Beyond the physical: Digital phenotyping and the complexity of surgical recovery.

Digital phenotyping, the moment-by-moment quantification of human behavior in situ using data from personal digital devices, is a potentially powerful tool for increasing understanding of recovery from surgery. While physical metrics are often emphasized, measures of emotional, cognitive, and psychosocial function are important aspects for the surgeon, a better understanding of which can lead to improved preoperative counseling and optimization, shared decision-making, and monitoring of recovery after surgery. A growing number of studies have begun to characterize these techniques. Ultimately, this tool may provide rich data about the perioperative period that will help surgeons and patients alike.

Phase 1 randomized trial of inpatient high-intensity interval training after major surgery.

BACKGROUND: High-intensity interval training (HIT) can provide physiologic benefits and may improve postoperative recovery but has not been evaluated in inpatients. This study aimed to evaluate the safety and tolerability of HIT after major surgery. METHODS: We performed a phase I randomized study comparing HIT with low-intensity continuous ambulation (40 m) during the initial inpatient stay after major surgery at a large academic center. Clinicopathologic and pre- and post-exercise physiologic data were captured. Perceived exertion was measured throughout the intervention. RESULTS: Twenty-two subjects were enrolled and randomized with 90% (20 subjects, 10 per arm) completing all aspects of the study. One patient declined participation in the exercise intervention. The HIT and continuous ambulation groups were relatively similar in terms of median age (65.5 vs 63.5), female sex (20% vs 40%), White race (90% vs 90%), having a cancer diagnosis (100% vs 80%), undergoing gastrointestinal surgery (60% vs 80%), median Karnofsky score (60 vs 60), and ability to independently ambulate preoperatively (100% vs 90%). All subjects completed the exercise without protocol deviation, cohort crossover, or safety events. Compared with the continuous ambulation group, the HIT group had higher end median perceived exertion (5.0 [IQR, 5.5] vs 3.0 [IQR, 1.8]), shorter overall time to complete assigned exercise (56.6 seconds vs 91.8 seconds), and a trend toward higher median gait speed over 40 m (0.71 m/s vs 0.44 m/s, P = .126). CONCLUSION: HIT in the hospitalized postoperative patient is safe and may be implemented to help promote positive physiologic outcomes and recovery.

The Impact of Frailty on Adjuvant Therapies Not Offered to or Declined by Breast Cancer Surgery Patients.

INTRODUCTION: The impact of frailty on adjuvant therapies not offered to or declined by elderly breast cancer surgery patients has been understudied. METHODS: This is a retrospective review of a prospectively managed single-center database including all breast cancer patients >65 years undergoing surgery in 2021. Frailty was determined using an electronic frailty index (eFI) derived from electronic health data. Patients were categorized as Fit (eFI ≤ .10), Pre-frail (.10 < eFI ≤.21), or Frail (eFI > .21). Chart review was performed to collect data on adjuvant therapies not offered or declined. Descriptive statistics and logistic regression were performed. RESULTS: Of 133 patients, 16.5% were frail, 46.6% were pre-frail, and 36.8% were fit. Demographics were similar among groups except age and comorbidities. Of those with adjuvant therapy indicated (n = 123), 15.4% were not offered at least one indicated therapy. Of those offered therapy, some therapy was declined in 22.7%. Frail patients more often were not offered or declined some therapy (frail: 63.2%, pre-frail 36.2%, fit: 28.2%, P = .03). Frailty was associated with having some therapy not offered or declined on univariate modeling (OR 4.4 95% CI 1.4-13.5, P = .01) but not on multivariate. Being frail was associated with higher odds of readmission at 6 months on multivariate analysis (OR 9.5, 95% CI: 1.7-54.2. P = .01). CONCLUSION: Over half of frail patients are not offered or decline some adjuvant therapy. The impact of this requires further study. Given their higher odds of readmission, frail patients require close postoperative monitoring to prevent the interruption of adjuvant therapies.

Distance Traveled and Disparities in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: The impact of distance traveled on cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) outcomes needs further investigation. METHODS: This retrospective study reviewed a prospectively managed single-center CRS/HIPEC 1992-2022 database. Zip codes were used to calculate distance traveled and to obtain data on income and education via census data. Patients were separated into three groups based on distance traveled in miles (local: ≤50 miles, regional: 51-99 miles, distant: ≥100 miles). Descriptive statistics, Kaplan-Meier method, and Cox regression were performed. RESULTS: The 1614 patients in the study traveled a median distance of 109.5 miles (interquartile range [IQR], 53.36-202.29 miles), with 23% traveling locally, 23.9% traveling regionally, and 53% traveling distantly. Those traveling distantly or regionally tended to be more white (distant: 87.8%, regional: 87.2%, local: 83.2%), affluent (distant: $61,944, regional: $65,014, local: $54,390), educated (% without high school diploma: distant: 10.6%, regional: 11.5%, local: 13.0%), less often uninsured (distant: 2.3%, regional: 4.6%, local: 5.2%) or with Medicaid (distant: 3.3%, regional: 1.3%, local: 9.7%). They more often had higher Peritoneal Carcinomatosis Index (PCI) scores (distant: 15.4, regional: 15.8, local: 12.7) and R2 resections (distant: 50.3%, regional: 52.2%, local: 40.5%). Median survival did not differ between the groups, and distance traveled was not a predictor of survival. CONCLUSION: More than 50% of the patients traveled farther than 100 miles for treatment. Although regionalization of CRS/HIPEC may be appropriate given the lack of survival difference based on distance traveled, those who traveled further had fewer health care disparities but higher PCI scores and more R2 resections, which raises concerns about access to care for the underserved, time to treatment, and surgical quality.

Quality-of-Life Outcomes for Patients Taking Opioids and Psychotropic Medications Before Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: The impact of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) on quality of life (QoL) for patients taking opioids and psychotropic medications preoperatively is unclear. METHODS: This study retrospectively reviewed a CRS-HIPEC single-center prospectively maintained database for 2012-2016. Demographics and clinical data on opioids/psychotropic medication use were collected via chart review. The study collected QoL outcomes at baseline, then 3, 6, and 12 months postoperatively via the Center for Epidemiologic Studies Depression Scale (CES-D), Brief Pain Inventory, Functional Assessment of Cancer Therapy, and 36-Item Short-Form Health Survey. Differences in QoL between the groups were calculated using repeated measures analysis of variance regression. Descriptive statistics and Kaplan-Meier analyses were performed. RESULTS: Of 388 patients, 44.8% were taking opioids/psychotropic medications preoperatively. At baseline, those taking opioids/psychotropic medications preoperatively versus those not taking these medications had significantly worse QoL. By 1 year postoperatively, the QoL measures did not differ significantly except for emotional functioning (e.g., no medications vs. opioids/psychotropic medications: CES-D, 5.6 vs. 10.1). Median survival did not differ significantly (opioids/psychotropic medications vs. no medications: 52.3 vs. 60.6 months; p = 0.66). At 1 year after surgery, a greater percentage of patients were taking opioids, psychotropic medications, or both than at baseline (63.2% vs. 44.8%; p < 0.001). CONCLUSION: Despite worse baseline QoL, patients who took opioids/psychotropic medications had QoL scores 1 year postoperatively similar to the scores of those who did not except in the emotional domains. These data point to the potential utility of a timed psychosocial intervention to enhance emotional adaptation and further support the role of CRS-HIPEC in improving QoL.

Comparison of survival for metastatic pancreatic cancer patients treated with CPI-613 versus resected borderline-resectable pancreatic cancer patients.

INTRODUCTION: Treatment of advanced pancreatic adenocarcinoma remains suboptimal. Therapeutic agents with a novel mechanism of action are desperately needed; one such novel agent is CPI-613 targets. We here analyze the outcomes of 20 metastatic pancreatic cancer patients treated with CPI-613 and FOLFIRINOX in our institution and evaluate their outcomes to borderline-resectable patients treated with curative surgery. METHODS: A post hoc analysis was performed of the phase I CPI-613 trial data (NCT03504423) comparing survival outcomes to borderline-resectable cases treated with curative resection at the same institution. Survival was measured by overall survival (OS) for all study cases and disease-free survival (DFS) for resected cases with progression-free survival for CPI-613 cases. RESULTS: There were 20 patients in the CPI-613 cohort and 60 patients in the surgical cohort. Median follow-up times were 441 and 517 days for CPI-613 and resected cases, respectively. There was no difference in survival times between CPI-613 and resected cases with a mean OS of 1.8 versus 1.9 year (p = 0.779) and mean PFS/DFS of 1.4 versus 1.7 years (p = 0.512). There was also no difference in 3-year survival rates for OS (hazard ratio [HR] = 1.063, 95% confidence interval [CI] 0.302-3.744, p = 0.925) or DFS/PFS (HR = 1.462, 95% CI 0.285-7.505, p = 0.648). CONCLUSION: The first study to evaluate the survival between metastatic patients treated with CPI-613 versus borderline-resectable cases undergoing curative resection. Analysis revealed no significant differences in survival outcomes between the cohorts. Study results are suggestive that there may be potential utility with the addition of CPI-613 to potentially resectable pancreatic adenocarcinoma, although additional research with more comparable study groups are required.

Potentially Avoidable Admissions and Prolonged Hospitalization in Patients with Suspected Colon Cancer.

BACKGROUND: Suspicion of cancer in the Emergency Department (ED) may lead to potentially avoidable and prolonged admissions. We aimed to examine the reasons for potentially avoidable and prolonged hospitalizations after admissions from the ED for new colon cancer diagnoses (ED-dx). METHODS: A retrospective, single-institution analysis was conducted of patients with ED-dx between 2017 and 2018. Defined criteria were used to identify potentially avoidable admissions. Patients without avoidable admissions were examined for ideal length of stay (iLOS), using separate defined criteria. Prolonged length of stay (pLOS) was defined as actual length of stay (aLOS) being greater than 1 day longer than iLOS. RESULTS: Of 97 patients with ED-dx, 12% had potentially avoidable admissions, most often (58%) for cancer workup. Very little difference in demographic, tumor characteristics, or symptoms were found, except patients with potentially avoidable admissions were more functional (Eastern Cooperative Oncology Group [ECOG] score 0-1: 83% vs. 46%; p = 0.049) and had longer symptom duration prior to ED presentation {24 days (interquartile range [IQR] 7-75) vs. 7 days (IQR 2-21)}. Among the 60 patients who had necessary admissions but did not require urgent intervention, 78% had pLOS, most often for non-urgent surgery (60%) and further oncologic workup. The median difference between iLOS and aLOS was 12 days (IQR 8-16) for pLOS. CONCLUSIONS: Potentially avoidable admissions following Ed-dx were uncommon but were mostly for oncologic workup. Once admitted, the majority of patients had pLOS, most often for definitive surgery and further oncologic workup. This suggests a lack of systems to safely transition to outpatient cancer management.

Conditional Survival After Hepatectomy for Colorectal Liver Metastasis: Results from the Colorectal Liver Operative Metastasis International Collaborative (COLOMIC).

INTRODUCTION: Complete resection of colorectal liver metastasis (CLM) improves long-term survival in colorectal cancer. However, there is limited recent data on conditional survival (CS) as postoperative survival milestones are achieved post-hepatectomy. METHODS: A retrospective analysis was performed on the penta-institutional Colorectal Liver Operative Metastasis International Collaborative (COLOMIC), with 906 consecutive CLM hepatectomy cases. CS was calculated using Bayes' theorem and Kaplan-Meier analysis. Additional CS analyses were performed on additional clinicopathologic risk factors, including colon cancer laterality, KRAS mutation status, and extrahepatic disease. RESULTS: The 5-year CS was 40.6%, 45.3%, 52.8%, and 65.3% at 0, 1, 2, and 3 years postoperatively, with significant improvements each year (p < 0.005). CS was not significantly different between right-sided and left-sided colorectal cancers by 3 years postoperatively. Patients with KRAS mutations had worse CS at all timepoints (p < 0.001). Extrahepatic disease was a poor prognostic factor for OS and CS (p < 0.001). However, CS for patients with KRAS mutations or extrahepatic disease improved significantly as 2-year, postoperative survival was achieved (p < 0.05). CONCLUSIONS: Five-year CS after hepatectomy for CLM improved with each passing year of survival postoperatively. Although extrahepatic disease and KRAS mutations are poor prognostic factors for OS, these populations still had improved CS after 2 years postoperatively.

Survival Outcomes of Optimally Treated Colorectal Metastases: The Importance of R0 Status in Surgical Treatment of Hepatic and Peritoneal Surface Disease.

BACKGROUND: Although colorectal hepatic metastases (HM) and peritoneal surface disease (PSD) are distinct biologic diseases, they may have similar long-term survival when optimally treated with surgery. METHODS: This study retrospectively reviewed prospectively managed databases. Patients undergoing R0 or R1 resections were analyzed with descriptive statistics, the Kaplan-Meier method, and Cox regression. Survival was compared over time for the following periods: 1993-2006, 2007-2012, and 2013-2020. RESULTS: The study enrolled 783 HM patients undergoing liver resection and 204 PSD patients undergoing cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). Compared with PSD patients, HM patients more often had R0 resections (90.3% vs. 32.4%), less often had pre-procedure chemotherapy (52.4% vs. 92.1%), and less often were functionally independent (79.7% vs. 95.6%). The 5-year overall survival for HM was 40.9%, with a median survival period of 45.8 months versus 25.8% and 33.4 months, respectively, for PSD (p < 0.05). When stratified by resection status, R0 HM and R0 PSD did not differ significantly in median survival (49.0 vs. 45.4 months; p = 0.83). The median survival after R1 resection also was similar between HM and PSD (32.6 vs. 26.9 months; p = 0.59). Survival between the two groups again was similar over time when stratified by resection status. The predictors of survival for HM patients were R0 resection, number of lesions, intraoperative transfusion, age, and adjuvant chemotherapy. For the PSD patients, the predictors were peritoneal cancer index (PCI) score, estimated blood loss (EBL), and female gender. CONCLUSION: The study showed that R0 resections are associated with improved outcomes and that median survival is similar between HM and PSD patients when it is achieved. Surveillance and treatment strategies that facilitate R0 resections are needed to improve results, particularly for PSD.

Long-Term Survival in Patients Treated with Cytoreduction and Heated Intraperitoneal Chemotherapy for Peritoneal Mesothelioma at a Single High-Volume Center.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare diagnosis with a dismal prognosis if untreated. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is shown to significantly improve survival. Our institution is uniquely positioned to report long-term outcomes in MPM with CRS-HIPEC, due to our robust peritoneal surface disease program existing over the past three decades. METHODS: Our prospectively maintained, single-institution database of CRS-HIPEC cases was reviewed, identifying 111 consecutive patients with MPM over 28 years (1993-2021). Prognostic, operative, and pathologic factors were reviewed. Overall survival (OS) and conditional survival (CS) analyses were performed. RESULTS: The average age was 55.1 years; 58.6% of patients were male; 17 of 111 patients (15.3%) had a second CRS-HIPEC. At first CRS-HIPEC, the average PCI score was 18.7, and the perfusate drugs were platinum-based (72.1%) and mitomycin C (27.9%). The resection status at first CRS-HIPEC was R2a (46.4%), followed by R0-1 (29.1%), and R2b-c (24.5%). Median OS was 3.3 years for the entire cohort, with 75th and 25th percentiles at 10.7 months and 10.6 years. Median CS was improved if patients survived to the 1-year postoperative mark (4.9 years, p < 0.01) and trended toward further improvement with each passing year. If 3-year postoperative survival was achieved, the median CS improved to 6.1 years. CONCLUSIONS: This represents one of the largest and lengthiest, single-center, longitudinal, case series of peritoneal mesothelioma treated with CRS-HIPEC. The OS suggests efficacy for CRS-HIPEC for MPM. Long-term survival improves significantly after patients achieve the 1-year, postoperative mark.

Exposure to Neoadjuvant Oxaliplatin-Containing Chemotherapy, Does it Effect Intraperitoneal Hyperthermic Chemotherapy Perfusion?

INTRODUCTION: Patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) are commonly exposed to oxaliplatin neoadjuvant chemotherapy (NAT) regimens. The impact of systemic exposure to oxaliplatin prior to HIPEC with oxaliplatin is unknown. METHODS: We conducted a retrospective review of our institutional registry of CRS/HIPEC cases who received oxaliplatin-containing NAT, and compared patients who underwent HIPEC with oxaliplatin versus cases perfused with mitomycin C. The primary outcome was survival, defined by overall survival (OS) and disease-free survival (DFS). Subgroup analysis was performed based on primary tumor etiology and completeness of cytoreduction. RESULTS: A total of 333 cases satisfied the selection criteria-159 appendiceal primaries (all high-grade disease) and 174 colorectal cases. Thirty-one cases (9.3%) underwent HIPEC with oxaliplatin, with the remaining 302 cases (90.7%) receiving mitomycin C. Both cohorts were identical in regard to baseline characteristics, and both groups were alike in regard to NAT regimens and oxaliplatin exposure. There was no difference in survival outcomes. OS times were 2.9 (± 2.8) and 2.8 ( ± 3.6) years for oxaliplatin and mitomycin C perfusions, respectively (p = 0.94), and the 5-year OS rates were also similar at 9.7 and 18.5% (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.14-1.67, p = 0.24) for oxaliplatin and mitomycin cases, respectively. Likewise, DFS findings were similar, with survival of 2.5 (± 4.5) and 1.8 (± 2.4) years for oxaliplatin and mitomycin perfusions, respectively (p = 0.21). There was no difference in 5-year DFS rates, at 10.5 and 7.8% (OR 1.39, 95% CI 0.30-6.56, p = 0.68) for oxaliplatin and mitomycin C, respectively. Subgroup analysis found minimal discordant findings from the main results. CONCLUSION: This analysis found no discernable association with NAT oxaliplatin exposure in regard to survival outcomes following CRS/HIPEC stratified out by perfusion agent.

Impact of myometrium invasion on survival outcomes following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC).

INTRODUCTION: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is an effective surgical intervention for peritoneal surface malignancy. The effect of myometrium invasion on outcomes is unknown. METHODS: Retrospective review of our institutional registry with analysis of CRS-HIPEC cases involving a hysterectomy. Compared cases with myometrium invasion versus those without invasion. Primary outcome was survival as measured by overall survival (OS) and disease-free survival (DFS). Secondary outcome was the evaluation of risk factors for myometrium invasion based on multivariate analysis. RESULTS: A total of 126 cases of CRS-HIPEC involving a hysterectomy were identified. Ninety-seven cases (76.9%) had no myometrium invasion and the remaining 29 cases (23.1%) had malignant invasion. The presence of myometrial invasion was a significant negative survival prognostic factor. The OS was halved with mean survival times of 2.8 (±2.3) versus 5.8 (±4.7) years for cases with and without invasion, respectively (p = 0.002). Five-year OS rates were also inferior with myometrium invasion at 17.4% versus 53.8% (odds ratio [OR] = 0.181, 95% confidence interval [CI]: 0.057-0.580, p = 0.002). A similar trend was present with DFS with mean survival times of 1.4 (±0.9) versus 3.7 (±3.9) years for noninvasion and invasion cases (p = 0.009). The 5-year DFS rates were 0% versus 34.8% (OR = 0.652, 95% CI: 0.549-0.775, p = 0.004). Secondary analysis significantly associated several risk factors with myometrium invasion to include lymph node positivity (OR = 2.539, 95% CI: 1.074-6.003, p = 0.012), colorectal primary tumors (OR = 2.248, 95% CI: 1.094-5.161, p = 0.035), and high-grade tumors (OR = 2.160, 95% CI: 1.080-4.820, p = 0.038). CONCLUSION: Myometrium invasion is a significant negative prognostic factor for survival following CRS-HIPEC. Several risk factors are potentially predictive of identifying those at high-risk for myometrium invasion.

Switching Perfusion Agents for Repeat Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy: Surgical Dogma or Evidence-Based Practice?

BACKGROUND: A common practice is to switch chemotherapy perfusion agents for repeat cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). However, there is a paucity of objective benefit with this practice. METHODS: A retrospective review of our institutional registry involving repeat CRS-HIPEC cases was conducted, comparing cases that underwent a perfusion agent switch versus those cases with no switch. The primary outcome of this study was survival, measured by overall survival (OS) and disease-free survival (DFS). A subgroup analysis was performed on the basis of primary etiology. RESULTS: A total of 101 cases met selection criteria. Mitomycin C was used as the index perfusion agent in 84% of cases, while oxaliplatin was utilized in the remaining 16% of cases. In total, 66 cases underwent a perfusion switch, with 35 cases using the same agent. Analysis revealed no survival benefit with HIPEC perfusion switch. For OS, there were similar mean survival times of 5.2 (± 4.1) years and 5.1 (± 3.6) years for cases with perfusion switch and no perfusion switch, respectively (P = 0.985). The 5-year OS rates were also similar at 61.4% and 53.3% for switch and non-switch cases, respectively [odds ratio (OR) 0.41, 95% confidence interval (CI) 0.54-3.56, P = 0.49]. Mean DFS was 4.0 (± 4.2) years and 3.6 (± 3.8) years for switch and non-switch cases, respectively (P = 0.74). The 5-year DFS rates had a greater difference with statistical trend, with rates of 53% versus 28% for switch and non-switch cases, respectively (OR 2.91, 95% CI 0.86-9.86, P = 0.081). Subgroup analysis had a similar trend to the main results. CONCLUSIONS: The study findings revealed no survival benefit with switching perfusion agents. Analysis suggests that the practice of perfusion switch is ineffective.

Smartphone-based Assessment of Preoperative Decision Conflict and Postoperative Physical Activity Among Patients Undergoing Cancer Surgery: A Prospective Cohort Study.

OBJECTIVE: To determine the prevalence of clinically significant decision conflict (CSDC) among patients undergoing cancer surgery and associations with postoperative physical activity, as measured through smartphone accelerometer data. BACKGROUND: Patients with cancer face challenging treatment decisions, which may lead to CSDC. CSDC negatively affects patient-provider relationships, psychosocial functioning, and health-related quality of life; however, physical manifestations of CSDC remain poorly characterized. METHODS: Adult smartphone-owners undergoing surgery for breast, skin-soft-tissue, head-and-neck, or abdominal cancer (July 2017-2019) were approached. Patients downloaded the Beiwe application that delivered the Decision Conflict Scale (DCS) preoperatively and collected smartphone accelerometer data continuously from enrollment through 6 months postop-eratively. Restricted-cubic-spline regression, adjusting for a priori potential confounders (age, type of surgery, support status, and postoperative complications) was used to determine trends in postoperative daily physical activity among patients with and without CSDC (DCS score >25/100). RESULTS: Among 99 patients who downloaded the application, 85 completed the DCS (86% participation rate). Twenty-three (27%) reported CSDC. These patients were younger (mean age 48.3 years [standard deviation 14.2]-vs-55.0 [13.3], P = 0.047) and more frequently lived alone (22%-vs-6%, P = 0.042). There were no differences in preoperative physical activity (115.4 minutes [95%CI 90.9, 139.9]-vs-110.8 [95%CI 95.7, 126.0], P = 0.753). Adjusted postoperative physical activity was lower among patients reporting CSDC at 30 days (difference 33.1 minutes [95%CI 5.93,60.2], P = 0.017), 60 days 35.5 [95%CI 8.50, 62.5], P = 0.010 and 90 days 31.8 [95%CI 5.44, 58.1], P = 0.018 postoperatively. CONCLUSIONS: CSDC was prevalent among patients who underwent cancer surgery and associated with lower postoperatively daily physical activity. These data highlight the importance of addressing modifiable decisional needs of patients through enhanced shared decision-making.