Society for Surgery of the Alimentary Tract State-of-the-Art Session 2022: Frailty in Surgery.

Given the exponentially aging population and rising life expectancy in the United States, surgeons are facing a challenging frail population who may require surgery but may not qualify based on their general fitness. There is an urgent need for greater awareness of the importance of frailty measurement and the implementation of universal assessment of frail patients into clinical practice. Pairing risk stratification with stringent protocols for prehabilitation and minimally invasive surgery and appropriate enhanced recovery protocols could optimize and condition frail patients before, during, and immediately after surgery to mitigate postoperative complications and consequences on patient function and quality of life. In this paper, highlights from the 2022 Society for Surgery of the Alimentary Tract State-of-the-Art Session on frailty in surgery are presented. This work aims to improve the understanding of the impact of frailty on patients and the methods used to augment the outcomes for frail patients during their surgical experience.

Impact of preoperative uni- or multimodal prehabilitation on postoperative morbidity: meta-analysis.

BACKGROUND: Postoperative complications occur in up to 43% of patients after surgery, resulting in increased morbidity and economic burden. Prehabilitation has the potential to increase patients' preoperative health status and thereby improve postoperative outcomes. However, reported results of prehabilitation are contradictory. The objective of this systematic review is to evaluate the effects of prehabilitation on postoperative outcomes (postoperative complications, hospital length of stay, pain at postoperative day 1) in patients undergoing elective surgery. METHODS: The authors performed a systematic review and meta-analysis of RCTs published between January 2006 and June 2023 comparing prehabilitation programmes lasting ≥14 days to 'standard of care' (SOC) and reporting postoperative complications according to the Clavien-Dindo classification. Database searches were conducted in PubMed, CINAHL, EMBASE, PsycINFO. The primary outcome examined was the effect of uni- or multimodal prehabilitation on 30-day complications. Secondary outcomes were length of ICU and hospital stay (LOS) and reported pain scores. RESULTS: Twenty-five studies (including 2090 patients randomized in a 1:1 ratio) met the inclusion criteria. Average methodological study quality was moderate. There was no difference between prehabilitation and SOC groups in regard to occurrence of postoperative complications (OR = 1.02, 95% c.i. 0.93 to 1.13; P = 0.10; I2 = 34%), total hospital LOS (-0.13 days; 95% c.i. -0.56 to 0.28; P = 0.53; I2 = 21%) or reported postoperative pain. The ICU LOS was significantly shorter in the prehabilitation group (-0.57 days; 95% c.i. -1.10 to -0.04; P = 0.03; I2 = 46%). Separate comparison of uni- and multimodal prehabilitation showed no difference for either intervention. CONCLUSION: Prehabilitation reduces ICU LOS compared with SOC in elective surgery patients but has no effect on overall complication rates or total LOS, regardless of modality. Prehabilitation programs need standardization and specific targeting of those patients most likely to benefit.

GITR and TIGIT immunotherapy provokes divergent multicellular responses in the tumor microenvironment of gastrointestinal cancers.

BACKGROUND: Understanding the mechanistic effects of novel immunotherapy agents is critical to improving their successful clinical translation. These effects need to be studied in preclinical models that maintain the heterogenous tumor microenvironment (TME) and dysfunctional cell states found in a patient's tumor. We investigated immunotherapy perturbations targeting co-stimulatory molecule GITR and co-inhibitory immune checkpoint TIGIT in a patient-derived ex vivo system that maintains the TME in its near-native state. Leveraging single-cell genomics, we identified cell type-specific transcriptional reprogramming in response to immunotherapy perturbations. METHODS: We generated ex vivo tumor slice cultures from fresh surgical resections of gastric and colon cancer and treated them with GITR agonist or TIGIT antagonist antibodies. We applied paired single-cell RNA and TCR sequencing to the original surgical resections, control, and treated ex vivo tumor slice cultures. We additionally confirmed target expression using multiplex immunofluorescence and validated our findings with RNA in situ hybridization. RESULTS: We confirmed that tumor slice cultures maintained the cell types, transcriptional cell states and proportions of the original surgical resection. The GITR agonist was limited to increasing effector gene expression only in cytotoxic CD8 T cells. Dysfunctional exhausted CD8 T cells did not respond to GITR agonist. In contrast, the TIGIT antagonist increased TCR signaling and activated both cytotoxic and dysfunctional CD8 T cells. This included cells corresponding to TCR clonotypes with features indicative of potential tumor antigen reactivity. The TIGIT antagonist also activated T follicular helper-like cells and dendritic cells, and reduced markers of immunosuppression in regulatory T cells. CONCLUSIONS: We identified novel cellular mechanisms of action of GITR and TIGIT immunotherapy in the patients' TME. Unlike the GITR agonist that generated a limited transcriptional response, TIGIT antagonist orchestrated a multicellular response involving CD8 T cells, T follicular helper-like cells, dendritic cells, and regulatory T cells. Our experimental strategy combining single-cell genomics with preclinical models can successfully identify mechanisms of action of novel immunotherapy agents. Understanding the cellular and transcriptional mechanisms of response or resistance will aid in prioritization of targets and their clinical translation.

Barriers and Facilitators of Surgical Prehabilitation Adherence from the Patient Perspective: a Mixed Method Study.

BACKGROUND: Adherence to prehabilitation is crucial for optimal benefit, but reasons for low adherence to home-based programs remain unexplored. Our aim was to identify and explore barriers and facilitators to prehabilitation adherence among patients undergoing abdominal surgery. METHODS: Nested in a single-center randomized controlled trial on prehabilitation (Perioperative Optimization With Enhanced Recovery (POWER)), this study had an explanatory sequential design with a connect integration. Patients randomized to the intervention arm were included in the quantitative analysis, and a subset of them was invited for a semi-structured interview. The exposure was the frequency of barriers to physical activity and healthy eating, and the outcome was adherence to those components of prehabilitation. Logistic or linear regression was used as appropriate. RESULTS: Among 133 participants in the intervention arm, 116 (87.2%) completed the initial survey ((56.9% women, median age 61 years old (IQR 49.0; 69.4)). The most frequent barriers to exercise and healthy eating were medical issues (59%) and lack of motivation (31%), respectively. There was no significant association between the barriers to physical activity score and adherence to this component of the program (OR 0.89, 95% CI 0.78-1.02, p=0.09). Higher barriers to healthy eating scores were associated with lower Mediterranean diet scores pre- and post-intervention (coef.: -0.32, 95% CI: -0.49; -0.15, p<0.001; and coef.: -0.27, 95% CI: -0.47; -0.07, p=0.01, respectively). Interviews with 15 participants revealed that participating in prehabilitation was a motivator for healthy eating and exercising through goal setting, time-efficient workouts, and promoting self-efficacy. CONCLUSIONS: We identified key barriers to be addressed and facilitators to be leveraged in future prehabilitation programs. TRIAL REGISTRATION: NCT04504266.

GITR and TIGIT immunotherapy provokes divergent multi-cellular responses in the tumor microenvironment of gastrointestinal cancers.

Understanding the cellular mechanisms of novel immunotherapy agents in the human tumor microenvironment (TME) is critical to their clinical success. We examined GITR and TIGIT immunotherapy in gastric and colon cancer patients using ex vivo slice tumor slice cultures derived from cancer surgical resections. This primary culture system maintains the original TME in a near-native state. We applied paired single-cell RNA and TCR sequencing to identify cell type specific transcriptional reprogramming. The GITR agonist was limited to increasing effector gene expression only in cytotoxic CD8 T cells. The TIGIT antagonist increased TCR signaling and activated both cytotoxic and dysfunctional CD8 T cells, including clonotypes indicative of potential tumor antigen reactivity. The TIGIT antagonist also activated T follicular helper-like cells and dendritic cells, and reduced markers of immunosuppression in regulatory T cells. Overall, we identified cellular mechanisms of action of these two immunotherapy targets in the patients' TME.

Using AI and computer vision to analyze technical proficiency in robotic surgery.

BACKGROUND: Intraoperative skills assessment is time-consuming and subjective; an efficient and objective computer vision-based approach for feedback is desired. In this work, we aim to design and validate an interpretable automated method to evaluate technical proficiency using colorectal robotic surgery videos with artificial intelligence. METHODS: 92 curated clips of peritoneal closure were characterized by both board-certified surgeons and a computer vision AI algorithm to compare the measures of surgical skill. For human ratings, six surgeons graded clips according to the GEARS assessment tool; for AI assessment, deep learning computer vision algorithms for surgical tool detection and tracking were developed and implemented. RESULTS: For the GEARS category of efficiency, we observe a positive correlation between human expert ratings of technical efficiency and AI-determined total tool movement (r = - 0.72). Additionally, we show that more proficient surgeons perform closure with significantly less tool movement compared to less proficient surgeons (p < 0.001). For the GEARS category of bimanual dexterity, a positive correlation between expert ratings of bimanual dexterity and the AI model's calculated measure of bimanual movement based on simultaneous tool movement (r = 0.48) was also observed. On average, we also find that higher skill clips have significantly more simultaneous movement in both hands compared to lower skill clips (p < 0.001). CONCLUSIONS: In this study, measurements of technical proficiency extracted from AI algorithms are shown to correlate with those given by expert surgeons. Although we target measurements of efficiency and bimanual dexterity, this work suggests that artificial intelligence through computer vision holds promise for efficiently standardizing grading of surgical technique, which may help in surgical skills training.

Is It Really Gone? Assessing Response to Neoadjuvant Therapy in Rectal Cancer.

PURPOSE: Non-operative management of rectal cancer is a feasible and appealing treatment option for patients who develop a complete response after neoadjuvant therapy. However, identifying patients who are complete responders is often a challenge. This review aims to present and discuss current evidence and recommendations regarding the assessment of treatment response in rectal cancer. METHODS: A review of the current literature on rectal cancer restaging was performed. Studies included in this review explored the optimal interval between the end of neoadjuvant therapy and restaging, as well as modalities of assessment and their diagnostic performance. RESULTS: The current standard for restaging rectal cancer is a multimodal assessment with the digital rectal examination, endoscopy, and T2-weighted MRI with diffusion-weighted imaging. Other diagnostic procedures under investigation are PET/MRI, radiomics, confocal laser endomicroscopy, artificial intelligence-assisted endoscopy, cell-free DNA, and prediction models incorporating one or more of the above-mentioned exams. CONCLUSION: Non-operative management of rectal cancer requires a multidisciplinary approach. Understanding of the robustness and limitations of each exam is critical to inform patient selection for that treatment strategy.

Association of an Online Home-Based Prehabilitation Program With Outcomes After Colorectal Surgery.

This quality improvement study evaluates the association of an online home-based patient prehabilitation program with colorectal surgery outcomes.

Augmented Reality Neuronavigation for En Bloc Resection of Spinal Column Lesions.

BACKGROUND: Primary tumors involving the spine are relatively rare but represent surgically challenging procedures with high patient morbidity. En bloc resection of these tumors necessitates large exposures, wide tumor margins, and poses risks to functionally relevant anatomical structures. Augmented reality neuronavigation (ARNV) represents a paradigm shift in neuronavigation, allowing on-demand visualization of 3D navigation data in real-time directly in line with the operative field. METHODS: Here, we describe the first application of ARNV to perform distal sacrococcygectomies for the en bloc removal of sacral and retrorectal lesions involving the coccyx in 2 patients, as well as a thoracic 9-11 laminectomy with costotransversectomy for en bloc removal of a schwannoma in a third patient. RESULTS: In our experience, ARNV allowed our teams to minimize the length of the incision, reduce the extent of bony resection, and enhanced visualization of critical adjacent anatomy. All tumors were resected en bloc, and the patients recovered well postoperatively, with no known complications. Pathologic analysis confirmed the en bloc removal of these lesions with negative margins. CONCLUSIONS: We conclude that ARNV is an effective strategy for the precise, en bloc removal of spinal lesions including both sacrococcygeal tumors involving the retrorectal space and thoracic schwannomas.

Association of Prehabilitation With Postoperative Opioid Use in Colorectal Surgery: An Observational Cohort Study.

INTRODUCTION: Preoperative optimization programs have demonstrated positive effects on perioperative physical function and surgical outcomes. In nonsurgical populations, physical activity and healthy diet may reduce pain and pain medication requirement, but this has not been studied in surgical patients. Our aim was to determine whether a preoperative diet and exercise intervention affects postoperative pain and pain medication use. METHODS: Patients undergoing abdominal colorectal surgery were invited to participate in a web-based patient engagement program. Those enrolling in the first and third time periods received information on the standard perioperative pathway (enhanced recovery after surgery [ERAS]). Those enrolling in the second time period also received reminders on nutrition and exercise (PREHAB + ERAS). The primary outcome was postoperative inpatient opioid use. The secondary outcomes were inpatient postoperative pain scores and nonopioid pain medication use. RESULTS: The ERAS and PREHAB + ERAS groups were similar in demographic and operative characteristics. Subgroup analysis of patients who activated their accounts demonstrated that the two groups had similar average maximum daily pain scores, but the PREHAB + ERAS group (n = 158) used 15.9 fewer oral morphine equivalents per postoperative inpatient day than the ERAS group (n = 92), representing a 30% decrease (53 mg versus 37.1 mg, P = 0.04). The two groups used comparable amounts of acetaminophen, gabapentin, and ketorolac. Generalized linear models demonstrated that PREHAB + ERAS, minimally invasive surgery, and older age were associated with lower inpatient opioid use. CONCLUSIONS: Access to a web-based preoperative diet and exercise program may reduce inpatient opioid use after major elective colorectal surgery. Further studies are necessary to determine whether the degree of adherence to nutrition and physical activity recommendations has a dose-dependent effect on opioid use.

Are You Really the Doctor? Physician Experiences with Gendered Microaggressions from Patients.

Background: In contrast to physician implicit bias toward patients, bias and microaggressions from patients toward physicians have received comparatively less attention. Materials and Methods: We captured physician experiences of gendered microaggressions from patients by conducting a mixed-methods survey-based study of physicians at a single academic health care institution in May 2019. A quantitative portion assessed the frequency of gendered microaggressions (microaggression experiences [ME] score) and the association with measures of perceived impacts (job satisfaction, burnout, perceived career impacts, behavioral modifications). A one-tailed Wilcoxon rank sum test compared distributional frequencies of microaggressions by gender, and by gender and race. Chi-square tests measured the associations between gendered microaggressions and perceived impacts. Welch two-sample t-tests assessed differences in ME scores by rank and specialty. Linear regression assessed the association of ME scores and job satisfaction/burnout. A qualitative portion solicited anecdotal experiences, analyzed by inductive thematic analysis. Results: There were 297 completed surveys (response rate 27%). Female physicians experienced a significantly higher frequency of gendered microaggressions (p < 0.001) compared with male physicians. Microaggressions were significantly associated with job satisfaction (chi-square 6.83, p = 0.009), burnout (chi-square 8.76, p = 0.003), perceived career impacts (chi-square 18.67, p < 0.001), and behavioral modifications (chi-square 19.96, p < 0.001). Trainees experienced more microaggressions (p = 0.009) and burnout (p = 0.009) than faculty. Higher ME scores predicted statistically significant increases in burnout (p < 0.0001) and reduced job satisfaction (p = 0.02). Twelve microaggressions themes emerged from the qualitative responses, including role questioning and assumption of inexperience. The frequency of microaggressions did not vary significantly by race; however, qualitative responses described race as a factor. Conclusions: Physicians experience gendered microaggressions from patients, which may influence job satisfaction, burnout, career perceptions, and behavior. Future research may explore the multidirectionality of microaggressions and tools for responding at the individual and institutional level.

Integrated Single-cell and Plasma Proteomic Modeling to Predict Surgical Site Complications: A Prospective Cohort Study.

OBJECTIVE: The aim of this study was to determine whether single-cell and plasma proteomic elements of the host's immune response to surgery accurately identify patients who develop a surgical site complication (SSC) after major abdominal surgery. SUMMARY BACKGROUND DATA: SSCs may occur in up to 25% of patients undergoing bowel resection, resulting in significant morbidity and economic burden. However, the accurate prediction of SSCs remains clinically challenging. Leveraging high-content proteomic technologies to comprehensively profile patients' immune response to surgery is a promising approach to identify predictive biological factors of SSCs. METHODS: Forty-one patients undergoing non-cancer bowel resection were prospectively enrolled. Blood samples collected before surgery and on postoperative day one (POD1) were analyzed using a combination of single-cell mass cytometry and plasma proteomics. The primary outcome was the occurrence of an SSC, including surgical site infection, anastomotic leak, or wound dehiscence within 30 days of surgery. RESULTS: A multiomic model integrating the single-cell and plasma proteomic data collected on POD1 accurately differentiated patients with (n = 11) and without (n = 30) an SSC [area under the curve (AUC) = 0.86]. Model features included coregulated proinflammatory (eg, IL-6- and MyD88- signaling responses in myeloid cells) and immunosuppressive (eg, JAK/STAT signaling responses in M-MDSCs and Tregs) events preceding an SSC. Importantly, analysis of the immunological data obtained before surgery also yielded a model accurately predicting SSCs (AUC = 0.82). CONCLUSIONS: The multiomic analysis of patients' immune response after surgery and immune state before surgery revealed systemic immune signatures preceding the development of SSCs. Our results suggest that integrating immunological data in perioperative risk assessment paradigms is a plausible strategy to guide individualized clinical care.

Worse outcomes and higher costs of care in fibrostenotic Crohn's disease: a real-world propensity-matched analysis in the USA.

BACKGROUND: Patients with Crohn's disease (CD) may develop fibrostenotic strictures. No currently available therapies prevent or treat fibrostenotic CD (FCD), making this a critical unmet need. AIM: To compare health outcomes and resource utilisation between CD patients with and without fibrostenotic disease. METHODS: Patients aged ≥18 years with FCD and non-FCD between 30 October 2015 and 30 September 2018 were identified in the Truven MarketScan Commercial Claims and Encounters Database. We conducted 1:3 nearest neighbour propensity score matching on age, sex, malnutrition, payer type, anti-tumour necrosis factor use, and Charlson Comorbidity Index score. Primary outcomes up to 1 year from the index claim were ≥1 hospitalisation, ≥1 procedure, ≥1 surgery, and steroid dependency (>100 day supply). Associations between FCD diagnosis and outcomes were estimated with a multivariable logistic regression model. This study was exempt from institutional review board approval. RESULTS: Propensity score matching yielded 11 022 patients. Compared with non-FCD, patients with FCD had increased likelihood of hospitalisations (17.1% vs 52.4%; p<0.001), endoscopic procedures (4.4% vs 8.6%; p<0.001), IBD-related surgeries (4.7% vs 9.1%; p<0.001), steroid dependency (10.0% vs 15.7%; p<0.001), and greater mean annual costs per patient ($47 575 vs $77 609; p<0.001). FCD was a significant risk factor for ≥1 hospitalisation (adjusted OR (aOR), 6.1), ≥1 procedure (aOR, 2.1), ≥1 surgery (aOR, 2.0), and steroid dependency (aOR, 1.7). CONCLUSIONS: FCD was associated with higher risk for hospitalisation, procedures, abdominal surgery, and steroid dependency. Patients with FCD had a greater mean annual cost per patient. FCD represents an ongoing unmet medical need.

Engagement and Adherence with a Web-Based Prehabilitation Program for Patients Awaiting Abdominal Colorectal Surgery.

BACKGROUND: Understanding the drivers of patient engagement and adherence is critical to developing and implementing preoperative optimization programs. The aim of this project is to determine whether existing health beliefs are associated with engagement and adherence in a home-based online prehabilitation program. METHODS: Patients undergoing abdominal colorectal operations were enrolled in an online nutrition and exercise program. We collected baseline health beliefs and mindsets, daily exercises, and weekly diet recalls. Multivariable binary logistic regression predicted engagement, multivariable ordinary least squares regression predicted diet adherence, and generalized linear models with a binomial distribution predicted engagement and exercise adherence. RESULTS: Of the 227 patients who agreed to participate, 75% activated their accounts; of those, 75% used the program. Engagement with the program was unrelated to health beliefs or mindsets. Positive diet-related health beliefs and a growth mindset were associated with positive diet behaviors and inversely associated with negative diet behaviors. Exercise-related health beliefs and mindsets were not associated with exercise adherence. Patients enrolled within 4 weeks of surgery used the program more than those enrolled more than 4 weeks from surgery. CONCLUSIONS: This app-based prehabilitation program demonstrated moderate acceptability, engagement, and adherence. Addressing health beliefs and mindsets may be an effective way of increasing adherence to diet recommendations. To increase adherence to exercise recommendations, further assessment of potential barriers is critical. While an online platform is a highly promising scalable strategy, more customization and user engagement are necessary to make it an effective way of delivering a preoperative health behavior change intervention.

Measuring the human immune response to surgery: multiomics for the prediction of postoperative outcomes.

PURPOSE OF REVIEW: Postoperative complications including infections, cognitive impairment, and protracted recovery occur in one-third of the 300 million surgeries performed annually worldwide. Complications cause personal suffering along with a significant economic burden on our healthcare system. However, the accurate prediction of postoperative complications and patient-targeted interventions for their prevention remain as major clinical challenges. RECENT FINDINGS: Although multifactorial in origin, the dysregulation of immunological mechanisms that occur in response to surgical trauma is a key determinant of postoperative complications. Prior research, primarily focusing on inflammatory plasma markers, has provided important clues regarding their pathogenesis. However, the recent advent of high-content, single-cell transcriptomic, and proteomic technologies has considerably improved our ability to characterize the immune response to surgery, thereby providing new means to understand the immunological basis of postoperative complications and to identify prognostic biological signatures. SUMMARY: The comprehensive and single-cell characterization of the human immune response to surgery has significantly advanced our ability to predict the risk of postoperative complications. Multiomic modeling of patients' immune states holds promise for the discovery of preoperative predictive biomarkers, ultimately providing patients and surgeons with actionable information to improve surgical outcomes. Although recent studies have generated a wealth of knowledge, laying the foundation for a single-cell atlas of the human immune response to surgery, larger-scale multiomic studies are required to derive robust, scalable, and sufficiently powerful models to accurately predict the risk of postoperative complications in individual patients.

Opioid use among patients with pain syndromes commonly seeking surgical consultation: A retrospective cohort.

BACKGROUND: Surgeons often see patients with pain to exclude organic pathology and consider surgical treatment. We examined factors associated with long-term opioid therapy among patients with foot/ankle, anorectal, and temporomandibular joint pain to aid clinical decision making. METHODS: Using the IBM MarketScan® Research Database, we conducted a retrospective cohort analysis of patients aged 18-64 with a clinical encounter for foot/ankle, anorectal, or temporomandibular joint pain (January 2007-September 2015). Multivariable logistic regression was used to estimate adjusted odds ratios for factors associated with long-term opioid therapy, including age, sex, geographic region, pain condition, psychiatric diagnoses, and surgical procedures in the previous year. RESULTS: The majority of the cohort of 1,500,392 patients were women (61%). Within the year prior to the first clinical encounter for a pain diagnosis, 14% had an encounter for a psychiatric diagnosis, and 11% had undergone a surgical procedure. Long-term opioid therapy was received by 2.7%. After multivariable adjustment, older age (age 50-64 vs. 18-29: aOR 4.47, 95% CI 4.24-4.72, p < 0.001), region (South vs. Northeast, aOR 1.76, 95% CI 1.70-1.81, p < 0.001), recent surgical procedure (aOR 1.83, 95% CI 1.78-1.87, p < 0.001), male sex (aOR 1.14, 95% CI 1.12-1.16, p < 0.001) and recent psychiatric diagnosis (aOR 2.49, 95% CI 2.43-2.54, p < 0.001) were independently associated with long-term opioid therapy. CONCLUSION: Among patients with foot/ankle, anorectal, or temporomandibular joint pain, the risk of long-term opioid therapy significantly increased with older age, recent psychiatric diagnoses and surgical history. Surgeons should be aware of these risk factors in order to make high quality clinical decisions in consultations with these patients.