaws by utilizing a system of laminar flow and CO2 recirculation. The purpose of this paper is to examine the effect of the AirSeal® versus a traditional trocar system in operative time, EBL and post-operative complications. To the best of our knowledge, this is the first analysis of this system in robotic colorectal surgery. METHODS: A single surgeon's database was reviewed and all LAR and right hemicolectomy robotic cases from 2014-2015 and 2017-2018 were included for analysis. Patient demographic information was evaluated and primary outcomes examined were operative time, EBL, post-operative complications and hospital LOS. RESULTS: Ninety four patients were identified in the LAR cohort and 56 patients were identified in the right hemicolectomy cohort. Mean operative time for LAR was 293 ± 91.6 min in 2014-2015 and 232 ± 74.6 min in 2017-2018 (p = 0.001); however, this significant difference was not seen between right hemicolectomies. Mean EBL for LAR was 209 ± 189 cc in 2014-2015 and 150 ± 173.9 cc in 2017-2018 (p = 0.05); again, this significant difference was not appreciated for right hemicolectomies. There was no statistically significant difference in rates of wound infections, pneumonia, post-operative pneumonia, DVT/PE, intra-abdominal/pelvic abscesses, or unplanned 30-day readmission rate between 2014-2015 and 2017-2018. Length of stay was reduced in both populations between 2014-2015 and 2017-2018; however, it neither reached statistical significance. CONCLUSION: In patients undergoing low anterior resections, the AirSeal® trocar system demonstrated a statistically significant reduction in mean operative time and EBL compared to the traditional trocar system. There was also a trend towards decreased length of stay and post-operative complications with AirSeal® use in low anterior resections and right hemicolectomies. In patients undergoing distal colorectal procedures, the AirSeal® trocar system should be considered.
Subject(s)
Abdominal Abscess/epidemiology , Colectomy/instrumentation , Colon/surgery , Operative Time , Pneumonia/epidemiology , Postoperative Complications/epidemiology , Rectum/surgery , Robotic Surgical Procedures/instrumentation , Surgical Wound/epidemiology , Abdominal Abscess/etiology , Colectomy/adverse effects , Colectomy/methods , Female , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Patient Readmission/statistics & numerical data , Pneumonia/etiology , Postoperative Complications/etiology , Retrospective Studies , Robotic Surgical Procedures/adverse effects , Robotic Surgical Procedures/methods , Surgical Wound/etiology , Treatment OutcomeABSTRACT
BACKGROUND: Robotic-assisted techniques in colorectal surgery have dramatically increased. Comparative data on the management of uncomplicated and complicated diverticulitis using robotics is lacking. The purpose of this study is to examine outcomes of patients who underwent robotic-assisted resection in diverticulitis. METHODS: A prospectively maintained database performed by a single surgeon was retrospectively reviewed to identify patients who underwent robotic-assisted surgery (RAS) for diverticulitis from October 2009 to November 2018. Demographic data, preoperative and intraoperative parameters and postoperative outcomes were assessed using χ2 or Fisher exact test with p values <0.05 considered significant. IRB approval was obtained for this study, #NCR190935. RESULTS: Comparison revealed significant differences in operative times (222 vs. 291 min, p < 0.00001), mean estimated blood loss (130 vs. 304 cc, p = 0.0003) and mean length of stay (3.9 vs. 5.0 days, p = 0.006). Low rates of postoperative complications were observed, with no significant differences noted for conversion to laparoscopy, surgical site infection, leak, intra-abdominal abscess, 30-day unplanned readmission or recurrence. CONCLUSION: Patients with complicated diverticulitis required longer operative time, had increased estimated blood loss and more often converted to an open procedure; however, overall rates of post-operative complications were low in both groups. RAS shows promise for use in complicated diverticulitis.
Subject(s)
Diverticulitis , Laparoscopy , Robotic Surgical Procedures , Surgeons , Diverticulitis/surgery , Humans , Postoperative Complications , Retrospective Studies , Treatment OutcomeABSTRACT
Historically, T4 tumors of the colon have been a contraindication to minimally invasive resection. The purpose of this study was to conduct a National Cancer Database analysis to compare the outcomes after curative treatment for T4 colon cancer between robotic, laparoscopic, and open approaches. The US National Cancer Database was queried for patients with T4 adenocarcinoma of the colon who underwent curative resection. Groups were separated based on approach (open, laparoscopic, robotic). One to one nearest neighbor propensity score matching (PSM) ± 1% caliper was performed across surgical approach cohorts to balance potential confounding covariates. Kaplan-Meier estimation and Cox-proportional hazards regression were used to analyze primary outcome of survival. Secondary outcomes were analyzed by way of logistic regression. Inclusion criteria and PSM identified 876 cases per treatment approach (n = 2628). PSM provided adequate discrimination between treatment cohorts (0.6 < AUC < 0.8) and potential confounding covariates did not significantly differ between cohorts (all respective P > 0.05). Patients who underwent a robotic approach had lower odds of conversion to laparotomy compared to the laparoscopic cohort (P < 0.0001). Laparoscopic and robotic approaches were associated with increased odds of > 12 lymph nodes examined, decreased odds of positive margins, and decreased odds of 30-day readmission, 30-day mortality, and 90-day mortality compared to the open approach. Cox-proportional hazards regression showed that both robotic and laparoscopic approaches were significantly associated with decreased mortality hazards relative to open. Both laparoscopic and robotic-assisted surgeries achieved improved oncologic outcomes and survival compared to open resection of T4 cancers. A robotic-assisted approach was significantly associated with a lower conversion rate compared to the laparoscopic approach. This case-matched study demonstrates safety of using minimally invasive techniques in T4 cancers.
Subject(s)
Colonic Neoplasms , Laparoscopy , Robotic Surgical Procedures , Colonic Neoplasms/surgery , Humans , Propensity Score , Retrospective Studies , Robotic Surgical Procedures/methods , Treatment OutcomeABSTRACT
INTRODUCTION: Ulcerative colitis (UC) is a chronic inflammatory intestinal disorder that can be managed surgically with a proctocolectomy. Minimally invasive techniques such as laparoscopic or robotic-assisted surgery are available based on the surgeon's preference and familiarity. To date, there is a paucity of literature evaluating the safety of these techniques in comparison to the open approach in patients with UC. METHODS: We surveyed the National Surgical Quality Improvement Program (NSQIP) database to select patients with the diagnosis of UC who underwent either robotic, laparoscopic, or open proctocolectomy between 2012 and 2017. A total of 2129 patients were included in the study. The 30-day postoperative outcomes were compared using multivariable logistic regression models after adjusting for confounding variables. The confounding variables were defined as any preoperative variable that was associated with the type of procedure. RESULTS: The 30-day postoperative outcomes reported in the NSQIP database were reviewed for each of the treatment groups (open, laparoscopic, and robotic). The anastomotic leak rate was significantly higher in the open group (P = .022). The robotic and laparoscopic groups had significantly fewer occurrences of postoperative ileus (P = .0006) and wound infections (P < .0001). There were significantly more strokes, cardiac events, and pulmonary events in the open surgical group. Operative time was significantly shorter in the open group (P < .0001). Reintervention rates were not significantly different among the groups. CONCLUSIONS: Minimally invasive proctocolectomy has significantly fewer postoperative complications compared with open proctocolectomy for UC. There is no significant difference in the postoperative outcomes between robotic-assisted and laparoscopic proctocolectomy.
Subject(s)
Colitis, Ulcerative/surgery , Laparoscopy/adverse effects , Postoperative Complications/epidemiology , Proctocolectomy, Restorative/adverse effects , Robotic Surgical Procedures/adverse effects , Adult , Aged , Databases, Factual , Female , Humans , Male , Middle Aged , Minimally Invasive Surgical Procedures , Operative Time , Quality Improvement , Retrospective Studies , United StatesABSTRACT
BACKGROUND: Data regarding the effect of conversion from minimally invasive surgery (MIS) to laparotomy in rectal cancer is limited. This study examines the impact of conversion from laparoscopic or robotic-assisted techniques to open resection on oncologic outcomes in a large population database. METHODS: The National Cancer Database from 2010 to 2016 was reviewed for all cases of invasive adenocarcinoma of the rectum or rectosigmoid junction managed surgically. Patients were divided into 3 cohorts by approach: laparoscopic/robotic (MIS), converted proctectomy (CP), and open proctectomy (OP). Kaplan-Meier estimation was used for unadjusted survival analysis, followed by adjusted multivariable Cox-Proportional Hazards regression. Secondary outcomes were analyzed by multivariable logistic regression. RESULTS: The inclusion criteria identified 57 574 patients cases of adenocarcinoma of the rectum managed surgically. Of these patients, 23 579 (41.0%) underwent MIS, 3591 (6.2%) CP, and 30 404 (52.8%) OP. Five-year overall survival was greater in the MIS (70.4%) versus CP and OP (64.4% and 61.4%). No differences were detected for positive margins, 30-day, or 90-day mortality between CP and OP. MIS and CP approaches were significantly associated with increased odds of 12 or more regional lymph nodes examined and decreased overall mortality hazard compared with OP (all respective significant P < .05). DISCUSSION: While similar odds of positive margins and short-term mortality is seen in patients whose procedure converts to laparotomy compared with planned laparotomy, both short-term and long-term oncologic benefit is seen in those who undergo a minimally invasive approach. Thus, a minimally invasive approach should be attempted for patients with rectal cancer.
Subject(s)
Conversion to Open Surgery , Laparoscopy , Laparotomy , Proctectomy , Rectal Neoplasms/surgery , Robotic Surgical Procedures , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Adult , Aged , Databases, Factual , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Rectal Neoplasms/mortality , Rectal Neoplasms/pathology , Retrospective Studies , Treatment Outcome , United StatesABSTRACT
Colorectal cancer remains the third most common cancer effecting adults. Surgical guidelines recommend transanal excision of early rectal neoplasia up to 8 cm from the anal verge. A retrospective review of two novel approaches for transanal robotic local excision with R0 resections of rectal cancers which was, on average, higher than 8 cm. Twenty-one cases of robotic assisted transanal surgery for early stage disease (T0-T1, N0) were reviewed. The first 10 cases performed with the da Vinci® Si robotic platform between 2013 and 2016, and the first 11 cases performed using the Flex® Medrobotics platform between August 2017 and August 2018. The average distance from the anal verge was 11.1 cm and 9.5 cm for the da Vinci® Si and Flex® Colorectal Drive, respectively. The average operative time was 167.6 min for the da Vinci® Si and 110.1 min for the Flex® Colorectal Drive; the average EBL was 37.5 cc and 9.1 cc for the da Vinci® Si and Flex® Colorectal Drive. In the da Vinci® series, four cases required intraoperative conversion. In the Flex® series, one case was aborted due to unfavorable robotic positioning. All margins were histologically negative when surgically complete with no recurrences to date. Transanal robotic surgery may provide a method to address rectal lesions farther from the anal verge than previously described. The Flex® Colorectal Drive platform may provide superior ability to navigate the nonlinear anatomy of the rectum and distal sigmoid colon.
Subject(s)
Anal Canal/surgery , Colorectal Neoplasms/surgery , Rectum/surgery , Robotic Surgical Procedures/instrumentation , Robotic Surgical Procedures/methods , Transanal Endoscopic Surgery/instrumentation , Transanal Endoscopic Surgery/methods , Adult , Aged , Colorectal Neoplasms/pathology , Female , Humans , Male , Margins of Excision , Middle Aged , Neoplasm Staging , Operative Time , Retrospective StudiesABSTRACT
Traumatic brain injuries in patients on antithrombotic agents carry significant morbidity. Initial therapy is centered around reversal of these agents. The thromboelastogram (TEG) maps the clotting cascade to guide reversal. A retrospective chart review was conducted for 118 patients presenting with a traumatic brain injury while on antithrombotics. Patients were divided between those who received a TEG on arrival and those who did not. The primary endpoint was overall mortality. Secondary endpoints included blood product utilization, and outcomes associated with specific novel anticoagulants. Mortality in the control group was 20.3 per cent compared with 18.5 per cent in the TEG group (P = 0.81). For less severe injuries, the control group mortality was 3.8 per cent and the TEG group mortality was 8.7 per cent (P = 0.64). For more severe injuries, mortality in the control versus TEG groups were 31.6 per cent and 25.8 per cent, respectively (P = 0.73). Blood product utilization was significantly lower in the TEG group (P = 0.002). Overall mortality was not significantly different between the groups. However, when stratified by severity of injury, mortality was reduced in the TEG-guided group in severely injured patients. Blood product utilization was significantly reduced with TEG-guided reversal. Trauma centers can improve the utilization of blood products in reversal of antithrombotics with the use of TEG.
Subject(s)
Anticoagulants/administration & dosage , Brain Injuries, Traumatic/blood , Intracranial Hemorrhages/blood , Resuscitation/methods , Thrombelastography , Adult , Aged , Aged, 80 and over , Blood Component Transfusion/statistics & numerical data , Brain Injuries, Traumatic/diagnostic imaging , Brain Injuries, Traumatic/mortality , Female , Humans , Injury Severity Score , Intracranial Hemorrhages/diagnostic imaging , Intracranial Hemorrhages/mortality , Length of Stay/statistics & numerical data , Male , Middle Aged , Retrospective Studies , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
IMPORTANCE: An overwhelming amount of data suggest that cardiovascular exercise has a positive effect on the mind and body, although the precise mechanism is not always clear. OBJECTIVE: To assess the clinical and biochemical effects of voluntary cardiovascular exercise on pedicled flaps in a rodent model. DESIGN, SETTING, AND PARTICIPANTS: Eighteen adult Sprague-Dawley male rats were randomized into a resting animal group (RAG) (n=9) and an exercise animal group (EAG) (n=9) for 14 days (July 23, 2013, through July 30, 2013). A pedicled transposition flap was performed on the ventral surface of the rat, and biopsy specimens were taken from the proximal, middle, and distal portions on postoperative days 0, 2, 5, and 9. Flap survival was analyzed planimetrically, and biopsy specimens were analyzed by hematoxylin-eosin-stained microscopy and immunoblotting. The housing, exercise, surgery, and analysis of the rats were conducted at a single basic science research laboratory at the tertiary care center campus of Thomas Jefferson University in Philadelphia, Pennsylvania. EXPOSURES: The rats were caged for 14 days or housed in a cage connected to an exercise wheel and pedometer. MAIN OUTCOMES AND MEASURES: Study measures were gross and micrographic necrosis and expression of proteins within cell survival and apoptosis pathways. RESULTS: A total of 18 rats were studied, 9 in the RAG and 9 in the EAG. the mean (SEM) amount of necrosis in flaps was 41.3% (3%) in the RAG rats and 10.5% (3.5%) in the EAG rats (P < .001). Immunoblotting revealed increased Caspase-9 activity resulting in poly-(adenosine diphosphate-ribose) polymerase 1 cleavage in the RAG vs the EAG, as well as lower phosphorylated protein kinase B (also known as Akt), signal transducer and activator of transcription 3, and total B-cell leukemia/lymphoma 2 protein levels. Throughout the postoperative period, the cumulative vascular endothelial growth factor A levels of the EAG flaps were significantly higher than those of the RAG flaps (2.30 vs 1.25 fold induction [FI], P = .002), with differences of 2.76 vs 1.54 FI in the proximal segment, 2.40 vs 1.20 FI in the middle segment, and 1.90 vs 0.79 FI in the distal segment. A similar response was noted when comparing phosphorylated Akt, with cumulative mean (SEM) p-Akt expression levels of 0.62 (0.04) for RAG and 1.98 (0.09) for EAG (P = .002 between the 2 groups). CONCLUSIONS AND RELEVANCE: Voluntary preoperative exercise improves survival in pedicled fasciocutaneous flaps; the EAG rats had less necrosis, decreased apoptotic markers, and increased amounts of vascular endothelial growth factor A and prosurvival proteins. These results have implications to increase flap survival in other mammal populations, such as humans. LEVEL OF EVIDENCE: 3.
Subject(s)
Biomechanical Phenomena/physiology , Disease Models, Animal , Graft Survival/physiology , Physical Conditioning, Animal , Surgical Flaps/pathology , Surgical Flaps/physiology , Animals , Apoptosis/physiology , Male , Necrosis , Proteins/metabolism , Rats , Rats, Sprague-Dawley , Vascular Endothelial Growth Factor A/metabolismABSTRACT
BACKGROUND: Poorer surgical outcomes in older patients undergoing locoregional head and neck reconstruction have raised questions about tolerance of aging tissue to iatrogenic ischemic insults. METHODS: We examined the effects of aging on viability of pedicled composite flaps in 2-month and 6-month old Sprague-Dawley male rats and correlated flap survival with vascular endogenous growth factor (VEGF) and VEGF receptor 2-mediated signaling events. Flap segments were assessed for gross/cellular necrosis by optical microscopy and for proangiogenic, apoptotic, and proliferative protein-marker content. RESULTS: Flap necrosis significantly increased with age (4.2% in young vs 49.17% in old), correlating with reduced expression of VEGF, inhibition of signal transducer and activator of transcription 3 (STAT3), and Akt activation, impaired Akt-dependent endothelial nitric oxide synthase (eNOS) phosphorylation, elevated Bax/Bcl-2 ratio, activation of Caspase-3, upregulated nuclear poly (ADP-ribose) polymerase-1 (PARP-1) cleavage and lower proliferating cell nuclear antigen (PCNA) levels. CONCLUSION: Pedicled flap survival is higher in younger rats in part because of unhindered expression of VEGF and enhanced activity of cell survival and promigratory signaling pathways. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1152-E1162, 2016.