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.

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.

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.

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.

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.

Predischarge Prediction of Readmission After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Derivation and Validation of a Risk Prediction Score.

BACKGROUND: Ninety-day hospital readmission rates following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) range from 20 to 40%. OBJECTIVE: The aim of this study was to develop and validate a simple score to predict readmissions following CRS/HIPEC. STUDY DESIGN: Using a prospectively maintained database, we retrospectively reviewed clinicopathologic, perioperative, and day-of-discharge data for patients undergoing CRS/HIPEC for peritoneal surface malignancies between 2010 and 2018. In-hospital mortalities and discharges to hospice were excluded. Multivariate logistic regression was utilized to identify predictors of unplanned readmission, with three-quarters of the sample randomly selected as the derivation cohort and one-quarter as the validation cohort. Using regression coefficient-based scoring methods, we developed a weighted 7-factor, 10-point predictive score for risk of readmission. RESULTS: Overall, 1068 eligible discharges were analyzed; 379 patients were readmitted within 90 days (35.5%). Seven factors were associated with readmission: stoma creation, Peritoneal Cancer Index score ≥ 15, hyponatremia, in-hospital major complication, preoperative chemotherapy, anemia, and discharge to nursing home. In the validation cohort, 25 patients (9.2%) were categorized as high risk for readmission, with a predicted rate of readmission of 69.3% and an observed rate of 76.0%. The score had fair discrimination (area under the curve 0.70) and good calibration (Hosmer-Lemeshow goodness-of-fit p-value of 0.77). CONCLUSION: Our proposed risk score, easily obtainable on day of discharge, distinguishes patients at high risk for readmission over 90 days following CRS/HIPEC. This score has the potential to target high-risk individuals for intensive follow-up and other interventions.

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.

Impact of Socioeconomic Status on Presentation and Outcomes in Colorectal Peritoneal Metastases Following Cytoreduction and Chemoperfusion: Persistent Inequalities in Outcomes at a High-Volume Center.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion (CRS HIPEC) can offer significant survival advantage for select patients with colorectal peritoneal metastases (CRPM). Low socioeconomic status (SES) is implicated in disparities in access to care. We analyze the impact of SES on postoperative outcomes and survival at a high-volume tertiary CRS HIPEC center. PATIENTS AND METHODS: We conducted a retrospective cohort study examining patients who underwent CRS HIPEC for CRPM from 2000 to 2018. Patients were grouped according to SES. Baseline characteristics, perioperative outcomes, and survival were examined between groups. RESULTS: A total of 226 patients were analyzed, 107 (47%) low-SES and 119 (53%) high-SES patients. High-SES patients were younger (52 vs. 58 years, p = 0.01) and more likely to be White (95.0% vs. 91.6%, p = 0.06) and privately insured (83% vs. 57%, p < 0.001). They traveled significantly further for treatment and had lower burden of comorbidities and frailty (p = 0.01). Low-SES patients more often presented with synchronous peritoneal metastases (48% vs. 35%, p = 0.05). Following CRS HIPEC, low-SES patients had longer length of stay and higher burden of postoperative complications, 90-day readmission, and 30-day mortality. Median overall survival following CRS HIPEC was worse for low-SES patients (17.8 vs. 32.4 months, p = 0.02). This disparity persisted on multivariate survival analysis (low SES: HR = 1.46, p = 0.03). CONCLUSIONS: Despite improving therapies for CRPM, low-SES patients remain at a significant disadvantage. Even patients who overcome barriers to care experience worse short- and long-term outcomes. Improving access and addressing these disparities is crucial to ensure equitable outcomes and improve patient care.

A Pancreatic Cancer Multidisciplinary Clinic Eliminates Socioeconomic Disparities in Treatment and Improves Survival.

AIMS: National studies have demonstrated disparities in the treatment and survival of pancreatic cancer patients based on socioeconomic status (SES). This study aimed to identify specific differences in perioperative management and outcomes based on patient SES and to study the role of a multidisciplinary clinic (MDC) in mitigating any variations. METHODS: The study analyzed patients undergoing pancreaticoduodenectomy for pancreatic ductal adenocarcinoma in a large hospital system. The patients were categorized into groups of high and low SES and whether they were managed by the authors' pancreatic cancer MDC or not. The study compared differences in disease characteristics, receipt of multimodality therapy, perioperative outcomes, and recurrence-free and overall survival. RESULTS: Of the 162 low-SES patients and 119 high-SES patients, 54% were managed in the MDC. Outside the MDC, low-SES patients were less likely to receive neoadjuvant chemotherapy and had less minimally invasive surgery, a longer OR time, less enhanced recovery participation, and more major complications (p < 0.05). No SES disparities were observed among the MDC patients. Despite similar tumor characteristics, the low-SES patients had inferior median overall survival (21 vs 32 months; p = 0.005), but the MDC appeared to eliminate this disparity. Low SES correlated with inferior survival for the non-MDC patients (17 vs 32 months; p < 0.001), but not for the MDC patients (24 vs 25 months; p = 0.33). These findings persisted in the multivariable analysis. CONCLUSION: A pancreatic cancer MDC standardizes treatment decisions, eliminates disparities in surgical outcomes, and improves survival for low-SES patients.

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.

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.

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.

Impact of postoperative pancreatic fistula on long-term oncologic outcomes after pancreatic resection.

BACKGROUND: The short-term morbidity associated with post-operative pancreatic fistula (POPF) is well established, however data regarding the long-term impact are lacking. We aim to characterize long-term oncologic outcomes of POPF after pancreatic resection through a single institution, retrospective study of pancreatic resections performed for adenocarcinoma from 2009 to 2016. METHODS: Kaplan-Meier survival analysis, logistic regression, and multivariate analysis (MVA) were used to evaluate impact of POPF on overall survival (OS), disease free survival (DFS), and receipt of adjuvant chemotherapy (AC). RESULTS: 767 patients were included. 82 (10.6%) developed grade B (n = 67) or C (n = 15) POPF. Grade C POPF resulted in decreased OS when compared to no POPF (20.22 vs 26.33 months, p = 0.027) and to grade B POPF (20.22 vs. 26.87 months, p = 0.049). POPF patients were less likely to receive AC than those without POPF (59.5% vs 74.9%, p = 0.003) and grade C POPF were less likely to receive AC than all others (26.7% vs 74.2%, p = 0.0001). CONCLUSION: POPF patients are less likely to receive AC and more likely to have delay in time to AC. These factors are exacerbated in grade C POPF and likely contribute to decreased OS. These findings validate the clinical significance of the ISGPF definition of POPF.

CA19-9 Change During Neoadjuvant Therapy May Guide the Need for Additional Adjuvant Therapy Following Resected Pancreatic Cancer.

BACKGROUND: Neoadjuvant therapy (NAT) is increasingly utilized for pancreatic cancer, however the added benefit of adjuvant therapy (AT) in this setting is unknown. We hypothesized that the magnitude of CA19-9 response to NAT can guide the need for further AT in resected pancreatic cancer. METHODS: CA19-9 secretors who received NAT for pancreatic cancer during 2008-2016 at a single institution were analyzed and CA19-9 response (difference between pre- and post-NAT values) was measured. Kaplan-Meier estimators and Cox proportional hazard ratio models were used to determine the optimal CA19-9 response at which AT ceases to confer any additional survival benefit after NAT. RESULTS: A total of 241 patients (mean age 65.4 years, 50% female) with complete CA19-9 data who underwent NAT followed by resection were analyzed. In a cohort of patients (n = 78) in whom CA19-9 normalized with a decrease > 50% after NAT (optimal responders), AT was not associated with additional survival benefit (40.6 vs. 39.0 months, p = 0.815). Conversely, in the cohort of patients (n = 163) in whom NAT was not associated with normalization and a decrease of ≤ 50% in CA19-9 (suboptimal responders), receipt of AT was associated with a survival benefit (34.5 vs. 19.1 months, p < 0.001) following NAT. A Cox proportional hazards model confirmed CA19-9 normalization and decrease > 50% during NAT to predict no additional survival benefit from AT. CONCLUSIONS: The magnitude of CA19-9 response to NAT may predict the need for further AT in resected pancreatic cancer. Prospective studies are needed to elucidate the optimal interplay of NAT and AT in pancreatic cancer.

Correction to: Serum CA19-9 Response to Neoadjuvant Therapy Predicts Tumor Size Reduction and Survival in Pancreatic Adenocarcinoma.

In the original article, Caroline J. Rieser's last name is spelled wrong. It is correct as reflected here.

Prognostic Value of the Systemic Immune-Inflammation Index (SII) After Neoadjuvant Therapy for Patients with Resected Pancreatic Cancer.

BACKGROUND: The systemic immune-inflammation index (SII), calculated using absolute platelet, neutrophil, and lymphocyte counts, has recently emerged as a predictor of survival for patients with pancreatic ductal adenocarcinoma (PDAC) when assessed at diagnosis. Neoadjuvant therapy (NAT) is increasingly used in the treatment of PDAC. However, biomarkers of response are lacking. This study aimed to determine the prognostic significance of SII before and after NAT and its association with the pancreatic tumor biomarker carbohydrate-antigen 19-9 (CA 19-9). METHODS: This study retrospectively analyzed all PDAC patients treated with NAT before pancreatic resection at a single institution between 2007 and 2017. Pre- and post-NAT lab values were collected to calculate SII. Absolute pre-NAT, post-NAT, and change in SII after NAT were evaluated for their association with clinical outcomes. RESULTS: The study analyzed 419 patients and found no significant correlation between pre-NAT SII and clinical outcomes. Elevated post-NAT SII was an independent, negative predictor of overall survival (OS) when assessed as a continuous variable (hazard ratio [HR], 1.0001; 95% confidence interval [CI] 1.00003-1.00014; p = 0.006). Patients with a post-NAT SII greater than 900 had a shorter median OS (31.9 vs 26.1 months; p = 0.050), and a post-NAT SII greater than 900 also was an independent negative predictor of OS (HR, 1.369; 95% CI 1.019-1.838; p = 0.037). An 80% reduction in SII independently predicted a CA 19-9 response after NAT (HR, 4.22; 95% CI 1.209-14.750; p = 0.024). CONCLUSION: Post-treatment SII may be a useful prognostic marker in PDAC patients receiving NAT.