December 2020

Synopsis: Obesity is a worldwide epidemic, affecting nearly 33% of adults in the United States. Type II diabetes is present in up to 85% of the overweight and obese population, and for obese diabetic patients who fail medical weight management, bariatric surgery is highly effective at inducing durable glycemic control. In comparison to procedures that maintain gastrointestinal continuity, those that bypass the upper gastrointestinal tract, such as the Roux-en-Y gastric bypass (RYGB), are thought to be most effective, with improvements often evident within days to weeks of surgery. The rapid improvements witnessed following these bypass procedures have led many to believe that the effects on glucose metabolism are not completely explained by weight loss alone. Proponents of this theory hypothesize that upper gastrointestinal tract bypass leads to alterations in metabolic and neuroendocrine pathways, impacting the main pathophysiologic inducers of type II diabetes, including multiorgan insulin resistance and inadequate beta call function. Although much effort has been spent trying to prove this, many of the reported studies differ in methodology, endpoints, and, most notably, extent of weight loss among the surgical and medical cohorts, confounding the exact mechanisms behind improvements in glycemic control following gastrointestinal bypass. To address these limitations, the present study by Yoshino et al. was designed to determine whether RYGB has therapeutic metabolic effects that are independent of weight loss in patients with type II diabetes who achieved a similar targeted weight loss goal.

This matched, prospective cohort study compared patients with marked weight loss following RYGB (surgery group) to patients with the same weight loss induced by medical therapy (diet group). The primary outcome evaluated was change in hepatic insulin sensitivity, and secondary outcomes included changes in diabetes medication management (calculated as a diabetes medication score), 24-hour plasma glucose, beta cell function, and evaluation of variations in several metabolic factors postulated to induce glycemic improvements independent of weight loss. The diet group achieved weight loss mainly via low caloric intake with shakes and prepackaged meals provided by study coordinators. After achievement of targeted weight loss in both groups (16%-24% of baseline weight), a constant body weight was maintained for 3 weeks, and all oral hypoglycemics or insulin were stopped at pre-determined intervals prior to testing. Following enrollment, 11 patients in the surgery group and 11 patients in the medical group achieved targeted weight loss and were compared. Both groups were similar in demographic and baseline diabetes characteristics, and the mean weight loss was 17.8% in the medical group compared to 18.7% in the surgery group. Hepatic insulin sensitivity and beta cell function increased equally in both groups following weight loss. Likewise, both groups had proportional decreases in their diabetes medication score, and similar improvements in 24-hour plasma glucose. Branched chain amino acids decreased in the surgery group but not in the medical group, and plasma bile acids decreased in the medical group but increased in the surgery group. Gut microbiome composition changed in both cohorts, but more so in the surgery group. 

Take-aways: Following marked weight loss induced by either diet therapy or RYGB, equal, considerable improvements in hepatic insulin sensitivity, medications required for glycemic control, 24-hour plasma glucose and beta cell function were seen. Branched chain amino acids and gut microbiome did change more in those who underwent surgery, confirming the known effects gastrointestinal bypass has on these parameters, but this did not appear to have much impact on improving metabolic function. While this study demonstrates that it is likely just weight loss, that leads to improvements in glycemic control following bariatric surgery, it is crucial to realize that the methodology by which weight loss was achieved in the diet group this study is not a realistic option for widespread implementation. Given the notoriously challenging and often unsuccessful nature of weight loss with lifestyle management and dietary modifications alone in the general population, coupled with the well-established durability of weight loss induced by bariatric surgery, this study strongly contributes to the pre-existing literature supporting bariatric surgery as a first-line therapy option for coexisting diabetes in the obese population. 

Synopsis: NSAIDS, and ketorolac in particular, are an area of frequent controversy between anesthesia teams and surgeons due to the concern of increased risk of bleeding associated with its perioperative use. Physiologically, this concern is derived from the fact that ketorolac blocks the production of thromboxane A2, an essential component needed for platelet aggregation. Within surgical literature, early data that suggested increased risk of bleeding was derived specifically from the ENT experience (tonsillectomies, adenoidectomies). However, there is a paucity of randomized, prospective analysis in General Surgery to address this association for our patient population, and as such we should use data compiled from other surgical fields.

This group focused on a collection of studies related to NSAID and ketorolac use in plastic surgery procedures involving the breast, abdomen, craniofacial, upper extremities, and hand. Inclusion criteria were broad, covering epidemiological studies, retrospective chart reviews or randomized trials all with primary outcomes associated with intraoperative or postoperative hematoma and increased bleeding risk with perioperative NSAID administration. A total of 15 studies met these inclusion criteria with 9 focused on ketorolac, 2 for celecoxib and 4 for ibuprofen with a total of 3064 patients. There were a total of 1670 patients in the NSAID group and 1385 in the control group receiving no NSAIDS. 

Overall, there was no increase in bleeding or hematoma formation between the treatment or control groups (OR, 1.2 [0.73-1.97]; P = 0.48) and when separated into specific drug groups there was no increased risk of bleeding with ketorolac (OR, 1.48[0.86-2.56] P= 0.57). The findings of the current meta-analysis are in congruence with a previous meta-analysis by Gobble et al, 2014, who studied only the effect of ketorolac on postoperative bleeding, finding no increased risk (OR, 1.1 [0.61-2.06]; P = 0.72). 

Ketorolac has a relatively flat dose-response curve and evidence suggests that there is no difference in analgesic effectiveness between 10, 15 and 30mg doses when treating acute pain (Motov et al, 2017). These findings suggest that there can be conservative use of ketorolac while taking advantage of its clinical effectiveness. In fact, Oliviera et al, 2012 found that a single dose of IM or IV ketorolac was able to reduce the amount of rescue opioids needed for pain. 

The findings of the above study in conjunction with previous literature suggest that there is no increased risk of bleeding associated with the use of ketorolac in a wide range of plastic surgery procedures. Further studies are needed within General Surgery subspecialties to determine whether this generalization is applicable to all patient cohorts, as the use of NSAIDS and Ketorolac are an invaluable tool to reduce opioid use while effectively reducing post-operative pain. 

Synopsis: Retroperitoneal Sarcoma (RPS) is a rare disease, with surgical resection the only potentially curative treatment. RPS represents a multitude of histologies despite the rare nature of the disease. Given these factors, there is great variability in reported outcomes and treatment strategies for RPS. The utility of radiation in RPS has largely been extrapolated from the experience in extremity sarcoma and remains controversial.

This is a randomized, phase 3, controlled trial undertaken in 31 centers across Europe and North America. 266 adults with histologically documented, localized, operatively resectable, primary RPS were randomized to receive surgery alone or preoperative radiotherapy followed by surgery. The objective of surgery was macroscopically complete resection of the tumor as well as en-bloc organ resection as needed. The primary endpoint was abdominal recurrence free survival- which was a composite endpoint defined by progressive disease to the point of non-resection, macroscopically incomplete resection, sarcomatosis or local relapse. 

133 patients were assigned to each group and followed for a median of 43.1 months. 128 (96%) patients in the surgery only group underwent surgery, and 119 (89%) of patients of patients in the radiation group underwent surgery. Median recurrence free survival in the surgery alone group was 5.0 years, and 4.5 years in the radiation + surgery group. Abdominal recurrence-free survival at 3 years was 58.7% (95% CI 49.5–66.7) in the surgery alone group and 60.4% (51.4–68.2) in the radiation + surgery group. Based on these data, the authors concluded that neoadjuvant radiotherapy does not have additional benefit in RPS. 

There are several interesting facets of this trial design and analysis that bear discussion. Firstly, this trial was able to complete accrual and obtain results, whereas a similar trial out of MD Anderson was unable to accrue. This highlights the challenge in performing randomized trials on rare, heterogeneous tumors. Secondly, this trial included a mix of histologic subtypes, including mostly liposarcomas (75%) and leiomyosarcomas (15%). These tumors recur in different fashions – liposarcomas tending to recur locally and leiomyosarcomas tending to recur with distant disease. A subset analysis of liposarcomas suggested some benefit of radiation, however, given small sample sizes the analysis was underpowered. Ultimately, more collaborative work will be needed on specific histologies to better understand the role of radiotherapy in retroperitoneal sarcoma.