Perioperative mental health intervention for depression and anxiety symptoms in older adults study protocol: design and methods for three linked randomised controlled trials.

INTRODUCTION: Preoperative anxiety and depression symptoms among older surgical patients are associated with poor postoperative outcomes, yet evidence-based interventions for anxiety and depression have not been applied within this setting. We present a protocol for randomised controlled trials (RCTs) in three surgical cohorts: cardiac, oncological and orthopaedic, investigating whether a perioperative mental health intervention, with psychological and pharmacological components, reduces perioperative symptoms of depression and anxiety in older surgical patients. METHODS AND ANALYSIS: Adults ≥60 years undergoing cardiac, orthopaedic or oncological surgery will be enrolled in one of three-linked type 1 hybrid effectiveness/implementation RCTs that will be conducted in tandem with similar methods. In each trial, 100 participants will be randomised to a remotely delivered perioperative behavioural treatment incorporating principles of behavioural activation, compassion and care coordination, and medication optimisation, or enhanced usual care with mental health-related resources for this population. The primary outcome is change in depression and anxiety symptoms assessed with the Patient Health Questionnaire-Anxiety Depression Scale from baseline to 3 months post surgery. Other outcomes include quality of life, delirium, length of stay, falls, rehospitalisation, pain and implementation outcomes, including study and intervention reach, acceptability, feasibility and appropriateness, and patient experience with the intervention. ETHICS AND DISSEMINATION: The trials have received ethics approval from the Washington University School of Medicine Institutional Review Board. Informed consent is required for participation in the trials. The results will be submitted for publication in peer-reviewed journals, presented at clinical research conferences and disseminated via the Center for Perioperative Mental Health website. TRIAL REGISTRATION NUMBERS: NCT05575128, NCT05685511, NCT05697835, pre-results.

Bioresorbable, wireless, passive sensors for continuous pH measurements and early detection of gastric leakage.

Continuous monitoring of biomarkers at locations adjacent to targeted internal organs can provide actionable information about postoperative status beyond conventional diagnostic methods. As an example, changes in pH in the intra-abdominal space after gastric surgeries can serve as direct indicators of potentially life-threatening leakage events, in contrast to symptomatic reactions that may delay treatment. Here, we report a bioresorbable, wireless, passive sensor that addresses this clinical need, designed to locally monitor pH for early detection of gastric leakage. A pH-responsive hydrogel serves as a transducer that couples to a mechanically optimized inductor-capacitor circuit for wireless readout. This platform enables real-time monitoring of pH with fast response time (within 1 hour) over a clinically relevant period (up to 7 days) and timely detection of simulated gastric leaks in animal models. These concepts have broad potential applications for temporary sensing of relevant biomarkers during critical risk periods following diverse types of surgeries.

Bioresorbable shape-adaptive structures for ultrasonic monitoring of deep-tissue homeostasis.

Monitoring homeostasis is an essential aspect of obtaining pathophysiological insights for treating patients. Accurate, timely assessments of homeostatic dysregulation in deep tissues typically require expensive imaging techniques or invasive biopsies. We introduce a bioresorbable shape-adaptive materials structure that enables real-time monitoring of deep-tissue homeostasis using conventional ultrasound instruments. Collections of small bioresorbable metal disks distributed within thin, pH-responsive hydrogels, deployed by surgical implantation or syringe injection, allow ultrasound-based measurements of spatiotemporal changes in pH for early assessments of anastomotic leaks after gastrointestinal surgeries, and their bioresorption after a recovery period eliminates the need for surgical extraction. Demonstrations in small and large animal models illustrate capabilities in monitoring leakage from the small intestine, the stomach, and the pancreas.

Decreasing Perioperative Opiate Use During Pancreaticoduodenectomy Using Transversus Abdominus Plane Blocks: A Review of the Literature.

BACKGROUND: Pancreatoduodenectomy is a highly complex surgical procedure associated with high postoperative morbidity and mortality. Treatment of postoperative pain is crucial to preventing chronic pain and further complications. Opioids are the leading treatment modality for acute postoperative pain for all surgical procedures in the US, contributing to the opioid epidemic, a crisis causing death and lifelong impairment in many patients. Multimodal analgesia techniques, such as the transversus abdominis plane (TAP) block, are suggested to reduce perioperative opioid usage. This exploratory literature review aims to investigate the use of TAP block in postoperative pain and opioid use in patients undergoing pancreatoduodenectomy. MATERIALS AND METHODS: A search strategy developed from Cochrane best practice recommendations was applied to a comprehensive search of PubMed, Scopus, and PsycINFO databases, yielding three articles of relevance in patients having pancreatic surgery. RESULTS: Previous research demonstrates TAP block efficacy in decreasing opiate consumption after major abdominal surgery; however, there is a paucity of data regarding opioid consumption in pancreatoduodenectomy patients. CONCLUSION: Research in relation to TAP block analgesia is varied given the variety of approaches, techniques, and timing of the TAP block procedure. Future research should seek to elucidate the role of TAP blocks in reducing postoperative pain and opioid consumption in pancreatoduodenectomy patients.

Race and Odds of Surgery Offer in Small Bowel and Pancreas Neuroendocrine Neoplasms.

BACKGROUND: Despite existing society guidelines, management of pancreatic (PanNEN) and small bowel (SBNEN) neuroendocrine neoplasms remains inconsistent. The purpose of this study was to identify patient- and/or disease-specific characteristics associated with increased odds of being offered surgery for PanNEN and SBNEN. PATIENTS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) Program database and the National Cancer Database (NCDB) were queried for patients with PanNEN/SBNEN. Demographic and pathologic data were compared between patients who were offered surgery and those who were not. Multivariate logistic regression was performed to identify factors independently associated with being offered surgery. RESULTS: In SEER, there were 3641 patients with PanNEN (54.7% were offered surgery) and 5720 with SBNEN (86.0% were offered surgery). On multivariate analysis of SEER, non-white race was associated with decreased odds of surgery offer for SBNEN [odds ratio (OR) 0.58, p < 0.001], but not PanNEN (p = 0.187). In NCDB, there were 28,483 patients with PanNEN (57.5% were offered surgery) and 42,675 with SBNEN (86.9% were offered surgery). On multivariate analysis of NCDB, non-white race was also associated with decreased odds of surgery offer for SBNEN (OR 0.61, p < 0.001) but not PanNEN (p = 0.414). CONCLUSIONS: This study's findings suggest that, in addition to previously reported disparities in surgical resection and surgery refusal rates, racial/ethnic disparities also exist earlier in the course of treatment, with non-white patients being less likely to be offered surgery for SBNEN but not for PanNEN; this is potentially due to discrepancies in rates of referral to academic centers for pancreas and small bowel malignancies.

Transgender Males on Gender-Affirming Hormone Therapy and Hepatobiliary Neoplasms: A Systematic Review.

OBJECTIVE: Behavioral therapy, gender-affirming hormone therapy (GAHT), and surgery are all components of a successful gender transition, but due to a historical lack of access, there is paucity of long-term data in this population. We sought to better characterize the risk of hepatobiliary neoplasms in transgender males undergoing GAHT with testosterone. METHODS: In addition to the 2 case reports, a systematic literature review of hepatobiliary neoplasms in the setting of testosterone administration or endogenous overproduction across indications was conducted. The medical librarian created search strategies using keywords and controlled vocabulary in Ovid Medline, Embase.com, Scopus, Cochrane Database of Systematic Reviews, and clinicaltrials.gov. A total of 1273 unique citations were included in the project library. All unique abstracts were reviewed, and abstracts were selected for complete review. Inclusion criteria were articles reporting cases of hepatobiliary neoplasm development in patients with exogenous testosterone administration or endogenous overproduction. Non-English language articles were excluded. Cases were collated into tables based on indication. RESULTS: Forty-nine papers had cases of hepatocellular adenoma, hepatocellular carcinoma, cholangiocarcinoma, or other biliary neoplasm in the setting of testosterone administration or endogenous overproduction. These 49 papers yielded 62 unique cases. CONCLUSION: Results of this review are not sufficient to conclude that there is an association between GAHT and hepatobiliary neoplasms. This supports current evaluation and screening guidelines for initiation and continuation of GAHT in transgender men. The heterogeneity of testosterone formulations limits the translation of risks of hepatobiliary neoplasms in other indications to GAHT.

Impact of Prehabilitation on Postoperative Mortality and the Need for Non-Home Discharge in High-Risk Surgical Patients.

BACKGROUND: The preoperative period is an important target for interventions (eg Surgical Prehabilitation and Readiness [SPAR]) that can improve postoperative outcomes for older patients with comorbidities. STUDY DESIGN: To determine whether a preoperative multidisciplinary prehabilitation program (SPAR) reduces postoperative 30-day mortality and the need for non-home discharge in high-risk surgical patients, surgical patients enrolled in a prehabilitation program targeting physical activity, pulmonary function, nutrition, and mindfulness were compared with historical control patients from 1 institution's American College of Surgeons (ACS) NSQIP database. SPAR patients were propensity score-matched 1:3 to pre-SPAR NSQIP patients, and their outcomes were compared. The ACS NSQIP Surgical Risk Calculator was used to compare observed-to-expected ratios for postoperative outcomes. RESULTS: A total of 246 patients were enrolled in SPAR. A 6-month compliance audit revealed that overall patient adherence to the SPAR program was 89%. At the time of analysis, 118 SPAR patients underwent surgery with 30 days of follow-up. Compared with pre-SPAR NSQIP patients (n = 4,028), SPAR patients were significantly older with worse functional status and more comorbidities. Compared with propensity score-matched pre-SPAR NSQIP patients, SPAR patients had significantly decreased 30-day mortality (0% vs 4.1%, p = 0.036) and decreased need for discharge to postacute care facilities (6.5% vs 15.9%, p = 0.014). Similarly, SPAR patients exhibited decreased observed 30-day mortality (observed-to-expected ratio 0.41) and need for discharge to a facility (observed-to-expected ratio 0.56) compared with their expected outcomes using the ACS NSQIP Surgical Risk Calculator. CONCLUSIONS: The SPAR program is safe and feasible and may reduce postoperative mortality and the need for discharge to postacute care facilities in high-risk surgical patients.

Postoperative Proton Pump Inhibitors are associated with a significantly higher rate of delayed gastric emptying after pancreatoduodenectomy.

BACKGROUND: Proton pump inhibitors (PPIs) are effective in reducing marginal ulcers after pancreatoduodenectomy. However, their impact on perioperative complications has not been defined. METHODS: We retrospectively analyzed the effect of postoperative PPIs on 90-day perioperative outcomes in all patients who underwent pancreatoduodenectomy at our institution from April 2017 to December 2020. RESULTS: 284 patients were included; 206 (72.5%) received perioperative PPIs, 78 (27.5%) did not. The two cohorts were similar in demographics and operative variables. Postoperatively, the PPI cohort had significantly higher rates of overall complications (74.3% vs. 53.8%) and delayed gastric emptying (28.6% vs. 11.5%), p < 0.05. However, no differences in infectious complications, postoperative pancreatic fistula, or anastomotic leaks were seen. On multivariate analysis, PPI was independently associated with a higher risk of overall complications (OR 2.46, CI 1.33-4.54) and delayed gastric emptying (OR 2.73, CI 1.26-5.91), p = 0.011. Four patients developed marginal ulcers within 90-days postoperatively; all were in the group who received PPIs. CONCLUSION: Postoperative proton pump inhibitor use was associated with a significantly higher rate of overall complications and delayed gastric emptying after pancreatoduodenectomy.

Low vs Standard-Dose Indocyanine Green in the Identification of Biliary Anatomy Using Near-Infrared Fluorescence Imaging: A Multicenter Randomized Controlled Trial.

BACKGROUND: Near-infrared fluorescence imaging using intravenous indocyanine green (ICG) facilitates intraoperative identification of biliary anatomy. We hypothesize that a much lower dose of ICG than the standard decreases hepatic and background fluorescence and improves bile duct visualization. STUDY DESIGN: In this multicenter randomized controlled trial, 55 adult patients undergoing laparoscopic cholecystectomy were randomized to low-dose (0.05 mg) or standard-dose (2.5 mg) ICG preoperatively on the day of surgery. A quantitative assessment was performed on recorded videos from the operation using ImageJ software to quantify the fluorescence intensity of the bile duct, liver, and surrounding/background fat. Operating surgeons blinded to ICG dose provided a qualitative assessment of various aspects of the visualization of the extrahepatic biliary tree comparing near-infrared fluorescence to standard visible light imaging using a scale of 1 to 5 (1, unsatisfactory; 5, excellent). Quantitative and qualitative scores were compared between the groups to determine any significant differences between the doses. RESULTS: The bile duct-to-liver and bile duct-to-background fat fluorescence intensity ratios were significantly higher for the low-dose group compared with the standard-dose group (3.6 vs 0.68, p < 0.0001; and 7.5 vs 3.3, p < 0.0001, respectively). Low-dose ICG had a slightly higher (ie better) mean score on the qualitative assessment compared to the standard dose, although the differences were not statistically significant. CONCLUSIONS: Low-dose ICG leads to quantitative improvement of biliary visualization using near-infrared fluorescence imaging by minimizing liver fluorescence; this further facilitates routine use during hepatobiliary operations.

Development of de novo nonalcoholic fatty liver disease following pancreatectomy.

De novo non-alcoholic fatty liver disease (NAFLD) after pancreatectomy is a recognized phenomenon; however, its pathophysiology is poorly understood. This study aimed to determine the incidence and identify peri-operative risk factors for the development of de novo NAFLD within various pancreatectomy groups. This single-center retrospective cohort study included patients who underwent pancreatectomy between 2000 and 2020. The incidence rate of de novo NAFLD and time to diagnosis were recorded across patients with malignant versus benign indications for pancreatectomy. The overall incidence of de novo NAFLD after pancreatectomy was 17.5% (24/136). Twenty-one percent (20/94) of patients with malignant indications for surgery developed NAFLD compared to 9.5% (4/42) with benign indications (P = .09). Time to development of hepatic steatosis in the malignant group was 26.4 months and was significantly shorter by an average of 6 months when compared to the benign group (32.8 months, P = .03). Higher pre-operative body mass index was associated with new-onset NAFLD (P = .03). Pre-operative body mass index is a significant predictor for de novo NAFLD and highlights a group that should be closely monitored post-operatively, especially after resections for pancreatic malignancy.

4,300 steps per day prior to surgery are associated with improved outcomes after pancreatectomy.

BACKGROUND: Decreased preoperative physical fitness and low physical activity have been associated with preoperative functional reserve and surgical complications. We sought to evaluate daily step count as a measure of physical activity and its relationship with post-pancreatectomy outcomes. METHODS: Patients undergoing pancreatectomy were given a remote telemonitoring device to measure their preoperative levels of physical activity. Patient activity, demographics, and perioperative outcomes were collected and compared in univariate and multivariate logistic regression analysis. RESULTS: 73 patients were included. 45 (61.6%) patients developed complications, with 17 (23.3%) of those patients developing severe complications. These patients walked 3437.8 (SD 1976.7) average daily steps, compared to 5918.8 (SD 2851.1) in patients without severe complications (p < 0.001). In logistic regression analysis, patients who walked less than 4274.5 steps had significantly higher odds of severe complications (OR = 7.5 (CI 2.1, 26.8), p = 0.002). CONCLUSION: Average daily steps below 4274.5 before surgery are associated with severe complications after pancreatectomy. Preoperative physical activity levels may represent a modifiable target for prehabilitation protocols.

Racial Disparity in Pathologic Response following Neoadjuvant Chemotherapy in Resected Pancreatic Cancer: A Multi-Institutional Analysis from the Central Pancreatic Consortium.

BACKGROUND: Major pathologic response (MPR) following neoadjuvant therapy (NAT) in pancreatic ductal adenocarcinoma (PDAC) patients undergoing resection is associated with improved survival. We sought to determine whether racial disparities exist in MPR rates following NAT in patients with PDAC undergoing resection. METHODS: Patients with potentially operable PDAC receiving at least 2 cycles of neoadjuvant FOLFIRINOX or gemcitabine/nab-paclitaxel ± radiation followed by pancreatectomy (2010-2019) at 7 high-volume centers were reviewed. Self-reported race was dichotomized as Black and non-Black, and multivariable models evaluated the association between race and MPR (i.e., pathologic complete response [pCR] or near-pCR). Cox regression evaluated the association between race and disease-free (DFS) and overall survival (OS). RESULTS: Results of 486 patients who underwent resection following NAT (mFOLFIRINOX 56%, gemcitabine/nab-paclitaxel 25%, radiation 29%), 67 (13.8%) patients were Black. Black patients had lower CA19-9 at diagnosis (median 67 vs. 204 U/mL; P = 0.003) and were more likely to undergo mild/moderate chemotherapy dose modification (40 vs. 20%; P = 0.005) versus non-Black patients. Black patients had significantly lower rates of MPR compared with non-Black patients (13.4 vs. 25.8%; P = 0.039). Black race was independently associated with worse MPR (OR 0.26, 95% confidence interval [CI] 0.10-0.69) while controlling for NAT duration, CA19-9 dynamics, and chemotherapy modifications. There was no significant difference in DFS or OS between Black and non-Black cohorts. CONCLUSIONS: Black patients undergoing pancreatectomy appear less likely to experience MPR following NAT. The contribution of biologic and nonbiologic factors to reduced chemosensitivity in Black patients warrants further investigation.

MR-Guided Radiation Therapy With Concurrent Gemcitabine/Nab-Paclitaxel Chemotherapy in Inoperable Pancreatic Cancer: A TITE-CRM Phase I Trial.

PURPOSE: Ablative radiation therapy for borderline resectable or locally advanced pancreatic ductal adenocarcinoma (BR/LA-PDAC) may limit concurrent chemotherapy dosing and usually is only safely deliverable to tumors distant from gastrointestinal organs. Magnetic resonance guided radiation therapy may safely permit radiation and chemotherapy dose escalation. METHODS AND MATERIALS: We conducted a single-arm phase I study to determine the maximum tolerated dose of ablative hypofractionated radiation with full-dose gemcitabine/nab-paclitaxel in patients with BR/LA-PDAC. Patients were treated with gemcitabine/nab-paclitaxel (1000/125 mg/m2) x 1c then concurrent gemcitabine/nab-paclitaxel and radiation. Gemcitabine/nab-paclitaxel and radiation doses were escalated per time-to-event continual reassessment method from 40 to 45 Gy 25 fxs with chemotherapy (600-800/75 mg/m2) to 60 to 67.5 Gy/15 fractions and concurrent gemcitabine/nab-paclitaxel (1000/100 mg/m2). The primary endpoint was maximum tolerated dose of radiation as defined by 60-day dose limiting toxicity (DLT). DLT was treatment-related G5, G4 hematologic, or G3 gastrointestinal requiring hospitalization >3 days. Secondary endpoints included resection rates, local progression free survival (LPFS), distant metastasis free survival (DMFS), and overall survival (OS). RESULTS: Thirty patients enrolled (March 2015-February 2019), with 26 evaluable patients (2 progressed before radiation, 1 was determined ineligible for radiation during planning, 1 withdrew consent). One DLT was observed. The DLT rate was 14.1% (3.3%-24.9%) with a maximum tolerated dose of gemcitabine/nab-paclitaxel (1000/100 mg/m2) and 67.5 Gy/15 fractions. At a median follow-up of 40.6 months for living patients the median OS was 14.5 months (95% confidence interval [CI], 10.9-28.2 months). The median OS for patients with Eastern Collaborative Oncology Group 0 and carbohydrate antigen 19-9 <90 were 34.1 (95% CI, 13.6-54.1) and 43.0 (95% CI, 8.0-not reached) months, respectively. Two-year LPFS and DMFS were 85% (95% CI, 63%-94%) and 57% (95% CI, 34%-73%), respectively. CONCLUSIONS: Full-dose gemcitabine/nab-paclitaxel with ablative magnetic resonance guided radiation therapy dosing is safe in patients with BR/LA-PDAC, with promising LPFS and DMFS.

Preoperative transversus abdominis plane block decreases intraoperative opiate consumption during minimally invasive cholecystectomy.

BACKGROUND: The ongoing epidemic of prescription opiate abuse is one of the most pressing health issues in the United States today. Consequently, analgesic adjuncts, such as multimodal drug regimens and regional anesthetic blocks (like transversus abdominis plane (TAP) block), have been introduced to the perioperative period in hopes of decreasing postoperative opiate use. However, the effect of these interventions on intraoperative opiate use has not been examined. We hypothesized that preoperative TAP block would be associated with decreased intraoperative opiate use during minimally invasive cholecystectomy. METHODS: This was a retrospective review of patients undergoing minimally invasive cholecystectomy between June 2018 and January 2021. Perioperative data, operative times, and medication administration data were collected. Intraoperative opiate use was calculated in total morphine equivalent doses (MED) for each patient and adjusted for operative time. Univariate analysis and multivariate linear regression were performed to determine factors affecting intraoperative opiate requirements. RESULTS: 261 patients were included in this study, of which 62 (23.8%) received preoperative TAP block and 199 (76.2%) did not. Preoperative TAP block was associated with decreased intraoperative opiate use (0.199 vs 0.312, p < 0.001), while there were no statistically significant differences associated with other analgesic adjuncts including preoperative acetaminophen (p = 0.485), celecoxib (p = 0.112), gabapentin (p = 0.165), or intraoperative ketorolac (p = 0.200). On multivariate analysis, preoperative TAP block was independently associated with decreased intraoperative opiate use (< 0.001), while chronic cholecystitis on final pathology was associated with increased intraoperative opiate use (p = 0.002). CONCLUSION: The use of preoperative TAP block was associated with decreased intraoperative opiate use during minimally invasive cholecystectomy and should be considered for routine use. Future research should investigate whether preoperative TAP blocks and a subsequent decrease of intraoperative opiates, also result in a decrease in postoperative opiate use and improvements in postoperative outcomes.

Acinar cell carcinoma with PRKAR1A and PTEN alterations and paraneoplastic panniculitis.

Pancreatic acinar cell carcinoma is a rare type of pancreatic malignancy, which can be confused with pancreatic neuroendocrine neoplasm. Here, we describe a woman in her 80s who presented with abdominal pain and bilateral lower extremity panniculitis. She underwent surgery for a presumed diagnosis of neuroendocrine tumour with PTEN and PRKAR1A alterations; 19 months, later, a recurrence of her pancreatic malignancy was discovered. The patient underwent repeat resection and this time immunohistochemical staining confirmed the diagnosis of acinar cell carcinoma. Staining for acinar cell carcinoma should be prompted based on clinical suspicion in context of PTEN or PRKAR1A mutation when appropriate.

Preliminary experience with a new institutional tumor board dedicated to patients with neuroendocrine neoplasms.

PURPOSE: To determine the decision patterns of a neuroendocrine neoplasm (NEN) tumor board (TB) and the factors behind those. METHODS: We retrospectively reviewed all NEN-TB recommendations from 07/2018 to 12/2021 and recorded patient characteristics, TB outcomes and associations between them. RESULTS: A total of 652 patient entries were identified. Median age of participants was 61 years and an equal number of men and women were presented. Most patients (33.4%) had tumors originating in the small bowel with 16.8% of high grade and 25.9% of pancreatic origin. Imaging was reviewed 97.2% of the time, with most frequently reviewed modalities being PET (55.3%) and CT (44.3%). Imaging review determined that there was no disease progression 20.8% of the time and significant treatment changes were recommended in 36.1% of patients. Major pathology amendments occurred in 3.7% of cases and a clinical trial was identified in 2.6%. There was no association between patient or disease presentation with the tumor board outcomes. There was a slight decrease in number of patients discussed per session, from 10.0 to 8.2 (p < 0.001) when the TB transitioned to a virtual format during the COVID-19 pandemic but all other factors remained unchanged. CONCLUSION: NEN-TB relies heavily on image review, can impact significant treatment changes in patients with rare tumors like NENs, and was not affected by the switch to a virtual format. Finally, none of the examined factors were predictive of the tumor board recommendations.