Faculty Bibliography
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REDISCOVER International Guidelines on the Perioperative Care of Surgical Patients With Borderline-resectable and Locally Advanced Pancreatic Cancer
OBJECTIVE:The REDISCOVER consensus conference aimed at developing and validating guidelines on the perioperative care of patients with borderline-resectable (BR-) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC). BACKGROUND:Coupled with improvements in chemotherapy and radiation, the contemporary approach to pancreatic surgery supports the resection of BR-PDAC and, to a lesser extent, LA-PDAC. Guidelines outlining the selection and perioperative care for these patients are lacking. METHODS:The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used to develop the REDISCOVER guidelines and create recommendations. The Delphi approach was used to reach a consensus (agreement ≥80%) among experts. Recommendations were approved after a debate and vote among international experts in pancreatic surgery and pancreatic cancer management. A Validation Committee used the AGREE II-GRS tool to assess the methodological quality of the guidelines. Moreover, an independent multidisciplinary advisory group revised the statements to ensure adherence to nonsurgical guidelines. RESULTS:Overall, 34 recommendations were created targeting centralization, training, staging, patient selection for surgery, possibility of surgery in uncommon scenarios, timing of surgery, avoidance of vascular reconstruction, details of vascular resection/reconstruction, arterial divestment, frozen section histology of perivascular tissue, extent of lymphadenectomy, anticoagulation prophylaxis, and role of minimally invasive surgery. The level of evidence was however low for 29 of 34 clinical questions. Participants agreed that the most conducive means to promptly advance our understanding in this field is to establish an international registry addressing this patient population ( https://rediscover.unipi.it/ ). CONCLUSIONS:The REDISCOVER guidelines provide clinical recommendations pertaining to pancreatectomy with vascular resection for patients with BR-PDAC and LA-PDAC, and serve as the basis of a new international registry for this patient population.
PMCID:11161250
PMID: 38407228
ISSN: 1528-1140
CID: 5664592
Bipartite Diameter and Other Measures Under Translation
Let A and B be two sets of points in Rd, where | A| = | B| = n and the distance between them is defined by some bipartite measure dist(A,B). We study several problems in which the goal is to translate the set B, so that dist(A,B) is minimized. The main measures that we consider are (i) the diameter in two and higher dimensions, that is diam(A,B)=max{d(a,b)∣a∈A,b∈B}, where d(a, b) is the Euclidean distance between a and b, (ii) the uniformity in the plane, that is uni(A,B)=diam(A,B)-d(A,B), where d(A,B)=min{d(a,b)∣a∈A,b∈B}, and (iii) the union width in two and three dimensions, that is union_width(A,B)=width(A∪B). For each of these measures, we present efficient algorithms for finding a translation of B that minimizes the distance: For diameter we present near-linear-time algorithms in R2 and R3 and a subquadratic algorithm in Rd for any fixed d≥ 4 , for uniformity we describe a roughly O(n9 / 4) -time algorithm in the plane, and for union width we offer a near-linear-time algorithm in R2 and a quadratic-time one in R3.
SCOPUS:85137816295
ISSN: 0179-5376
CID: 5330602
Predicting Sepsis in Patients with Ureteral Stones in the Emergency Department
BACKGROUND:In the absence of overt infectious signs, clinical criteria for early intervention in patients with ureteral stones are poorly defined. We aimed to develop a model that can identify patients who are at risk for developing sepsis if discharged home from the emergency department (ED). MATERIALS AND METHODS/METHODS:We retrospectively reviewed patients between January 2010 and December 2019 who were discharged from the ED after diagnosis of ureteral stones. The primary outcome was sepsis requiring urgent surgical decompression. We used multivariable logistic regression to identify predictors of sepsis. We refined the model using backwards stepwise regression with a threshold p-value 0.05. RESULTS:We identified 1,331 patients who were discharged from the ED with ureteral stones. Of these patients, 22 (2%) subsequently developed sepsis requiring urgent decompression. In the initial multivariable model, female gender (OR 2.82, p=0.039) and urine white blood cells (WBC) (OR 1.02 per cell count, p<0.001) were predictive of sepsis. After performing backwards stepwise regression, female gender, urine WBC, and leukocytosis (WBC > 15,000/mm3) met criteria for inclusion in the model. A logistic model including these variables predicted sepsis with an internally cross-validated area under the curve of 0.79. Among patients with urine cultures completed in the ED, rates of sepsis were 9% in patients with positive cultures and 1% in patients with negative cultures (p<0.001). Antibiotic usage was not protective against developing sepsis. CONCLUSIONS:Sepsis is a rare complication among patients with ureteral stones selected for conservative management. The presence of elevated urine WBC and female gender can help identify patients who are at risk of developing sepsis. Patients with risk factors should be managed with an increased index of suspicion for infection and may benefit from early intervention to reduce the risk of sepsis. Sepsis is more common in patients with positive urine cultures.
PMID: 35156856
ISSN: 1557-900x
CID: 5175572
Dynamic Approximate Multiplicatively-Weighted Nearest Neighbors
[S.l.] : Schloss Dagstuhl- Leibniz-Zentrum fur Informatik GmbH, Dagstuhl Publishing, 2022
pp. ?-?
ISBN: 9783959772365
CID: 5315922
Intersection Queries for Flat Semi-Algebraic Objects in Three Dimensions and Related Problems
[S.l.] : Schloss Dagstuhl- Leibniz-Zentrum fur Informatik GmbH, Dagstuhl Publishing, 2022
pp. ?-?
ISBN: 9783959772273
CID: 5316582
Management of BPH and LUTS
Cham, Switzerland : Springer, [2021]
pp. 127-152
ISBN: 9783030544812
CID: 5522452
Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes
Most patients diagnosed with resected pancreatic adenocarcinoma (PDAC) survive less than 5 years, but a minor subset survives longer. Here, we dissect the role of the tumor microbiota and the immune system in influencing long-term survival. Using 16S rRNA gene sequencing, we analyzed the tumor microbiome composition in PDAC patients with short-term survival (STS) and long-term survival (LTS). We found higher alpha-diversity in the tumor microbiome of LTS patients and identified an intra-tumoral microbiome signature (Pseudoxanthomonas-Streptomyces-Saccharopolyspora-Bacillus clausii) highly predictive of long-term survivorship in both discovery and validation cohorts. Through human-into-mice fecal microbiota transplantation (FMT) experiments from STS, LTS, or control donors, we were able to differentially modulate the tumor microbiome and affect tumor growth as well as tumor immune infiltration. Our study demonstrates that PDAC microbiome composition, which cross-talks to the gut microbiome, influences the host immune response and natural history of the disease.
PMID: 31398337
ISSN: 1097-4172
CID: 5892992
Circulating Nucleic Acids Are Associated With Outcomes of Patients With Pancreatic Cancer
BACKGROUND & AIMS:We aimed to investigate the clinical utility of circulating tumor cell DNA (ctDNA) and exosome DNA (exoDNA) in pancreatic cancer. METHODS:We collected liquid biopsy samples from 194 patients undergoing treatment for localized or metastatic pancreatic adenocarcinoma from April 7, 2015, through October 13, 2017 (425 blood samples collected before [baseline] and during therapy). Additional liquid biopsy samples were collected from 37 disease control individuals. Droplet digital polymerase chain reaction was used to determine KRAS mutant allele fraction (MAF) from ctDNA and exoDNA purified from plasma. For the longitudinal analysis, we analyzed exoDNA and ctDNA in 123 serial blood samples from 34 patients. We performed analysis including Cox regression, Fisher exact test, and Bayesian inference to associate KRAS MAFs in exoDNA and ctDNA with prognostic and predictive outcomes. RESULTS:In the 34 patients with potentially resectable tumors, an increase in exoDNA level after neoadjuvant therapy was significantly associated with disease progression (P = .003), whereas ctDNA did not show correlations with outcomes. Concordance rates of KRAS mutations present in surgically resected tissue and detected in liquid biopsy samples were greater than 95%. On univariate analysis, patients with metastases and detectable ctDNA at baseline status had significantly shorter times of progression-free survival (PFS) (hazard ratio [HR] for death, 1.8; 95% CI, 1.1-3.0; P = .019), and overall survival (OS) (HR, 2.8; 95% CI, 1.4-5.7; P = .0045) compared with patients without detectable ctDNA. On multivariate analysis, MAFs ≥5% in exoDNA were a significant predictor of PFS (HR, 2.28; 95% CI, 1.18-4.40; P = .014) and OS (HR, 3.46; 95% CI, 1.40-8.50; P = .007). A multianalyte approach showed detection of both ctDNA and exoDNA MAFs ≥5% at baseline status to be a significant predictor of OS (HR, 7.73, 95% CI, 2.61-22.91, P = .00002) on multivariate analysis. In the longitudinal analysis, an MAF peak above 1% in exoDNA was significantly associated with radiologic progression (P = .0003). CONCLUSIONS:In a prospective cohort of pancreatic cancer patients, we show how longitudinal monitoring using liquid biopsy samples through exoDNA and ctDNA provides both predictive and prognostic information relevant to therapeutic stratification.
PMID: 30240661
ISSN: 1528-0012
CID: 5894632
Effect of Malnutrition on Radical Nephroureterectomy Morbidity and Mortality: Opportunity for Preoperative Optimization
INTRODUCTION/BACKGROUND:Nutritional status has been increasingly recognized as an important predictor of prognosis and surgical outcomes for cancer patients. We evaluated the effect of preoperative malnutrition on the development of surgical complications and mortality after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). MATERIALS AND METHODS/METHODS:Using data from the American College of Surgeons National Surgical Quality Improvement Program, we evaluated the association of poor nutritional status with 30-day postoperative complications and overall mortality after RNU from 2005 to 2015. The preoperative variables suggestive of poor nutritional status included hypoalbuminemia (< 3.5 g/dL), weight loss within 6 months before surgery (> 10%), and a low body mass index. RESULTS:A total of 1200 patients were identified who had undergone RNU for UTUC. The overall complication rate was 20.5% (n = 246), and mortality rate was 1.75% (n = 21). On univariate analysis, patients who experienced a postoperative complication were more likely to have hypoalbuminemia (25.0% vs. 11.4%; P < .001) and weight loss (3.7% vs. 1.0%; P = .003). After controlling for baseline characteristics and comorbidities, hypoalbuminemia was found to be a significant independent predictor of postoperative complications (odds ratio, 2.09; 95% confidence interval, 1.29-3.38; P = .003). Hypoalbuminemia was also a significant independent predictor of mortality (odds ratio, 4.31; 95% confidence interval, 1.45-12.79; P = .008) on multivariable regression analysis. CONCLUSION/CONCLUSIONS:Our results have shown that hypoalbuminemia is a significant predictor of surgical complications and mortality after RNU for UTUC. This finding supports the importance of patients' preoperative nutritional status in this population and suggests that effective nutritional interventions in the preoperative setting could improve patient outcomes.
PMID: 29550201
ISSN: 1938-0682
CID: 3001362
Dynamic changes during the treatment of pancreatic cancer
This manuscript follows a single patient with pancreatic adenocarcinoma for a five year period, detailing the clinical record, pathology, the dynamic evolution of molecular and cellular alterations as well as the responses to treatments with chemotherapies, targeted therapies and immunotherapies. DNA and RNA samples from biopsies and blood identified a dynamic set of changes in allelic imbalances and copy number variations in response to therapies. Organoid cultures established from biopsies over time were employed for extensive drug testing to determine if this approach was feasible for treatments. When an unusual drug response was detected, an extensive RNA sequencing analysis was employed to establish novel mechanisms of action of this drug. Organoid cell cultures were employed to identify possible antigens associated with the tumor and the patient's T-cells were expanded against one of these antigens. Similar and identical T-cell receptor sequences were observed in the initial biopsy and the expanded T-cell population. Immunotherapy treatment failed to shrink the tumor, which had undergone an epithelial to mesenchymal transition prior to therapy. A warm autopsy of the metastatic lung tumor permitted an extensive analysis of tumor heterogeneity over five years of treatment and surgery. This detailed analysis of the clinical descriptions, imaging, pathology, molecular and cellular evolution of the tumors, treatments, and responses to chemotherapy, targeted therapies, and immunotherapies, as well as attempts at the development of personalized medical treatments for a single patient should provide a valuable guide to future directions in cancer treatment.
PMCID:5871077
PMID: 29599906
ISSN: 1949-2553
CID: 5894572
