EAES and SAGES 2018 consensus conference on acute diverticulitis management:evidence-based recommendations for clinical practice

Background Acute diverticulitis (AD) presents a unique diagnostic and therapeutic challenge for general surgeons. This collaborative project between EAES and SAGES aimed to summarize recent evidence and draw statements of recommendation to guide our members on comprehensive AD management. Methods Systematic reviews of the literature were conducted across six AD topics by an international steering group including experts from both societies. Topics encompassed the epidemiology, diagnosis, management of non-complicated and complicated AD as well as emergency and elective operative AD management. Consensus statements and recommendations were generated, and the quality of the evidence and recommendation strength rated with the GRADE system. Modified Delphi methodology was used to reach consensus among experts prior to surveying the EAES and SAGES membership on the recommendations and likelihood to impact their practice. Results were presented at both EAES and SAGES annual meetings with live re-voting carried out for recommendations with < 70% agreement. Results A total of 51 consensus statements and 41 recommendations across all six topics were agreed upon by the experts and submitted for members’ online voting. Based on 1004 complete surveys and over 300 live votes at the SAGES and EAES Diverticulitis Consensus Conference (DCC), consensus was achieved for 97.6% (40/41) of recommendations with 92% (38/41) agreement on the likelihood that these recommendations would change practice if not already applied. Areas of persistent disagreement included the selective use of imaging to guide AD diagnosis, recommendations against antibiotics in non-complicated AD, and routine colonic evaluation after resolution of non-complicated diverticulitis. Conclusion This joint EAES and SAGES consensus conference updates clinicians on the current evidence and provides a set of recommendations that can guide clinical AD management practice

Combining short-term interval training with caloric restriction improves ß-cell function in obese adults

Although low-calorie diets (LCD) improve glucose regulation, it is unclear if interval exercise (INT) is additive. We examined the impact of an LCD versus LCD + INT training on ß-cell function in relation to glucose tolerance in obese adults. Twenty-six adults (Age: 46 ± 12 year; BMI 38 ± 6 kg/m2) were randomized to 2-week of LCD (~1200 kcal/day) or energy-matched LCD + INT (60 min/day alternating 3 min at 90 and 50% HRpeak). A 2 h 75 g oral glucose tolerance test (OGTT) was performed. Insulin secretion rates (ISR) were determined by deconvolution modeling to assess glucose-stimulated insulin secretion ([GSIS: ISR/glucose total area under the curve (tAUC)]) and ß-cell function (Disposition Index [DI: GSIS/IR]) relative to skeletal muscle (Matsuda Index), hepatic (HOMA-IR) and adipose (Adipose-IRfasting) insulin resistance (IR). LCD + INT, but not LCD alone, reduced glucose and total-phase ISR tAUC (Interactions: p = 0.04 and p = 0.05, respectively). Both interventions improved skeletal muscle IR by 16% (p = 0.04) and skeletal muscle and hepatic DI (Time: p \u3c 0.05). Improved skeletal muscle DI was associated with lower glucose tAUC (r = −0.57, p \u3c 0.01). Thus, LCD + INT improved glucose tolerance more than LCD in obese adults, and these findings relate to ß-cell function. These data support LCD + INT for preserving pancreatic function for type 2 diabetes prevention

Pre-operative aerobic exercise on metabolic health and surgical outcomes in patients receiving bariatric surgery: A pilot trial.

ObjectiveExamine if adding aerobic exercise to standard medical care (EX+SC) prior to bariatric surgery improves metabolic health in relation to surgical outcomes.MethodsFourteen bariatric patients (age: 42.3±2.5y, BMI: 45.1±2.5 kg/m2) met inclusion criteria and were match-paired to pre-operative SC (n = 7) or EX+SC (n = 7; walking 30min/d, 5d/wk, 65-85% HRpeak) for 30d. A 120min mixed meal tolerance test was performed pre- and post-intervention (~2d prior to surgery) to assess insulin sensitivity (Matsuda Index) and metabolic flexibility (indirect calorimetry). Aerobic fitness (VO2peak), body composition (BodPod), and adipokines (adiponectin, leptin) were also measured. Omental adipose tissue was collected during surgery to quantify gene expression of adiponectin and leptin, and operating time and length of hospital stay were recorded. ANOVA and Cohen's d effect size (ES) was used to test group differences.ResultsSC tended to increase percent body fat (P = 0.06) after the intervention compared to EX+SC. Although SC and EX+SC tended to raise insulin sensitivity (P = 0.11), EX+SC enhanced metabolic flexibility (P = 0.01, ES = 1.55), reduced total adiponectin (P = 0.01, ES = 1.54) with no change in HMW adiponectin and decreased the length of hospital stay (P = 0.05) compared to SC. Albeit not statistically significant, EX+SC increased VO2peak 2.9% compared to a 5.9% decrease with SC (P = 0.24, ES = 0.91). This increased fitness correlated to shorter operating time (r = -0.57, P = 0.03) and length of stay (r = -0.58, P = 0.03). Less omental total adiponectin (r = 0.52, P = 0.09) and leptin (r = 0.58, P = 0.05) expression correlated with shorter operating time, and low leptin expression was linked to shorter length of stay (r = 0.70, P = 0.01), and low leptin expression was linked to shorter length of stay (r = 0.70, P = 0.01).ConclusionAdding pre-operative aerobic exercise to standard care may improve surgical outcomes through a fitness and adipose tissue derived mechanism

Racial-ethnic variations in phyllodes tumors among a multicenter United States cohort.

BACKGROUND AND OBJECTIVES: Previous studies have identified racial-ethnic differences in the diagnostic patterns and recurrence outcomes of women with phyllodes tumors (PT). However, these studies are generally limited in size and generalizability. We therefore sought to explore racial-ethnic differences in age, tumor size, subtype, and recurrence in a large US cohort of women with PT. METHODS: We performed an 11-institution retrospective review of women with PT from 2007 to 2017. Differences in age at diagnosis, tumor size and subtype, and recurrence-free survival according to race-ethnicity. RESULTS: Women of non-White race or Hispanic ethnicity were younger at the time of diagnosis with phyllodes tumor. Non-Hispanic Other women had a larger proportion of malignant PT. There were no differences in recurrence-free survival in our cohort. CONCLUSIONS: Differences in age, tumor size, and subtype were small. Therefore, the workup of young women with breast masses and the treatment of women with PT&nbsp;should not differ according to race-ethnicity. These conclusions are supported by our finding that there were no differences in recurrence-free survival

Germline Genetic Mutations in a Multi-center Contemporary Cohort of 550 Phyllodes Tumors: An Opportunity for Expanded Multi-gene Panel Testing

BackgroundA paucity of data exists regarding inherited mutations associated with phyllodes tumors (PT); however, some are reported (TP53, BRCA1, and RB1). A PT diagnosis does not meet NCCN criteria for testing, including within Li-Fraumeni Syndrome (TP53). We sought to determine the prevalence of mutations associated with PT.MethodsWe performed an 11-institution review of contemporary (2007-2017) PT practice. We recorded multigenerational family history and personal history of genetic testing. We identified patients meeting NCCN criteria for genetic evaluation. Logistic regression estimated the association of select covariates with likelihood of undergoing genetic testing.ResultsOf 550 PT patients, 59.8% (n = 329) had a close family history of cancer, and 34.0% (n = 112) had ≥ 3 family members affected. Only 6.2% (n = 34) underwent genetic testing, 38.2% (n = 13) of whom had only BRCA1/BRCA2 tested. Of 34 patients tested, 8.8% had a deleterious mutation (1 BRCA1, 2 TP53), and 5.9% had a BRCA2 VUS. Of women who had TP53 testing (N = 21), 9.5% had a mutation. Selection for testing was not associated with age (odds ratio [OR] 1.01, p = 0.55) or PT size (p = 0.12) but was associated with grade (malignant vs. benign: OR 9.17, 95% CI 3.97-21.18) and meeting NCCN criteria (OR 3.43, 95% confidence interval 1.70-6.94). Notably, an additional 86 (15.6%) patients met NCCN criteria but had no genetic testing.ConclusionsVery few women with PT undergo germline testing; however, in those selected for testing, a deleterious mutation was identified in ~ 10%. Multigene testing of a PT cohort would present an opportunity to discover the true incidence of germline mutations in PT patients

Contemporary Multi-Institutional Cohort of 550 Cases of Phyllodes Tumors (2007-2017) Demonstrates a Need for More Individualized Margin Guidelines.

PurposePhyllodes tumors (PTs) are rare breast neoplasms, which have little granular data on margins. Current guidelines recommend ≥ 1 cm margins; however, recent data suggest narrower margins are sufficient, and for benign PT, a negative margin may not be necessary.MethodsWe performed an 11-institution contemporary (2007-2017) review of PT practices. Demographics, surgical, and histopathologic data were captured. Logistic regression was used to estimate the association of select covariates with local recurrence (LR).ResultsOf 550 PT patients, the majority underwent excisional biopsy (55.3%, n = 302/546) or lumpectomy (wide excision) (38.5%, n = 210/546). Median tumor size was 30 mm, 68.9% (n = 379) were benign, 19.6% (n = 108) borderline, and 10.5% (n = 58) malignant. Surgical margins were positive in 42% (n = 231) and negative in 57.3% (n = 311). A second operation was performed in 38.0% (n = 209) of the total cohort, including 51 patients with an initial negative margin (82.4% with &lt; 2 mm), and 157 with an initial positive margin, with residual disease only found in six (2.9%). Notably, 32.0% (n = 74) of those with an initial positive margin did not undergo a second operation, among whom only 2.7% (n = 2) recurred. Recurrence occurred in 3.3% (n = 18) of the total cohort (n = 15 LR, n = 3 distant), at median follow-up of 36.7 months. LR (all PT grades) was not reduced with wider negative margin width (≥ 2 mm v &lt; 2 mm: odds ratio [OR] = 0.39; 95% CI, 0.07 to 2.10; P = .27) or final margin status (positive v negative: OR = 0.96; 95% CI, 0.26 to 3.52; P = .96).ConclusionIn current practice, many patients are managed outside of current guidelines. For the entire cohort, a wider margin width was not associated with a reduced risk of LR. We do not recommend re-excision of a negative margin for benign PT, regardless of margin width, as a progressively wider surgical margin is unlikely to reduce LR

Short-Course Antimicrobial Therapy Does Not Increase Treatment Failure Rate in Patients with Intra-Abdominal Infection Involving Fungal Organisms

Background: Fungi frequently are isolated in intra-abdominal infections (IAI). The Study to Optimize Peritoneal Infection Therapy (STOP-IT) recently suggested short-course treatment for patients with IAI. It remains unclear whether the presence of fungi in IAI affects the optimal duration of Antimicrobial therapy. We hypothesized that a shorter treatment course in IAI with fungal organisms would be associated with a higher rate of treatment failure. Methods: Patients enrolled in the STOP-IT trial were stratified according to the presence or absence of a fungal isolate. They were analyzed as a subgroup based on original randomization to either the control group or an experimental group that received a four-day course of Antimicrobial therapy and by comparison with those without a fungal component to their infection. Descriptive comparisons were performed using a χ 2 , Fisher exact, or Kruskal-Wallis test as appropriate. The primary outcome was a composite of recurrent IAI, surgical site infection, and death. Results: A total of 411 patients in the study (79%) had available culture data, of which 58 (14%) had positive fungal cultures. The most common organisms were Candida albicans and C. glabrata . The treatment failure rate was equivalent in the experimental and control arms (29.6% vs. 22.6%; p = 0.54). Patients with fungal isolates were more likely to have malignant disease (25.9% vs. 9.6%; p = 0.0004) and coronary artery disease (22% vs. 12%; p = 0.04), but were otherwise similar to those without fungal isolates. Patients with fungal isolates had more hospital days (median 10 vs. 7; p < 0.0001) and more days to resumption of enteral intake (median 5 vs. 3; p = 0.0006), but there was no difference in the composite outcome. Conclusions: Patients with IAI involving fungal organisms randomized to a shorter course of Antimicrobial therapy had no difference in the rate of treatment failure. These results suggest that the presence of fungi in IAI may not indicate independently the need for a longer course of Antimicrobial therapy

Limited Reporting of Histopathologic Details in a Multi-Institutional Academic Cohort of Phyllodes Tumors: Time for Standardization

BackgroundPhyllodes tumors are rare fibroepithelial neoplasms that are classified by tiered histopathologic features. While there are protocols for the reporting of cancer specimens, no standardized reporting protocol exists for phyllodes.MethodsWe performed an 11-institution contemporary review of phyllodes tumors. Granular histopathologic details were recorded, including the features specifically considered for phyllodes grade classification.ResultsOf 550 patients, median tumor size was 3.0&nbsp;cm, 68.9% (n&nbsp;=&nbsp;379) of tumors were benign, 19.6% (n&nbsp;=&nbsp;108) were borderline, and 10.5% (n&nbsp;=&nbsp;58) were malignant. All cases reported the final tumor size and grade classification. Complete pathologic reporting of all histopathologic features was present in 15.3% (n&nbsp;=&nbsp;84) of cases, while an additional 35.6% (n&nbsp;=&nbsp;196) were missing only one or two features in the report. Individual details regarding the degree of stromal cellularity was not reported in 53.5% (n&nbsp;=&nbsp;294) of cases, degree of stromal atypia in 58.0% (n&nbsp;=&nbsp;319) of cases, presence of stromal overgrowth in 56.2% (n&nbsp;=&nbsp;309) of cases, stromal cell mitoses in 37.5% (n&nbsp;=&nbsp;206) of cases, and tumor border in 54.2% (n&nbsp;=&nbsp;298) of cases. The final margin status (negative vs. positive) was omitted in only 0.9% of cases, and the final negative margin width was specifically reported in 73.8% of cases. Reporting of details was similar across all sites.ConclusionIn this academic cohort of phyllodes tumors, one or more histopathologic features were frequently omitted from the pathology report. While all features were considered by the pathologist for grading, this limited reporting reflects a lack of reporting consensus. We recommend that standardized reporting in the form of a synoptic-style cancer protocol be implemented for phyllodes tumors, similar to other rare tumors

Longer-Duration Antimicrobial Therapy Does Not Prevent Treatment Failure in High-Risk Patients with Complicated Intra-Abdominal Infections

Background: Recent studies have suggested the length of treatment of intra-abdominal infections (IAIs) can be shortened without detrimental effects on patient outcomes. However, data from high-risk patient populations are lacking. We hypothesized that patients at high risk for treatment failure will benefit from a longer course of antimicrobial therapy. Methods: Patients enrolled in the Study to Optimize Peritoneal Infection Therapy (STOP-IT) trial were evaluated retrospectively to identify risk factors associated with treatment failure, which was defined as the composite outcome of recurrent IAI, surgical site infection, or death. Variables were considered risk factors if there was a positive statistical association with treatment failure. Patients were then stratified according to the presence and number of these risk factors. Univariable analyses were performed using the Kruskal-Wallis, χ 2 , and Fisher exact tests. Logistic regression controlling for risk factors and original randomization group, either a fixed four-day antimicrobial regimen (experimental) or a longer course based on clinical response (control), also was performed. Results: We identified corticosteroid use, Acute Physiology and Chronic Health Evaluation II score ≥5, hospital-acquired infection, or a colonic source of IAI as risk factors associated with treatment failure. Of the 517 patients enrolled, 263 (50.9%) had one or two risk factors and 16 (3.1%) had three or four risk factors. The rate of treatment failure rose as the number of risk factors increased. When controlling for randomization group, the presence and number of risk factors were independently associated with treatment failure, but the duration of antimicrobial therapy was not. Conclusions: We were able to identify patients at high risk for treatment failure in the STOP-IT trial. Such patients did not benefit from a longer course of antibiotic administration. Further study is needed to determine the optimum duration of antimicrobial therapy in high-risk patients

Longer-Duration Antimicrobial Therapy Does Not Prevent Treatment Failure in High-Risk Patients with Complicated Intra-Abdominal Infections

BackgroundRecent studies have suggested the length of treatment of intra-abdominal infections (IAIs) can be shortened without detrimental effects on patient outcomes. However, data from high-risk patient populations are lacking. We hypothesized that patients at high risk for treatment failure will benefit from a longer course of antimicrobial therapy.MethodsPatients enrolled in the Study to Optimize Peritoneal Infection Therapy (STOP-IT) trial were evaluated retrospectively to identify risk factors associated with treatment failure, which was defined as the composite outcome of recurrent IAI, surgical site infection, or death. Variables were considered risk factors if there was a positive statistical association with treatment failure. Patients were then stratified according to the presence and number of these risk factors. Univariable analyses were performed using the Kruskal-Wallis, χ2, and Fisher exact tests. Logistic regression controlling for risk factors and original randomization group, either a fixed four-day antimicrobial regimen (experimental) or a longer course based on clinical response (control), also was performed.ResultsWe identified corticosteroid use, Acute Physiology and Chronic Health Evaluation II score ≥5, hospital-acquired infection, or a colonic source of IAI as risk factors associated with treatment failure. Of the 517 patients enrolled, 263 (50.9%) had one or two risk factors and 16 (3.1%) had three or four risk factors. The rate of treatment failure rose as the number of risk factors increased. When controlling for randomization group, the presence and number of risk factors were independently associated with treatment failure, but the duration of antimicrobial therapy was not.ConclusionsWe were able to identify patients at high risk for treatment failure in the STOP-IT trial. Such patients did not benefit from a longer course of antibiotic administration. Further study is needed to determine the optimum duration of antimicrobial therapy in high-risk patients