Enhancing Lymph Node Yield in Gastric Cancer Resection: Impact of Back Table Dissection on Number of Lymph Node Examined.

INTRODUCTION: During gastric cancer resection, back table dissection (BTD) involves examination and separation of lymph node (LN) packets from the surgical specimen based on LN stations, which are sent to pathology as separately labeled specimens. With potential impact on clinical outcomes, we aimed to explore how BTD affects number of LNs examined. METHODS: A retrospective review of a gastric cancer database was performed, including all cases of gastrectomy with D2 lymphadenectomy from January 2009 to March 2022. Back table dissection and conventional groups were compared using Mann-Whitney U and Fisher's exact tests. Multiple linear regression modeling was used to identify potential predictors of number of LN examined. RESULTS: A total of 174 patients were identified: 39 (22%) BTD and 135 (78%) conventional. More patients in the BTD group underwent neoadjuvant chemotherapy (62% vs 29%, P < .05). Compared to the conventional group, the BTD group had a greater number of LNs examined (42 [26-59] vs 21[15-33], median [IQR], P < .001), lower LN positivity ratio (.01 vs .07, P = .013), and greater number of LNs in patients with BMI >35 (32.5[27.5-39] vs 22[13-27], P = .041). A multiple linear regression model controlling for age, BMI, preoperative N stage, neoadjuvant chemotherapy, surgeon experience, and operative approach identified BTD as a significant positive predictor of number of LN examined (ß = 19.7, P = .001). CONCLUSION: Back table dissection resulted in improved LN yield during gastric cancer resection. As a simple technical addition, BTD helps enhance pathology examination and improve surgeon awareness, which may ultimately translate to improve oncologic outcomes.

Real world study of sacituzumab govitecan in metastatic triple-negative breast cancer in the United Kingdom.

BACKGROUND: Treatment options for pre-treated patients with metastatic triple-negative breast cancer (mTNBC) remain limited. This is the first study to assess the real-world safety and efficacy of sacituzumab govitecan (SG) in the UK. METHODS: Data was retrospectively collected from 16 tertiary UK cancer centres. Pts had a diagnosis of mTNBC, received at least two prior lines of treatment (with at least one being in the metastatic setting) and received at least one dose of SG. RESULTS: 132 pts were included. Median age was 56 years (28-91). All patients were ECOG performance status (PS) 0-3 (PS0; 39, PS1; 76, PS2; 16, PS3;1). 75% (99/132) of pts had visceral metastases including 18% (24/132) of pts with CNS disease. Median PFS (mPFS) was 5.2 months (95% CI 4.5-6.6) with a median OS (mOS) of 8.7 months (95% CI 6.8-NA). The most common adverse events (AEs) were fatigue (all grade; 82%, G3/4; 14%), neutropenia (all grade; 55%, G3/4; 29%), diarrhoea (all grade; 58%, G3/4, 15%), and nausea (all grade; 38%, G3/4; 3%). SG dose reduction was required in 54% of pts. CONCLUSION: This study supports significant anti-tumour activity in heavily pre-treated pts with mTNBC. Toxicity data aligns with clinical trial experience.

A Prospective Study of Sentinel Node Biopsy Omission in Women Age ≥ 65 Years with ER+ Breast Cancer.

BACKGROUND: National guidelines recommend omitting SNB in older patients with favorable invasive breast cancer. However, there is a lack of prospective data specifically addressing this issue. This study evaluates recurrence and survival in estrogen receptor-positive/Her2- (ER+) breast cancer patients, aged ≥ 65 years who have breast-conserving surgery (BCS) without SNB. METHODS: This is a prospective, observational study at a single institution where 125 patients aged ≥ 65 years with clinical T1-2N0 ER+ invasive breast cancer undergoing BCS were enrolled. Patients were treated with BCS without SNB. Primary outcome measure was axillary recurrence. Secondary outcome measures include recurrence-free survival (RFS), disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS). RESULTS: From January 2016 to July 2022, 125 patients were enrolled with median follow-up of 36.7 months [95% confidence interval (CI) 35.0-38.0]. Median age was 77.0 years (range 65-93). Median tumor size was 1 cm (range 0.1-5.0). Most tumors were ductal (95/124, 77.0%), intermediate grade (60/116, 51.7%), and PR-positive (117/123, 91.7%). Radiation therapy was performed in 37 of 125 (29.6%). Only 60 of 125 (48.0%) who were recommended hormonal therapy were compliant at 2 years. Chemotherapy was administered to six of 125 (4.8%) patients. There were two of 125 (1.6%) axillary recurrences. Estimated 3-years rates of regional RFS, DFS, and OS were 98.2%, 91.2%, and 94.8%, respectively. Univariate Cox regression identified hormonal therapy noncompliance to be significantly associated with recurrence (p = 0.02). CONCLUSIONS: Axillary recurrence rates were extremely low in this cohort. These results provide prospective data to support omission of SNB in this patient population TRIAL REGISTRATION: ClinicalTrials.gov ID NCT02564848.

Use of fluorescence imaging and indocyanine green during laparoscopic cholecystectomy: Results of an international Delphi survey.

BACKGROUND: Published empirical data have increasingly suggested that using near-infrared fluorescence cholangiography during laparoscopic cholecystectomy markedly increases biliary anatomy visualization. The technology is rapidly evolving, and different equipment and doses may be used. We aimed to identify areas of consensus and nonconsensus in the use of incisionless near-infrared fluorescent cholangiography during laparoscopic cholecystectomy. METHODS: A 2-round Delphi survey was conducted among 28 international experts in minimally invasive surgery and near-infrared fluorescent cholangiography in 2020, during which respondents voted on 62 statements on patient preparation and contraindications (n = 12); on indocyanine green administration (n = 14); on potential advantages and uses of near-infrared fluorescent cholangiography (n = 18); comparing near-infrared fluorescent cholangiography with intraoperative x-ray cholangiography (n = 7); and on potential disadvantages of and required training for near-infrared fluorescent cholangiography (n = 11). RESULTS: Expert consensus strongly supports near-infrared fluorescent cholangiography superiority over white light for the visualization of biliary structures and reduction of laparoscopic cholecystectomy risks. It also offers other advantages like enhancing anatomic visualization in obese patients and those with moderate to severe inflammation. Regarding indocyanine green administration, consensus was reached that dosing should be on a milligrams/kilogram basis, rather than as an absolute dose, and that doses >0.05 mg/kg are necessary. Although there is no consensus on the optimum preoperative timing of indocyanine green injections, the majority of participants consider it important to administer indocyanine green at least 45 minutes before the procedure to decrease the light intensity of the liver. CONCLUSION: Near-infrared fluorescent cholangiography experts strongly agree on its effectiveness and safety during laparoscopic cholecystectomy and that it should be used routinely, but further research is necessary to establish optimum timing and doses for indocyanine green.

Efficacy of Eribulin in Soft Tissue Sarcomas.

Soft tissue sarcomas are a highly heterogenous group of tumors with limited systemic therapy options. Eribulin, a synthetic analogue of halichondrin B, is a potent mitotic inhibitor. A phase 3 trial of previously treated advanced Liposarcoma and Leiomyosarcoma demonstrated superiority of eribulin to dacarbazine. Eribulin appears to be particularly effective for liposarcomas. It has also been shown to be a safe and effective treatment alternative to doxorubicin in patients where doxorubicin is contraindicated. From retrospective studies, eribulin has demonstrated efficacy in patients with angiosarcoma, pleomorphic sarcomas, synovial sarcomas, rhabdomyosarcomas, angiosarcomas, and myxofibrosarcomas. Future areas of development include liposomal eribulin, which may provide increased efficacy and lower toxicity, and delineation of biomarkers of response and resistance, allowing better selection of patients for treatment.

Outcomes Following Percutaneous Cholecystostomy Tube Placement for Acalculous Versus Calculous Cholecystitis.

BACKGROUND: Acute acalculous cholecystitis (AAC) is often diagnosed in critically ill patients. Percutaneous cholecystostomy tube (PCT) placement facilitates less invasive gallbladder decompression in patients who are poor surgical candidates. Specific guidelines for optimal management of AAC patients following PCT placement remain to be defined. We hypothesize that AAC patients are at lower risk of recurrent cholecystitis than acute calculous cholecystitis (ACC) patients and do not require cholecystectomy after PCT placement. METHODS: A retrospective review of patients who underwent PCT placement for AAC or ACC between 6/1/2007 and 5/31/2019 was performed. Primary outcome was recurrent cholecystitis and interval cholecystectomy for patients surviving 30 days after PCT placement. Secondary outcome was 30 day mortality. A cox regression model calculated the adjusted hazard ratio (AHR) for the outcomes. RESULTS: Eighty-four AAC and 85 ACC patients underwent PCT placement. Compared to ACC patients, more AAC patients were male (72.6 vs. 48.2%; p < 0.01), younger (median age 62 vs. 73 years; p < 0.01), and required intensive care (69.0 vs. 52.9%; p = 0.04), with lower median Charlson Comorbidity Index (4.0 vs. 6.0; p < 0.01). 30 day mortality was higher among AAC patients than ACC patients (45.2 vs. 21.2%; p < 0.01). 2/24 (8.3%) AAC patients and 5/31 (16.1%) ACC patients developed recurrent cholecystitis at a median 208.0 days (IQR:64.0-417.0) after PCT placement and 115.0 days (IQR:7.0-403.0) following PCT removal. Cox regression analysis demonstrated that AAC patients had lower likelihood of interval cholecystectomy compared to ACC patients (AHR 2.35; 95% CI:1.11,4.96). CONCLUSION: Recurrent cholecystitis is rare in patients surviving 30 days following PCT placement. When compared with ACC patients, fewer AAC patients require cholecystectomy.

Operative approach and case volume are associated with negative resection margins for adrenocortical carcinoma.

BACKGROUND: Surgical resection with negative margins is the treatment of choice for adrenocortical carcinoma (ACC). This study was undertaken to determine factors associated with negative resection margins. METHODS: National Cancer Database was queried from 2010 to 2016 to identify patients with AJCC/ENSAT Stage I-III ACC who underwent adrenalectomy. Patient, tumor, facility, and operative characteristics were compared by margin status (positive-PM or negative-NM) and operative approach (open-OA, laparoscopic-LA, or robotic-RA). Multivariable logistic regression was used to identify factors associated with PM. RESULTS: Eight hundred and eighty-one patients were identified, of which 18.4% had PM and 81.6% had NM. Patients with advanced pathologic T stage and pathologic N1 stage were more likely to have PM (vs. NM) (T3, 49.7% vs. 24.8%, p < 0.01; T4, 26.2% vs. 10.0%, p < 0.01; N1, 6.7% vs. 3.5%, p < 0.01). Patients undergoing OA (vs. LA and RA) were more likely to have advanced clinical T stage (T4, 16.6% vs. 5.7% vs. 7.8%, p < 0.01) and larger tumors (> 6 cm, 84.6% vs. 64.1% vs. 62.3%, p < 0.01). High-volume centers (≥ 5 cases) were more likely to utilize OA. Patients undergoing LA (vs. RA) were more likely to require conversion to open (20.3% vs. 7.8%, p = 0.011). On multivariable analysis, factors associated with higher odds of PM included T3 disease (OR 7.02, 95% CI 2.66-18.55), T4 disease (OR 10.22, 95% CI 3.66-28.53), and LA (OR 1.99, 95% CI 1.28-3.09). High-volume centers were associated with lower odds of PM (OR 0.67, 95% CI 0.45-0.98). There was no significant difference in margin status between OA and RA (OR 1.44, 95% CI 0.71-2.90). CONCLUSION: Centers with higher ACC case volumes have lower odds of PM and utilize OA more often. LA is associated with higher odds of PM, whereas RA is not. These factors should be considered when planning the operative approach for ACC.

Evaluation of a Whole Health-Lifestyle Medicine Curriculum for Physician Assistant Students: a Mixed Methods Analysis.

There is increased urgency to train healthcare professionals in lifestyle medicine (LM) to mitigate the impact of lifestyle factors on chronic disease (Trilk et al. in Am J Prevent Medic. 2019:e169-e75, 2019; Polak et al. in Am J Lifestyle Med. 2015;9:361-7, 2015). This training addresses physical activity, nutrition, stress management, sleep hygiene, relationships, tobacco cessation (Lifestyle medicine in ACLM Home, 2020), and self-care. Several studies have evaluated the impact of this training on physician assistant (PA) students (Keyes and Gardner in Clin Teach. 2020, 2020; Phillips et al. Med Sci Educ. 1-5). The current paper extends previous quantitative findings from Phillips et al., 2021, revealing positive qualitative changes in PA student language and approach to clinical vignettes after completion of a novel Whole Health/lifestyle medicine (WH-LM) curriculum.

Percutaneous Cholecystostomy Tube for Acute Cholecystitis: Quantifying Outcomes and Prognosis.

BACKGROUND: Percutaneous cholecystostomy tubes (PCT) are utilized in the management of acute cholecystitis in patients deemed unsuitable for surgery. However, the drive for these decisions and the outcomes remain understudied. We sought to characterize the practices and utilization of PCT and evaluate associated outcomes at an urban medical center. METHODS: Patients undergoing PCT placement over a 12-y study period ending May 2019 were reviewed. Demographics, clinical presentation, labs, imaging studies, and outcomes were abstracted. The primary and secondary outcomes were 30-d mortality and interval cholecystectomy, respectively. RESULTS: Two hundred and four patients met inclusion criteria: 59.3% were male with a median age of 67.5 y and a National Surgical Quality Improvement Program (NSQIP) risk of serious complication of 8.0%. Overall, 57.8% of patients were located in an intensive care unit setting. The majority (80.9%) had an ultrasound and 48.5% had a hepatobiliary iminodiacetic acid scan. The overall 30-d mortality was 31.9%: 41.5% for intensive care unit and 18.6% for ward patients (P < 0.01). Of patients surviving beyond 30 d (n = 139), the PCT was removed from 106 (76.3%), and a cholecystectomy was performed in 55 (39.6%) at a median interval of 58.0 d. A forward logistic regression identified total bilirubin (Adjusted Odds Ratio: 1.12, adjusted P < 0.01) and NSQIP risk of serious complication (Adjusted Odds Ratio: 1.16, adjusted P < 0.01) as the only predictors for 30-d mortality. CONCLUSIONS: Patients selected for PCT placement have a high mortality risk. Despite subsequent removal of the PCT, the majority of surviving patients did not undergo an interval cholecystectomy. Total bilirubin and NSQIP risk of serious complication are useful adjuncts in predicting 30-d mortality in these patients.

The role of Cushing's reflex and the vasopressin-mediated oligoanuric response to intracranial hypertension in patients with abdominal compartment syndrome.

BACKGROUND: We examined the link between increased intra-abdominal pressure, intracranial pressure, and vasopressin release as a potential mechanism. Intra-abdominal pressure, produced by abdominal-cavity insufflation with carbon dioxide (CO2) during laparoscopic abdominal procedures to facilitate visualization, is associated with various complications, including arterial hypertension and oliguria. METHODS: Mean arterial pressure, optic nerve sheath diameter, measured as a proxy for intracranial pressure, plasma vasopressin, serum and urine osmolarity, and urine output were measured 4 times during laparoscopic sleeve gastrectomy in 42 patients: before insufflation with CO2 (T0); after insufflation to 15 cm water (H2O) pressure, with 5 cm H2O positive end-expiratory pressure (T1); after positive end-expiratory pressure was raised to 10 cm H2O (T2); and after a return to the baseline state (T3). Mean values at T0 to T3 and the directional consistency of changes (increase/decrease/ unchanged) were compared among the 4 data-collection points. RESULTS: Statistically significant elevations (all P ≤ .001) were noted from T0 to T1 and from T0 to T2 in mean arterial pressure, optic nerve sheath diameter, and vasopressin, followed by decreases at T3. For optic nerve sheath diameter and vasopressin, the increases at T1 and T2 occurred in 98% and 100% of patients, ultimately exceeding normal levels in 88 and 97%, respectively. Conversely, urine output fell from T0 to T1 and T2 by 60.9 and 73.4%, decreasing in 88.1% of patients (all P < .001). Patients with class II obesity exhibited statistically greater increases in optic nerve sheath diameter and vasopressin, but statistically less impact on urine output, than patients with class III obesity. CONCLUSION: Increased mean arterial pressure, intracranial pressure, and vasopressin release appear to be intermediary steps between increased intra-abdominal pressure and oliguria. Further research is necessary to determine any causative links between these physiological changes.

Adrenocortical Carcinoma: The Value of Lymphadenectomy.

BACKGROUND: Adrenocortical carcinoma (ACC) staging does not account for the number of positive nodes. The prognostic value of quantitative metastatic nodal burden is unknown. METHODS: The National Cancer Database was retrospectively queried from 2004-2016 to identify patients with Stage I-III ACC undergoing adrenalectomy. Patients who underwent lymphadenectomy (LAD) were further studied. Demographics, TNM staging, tumor characteristics, and surgical approach were analyzed. RESULTS: 386 LADs were identified. The median number of nodes examined was 2 (IQR 2-6), with no difference by surgical approach '[laparoscopic, 3 (1-3); robotic, 1.5 (1-4.5); open, 2 (1-7), p = 0.493]. In LADs with cN0 disease, positive nodes were seen in 17.5% of patients; an average of 6 (1-12) nodes were examined in patients who upstaged to pN1 disease compared with an average of 2 (1-6) nodes in those who remained pN0. Median survival was incrementally worse for patients with more positive nodes (62.8 vs. 21.9 vs. 13.7 vs. 11.3 vs. 10.7 months for 0, 1, 2, 3, and ≥ 4 positive nodes, respectively, p < 0.01). On multivariate analysis, significant prognostic factors for poor survival included older age, ≥ 2 comorbidities, pT3, and pT4. The strongest prognostic factor for poor survival was the number of positive nodes (1 node, hazards ratio [HR] 2.3, 95% confidence interval [CI] 1.5-3.6; 2 nodes, HR 1.3, 95% CI 0.6-3.0; 3 nodes, HR 3.0, 95% CI 1.1-8.0; ≥ 4 nodes, HR 4.0, 95% CI 2.5-6.2). Lymphadenectomy was associated with improved survival (HR 0.82, 95% CI 0.67-0.99). CONCLUSIONS: Higher quantitative metastatic nodal burden is a robust prognostic factor for worse survival in ACC.

Management of Postcholecystectomy Complications.

Cholecystectomy is one of the most common general surgery procedures performed worldwide. Complications include bile duct injury, strictures, bleeding, infection/abscess, retained gallstones, hernias, and postcholecystectomy syndrome. Obtaining a critical view of safety and following the other tenets of the Safe Cholecystectomy Task Force will aid in the prevention of bile duct injury and other morbidity associated with cholecystectomy.

Factors Associated with Non-Operative Management of Resectable Adrenocortical Carcinoma.

INTRODUCTION: Surgery is the initial treatment of choice for patients with resectable adrenocortical carcinoma (ACC). We sought to determine factors associated with non-operative management of resectable ACC. METHODS: 2004-2016 National Cancer Database (NCDB) was queried to identify patients with AJCC/ENSAT Stage I-III ACC. Patients who underwent surgery (S) were compared to those who did not undergo surgery (NS). Multivariate logistic regression was used to identify factors associated with NS. Kaplan-Meier estimates used to assess survival. RESULTS: Two thousand-seventy patients with Stage I-III ACC were identified, of which 17.5% were NS. 85.9% of NS patients were not offered surgery; 69.9% of NS patients did not receive chemotherapy or radiation therapy. NS were older and less likely to receive care at an Academic center or high volume center (≥5 cases during the study period). NS patients were more likely to have advanced T stage and N1 disease. On multivariate regression, factors associated with lower odds of surgery include older age (OR 1.03, 95% CI 1.02-1.06), T4 disease (OR 3.34, 95% CI 1.05-10.68), and treatment at a community center (OR 2.92, 95% CI 1.58-5.40). Overall median survival was significantly poorer for NS patients (50.4 versus 78.4 months, P < 0.01). CONCLUSION: Patients with locally advanced ACC are less likely to undergo an operation, while those treated at centers with more operative experience or Academic facilities are more likely to undergo an operation. As the surgery-first approach is the current standard of care for resectable ACC, these patients may be best served at high volume Academic facilities.

Safety and effectiveness of REALIZE adjustable gastric band: 5-year prospective study.

BACKGROUND: The long-term safety results of the REALIZE (Ethicon Endo-Surgery, Inc., Cincinnati, OH) adjustable gastric band collected in this prospective, multicenter study in patients with morbid obesity are presented. OBJECTIVES: To determine the reoperation rate, including band revisions, replacements, and explants, resulting from a serious adverse device-related event through years 4 and 5. Various efficacy measures were also assessed as secondary objectives. SETTING: Nine academic and/or private institutions. METHODS: The participating institutions enrolled 303 patients, who were then assessed on an annual basis, with 231 patients completing 5 years of follow-up. The study parameters included reoperation rates, changes in percentage of excess weight loss (%EWL), and changes in body mass index (BMI), as well as parameters of diabetes and dyslipidemia. Quality of life was assessed using the Short Form (SF)-36 and the Impact of Weight on Quality of Life-Lite questionnaires. RESULTS: The reoperation rate due to a serious adverse event in this population at 5 years after implantation with the REALIZE gastric band was 8.9%. The most common serious adverse event was band slippage, which affected 6.9% of the study population. The mean %EWL was 35.6% ± 26.84%, and the decrease in mean BMI was -7.01 ± 5.45 kg/m2 at 5 years. Patients experienced improvements in mean glycated hemoglobin and serum lipid levels, in addition to improvements in the quality of life measures. CONCLUSION: No new safety concerns were identified during the 5 years of follow-up. Although the results of this study did not meet the predefined safety criteria of 8% or less, the safety profile and long-term effectiveness observed in this study are consistent with those in the current literature.

Lifestyle Medicine.

Lifestyle medicine is a growing field of medicine that addresses key health behaviors, which are the root causes of most premature death, chronic disease, and health care costs. Coaching patients with evidence-based behavior change strategies can help them to make lasting habits in key areas, such as physical activity, healthy eating, improved sleep, cessation of tobacco, forming and maintaining relationships, and stress management. Similarities in philosophy between lifestyle medicine and physical medicine and rehabilitation make them complementary and synergistic in treating the whole patient in their social context.

SAGES and EAES recommendations for minimally invasive surgery during COVID-19 pandemic.

The unprecedented pandemic of COVID-19 has impacted many lives and affects the whole healthcare systems globally. In addition to the considerable workload challenges, surgeons are faced with a number of uncertainties regarding their own safety, practice, and overall patient care. This guide has been drafted at short notice to advise on specific issues related to surgical service provision and the safety of minimally invasive surgery during the COVID-19 pandemic. Although laparoscopy can theoretically lead to aerosolization of blood borne viruses, there is no evidence available to confirm this is the case with COVID-19. The ultimate decision on the approach should be made after considering the proven benefits of laparoscopic techniques versus the potential theoretical risks of aerosolization. Nevertheless, erring on the side of safety would warrant treating the coronavirus as exhibiting similar aerosolization properties and all members of the OR staff should use personal protective equipment (PPE) in all surgical procedures during the pandemic regardless of known or suspected COVID status. Pneumoperitoneum should be safely evacuated via a filtration system before closure, trocar removal, specimen extraction, or conversion to open. All emergent endoscopic procedures performed during the pandemic should be considered as high risk and PPE must be used by all endoscopy staff.

Prioritized Research for the Prevention, Treatment, and Reversal of Chronic Disease: Recommendations From the Lifestyle Medicine Research Summit.

Declining life expectancy and increasing all-cause mortality in the United States have been associated with unhealthy behaviors, socioecological factors, and preventable disease. A growing body of basic science, clinical research, and population health evidence points to the benefits of healthy behaviors, environments and policies to maintain health and prevent, treat, and reverse the root causes of common chronic diseases. Similarly, innovations in research methodologies, standards of evidence, emergence of unique study cohorts, and breakthroughs in data analytics and modeling create new possibilities for producing biomedical knowledge and clinical translation. To understand these advances and inform future directions research, The Lifestyle Medicine Research Summit was convened at the University of Pittsburgh on December 4-5, 2019. The Summit's goal was to review current status and define research priorities in the six core areas of lifestyle medicine: plant-predominant nutrition, physical activity, sleep, stress, addictive behaviors, and positive psychology/social connection. Forty invited subject matter experts (1) reviewed existing knowledge and gaps relating lifestyle behaviors to common chronic diseases, such as cardiovascular disease, diabetes, many cancers, inflammatory- and immune-related disorders and other conditions; and (2) discussed the potential for applying cutting-edge molecular, cellular, epigenetic and emerging science knowledge and computational methodologies, research designs, and study cohorts to accelerate clinical applications across all six domains of lifestyle medicine. Notably, federal health agencies, such as the Department of Defense and Veterans Administration have begun to adopt "whole-person health and performance" models that address these lifestyle and environmental root causes of chronic disease and associated morbidity, mortality, and cost. Recommendations strongly support leveraging emerging research methodologies, systems biology, and computational modeling in order to accelerate effective clinical and population solutions to improve health and reduce societal costs. New and alternative hierarchies of evidence are also be needed in order to assess the quality of evidence and develop evidence-based guidelines on lifestyle medicine. Children and underserved populations were identified as prioritized groups to study. The COVID-19 pandemic, which disproportionately impacts people with chronic diseases that are amenable to effective lifestyle medicine interventions, makes the Summit's findings and recommendations for future research particularly timely and relevant.

Predictors of antiproliferative effect of lanreotide autogel in advanced gastroenteropancreatic neuroendocrine neoplasms.

PURPOSE: The antiproliferative properties of lanreotide autogel (LAN) in gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) were demonstrated in the CLARINET study. However, there is limited literature regarding factors that affect progression-free survival (PFS) in patients with GEP NENs treated with LAN. METHODS: We identified a total of 191 treatment-naive patients with advanced GEP NENs and positive SSTR uptake on imaging (Octreoscan or 68Gallium DOTATATE Positron Emission Tomography [68GaPET]) who received first-line LAN monotherapy, albeit at various starting doses (60, 90 or 120 mg/month). A group of 102 patients who initiated treatment at the standard dose of 120 mg/month were included in the study and further evaluated by univariate and multivariate analyses to identify predictors of PFS. RESULTS: The location of tumour primary was in the small bowel in 63 (62%), pancreas in 31 (30%) and colon/rectum in 8 patients (8%). The tumours were well-differentiated, and the majority were grade 1 (52%), or 2 (38%). About 60% of cases had progressive disease at the time of treatment initiation. Most patients with available pretreatment nuclear medicine imaging (Octreoscan or 68Ga PET) had a Krenning score of 3 (44%) or 4 (50%). The median PFS for the entire cohort was 19 months (95% CI 12, 26 months). The univariate analysis demonstrated that grade 2 tumours, progressive disease at baseline and metastatic liver disease were associated with a significantly shorter PFS, while other evaluated variables did not affect PFS at a statistically significant level. However, at multivariate analysis only the tumour grade remained statistically significant. CONCLUSIONS: The current study showed that, of many evaluated variables, only the tumour grade was predictive of PFS duration and this should be considered during patient selection for treatment.