July 2022

Ten year follow up of the SLEEVEPASS Trial comparing laparoscopic sleeve gastrectomy versus Roux-en-Y gastric bypass found that both surgeries resulted in sustained weight loss and comparable resolution of metabolic comorbidities, but patients undergoing bypass had greater 5-year percentage excess weight loss and decreased incidence esophagitis. 

Summary: SLEEVEPASS was a multicenter open-label randomized clinical trial comparing laparoscopic sleeve gastrectomy (LSG) with laparoscopic Roux-en-Y gastric bypass (LRYGB) in 240 patients, recruited from April 2008-June 2010. The original primary end points of the study were % excess weight loss (%EWL) and % total weight loss (%TWL), and secondary end points included remission of obesity-associated comorbidities, including type 2 diabetes, dyslipidemia, hypertension, obstructive sleep apnea (OSA), quality of life (QOL), overall morbidity, and mortality. Additional outcomes analyzed at the 10-year mark included GERD symptoms, PPI usage, and endoscopic findings of esophagitis and/or Barrett’s esophagus. At the 10-year follow-up patients provided a retrospective assessment of GERD symptoms (through a health-related GERD questionnaire) and were offered an endoscopy to assess for esophagitis. 

Of the 228 available patients, 193 (85%) completed the 10-year follow-up. The mean %EWL was 43.5% after LSG and 51.9% after LRYGB (p<0.001). Additionally, the mean %TWL was 23.4% after LSG and 26.9% after LRYGB (p<0.001). Median weight regain was 35% after LSG and 24.7% after LRYGB, although this difference was not statistically different (p=0.16). There were no differences between the two groups in rates of remission of type 2 diabetes (26% LSG vs. 33% LRYGB, p=0.63), dyslipidemia (19% LSG vs. 35% LRYGB, p=0.23), or OSA (42% LSG vs. 45% LRYGB, p=0.30) although hypertension remission was superior after LRYGB (40% LSG vs. 48% LRYGB, p=0.04). Notably, patients in the LSG group had significantly higher presence of esophagitis (31% vs. 7%, p<0.001), increased PPI usage (64% vs. 36%, p<0.001), and higher GERD-HRQL scores (10.5 vs. 0.0, p<0.001). However, there was no difference in rates of Barrett’s esophagus (4% LSG vs. 4% LRYGB, p=0.29). Rates of major and minor complications were equal between the two groups. However, 18 patients in the LSG cohort underwent conversion to LRYGB due to GERD symptoms. 

At 10 years, both LSG and LRYGB have significant and sustained long-term weight loss, with LRGB associated with greater weight loss at 10 years. Additionally, remission in obesity associated comorbidities were largely equal between the two groups, although hypertension remission was superior after LRYGB. We find the results specific to GERD to be particularly notable, as GERD symptoms were not a consideration at the initiation of the study. At the timing of randomization, all patients underwent an upper endoscopy although not an upper GI, which we currently perform on all patients during bariatric surgery evaluation to assess for the presence of reflux. The absence of GERD assessment preoperatively may have influenced the high rates of PPI use, GERD symptoms, and esophagitis in the LSG cohort; many of these patients may have been noted to have reflux on a pre-operative UGI, which could have made LRYGB a more favorable operation from the start. As it were, 18 LSG patients underwent conversion to LRYGB for GERD symptoms. While the overall re-operation rates were comparable between the two cohorts, if GERD had been adequately evaluated pre-operatively, this may have reduced the percent of patients requiring conversion to LRYGB, thus causing LRYGB to have the higher morbidity rate due to internal hernias (18/22 re-operations).  

Key takeaway: LSG and LRYGB both give patients sustained weight loss with reductions in obesity-related comorbidities. However, LSG patients have increased PPI usage, subjective GERD symptoms and endoscopic findings of esophagitis, with a non-insignificant rate of conversion to LRYGB due to GERD symptoms. Accurate evaluation of patients pre-operatively to assess for reflux with an EGD and UGI can appropriately identify patients for whom LRYGB would be preferable, thus preventing future complications and reoperations.

Remote ischemic conditioning (RIC) is a therapeutic strategy in which brief cycles of ischemia and reperfusion are applied to a limb to protect internal organs from sustained ischemic damage. The authors present pre-clinical evidence of decreased intestinal injury and prolonged survival after RIC in a murine NEC model. These findings are then translated to ongoing Phase I and Phase II clinical trials applying RIC to neonatal NEC. 

Summary: Necrotizing enterocolitis (NEC) affects up to 10% of preterm infants and is associated with mortality rates of up to 50%. The etiology of NEC remains imperfectly understood, though in premature infants there is a high association with enteral feeds, suggesting an immature intestinal vasculature resulting in feeding-induced ischemic injury. Remote ischemic conditioning (RIC), in which brief cycles of ischemia and reperfusion are applied to a limb, has been shown to be protective for the heart, lung, and kidneys during episodes of relative ischemia such as during cardiopulmonary bypass. This group presents the findings of a Phase I clinical trial and the protocol for a Phase II randomized control trial evaluating the benefit of RIC in neonatal NEC. 

In retrospective review from this group, 40% of NEC patients progressed to requiring an abdominal operation with 42% mortality despite operative intervention. The progression to surgical NEC occurred at a mean of 3 days, suggesting a window of opportunity for RIC intervention prior to disease progression. In their Phase I trial (Ganji et al), RIC, given as 4 cycles per day of 4 minutes of limb ischemia followed by 4 minutes of reperfusion on 2 consecutive days was demonstrated to be safe in preterm neonates and prolonged survival when administered in the early stage of NEC. Once intestinal necrosis had occurred, there was no benefit to RIC. 

This trial is based on pre-clinical findings from the same group (Koike et al) in which NEC was induced in neonatal mice. When RIC was applied both before onset of intestinal damage or when intestinal changes were first detected, there was notable attenuation of inflammation, recovery of intestinal architecture, and improved survival. RIC applied later in the time course after significant intestinal changes had occurred provided no protection and did not improve survival. The mechanism of protection was determined to be dependent on endothelium-mediated vasodilation, specifically via vasodilators NO and H¬¬2S likely released by the ischemic hind limb tissues. 

Given the significant morbidity and mortality associated with NEC in the neonate, these findings and the ongoing clinical trials represent a promising new therapy for this disease. Furthermore, there is potential for translation to other diseases processes. Many of the trials in adult populations have been in ischemic ‘preconditioning’ which in practice is limited to elective procedures. However, with the biochemical pathways and clinical results presented by this group, there may be a role for extending RIC treatment to other diseases such as mesenteric ischemia or inflammatory bowel disease.

This multi-center retrospective review seeking to determine the ideal combination of anticoagulant and antiplatelet to preserve graft patency after femoropopliteal bypass procedures did not find that a particular combination was superior, suggesting regimens can be individualized based on a given patient’s other comorbidities.

Summary: Surgical bypass has been a cornerstone of treatment for femoropopliteal occlusive disease for many years. Traditionally, postoperative care required daily low dose aspirin and routine duplexes to support a long-term goal of maintaining graft patency. More recently, the VOYAGER PAD trial confirmed results of the COMPASS trial that taking low-dose Xarelto and aspirin daily resulted in better limb outcomes in peripheral arterial disease (PAD) patients as compared to aspirin alone.  With the advent of multiple new antiplatelet and anticoagulation medications, the optimal postoperative regimen for maintenance of a femoropopliteal bypass patency is unknown. 

In their paper “Impact of anticoagulation/antiplatelet therapy on femoropopliteal bypass graft outcomes,” Kim et. al present a retrospective review of bypasses found in the Research Patient Data Registry (RPDR) database. 1292 patients who underwent primary femoropopliteal bypass between the years of 1995 and 2020 were identified and then grouped by postoperative antiplatelet and anticoagulation regimen. These groups consisted of no regimen (4%), monoantiplatelet therapy (45.4%), dual antiplatelet therapy (DAPT; 16.6%), anticoagulation alone (5.7%), anticoagulation and monoantiplatelet therapy (24.7%), and anticoagulation and DAPT (3.3%). Patients in this study had a median follow up time of two years, with 8.6% being lost to follow up within 30 days. Bypasses were done with greater saphenous vein (GSV) in 661 patients (51.1%), and prosthetic in 631 (48.8%) patients. Patients who underwent prosthetic bypass were more frequently placed on regimens using anticoagulation.

The primary endpoint examined in this study was major adverse limb events (MALE) after bypass. The investigators considered either major amputation or reintervention for patency as a MALE. There were no differences in immediate postoperative complications (hematoma, pseudoaneurysm, wound infection, lymphocele, lymphocutaneous fistula, or postop MI) in any group on univariate analysis. No specific antiplatelet/anticoagulation regimen was associated with increased rates of MALE. Below-knee target (HR 1.25, CI 1.04-1.52 P=.019) and surgical indication of tissue loss (HR 1.4, CI 1.04-1.88, P = .028) were both associated with MALE after adjusting for patient factors. Use of a GSV conduit was associated with decreased MALE (HR 0.84, CI 0.7-1.01), but was not a statistically significant finding (P = 0.06). Freedom from MALE was plotted on Kaplan-Meier curves, however at 4-5 years all groups had a >50% cumulative MALE rate. 

Overall, this study highlighted the heterogeneity of patient response to various regimens and suggested a patient-specific approach continue to be utilized in managing postoperative antiplatelet/anticoagulation regimens. Using above the knee targets and autogenous vein whenever possible remain the gold standard for femoropopliteal bypass. There was no benefit seen in more aggressive (triple therapy) regimens, however also no increased bleeding risk in the short term. More research needs to be done to discover the optimal treatment strategy for postoperative bypass patients.