Neoadjuvant Chemotherapy Versus Upfront Surgery for Resectable Pancreatic Adenocarcinoma: An Updated Nationwide Study.

OBJECTIVE: The objective of this study was to assess the association of survival with neoadjuvant chemotherapy (NAC) in resectable pancreatic adenocarcinoma (PDAC). BACKGROUND: The early control of potential micrometastases and patient selection using NAC has been advocated for patients with PDAC. However, the role of NAC for resectable PDAC remains unclear. METHODS: Patients with clinical T1 and T2 PDAC were identified in the National Cancer Database from 2010 to 2017. Kaplan-Meier estimates, and Cox regression models were used to compare survival. To address immortal time bias, landmark analysis was performed. Interactions between preoperative factors and NAC were investigated in subgroup analyses. A propensity score analysis was performed to compare survival between multiagent NAC and upfront surgery. RESULTS: In total, 4041 patients were treated with upfront surgery and 1,175 patients were treated with NAC (79.4% multiagent NAC, 20.6% single-agent NAC). Using a landmark time of 6 months after diagnosis, patients treated with multiagent NAC had longer median overall survival compared with upfront surgery and single-agent NAC. (35.8 vs 27.1 vs 27.4 mo). Multiagent NAC was associated with lower mortality rates compared with upfront surgery (adjusted hazard ratio, 0.77; 95% CI, 0.70-0.85), whereas single-agent NAC was not. The association of survival with multiagent NAC were consistent in analyses using the matched data sets. Interaction analysis revealed that the association between multiagent NAC and a lower mortality rate did not significantly differ across age, facility type, tumor location, CA 19-9 levels, and clinical T/N stages. CONCLUSIONS: The findings suggest that multiagent NAC followed by resection is associated with improved survival compared with upfront surgery.

Evaluation of Survival Following Surgical Resection for Small Nonfunctional Pancreatic Neuroendocrine Tumors.

Importance: The number of patients with small nonfunctional pancreatic neuroendocrine tumors (NF-PanNETs) is increasing. However, the role of surgery for small NF-PanNETs remains unclear. Objective: To evaluate the association between surgical resection for NF-PanNETs measuring 2 cm or smaller and survival. Design, Setting, and Participants: This cohort study used data from the National Cancer Database and included patients with NF-pancreatic neuroendocrine neoplasms who were diagnosed between January 1, 2004, and December 31, 2017. Patients with small NF-PanNETs were divided into 2 groups: group 1a (tumor size, ≤1 cm) and group 1b (tumor size, 1.1-2.0 cm). Patients without information on tumor size, overall survival, and surgical resection were excluded. Data analysis was performed in June 2022. Exposures: Patients with vs without surgical resection. Main Outcomes and Measures: The primary outcome was overall survival of patients in group 1a or group 1b who underwent surgical resection compared with those who did not, which was evaluated using Kaplan-Meier estimates and multivariable Cox proportional hazards regression models. Interactions between preoperative factors and surgical resection were analyzed with a multivariable Cox proportional hazards regression model. Results: Of the 10 504 patients with localized NF-PanNETs identified, 4641 were analyzed. These patients had a mean (SD) age of 60.5 (12.7) years and included 2338 males (50.4%). The median (IQR) follow-up time was 47.1 (28.2-71.6) months. In total, 1278 patients were in group 1a and 3363 patients were in group 1b. The surgical resection rates were 82.0% in group 1a and 87.0% in group 1b. After adjustment for preoperative factors, surgical resection was associated with longer survival for patients in group 1b (hazard ratio [HR], 0.58; 95% CI, 0.42-0.80; P < .001) but not for patients in group 1a (HR, 0.68; 95% CI, 0.41-1.11; P = .12). In group 1b, interaction analysis found that age of 64 years or younger, absence of comorbidities, treatment at academic institutions, and distal pancreatic tumors were factors associated with increased survival after surgical resection. Conclusions and Relevance: Findings of this study support an association between surgical resection and increased survival in select patients with NF-PanNETs measuring 1.1 to 2.0 cm who were younger than 65 years, had no comorbidities, received treatment at academic institutions, and had tumors of the distal pancreas. Future investigations of surgical resection for small NF-PanNETs that include the Ki-67 index are warranted to validate these findings.

Prevalence and progression of intraductal papillary mucinous neoplasms of the pancreas in solid organ transplant recipients: A systematic review.

Solid organ transplantation (SOT) recipients are known to carry an increased risk of malignancy because of long-term immunosuppression. However, the progression of intraductal papillary mucinous neoplasm of the pancreas (IPMN) in this population remains unclear. We performed a systematic review by searching PubMed, Embase, Scopus, and Google Scholar. All studies containing IPMNs in solid organ transplantation recipients were screened. We included 11 studies in our final analysis, totaling 274 patients with IPMNs of the 8213 SOT recipients. The prevalence from 8 studies was 4.7% (95% CI 2.4%-7.7%) in a random-effects model with median study periods of 24 to 220 months. The median rate for all progressions from 10 studies was 20% (range, 0%-88%) within 13 to 41 months of the median follow-up time. By utilizing the results of 3 case-control studies, the relative risk from a random-effects model for progression (worrisome features and high-risk stigmata) of IPMNs was 0.39 (95% CI 0.12-1.31). No adenocarcinoma derived from IPMN was reported in the included studies. Overall, this study indicates that the progression of pretransplant IPMN does not increase drastically compared with the general nontransplant population. However, considering the limited literature, further studies are required for confirmation.

Association of Adjuvant Chemotherapy in Patients With Resected Pancreatic Adenocarcinoma After Multiagent Neoadjuvant Chemotherapy.

Importance: The total number of patients with pancreatic ductal adenocarcinoma (PDAC) who receive neoadjuvant chemotherapy (NAC) is increasing. However, the added role of adjuvant chemotherapy (AC) in these patients remains unknown. Objective: To evaluate the association of AC with overall survival (OS) in patients with PDAC who received multiagent NAC followed by curative-intent surgery. Design, Setting, and Participants: This retrospective, matched-cohort study used data from the National Cancer Database and included patients with PDAC diagnosed between 2010 and 2018. The study included patients at least 18 years of age who received multiagent NAC followed by surgical resection and had available records of the pathological findings. Patients were excluded if they had clinical or pathological stage IV disease or died within 90 days of their operation. Exposures: All included patients received NAC and underwent resection for primary PDAC. Some patients received adjuvant chemotherapy. Main Outcomes and Measures: The main outcome was the OS of patients who received AC (AC group) vs those who did not (non-AC group). Interactions between pathological findings and AC were investigated in separate multivariable Cox regression models. Results: In total, 1132 patients (mean [SD] age, 63.5 [9.4] years; 577 [50.1%] male; 970 [85.7%] White) were included, 640 patients in the non-AC group and 492 patients in the AC group. After being matched by propensity score according to demographic and pathological characteristics, 444 patients remained in each group. The multivariable Cox regression model adjusted for all covariates revealed an association between AC and improved survival (hazard ratio, 0.71; 95% CI, 0.59-0.85; P < .001). Subgroup interaction analysis revealed that AC was significantly associated with better OS (26.6 vs 21.2 months; P = .002), but the benefit varied by age, pathological T category, and tumor differentiation. Of note, AC was associated with better survival in patients with any pathological N category and positive margin status. Conclusions and Relevance: In this cohort study, AC following multiagent NAC and resection in patients with PDAC was associated with significant survival benefit compared with that in patients who did not receive AC. These findings suggest that patients with aggressive tumors may benefit from AC to achieve prolonged survival, even after multiagent NAC and curative-intent resection.

Solid Pseudopapillary Neoplasm: A Single Institutional Case Series of a Rare Pancreatic Tumor.

Purpose: Solid pseudopapillary neoplasms (SPN) are rare pancreatic cystic neoplasms with low malignant potential that tend to occur in young women. Due to the rarity of this disease, there are few large case series in the literature, and the exact pathophysiology remains unknown. In this article, we aim to share our institutional experience. Methods: Retrospective clinical data collection and analysis was performed on all patients with a diagnosis of SPN at the University of Colorado Hospital and Children's Hospital of Colorado (n = 28). Results: Twenty-eight patients were diagnosed with SPN during the study period. The median age was 21.5 years, and the majority of patients were female (89.3%) and Caucasian (60.7%). Six patients were diagnosed incidentally (21.4%). The majority of tumors were in the pancreatic tail (46.4%), and most underwent distal pancreatectomy (64.3%). The mean tumor size was 5.4 cm, and R0 resection was achieved in 25 patients (89.3%). Ten patients underwent laparoscopic resection (35.7%). The median hospital length of stay was 8.5 days, and postoperative complication rate was 39.3%. Median follow-up was 41 months, with 78.6% of patients alive without evidence of disease, while 2 patients were lost to follow-up. Two patients developed recurrence/metastases, which were resected; both are alive without evidence of disease. Conclusion: SPN are rare pancreatic tumors diagnosed most frequently in young women. Surgical resection is the mainstay of treatment, and outcomes are excellent if complete resection is achieved. Predictors of malignant disease are inconsistent in current literature. Considerations should be made for a minimally invasive approach in patients with SPN. Multidisciplinary clinics may be helpful in the diagnosis, management, and surveillance of pancreatic cystic lesions, with major potential for the advanced practitioner role.

High Rates of Recurrent Revascularization in Acute Limb Ischemia - A National Surgical Quality Improvement Program Study.

BACKGROUND: We queried the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database to review outcomes of acute limb ischemia (ALI) patients following open surgical intervention for ALI. METHODS: A previously validated tool was used to identify ALI patients in NSQIP undergoing open surgical revascularization from 2012 to 2017. Multivariable analysis was performed for the primary outcome of reoperation and secondary outcome of readmission and infection. RESULTS: A total of 2,878 ALI patients underwent open revascularization; 35.7% were transfers from another acute care hospital. A total of 13.8% required reoperation and 7.9% required readmission within 30 days. A total of 32% of reoperations were recurrent revascularization, representing 4.4% of all ALI patients. A total of 58.7% of patients were female and either overweight or obese. Younger age (odds ratio OR 0.991 [0.984-0.999], P = 0.02), underweight patients (OR 1.159 [0.667-2.01], P = 0.05), pre-operative steroid use (OR 1.61 [1.07-2.41], P = 0.02), and perioperative transfusion (OR 2.02 [1.04-3.95], P = 0.04) predicted reoperations. CONCLUSIONS: This registry series demonstrates all-cause ALI patients are a different population than PAD with different risk factors. Despite being a time-critical condition, ALI has higher interhospital transfer rates than ACS or ruptured aneurysm. Following open revascularization, ALI outcomes are worse than ACS but better than ruptured AAA. These outcomes do not appear related to patient factors in contrast to revascularization for chronic PAD.

Comparing neoadjuvant chemotherapy with or without radiation therapy for pancreatic ductal adenocarcinoma: National Cancer Database cohort analysis.

BACKGROUND: Neoadjuvant treatment is important for improving the rate of R0 surgical resection and overall survival outcome in treating patients with pancreatic ductal adenocarcinoma (PDAC). However, the true efficacy of radiotherapy (RT) for neoadjuvant treatment of PDAC is uncertain. This retrospective study evaluated the treatment outcome of neoadjuvant RT in the treatment of PDAC. METHODS: Collected from the National Cancer Database, information on patients with PDAC who underwent neoadjuvant chemotherapy (NAC) and pancreatectomy between 2010 to 2016 was used in this study. Short- and long-term outcomes were compared between patients who received neoadjuvant chemoradiotherapy (NACRT) and NAC. RESULTS: The study included 6936 patients, of whom 3185 received NACRT and 3751 NAC. The groups showed no difference in overall survival (NACRT 16.1 months versus NAC 17.4 months; P = 0.054). NACRT is associated with more frequent margin negative resection (86.1 versus 80.0 per cent; P < 0.001) but a more unfavourable 90-day mortality than NAC (6.4 versus 3.6 per cent; P < 0.001). The odds of 90-day mortality were higher in the radiotherapy group (odds ratio 1.81; P < 0.001), even after adjusting for significant covariates. Patients who received NACRT received single-agent chemotherapy more often than those who received NAC (31.5 versus 10.7 per cent; P < 0.001). CONCLUSION: This study failed to show a survival benefit for NACRT over NAC alone, despite its association with negative margin resection. The significantly higher mortality in NACRT warrants further investigation into its efficacy in the treatment of pancreatic cancer.

Prognosis Based Definition of Resectability in Pancreatic Cancer: A Road Map to New Guidelines.

OBJECTIVE: To identify objective preoperative prognostic factors that are able to predict long-term survival of patients affected by PDAC. SUMMARY OF BACKGROUND DATA: In the modern era of improved systemic chemotherapy for PDAC, tumor biology, and response to chemotherapy are essential in defining prognosis and an improved approach is needed for classifying resectability beyond purely anatomic features. METHODS: We queried the National Cancer Database regarding patients diagnosed with PDAC from 2010 to 2016. Cox proportional hazard models were used to select preoperative baseline factors significantly associated with survival; final models for overall survival (OS) were internally validated and formed the basis of the nomogram. RESULTS: A total of 7849 patients with PDAC were included with a median follow-up of 19 months. On multivariable analysis, factors significantly associated with OS included carbohydrate antigen 19-9, neoadjuvant treatment, tumor size, age, facility type, Charlson/Deyo score, primary site, and sex; T4 stage was not independently associated with OS. The cumulative score was used to classify patients into 3 groups: good, intermediate, and poor prognosis, respectively. The strength of our model was validated by a highly significant randomization test, Log-rank test, and simple hazard ratio; the concordance index was 0.59. CONCLUSION: This new PDAC nomogram, based solely on preoperative variables, could be a useful tool to patients and counseling physicians in selecting therapy. This model suggests a new concept of resectability that is meant to reflect the biology of the tumor, thus partially overcoming existing definitions, that are mainly based on tumor anatomic features.

Global Survey on Pancreatic Surgery During the COVID-19 Pandemic.

OBJECTIVE: The aim of this study was to clarify the role of pancreatic surgery during the COVID-19 pandemic to optimize patients' and clinicians' safety and safeguard health care capacity. SUMMARY BACKGROUND DATA: The COVID-19 pandemic heavily impacts health care systems worldwide. Cancer patients appear to have an increased risk for adverse events when infected by COVID-19, but the inability to receive oncological care seems may be an even larger threat, particularly in case of pancreatic cancer. METHODS: An online survey was submitted to all members of seven international pancreatic associations and study groups, investigating the impact of the COVID-19 pandemic on pancreatic surgery using 21 statements (April, 2020). Consensus was defined as >80% agreement among respondents and moderate agreement as 60% to 80% agreement. RESULTS: A total of 337 respondents from 267 centers and 37 countries spanning 5 continents completed the survey. Most respondents were surgeons (n = 302, 89.6%) and working in an academic center (n = 286, 84.9%). The majority of centers (n = 166, 62.2%) performed less pancreatic surgery because of the COVID-19 pandemic, reducing the weekly pancreatic resection rate from 3 [interquartile range (IQR) 2-5] to 1 (IQR 0-2) (P < 0.001). Most centers screened for COVID-19 before pancreatic surgery (n = 233, 87.3%). Consensus was reached on 13 statements and 5 statements achieved moderate agreement. CONCLUSIONS: This global survey elucidates the role of pancreatic surgery during the COVID-19 pandemic, regarding patient selection for the surgical and oncological treatment of pancreatic diseases to support clinical decision-making and creating a starting point for further discussion.

Multifocal/diffuse pancreatic serous cystic neoplasms: Systematic review with a new case.

BACKGROUND/OBJECTIVES: Pancreatic cystic neoplasms (PCNs) are common, among which 13%-23% are serous cystic neoplasms (SCNs). However, diffuse and multifocal variants of SCNs are extremely rare. The differential diagnosis of SCNs from other PCNs is important as the former entities are benign and do not become invasive. OBJECTIVE: This study analyzes the clinical characteristics of multifocal/diffuse SCN through a systematic review of the literature and a case report. METHODS: A comprehensive literature search was executed in the Ovid MEDLINE, Embase, and Google Scholar databases. The search strategy was designed to capture the concept of multifocal/diffuse SCN cases with sufficient clinical information for detailed analysis. Using the final included articles, we analyzed tumor characteristics, diagnostic modalities used, initial management and indications, and patient outcomes. RESULTS: A review of 262 articles yielded 19 publications with 22 cases that had detailed clinical information. We presented an additional case from our institution database. The systematic review of 23 cases revealed that the diffuse variant is more common than the multifocal variant (15 vs 8 cases, respectively). Patients were managed with surgical intervention, conservative treatment, or conservative treatment followed by surgical intervention. Indications for surgery following conservative management mainly included new onset or worsening of symptoms. Only one case reported significant tumor growth after attempting an observational approach. No articles reported recurrence of SCN after pancreatectomy, and no articles reported mortality related to multifocal/diffuse SCNs. CONCLUSION: Despite their expansive-growing and space-occupying characteristics, multifocal/diffuse SCNs should be treated similarly to their more common unifocal counterpart.

Neoadjuvant Treatment in Pancreatic Cancer.

Thanks to the development of modern chemotherapeutic regimens, survival after surgery for pancreatic ductal adenocarcinoma (PDAC) has improved and pancreatologists worldwide agree that the treatment of PDAC demands a multidisciplinary approach. Neoadjuvant treatment (NAT) plays a major role in the treatment of PDAC since only about 20% of patients are considered resectable at the time of diagnosis. Moreover, increasing data demonstrating the benefits of NAT for borderline resectable/locally advanced PDAC are driving a shift from up-front surgery to NAT in the multidisciplinary treatment of even resectable PDAC. Our understanding of the role of NAT in PDAC has evolved from tumor shrinkage to controlling potential micrometastases and selecting patients who may benefit from radical resection. The present review gives an overview on the current literature of NAT concepts for BR/LA PDAC and resectable PDAC.

Conversion to open surgery during minimally invasive esophagectomy portends worse short-term outcomes: an analysis of the National Cancer Database.

OBJECTIVE: The objectives were to determine factors associated with conversion to open surgery in patients with esophageal cancer who underwent minimally invasive esophagectomy (MIE, including laparo-thoracoscopic and robotic) and the impact of conversion to open surgery on patient outcomes. METHODS: We included patients from the National Cancer Database with esophageal and gastroesophageal junction cancer who underwent MIE from 2010 to 2015. Patient-, tumor-, and facility-related characteristics as well as short-term and oncologic outcomes were compared between patients who were converted to open surgery and those who underwent successful MIE without conversion to open surgery. Multivariable logistic regression models were used to analyze risk factors for conversion to open surgery from attempted MIE. RESULTS: 7306 patients underwent attempted MIE. Of these patients, 82 of 1487 (5.2%) robotic-assisted esophagectomies were converted to open, compared to 691 of 5737 (12.0%) laparo-thoracoscopic esophagectomies (p < 0.001). Conversion rates decreased significantly over the study period (ptrend = 0.010). Patient age, tumor size, and nodal involvement were independently associated with conversion. Facility minimally invasive cumulative volume and robotic approach were associated with decreased conversion rates. Patients whose MIEs were converted had increased 90-day mortality [Odds Ratio (OR) 1.49; 95% Confidence Interval (CI) 1.10, 2.02], prolonged hospital stay (OR 1.39; 95% CI 1.17, 1.66), and higher rates of unplanned readmission (OR 1.67; 95% CI 1.27, 2.20). No significant differences were found in surgical margins or number of lymph nodes harvested. CONCLUSION: Patients undergoing attempted MIE requiring conversion to open surgery had significantly worse short-term outcomes including postoperative mortality. Patient factors and hospital experience contribute to conversion rates. These findings should inform surgeons and patients considering esophagectomy for cancer.