Sheraz R. Markar

Salvage Surgery After Chemoradiotherapy in the Management of Esophageal Cancer: Is It a Viable Therapeutic Option?

PURPOSE The aim of this large multicenter study was to assess the impact of salvage esophagectomy after definitive chemoradiotherapy (SALV) on clinical outcome. PATIENTS AND METHODS Data from consecutive adult patients undergoing resection for esophageal cancer in 30 European centers from 2000 to 2010 were collected. First, groups undergoing SALV (n = 308) and neoadjuvant chemoradiotherapy followed by planned esophagectomy (NCRS; n = 540) were compared. Second, patients who benefited from SALV for persistent (n = 234) versus recurrent disease (n = 74) were compared. Propensity score matching and multivariable analyses were used to compensate for differences in some baseline characteristics. RESULTS SALV versus NCRS groups: In-hospital mortality was similar in both groups (8.4% v 9.3%). The only significant differences in complications were seen for anastomotic leak (17.2% v 10.7%; P = .007) and surgical site infection, which were both more frequent in the SALV group. At 3 years, groups had similar overall (43.3% v 40.1%; P = .542) and disease-free survival (39.2% v 32.8%; P = .232) after matching, along with a similar recurrence pattern. Persistent versus recurrent disease groups: There were no significant differences between groups in incidence of in-hospital mortality or major complications. At 3 years, overall (40.9% v 56.2%; P = .046) and disease-free survival (36.6% v 51.6%; P = .095) were lower in the persistent disease group. CONCLUSION The results of this large multicenter study from the modern era suggest that SALV can offer acceptable short- and long-term outcomes in selected patients at experienced centers. Persistent cancer after definitive chemoradiotherapy seems to be more biologically aggressive, with poorer survival compared with recurrent cancer.

The impact of severe anastomotic leak on long-term survival and cancer recurrence after surgical resection for esophageal malignancy

Objective: The aim of this study was to the determine impact of severe esophageal anastomotic leak (SEAL) upon long-term survival and locoregional cancer recurrence. Background: The impact of SEAL upon long-term survival after esophageal resection remains inconclusive with a number of studies demonstrating conflicting results. Methods: A multicenter database for the surgical treatment of esophageal cancer collected data from 30 university hospitals (2000–2010). SEAL was defined as a Clavien-Dindo III or IV leak. Patients with SEAL were compared with those without in terms of demographics, tumor characteristics, surgical technique, morbidity, survival, and recurrence. Results: From a database of 2944 operated on for esophageal cancer between 2000 and 2010, 209 patients who died within 90 days of surgery and 296 patients with a R1/R2 resection were excluded, leaving 2439 included in the final analysis; 208 (8.5%) developed a SEAL and significant independent association was observed with low hospital procedural volume, cervical anastomosis, tumoral stage III/IV, and pulmonary and cardiovascular complications. SEAL was associated with a significant reduction in median overall (35.8 vs 54.8 months; P = 0.002) and disease-free (34 vs 47.9 months; P = 0.005) survivals. After adjustment of confounding factors, SEAL was associated with a 28% greater likelihood of death [hazard ratio = 1.28; 95% confidence interval (CI): 1.04–1.59; P = 0.022], as well as greater overall (OR = 1.35; 95% CI: 1.15–1.73; P = 0.011), locoregional (OR = 1.56; 95% CI: 1.05–2.24; P = 0.030), and mixed (OR = 1.81; 95% CI: 1.20–2.71; P = 0.014) recurrences. Conclusions: This large multicenter study provides strong evidence that SEAL adversely impacts cancer prognosis. The mechanism through which SEAL increases local recurrence is an important area for future research.

Peroral endoscopic myotomy for the treatment of esophageal achalasia: systematic review and pooled analysis.

Peroral endoscopic myotomy (POEM) is a novel approach to performing esophageal myotomy for the treatment of achalasia. This review aims to assess subjective and objective metrics of achalasia treatment efficacy, perioperative adverse events and the incidence of postoperative gastroesophageal reflux disease in patients treated with POEM. Secondary aims include a pooled analysis comparison of the clinical outcomes and procedural safety of POEM versus laparoscopic Hellers myotomy (LHM). A systematic review of the literature, up to and including January 15, 2015, was conducted for studies reporting POEM outcomes. Studies comparing POEM to LHM were also included for the purpose of pooled analysis. Outcomes from 1122 POEM patients, from 22 studies, are reported in this systematic review. Minor operative adverse events included capno/pneumo-peritoneum (30.6%), capno/pneumo-thorax (11.0%) and subcutaneous emphysema (31.6%). Major operative adverse events included mediastinal leak (0.3%), postoperative bleeding (1.1%) and a single mortality (0.09%). There was an improvement in lower esophageal sphincter pressure and timed barium esophagram column height of 66% and 80% post-POEM, respectively. Symptom improvement was demonstrated with a pre- and post-POEM Eckardt score ± standard deviation of 6.8 ± 1.0 and 1.2 ± 0.6, respectively. Pre- and post-POEM endoscopy showed esophagitis in 0% and 19% of patients, respectively. The median (interquartile range) points scored for study quality was 15 (14-16) out of total of 32. Pooled analysis of three comparative studies between LHM and POEM showed similar results for adverse events, perforation rate, operative time and a nonsignificant trend toward a reduced length of hospital stay in the POEM group. In conclusion, POEM is a safe and effective treatment for achalasia, showing significant improvements in objective metrics and achalasia-related symptoms. Randomized comparative studies of LHM and POEM are required to determine the most effective treatment modality for achalasia.

Laparoscopic vs Open Appendectomy in Older Patients

HYPOTHESIS The results of a meta-analysis of individual studies comparing laparoscopic vs open appendectomy in older patients may guide the choice of surgical approach. DESIGN Meta-analysis. SETTING Academic research. PATIENTS MEDLINE, EMBASE, Web of Science, and Cochrane databases were searched for comparative studies of older patients with a diagnosis of acute appendicitis. MAIN OUTCOME MEASURES Primary outcomes were postoperative mortality and overall morbidity. Secondary outcomes were operative time, length of hospital stay, postoperative wound infection, and intra-abdominal collection. Using the lowest threshold from the articles included, older patients were defined as those older than 60 years. RESULTS Analyzed were 6 studies comprising 15 852 appendectomies (4398 laparoscopic and 11 454 open procedures). Laparoscopic appendectomy was associated with significant reductions in postoperative mortality (pooled odds ratio, 0.24; 95% CI, 0.15-0.37), postoperative complications (pooled odds ratio, 0.61; 95% CI, 0.50-0.73), and length of hospital stay (weighted mean difference, -0.51 days; 95% CI, -0.64 to -0.37 days) (P < .05 for all). No significant group differences were observed in operative time, postoperative wound infection, or intra-abdominal collection. CONCLUSIONS In older patients, laparoscopic appendectomy is associated with reduced postoperative mortality and morbidity, although randomized data are required to infer causality. A health economic analysis with quality-of-life metrics is needed to investigate potential benefits of the reduced length of hospital stay observed following laparoscopic appendectomy in this cohort.

Application of gold nanoparticles for gastrointestinal cancer theranostics: A systematic review

UNLABELLED Gold nanoparticles (GNPs) are readily synthesised structures that absorb light strongly to generate thermal energy which induces photothermal destruction of malignant tissue. This review examines the efficacy, potential challenges and toxicity from in vitro and in vivo applications of GNPs in oesophageal, gastric and colon cancers. A systematic literature search of Medline, Embase, Web of Science and Cochrane databases was performed using PRISMA guidelines. Two hundred and eighty-four papers were reviewed with sixteen studies meeting the inclusion criteria. The application of GNPs in eleven in vivo rodent studies with GI adenocarcinoma demonstrated excellent therapeutic outcomes but poor corroboration in terms of the cancer cells used, photothermal irradiation regimes, fluorophores and types of nanoparticles. There is compelling evidence of the translational potential of GNPs to be complimentary to surgery and feasible in the photothermal therapy of GI cancer but reproducibility and standardisation require development prior to GI cancer clinical trials. FROM THE CLINICAL EDITOR Gold nanoparticles are one of the most potentially useful nanoparticles. This is especially true in cancer therapeutics because of their photothermal properties. In this comprehensive article, the authors reviewed the application and efficacy of gold nanoparticles in both the diagnosis and treatment of GI cancers. This review should provide a stimulus for researchers to further develop and translate these nanoparticles into future clinical trials.

Management and Outcomes of Esophageal Perforation: A National Study of 2,564 Patients in England.

OBJECTIVES:Traditionally esophageal perforation is a rare clinical emergency that confers a high rate of mortality and major morbidity. The objective of this study was to establish the annual rate and mortality from esophageal perforation and determine the effect of hospital volume on clinical outcomes.METHODS:Hospital Episode Statistics database was used for the identification of patients admitted to hospitals within England with esophageal perforation between 2001 and 2012. The influence of hospital volume and treatment approach upon clinical outcomes was analyzed using multivariable analysis to control for patient age and medical comorbidities that may influence outcome.RESULTS:Over the 12-year study period 2,564 patients with esophageal perforation were treated at 158 hospitals. The 30- and 90-day mortality rates were 30.0 and 38.8%, respectively. Esophageal perforation etiology was spontaneous in 81.9% and iatrogenic in 5.9% of cases. There was a significant increase in the percentage of patients managed supportively and a reduction in surgical management over time. Furthermore there were significant reductions in 30-day (36.6% to 24.9%; P<0.001) and 90-day mortality (44.1% to 35.4%; P=0.006) over the 12-year study period. Important patient demographics associated with 30- and 90-day mortality included age ≥70 years, preoperative congestive cardiac failure, ischemic heart, liver, and renal disease. High hospital volume was associated with significant reductions in 30- (odds ratio (OR)=0.68; P=0.001) and 90-day mortality (OR=0.69; P=0.001). In a subset analysis of patients undergoing endoscopic intervention, hospital volume was identified as an important factor associated with mortality.CONCLUSIONS:This study provides evidence for the centralization of management of esophageal perforation to high volume centers with appropriate multi-disciplinary infrastructure to treat these complex patients.

Surgical Proficiency Gain and Survival After Esophagectomy for Cancer

PURPOSE We aimed to identify the presence and length of esophagectomy proficiency gain curves in terms of short- and long-term mortality for esophageal cancer. PATIENTS AND METHODS Patients who underwent esophagectomy for esophageal cancer between 1987 and 2010 with follow-up until 2014 were identified from a well-established, population-based, nationwide Swedish cohort study. Proficiency gain curves were created by using risk-adjusted cumulative sum analysis for 30-day, 90-day, 1-year, 3-year, and 5-year all-cause and disease-specific mortality measures. Similarly, the proficiency gain curves for lymph node harvest, resection margin status, and reoperation incidence were assessed as performance-contributing factors to the observed changes in long-term survival. RESULTS Esophagectomies in 1,821 patients with esophageal cancer were conducted by 139 surgeons. The change-point in proficiency gain curve for all-cause 30-day mortality was early, at 15 cases, when mortality decreased from 7.9% to 3.1% (P < .001). Later change-points, which ranged from 35 to 59 cases, were observed for 1-, 3- and 5-year mortality rates, for which all-cause mortality decreased from 34.9% to 27.7% (P = .011), from 47.4% to 41.5% (P = .049), and from 31.4% to 19.1% (P = .009), respectively. Similar change-points were observed in disease-specific mortality at 1 and 3 years. There was a continuous increase in lymph node harvest, which did not plateau. Also, change-points were observed for resection margin with tumor involvement at 17 cases, with a reduction from 20.9% to 15.2% (P = .004), and for reoperation rate at 55 cases, with a reduction from 12.6% to 5.0% (P < .001). CONCLUSION The gain of proficiency in esophagectomy for cancer is associated with measurable changes in short- and long-term mortality results. These findings indicate a need for structured national training and mentorship programs for esophageal cancer surgery.

National proficiency‐gain curves for minimally invasive gastrointestinal cancer surgery

Minimal access surgery for gastrointestinal cancer has short‐term benefits but is associated with a proficiency‐gain curve. The aim of this study was to define national proficiency‐gain curves for minimal access colorectal and oesophagogastric surgery, and to determine the impact on clinical outcomes.

Laparoscopic Approach to Appendectomy Reduces the Incidence of Short- and Long-Term Post-operative Bowel Obstruction: Systematic Review and Pooled Analysis

BackgroundThe aim of this meta-analysis was to determine the effect of laparoscopic appendectomy (LA) compared to open appendectomy (OA) on short-term and long-term post-operative bowel obstruction.MethodsMedline, Embase, trial registries, conference proceedings and reference lists were searched. Subset analysis was performed for paediatric patients, patients who presented with perforated appendicitis and studies with long-term follow-up and surveillance for bowel obstruction and with surgery for bowel obstruction.ResultsOverall, 29 studies comprising 159,729 patients (60,875 LA versus 98,854 OA) were included. LA was associated with a significant reduction in the incidence of post-operative bowel obstruction in the general population (pooled odds ratio (POR) = 0.43 [95 %C.I. 0.3–0.63]). Subset analysis demonstrated that LA significantly reduced the incidence of post-operative bowel obstruction in paediatric patients (POR = 0.48 [95 %C.I. 0.3–0.78]) and patients with perforated appendicitis (POR = 0.44 [95 %C.I. 0.26–0.74]). Furthermore, LA was associated with a significantly reduced incidence of long-term bowel obstruction (POR = 0.33 [95 %C.I. 0.19–0.56]) and bowel obstruction requiring surgery (POR = 0.31 [95 %C.I. 0.2–0.48]).DiscussionsThis present meta-analysis provides evidence to clearly demonstrate the benefits of a laparoscopic approach to appendectomy as reflected by a reduction in short- and long-term adhesive bowel obstruction. Important future areas for assessment include the influence of surgical approach on long-term quality of life following appendectomy.

The Impact of Pancreatic Duct Drainage Following Pancreaticojejunostomy on Clinical Outcome

BackgroundThe aim of this meta-analysis is to evaluate the effect of stenting the pancreatic duct during pancreaticojejunostomy formation on perioperative outcomes.MethodsPrimary outcome measures were operative mortality and pancreatic fistula. Secondary outcomes were length of hospital stay, reoperation, delayed gastric emptying, estimated blood loss, and length of operation. Internal and external pancreatic stents were grouped together for the purposes of analysis.ResultsSix trials were included in this analysis comprising 732 patients. Pancreatic stent placement had no significant effect on operative mortality; however, there was a non-significant trend towards reduced pancreatic fistula. Estimated blood loss, length of operation, and length of hospital stay were significantly increased in association with pancreatic stent placement. There were no significant effects on reoperation or delayed gastric emptying.ConclusionThis analysis demonstrates a trend towards reduced pancreatic fistula with the use of pancreatic stents in pancreaticojejunostomy. However, there were insufficient data to confidently reject the null hypothesis that stenting has no beneficial effect. Further research is required to identify whether in certain subgroups, such as those with soft pancreatic texture and a non-dilated duct, stents may have a more important role in reducing fistula formation.