David A. Margolin

Effect of Laparoscopic-Assisted Resection vs Open Resection of Stage II or III Rectal Cancer on Pathologic Outcomes: The ACOSOG Z6051 Randomized Clinical Trial

IMPORTANCE Evidence about the efficacy of laparoscopic resection of rectal cancer is incomplete, particularly for patients with more advanced-stage disease. OBJECTIVE To determine whether laparoscopic resection is noninferior to open resection, as determined by gross pathologic and histologic evaluation of the resected proctectomy specimen. DESIGN, SETTING, AND PARTICIPANTS A multicenter, balanced, noninferiority, randomized trial enrolled patients between October 2008 and September 2013. The trial was conducted by credentialed surgeons from 35 institutions in the United States and Canada. A total of 486 patients with clinical stage II or III rectal cancer within 12 cm of the anal verge were randomized after completion of neoadjuvant therapy to laparoscopic or open resection. INTERVENTIONS Standard laparoscopic and open approaches were performed by the credentialed surgeons. MAIN OUTCOMES AND MEASURES The primary outcome assessing efficacy was a composite of circumferential radial margin greater than 1 mm, distal margin without tumor, and completeness of total mesorectal excision. A 6% noninferiority margin was chosen according to clinical relevance estimation. RESULTS Two hundred forty patients with laparoscopic resection and 222 with open resection were evaluable for analysis of the 486 enrolled. Successful resection occurred in 81.7% of laparoscopic resection cases (95% CI, 76.8%-86.6%) and 86.9% of open resection cases (95% CI, 82.5%-91.4%) and did not support noninferiority (difference, -5.3%; 1-sided 95% CI, -10.8% to ∞; P for noninferiority = .41). Patients underwent low anterior resection (76.7%) or abdominoperineal resection (23.3%). Conversion to open resection occurred in 11.3% of patients. Operative time was significantly longer for laparoscopic resection (mean, 266.2 vs 220.6 minutes; mean difference, 45.5 minutes; 95% CI, 27.7-63.4; P < .001). Length of stay (7.3 vs 7.0 days; mean difference, 0.3 days; 95% CI, -0.6 to 1.1), readmission within 30 days (3.3% vs 4.1%; difference, -0.7%; 95% CI, -4.2% to 2.7%), and severe complications (22.5% vs 22.1%; difference, 0.4%; 95% CI, -4.2% to 2.7%) did not differ significantly. Quality of the total mesorectal excision specimen in 462 operated and analyzed surgeries was complete (77%) and nearly complete (16.5%) in 93.5% of the cases. Negative circumferential radial margin was observed in 90% of the overall group (87.9% laparoscopic resection and 92.3% open resection; P = .11). Distal margin result was negative in more than 98% of patients irrespective of type of surgery (P = .91). CONCLUSIONS AND RELEVANCE Among patients with stage II or III rectal cancer, the use of laparoscopic resection compared with open resection failed to meet the criterion for noninferiority for pathologic outcomes. Pending clinical oncologic outcomes, the findings do not support the use of laparoscopic resection in these patients. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00726622.

Sacral nerve stimulation for fecal incontinence: Results of a 120-patient prospective multicenter study

Background:Sacral nerve stimulation has been approved for use in treating urinary incontinence in the United States since 1997, and in Europe for both urinary and fecal incontinence (FI) since 1994. The purpose of this study was to determine the safety and efficacy of sacral nerve stimulation in a large population under the rigors of Food and Drug Administration-approved investigational protocol. Methods:Candidates for SNS who provided informed consent were enrolled in this Institutional Review Board-approved multicentered prospective trial. Patients showing ≥50% improvement during test stimulation received chronic implantation of the InterStim Therapy (Medtronic; Minneapolis, MN). The primary efficacy objective was to demonstrate that ≥50% of subjects would achieve therapeutic success, defined as ≥50% reduction of incontinent episodes per week at 12 months compared with baseline. Results:A total of 133 patients underwent test stimulation with a 90% success rate, and 120 (110 females) of a mean age of 60.5 years and a mean duration of FI of 6.8 years received chronic implantation. Mean follow-up was 28 (range, 2.2–69.5) months. At 12 months, 83% of subjects achieved therapeutic success (95% confidence interval: 74%–90%; P < 0.0001), and 41% achieved 100% continence. Therapeutic success was 85% at 24 months. Incontinent episodes decreased from a mean of 9.4 per week at baseline to 1.9 at 12 months and 2.9 at 2 years. There were no reported unanticipated adverse device effects associated with InterStim Therapy. Conclusion:Sacral nerve stimulation using InterStim Therapy is a safe and effective treatment for patients with FI.

Surgical treatment of hemorrhoids: prospective, randomized trial comparing closed excisional hemorrhoidectomy and the Harmonic Scalpel technique of excisional hemorrhoidectomy.

PURPOSE: The object of this study was to evaluate technique using the ultrasonically activated scalpel as an alternative to closed hemorrhoidectomy in an unbiased evaluation of this new technology. METHODS: Thirty patients with Grade 2 or 3 symptomatic hemorrhoids were prospectively randomized to undergo closed hemorrhoidectomy assisted by electrocautery or hemorrhoidectomy with the ultrasonically activated scalpel,i.e., the Harmonic Scalpel®. We evaluated the difference between techniques in operative time, postoperative pain, incontinence, and quality of life (using the Short Form-36 survey), as well as complications. RESULTS: Mean operative time for closed hemorrhoidectomy with electrocautery was 35.7 ± 3 minutes; for Harmonic Scalpel® patients, it was 31.7 ± 2 minutes (P<0.37). There was no statistical difference in operative time for two- or three-column hemorrhoidectomy. There was no significant difference in pain measurements reported on Day 1 (5.8 ± 0.4 for electrocautery and 5.6 ± 0.6 for Harmonic Scalpel®,P<0.82). On postoperative Dayaq 7, the difference in pain between groups approached significance, with pain reported as 3.7 ± 0.3 for electrocautery and 5.1 ± 0.7 for Harmonic Scalpel® (P<0.06). At six weeks, both groups were pain free. There was a significant decrease in pain between postoperative Days 1 and 7 in the electrocautery patients that was not seen in the Harmonic Scalpel® patients. Incontinence measured preoperatively, at postoperative Day 7, and at postoperative Week 6 was similar for both groups and reflected occasional incontinence of gas. When the various items of the Short Form-36 survey were compared, there was no significant difference between posttreatment and preoperative values. There was no difference in the number of complications between patient groups. CONCLUSION: Although the Harmonic Scalpel® is an effective tool in the treatment of hemorrhoidal disease, we found no specific advantage in postoperative pain, fecal incontinence, operative time, quality of life, or complications compared with traditional closed hemorrhoidectomy.

A study to determine the nitroglycerin ointment dose and dosing interval that best promote the healing of chronic anal fissures

AbstractPURPOSE: The aim of this study was to determine the optimal dose and dosing interval of nitroglycerin ointment to heal chronic anal fissures. METHOD: A randomized, double-blind study of intra-anally applied nitroglycerin ointment (Anogesic™) was conducted in 17 centers in 304 patients with chronic anal fissures. The patients were randomly assigned to one of eight treatment regimens (0.0, 0.1, 0.2, 0.4 percent nitroglycerin ointment applied twice or three times per day), for up to eight weeks. A dose-measuring device standardized the delivery of 374 mg ointment. Healing of fissures (complete reepithelialization) was assessed by physical examination using an observer unaware of treatment allocation. The subjects assessed pain intensity daily by completing a diary containing a visual analog scale for average pain intensity for the day, the worst pain intensity for the day, and pain intensity at the last defecation. RESULTS: There were no significant differences in fissure healing among any of the treatment groups; all groups, including placebo had a healing rate of approximately 50 percent. This rate of placebo response was inexplicably higher than previously reported in the literature. Treatment with 0.4 percent (1.5 mg) nitroglycerin ointment was associated with a significant (P < 0.0002) decrease in average pain intensity compared with vehicle as assessed by patients with a visual analog scale. The decreases were observed by Day 4 of treatment. At 8 weeks the magnitude of the difference between 0.4 percent nitroglycerin and control was a 21 percent reduction in average pain. Treatment was well tolerated, with only 3.29 percent of patients discontinuing treatment because of headache. Headaches were the primary adverse event and were dose related. CONCLUSION: Nitroglycerin ointment did not alter healing but significantly and rapidly reduced the pain associated with chronic anal fissures.

Epidemiology and Pathophysiology of Diverticular Disease

Diverticular disease is common and thought to result from structural abnormalities of the colonic wall, disordered intestinal motility, or deficiencies of dietary fiber. Signs and symptoms of inflammation include fever, abdominal pain, and leukocytosis.

Increased platelet-derived growth factor production and intimal thickening during healing of Dacron grafts in a canine model*

PURPOSE Growth factor production by endothelial cells on grafts may play a role in the development of intimal hyperplasia and subsequent graft failure. METHODS To study the relationship between platelet-derived growth factor production and graft healing, 26 beagles underwent placement of 20 cm long, 6 mm internal diameter, knitted Dacron thoracoabdominal grafts, either seeded with autologous endothelial cells (n = 14) or unseeded controls (n = 12). The grafts and adjacent arteries were removed 4 or 20 weeks after implantation for measurement of platelet-derived growth factor production in organ culture, endothelial cell coverage, and intimal thickness. RESULTS Midgraft platelet-derived growth factor production by seeded graft segments increased from 41 +/- 6 to 148 +/- 27 pg/cm2/72 hr (p < 0.002) between 4 and 20 weeks. This was accompanied by a significant increase in inner-capsule thickness. Platelet-derived growth factor production by control graft segments also increased from 58 +/- 21 to 163 +/- 42 pg (p < 0.05) and was similar to that of seeded grafts despite more rapid endothelialization of seeded grafts. The increase in growth factor production by Dacron grafts was greater than that of the expanded polytetrafluoroethylene grafts studied previously despite similar endothelial cell coverage. CONCLUSION This increase corresponded with the rapid appearance of smooth muscle cells in the pseudointima of Dacron grafts, suggesting that these cells may be responsible for the observed increase in platelet-derived growth factor production.

The Role of Endoscopic Colon Surveillance in the Transplant Population

AbstractPURPOSE: Long-term immunosuppression increases the risks of developing certain malignancies. This study examines the effects of long-term immunosuppression on the development of metachronous adenomatous polyps and attempts to formulate a sound surveillance plan for these individuals. METHOD: A retrospective analysis was performed of all solid organ transplant patients at Henry Ford Hospital from 1989 to 1999, with a specific focus on endoscopic evaluation and outcomes after three years of surveillance. Comparison was made to an agematched and gender-matched control group from the same endoscopic database. Variables were compared using the chisquared test, Fisher’s exact probability test, and Hochberg’s test. RESULTS: A total of 992 solid organ transplants were performed. Two hundred twenty-nine (23 percent) of the transplant recipients underwent pretransplant colonoscopy, of which 178 patients ( 78 percent) were age 50 years or older. Seventy-four (32 percent) of the prescreened population had polyps, of which 45 patients (61 percent) had adenomas. Twenty-seven patients (36 percent) had synchronous polyps, of which 12 patients (16 percent) had synchronous adenomas. At 3-year follow-up 59 patients (80 percent) had metachronous polyps. Twenty-eight patients (38 percent) had metachronous adenomas. Eleven patients (15 percent) with hyperplastic polyps on initial colonoscopy developed adenomas. The control group consisted of 25 females and 50 males with a mean age of 65.5 ± 1.1 years. Fifty-one patients (68 percent) had adenomas on endoscopy. Twenty-four patients (32 percent) had synchronous lesions, of which 13 patients (17 percent) had synchronous adenomas. Sixty-one patients (84 percent) developed metachronous lesions, of which 33 patients (43 percent) had metachronous adenomas at 3 years. There was no difference in the polyp size or histology between the two groups. There was no statistically significant difference between the transplant patients and the control group in all analyses. CONCLUSION: Because of an equivalent incidence of adenomatous polyps compared with the general population, current screening criteria should be used in patients posttransplant. Transplant patients are not more likely to develop metachronous polyps than the general population. Therefore, posttransplant polyp surveillance should not be more frequent than currently recommended for nontransplant patients with adenomatous polyps.

Continent Ileostomy: Current Experience

PURPOSEThis study was designed to review our recent experience with continent ileostomies and evaluate patient outcomes.METHODSRetrospective chart reviews and phone interviews of patients who underwent a continent ileostomy operation from 1993 to 2003 at the Ochsner Clinic Foundation were performed.RESULTSTwenty-four patients (19 females; age range, 22–73 years) had construction of continent ileostomies (modified Kock pouch). There were no intraoperative mortalities or stoma-related deaths. The mean operating room time for primary construction was 3.9 ± 0.57 hours with a mean length of stay of 7 ± 2 days. The average follow-up period was 66 (range, 6–134) months. The most common underlying indication for the construction of a continent ileostomy was ulcerative colitis (71 percent). Thirteen patients had a continent ileostomy created for conversion of a Brooke ileostomy and seven for a failed ileoanal pouch. Other indications included colonic inertia and incontinence in three patients and one patient who had failed multiple operations for Hirschsprung’s disease. A total of 28 revisions were performed in 14 patients (58 percent). Six patients required multiple procedures. Operative revisions included 12 skin level revision for stenosis, 11 operations for valve repairs, and 1 each for peristomal hernia repair, stomal relocation, and pouch repair for fistulas. Two patients had their pouches removed (Crohn’s disease and inability to manage pouch). The need for revision by 12 months was 29 percent, and the average time period before the first revision was 24 months (range, 4 days to 109 months). The overall failure rate (converted to conventional ileostomy) was only 8.3 percent. Ninety percent of the patients have continent pouches and are satisfied with their pouch function.CONCLUSIONSContinent ileostomies continue to have a high rate of reoperations, reasonable functional results, and are a viable option for failed ileal pouch-anal pouch patients. Surgeons electing to perform continent ileostomies must carefully select their patients and advise them of the high potential for reoperations. Despite a high reoperation rate, patients are pleased with their continent ileostomies.

Emerging Trends in the Etiology, Prevention, and Treatment of Gastrointestinal Anastomotic Leakage

Anastomotic leaks represent one of the most alarming complications following any gastrointestinal anastomosis due to the substantial effects on post-operative morbidity and mortality of the patient with long-lasting effects on the functional and oncologic outcomes. There is a lack of consensus related to the definition of an anastomotic leak, with a variety of options for prevention and management. A number of patient-related and technical risk factors have been found to be associated with the development of an anastomotic leak and have inspired the development of various preventative measures and technologies. The International Multispecialty Anastomotic Leak Global Improvement Exchange group was convened to establish a consensus on the definition of an anastomotic leak as well as to discuss the various diagnostic, preventative, and management measures currently available.

Response after out-of-hospital cardiac arrest in the trauma patient should determine aeromedical transport to a trauma center

OBJECTIVE To evaluate whether aeromedical transport of trauma patients who sustain an out-of-hospital cardiac arrest (OHCA) is justified. DESIGN Retrospective chart review. METHODS We reviewed the outcome of 67 consecutive patients after OHCA with initial resuscitation who were transported to a Level I trauma center. Statistical analysis was used to develop a predictive model for survival. RESULTS The overall survival was 19%. One of 28 patients with a second OHCA survived (p = 0.005). Logistic regression analysis demonstrated that the Revised Trauma Score at trauma center arrival (1.0 +/- 0.25, nonsurvivors vs. 5.15 +/- 0.86, survivors, p = 0.0001), Injury Severity Score (34.9 +/- 2.9, nonsurvivors vs. 21.3 +/- 4.1, p = 0.037) and a sinus-based cardiac rhythm at the time of aeromedical team arrival were predictive of survival (R2 = 0.57, p = 0.0001). Survivors were more likely to have been transported from an outside hospital (28% vs. 8% for scene runs), had a sinus rhythm on team arrival (42% vs. 3%), and maintained a sinus rhythm on arrival at the trauma center (41% vs. 0%); however, these parameters were not predictive of survival in the statistical model. The neurologic outcome of the 13 survivors was good (preinjury state) in three cases, moderate disability (independent living) in three, severe disability (needing assistance) in five, and persistent vegetative state in two. Regression analysis was unable to differentiate survivors with a good neurologic recovery from the rest of the patient population. CONCLUSIONS These results suggest that: (1) trauma patients who are resuscitated to a sinus rhythm after OHCA should be transported to a trauma center; (2) Revised Trauma Score and Injury Severity Score are useful to predict survival; and (3) neurologic outcome is not accurately predicted by this model.