The aim of the study was to identify the survival of patients with locally advanced pancreatic cancer (LAPC) and assess the effect of surgical resection after neoadjuvant therapy on patient outcomes.
...An increasing number of LAPC patients who respond favorably to neoadjuvant therapy undergo surgical resection. The impact of surgery on patient survival is largely unknown.
All LAPC patients who presented to the institutional pancreatic multidisciplinary clinic (PMDC) from January 2013 to September 2017 were included in the study. Demographics and clinical data on neoadjuvant treatment and surgical resection were documented. Primary tumor resection rates after neoadjuvant therapy and overall survival (OS) were the primary study endpoints.
A total of 415 LAPC patients were included in the study. Stratification of neoadjuvant therapy in FOLFIRINOX-based, gemcitabine-based, and combination of the two, and subsequent outcome comparison did not demonstrate significant differences in OS of 331 non-resected LAPC patients (P = 0.134). Eighty-four patients underwent resection of the primary tumor (20%), after a median duration of 5 months of neoadjuvant therapy. FOLFIRINOX-based therapy and stereotactic body radiation therapy correlated with increased probability of resection (P = 0.006). Resected patients had better performance status, smaller median tumor size (P = 0.029), and lower median CA19-9 values (P < 0.001) at PMDC. Patients who underwent surgical resection had significant higher median OS compared with those who did not (35.3 vs 16.3 mo, P < 0.001). The difference remained significant when non-resected patients were matched for time of neoadjuvant therapy (19.9 mo, P < 0.001).
Surgical resection of LAPC after neoadjuvant therapy is feasible in a highly selected cohort of patients (20%) and is associated with significantly longer median overall survival.
To establish an evidence-based cut-off to differentiate between early and late recurrence and to compare clinicopathologic risk factors between the two groups.
A clear definition of "early ...recurrence" after pancreatic ductal adenocarcinoma resection is currently lacking.
Patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma between 2000 and 2013 were included. Exclusion criteria were neoadjuvant therapy and incomplete follow-up. A minimum P-value approach was used to evaluate the optimal cut-off value of recurrence-free survival to divide the patients into early and late recurrence cohorts based on subsequent prognosis. Potential risk factors for early recurrence were assessed with logistic regression models.
Of 957 included patients, 204 (21.3%) were recurrence-free at last follow-up. The optimal length of recurrence-free survival to distinguish between early (n = 388, 51.5%) and late recurrence (n = 365, 48.5%) was 12 months (P < 0.001). Patients with early recurrence had 1-, and 2-year post-recurrence survival rates of 20 and 6% compared with 45 and 22% for the late recurrence group (both P < 0.001). Preoperative risk factors for early recurrence included a Charlson age-comorbidity index ≥4 (OR 1.65), tumor size > 3.0 cm on computed tomography (OR 1.53) and CA 19-9 > 210 U/mL (OR 2.30). Postoperative risk factors consisted of poor tumor differentiation grade (OR 1.66), microscopic lymphovascular invasion (OR 1.70), a lymph node ratio > 0.2 (OR 2.49), and CA 19-9 > 37 U/mL (OR 3.38). Adjuvant chemotherapy (OR 0.28) and chemoradiotherapy (OR 0.29) were associated with a reduced likelihood of early recurrence.
A recurrence-free interval of 12 months is the optimal threshold for differentiating between early and late recurrence, based on subsequent prognosis.
The outcomes of sporadic pancreatic ductal adenocarcinoma (PDAC) patients with germline mutations of BRCA1/BRCA2 remains unclear. The prognostic significance of BRCA1/BRCA2 mutations on survival is ...not well established.
We performed targeted next-generation sequencing (NGS) to identify BRCA1/BRCA2 germline mutations in resected sporadic PDAC cases from 2000 to 2015. Germline BRCA mutation carriers were matched by age and tumor location to those with BRCA1/BRCA2 wild-type genes from our institutional database. Demographics, clinicopathologic features, overall survival (OS), and disease-free survival (DFS) were abstracted from medical records and compared between the 2 cohorts.
Twenty-two patients with sporadic cancer and BRCA1 (n = 4) or BRCA2 (n = 18) germline mutations and 105 wild-type patients were identified for this case-control study. The BRCA1/BRCA2 mutations were associated with inferior median OS (20.2 vs 27.8 months, p = 0.034) and DFS (8.4 vs 16.7 months, p < 0.001) when compared with the matched wild-type controls. On multivariable analyses, a BRCA1/BRCA2 mutation (hazard ratio HR 2.10, p < 0.001), positive margin status (HR 1.72, p = 0.021), and lack of adjuvant therapy (HR 2.38, p < 0.001), were all independently associated with worse survival. Within the BRCA1/BRCA2 mutated group, having had platinum-based adjuvant chemotherapy (n = 10) was associated with better survival than alternative chemotherapy (n = 8) or no adjuvant therapy (n = 4) (31.0 vs 17.8 vs 9.3 months, respectively, p < 0.001).
Carriers of BRCA1/BRCA2 mutation with sporadic PDAC had a worse survival after pancreatectomy than their BRCA wild-type counterparts. However, platinum-based chemotherapy regimens were associated with markedly improved survival in patients with BRCA1/BRCA2 mutations, with survival differences no longer appreciated with wild-type patients.
Coronary stents for treating atherosclerosis are traditionally manufactured from metallic alloys. However, metal stents permanently reside in the body and may trigger undesirable immunological ...responses. Bioresorbable polymer stents can provide a temporary scaffold that resorbs once the artery heals but are mechanically inferior, requiring thicker struts for equivalent radial support, which may increase thrombosis risk. This study addresses the challenge of designing mechanically effective but sufficiently thin poly(L-lactic acid) stents through a computational approach that optimises material properties and stent geometry. Forty parametric stent designs were generated: cross-sectional area (post-dilation), foreshortening, stent-to-artery ratio and radial collapse pressure were evaluated computationally using finite element analysis. Response surface methodology was used to identify performance trade-offs by formulating relationships between design parameters and response variables. Multi-objective optimisation was used to identify suitable stent designs from approximated Pareto fronts and an optimal design is proposed that offers comparable performance to designs in clinical practice. In summary, a computational framework has been developed that has potential application in the design of high stiffness, thin strut polymeric stents.
Surgeon-scientists are an essential component of the field of academic surgery, contributing to the fundamental understanding of disease and the discovery of innovative therapies. Despite this ...recognized value, the current landscape of academic medicine presents significant barriers to establishing and maintaining a successful career as a surgeon performing basic/translational research. Our objective is to define these barriers to academic success for surgeons, and to provide a consensus strategy for optimizing the chances of success.
There is a significant decline in the proportion of academic surgeons who are pursuing basic science/translational research, which represents a potential threat to the very identify of the translational surgeon-scientist.
Based on published literature and expert opinion, the Basic Science Committee of the Society of University of Surgeons prepared this roadmap to encourage and guide the next generation of surgeon-scientists as they embark on their academic careers.
This roadmap highlights key elements to consider in choosing an initial job and the importance of identifying a team of committed mentors. Expectations and guidelines for the first several years in practice are offered.
With guidance and mentorship, aspiring surgeonscientists can overcome the challenges inherent in choosing this career path and sustain the important legacy of those before them.
Background
Proximal gastrectomy (PG) has been excluded from the arsenal of western surgical oncologists for fear of bile reflux and diet intolerance. However, it is often an appropriate, less morbid ...operation for patients requiring resection of a proximal gastric cancer.
Methods
Between 2013 and 2017, we performed 19 PG and 37 total gastrectomies (TGs), of whom 15 and 25 were alive at the time of data collection. In this single-center series, we present findings of a 10-question interview of patients who underwent proximal (n = 8) or TG (n = 16) regarding postgastrectomy food-related symptoms, based on a modified version of the validated Postgastrectomy Syndrome Assessment Scale.
Results
Out of 7 Likert scale questions, there were no statistically significant differences between the groups regarding bile reflux, early satiety, appetite, energy level, physical activity limitations, pain, or general dissatisfaction with their surgery. Patients from both groups reported eating similar amounts of their preoperative volume per meal and overall food volume for the day. Both groups reported eating a similar number of snacks and meals throughout the day. Food satisfaction scores, calculated by summation of the Likert scores, were not different.
Conclusion
Although limited by the small population, we did not find a clinically relevant difference in food-related symptoms comparing PG and TG patients. This pilot study suggests that PG is an appropriate alternative to TG in certain populations. Anecdotal beliefs regarding potential bile reflux or diet intolerance should be reconsidered.
Background
After radical resection of pancreatic ductal adenocarcinoma (PDAC), approximately 80% of patients will develop disease recurrence. It remains unclear to what extent the location of ...recurrence carries prognostic significance. Additionally, stratifying the pattern of recurrence may lead to a deeper understanding of the heterogeneous biological behavior of PDAC.
Objective
The aim of this study was to characterize the relationship of recurrence patterns with survival in patients with resected PDAC.
Methods
This single-center cohort study included patients undergoing pancreatectomy at the Johns Hopkins Hospital between 2000 and 2013. Exclusion criteria were neoadjuvant therapy and incomplete follow-up. Sites of first recurrence were stratified into five groups and survival outcomes were estimated using Kaplan–Meier curves. The association of specific recurrence locations with overall survival (OS) was analyzed using Cox proportional-hazards models with and without landmark analysis.
Results
Accurate follow-up data were available for 877 patients, 662 (75.5%) of whom had documented recurrence at last follow-up. Patients with multiple-site (
n
= 227, 4.7 months) or liver-only recurrence (
n
= 166, 7.2 months) had significantly worse median survival after recurrence when compared with lung- (
n
= 93) or local-only (
n
= 158) recurrence (15.4 and 9.7 months, respectively). On multivariable analysis, the unique recurrence patterns had variable predictive values for OS. Landmark analyses, with landmarks set at 12, 18, and 24 months, confirmed these findings.
Conclusions
This study demonstrates that specific patterns of PDAC recurrence result in different survival outcomes. Furthermore, distinct first recurrence locations have unique independent predictive values for OS, which could help with prognostic stratification and decisions regarding treatment after the diagnosis of recurrence.
The incidence, timing, and implications of recurrence in patients who underwent neoadjuvant treatment and surgical resection of borderline resectable (BRPC) or locally advanced (LAPC) pancreatic ...cancer are not well established.
Patients with BRPC/LAPC who underwent post-neoadjuvant resection between 2007 and 2015 were included. Associations between clinicopathologic characteristics and specific recurrence locations, recurrence-free survival (RFS), and overall survival from resection (OS) were assessed using Cox regression analyses.
For 231 included patients, median survival from diagnosis and resection were 28.0 and 19.8 months, respectively. After a median RFS of 7.9 months, 189 (81.8%) patients had recurred. Multiple-site (n = 87, 46.0%) and liver-only recurrence (n = 28, 14.8%) generally occurred earlier and resulted in significantly worse OS when compared to local-only (n = 52, 27.5%) or lung-only recurrence (n = 18, 9.5%). Microscopic perineural invasion, yN1-yN2 status and elevated pre-surgery CA 19-9 >100 U/mL were associated with both local-only and multiple-site/liver-only recurrence. R1-margin was associated with local-only recurrence (HR 2.03). yN1-yN2 status and microscopic perineural invasion were independent predictors for both poor RFS and OS, while yT3-yT4 tumor stage (HR 1.39) and poor tumor differentiation (HR 1.60) were only predictive of poor OS. Adjuvant therapy was independently associated with both prolonged RFS (HR 0.73; median 7.0 vs. 10.9 months) and OS (HR 0.69; median 15.4 vs. 22.7 months).
Despite neoadjuvant therapy leading to resection and relatively favorable pathologic tumor characteristics in BRPC/LAPC patients, more than 80% of patients experienced disease recurrence, 72.5% of which occurred at distant sites.
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