Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 198
Filtrar
1.
Surg Oncol Clin N Am ; 30(4): 747-758, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34511194

RESUMO

There is increasing interest in the role of minimally invasive surgery (MIS) for pancreatectomy. Prospective data indicate significant advantages for MIS when performed for left-sided pancreatic pathologies and may be deemed as the standard of care. However, there is reluctance in implementing this technique to pancreaticoduodenectomy because of the complexity of the operation and the mixed results from randomized trials. A detailed description of the technical aspects of robotic pancreaticoduodenectomy and distal pancreatectomy is presented in this article in addition to a summary of the most important prospective and cohort studies. We also provide insights into patient selection and the learning curve of MIS surgery for pancreatectomy.

2.
Dis Colon Rectum ; 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34508015

RESUMO

BACKGROUND: Right hemicolectomy is recommended for appendiceal adenocarcinoma but may not be needed for early-stage disease. OBJECTIVE: This study aimed to determine whether appendectomy offers adequate oncologic outcomes for T1 appendiceal adenocarcinoma from a national cohort of patients. DESIGN: Patients with T1 appendiceal adenocarcinoma (mucinous and non-mucinous histology) treated with either a right hemicolectomy or appendectomy between 2004-2016 were retrieved. Multivariate Cox-regression analysis was used to identify predictors of overall survival. SETTING: National cancer database. PATIENTS: A total 320 patients (median age 62yrs, 47% females) were identified: 69 (22%) underwent an appendectomy and 251 (78%) underwent a right hemicolectomy. MAIN OUTCOME MEASURE: Overall survival. RESULTS: Non-mucinous adenocarcinoma was identified in 194 (61%) while 126 (39%) had mucinous adenocarcinoma. Out of the overall cohort, 43% had well differentiated histology, 39% had moderately differentiated disease and 4% had poorly differentiated tumors. The rate of lymph node metastasis was lower in well differentiated tumors (3%) compared to moderately (10%) or poorly differentiated tumors (25%). On univariate survival analysis, right hemicolectomy was associated with improved 1-,3- and 5-year overall survival in patients with moderately/poorly differentiated disease (P<0.001) but not for well differentiated disease (p=1.000). After adjustment, right hemicolectomy was associated with overall survival improvement for moderately/poorly differentiated T1 adenocarcinoma (HR=0.26, 95% CI: 0.08-0.82, p=0.02) but not for well differentiated disease. LIMITATIONS: This study was limited by its retrospective nature. CONCLUSION: The current analysis from the national cancer database demonstrates that appendectomy is associated with equivalent survival to right hemicolectomy for well differentiated T1 adenocarcinoma, while for moderately and poorly differentiated disease, right hemicolectomy is oncologically superior to appendectomy. See Video Abstract at http://links.lww.com/DCR/B689.

3.
Cancer Med ; 10(20): 7233-7241, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34559451

RESUMO

INTRODUCTION: Preoperative autophagy inhibition with hydroxychloroquine (HCQ) in combination with gemcitabine in pancreatic adenocarcinoma (PDAC) has been shown to be safe and effective in inducing a serum biomarker response and increase resection rates in a previous phase I/II clinical trial. We aimed to analyze the long-term outcomes of preoperative HCQ with gemcitabine for this cohort. METHODS: A review of patients enrolled between July 2010 and February 2013 in the completed phase I/II single arm (two doses of fixed-dose gemcitabine (1500 mg/m2 ) in combination with oral hydroxychloroquine administered for 31 consecutive days until the day of surgery for high-risk pancreatic cancer) was undertaken. Progression-free survival (PFS) and overall survival analysis (OS) using Kaplan-Meier estimates were performed. RESULTS: Of 35 patients initially enrolled, 29 patients underwent surgical resection (median age at diagnosis: 62 years, 45% females). Median duration of follow-up was 7.5 years. There was a median 15% decrease in the serum CA19-9 levels following completion of neoadjuvant therapy and 83% of the cohort underwent a pancreaticoduodenectomy, 7 (24%) patients had a concomitant venous resection. On histopathology, 14 (48%) patients had at least a partial treatment response. The median PFS and OS were 11 months (95% Confidence interval [CI]: 7-28) and 31 months (95% CI: 13-47), respectively, while 9 (31%) patients survived beyond 5 years from diagnosis; a rate that compares very favorably with contemporaneous series. CONCLUSION: Compared to historical data, neoadjuvant autophagy inhibition with HCQ plus gemcitabine is associated with encouraging long-term survival for patients with PDAC.

4.
Am J Physiol Gastrointest Liver Physiol ; 321(5): G449-G460, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34523348

RESUMO

Chronic pancreatitis (CP) is a complex inflammatory disorder with numerous associated genetic and environmental risk factors. The most distressing characteristic of CP is recalcitrant pain, often requiring surgical resection including total pancreatectomy with islet autotransplantation (TPIAT). We studied five consented subjects undergoing pancreatic resection and processed isolated cells for single-cell RNA sequencing (scRNA-Seq). Using high-dimensional transcriptomic cluster analysis, we identified 11 unique cell clusters in the pancreas tissue. These cell clusters include a cluster of undifferentiated/dedifferentiated cells and two unique clusters of acinar cells, one of which appears to be in a transitional stage. To determine the cellular response to protease inhibitor and stimulation, we treated aliquots of cells from one subject with a protease inhibitor cocktail with and without bethanechol (a muscarinic receptor agonist) at 100 and 400 µM and compared gene expression profiles. The protease inhibitors appeared to reduce cell stress. Pancreatic digestive enzymes and islet hormones were upregulated in both doses of bethanechol-treated cells compared with naïve cells. High-dose bethanechol appeared to be toxic and consistent with hyperstimulation. These studies demonstrate the feasibility of investigating human acinar cell physiology at the single-cell level and initial evidence that these cells retain responsiveness to agonist stimulation with predicted second messenger and transcriptomic responses.NEW & NOTEWORTHY We conducted single cell RNA sequencing on pancreas tissue from five individuals. We identified eleven unique cell clusters including a large population of dedifferentiated cells as well as two unique clusters of acinar cells, one of which appears to exist in a transitional state. We also examined the cellular response of pancreas tissue to stimulation and identified affected genes and pathways, including pancreatic digestive enzymes.

6.
Ann Surg Oncol ; 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34409541

RESUMO

BACKGROUND: Appendiceal goblet cell adenocarcinomas (GCC) are rare tumors with clinical behavior between classic carcinoids and adenocarcinomas. Current guidelines recommend right hemicolectomy for all GCCs. PATIENTS AND METHODS: The National Cancer Database was retrospectively queried for appendiceal GCCs undergoing appendectomy or right hemicolectomy between 2004 and 2016. Demographics, tumor characteristics, and post-operative outcomes were collected. The primary outcome was overall survival, which was examined by surgical type and tumor T stage. Multivariate logistic regression was utilized to identify predictors of survival. RESULTS: In total, 1083 GCCs were included, and 81.8% underwent right hemicolectomy. Mean age was 57 years, and 89% were White. Patients undergoing hemicolectomy had higher T-stage tumors (66.6%/14.4% T3/T4 vs. 55.8%/8.1%, p < 0.001). Lymph node positivity increased with T stage (1.1%, 2.1%, 9.9%, and 29.1% for T1-T4). GCCs undergoing colectomy were more frequently moderately or poorly differentiated (16.7%/9.0% vs. 12.2%/6.6%, p = 0.011). Appendectomy surgical margins were positive in 17.3% (3.4% hemicolectomy, p < 0.001). In T3/T4 tumors, a significant survival benefit at 5 years was observed in patients undergoing colectomy as compared with appendectomy (85.4% vs. 82.0%, p = 0.028). On multivariate analysis, lymph node positivity markedly decreased survival overall for the entire cohort (HR 7.58, p < 0.001) and for T3/T4 tumors (HR 7.63, p < 0.001). In patients with T3/T4 tumors, there was a trend towards improved survival with right hemicolectomy (HR 0.42, p = 0.068). CONCLUSION: Omitting right hemicolectomy can be considered for select T1/T2 appendiceal GCCs with negative appendectomy margins, given low rates of lymph node metastases and lack of survival benefit with right hemicolectomy.

7.
Surgery ; 2021 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-34433515

RESUMO

BACKGROUND: Intraperitoneal drain placement decreases morbidity and mortality in patients who develop a clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD). It is unknown whether multiple drains mitigate CR-POPF better than a single drain. We hypothesize that multiple drains decrease the complication burden more than a single drain in cases at greater risk for CR-POPF. METHODS: The Fistula Risk Score (FRS), mitigation strategies (including number of drains placed), and clinical outcomes were obtained from a multi-institutional database of PDs performed from 2003 to 2020. Outcomes were compared between cases utilizing 0, 1, or 2 intraperitoneal drains. Multivariable regression analysis was used to evaluate the optimal drainage approach. RESULTS: A total of 4,292 PDs used 0 (7.3%), 1 (45.2%), or 2 (47.5%) drains with an observed CR-POPF rate of 9.6%, which was higher in intermediate/high FRS zone cases compared with negligible/low FRS zone cases (13% vs 2.4%, P < .001). The number of drains placed also correlated with FRS zone (median of 2 in intermediate/high vs 1 in negligible/low risk cases). In intermediate/high risk cases, the use of 2 drains instead of 1 was not associated with a reduced rate of CR-POPF, average complication burden attributed to a CR-POPF, reoperations, or mortality. Obviation of drains was associated with significant increases in complication burden and mortality - regardless of the FRS zone. CONCLUSION: In intermediate/high risk zone cases, placement of a single drain or multiple drains appears to mitigate the complication burden while use of no drains is associated with inferior outcomes.

8.
J Surg Res ; 267: 695-704, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34348185

RESUMO

BACKGROUND: A virtual reality (VR) curriculum performed on the da Vinci Simulation System (DVSS) was previously shown to be effective in training fellows. The dV-Trainer is a separate platform with similar features to the da Vinci console, but its efficacy and utility versus the DVSS simulator are not well known. MATERIALS AND METHODS: A mastery-based VR curriculum was completed by surgical fellows on the DVSS (2014-2016) and on the dV-Trainer (2016-2018) at a large academic center. Pre-test/post-test scores were used to evaluate performance between the two groups. Data was collected prospectively. RESULTS: Forty-six fellows enrolled in the curriculum: surgical oncology (n=31), hepatobiliary (n=5), head/neck (n=4), endocrine (n=2), cardiothoracic (n=2), gynecology (n=1) and transplant surgery (n=1). Twenty-four used the DVSS and twenty-two used the dV-Trainer. Compared to the DVSS, the dV-Trainer was associated with lower scores on 2 of 3 VR modules in the pre-test (P=0.027, P<0.001, respectively) and post-test (P=0.021, P<0.001, respectively). Fellows in the dV-Trainer era scored lower on inanimate drills as well. Average VR curriculum score was lower on the dV-Trainer (71.3% vs 83.34%, P<0.001). dV-Trainer users spent more time completing the pre-test and post-test; however, overall simulator time to complete the curriculum was not significantly different (297 vs 231 minutes, P=0.142). Both groups showed improvement in scores after completion of the VR curriculum. CONCLUSIONS: The dV-Trainer simulator allows for more usability outside the operating room to complete VR modules; however, the DVSS simulator group outperformed the dV-Trainer group on the post-test.

9.
Ann Surg Oncol ; 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34224045

RESUMO

INTRODUCTION: Early recurrence (ER) is a significant challenge for patients with colorectal peritoneal metastases (CRPM) following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS HIPEC). Preoperative risk stratification for ER would improve preoperative decision making. METHODS: We conducted a retrospective study examining patients who underwent CRS HIPEC for CRPM from 2000 to 2018. Optimal definition of ER was determined via minimum p-value approach based on differentiation of post-recurrence survival. Risk factors for ER were assessed in a derivation cohort by uni- and multivariate logistic regression. A predictive score for ER was generated using preoperative variables and validated in an independent cohort. RESULTS: 384 patients were analyzed, 316 (82%) had documented recurrence. Optimal length of post-operative RFS to distinguish ER (n = 144, 46%) vs. late recurrence (LR) (n = 172, 63%) was 8 mos (p<0.01). ER patients had shorter median OS post-CRS-HIPEC (13.6 vs. 39.4 mos, p<0.01). Preoperative BMI (OR 1.88), liver lesions (OR 1.89), progression on chemotherapy (OR 2.14), positive lymph nodes (OR 2.47) and PCI score (16-20: OR 1.7; >20: OR 4.37) were significant predictors of ER (all p<0.05). Using this model, patients were assigned risk scores from 0 to 9. Intermediate (scores 4-6) and high-risk patients (score 7-9) had observed rates of ER of 56% and 79% and overall 2-year survival rates of 27% and 0% respectively. The model showed fair discrimination (AUC 0.72) and good calibration (Hosmer-Lemeshow GOF p = 0.68). CONCLUSIONS: ER predicts markedly worse OS following surgery. Preoperative factors can accurately stratify risk for ER and identify patients in whom CRS-HIPEC for CPRM is futile.

10.
J Gastrointest Surg ; 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34291365

RESUMO

BACKGROUND: Appendiceal adenocarcinoma (AA) represents a heterogenous group of neoplasms with distinct histologic features. The role and efficacy of adjuvant chemotherapy (AC) in non-metastatic disease remain controversial. The aim of this study was to ascertain the role of AC in non-metastatic AA in a national cohort of patients. METHODS: The National Cancer Database (NCDB) was queried to identify patients diagnosed with stage I-III mucinous and nonmucinous AA who underwent right hemicolectomy between 2006 and 2016. Kaplan-Meier and Cox regression analyses were used to evaluate the impact of AC on overall survival (OS) stratified by each pathologic stage. RESULTS: A total of 1433 mucinous and 1954 nonmucinous AA were identified; 578 (40%) and 722 (40%) received AC respectively. In both AC groups, there was a higher proportion of T4 disease, lymph node metastasis, pathologic stage III, and poorly/undifferentiated grade (all P<0.05). On unadjusted analysis, there was no significant association between AC and OS for stage I-III mucinous AA. For nonmucinous AA, AC significantly improved OS only for stage II and III disease. On adjusted analysis, AC was independently associated with an improved OS for stage III nonmucinous AA (HR: 0.61, 95%CI 0.45-0.84, P=0.002), while for mucinous AA, AC was associated with worse outcomes for stage I/II disease (HR: 1.4, 95%CI 1.02-1.91, P=0.038) and had no significant association with OS for stage III disease. CONCLUSION: This current analysis of a national cohort of patients suggests a beneficial role for AC in stage III nonmucinous AA and demonstrates no identifiable benefit for stage I-III mucinous AA.

11.
J Surg Oncol ; 124(5): 801-809, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34231222

RESUMO

INTRODUCTION: Neoadjuvant therapy (NAT) is an emerging strategy for operable pancreatic ductal adenocarcinoma (PDAC). While NAT increases multimodal therapy completion, it risks functional decline and treatment dropout. We used decision analysis to determine optimal management of localized PDAC and consider risks faced by elderly patients. METHODS: A Markov cohort decision analysis model evaluated treatment options for a 60-year-old patient with resectable PDAC: (1) upfront pancreaticoduodenectomy or (2) NAT. One-way and probabilistic sensitivity analyses were performed. A subanalysis considered the scenario of a 75-year-old patient. RESULTS: For the base case, NAT offered an incremental survival gain of 4.6 months compared with SF (overall survival: 26.3 vs. 21.7 months). In one-way sensitivity analyses, findings were sensitive to recurrence-free survival for NAT patients undergoing adjuvant, probability of completing NAT, and probability of being resectable at exploration after NAT. On probabilistic analysis, NAT was favored in a majority of trials (97%) with a median survival benefit of 5.1 months. In altering the base case for the 75-year-old scenario, NAT had a survival benefit of 3.8 months. CONCLUSIONS: This analysis demonstrates a significant benefit to NAT in patients with localized PDAC. This benefit persists even in the elderly cohort.


Assuntos
Adenocarcinoma/terapia , Carcinoma Ductal Pancreático/terapia , Técnicas de Apoio para a Decisão , Cadeias de Markov , Terapia Neoadjuvante/mortalidade , Pancreatectomia/mortalidade , Neoplasias Pancreáticas/terapia , Adenocarcinoma/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/patologia , Terapia Combinada , Seguimentos , Humanos , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
12.
HPB (Oxford) ; 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-34059420

RESUMO

BACKGROUND: Minimally invasive distal pancreatectomy is the accepted standard of care. The robotic distal (RDP) learning curve is 20-40 surgeries with operating time (ORT) as the most significant factor. This study evaluates how formal mentorship and a robotic skills curriculum impact the learning curve for subsequent generation surgeons. METHODS: Consecutive RDP from 2008 to 2017 were evaluated. First Generation was two surgeons who started program without training or mentorship. Second Generation was the two surgeons who joined the program with mentorship. Third Generation was fellows who benefited from both formal training and mentorship. Multivariable models (MVA) were performed for ORT, clinically relevant pancreatic fistula (CR-POPF), and major complications (Clavien≥3). RESULTS: A total of 296 RDP were performed of which 187 did not include other procedures: First Generation (n = 71), Second Generation (n = 50), and Third Generation (n = 66). ORT decreased by generation (p < 0.001) without any differences in CR-POPF or Clavien≥3. On MVA, earlier generation (p = 0.019), pre-operative albumin (p = 0.001) and pancreatic adenocarcinoma (p = 0.019) were predictive of ORT. Increased BMI (p = 0.049) and neoadjuvant therapy (p = 0.046) were predictive of CR-POPF. Fellow participation at the console increased over time. CONCLUSION: Formal mentorship and a skills curriculum decreased the learning curve and complications were largely dependent on patient factors.

13.
J Surg Oncol ; 124(3): 324-333, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33939838

RESUMO

BACKGROUND: Medicaid expansion under the Affordable Care Act has improved access to screening and treatment for certain cancers. It is unclear how this policy has affected the diagnosis and management of pancreatic cancer. METHODS: Using a quasi-experimental difference-in-differences (DID) approach, we analyzed Medicaid and uninsured patients in the National Cancer Data Base during two time periods: pre-expansion (2011-2012) and postexpansion (2015-2016). We investigated changes in cancer staging, treatment decisions, and surgical outcomes. RESULTS: In this national cohort, pancreatic cancer patients in expansion states had increased Medicaid coverage relative to those in nonexpansion states (DID = 17.49, p < 0.01). Medicaid expansion also led to an increase in early-stage diagnoses (Stage I/II, DID = 4.71, p = 0.03), higher comorbidity scores among surgical patients (Charlson/Deyo score 0: DID = -13.69, p = 0.02), a trend toward more neoadjuvant radiation (DID = 6.15, p = 0.06), and more positive margins (DID = 11.69, p = 0.02). There were no differences in rates of surgery, postoperative outcomes, or overall survival. CONCLUSION: Medicaid expansion was associated with improved insurance coverage and earlier stage diagnoses for Medicaid and uninsured pancreatic cancer patients, but similar surgical outcomes and overall survival. These findings highlight both the benefits of Medicaid expansion and the potential limitations of policy change to improve outcomes for such an aggressive malignancy.


Assuntos
Cobertura do Seguro/estatística & dados numéricos , Medicaid/estatística & dados numéricos , Neoplasias Pancreáticas/economia , Neoplasias Pancreáticas/mortalidade , Adulto , Idoso , Estudos de Coortes , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgia , Patient Protection and Affordable Care Act , Sistema de Registros , Estudos Retrospectivos , Estados Unidos/epidemiologia
14.
Surgery ; 170(4): 1195-1204, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33931208

RESUMO

BACKGROUND: The association between intraoperative estimated blood loss and outcomes after pancreatoduodenectomy has, thus far, been rarely explored. METHODS: In total, 7,706 pancreatoduodenectomies performed at 18 international institutions composing the Pancreas Fistula Study Group were examined (2003-2020). High estimated blood loss (>700 mL) was defined as twice the median. Propensity score matching (1:1 exact-match) was employed to adjust for variables associated with high estimated blood loss and clinically relevant pancreatic fistula occurrence. The study was powered to detect a 33% clinically relevant pancreatic fistula increase in the high estimated blood loss group, with α = 0.05 and ß = 0.2. RESULTS: The propensity score model included 966 patients with high estimated blood loss and 966 patients with lower estimated blood loss; all covariate imbalantces were solved. Patients with high estimated blood loss patients experienced higher clinically relevant pancreatic fistula rates (19.4 vs 12.6%, odds ratio 1.66; P < .001), as well as higher severe complication rates (27.8 vs 15.6%), transfusions (50.1 vs 14.3%), reoperations (9.2 vs 4.0%), intensive care unit transfers (9.9 vs 4.8%) and 90-day mortality (4.7 vs 2.0%, all P < .001). High estimated blood loss was an independent predictor for clinically relevant pancreatic fistula (odds ratio 1.78, 95% confidence interval 1.37-2.32), as were prophylactic Octreotide administration (odds ratio 1.95, 95% confidence interval 1.46-2.61) and soft pancreatic texture (odds ratio 5.32, 95% confidence interval 3.74-5.57; all P < .001). Moreover, a second model including 1,126 pancreatoduodenectomies was derived including vascular resections as additional confounder (14.0% vascular resections performed in each group). On multivariable regression, high estimated blood loss was confirmed an independent predictor for clinically relevant pancreatic fistula reduction (odds ratio 1.80, 95% confidence interval 1.32-2.44; P < .001), whereas vascular resection was not (odds ratio 0.64, 95% confidence interval 0.34-1.88; P = .156). CONCLUSION: This study better establishes the relationship between estimated blood loss and outcomes after pancreatoduodenectomy. Despite inherent contributions to blood loss, its minimization is an actionable opportunity for clinically relevant pancreatic fistula reduction and performance optimization in pancreatoduodenectomy. Accordingly, practical insights are offered to achieve this goal.

15.
Ann Surg Oncol ; 28(12): 7759-7769, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34027585

RESUMO

INTRODUCTION: A positive microscopic margin (R1) following resection of pancreatic ductal adenocarcinoma (PDAC) can occur in up to 80% of patients and is associated with reduced survival and increased recurrence. Our aim was to characterize the impact of neoadjuvant therapy (NAT) on survival and recurrence in patients with PDAC following an R1 resection. METHODS: A retrospective analysis of patients with PDAC who underwent pancreatectomy from 2008 to 2017 was performed. Patients were staged according to the American Joint Committee on Cancer 8th edition and stratified based on resection margin (R0 vs. R1) and treatment sequence (NAT vs. surgery first [SF]). Conditional survival analysis was performed using Cox regression and inverse probability weighted estimates. RESULTS: Among 580 patients, 59% received NAT and 41% underwent SF. On final pathology, the NAT cohort had smaller tumors and less lymph node (LN) positivity (p < 0.05). NAT was not associated with an R1 resection (50%, p = 0.653). Compared with the R1 cohort, the R0 cohort had a higher median overall survival (OS; 39.6 vs. 22.8 months; hazard ratio [HR] 1.6, p < 0.001) and disease-free survival (DFS; 19 vs. 13 months; HR 1.35, p = 0.004). After risk adjustment, NAT was not associated with OS, regardless of margin status (R0, 95% confidence interval [CI] (-)7.31-27.07, p = 0.26; or R1, 95% CI (-)36.99-15.25, p = 0.42). However, NAT was associated with improved DFS in the R1 cohort (95% CI 1.79-11.91, p = 0.008) but not in the R0 cohort (95% CI (-)11.22-10.54, p = 0.95). CONCLUSION: An R0 resection remains an important determinant of overall and disease-free survival, even when NAT is administered. For patients with an R1 resection, receipt of NAT may prolong DFS.

16.
Clin Transl Sci ; 14(5): 1822-1829, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34002944

RESUMO

SMAD4, a tumor suppressor gene, is lost in up to 60%-90% of pancreatic adenocarcinomas (PDAs). Loss of SMAD4 allows tumor progression by upregulating autophagy, a cell survival mechanism that counteracts apoptosis and allows intracellular recycling of macromolecules. Hydroxychloroquine (HCQ) is an autophagy inhibitor. We studied whether HCQ treatment in SMAD4 deficient PDA may prevent therapeutic resistance induced by autophagy upregulation. We retrospectively analyzed the SMAD4 status of patients with PDA enrolled in two prospective clinical trials evaluating pre-operative HCQ. The first dose escalation trial demonstrated the safety of preoperative gemcitabine with HCQ (NCT01128296). More recently, a randomized trial of gemcitabine/nab-paclitaxel +/- HCQ evaluated Evans Grade histopathologic response (NCT01978184). The effect of SMAD4 loss on response to HCQ and chemotherapy was studied for association with clinical outcome. Fisher's exact test and log-rank test were used to assess response and survival. Fifty-two patients receiving HCQ with neoadjuvant chemotherapy were studied. Twenty-five patients had SMAD4 loss (48%). 76% of HCQ-treated patients with SMAD4 loss obtained a histopathologic response greater than or equal to 2A, compared with only 37% with SMAD4 intact (p = 0.006). Although loss of SMAD4 has been associated with worse outcomes, in the current study, loss of SMAD4 was not associated with a detriment in median overall survival in HCQ-treated patients (34.43 months in SMAD4 loss vs. 27.27 months in SMAD4 intact, p = 0.18). The addition of HCQ to neoadjuvant chemotherapy in patients with PDA may improve treatment response in those with SMAD4 loss. Further study of the relationship among SMAD4, autophagy, and treatment outcomes in PDA is warranted.

17.
J Immunother ; 44(5): 185-192, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33935273

RESUMO

Despite its increased application in pancreatic ductal adenocarcinoma (PDAC), complete response to neoadjuvant therapy (NAT) is rare. Given the critical role of host immunity in regulating cancer, we sought to correlate baseline inflammatory profiles to significant response to NAT. PDAC patients receiving NAT were classified as responders (R) or nonresponders (NR) by carbohydrate antigen 19-9 response, pathologic tumor size, and lymph node status in the resected specimen. Baseline (treatment-naive) plasma was analyzed to determine levels of 27 inflammatory mediators. Logistic regression was used to correlate individual mediators with response. Network analysis and Pearson correlation maps were derived to determine baseline inflammatory mediator profiles. Forty patients (20R and 20NR) met study criteria. The R showed significantly higher overall survival (59.4 vs. 21.25 mo, P=0.002) and disease-free survival (50.97 vs. 10.60 mo, P=0.005), compared with NR. soluble interleukin-2 receptor alpha was a significant predictor of no response to NAT (P=0.045). Analysis of inflammatory profiles using the Pearson heat map analysis followed by network analysis depicted increased inflammatory network complexity in NR compared with R (1.69 vs. 1), signifying a more robust baseline inflammatory status of NR. A panel of inflammatory mediators identified by logistic regression and Fischer score analysis was used to create a potential decision tree to predict NAT response. We demonstrate that baseline inflammatory profiles are associated with response to NAT in PDAC, and that an upregulated inflammatory status is associated with a poor response to NAT. Further analysis into the role of inflammatory mediators as predictors of chemotherapy response is warranted.

18.
J Laparoendosc Adv Surg Tech A ; 31(5): 561-564, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33989062

RESUMO

The implementation of robotic surgery in the field of hepato-pancreato-biliary (HPB) has been a slow but significant process. HPB procedures offer a unique challenge when for new technologies, as the surgeries themselves are complex, with long learning curves. Yet the benefits of the robotic approach for this patient population are notable: decreased length of stay, blood loss, postoperative complications, and improving quality of life. The use of robotic simulation focused curriculum plays a crucial role in mentoring experienced surgeons and surgical trainees. Although further study remains, early studies suggest a structured simulation curriculum decreases time, technical errors, and improves proficiency, ultimately leading to a more expedited and safe implementation of robotic techniques in the HPB field.


Assuntos
Competência Clínica , Procedimentos Cirúrgicos do Sistema Digestório/educação , Educação de Pós-Graduação em Medicina/métodos , Procedimentos Cirúrgicos Robóticos/educação , Treinamento por Simulação/métodos , Procedimentos Cirúrgicos do Sistema Biliar/educação , Procedimentos Cirúrgicos do Sistema Biliar/métodos , Simulação por Computador , Currículo , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Humanos , Curva de Aprendizado , Fígado/cirurgia , Pâncreas/cirurgia , Estados Unidos
20.
Ann Surg Oncol ; 28(11): 6273-6282, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33791900

RESUMO

INTRODUCTION: To implement a mastery-based robotic surgery curriculum using virtual reality (VR) and inanimate reality (IR) drills at multiple Complex General Surgical Oncology (CGSO) fellowships. PATIENTS AND METHODS: A prospective study of curriculum feasibility and efficacy was conducted at four CGSO fellowship sites. All sites had simulators, and kits were provided to perform 19 biotissue drills. Fellows from three non-UPMC sites (n = 15) in 2016-2018 were compared with fellows from University of Pittsburgh (UPMC; n = 15) where the curriculum was validated in 2014-2018. RESULTS: All fellows completed the pre- and post-test. There was no difference in pre-test scores between UPMC and non-UPMC sites. Only 7 of 15 non-UPMC fellows completed the VR curriculum (47% compliance) compared with all 15 UPMC fellows completing the VR curriculum (100% compliance). UPMC had higher curriculum times (217 versus 93 mins) and % mastery (86% versus 55%). Time spent on curriculum was associated with % mastery (p = 0.01). Both groups showed improvement between pre- and post-test. Post-test VR scores trended higher for UPMC (221 versus 180). Between the non-UPMC sites, there was a difference in compliance (p = 0.03) and % mastery (p = 0.03). Zero non-UPMC fellows performed the biotissue drills, while five contemporary UPMC fellows completed 253 biotissue drills. Approximately 140 UPMC faculty and 300 staff hours were spent on the pilot. CONCLUSIONS: A proficiency curriculum can result in improved robotic console skills. However, multiple barriers to implementation potentially exist, including availability of simulators, availability of a training robot, on-site support staff, and universal buy-in from fellows, faculty, and leadership.


Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Oncologia Cirúrgica , Competência Clínica , Currículo , Humanos , Projetos Piloto , Estudos Prospectivos , Oncologia Cirúrgica/educação
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...