Distinguishing Clinical from Statistical Significances in Contemporary Comparative Effectiveness Research.

OBJECTIVE: To determine the prevalence of clinical significance reporting in contemporary comparative effectiveness research (CER). BACKGROUND: In CER, a statistically significant difference between study groups may or may not be clinically significant. Misinterpreting statistically significant results could lead to inappropriate recommendations that increase healthcare costs and treatment toxicity. METHODS: CER studies from 2022 issues of Annals of Surgery, Journal of the American Medical Association, Journal of Clinical Oncology, Journal of Surgical Research, and Journal of the American College of Surgeons were systematically reviewed by two different investigators. The primary outcome of interest was whether authors specified what they considered to be a clinically significant difference in the Methods. RESULTS: Of 307 reviewed studies, 162 were clinical trials and 145 were observational studies. Authors specified what they considered to be a clinically significant difference in 26 studies (8.5%). Clinical significance was defined using clinically validated standards in 25 studies and subjectively in 1 study. Seven studies (2.3%) recommended a change in clinical decision-making, all with primary outcomes achieving statistical significance. Five (71.4%) of these studies did not have clinical significance defined in their methods. In randomized controlled trials with statistically significant results, sample size was inversely correlated with effect size (r=-0.30, P=0.038). CONCLUSION: In contemporary CER, most authors do not specify what they consider to be a clinically significant difference in study outcome. Most studies recommending a change in clinical-decision making did so based on statistical significance alone, and clinical significance was usually defined with clinically validated standards.

The Revised R Status is an Independent Predictor of Postresection Survival in Pancreatic Cancer After Neoadjuvant Treatment.

OBJECTIVE: To investigate the oncological outcomes of patients with pancreatic ductal adenocarcinoma (PDAC) who had an R 0 or R 1 resection based on the revised R status (1 mm) after neoadjuvant therapy (NAT). BACKGROUND: The revised R status is an independent prognostic factor in upfront-resected PDAC; however, the significance of 1 mm margin clearance after NAT remains controversial. METHODS: Patients undergoing pancreatectomy after NAT for PDAC were identified from 2 prospectively maintained databases. Clinicopathological and survival data were analyzed. The primary outcomes were overall survival (OS), recurrence-free survival (RFS), and pattern of recurrence in association with R 0 >1 mm and R 1 ≤1 mm resections. RESULTS: Three hundred fifty-seven patients with PDAC were included after NAT and subsequent pancreatic resection. Two hundred eight patients (58.3%) received FOLFIRINOX, 41 patients (11.5%) received gemcitabine-based regimens, and 299 individuals (83.8%) received additional radiotherapy. R 0 resections were achieved in 272 patients (76.2%) and 85 patients (23.8%) had R 1 resections. Median OS after R 0 was 41.0 months, compared with 20.6 months after R 1 resection ( P = 0.002), and even longer after additional adjuvant chemotherapy ( R 0 44.8 vs R1 20.1 months; P = 0.0032). Median RFS in the R 0 subgroup was 17.5 months versus 9.4 months in the R 1 subgroup ( P < 0.0001). R status was confirmed as an independent predictor for OS ( R 1 hazard ratio: 1.56, 95% CI: 1.07-2.26) and RFS ( R 1 hazard ratio: 1.52; 95% CI: 1.14-2.0). In addition, R 1 resections were significantly associated with local but not distant recurrence ( P < 0.0005). CONCLUSIONS: The revised R status is an independent predictor of postresection survival and local recurrence in PDAC after NAT. Achieving R 0 resection with a margin of at least 1 mm should be a primary goal in the surgical treatment of PDAC after NAT.

Tumor Size Reduction and Serum Carbohydrate Antigen 19-9 Kinetics After Neoadjuvant FOLFIRINOX in Patients With Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Changes in tumor size and serum carbohydrate antigen 19-9 are commonly reported markers used to assess response to neoadjuvant therapy in pancreatic ductal adenocarcinoma. We evaluated the impact of the percentual tumor size reduction and carbohydrate antigen 19-9 kinetics on resectability and response to neoadjuvant FOLFIRINOX. METHODS: This was an institutional analysis of patients with non-metastatic (upfront resectable, borderline resectable, and locally advanced) pancreatic ductal adenocarcinoma who underwent neoadjuvant FOLFIRINOX. Resectability, pathologic response, disease recurrence, and overall survival were evaluated. RESULTS: Among 193 patients who completed FOLFIRINOX, 60% underwent resection, and 91% were R0. Pathologically, complete, and near-complete responses were achieved in 4% and 40% of patients, respectively. Tumor size reduction (odds ratio 1.02 per 1%, P = .024) and normalization of carbohydrate antigen 19-9 (odds ratio 2.61, P = .035) were associated with increased odds of resectability. Concerning pathologic response, tumor size reduction (odds ratio 1.03 per 1%, P = .018) was associated with increased odds of a complete and near-complete response. Lastly, in resected patients, a postoperative increase in carbohydrate antigen 19-9 after prior normalization after neoadjuvant therapy were at an increased risk of recurrence (hazard ratio 9.58, P < .001) and worse survival (hazard ratio 10.4, P < .001) compared to patients who maintained normalization. CONCLUSION: In patients with non-metastatic pancreatic ductal adenocarcinoma who underwent neoadjuvant therapy, tumor size reduction was a significant predictor of resectability and pathologic response, including complete and near complete responses, whereas serum carbohydrate antigen 19-9 normalization predicted resectability, disease recurrence, and survival. Patients with a postoperative carbohydrate antigen 19-9 rise after prior normalization after administration of neoadjuvant therapy were at an increased risk of recurrence and worse overall survival.

The impact of surgical-oncologic textbook outcome in patients with stage I to III pancreatic ductal adenocarcinoma: A cross-validation study of two national registries.

BACKGROUND: Using national registries, we aimed to evaluate oncologic textbook outcomes in pancreatic ductal adenocarcinoma patients. METHODS: Patients with stage I to III pancreatic ductal adenocarcinoma and surgical resection from 2010 to 2020 in the US and Germany were identified using the National Cancer Database and National Cancer Registries data. The surgical-oncologic textbook outcome was defined as complete oncologic resection with no residual tumor and ≥12 harvested lymph nodes. The composite endpoint was defined as surgical-oncologic textbook outcome and receipt of perioperative systemic and/or radiation therapy. RESULTS: In total, 33,498 patients from the National Cancer Database and 14,589 patients from the National Cancer Registries were included. In the National Cancer Database, 28,931 (86%) patients had complete oncologic resection with no residual tumor, and 11,595 (79%) in the National Cancer Registries. 8,723 (26%) patients in the National Cancer Database and 556 (4%) in the National Cancer Registries had <12 lymph nodes harvested. The National Cancer Database shows 26,135 (78%) underwent perioperative therapy and 8,333 (57%) in the National Cancer Registries. Surgical-oncologic textbook outcome was achieved in 21,198 (63%) patients in the National Cancer Database and in 11,234 (77%) patients from the National Cancer Registries. 16,967 (50%) patients in the National Cancer Database and 7,878 (54%) patients in the National Cancer Registries had composite textbook outcome. Median overall survival in patients with composite textbook outcomes was 32 months in the National Cancer Database and 27 months in the National Cancer Registries (P < .001). In contrast, those with non-textbook outcomes had a median overall survival of 23 months in the National Cancer Database and 20 months in the National Cancer Registries (P < .001). CONCLUSION: Surgical-oncologic textbook outcomes were achieved in > 50% of stage I to III pancreatic ductal adenocarcinoma for both the National Cancer Database and the National Cancer Registries. Failure to achieve textbook outcomes was associated with impaired survival across both registries.

Caregiver-reported quality of communication in pancreatic and periampullary cancer.

BACKGROUND: Communication between caregivers and clinical team members is critical for transitional care, but its quality and potential impact on outcomes are not well understood. This study reports on caregiver-reported quality of communication with clinical team members in the postpancreatectomy period and examines associations of these reports with patient and caregiver outcomes. METHODS: Caregivers of patients with pancreatic and periampullary malignancies who had undergone pancreatectomy were surveyed. Instrument measures assessed care experiences using the Caregiver Perceptions About Communication with Clinical Team Members (CAPACITY) instrument. The instrument has two main subscales: communication, assessing the extent to which providers helped caregivers comprehend details of clinical visits, and capacity, defined as the extent to which providers assessed whether caregivers were able to care for patients. RESULTS: Of 265 caregivers who were approached, 240 (90.6%) enrolled in the study. The mean communication and capacity subscale scores were 2.7 ± 0.6 and 1.5 ± 0.6, respectively (range, 0-4 [higher = better]). Communication subscale scores were lower among caregivers of patients who experienced (vs. those who did not experience) a 30-day readmission (2.6 ± 0.5 vs. 2.8 ± 0.6, respectively; p = .047). Capacity subscale scores were inversely associated with restriction in patient daily activities (a 0.04 decrement in the capacity score for every 1 point in daily activity restriction; p = .008). CONCLUSIONS: After pancreatectomy, patients with pancreatic and periampullary cancer whose caregivers reported worse communication with care providers were more likely to experience readmission. Caregivers of patients with greater daily activity restrictions were less likely to report being asked about the caregiver's skill and capacity by clinicians. PLAIN LANGUAGE SUMMARY: This prospective study used a validated survey instrument and reports on the quality of communication between health care providers and caregivers as reported by caregivers of patients with pancreatic and periampullary cancer after pancreatectomy. In an analysis of 240 caregivers enrolled in the study, lower communication scores (the extent to which providers helped caregivers understand clinical details) were associated with higher odds of 30-day patient readmission to the hospital. In addition, lower capacity scores (the extent to which providers assessed caregivers' ability to care for patients) were associated with greater impairment in caregivers. The strikingly low communication quality and capacity assessment scores suggest substantial room for improvement, with the potential to improve both caregiver and patient outcomes.

Feasibility, Safety, and Efficacy of Aggressive Multimodal Management of Elderly Patients with Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: We aimed to evaluate the safety and efficacy of NAT followed by surgical resection in patients with PDAC aged ≥75 years. SUMMARY BACKGROUND DATA: Whether administration of neoadjuvant therapy (NAT) followed by surgical resection in elderly patients with pancreatic ductal adenocarcinoma (PDAC) is safe and effective is unknown. METHODS: The present study is a three-part comparison of older (≥ 75 years) versus younger (< 75 years) patients in different settings throughout the continuum of PDAC care. The first analysis was a comparison of older versus younger consecutive patients with non-metastatic PDAC who were initiated on FOLFIRINOX. The second was a comparison of older vs. younger patients who underwent NAT followed by surgical resection, and the third and final analysis was a comparison of older patients who underwent either NAT followed by surgical resection vs. upfront surgical resection. Postoperative complications, overall survival (OS), and time to recurrence (TTR), were compared. Propensity-score matching (PSM) analysis was performed to adjust for potential confounders. RESULTS: In the first analysis, a lower proportion of older patients (n=40) were able to complete the intended neoadjuvant FOLFIRINOX (8) cycles compared to younger patients (n=214) (65.0% vs. 81.4%, P=0.021). However, older patients were just as likely to undergo surgical exploration as younger patients (77.5% vs 78.5%, P=0.89) as well as surgical resection (57.5% vs 55.6%, P=0.70). In the second analysis, PSM was conducted to compare older (n=54) vs. younger patients (n=54) who underwent NAT followed by surgical resection. There were no significant differences in postoperative complications between the matched groups. While there was a significant difference in overall survival (OS) between older and younger patients (median OS: 16.43 months vs. 30.83 months, P=0.002), importantly, there was no significant difference in time to recurrence (TTR, median: 7.65 months vs. 11.83 months, P=0.215). In the third analysis, older patients who underwent NAT followed by surgical resection (n=48) were compared with similar older patients who underwent upfront surgical resection (n=48). After PSM, there was a significant difference in OS (median OS: 15.78 months vs. 11.51 months, P=0.037) as well as TTR (median TTR: 8.81 months vs. 7.10 months, P=0.046) representing an association with improved outcomes that favored the neoadjuvant approach among older patients alone. CONCLUSIONS: This comprehensive three-part study showed that administration of NAT followed by surgical resection appears to be safe and effective among patients ≥ 75 years of age. An aggressive approach should be offered to older adults undergoing multimodal treatment of PDAC.

The Role of Adjuvant Therapy in Duodenal Adenocarcinoma and Intestinal Subtype Ampullary Carcinoma after Curative Resection.

OBJECTIVE: Defining the role of adjuvant therapy in duodenal adenocarcinoma (DAC) and intestinal subtype ampullary carcinoma (iAC). SUMMARY BACKGROUND DATA: DAC and iAC share a similar histological differentiation but the benefit of adjuvant therapy remains unclear. METHODS: Patients undergoing curative-intent surgical resection for DAC and iAC between 2010 and 2021 at five high-volume centers were included. Patient baseline, perioperative and long-term oncological outcomes were evaluated. Statistical testing was performed with SPSS 25 (IBM). RESULTS: A total of 136 patients with DAC and 171 with iAC were identified. Patients with DAC had more advanced tumors than those with iAC. Median overall survival (OS) in DAC patients was 101 months versus 155 months for iAC patients (P=0.098). DAC had a higher rate of local (14.1% vs. 1.2%, P<0.001) and systemic recurrence (30.4% vs. 3.5%, P<0.001). Adjuvant therapy failed to improve overall survival in all patients with DAC and iAC. For DAC, patients with perineural invasion, but not other negative prognostic factors had improved OS rates with adjuvant therapy (72 m vs. 44 m, P=0.044). IAC patients with N+ (190 m vs. 57 m, P=0.003), T3-4 (177 m vs. 59 m, P=0.050) and perineural invasion (150 m vs. 59 m, P=0.019) had improved OS rates with adjuvant therapy. CONCLUSION: While adjuvant therapy fails to improve OS in all patients with DAC and iAC in the current study, it improved overall survival in DAC patients with perineural invasion and in iAC patients with T3-4 tumors, positive lymph nodes, and perineural invasion.

Smoking impairs the effect of neoadjuvant FOLFIRINOX on postresection survival in pancreatic cancer.

INTRODUCTION: Smoking plays an important role in carcinogenesis, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about the association between smoking status and prognosis in resected PDAC. METHODS: All patients who underwent resection for PDAC were identified from two prospective institutional databases. Clinicopathologic data as well as demographics including smoking status were extracted. Survival analysis and multivariable Cox regression modelling was performed. Restricted cubic splines were used for linear data to define cut-off points. RESULTS: Out of 848 patients, 357 (42.1%) received neoadjuvant treatment (NAT), 491 upfront resection (57.9%), and 475 (56%) adjuvant therapy. The median overall survival (OS) was 27.8 months, 36.1 months, and 23.0 months for the entire cohort, after NAT and upfront resection. 464 patients were never smokers (54.7%), 250 former smokers (29.5%), and 134 active smokers (15.8%). In the multivariable model, the interaction of neoadjuvant FOLFIRINOX and active smoking was associated with the highest risk for decreased OS (harzard ratio (HR) 2.35; 95% confidence interval 1.13-4.90) and strongly mitigated the benefit of FOLFIRNOX (HR 0.40; 95% CI 0.25-0.63). Adjusted median OS in NAT patients with FOLFIRINOX was not reached for never and former smokers, compared to 26.2 months in active smokers. Based on the model, a nomogram was generated to illustrate the probability of 5-year survival after PDAC resection. CONCLUSION: The present study confirms that neoadjuvant FOLFIRINOX is associated with excellent survival and demonstrates that active smoking reduces its benefit. The nomogram can assist in daily clinical practice and emphasises the importance of smoking cessation in patients with PDAC, especially prior to NAT with FOLFIRINOX.

Long-Term Outcomes of Tuberous Sclerosis Complex-Associated Non-functional Pancreatic Neuroendocrine Tumors: Should We Be More Conservative?

BACKGROUND: Hereditary syndromes such as tuberous sclerosis complex (TSC) account for 10% of pancreatic neuroendocrine tumors (PNETs). Surgical intervention is the current standard of care for sporadic PNETs (spPNETs) that are >2 cm in size. We compared the long-term outcomes of resected TSC-PNETs with patients with spPNETs. METHODS: We conducted a retrospective review of perioperative data and outcomes of TSC-PNETs compared with spPNETs. Inclusion criteria involved selecting patients whose tumors were no larger than 5.1 cm, the maximum size observed in the TSC-PNET group. RESULTS: Of the 347 patients resected for PNETs, 14 were TSC-PNETs and 241 were non-functional spPNETs. The median age for the whole cohort was 56 years (interquartile range [IQR] 21.0) and 47% were female. The median follow-up was 103.8 months (95% confidence interval [CI] 89.2-118.6). Specifically, 14 patients with TSC-PNETs and 194 patients with spPNETs were included. Compared with spPNETs, patients with TSC-PNETs were operated on at a younger age (24.0 vs. 57.5 years; p < 0.001), were more frequently multifocal (28.5% vs. 0.0%; p < 0.001), were more likely to undergo minimally invasive operations (78.6% vs. 24.3%; p < 0.001), and had more R1 resections (28.6% vs. 5.7%; p = 0.006). Local and distant tumor recurrence was only observed in the spPNET group. The 5-year mortality rates for the spPNET and TSC-PNET groups were 6.2% and 0.0%, respectively. No PNET-related deaths were observed among TSC-PNETs. CONCLUSION: None of the TSC-PNET patients recurred after a median follow-up of 78.0 months. The risk-benefit of aggressive pancreatic operations in TSC-PNET patients is still unclear and our findings suggest a conservative approach should be considered.

Portal Vein or Superior Mesenteric Vein Thrombosis with Dose-Escalated Radiation for Borderline or Locally Advanced Pancreatic Cancer.

PURPOSE: Portal vein and superior mesenteric vein thrombosis (PVT/SMVT) are potentially morbid complications of radiation dose-escalated local therapy for pancreatic cancer. We retrospectively reviewed records for patients treated with and without intraoperative radiation (IORT) to identify risk factors for PVT/SMVT. METHODS: Ninety-six patients with locally advanced or borderline resectable pancreatic adenocarcinoma received neoadjuvant therapy followed by surgical exploration from 2009 to 2014. Patients at risk for close or positive surgical margins received IORT boost to a biologically effective dose (BED10) > 100. Prognostic factors for PVT/SMVT were evaluated using competing risks regression. RESULTS: Median follow-up was 79 months for surviving patients. Fifty-six patients (58%) received IORT. Twenty-nine patients (30%) developed PVT/SMVT at a median time of 18 months. On univariate competing risks regression, operative blood loss and venous repair with a vascular interposition graft, but not IORT dose escalation or diabetes history, were significantly associated with PVT/SMVT. The development of thrombosis in the absence of recurrence was significantly associated with a longstanding diabetes history, post-neoadjuvant treatment CA19-9, and operative blood loss. All 4 patients who underwent both IORT and vascular repair with a graft developed PVT/SMVT. PVT/SMVT in the absence of recurrence is not associated with significantly worsened overall survival but led to frequent medical interventions. CONCLUSIONS: Approximately 30% of patients who underwent neoadjuvant chemoradiation for PDAC developed PVT/SMVT a median of 18 months following surgery. This was significantly associated with venous reconstruction with vascular grafts, but not with escalating radiation dose. PVT/SMVT in the absence of recurrence was associated with significant morbidity.

Bibliometric analysis of academic journal recommendations and requirements for surgical and anesthesiologic adverse events reporting.

BACKGROUND: Standards for reporting surgical adverse events (AEs) vary widely within the scientific literature. Failure to adequately capture AEs hinders efforts to measure the safety of healthcare delivery and improve the quality of care. The aim of the present study is to assess the prevalence and typology of perioperative AE reporting guidelines among surgery and anesthesiology journals. MATERIALS AND METHODS: In November 2021, three independent reviewers queried journal lists from the SCImago Journal & Country Rank (SJR) portal (www.scimagojr.com), a bibliometric indicator database for surgery and anesthesiology academic journals. Journal characteristics were summarized using SCImago, a bibliometric indicator database extracted from Scopus journal data. Quartile 1 (Q1) was considered the top quartile and Q4 bottom quartile based on the journal impact factor. Journal author guidelines were collected to determine whether AE reporting recommendations were included and, if so, the preferred reporting procedures. RESULTS: Of 1409 journals queried, 655 (46.5%) recommended surgical AE reporting. Journals most likely to recommend AE reporting were: by category surgery (59.1%), urology (53.3%), and anesthesia (52.3%); in top SJR quartiles (i.e. more influential); by region, based in Western Europe (49.8%), North America (49.3%), and the Middle East (48.3%). CONCLUSIONS: Surgery and anesthesiology journals do not consistently require or provide recommendations on perioperative AE reporting. Journal guidelines regarding AE reporting should be standardized and are needed to improve the quality of surgical AE reporting with the ultimate goal of improving patient morbidity and mortality.

Profile of the Postoperative Care Provided for Patients With Pancreatic and Periampullary Cancers by Family and Unpaid Caregivers.

PURPOSE: Patients with pancreatic and periampullary cancers may experience significant reduction in their quality of life and often rely on family and unpaid caregivers for assistance after surgery. However, as caregivers are not systematically identified, little is known about the nature, difficulty, and personal demands of assistance they provide. We aim to assess the frequency and difficulty of specific assistance caregivers provide and identify potential interventions that could alleviate the caregiving demands. METHODS: This was a prospective, multi-institutional study of caregivers accompanying patients with periampullary and pancreatic cancer at their 1-month postpancreatectomy office visit. An instrument that drew heavily on the National Study of Caregiving was administered to caregivers. RESULTS: Of 240 caregivers, more than half (58.3%) of caregivers were the patients' spouse, a quarter (25.8%) were daughters or sons, 12.9% other relatives, and 2.9% nonrelatives. Caregivers least frequently provided assistance with transportation (14.6% every day) and most frequently provided assistance with housework (65.0% every day, P = .003) and diet (56.5% every day, P = .004). Caregivers reported the least difficulty helping patients with exercise (1.5% somewhat difficult). Caregivers reported significantly more difficulty with assisting with housework (14.5% somewhat difficult, P < .001) and diet (14.9% somewhat difficult, P < .001). Caregivers identified the immediate postpancreatectomy and early discharge periods as the most stressful phases. They also reported having received very little information about available services that could have supported their efforts. CONCLUSION: Caregivers of patients with periampullary or pancreatic cancer provide considerable assistance in the postoperative period and many reported difficulty in assisting with housework and diet. Work is needed to better prepare and support caregivers to better enable them to adequately care for patients with pancreas and periampullary cancer.

Emerging From the Pandemic: How Has Academic Surgery Changed?

Academic surgery has changed along with the rest of the world in response to the COVID pandemic. With increasing rates of vaccination against COVID over the past 2 y, we have slowly but steadily made progress toward controlling the spread of the virus. Surgeons, academic surgery departments, health systems, and trainees are all attempting to establish a new normal in various domains-clinical, research, teaching, and in their personal lives. How has the pandemic changed these areas? At the 2022 Academic Surgical Congress Hot Topics session, we attempted to address these issues.

IPMN-LEARN: A linear support vector machine learning model for predicting low-grade intraductal papillary mucinous neoplasms.

Backgrounds/Aims: We aimed to build a machine learning tool to help predict low-grade intraductal papillary mucinous neoplasms (IPMNs) in order to avoid unnecessary surgical resection. IPMNs are precursors to pancreatic cancer. Surgical resection remains the only recognized treatment for IPMNs yet carries some risks of morbidity and potential mortality. Existing clinical guidelines are imperfect in distinguishing low-risk cysts from high-risk cysts that warrant resection. Methods: We built a linear support vector machine (SVM) learning model using a prospectively maintained surgical database of patients with resected IPMNs. Input variables included 18 demographic, clinical, and imaging characteristics. The outcome variable was the presence of low-grade or high-grade IPMN based on post-operative pathology results. Data were divided into a training/validation set and a testing set at a ratio of 4:1. Receiver operating characteristics analysis was used to assess classification performance. Results: A total of 575 patients with resected IPMNs were identified. Of them, 53.4% had low-grade disease on final pathology. After classifier training and testing, a linear SVM-based model (IPMN-LEARN) was applied on the validation set. It achieved an accuracy of 77.4%, with a positive predictive value of 83%, a specificity of 72%, and a sensitivity of 83% in predicting low-grade disease in patients with IPMN. The model predicted low-grade lesions with an area under the curve of 0.82. Conclusions: A linear SVM learning model can identify low-grade IPMNs with good sensitivity and specificity. It may be used as a complement to existing guidelines to identify patients who could avoid unnecessary surgical resection.

Tolerability, Attrition Rates, and Survival Outcomes of Neoadjuvant FOLFIRINOX for Nonmetastatic Pancreatic Adenocarcinoma: Intent-to-Treat Analysis.

BACKGROUND: FOLFIRINOX is increasingly used in the management of pancreatic ductal adenocarcinoma (PDAC). However, neoadjuvant therapy is associated with toxicity, possible disease progression, and biopsy-related and biliary complications that may preclude operative exploration. Data on the true attrition rate outside of clinical trials or resected surgical series are lacking. STUDY DESIGN: Patients with nonmetastatic PDAC who initiated FOLFIRINOX from 2015 to 2020 were identified from our institution's pharmacy records. Multivariable regression and Cox proportional hazard models were used for adjusted analyses of categorical and survival outcomes, respectively. RESULTS: Of 254 patients who initiated first-line neoadjuvant FOLFIRINOX, 199 (78.3%) underwent exploration, and 54 (21.3%) did not complete their chemotherapy cycles due to poor tolerability (46.3%), poor response (31.5%), or disease progression (14.8%), among other causes (7.4%). A total of 109 (42.9%) patients experienced grade 3/4 FOLFIRINOX-related toxicity, of whom 73 (28.7%) and 100 (39.4%) required an emergency department visit or inpatient admission, respectively. Finally, not undergoing surgical exploration was associated with impaired overall survival (hazard ratio 7.0; 95% CI 3.8 to 12.8; p < 0.001). Independent predictors of not undergoing exploration were remote history of chemotherapy receipt (odds ratio [OR] 0.06; p = 0.02), inability to complete FOLFIRINOX cycles (OR 0.2, p = 0.003), increase in ECOG score (OR 0.2, p < 0.001), and being single or divorced (OR 0.3, p = 0.018). CONCLUSIONS: Among 254 patients with nonmetastatic PDAC initiated on FOLFIRINOX, of whom 52% were locally advanced, a total of 199 (78.3%) were explored, 142 (71.4%) underwent successful resection, and 129 (90.8%) were resected with negative margins. Despite 109 (42.9)% of patients experiencing significant toxicity, most patients could be managed through treatment-related complications to complete planned neoadjuvant chemotherapy and undergo planned surgical exploration.

Uncinate Duct Dilatation Predicts Additional Risk for High-Grade Dysplasia or Invasive Carcinoma Among Fukuoka-Positive Intraductal Papillary Mucinous Neoplasms.

OBJECTIVE: To determine whether uncinate duct dilatation (UDD) increases the risk of high-grade dysplasia or invasive carcinoma (HGD/IC) in Fukuoka-positive intraductal papillary mucinous neoplasms (IPMNs). BACKGROUND: Though classified as a branch duct, the uncinate duct is the primary duct of the pancreatic ventral anlage. We hypothesized that UDD, like main duct dilatation, confers additional risk for HGD/IC. METHODS: A total of 467 patients met inclusion criteria in a retrospective cohort study of surgically resected IPMNs at the Massachusetts General Hospital. We used multivariable logistic regression to analyze the association between UDD (defined as ≥4 mm) and HGD/IC, controlling for Fukuoka risk criteria. In a secondary analysis, the modeling was repeated in the 194 patients with dorsal branch duct IPMNs (BD-IPMNs) in the pancreatic neck, body, or tail. RESULTS: Mean age at surgery was 70, and 229 (49%) patients were female. In total, 267 (57%) patients had only worrisome features and 200 (43%) had at least 1 high-risk feature. UDD was present in 164 (35%) patients, of whom 118 (73%) had HGD/IC. On multivariable analysis, UDD increased the odds of HGD/IC by 2.8-fold, even while controlling for Fukuoka risk factors (95% CI: 1.8-4.4, P <0.001). Prevalence of HGD/IC in all patients with UDD was 73%, compared with 74% in patients with high-risk stigmata and 73% in patients with main duct IPMNs. In the secondary analysis, UDD increased the odds of HGD/IC by 3.2-fold in patients with dorsal BD-IPMNs (95% CI: 1.3-7.7, P =0.010). CONCLUSIONS: UDD confers additional risk for HGD/IC unaccounted for by current Fukuoka criteria. Further research can extend this study to Fukuoka-negative patients, including unresected patients.

Identification of high-risk features in mucinous cystic neoplasms of the pancreas.

BACKGROUND: Mucinous cystic neoplasms of the pancreas are uncommon tumors that have the potential of becoming cancer. There is no consensus regarding the high-risk features of these tumors. Our study aimed to identify the preoperative demographic, clinical, or radiologic factors that can predict the presence of high-grade dysplasia or invasive carcinoma in mucinous cystic neoplasms of the pancreas. METHODS: We identified 157 patients who underwent resection and fulfilled the pathologic criteria for mucinous cystic neoplasms of the pancreas in a prospectively maintained database spanning 3 decades (1990-2020). Multivariable logistic regression was used to identify predictors of high-grade dysplasia or invasive carcinoma in mucinous cystic neoplasms of the pancreas. RESULTS: The rate of high-grade dysplasia or invasive carcinoma was 11%. Tumor size ≥4 cm (P < .001), mural nodularity (P = .04), and a serum CA 19-9 level >37 U/mL (P < .001) were associated with high-grade dysplasia or invasive carcinoma. In the multivariable analysis, tumor size ≥4 cm (odds ratio 16.9, 95% confidence interval 2.04-140, P = .009) and a CA 19-9 level >37 U/mL (odds ratio 5.68, 95% confidence interval 1.52-21.3, P = .010) were predictors of high-grade dysplasia or invasive carcinoma. There were no tumors with high-grade dysplasia or invasive carcinoma in patients with tumor size <4 cm in the absence of an elevated CA 19-9 or mural nodularity. CONCLUSION: Tumors with a size ≥4 cm and/or a high CA 19-9 level should be considered for prompt surgical resection. Conversely, tumors <4 cm with no other high-risk features have a negligible risk for high-grade dysplasia or invasive carcinoma and may benefit from nonoperative surveillance. Mural nodularity is an additional suspicious feature. These findings may contribute to future guidelines.