Interplay between B7-H3 and HLA class I in the clinical course of pancreatic ductal adenocarcinoma.

Human leukocyte antigen (HLA) class I defects are associated with cancer progression. However, their prognostic significance is controversial and may be modulated by immune checkpoints. Here, we investigated whether the checkpoint B7-H3 modulates the relationship between HLA class I and pancreatic ductal adenocarcinoma (PDAC) prognosis. PDAC tumors were analyzed for the expression of B7-H3, HLA class I, HLA class II molecules, and for the presence of tumor-infiltrating immune cells. We observed defective HLA class I and HLA class II expressions in 75% and 59% of PDAC samples, respectively. HLA class I and B7-H3 expression were positively related at mRNA and protein level, potentially because of shared regulation by RELA, a sub-unit of NF-kB. High B7-H3 expression and low CD8+ T cell density were indicators of poor survival, while HLA class I was not. Defective HLA class I expression was associated with unfavorable survival only in patients with low B7-H3 expression. Favorable survival was observed only when HLA class I expression was high and B7-H3 expression low. Our results provide the rationale for targeting B7-H3 in patients with PDAC tumors displaying high HLA class I levels.

Recurring Pancreatic Neuroendocrine Tumor: Timing and Pattern of Recurrence and Current Treatment.

OBJECTIVE: The objective of this study was to describe the pattern of recurrence, treatments received, as well the oncological outcomes, of pancreatic neuroendocrine tumors (PanNETs) following curative surgery. BACKGROUND: PanNETs recur in 10% to 15% of cases following surgery. Information on the natural history and management of recurring disease is lacking. MATERIALS AND METHODS: Patients with PanNET that underwent curative surgery at 4 institutions between 2000 and 2019 were identified. Patients with poorly differentiated tumors, unknown tumor grade and differentiation, hereditary syndromes, unknown margin or R2 status, metastatic, and those that had neoadjuvant treatment or perioperative mortality were excluded. Clinical variables were assessed including first site of recurrence, treatment received, and survival outcomes. RESULTS: A total of 1402 patients were included: 957 (74%) had grade 1, 322 (25%) had grade 2, and 13 (1%) had grade 3 tumors. Median follow-up was 4.8 years (interquartile range: 2-8.2 years). Cumulative incidence of recurrence at 5 years was 13% (95% CI: 11%-15.2%) for distant disease, 1.4% (95% CI: 0.8%-2.3%) for locoregional recurrence, and 0.8% (95% CI: 0.4%-1.5%) for abdominal nodal recurrence. Patients who recurred had 2.89 increased risk of death (95% CI: 2-4.1) as compared with patients who did not recur. Therapy postrecurrence included: somatostatin analogs in 111 (61.0%), targeted therapies in 48 (26.4%), liver-directed therapies in 61 (33.5%), peptide receptor radionuclide therapy in 30 (16.5%), and surgery in 46 (25.3%) patients. Multiple treatments were used in 103 (57%) cases. After the first recurrence, 5-year overall survival was 74.6% (95% CI: 67.4%-82.5%). CONCLUSIONS: Recurrence following surgery is infrequent but reduces survival. Most recurrences are distant and managed with multiple therapies. Prospective studies are needed to establish strategies for surveillance and the sequence of treatment to control the disease and prolong survival.

Predicting recurrence in pancreatic neuroendocrine tumours: role of ARX and alternative lengthening of telomeres (ALT).

BACKGROUND: While many pancreatic neuroendocrine tumours (PanNET) show indolent behaviour, predicting the biological behaviour of small nonfunctional PanNETs remains a challenge. Nonfunctional PanNETs with an epigenome and transcriptome that resemble islet alpha cells (ARX-positive) are more aggressive than neoplasms that resemble islet beta cells (PDX1-positive). In this study, we explore the ability of immunohistochemistry for ARX and PDX1 and telomere-specific fluorescence in situ hybridisation (FISH) for alternative lengthening of telomeres (ALT) to predict recurrence. METHODS: Two hundred fifty-six patients with PanNETs were identified, and immunohistochemistry for ARX and PDX1 was performed. Positive staining was defined as strong nuclear staining in >5% of tumour cells. FISH for ALT was performed in a subset of cases. RESULTS: ARX reactivity correlated with worse disease-free survival (DFS) (P = 0.011), while there was no correlation between PDX1 reactivity and DFS (P = 0.52). ALT-positive tumours (n = 63, 31.8%) showed a significantly lower DFS (P < 0.0001) than ALT-negative tumours (n = 135, 68.2%). ARX reactivity correlated with ALT positivity (P < 0.0001). Among nonfunctional tumours, recurrence was noted in 18.5% (30/162) of ARX-positive tumours and 7.5% (5/67) of ARX-negative tumours. Among WHO grade 1 and 2 PanNETs with ≤2 cm tumour size, 14% (6/43) of ARX-positive tumours recurred compared to 0 of 33 ARX-negative tumours and 33.3% (3/9) ALT-positive tumours showed recurrence versus 4.4% (2/45) ALT-negative tumours. CONCLUSION: Immunohistochemistry for ARX and ALT FISH status may aid in distinguishing biologically indolent cases from aggressive small low-grade PanNETs, and help to identify patients who may preferentially benefit from surgical intervention.

Learning Curve of Single-site Robotic Cholecystectomy: A Cumulative Sum Analysis.

BACKGROUND: Minimally invasive surgery has significantly improved cosmesis and clinical outcomes after either laparoscopic or robotic cholecystectomy. In an effort to minimize the number of incisions in multiport procedures, single-site approaches have been developed. However, single-site robotic cholecystectomy (SSRC) can be technically challenging for novice surgeons. The goal of this study is to establish the learning curve (LC) of SSRC through an assessment of operative times and clinical outcomes. MATERIALS AND METHODS: A retrospective analysis of patients undergoing SSRC over a period of 5 years was performed. Consecutive cholecystectomy cases were assessed based on the procedure setting (elective vs. emergent). Cumulative sum analysis were used to establish the LC through an evaluation of the skin-to-skin (STS) time and postoperative complications rate. Afterward, a direct comparison was performed between the established phases. RESULTS: This study included a total of 259 SSRCs with an overall mean STS time of 41.1 minutes. Elective cases took on average of 38.8 minutes, whereas emergent cases spanned over 60.5 minutes ( P= 0.005). The cumulative sum-LC was obtained by summing the differences between each procedure's STS time, revealing a quadratic best-fit line maximum and an inflection point between the early and late phases at case 91. A significant difference between STS time was seen between the early and late phases (53.8 vs. 30.0 min, P< 0.0001). There were no significant differences in terms of postoperative complications between the 2 phases. Incisional hernia rates were comparable between the 2 phases (early: 4.4% vs. late: 2.5%, P< 0.461). CONCLUSIONS: This is the largest study to assess the LC of SSRC through operative time and clinical outcomes. A steady decrease in STS time was observed during the completion of the first 91 consecutive cases.

Closed Incision Negative Pressure Therapy in Oncoplastic Breast Surgery: A Comparison of Outcomes.

We aim to discern the impact of closed incision negative pressure therapy (ciNPT) on wound healing in the oncoplastic breast surgery population. Methods: A retrospective analysis was conducted on patients who underwent oncoplastic breast surgery with and without ciNPT in a single health system over 6 years. Oncoplastic breast surgery was defined as breast conservation surgery involving partial mastectomy with immediate volume displacement or replacement techniques. Primary outcomes were rates of clinically significant complications requiring either medical or operative intervention, including seroma, hematoma, fat necrosis, wound dehiscence, and infection. Secondary outcomes were rates of minor complications. Results: ciNPT was used in 75 patients; standard postsurgical dressing was used in 142 patients. Mean age (P = 0.73) and Charlson Comorbidity Index (P = 0.11) were similar between the groups. The ciNPT cohort had higher baseline BMIs (28.23 ± 4.94 versus 30.55 ± 6.53; P = 0.004), ASA levels (2.35 ± 0.59 versus 2.62 ± 0.52; P = 0.002), and preoperative macromastia symptoms (18.3% versus 45.9%; P ≤ 0.001). The ciNPT cohort had statistically significant lower rates of clinically relevant complications (16.9% versus 5.3%; P = 0.016), the number of complications (14.1% versus 5.3% with one complication, 2.8% versus 0% with >2; P = 0.044), and wound dehiscence (5.6% versus 0%; P = 0.036). Conclusions: The use of ciNPT reduces the overall rate of clinically relevant postoperative complications, including wound dehiscence. The ciNPT cohort had higher rates of macromastia symptoms, BMI, and ASA, all of which put them at increased risk for complications. Therefore, ciNPT should be considered in the oncoplastic population, especially in those patients with increased risk for postoperative complications.

Grading Pancreatic Neuroendocrine Tumors Via Endoscopic Ultrasound-guided Fine Needle Aspiration: A Multi-institutional Study.

OBJECTIVES: To identify factors associated with concordance between World Health Organization (WHO) grade on cytological analysis (c-grade) and histopathological analysis (h-grade) of surgical specimen in patients with PanNETs and examine trends in utilization and accuracy of EUS-FNA in preoperatively predicting grade. BACKGROUND: WHO grading system is prognostic in pancreatic neuroendo-crine tumors (PanNETs). The concordance between c-grade and h-grade is reported to be between 50% and 92%. METHODS: A multicenter retrospective study was performed on patients undergoing resection for PanNETs at four high-volume centers between 2010 and 2019. Patients with functional or syndrome-associated tumors, and those receiving neoadjuvant therapy were excluded. Factors associated with concordance between c-grade and h-grade and trends of utilization of EUS-FNA were assessed. RESULTS: Of 869 patients included, 517 (59.5%) underwent EUS-FNA; 452 (87.4%) were diagnostic of PanNETs and WHO-grade was reported for 270 (59.7%) patients. The concordance between c-grade and h-grade was 80.4% with moderate concordance ( Kc = 0.52, 95% CI: 0.41-0.63). Significantly higher rates of concordance were observed in patients with smaller tumors (<2 vs. ≥2cm, 81.1% vs. 60.4%, P = 0.005). Highest concordance (98.1%) was observed in patients with small tumors undergoing assessment between 2015-2019 with a near-perfect concordance ( Kc = 0.88, 95% CI: 0.61-1.00). An increase in the utilization of EUS-FNA (56.1% to 64.1%) was observed over the last 2 decades ( P = 0.017) and WHO-grade was more frequently reported (44.2% vs. 77.6%, P < 0.001). However, concordance between c-grade and h-grade did not change significantly (P = 0.118). CONCLUSION: Recently, a trend towards increasing utilization and improved diagnostic accuracy of EUS-FNA has been observed in PanNETs. Concordance between c-grade and h-grade is associated with tumor size with near-perfect agreement when assessing PanNETs <2cm in size.

A novel tool to predict nodal metastasis in small pancreatic neuroendocrine tumors: A multicenter study.

BACKGROUND: Nonfunctional pancreatic neuroendocrine tumors display a wide range of biological behavior, and nodal disease is associated with metastatic disease and poorer survival. The aim of this study was to develop a tool to predict nodal disease in patients with small (≤2 cm) nonfunctional pancreatic neuroendocrine tumors. METHODS: A multicenter retrospective study was performed on patients undergoing resection for small nonfunctional pancreatic neuroendocrine tumors. Patients with genetic syndromes, metastatic disease at diagnosis, neoadjuvant therapy, or positive resection margin were excluded. Factors associated with nodal disease were identified to develop a predictive model. Internal validation was performed using bootstrap with 1,000 resamples. RESULTS: Nodal disease was observed in 39 (11.1%) of the 353 patients included. Presence of nodal disease was significantly associated with lower 5-year disease-free survival (71.6% vs 96.2%, P < .001). Two predictors were strongly associated with nodal disease: G2 grade (odds ratio: 3.51, 95% confidence interval: 1.71-7.22, P = .001) and tumor size (per mm increase, odds ratio: 1.14, 95% confidence interval: 1.03-1.25, P = .009). Adequate discrimination was observed with an area under the curve of 0.71 (95% confidence interval: 0.63-0.80). Based on risk distribution, 3 risk groups of nodal disease were identified; low (<5%), intermediate (≥5% to <20%), and high (≥20%) risk. The observed mean risk of nodal disease was 3.7% in the low-risk patients, 9.6% in the intermediate-risk patients, and 30.4% in the high-risk patients (P < .001). The 10-year disease-free survival in the low, intermediate, and high-risk groups was 100%, 88.8%, and 50.1%, respectively. CONCLUSION: Our model using tumor grade and size can predict nodal disease in small nonfunctional pancreatic neuroendocrine tumors. Integration of this tool into clinical practice could help guide management of these patients.

Long-term Outcomes of Parenchyma-sparing and Oncologic Resections in Patients With Nonfunctional Pancreatic Neuroendocrine Tumors <3 cm in a Large Multicenter Cohort.

INTRODUCTION: The role of parenchyma-sparing resections (PSR) and lymph node dissection in small (<3 cm) nonfunctional pancreatic neuroendocrine tumors (PNET) is unlikely to be studied in a prospective randomized clinical trial. By combining data from 4 high-volume pancreatic centers we compared postoperative and long-term outcomes of patients who underwent PSR with patients who underwent oncologic resections. METHODS: Retrospective review of prospectively collected clinicopathologic data of patients who underwent pancreatectomy between 2000 and 2021 was collected from 4 high-volume institutions. PSR and lymph node-sparing resections (enucleation and central pancreatectomy) were compared to those who underwent oncologic resections with lymphadenectomy (pancreaticoduodenectomy, distal pancreatectomy). Statistical testing was performed using χ 2 test and t test, survival estimates with Kaplan-Meier method and multivariate analysis using Cox proportional hazard model. RESULTS: Of 810 patients with small sporadic nonfunctional PNETs, 121 (14.9%) had enucleations, 100 (12.3%) had central pancreatectomies, and 589 (72.7%) patients underwent oncologic resections. The median age was 59 years and 48.2% were female with a median tumor size of 2.5 cm. After case-control matching for tumor size, 221 patients were selected in each group. Patients with PSR were more likely to undergo minimally invasive operations (32.6% vs 13.6%, P <0.001), had less intraoperative blood loss (358 vs 511 ml, P <0.001) and had shorter operative times (180 vs 330 minutes, P <0.001) than patients undergoing oncologic resections. While the mean number of lymph nodes harvested was lower for PSR (n=1.4 vs n=9.9, P <0.001), the mean number of positive lymph nodes was equivalent to oncologic resections (n=1.1 vs n=0.9, P =0.808). Although the rate of all postoperative complications was similar for PSR and oncologic resections (38.5% vs 48.2%, P =0.090), it was higher for central pancreatectomies (38.5% vs 56.6%, P =0.003). Long-term median disease-free survival (190.5 vs 195.2 months, P =0.506) and overall survival (197.9 vs 192.6 months, P =0.372) were comparable. Of the 810 patients 136 (16.7%) had no lymph nodes resected. These patients experienced less blood loss, shorter operations ( P <0.001), and lower postoperative complication rates as compared to patients who had lymphadenectomies (39.7% vs 56.9%, P =0.008). Median disease-free survival (197.1 vs 191.9 months, P =0.837) and overall survival (200 vs 195.1 months, P =0.827) were similar for patients with no lymph nodes resected and patients with negative lymph nodes (N0) after lymphadenectomy. CONCLUSION: In small <3 cm nonfunctional PNETs, PSRs and lymph node-sparing resections are associated with lower blood loss, shorter operative times, and lower complication rates when compared to oncologic resections, and have similar long-term oncologic outcomes.

Association between Preoperative Steroids and Outcomes in Patients Undergoing Pancreaticoduodenectomy using the National Surgical Quality Improvement Program.

BACKGROUND: A national study analyzing the association between preoperative steroid use and outcomes after pancreatic resections is lacking. The purpose of this study is to evaluate the association between preoperative steroids and outcomes after pancreaticoduodenectomy using a national database. MATERIALS AND METHODS: A retrospective analysis of patients undergoing pancreaticoduodenectomy was performed using the National Surgical Quality Improvement Program (NSQIP) database (2014-2019). In addition, we utilized propensity score matching to compare patients on preoperative steroids to those who were not. Outcomes measured included 30-day complications and mortality, need for readmission, a prolonged hospital length of stay, delayed gastric emptying, and pancreatic fistula. RESULTS: After propensity score matching, there were 438 patients in the steroid group and 876 patients in the no steroid group. There was no difference in pancreatic fistula (23.8% vs. 21.7%; p-0.3), delayed gastric emptying (21.1% vs.20.1%; p-0.06), major complications (31.8% vs. 30.1%; p-0.1), and mortality (3.5% vs. 3.2%; p-0.6) between the two groups. CONCLUSION: Glucocorticoids did not reduce the incidence of overall complications, postoperative fistula, and delayed gastric emptying following pancreaticoduodenectomy.

Conflicts of Interest in Studies Related to Mesh Use in Ventral Hernia Repair and Abdominal Wall Reconstruction.

OBJECTIVE: To examine the accuracy of the reporting of conflicts of interest (COI) among studies related to mesh use in ventral hernia repair and abdominal wall reconstruction. SUMMARY BACKGROUND DATA: Accurate declaration of COI is integral to ensuring transparency of study results. Multiple studies have demonstrated undeclared COI are prevalent in surgical literature. METHODS: Studies with at least 1 American author accepted between 2014 and 2018 in 12 major, peer-reviewed general surgery and plastic surgery journals were included. Declared COI were compared with payments listed in the "Open Payments" database [maintained by the Centers for Medicare & Medicaid Services (CMS)] during the year of acceptance and 1 year prior. Studies and authors were considered to have a COI if they received payments from any of 8 major mesh companies totaling >$100.00 from each company. Risk factors for undeclared COI were determined at the study and author levels. RESULTS: One hundred twenty-six studies (553 authors) were included. One hundred two studies (81.0%) had one or more authors who received payments from industry and inaccurately declared their COI. Two hundred forty-eight authors (44.8%) did not declare their COI accurately. On multivariate analysis, last authors were found to be at highest risk for undeclared payments (OR 3.59, 95%CI 2.02-6.20), whereas middle authors were at significantly higher risk for undeclared payments than first authors (OR 1.64, 95%CI 1.04-2.56). CONCLUSIONS: The majority of studies investigating the use of mesh in ventral hernia repairs and abdominal wall reconstructions did not accurately declare COI. Last authors are at highest risk of undisclosed payments. Current policies on disclosing COI seem to be insufficient to ensure transparency of publications.

Arterial involvement and resectability scoring system to predict R0 resection in patients with pancreatic ductal adenocarcinoma treated with neoadjuvant chemoradiation therapy.

OBJECTIVES: To derive a CT-based scoring system incorporating arterial involvement and resectability status to predict R0 resection in patients with pancreatic ductal adenocarcinoma (PDAC) undergoing neoadjuvant chemoradiation therapy (CRT). METHODS: This retrospective study included 112 patients with PDAC who underwent dynamic contrast-enhanced CT before and after neoadjuvant CRT. A 5-point score was used to determine arterial involvement (A score; 1 = no involvement, 2 = haziness, 3 = abutment, 4 = encasement, 5 = deformity) and 4-point score evaluating resectability status (R score; 1 = resectable, 2 = borderline resectable [BR] with venous involvement, 3 = BR with arterial involvement, 4 = locally advanced [LA]). A score before and after CRT were summed with R score before and after CRT to compute the AR score (ARtotal). The associations between ARtotal, R0 resection, overall survival (OS), and disease-free survival (DFS) were assessed. RESULTS: The ARtotal was associated with R0 resection (p < .001) and showed area under the ROC curve of 0.79 for differentiating R0 and R1 resections. Median OS was significantly lower for patients with ARtotal  > 9 (median: 35.2 months) compared to patients with ARtotal ≤ 9 (median: not estimable) (p < .001). Similar results were observed for DFS (median, 16.8 months in > 9 vs median, not estimable in ≤ 9; p < .001). CONCLUSIONS: A composite score which incorporates degree of arterial involvement and resectability status before and after neoadjuvant CRT is associated with R0 resection and discriminates between R0 and R1 resections in PDAC. KEY POINTS: • A scoring system incorporating arterial involvement and resectability status was associated with R0 resection. • ARtotal > 9 could predict patients' overall and disease-free survival.

Discordance in Oncotype DX Breast Recurrence Score® Results for Bilateral Breast Cancer.

BACKGROUND: The Oncotype DX Breast Recurrence Score® assay is a clinically useful tool to determine the benefit of chemotherapy in the treatment of early-stage, hormone-receptor-positive breast cancer. Bilateral breast cancer (BBC) is found in ~ 5% of patients with breast cancer, and data regarding discordance of Oncotype DX results between BBC defined by current TAILORx subgroups are limited. Our goals are to study the rate of Oncotype DX discordance between BBC and investigate whether such differences can affect chemotherapy treatment discussions. METHODS: Patients with BBC were identified in US samples submitted to Genomic Health for 21-gene testing between January 2019 and July 2020. The risk categories were defined as 0-25 and 26-100 as well as 0-17, 18-30, and 31-100 for all patients. Subgroup analysis was also performed for node-negative women age ≤ 50 years with Recurrence Score results of 0-15, 16-20, 21-25, and 26-100. RESULTS: 944 BBC patients with known nodal status (702 node negative, 242 node positive) were identified and included. Among node-negative patients aged > 50 years, the rate of discordance in Recurrence Score by group (0-25 and 26-100) was 4.2% (n = 598). For node-negative patients aged ≤ 50 years, the risk group was discordant in < 3% when considering the risk grouping of 0-25 and 26-100. However, upon subgroup analysis based on TAILORx analysis, the rate of discordance was 48.1% in these younger patients (n = 104). CONCLUSIONS: This study shows that a clinically relevant rate of discordance in Oncotype DX results in patients with BBC may impact medical decision-making regarding chemotherapy.

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.

Cost-Effectiveness Analysis: Lymph Node Transfer vs Lymphovenous Bypass for Breast Cancer-Related Lymphedema.

BACKGROUND: Lymph node transfer (LNT) and lymphovenous bypass (LVB) have been described as 2 major surgical options for patients with breast cancer-related lymphedema (BCRL) who have failed conservative therapy. The objective of our study was to perform a cost-effectiveness analysis comparing LNT and LVB for the treatment of BCRL. STUDY DESIGN: Rates of infection, lymph leak, and failure of LNT and LVB were obtained from a previously published meta-analysis. Failure of surgery was defined as the inability to cease compression therapy postoperatively. Procedural costs were calculated from Medicare reimbursement rates. Cost of conservative management of postoperative surgical site infection, lymph leak, and continued decongestive physiotherapy after failed surgery were obtained from literature review. Average utility scores for each health state were calculated using a visual analog scale survey, then converted to quality-adjusted life years (QALYs). A decision tree was constructed, and incremental cost-effectiveness ratio was assessed at $50,000/QALY. Deterministic and probabilistic sensitivity analyses were performed to evaluate the robustness of our findings. RESULTS: LNT was less costly ($22,492 vs $31,927) and more effective (31.82 QALY vs 29.24 QALY) than LVB. One-way (deterministic) sensitivity analysis demonstrated that LNT became cost-ineffective when its failure rate was more than 43.8%. LVB became more cost-effective than LNT when its failure rate was less than 21.4%. Probabilistic sensitivity analysis using Monte-Carlo simulation indicated that even with uncertainty present in the variables analyzed, the majority of simulations (97%) favored LNT as the more cost-effective strategy. CONCLUSIONS: LNT is a dominant, cost-effective strategy compared to LVB for the treatment of BCRL.

Conditional Survival in Resected Pancreatic Ductal Adenocarcinoma Patients Treated with Total Neoadjuvant Therapy.

BACKGROUND: Dynamic survival data based on time already survived are lacking for resected borderline resectable/locally advanced (BR/LA) pancreatic ductal adenocarcinoma (PDAC) patients who received total neoadjuvant therapy (TNT) with FOLFIRINOX followed by chemoradiation. Conditional survival, i.e., the probability of surviving an additional length of time after having already survived an amount of time, offers such information. We aimed to determine actuarial and conditional overall (OS, COS) and disease-free survival (DFS, CDFS) among this cohort. METHODS: Clinicopathologic data were retrospectively collected for resected BR/LA PDAC patients who received TNT (2011-2019). COS and CDFS rates were calculated for patients being event (death/recurrence)-free at multiple intervals and by recurrence status. RESULTS: After a median follow-up of 32.1 months, the 183 patients had a median OS and DFS of 39.1 months and 16.8 months, respectively. COS and CDFS increased as a function of time already survived. The probability of surviving an additional 24 months if a patient survived 2 years post-operatively was 70%, whereas the 4-year actuarial OS was 47%. Similarly, the probability of surviving disease-free an additional 24 months after 2 years was 66%, while actuarial 48-month DFS was 27%. COS for disease-free patients increased further over time. For patients remaining disease-free 12 months post-operatively, BR vs. LA status at diagnosis, tumor ≤ 4 cm at diagnosis, and R0 resection were independent predictors of favorable additional OS and DFS. CONCLUSIONS: For resected TNT-treated BR/LA PDAC patients, the probability of surviving an additional length of time increases as a function of survival already accrued. Dynamic survival estimates may allow personalized follow-up and counseling.

Intraoperative Radiation Mitigates the Effect of Microscopically Positive Tumor Margins on Survival Among Pancreatic Adenocarcinoma Patients Treated with Neoadjuvant FOLFIRINOX and Chemoradiation.

BACKGROUND: Microscopically positive margins (R1) negatively impact survival in pancreatic ductal adenocarcinoma (PDAC). For patients with close/positive margins, intraoperative radiotherapy (IORT) can improve local control. The prognostic impact of an R1 resection in patients who receive total neoadjuvant therapy (TNT; FOLFIRINOX with chemoradiation) and IORT is unknown. METHODS: Clinicopathologic data were retrospectively collected for borderline/locally advanced (BR/LA) PDAC patients who received TNT and underwent resection between 2011 and 2019. Disease-free (DFS) and overall survival (OS) measured from time of diagnosis were compared between groups. RESULTS: Two hundred one patients received TNT and were resected, with a median DFS and OS of 24 months and 47 months, respectively. Eighty-eight patients (44%) received IORT; of these, 69 (78%) underwent an R0 and 19 (22%) an R1 resection. There was no significant difference in clinicopathologic factors between the IORT and no-IORT groups, except for resectability status (LA: IORT 69%, no-IORT 53%, p = 0.021) and surgeons' concern for a positive/close margin. R1 resection was associated with worse DFS and OS in the no-IORT population. However, among patients who received IORT, there was no difference in DFS (R0: 29 months, IQR 14-47 vs R1: 20 months, IQR 15-28; p = 0.114) or OS (R0: 48 months, IQR 25-not reached vs R1: 37 months, IQR 30-47; p = 0.307) between patients who underwent R0 vs R1 resection. In multivariate analysis, within the IORT group, R1 resection was not associated with DFS or OS. CONCLUSION: IORT may mitigate the adverse effect of an R1 resection on DFS and OS in BR/LA PDAC patients receiving TNT.

Assessment of Conflicts of Interest in Studies of Breast Implants and Breast Implant Mesh.

BACKGROUND: With increased collaboration between surgeons and industry, there has been a push towards improving transparency of conflicts of interest (COI). METHODS: A literature search identified all articles published between 2016 - 2018 involving breast implants/implantable mesh from three major United States plastic surgery journals. Industry payment data from 8 breast implant/implantable mesh companies was collected using the CMS Open Payments database. COI discrepancies were identified by comparing author declaration statements with payments >$100.00 found for the year of publication and year prior. Risk factors for discrepancy were determined at study and author levels. RESULTS: A total of 162 studies (548 authors) were identified. 126 (78%) studies had at least one author receive undisclosed payments. 295 (54%) authors received undisclosed payments. Comparative studies were significantly more likely to have COI discrepancy than non- comparative studies (83% vs 69%, p < 0.05). Multivariate analysis showed no association between COI discrepancy and final product recommendation. Authors who accurately disclosed payments received higher payments compared to authors who did not accurately disclose payments (median $40,349 IQR 7278-190,413 vs median $1300 IQR 429-11,1544, p <0.001). CONCLUSIONS: The majority of breast implant-based studies had undisclosed COIs. Comparative studies were more likely to have COI discrepancy. Authors who accurately disclosed COIs received higher payments than authors with discrepancies. This study highlights the need for increased efforts to improve the transparency of industry sponsorship for breast implant-based studies.