Combined hepatic resection and ablation for high burden of colorectal liver metastases demonstrates safety and durable survival.

BACKGROUND: Hepatic resection (HR) and thermal ablation of Colorectal Liver Metastases (CRLM) have each individually demonstrated safety and survival benefit. We sought to provide our experience with the combination of HR + ablation within one operation for patients with multiple CRLM. METHODS: Review of a single institution database of patients who underwent HR + ablation between 2010 and 2019. RESULTS: 161 patients were identified who underwent HR + ablation for isolated CRLM (mean age: 59, male 63.4%). 125 (77.6%) patients had bilobar disease and 92 (57.1%) patients had ≥5 tumors. 28 (17.4%) patients experienced minor (grade 1 or 2) complications while 20 (12.4%) had grade 3-5 complications. Patients who underwent simultaneous colon resection with HR + ablation had a higher complication rate (22 of 47, 46.8%) than those undergoing HR + ablation only (26 of 114, 22.8%, p = 0.002). Median and 5-year OS for all patients undergoing HR + ablation was 38.2 months and 33.2%, respectively. 5-year hepatic recurrence free survival was 23.5%. Patients with 5 or more tumors demonstrated no difference in median survival compared to those with fewer than 5 tumors (37.0 months vs 38.4 months, p = 0.326). CONCLUSIONS: In this population of CRLM patients with a relatively high burden of disease, HR + ablation demonstrated an acceptable safety profile as well as durable long-term survival.

Prince and princesses: The current status of robotic surgery in surgical oncology.

Robotic surgery has experienced a dramatic increase in utilization across general surgery over the last two decades, including in surgical oncology. Although urologists and gynecologists were the first to show that this technology could be utilized in cancer surgery, the robot is now a powerful tool in the treatment of gastrointestinal, hepato-pancreatico-biliary, colorectal, endocrine, and soft tissue malignancies. While long-term outcomes are still pending, short-term outcomes have showed promise for this technologic advancement of cancer surgery.

Pancreatic Cancer Multidisciplinary Clinic is Associated with Improved Treatment and Elimination of Socioeconomic Disparities.

OBJECTIVE: To identify the association between multidisciplinary clinic (MDC) management and disparities in treatment for patients with pancreatic cancer. BACKGROUND: Socioeconomic status (SES) predicts treatment and survival for pancreatic cancer. Multidisciplinary clinics (MDCs) may improve surgical management for these patients. METHODS: This is a retrospective cohort study (2010-2018) of all pancreatic cancer patients within a large, regional hospital system with a high-volume pancreatic cancer MDC. The primary outcome was receipt of treatment (surgery, chemotherapy, radiation, clinical trial participation, and palliative care); the secondary outcomes were overall survival and MDC management. Multiple logistic regressions were used for binary outcomes. Survival was analyzed using Kaplan-Meier survival analysis, Cox proportional hazards, and inverse probability of treatment weighting (IPTW). RESULTS: Of the 4141 patients studied, 1420 (34.3%) were managed by the MDC. MDC management was more likely for patients who were younger age, married, and privately insured, while less likely for low SES patients (all p < 0.05). MDC patients were more likely to receive all treatments, including neoadjuvant chemotherapy (OR 3.33, 95% CI 2.82-3.93), surgery (OR 1.39, 95% CI 1.15-1.68), palliative care (OR 1.21, 95% CI 1.05-1.38), and clinical trial participation (OR 3.76, 95% CI 2.86-4.93). Low SES patients were less likely to undergo surgery outside of the MDC (OR 0.47, 95% CI 0.31-0.73) but there was no difference within the MDC (OR 1.10, 95% CI 0.68-1.77). Across multiple survival analyses, low SES predicted inferior survival outside of the MDC, but there was no association among MDC patients. CONCLUSION: Multidisciplinary team-based care increases rates of treatment and eliminates socioeconomic disparities for pancreatic cancer patients.

Sex, race, and socioeconomic distinctions in incisional hernia management.

BACKGROUND: We sought to explore the impact of sex, race, and insurance status on operative management of incisional hernias. METHODS: A retrospective cohort study was conducted to explore adult patients diagnosed with an incisional hernia. Adjusted odds for non-operative versus operative management and time to repair were queried. RESULTS: Of the 29,475 patients with an incisional hernia, 20,767 (70.5%) underwent non-operative management. In relation to private insurance, Medicaid (aOR 1.40, 95% CI 1.27-1.54), Medicare (aOR 1.53, 95% CI 1.42-1.65), and uninsured status (aOR 1.99, 95% CI 1.71-2.36) were independently associated with non-operative management. African American race (aOR 1.30, 95% CI 1.17-1.47) was associated with non-operative management while female sex (aOR 0.81, 95% CI 0.77-0.86) was predictive of elective repair. For patients who underwent elective repair, both Medicare (aOR 1.40, 95% CI 1.18-1.66) and Medicaid (aOR 1.49, 95% CI 1.29-1.71) insurance, but not race, were predictive of delayed repair (>90 days after diagnosis). CONCLUSIONS: Sex, race, and insurance status influence incisional hernia management. Development of evidence-based management guidelines may help to ensure equitable care.

Topical Diacerein Decreases Skin and Splenic CD11c+ Dendritic Cells in Psoriasis.

Psoriasis is an inflammatory skin disease characterized by increased neo-vascularization, keratinocyte hyperproliferation, a pro-inflammatory cytokine milieu and immune cell infiltration. Diacerein is an anti-inflammatory drug, modulating immune cell functions, including expression and production of cytokines, in different inflammatory conditions. Therefore, we hypothesized that topical diacerein has beneficial effects on the course of psoriasis. The current study aimed to evaluate the effect of topical diacerein on imiquimod (IMQ)-induced psoriasis in C57BL/6 mice. Topical diacerein was observed to be safe without any adverse side effects in healthy or psoriatic animals. Our results demonstrated that diacerein significantly alleviated the psoriasiform-like skin inflammation over a 7-day period. Furthermore, diacerein significantly diminished the psoriasis-associated splenomegaly, indicating a systemic effect of the drug. Remarkably, we observed significantly reduced infiltration of CD11c+ dendritic cells (DCs) into the skin and spleen of psoriatic mice with diacerein treatment. As CD11c+ DCs play a pivotal role in psoriasis pathology, we consider diacerein to be a promising novel therapeutic candidate for psoriasis.

No survival benefit with suboptimal CA19-9 response: defining effective neoadjuvant chemotherapy in resectable or borderline resectable pancreatic cancer.

BACKGROUND/PURPOSE: Neoadjuvant chemotherapy (NAC) is gaining popularity over a surgery-first (SF) approach in treating resectable and borderline resectable pancreatic ductal adenocarcinoma (PDAC). However, what constitutes effective neoadjuvant chemotherapy is unknown. METHODS: We retrospectively analyzed resectable and borderline resectable PDAC patients who underwent pancreaticoduodenectomy (2010-2019) at a single institution. Optimal CA19-9 response was defined as normalization AND >50% reduction. We utilized Kaplan-Meier and multivariable-adjusted Cox models and competing risk subdistribution methods for statistical analysis. RESULTS: 586 patients were included in this study. The multivariable-adjusted analysis demonstrated OS benefit in the NAC group only when OS was calculated from diagnosis (HR = 0.72, p = 0.02), but not from surgery (HR = 0.81, p = 0.1). However, in 59 patients who achieved optimal CA19-9 response, OS is significantly longer than the 134 patients with suboptimal CA19-9 response (39.3 m vs. 21.5 m, p = 0.005) or the 117 SF patients (39.3 m vs. 19.5 m, p < 0.001). Notably, a suboptimal CA19-9 response conferred no OS advantage compared to SF patients. The accumulative incidence of liver metastases (but not other metastases) was significantly reduced only in patients with optimal CA19-9 response to NAC (multivariable-adjusted subdistribution HR = 0.26, p = 0.03). CONCLUSION: CA19-9 response to NAC may serve as the marker for effective NAC. These findings warrant validation in a multi-institutional study.

Socioeconomic Barriers to CRS HIPEC for Appendiceal Cancer within a Regional Academic Hospital System.

BACKGROUND: Appendiceal cancer with peritoneal metastases (ACPM) is a complex disease requiring multidisciplinary care. Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion (CRS HIPEC) can significantly improve survival but requires evaluation by a surgical oncologist and significant treatment endurance. The impacts of socioeconomic status (SES) and other social determinants of health on rates of surgical evaluation and treatment have not been examined. METHODS: We conducted a retrospective cohort study examining all patients with ACPM from 2010 to 2018 in a regional healthcare system. Patient characteristics, oncologic details, treatment strategies, and survival were examined. The primary outcomes of interest were referral to Surgical Oncology, receipt of CRS HIPEC, and survival. RESULTS: Of 194 patients identified, 94% had synchronous ACPM. The majority of patients (95%) were referred to surgical oncology. Advanced age was the only predictor of nonreferral (p < 0.001). A total of 147 patients (76%) ultimately underwent CRS HIPEC. After adjusting for medical and tumor characteristics, CRS HIPEC was less likely for patients who were unmarried [odds ratio (OR) 0.253, p = 0.004] or of low SES (OR 0.372, p = 0.03). On subanalysis of patients undergoing CRS HIPEC, median overall survival was worse for patients of low SES [51 months versus not reached (NR), p = 0.05], and this disparity persisted on multivariate analysis [hazard ratio (HR) = 2.278, p = 0.001]. CONCLUSIONS: This analysis is the first to evaluate barriers to CRS HIPEC for ACPM. While most patients were evaluated by a multidisciplinary team, nonmedical factors may play a role in the treatment received and ultimate outcomes. Addressing these disparities is crucial for ensuring equitable outcomes and improving patient care.

Failure to Thrive Following Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy: Causes and Consequences.

BACKGROUND: Failure to thrive (FTT) is a complex syndrome of nutritional failure and functional decline. Readmission for FTT following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS HIPEC) is common but underexamined. This study aims to determine features, risk factors, and prognostic significance of FTT following CRS HIPEC. PATIENTS AND METHODS: We reviewed patients who underwent CRS HIPEC from 2010 to 2018 at our institution. Patients were categorized into no readmission, FTT readmission, and other readmission. FTT was determined by coding and chart review. We compared baseline characteristics, oncologic data, perioperative outcomes, and survival among the three cohorts. RESULTS: Of 1068 discharges examined, 379 patients (36%) were readmitted within 90 days, of which 134 (12.5%) were labeled as FTT. Patients with FTT readmission had worse preoperative functional status, higher rates of malnutrition, more complex resections, longer hospital stays, and more postoperative complications (all p < 0.001). Ostomy creation [relative risk ratio (RRR) 4.06], in-hospital venous thromboembolism (VTE), discharge to nursing home (RRR 2.48), pre-CRS HIPEC chemotherapy (RRR 1.98), older age (RRR 1.84), and female gender (RRR 1.69) were all independent predictors for FTT readmission on multinomial regression (all p < 0.01). FTT readmission was associated with worse median overall survival on multivariate analysis [hazard ratio (HR) 1.60, p < 0.001] after controlling for oncologic, perioperative, and baseline factors. CONCLUSIONS: FTT is common following CRS HIPEC and appears to be associated with baseline patient characteristics, operative burden, and postoperative complications. Perioperative strategies for improving nutrition and activity, along with early recognition and intervention in FTT may improve patient outcomes.

The Epidemiology of Extremity Threat and Amputation after Vasopressor-Dependent Sepsis.

Rationale: Extremity threat and amputation after sepsis is a well-publicized and devastating event. However, there is a paucity of data about the epidemiology of extremity threat after sepsis onset. Objectives: To estimate the incidence of extremity threat with or without surgical amputation in community sepsis. Methods: Retrospective cohort study of adults with Sepsis-3 hospitalized at 14 academic and community sites from 2013 to 2017. Vasopressor-dependent sepsis was identified by administration of epinephrine, norepinephrine, phenylephrine, vasopressin, or dopamine for more than 1 hour during the 48 hours before to 24 hours after sepsis onset. Outcomes included the incidence of extremity threat, defined as acute onset ischemia, with or without amputation, in the 90 days after sepsis onset. The association between extremity threat, demographics, comorbid conditions, and time-varying sepsis treatments was evaluated using a Cox proportional hazards model. Results: Among 24,365 adults with sepsis, 12,060 (54%) were vasopressor dependent (mean ± standard deviation age, 64 ± 16 years; male, 6,548 [54%]; sequential organ failure assessment [SOFA], 10 ± 4). Of these, 231 (2%) patients had a threatened extremity with 26 undergoing 37 amputations, a risk of 2.2 (95% confidence interval [CI], 1.4-3.2) per 1,000, and 205 not undergoing amputation, a risk of 17.0 (95% CI, 14.8-19.5) per 1,000. Most amputations occurred in lower extremities (95%), a median (interquartile range) of 16 (6-40) days after sepsis onset. Compared with patients with no extremity threat, patients with threat had a higher SOFA score (11 ± 4 vs. 10 ± 4; P < 0.001), serum lactate (4.6 mmol/L [2.4-8.7] vs. 3.1 [1.7-6.0]; P < 0.001), and more bacteremia (n = 37 [37%] vs. n = 2,087 [26%]; P < 0.001) at sepsis onset. Peripheral vascular disease, congestive heart failure, SOFA score, and norepinephrine equivalents were significantly associated with extremity threat. Conclusions: The evaluation of a threatened extremity resulting in surgical amputation occurred in 2 per 1,000 patients with vasopressor-dependent sepsis.

Definition and Prediction of Early Recurrence and Mortality Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastases: Towards Predicting Oncologic Futility Preoperatively.

INTRODUCTION: Early recurrence (ER) is a significant challenge for patients with colorectal peritoneal metastases (CRPM) following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS HIPEC). Preoperative risk stratification for ER would improve preoperative decision making. METHODS: We conducted a retrospective study examining patients who underwent CRS HIPEC for CRPM from 2000 to 2018. Optimal definition of ER was determined via minimum p-value approach based on differentiation of post-recurrence survival. Risk factors for ER were assessed in a derivation cohort by uni- and multivariate logistic regression. A predictive score for ER was generated using preoperative variables and validated in an independent cohort. RESULTS: 384 patients were analyzed, 316 (82%) had documented recurrence. Optimal length of post-operative RFS to distinguish ER (n = 144, 46%) vs. late recurrence (LR) (n = 172, 63%) was 8 mos (p<0.01). ER patients had shorter median OS post-CRS-HIPEC (13.6 vs. 39.4 mos, p<0.01). Preoperative BMI (OR 1.88), liver lesions (OR 1.89), progression on chemotherapy (OR 2.14), positive lymph nodes (OR 2.47) and PCI score (16-20: OR 1.7; >20: OR 4.37) were significant predictors of ER (all p<0.05). Using this model, patients were assigned risk scores from 0 to 9. Intermediate (scores 4-6) and high-risk patients (score 7-9) had observed rates of ER of 56% and 79% and overall 2-year survival rates of 27% and 0% respectively. The model showed fair discrimination (AUC 0.72) and good calibration (Hosmer-Lemeshow GOF p = 0.68). CONCLUSIONS: ER predicts markedly worse OS following surgery. Preoperative factors can accurately stratify risk for ER and identify patients in whom CRS-HIPEC for CPRM is futile.

Optimal management of patients with operable pancreatic head cancer: A Markov decision analysis.

INTRODUCTION: Neoadjuvant therapy (NAT) is an emerging strategy for operable pancreatic ductal adenocarcinoma (PDAC). While NAT increases multimodal therapy completion, it risks functional decline and treatment dropout. We used decision analysis to determine optimal management of localized PDAC and consider risks faced by elderly patients. METHODS: A Markov cohort decision analysis model evaluated treatment options for a 60-year-old patient with resectable PDAC: (1) upfront pancreaticoduodenectomy or (2) NAT. One-way and probabilistic sensitivity analyses were performed. A subanalysis considered the scenario of a 75-year-old patient. RESULTS: For the base case, NAT offered an incremental survival gain of 4.6 months compared with SF (overall survival: 26.3 vs. 21.7 months). In one-way sensitivity analyses, findings were sensitive to recurrence-free survival for NAT patients undergoing adjuvant, probability of completing NAT, and probability of being resectable at exploration after NAT. On probabilistic analysis, NAT was favored in a majority of trials (97%) with a median survival benefit of 5.1 months. In altering the base case for the 75-year-old scenario, NAT had a survival benefit of 3.8 months. CONCLUSIONS: This analysis demonstrates a significant benefit to NAT in patients with localized PDAC. This benefit persists even in the elderly cohort.

Medicaid expansion and the management of pancreatic cancer.

BACKGROUND: Medicaid expansion under the Affordable Care Act has improved access to screening and treatment for certain cancers. It is unclear how this policy has affected the diagnosis and management of pancreatic cancer. METHODS: Using a quasi-experimental difference-in-differences (DID) approach, we analyzed Medicaid and uninsured patients in the National Cancer Data Base during two time periods: pre-expansion (2011-2012) and postexpansion (2015-2016). We investigated changes in cancer staging, treatment decisions, and surgical outcomes. RESULTS: In this national cohort, pancreatic cancer patients in expansion states had increased Medicaid coverage relative to those in nonexpansion states (DID = 17.49, p < 0.01). Medicaid expansion also led to an increase in early-stage diagnoses (Stage I/II, DID = 4.71, p = 0.03), higher comorbidity scores among surgical patients (Charlson/Deyo score 0: DID = -13.69, p = 0.02), a trend toward more neoadjuvant radiation (DID = 6.15, p = 0.06), and more positive margins (DID = 11.69, p = 0.02). There were no differences in rates of surgery, postoperative outcomes, or overall survival. CONCLUSION: Medicaid expansion was associated with improved insurance coverage and earlier stage diagnoses for Medicaid and uninsured pancreatic cancer patients, but similar surgical outcomes and overall survival. These findings highlight both the benefits of Medicaid expansion and the potential limitations of policy change to improve outcomes for such an aggressive malignancy.

Patient Factors Limit Colon Cancer Survival at Safety-Net Hospitals: A National Analysis.

BACKGROUND: Safety-net hospitals serve a vital role in society by providing care for vulnerable populations. Existing data regarding oncologic outcomes of patients with colon cancer treated at safety-net hospitals are limited and variable. The objective of this study was to delineate disparities in treatment and outcomes for patients with colon cancer treated at safety-net hospitals. METHODS: This retrospective cohort study identified 802,304 adult patients with colon adenocarcinoma from the National Cancer Database between 2004-2016. Patients were stratified according to safety-net burden of the treating hospital as previously described. Patient, tumor, facility, and treatment characteristics were compared between groups as were operative and short-term outcomes. Cox proportional hazards regression was utilized to compare overall survival between patients treated at high, medium, and low burden hospitals. RESULTS: Patients treated at safety-net hospitals were demographically distinct and presented with more advanced disease. They were also less likely to receive surgery, adjuvant chemotherapy, negative resection margins, adequate lymphadenectomy, or a minimally invasive operative approach. On multivariate analysis adjusting for patient and tumor characteristics, survival was inferior for patients at safety-net hospitals, even for those with stage 0 (in situ) disease. CONCLUSION: This analysis revealed inferior survival for patients with colon cancer treated at safety-net hospitals, including those without invasive cancer. These findings suggest that unmeasured population differences may confound analyses and affect survival more than provider or treatment disparities.

Machine learning for the prediction of pathologic pneumatosis intestinalis.

BACKGROUND: The radiographic finding of pneumatosis intestinalis can indicate a spectrum of underlying processes ranging from a benign finding to a life-threatening condition. Although radiographic pneumatosis intestinalis is relatively common, there is no validated clinical tool to guide surgical management. METHODS: Using a retrospective cohort of 300 pneumatosis intestinalis cases from a single institution, we developed 3 machine learning models for 2 clinical tasks: (1) the distinction of benign from pathologic pneumatosis intestinalis cases and (2) the determination of patients who would benefit from an operation. The 3 models are (1) an imaging model based on radiomic features extracted from computed tomography scans, (2) a clinical model based on clinical variables, and (3) a combination model using both the imaging and clinical variables. RESULTS: The combination model achieves an area under the curve of 0.91 (confidence interval: 0.87-0.94) for task I and an area under the curve of 0.84 (confidence interval: 0.79-0.88) for task II. The combination model significantly (P < .05) outperforms the imaging model and the clinical model for both tasks. The imaging model achieves an area under the curve of 0.72 (confidence interval: 0.57-0.87) for task I and 0.68 (confidence interval: 0.61-0.74) for task II. The clinical model achieves an area under the curve of 0.87 (confidence interval: 0.83-0.91) for task I and 0.76 (confidence interval: 0.70-0.81) for task II. CONCLUSION: This study suggests that combined radiographic and clinical features can identify pathologic pneumatosis intestinalis and aid in patient selection for surgery. This tool may better inform the surgical decision-making process for patients with pneumatosis intestinalis.

Predictors of early recurrence following neoadjuvant chemotherapy and surgical resection for localized pancreatic adenocarcinoma.

BACKGROUND AND OBJECTIVES: Neoadjuvant chemotherapy (NAT) for pancreatic adenocarcinoma (PDAC) is increasingly being utilized. However, a significant number of patients will experience early recurrence, possibly negating the benefit of surgery. We aimed to identify factors implicated in early disease recurrence. METHODS: A retrospective review of pancreaticoduodenectomies performed between 2005 and 2017 at our institution for PDAC following NAT was performed. A 6-month cut-off was used to stratify patients into early/late recurrence groups. Multivariate analysis was performed to identify predictors of recurrence. RESULTS: Of 273 patients, 64 (23%) developed early recurrence or died within 90 days of surgery. The median time to recurrence was 4 months (95% confidence interval [CI]: 2.2-4.3) in the early group versus 16 months (95% CI: 13.7-19.9) in the late group. The former had higher baseline and post-NAT Ca19-9 levels than the latter (472 vs. 153 IU/ml, p = 0.001 and 71 vs. 39 IU/ml, p = 0.005, respectively). A higher positive lymph node ratio significantly increased the risk of early recurrence (hazard ratio [HR]: 15.9, p < 0.001) while adjuvant chemotherapy was protective (HR: 0.4, p < 0.001). CONCLUSION: Our findings acknowledge the limitations of clinically measured factors used to ascertain response to NAT and underline the need for individualized molecular markers that take into consideration the specific tumor biology.

Optimal Management of Resectable Pancreatic Head Cancer in the Elderly Patient: Does Neoadjuvant Therapy Offer a Survival Benefit?

INTRODUCTION: Neoadjuvant therapy (NAT) is a growing strategy for patients with resectable pancreatic ductal adenocarcinoma (PDAC). Elderly patients are at increased risk of treatment withdrawal due to functional decline, and the benefit of NAT in this cohort remains to be studied. OBJECTIVE: The objective of this study was to compare outcomes of elderly patients with resectable head PDAC who underwent NAT or a surgery-first (SF) approach. METHODS: All patients 75 years of age and older with radiographically resectable (National Comprehensive Cancer Network criteria) PDAC who underwent pancreaticoduodenectomy at a single institution from 2008 to 2017 were analyzed. Baseline characteristics and perioperative outcomes were compared between the SF and NAT cohorts. Recurrence-free survival and overall survival (OS) were analyzed by treatment strategy. RESULTS: Overall, 158 patients were identified: SF cohort = 90 (57%) and NAT cohort = 68 (43%). Patients in the SF cohort were older (80 vs. 78 years; p = 0.01) but there were no differences in preoperative comorbidities or frailty indices. SF patients had a trend toward higher rates of major complications (38% vs. 24%; p = 0.06) with higher Comprehensive Complication Index totals (20.9 vs. 20; p = 0.03). There were similar rates of adjuvant therapy. NAT was associated with significantly longer OS (24.6 vs. 17.6 months; p = 0.01) in both the intent-to-treat and resected cohorts. On multivariable analysis (MVA), NAT remained an independent predictor of OS (hazard ratio 0.60; p = 0.02). CONCLUSION: NAT is safe and effective for elderly patients with PDAC. This study suggests NAT is associated with fewer complications after surgery, equal rates of adjuvant therapy receipt, and increased OS over a surgery-first approach.