Education & Certifications
Bachelor of Arts, Carleton College, Biology (2015)
BACKGROUND AND OBJECTIVES: Lack of high-level evidence supporting adjuvant therapy for patients with resected gastroenteropancreatic neuroendocrine tumors (GEP NETs) warrants an evaluation of its non-standard of care use.METHODS: Patients with primary GEP NETs who underwent curative-intent resection at eight institutions between 2000 and 2016 were identified; 91 patients received adjuvant therapy. Recurrence-free survival (RFS) and overall survival (OS) were compared between adjuvant cytotoxic chemotherapy and somatostatin analog cohorts.RESULTS: In resected patients, 33 received cytotoxic chemotherapy, and 58 received somatostatin analogs. Five-year RFS/OS was 49% and 83%, respectively. Cytotoxic chemotherapy RFS/OS was 36% and 61%, respectively, lower than the no therapy cohort (P<.01). RFS with somatostatin analog therapy (compared to none) was lower (P<.01), as was OS (P=.01). On multivariable analysis, adjuvant cytotoxic therapy was negatively associated with RFS but not OS controlling for patient/tumor-specific characteristics (RFS P<.01).CONCLUSIONS: Our data, reflecting the largest reported experience to date, demonstrate that adjuvant therapy for resected GEP NETs is negatively associated with RFS and confers no OS benefit. Selection bias enriching our treatment cohort for individuals with unmeasured high-risk characteristics likely explains some of these results; future studies should focus on patient subsets who may benefit from adjuvant therapy.
View details for DOI 10.1002/jso.25896
View details for PubMedID 32153032
Insurance status predicts access to medical care in the USA. Previous studies have shown uninsured patients with some malignancies have worse outcomes than insured patients. The impact of insurance status on patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is unclear.A retrospective cohort study of adult patients with resected GEP-NETs was performed using the US Neuroendocrine Tumor Study Group (USNETSG) database (2000-2016). Demographic and clinical factors were compared by insurance status. Patients ≥ 65 years were excluded, as these patients are almost universally covered by Medicare. Kaplan-Meier and log-rank analyses were used for survival analysis. Logistic regression was used to assess factors associated with overall survival (OS).The USNETSG database included 2022 patients. Of those, 1425 were aged 18-64 years at index operation and were included in our analysis. Uninsured patients were more likely to have an emergent operation (7.9% versus 2.5%, p = 0.01) and less likely to receive postoperative somatostatin analog therapy (1.6% versus 9.9%, p = 0.03). OS at 1, 5, and 10 years was significantly higher for insured patients (96.3%, 88.2%, and 73.8%, respectively) than uninsured patients (87.7%, 71.9%, and 44.0%, respectively) (p < 0.01). On Cox multivariate regression analysis controlling for T/M stage, tumor grade, ASA class, and income level, being uninsured was independently associated with worse OS [hazard ratio (HR) 2.69, 95% confidence interval (CI) 1.32-5.48, p = 0.006].Insurance status is an independent predictor of survival in patients with GEP-NETs. Our study highlights the importance of access to medical care, disparities related to insurance status, and the need to mitigate these disparities.
View details for DOI 10.1245/s10434-020-08359-z
View details for PubMedID 32219725
The ACS established an online risk calculator to help surgeons make patient-specific estimates of postoperative morbidity and mortality. Our objective was to assess the accuracy of the ACS-NSQIP calculator for estimating risk after curative intent resection for primary GI neuroendocrine tumors (GI-NETs). Adult patients with GI-NET who underwent complete resection from 2000 to 2017 were identified using a multi-institutional database, including data from eight academic medical centers. The ability of the NSQIP calculator to accurately predict a particular outcome was assessed using receiver operating characteristic curves and the area under the curve (AUC). Seven hundred three patients were identified who met inclusion criteria. The most commonly performed procedures were resection of the small intestine with anastomosis (N = 193, 26%) and partial colectomy with anastomosis (N = 136, 18%). The majority of patients were younger than 65 years (N = 482, 37%) and ASA Class III (N = 337, 48%). The most common comorbidities were diabetes (N = 128, 18%) and hypertension (N = 395, 56%). Complications among these patients based on ACS NSQIP definitions included any complication (N = 132, 19%), serious complication (N = 118, 17%), pneumonia (N = 7, 1.0%), cardiac complication (N = 1, 0.01%), SSI (N = 80, 11.4%), UTI (N = 17, 2.4%), venous thromboembolism (N = 18, 2.5%), renal failure (N = 16, 2.3%), return to the operating room (N = 27, 3.8%), discharge to nursing/rehabilitation (N = 22, 3.1%), and 30-day mortality (N = 9, 1.3%). The calculator provided reasonable estimates of risk for pneumonia (AUC = 0.721), cardiac complication (AUC = 0.773), UTI (AUC = 0.716), and discharge to nursing/rehabilitation (AUC = 0.779) and performed poorly (AUC < 0.7) for all other complications Fig. 1). The ACS-NSQIP risk calculator estimates a similar proportion of risk to actual events in patients with GI-NET but has low specificity for identifying the correct patients for many types of complications. The risk calculator may require modification for some patient populations.
View details for PubMedID 31908214
View details for Web of Science ID 000504743000017
View details for Web of Science ID 000482195000029
BACKGROUND: Preoperative factors that reliably predict lymph node (LN) metastases in pancreatic neuroendocrine tumors (PanNETs) are unclear. The number of LNs needed to accurately stage PanNETs has not been defined.METHODS: Patients who underwent curative-intent resection of non-functional PanNETs at eight institutions from 2000 to 2016 were analyzed. Preoperative factors associated with LN metastases were identified. A procedure-specific target for LN retrieval to accurately stage patients was determined.RESULTS: Of 695 patients who underwent resection, 33% of tumors were proximal (head/uncinate) and 67% were distal (neck/body/tail). Twenty-six percent of patients (n=158) had LN-positive disease, which was associated with a worse 5-year recurrence-free survival (RFS; 60% vs. 86%; p<0.001). The increasing number of positive LNs was not associated with worse RFS. Preoperative factors associated with positive LNs included tumor size≥2cm (odds ratio [OR] 6.6; p<0.001), proximal location (OR 2.5; p<0.001), moderate versus well-differentiation (OR 2.1; p=0.006), and Ki-67≥3% (OR 3.1; p<0.001). LN metastases were also present in tumors without these risk factors:<2cm (9%), distal location (19%), well-differentiated (23%), and Ki-67<3% (16%). Median LN retrieval was 13 for pancreatoduodenectomy (PD), but only 9 for distal pancreatectomy (DP). Given that PD routinely includes a complete regional lymphadenectomy, a minimum number of LNs to accurately stage patients was not identified. However, for DP, removal of less than seven LNs failed to discriminate 5-year RFS between LN-positive and LN-negative patients (less than seven LNs: 72% vs. 83%, p=0.198; seven or more LNs: 67% vs. 86%; p=0.002).CONCLUSIONS: Tumor size≥2cm, proximal location, moderate differentiation, and Ki-67≥3% are preoperative factors that predict LN positivity in resected non-functional PanNETs. Given the 9-23% incidence of LN metastases in patients without such risk factors, routine regional lymphadenectomy should be considered. PD inherently includes sufficient LN retrieval, while DP should aim to remove seven or more LNs for accurate staging.
View details for PubMedID 31004295
Goal-directed animal behaviors are typically composed of sequences of motor actions whose order and timing are critical for a successful outcome. Although numerous theoretical models for sequential action generation have been proposed, few have been supported by the identification of control neurons sufficient to elicit a sequence. Here, we identify a pair of descending neurons that coordinate a stereotyped sequence of engagement actions during Drosophila melanogaster male courtship behavior. These actions are initiated sequentially but persist cumulatively, a feature not explained by existing models of sequential behaviors. We find evidence consistent with a ramp-to-threshold mechanism, in which increasing neuronal activity elicits each action independently at successively higher activity thresholds.
View details for DOI 10.1016/j.cub.2018.12.019
View details for Web of Science ID 000457772900018
View details for PubMedID 30661796
Packed red blood cell (PRBC) transfusion has been associated with worse survival in multiple malignancies but its impact on pancreatic neuroendocrine tumors (PNETs) is unknown. The aim of this study was to determine the impact of PRBC transfusion on survival following PNET resection.A retrospective cohort study of PNET patients was performed using the US Neuroendocrine Tumor Study Group database. Demographic and clinical factors were compared. Kaplan-Meier and log-rank analyses were performed. Factors associated with transfusion, overall (OS), recurrence-free (RFS) and progression-free survival (PFS) were assessed by logistic regression.Of 1129 patients with surgically resected PNETs, 156 (13.8%) received perioperative PRBC transfusion. Transfused patients had higher ASA Class, lower preoperative hemoglobin, larger tumors, more nodal involvement, and increased major complications (all p < 0.010). Transfused patients had worse median OS (116 vs 150 months, p < 0.001), worse RFS (83 vs 128 months, p < 0.01) in curatively resected (n = 1047), and worse PFS (11 vs 24 months, p = 0.110) in non-curatively resected (n = 82) patients. On multivariable analysis, transfusion was associated with worse OS (HR 1.80, p = 0.011) when controlling for TNM stage, tumor grade, final resection status, and pre-operative anemia.PRBC transfusion is associated with worse survival for patients undergoing PNET resection.
View details for DOI 10.1016/j.hpb.2019.10.2441
View details for PubMedID 31806388
Topical vancomycin has been demonstrated to be safe and effective for reducing surgical site infections (SSIs) following spine surgery in both adults and children, however, there are no studies of its efficacy in reducing SSIs in craniofacial surgery. The SSIs are one of the most common complications following craniofacial surgery. The complexity of craniofacial procedures, use of grafts and implants, long operative durations and larger surgical wounds all contribute to the heightened risk of SSIs in pediatric craniofacial cases. A retrospective review of all open and endoscopic pediatric craniofacial procedures performed between May 2014 and December 2017 at a single children's hospital was conducted to examine SSI rates between patients receiving topical vancomycin and a historical control group. The treatment group received topical vancomycin irrigation before wound closure. An ad-hoc cost analysis was performed to determine the cost-savings associated with topical vancomycin use. A total of 132 craniofacial procedures were performed during the study period, with 50 cases in the control group and 82 cases in the vancomycin group. Overall, SSI rate was 3.03%. Use of topical vancomycin irrigation led to a significant reduction in SSIs (4/50 SSI or 8.0% in control group vs 0/82 or 0% in vancomycin group, P = 0.04). No adverse events were observed with topical vancomycin use. The potential cost-savings associated with the use of topical vancomycin as SSI prophylaxis in this study was $102,152. Addition of topical vancomycin irrigation as routine surgical infection prophylaxis can be an effective and low-cost method for reducing SSI in pediatric craniofacial surgery.
View details for DOI 10.1097/SCS.0000000000005708
View details for PubMedID 31261326
View details for Web of Science ID 000440565901445
STUDY DESIGN: Retrospective cohort study.OBJECTIVE: To determine if topical vancomycin irrigation reduces the incidence of post-operative surgical site infections following pediatric spinal procedures. Surgical site infections (SSIs) following spinal procedures performed in pediatric patients represent a serious complication. Prophylactic use of topical vancomycin prior to closure has been shown to be effective in reducing incidence of SSIs in adult spinal procedures. Non-instrumented cases make up the majority of spinal procedures in pediatric patients, and the efficacy of prophylactic topical vancomycin in these procedures has not previously been reported.METHODS: This retrospective study reviewed all non-instrumented spinal procedures performed over a period from 05/2014-12/2016 for topical vancomycin use, surgical site infections, and clinical variables associated with SSI. Topical vancomycin was utilized as infection prophylaxis, and applied as a liquid solution within the wound prior to closure.RESULTS: Ninety-five consecutive, non-instrumented, pediatric spinal surgeries were completed between 01/2015 and 12/2016, of which the last 68 utilized topical vancomycin. There was a 11.1% SSI rate in the non-topical vancomycin cohort versus 0% in the topical vancomycin cohort (P=0.005). The number needed to treat was 9. There were no significant differences in risk factors for SSI between cohorts. There were no complications associated topical vancomycin use.CONCLUSIONS: Routine topical vancomycin administration during closure of non-instrumented spinal procedures can be a safe and effective tool for reducing SSIs in the pediatric neurosurgical population.
View details for PubMedID 29955942
View details for PubMedID 29405443
OBJECTIVE Topical antimicrobial compounds are safe and can reduce cost and complications associated with surgical site infections (SSIs). Topical vancomycin has been an effective tool for reducing SSIs following routine neurosurgical procedures in the spine and following adult craniotomies. However, widespread adoption within the pediatric neurosurgical community has not yet occurred, and there are no studies to report on the safety and efficacy of this intervention. The authors present the first institution-wide study of topical vancomycin following open craniotomy in the pediatric population. METHODS In this retrospective study the authors reviewed all open craniotomies performed over a period from 05/2014 to 12/2016 for topical vancomycin use, SSIs, and clinical variables associated with SSI. Topical vancomycin was utilized as an infection prophylaxis and was applied as a liquid solution following replacement of a bone flap or after dural closure when no bone flap was reapplied. RESULTS Overall, 466 consecutive open craniotomies were completed between 05/2014 and 12/2016, of which 43% utilized topical vancomycin. There was a 1.5% SSI rate in the nontopical cohort versus 0% in the topical vancomycin cohort (p = 0.045). The number needed to treat was 66. There were no significant differences in risk factors for SSI between cohorts. There were no complications associated with topical vancomycin use. CONCLUSIONS Routine topical vancomycin administration during closure of open craniotomies can be a safe and effective tool for reducing SSIs in the pediatric neurosurgical population.
View details for PubMedID 30141749
View details for PubMedID 30145186
Accurate preoperative staging helps avert morbidity, mortality, and cost associated with non-therapeutic laparotomy in gastric cancer (GC) patients. Diagnostic staging laparoscopy (DSL) can detect metastases with high sensitivity, but its cost-effectiveness has not been previously studied. We developed a decision analysis model to assess the cost-effectiveness of preoperative DSL in GC workup.Analysis was based on a hypothetical cohort of GC patients in the U.S. for whom initial imaging shows no metastases. The cost-effectiveness of DSL was measured as cost per quality-adjusted life-year (QALY) gained. Drivers of cost-effectiveness were assessed in sensitivity analysis.Preoperative DSL required an investment of $107 012 per QALY. In sensitivity analysis, DSL became cost-effective at a threshold of $100 000/QALY when the probability of occult metastases exceeded 31.5% or when test sensitivity for metastases exceeded 86.3%. The likelihood of cost-effectiveness increased from 46% to 93% when both parameters were set at maximum reported values.The cost-effectiveness of DSL for GC patients is highly dependent on patient and test characteristics, and is more likely when DSL is used selectively where procedure yield is high, such as for locally advanced disease or in detecting peritoneal and superficial versus deep liver lesions.
View details for PubMedID 29205366
The role of amino acid-RNA nucleobase interactions in the evolution of RNA translation and protein-mRNA autoregulation remains an open area of research. We describe the inference of pairwise amino acid-RNA nucleobase interaction preferences using structural data from known RNA-protein complexes. We observed significant matching between an amino acid's nucleobase affinity and corresponding codon content in both the standard genetic code and mitochondrial variants. Furthermore, we showed that knowledge of nucleobase preferences allows statistically significant prediction of protein primary sequence from mRNA using purely physiochemical information. Interestingly, ribosomal primary sequences were more accurately predicted than non-ribosomal sequences, suggesting a potential role for direct amino acid-nucleobase interactions in the genesis of amino acid-based ribosomal components. Finally, we observed matching between amino acid-nucleobase affinities and corresponding mRNA sequences in 35 evolutionarily diverse proteomes. We believe these results have important implications for the study of the evolutionary origins of the genetic code and protein-mRNA cross-regulation.
View details for DOI 10.1038/srep18054
View details for Web of Science ID 000366130500001
View details for PubMedID 26656258
View details for PubMedCentralID PMC4674897
Solid pseudopapillary tumors (SPT) of the pancreas are rare neoplasms predominantly found in females. The tumors are often histologically benign and patient outcomes are correspondingly favorable. This report presents the case of a 21-year-old woman who presented with metachronous metastatic SPT, and details the diagnosis and management of this patient. The patient underwent a distal pancreatectomy for resection of the primary neoplasm with negative margins. A surveillance ultrasound performed at 43 months post-operatively revealed new hepatic lesions; these lesions were surgically resected and pathologically demonstrated to be metastatic SPT of the pancreas. This case report demonstrates the potential for latent metastasis of resected SPT, imaging characteristics of metastatic disease, the need for surveillance of patients following resection of SPT of the pancreas and a review of relevant literature on SPT.
View details for DOI 10.4021/wjon692w
View details for PubMedID 29147356
View details for PubMedCentralID PMC5649928
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