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.

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.

Blue Ribbon Committee I Review: Findings and Impact.

OBJECTIVE: Review the subsequent impact of recommendations made by the 2004 American Surgical Association Blue Ribbon Committee (BRC I) Report on Surgical Education. BACKGROUND: Current leaders of the American College of Surgeons and the American Surgical Association convened an expert panel to review the impact of the BRC I report and make recommendations for future improvements in surgical education. METHODS: BRC I members reviewed the 2004 recommendations in light of the current status of surgical education. RESULTS: Some of the recommendations of BRC I have gained traction and have been implemented. There is a well-organized national curriculum and numerous educational offerings. There has been greater emphasis on preparing faculty to teach and there are ample opportunities for professional advancement as an educator. The number of residents has grown, although not at a pace to meet the country's needs either by total number or geographic distribution. The number of women in the profession has increased. There is greater awareness and attention to resident (and faculty) well-being. The anticipated radical change in the educational scheme has not been adopted. Training in surgical research still depends on the resources and interests of individual programs. Financing student and graduate medical education remains a challenge. CONCLUSIONS: The medical landscape has changed considerably since BRC I published its findings in 2005. A contemporary assessment of surgical education and training is needed to meet the future needs of the profession and our patients.

EGFR is a potential therapeutic target for highly glycosylated and aggressive pancreatic neuroendocrine neoplasms.

pNENs are relative indolent tumors with heterogeneous clinical presentation at diagnosis. It is important to establish aggressive subgroups of pNENs and identify potential therapeutic targets. Patients with pNEN (322 cases) were included to examine the association between glycosylation biomarkers and clinical/pathological traits. The molecular and metabolic features stratified by glycosylation status were assessed by RNA-seq/whole exome sequencing and immunohistochemistry. A considerable proportion of patients had elevated glycosylation biomarkers (carbohydrate antigen [CA] 19-9, 11.9%; CA125, 7.5%; carcinoembryonic antigen [CEA], 12.8%). CA19-9 (hazard ratio [HR] = 2.26, P = .019), CA125 (HR = 3.79, P = .004) and CEA (HR = 3.16, P = .002) were each independent prognostic variables for overall survival. High glycosylation group, defined as pNENs with elevated level of circulating CA19-9, CA125 or CEA, accounted for 23.4% of all pNENs. High glycosylation (HR = 3.14, P = .001) was an independent prognostic variable for overall survival and correlated with G3 grade (P < .001), poor differentiation (P = .001), perineural invasion (P = .004) and distant metastasis (P < .001). Epidermal growth factor receptor (EGFR) was enriched in high glycosylation pNENs using RNA-seq. EGFR was expressed in 21.2% of pNENs using immunohistochemistry and associated with poor overall survival (P = .020). A clinical trial focusing on EGFR expressed pNENs was initiated (NCT05316480). Thus, pNEN with aberrant glycosylation correlates with a dismal outcome and suggests potential therapeutic target of EGFR.

"Evolving Trends in Pancreatic Cystic Tumors: A 3-Decade Single-Center Experience With 1290 Resections".

OBJECTIVE: The aim of this study was to describe our institutional experience with resected cystic tumors of the pancreas with emphasis on changes in clinical presentation and accuracy of preoperative diagnosis. SUMMARY BACKGROUND DATA: Incidental discovery of pancreatic cystic lesions has increased and has led to a rise in pancreatic resections. It is important to analyze surgical outcomes from these procedures, and the prevalence of malignancy, pre-malignancy and resections for purely benign lesions, some of which may be unintended. METHODS: Retrospective review of a prospective database spanning 3 decades. Presence of symptoms, incidental discovery, diagnostic studies, type of surgery, postoperative outcomes, and concordance between presumptive diagnosis and final histopathology were recorded. RESULTS: A total of 1290 patients were identified, 62% female with mean age of 60 years. Fifty-seven percent of tumors were incidentally discovered. Ninety-day operative mortality was 0.9% and major morbidity 14.4%. There were 23 different diagnosis, but IPMN, MCN, and serous cystadenoma comprised 80% of cases. Concordance between preoperative and final histopathological diagnosis increased by decade from 45%, to 68%, and is presently 80%, rising in parallel with the use of endoscopic ultrasound, cytology, and molecular analysis. The addition of molecular analysis improved accuracy to 91%. Of misdiagnosed cases, half were purely benign and taken to surgery with the presumption of malignancy or premalignancy. The majority of these were serous cystadenomas. CONCLUSIONS: Indications and diagnostic work-up of cystic tumors of the pancreas have changed over time. Surgical resection can be performed with very low mortality and acceptable morbidity and diagnostic accuracy is presently 80%. About 10% of patients are still undergoing surgery for purely benign lesions that were presumed to be malignant or premalignant. Further refinements in diagnostic tests are required to improve accuracy.

A Combination of Biochemical and Pathological Parameters Improves Prediction of Postresection Survival After Preoperative Chemotherapy in Pancreatic Cancer: The PANAMA-score.

OBJECTIVE: To build a prognostic score for patients with primary chemotherapy undergoing surgery for pancreatic cancer based on pathological parameters and preoperative Carbohydrate antigen 19-9 (CA19-9) levels. BACKGROUND: Prognostic stratification after primary chemotherapy for pancreatic cancer is challenging and prediction models, such as the AJCC staging system, lack validation in the setting of preoperative chemotherapy. METHODS: Patients with primary chemotherapy resected at the Massachusetts General Hospital between 2007 and 2017 were analyzed. Tumor characteristics independently associated with overall survival were identified and weighted by Cox-proportional regression. The pancreatic neoadjuvant Massachusetts-score (PANAMA-score) was computed from these variables and its performance assessed by Harrel concordance index and area under the receiving characteristics curves analysis. Comparisons were made with the AJCC staging system and external validation was performed in an independent cohort with primary chemotherapy from Heidelberg, Germany. RESULTS: A total of 216 patients constituted the training cohort. The multivariate analysis demonstrated tumor size, number of positive lymph-nodes, R-status, and high CA19-9 to be independently associated with overall survival. Kaplan-Meier analysis according to low, intermediate, and high PANAMA-score showed good discriminatory power of the new metrics (P < 0.001). The median overall survival for the three risk-groups was 45, 27, and 12 months, respectively. External validation in 258 patients confirmed the prognostic ability of the score and demonstrated better accuracy compared with the AJCC staging system. CONCLUSION: The proposed PANAMA-score, based on independent predictors of postresection survival, including pathologic variables and CA19-9, not only provides better discrimination compared to the AJCC staging system, but also identifies patients at high-risk for early death.

ABO blood group distribution and risk of malignancy in patients undergoing resection for intraductal papillary mucinous neoplasm (IPMN).

BACKGROUND: The ABO blood type has been associated with risk of development of several malignancies, including pancreatic cancer. Data regarding IPMN is equivocal. To investigate this further, we analyzed the association between the ABO blood group and the presence of malignancy in a large cohort of resected IPMN and its influence in survival. METHODS: 819 patients who underwent pancreatic resection for IPMN in the Massachusetts General Hospital (MGH) and Cambridge University Hospitals NHS Foundation Trust (CUH) from January 1993 to December 2020 were identified from prospective institutional databases. Pathological characteristics and blood type were correlated. RESULTS: The distribution of blood types A, B, AB and O was 384 (47%), 92 (11%), 44 (5%) and 299 (37%), respectively. This blood type distribution was different than the reference population of the MGH and the CUH, which is 55% non-O blood group, and 45% type O. There was a significant predominance of non-O blood types when compared with O-blood type in patients with malignant IPMN (i.e. patients with high-grade dysplasia and invasive cancer) (67% vs 33%, OR 1.31 95%CI: 0.98-1.75, p = 0.069). The association was stronger for IPMN with invasive cancer (OR 1.43 95%CI: 1.01-2.02, p = 0.039). Blood group did not influence survival. CONCLUSION: Non-O blood type is associated with need for resection in IPMN and with presence of invasive carcinoma.

Simulated Volume-Based Regionalization of Complex Procedures: Impact on Spatial Access to Care.

OBJECTIVE: This study simulates the regionalization of pancreatectomies to assess its impact on spatial access in terms of patient driving times. BACKGROUND: Although policies to regionalize complex procedures to high-volume centers may improve outcomes, the impact on patient access is unknown. METHODS: Patients who underwent pancreatectomies from 2005 to 2014 were identified from California's statewide database. Round-trip driving times between patients' home ZIP code and hospital addresses were calculated via Google Maps. Regionalization was simulated by eliminating hospitals performing <20 pancreatectomies/yr, and reassigning patients to the next closest hospital that satisfied the volume threshold. Sensitivity analyses were performed for New York and Medicare patients to assess for influence of geography and insurance coverage, respectively. RESULTS: Of 13,317 pancreatectomies, 6335 (47.6%) were performed by hospitals with <20 cases/yr. Patients traveled a median of 49.8 minutes [interquartile range (IQR) 30.8-96.2] per round-trip. A volume-restriction policy would increase median round-trip driving time by 24.1 minutes (IQR 4.5-53.5). Population in-hospital mortality rates were estimated to decrease from 6.7% to 2.8% (P < 0.001). Affected patients were more likely to be racial minorities (44.6% vs 36.5% of unaffected group, P < 0.001) and covered by Medicaid or uninsured (16.3% vs 9.8% of unaffected group, P < 0.001). Sensitivity analyses revealed a 17.8 minutes increment for patients in NY (IQR 0.8-47.4), and 27.0 minutes increment for Medicare patients (IQR 6.2-57.1). CONCLUSIONS: A policy that limits access to low-volume pancreatectomy hospitals will increase round-trip driving time by 24 minutes, but up to 54 minutes for 25% of patients. Population mortality rates may improve by 1.5%.

Revision of Pancreatic Neck Margins Based on Intraoperative Frozen Section Analysis Is Associated With Improved Survival in Patients Undergoing Pancreatectomy for Ductal Adenocarcinoma.

OBJECTIVE: To test the hypothesis that complete, tumor-free resection at the pancreatic neck, achieved either en-bloc or non-en-bloc (ie, revision based on intraoperative frozen section [FS] analysis), is associated with improved survival as compared with incomplete resection (IR) in pancreatic ductal adenocarcinoma. SUMMARY BACKGROUND DATA: Given the likely systemic nature of pancreatic ductal adenocarcinoma, the oncologic benefit of achieving a histologically complete local resection, particularly through revision of a positive intraoperative FS at the pancreatic neck, remains controversial. METHODS: Clinicopathologic and treatment data were reviewed for 986 consecutive patients with ductal adenocarcinoma at the head, neck, or uncinate process of the pancreas who underwent open pancreatectomy as well as intraoperative FS analysis between 1998 and 2012 at Massachusetts General Hospital and between 1998 and 2013 at the University of Verona. Overall survival (OS) and perioperative morbidity and mortality were compared across 3 groups: complete resection achieved en-bloc (CR-EB), complete resection achieved non-en-bloc (CR-NEB), and IR. RESULTS: The CR-EB cohort comprised 749 (76%) patients, CR-NEB 159 patients (16%), and IR 78 patients (8%). Other than a higher incidence of vascular resection among CR-NEB and IR patients, no demographic, pathologic (eg, tumor grade, lymph node positivity, superior mesenteric artery involvement), or treatment factors (eg, neoadjuvant and adjuvant therapy use) differed between the groups. Median OS was significantly higher in patients with CR-EB (28 mo, P = 0.01) and CR-NEB resections (24 mo, P = 0.02) as compared with patients with IR resections (19 mo). After adjusting for clinicopathologic and treatment characteristics, CR-EB and CR-NEB margin status were found to be independent predictors of improved OS (relative to IR, CR-EB hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.49-0.86; CR-NEB HR 0.69, 95% CI 0.50-0.96). There were no intergroup differences in perioperative morbidity and mortality, including rates of pancreatic fistula. CONCLUSIONS: For patients with ductal adenocarcinoma at the head, neck, or uncinate process of the pancreas undergoing pancreatectomy, complete tumor extirpation via either en-bloc or non-en-bloc complete resection based on FS analysis is associated with improved OS, without an associated increased perioperative morbidity or mortality.

Assessment of the Long-Term Impact of Pancreatoduodenectomy on Health-Related Quality of Life Using the EORTC QLQ-PAN26 Module.

BACKGROUND: Long-term pancreatoduodenectomy (PD) survivors have previously reported favorable quality of life (QoL). However, there has been a paucity of studies utilizing pancreas-specific modules for QoL assessment, which may uncover disability that general modules cannot detect. METHODS: The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-PAN26 questionnaires were administered to PD survivors who were at least 5 years out of their operations for neoplasms (1998-2011, study cohort) and compared their scores with published preoperative scores of patients with pancreatic cancer (control cohort). The clinical relevance (CR) of differences was scored as small (5-10), moderate (10-20), or large (> 20) based on validated interpretation of clinically important differences. RESULTS: Of 1266 patients who underwent PD, there were 305 survivors with valid contact information, of whom 248 responded to the questionnaire (response rate 81.3%) and made up the study cohort. The median follow-up was 9.1 years (range 5.1-21.2 years). When compared with the control cohort, patients in the study cohort reported higher pancreatic pain (41.7 ± 17.6 vs. 18.1 ± 20.5, p < 0.001, CR large), sexuality dissatisfaction (63.0 ± 37.5 vs. 35.1 ± 34.3, p < 0.001, CR large), altered bowel habits (37.6 ± 30.6 vs. 20.0 ± 24.5, p < 0.001, CR moderate), and digestive symptoms (26.3 ± 29.5 vs. 18.7 ± 27.8, p = 0.002, CR small) scores. There was a higher prevalence of bloating, indigestion, and flatulence, but lower prevalence of future health worry (71.7% vs. 89.6%, p < 0.001) and limitation in planning activities (30.1% vs. 48.3%, p < 0.001) at 5 years. CONCLUSION: While post-PD patients had better long-term global QoL than healthy controls, a more granular, pancreas-specific questionnaire uncovered digestive abnormalities and sexuality dissatisfaction. These data can better inform clinical decision making and provide potential areas for improvement and patient support.

Patient and Caregiver Considerations and Priorities When Selecting Hospitals for Complex Cancer Care.

BACKGROUND: Healthcare policies have focused on centralizing care to high-volume centers in an effort to optimize patient outcomes; however, little is known about patients' and caregivers' considerations and selection process when selecting hospitals for care. We aim to explore how patients and caregivers select hospitals for complex cancer care and to develop a taxonomy for their selection considerations. METHODS: This was a qualitative study in which data were gathered from in-depth interviews conducted from March to November 2019 among patients with hepatopancreatobiliary cancers who were scheduled to undergo a pancreatectomy (n = 20) at a metropolitan, urban regional, or suburban medical center and their caregivers (n = 10). RESULTS: The interviews revealed six broad domains that characterized hospital selection considerations: hospital factors, team characteristics, travel distance to hospital, referral or recommendation, continuity of care, and insurance considerations. The identified domains were similar between participants seen at the metropolitan center and urban/suburban medical centers, with the following exceptions: participants receiving care specifically at the metropolitan center noted operative volume and access to specific services such as clinical trials in their hospital selection; participants receiving care at urban/suburban centers noted health insurance considerations and having access to existing medical records in their hospital selection. CONCLUSIONS: This study delineates the many considerations of patients and caregivers when selecting hospitals for complex cancer care. These identified domains should be incorporated into the development and implementation of centralization policies to help increase patient access to high-quality cancer care that is consistent with their priorities and needs.

Pancreatic acinar cell carcinoma: A multi-center series on clinical characteristics and treatment outcomes.

BACKGROUND: Acinar cell carcinoma (ACC) is a very rare tumor of the exocrine pancreas, representing less than 1% of all pancreatic malignancies. The majority of data regarding ACC are limited to small case series. METHODS: This is a retrospective study conducted at a large healthcare system from 1996 to 2019. Patients with pathologically confirmed ACC were included, and demographic data, tumor characteristics, and treatment outcomes were abstracted by chart review. Survival curves were obtained by using the Kaplan-Meier method and compared using the log-rank test. RESULTS: Sixty-six patients with ACC were identified. The median patient age at diagnosis was 64, and 42% presented with metastatic disease. The majority presented with abdominal pain or pancreatitis (69%), and laboratory parameters did not correlate with tumor size, metastatic disease, or survival. Several somatic abnormalities were noted in tumors (BRCA2, TP53, and mismatch-repair genes). In patients with localized disease that underwent resection, the median time to develop metastatic lesions was 13 months. The median overall survival (OS) was 24.7 months from diagnosis, with a survival difference based on metastatic disease at diagnosis (median 15 vs 38 mos). Surgery was associated with improved survival in non-metastatic cases (p = 0.006) but not metastatic cases (p = 0.22), and chemotherapy showed OS benefit in metastatic disease (p < 0.01). Patients with metastatic ACC treated after 2010 utilized more platinum-based agents, and there was a OS benefit to FOLFOX or FOLFIRINOX chemotherapy compared to gemcitabine or capecitabine-based regimens (p = 0.006). CONCLUSION: Pancreatic ACC patients often present with advanced disease. Surgery was associated with survival benefit among patients presenting with localized disease. The use of FOLFOX or FOLFIRINOX chemotherapy regimens was associated with improved OS in metastatic patients. These data add to our knowledge in this rare malignancy, and improves understanding about the genomic underpinnings, prognosis and treatment for acinar cancers.

Hedgehog signaling promotes angiogenesis directly and indirectly in pancreatic cancer.

INTRODUCTION: The inhibition of Hedgehog (Hh) signaling in pancreatic ductal adenocarcinoma (PDAC) reduces desmoplasia and promotes increased vascularity. In contrast to these findings, the Hh ligand Sonic Hedgehog (SHH) is a potent proangiogenic factor in non-tumor models. The aim of this study was to determine the molecular mechanisms by which SHH affects the tumor stroma and angiogenesis. METHODS: Mice bearing three different xenografted human PDAC (n = 5/group) were treated with neutralizing antibodies to SHH. After treatment for 7 days, tumors were evaluated and the expression of 38 pro- and antiangiogenic factors was assessed in the tumor cells and their stroma. The effect of SHH on the regulation of pro- and antiangiogenic factors in fibroblasts and its impact on endothelial cells was then further assessed in in vitro model systems. RESULTS: Inhibition of SHH affected tumor growth, stromal content, and vascularity. Its effect on the Hh signaling pathway was restricted to the stromal compartment of the three cancers. SHH-stimulated angiogenesis indirectly through the reduction of antiangiogenic THBS2 and TIMP2 in stromal cells. An additional direct effect of SHH on endothelial cells depended on the presence of VEGF. CONCLUSION: Inhibition of Hh signaling reduces tumor vascularity, suggesting that Hh plays a role in the maintenance or formation of the tumor vasculature. Whether the reduction in tumor growth and viability seen in the epithelium is a direct consequence of Hh pathway inhibition, or indirectly caused by its effect on the stroma and vasculature, remains to be evaluated.

Reappraising the Concept of Conditional Survival After Pancreatectomy for Ductal Adenocarcinoma: A Bi-institutional Analysis.

OBJECTIVE: To reappraise the concept of conditional survival (CS) following pancreatectomy for pancreatic ductal adenocarcinoma (PDAC), accounting for the patient's present disease status relative to recurrence. BACKGROUND: CS, defined as the probability of surviving an additional time frame based on accrued lifespan, offers dynamic survival projections as compared with baseline overall survival. METHODS: Patients undergoing pancreatectomy for PDAC at 2 institutions from 2000 to 2013 were retrospectively analyzed. The 12-month CS was estimated separately for patients who were disease-free or with recurrence at the given time points. Next, the conditional probability of reaching 60-months of survival was examined in each conditioning set across strata of prognostic covariates, including American Joint Committee on Cancer stage, tumor grade, R-status, and adjuvant treatment. RESULTS: The study population consisted of 1005 patients. In disease-free patients, the 12-month CS increased as a function of time already survived, showing an opposite trend compared with overall survival. In patients who recurred, the 12-month CS was lower than the disease-free counterpart, especially within 24 months postoperatively. When stratifying by the levels of prognostic covariates, the 60-months CS estimates for disease-free patients tended to level off progressively, indicating that factors independently associated with survival at the time of pancreatectomy lost power over time. This concept did not apply to the conditioning set of patients with recurrence, where CS estimates across variables strata diverged with accrued lifespan. CONCLUSION: This paper provides new information on how prognosis following pancreatectomy for PDAC evolves over time, adjusting for the time the patient already survived, and for the patient's present disease status relative to recurrence.

Timing But Not Patterns of Recurrence Is Different Between Node-negative and Node-positive Resected Pancreatic Cancer.

OBJECTIVE: Our aim was to evaluate recurrence patterns of surgically resected PDAC patients with negative (pN0) or positive (pN1) lymph nodes. SUMMARY BACKGROUND DATA: Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the second leading cause of cancer death by 2030. This is mostly due to early local and distant metastasis, even after surgical resection. Knowledge about patterns of recurrence in different patient populations could offer new therapeutic avenues. METHODS: Clinicopathologic data were collected for 546 patients who underwent resection of their PDAC between 2005 and 2016 from 2 tertiary university centers. Patients were divided into an upfront resection group (n = 394) and a neoadjuvant group (n = 152). RESULTS: Tumor recurrence was significantly less common in pN0 patients as compared with pN1 patients, (upfront surgery: 55% vs. 77%, P < 0.001 and 64% vs. 78%, P = 0.040 in the neoadjuvant group). In addition, time to recurrence was significantly longer in pN0 versus pN1 patients in the upfront resected patients (median 16 mo pN0 vs. 10 mo pN1 P < 0.001), and the neoadjuvant group (pN0 21 mo vs. 11 mo pN1, P < 0.001). Of the patients who recurred, 62% presented with distant metastases (63% of pN0 and 62% of pN1, P = 0.553), 24% with local disease (27% of pN0 and 23% of pN1, P = 0.672) and 14% with synchronous local and distant disease (10% of pN0 and 15% of pN1, P = 0.292). Similarly, there was no difference in recurrence patterns between pN0 and pN1 in the neoadjuvant group, in which 68% recurred with distant metastases (76% of pN0 and 64% of pN1, P = 0.326) and 18% recurred with local disease (pN0: 22% and pN1: 15%, P = 0.435). CONCLUSION: Time to recurrence was significantly longer for pN0 patients. However, patterns of recurrence for pN0 vs. pN1 patients were identical. Lymph node status was predictive of time to recurrence, but not location of recurrence.

Main Pancreatic Duct to Parenchymal Thickness Ratio at Preoperative Imaging is Associated with Overall Survival in Upfront Resected Pancreatic Cancer.

BACKGROUND: Pancreatic cancer induces parenchymal atrophy and duct dilation. The aim of this study was to evaluate whether these radiologic modifications are associated with outcomes. METHODS: Upfront pancreaticoduodenectomy patients with available preoperative contrast enhanced CT scan imaging were retrospectively analyzed. Thickness of the pancreas, size of the main pancreatic duct (MPD), and distance of the tumor from the ampulla were assessed. A training cohort was selected, including short- (3-12 months following surgery) and long-term (≥ 36 months) survivors. Identified survival determinants were validated in the overall cohort. RESULTS: Two-hundred-sixteen patients were analyzed. In the training cohort (N = 118), 68 patients (57.6%) were in the short-term and 50 (42.4%) in the long-term survival group. The short-term survival group had significantly higher CA 19-9 levels (p = 0.027), larger tumors (32.6 ± 12.1 mm vs. 26.5 ± 11.6 mm, p = 0.007), poorer differentiation (p = 0.003), higher rate of R < 1 mm resections (54% vs. 32%, p = 0.008), and reduced receipt of adjuvant chemotherapy (p = 0.020). The MPD-to-pancreatic thickness ratio was significantly lower in the short-term survivors (3.6 ± 6.2 vs. 8.2 ± 12.0, p = 0.016). In the entire cohort, an MPD-to-pancreatic thickness ratio ≥ 3.5 was associated with improved OS [median 33.0 months IQR (19.7-48.1) versus 17 months IQR (14.8-19.2), p = 0.004], and confirmed by a Cox-proportional hazards model independently associated with OS (HR = 0.58; p = 0.009), together with tumor size (HR = 1.02; p =0.012), R1/R2 status (HR = 1.53; p = 0.029), and receipt of adjuvant treatment (HR = 0.61; p = 0.021). CONCLUSIONS: High MPD-to-pancreatic thickness ratio was associated with improved long-term survival in pancreaticoduodenectomy for cancer. Whether these features are related to tumor chronicity, indolent biology, or local growth over metastasis remains to be determined.

Diabetes mellitus is associated with unfavorable pathologic features, increased postoperative mortality, and worse long-term survival in resected pancreatic cancer.

BACKGROUND: The risk of pancreatic ductal adenocarcinoma (PDAC) is increased in patients with diabetes mellitus (DM), particularly in those with new-onset DM. However, the impact of DM on outcomes following pancreatic surgery is not fully understood. We sought to explore the effects of DM on post-resection outcomes in patients undergoing either upfront resection or following neoadjuvant treatment (NAT). METHODS: Resections for PDAC between 2007 and 2016 were identified from a prospectively-maintained database. Data on demographics, pathology, and perioperative outcomes were compared between patients with or without DM. Survival analysis was performed using Kaplan-Meier curves and adjusted for confounders by a Cox-proportional hazards model. RESULTS: 662 patients were identified, of whom 277 (41.8%) had DM. Diabetics were more likely to be male, had higher BMI, and higher ASA-scores. At pathology, DM was associated with larger tumors (30 vs. 26 mm; p = 0.041), higher rates of lymph-node involvement (69% vs. 59%; p = 0.031) and perineural invasion (88% vs. 82%; p = 0.026). Despite having similar rates of complications, diabetics experienced higher 30-day mortality (3.2% vs. 0.8%; p = 0.019). Median overall survival was worse in diabetic patients (18 vs. 34 months; p < 0.001); this effect was more pronounced in patients with NAT (18 vs. 54 months; p < 0.001). At multivariate analysis, DM was confirmed as an independent predictor of post-resection survival. CONCLUSION: DM is a common comorbidity in PDAC and is associated with unfavorable pathology, as well as worse postoperative and oncologic outcomes. The blunted effect on survival is more pronounced in patients who undergo resection following NAT.

Impact of adjuvant therapy in patients with invasive intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND: There is limited data on the efficacy of adjuvant therapy (AT) in patients with invasive intraductal papillary mucinous neoplasms of the pancreas (IPMN). This single center retrospective cohort study aims to assess the impact of AT on survival in these patients. METHODS: Patients undergoing surgery for invasive IPMN between 1993 and 2018 were included in the study. We compared the clinicopathologic features and evaluated overall survival (OS) using multivariate Cox regression adjusting for adjuvant therapy, age, T and N stage, perineural and lymphovascular invasion. We also assessed survival differences between surgery alone and AT in node negative (N0) and node positive (N+) subgroups. RESULTS: 103 patients were included in the study; 69 underwent surgery alone while 34 also received AT. Patients in the AT group were significantly younger, presented at higher T and N stages and had more perineural and lymphovascular invasion. Median OS in the surgery alone group was 134 months and 65 months in the AT group, p = 0.052. On multivariate analysis, AT was not associated with improved OS; hazard ratio (HR) = 1.03 (0.52-2.05). In N0 patients, compared to surgery alone, AT was associated with a worse median OS (65 vs 167 months, p = 0.03), whereas in N+ patients there was a non-significant improvement (50.5 vs 20.4 months, p = 0.315). CONCLUSION: AT did not improve survival in the overall cohort even after multivariate analysis. N0 patients have excellent survival, and AT should probably be avoided in them, whereas it may be considered in patients with N+ disease.

Does preoperative pharmacologic prophylaxis reduce the rate of venous thromboembolism in pancreatectomy patients?

BACKGROUND: Whether the risk of venous thromboembolism (VTE) may be reduced by preoperative administration of prophylactic heparin is unknown. We hypothesized that timing of heparin administration does not significantly alter the incidence of VTE in pancreatic surgery. METHODS: An analysis was conducted using data from Massachusetts General Hospital's National Surgical Quality Improvement Program from 2012 to 2017. All patients admitted for elective pancreatic resection were included. The primary outcome was development of VTE. Multivariable regression was performed, adjusting for patient demographics and various clinical factors. RESULTS: In total, 1448 patients were analyzed, of whom 1062 received preoperative heparin (73.3%). Overall, 36 (2.5%) patients developed VTE. On unadjusted analysis, there was no statistically significant difference between patients who received preoperative heparin compared with those who did not (2.6% vs. 1.3%, respectively; p = 0.079). On adjusted analysis, there was an association with increased VTE rates among patients who received preoperative heparin (OR 2.93, 95% CI 1.10-7.81; p = 0.031). CONCLUSION: There was an association between preoperative heparin administration and increased incidence of VTE on adjusted analysis, possibly reflecting appropriate surgical judgment in patient selection for prophylaxis. These data question the inclusion of preoperative VTE pharmacologic prophylaxis as a reliable quality indicator.