[Show abstract][Hide abstract] ABSTRACT: The clinico-radiological characteristics and the natural history of postoperative omental infarct (OI) in patients who underwent distal pancreatectomy (DP) and splenectomy have not been defined.
Twelve patients who underwent DP over a period of 2 years and were postoperatively diagnosed with OI based on computed tomography (CT) findings were identified.
A total of 12 patients were diagnosed with an OI based on their postoperative imaging. Seven (58.3 %) patients had previously undergone laparoscopic DP, one (8.3 %) had undergone a robotic DP, and in one (8.3 %), a laparoscopic DP was converted to an open procedure. The remaining three (25.1 %) were treated with open DP. In five (41.6 %) patients, the diagnosis of OI was made during routine follow-up. One patient underwent surgical resection of OI, and two had drains placed in the mass. Nine patients were managed conservatively. During the study period, on review of CT imaging, the minimum prevalence of postoperative OI after DP was found to be 22.8 %. A review of literature identified nine articles that reported a total of 34 patients who were diagnosed with OI after abdominal surgery.
The management of an asymptomatic postoperative OI should be conservative while an early invasive intervention should be performed in patients who are symptomatic or have infected OI.
Journal of Gastrointestinal Surgery 08/2015; DOI:10.1007/s11605-015-2920-2 · 2.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the feasibility of genotyping pancreatic tumors via fine needle aspirates (FNAs).
FNA is a common method of diagnosis for pancreatic cancer, yet it has traditionally been considered inadequate for molecular studies due to the limited quantity of DNA derived from FNA specimens and tumor heterogeneity.
In vitro mixing studies were performed to deduce the minimum cellularity needed for genetic analysis. DNA from both simulated FNAs and clinical FNAs was sequenced. Mutational concordance was determined between simulated FNAs and that of the resected specimen.
Limiting dilution studies indicated that mutations present at allele frequencies as low as 0.12% are detectable. Comparison of simulated FNAs and matched tumor tissue exhibited a concordance frequency of 100% for all driver genes present. In FNAs obtained from 17 patients with unresectable disease, we identified at least 1 driver gene mutation in all patients including actionable somatic mutations in ATM and MTOR. The constellation of mutations identified in these patients was different than that reported for resectable pancreatic cancers, implying a biologic basis for presentation with locally advanced pancreatic cancer.
FNA sequencing is feasible and subsets of patients may harbor actionable mutations that could potentially impact therapy. Moreover, preoperative FNA sequencing has the potential to influence the timing of surgery relative to systemic therapy. FNA sequencing opens the door to clinical trials in which patients undergo neoadjuvant or a surgery-first approach based on their tumor genetics with the goal of utilizing cancer genomics in the clinical management of pancreatic cancer.
Annals of surgery 05/2015; DOI:10.1097/SLA.0000000000001156 · 7.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The significance of indeterminate pulmonary nodules (IPNs) in patients undergoing resection of pancreatic ductal adenocarcinoma (PDAC) is unknown. We sought to define the prevalence and impact of IPN in such patients.
We studied all patients who underwent surgical resection of PDAC between 1980 and 2013. IPN was defined as ≥1 well-defined lung nodule(s) less than 3 cm in diameter. Survival was assessed using univariate and multivariate Cox models.
Of the 2306 resected patients, 374 (16.2 %) had a preoperative chest computed tomography (CT) scan. Of these patients, 183 (49 %) had ≥1 IPN. Demographic and clinicopathological characteristics were similar among patients with or without IPN (all P > 0.05). Median survival was comparable among patients who did (15.6 months) or did not (18.0 months) have IPN (P = 0.66). Of the 183 patients with IPN, 29 (16 %) progressed to clinically recognizable metastatic lung disease compared to 13 % without IPN (P = 0.38). The presence of >1 IPN was associated with the development of lung metastasis (relative risk 1.58, 95 % CI 1.03-2.4; P = 0.05). However, lung metastasis was not associated with survival (P = 0.24).
An IPN proved to be a lung metastasis in only one of six patients with PDAC undergoing surgical resection in this study. Survival was not impacted, even among patients who developed lung metastasis. Patients with PDAC who have IPN should not be precluded from surgical consideration.
Journal of Gastrointestinal Surgery 01/2015; 19(5). DOI:10.1007/s11605-014-2740-9 · 2.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background Stereotactic body radiation therapy (SBRT) is a promising option for patients with pancreatic cancer (PCA); however, limited data support its efficacy. This study reviews our institutional experience of SBRT in the treatment of locally advanced (LAPC) and borderline resectable (BRPC) PCA. Methods Charts of all PCA patients receiving SBRT at our institution from 2010 to 2014 were reviewed. Most patients received pre-SBRT chemotherapy. Primary endpoints included overall survival (OS) and local progression-free survival (LPFS). Patients received a total dose of 25–33 Gy in five fractions. Results A total of 88 patients were included in the analysis, 74 with LAPC and 14 with BRPC. The median age at diagnosis was 67.2 years, and median follow-up from date of diagnosis for LAPC and BRPC patients was 14.5 and 10.3 months, respectively. Median OS from date of diagnosis was 18.4 months (LAPC, 14.4 mo; BRPC, 18.4 mo) and median PFS was 9.8 months (95 % CI 8.0–12.3). Acute toxicity was minimal with only three patients (3.4 %) experiencing acute grade ≥3 toxicity. Late grade ≥2 gastrointestinal toxicity was seen in five patients (5.7 %). Of the 19 patients (21.6 %) who underwent surgery, 79 % were LAPC patients and 84 % had margin-negative resections. Conclusions Chemotherapy followed by SBRT in patients with LAPC and BRPC resulted in minimal acute and late toxicity. A large proportion of patients underwent surgical resection despite limited radiographic response to therapy. Further refinements in the integration of chemotherapy, SBRT, and surgery might offer additional advancements toward optimizing patient outcomes.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE. Pancreatic adenocarcinoma is a rapidly progressive malignancy characterized by its tendency for early metastatic spread. MDCT is the primary diagnostic modality for the preoperative staging of patients with pancreatic cancer, with an accuracy established in multiple studies. However, for a variety of reasons, there is often a prolonged interval between staging MDCT and the surgical intervention. This study examines the relationship between the interval between imaging and surgery and the accuracy of MDCT in determining the presence or absence of metastatic disease at surgery in patients with pancreatic cancer. MATERIALS AND METHODS. Patients were identified who had undergone surgery for pancreatic cancer at our institution with a dedicated preoperative pancreas-protocol MDCT performed in our department. Findings from the preoperative MDCT report were correlated with the operative findings, as well as the time between imaging and surgery. RESULTS. Two hundred ninety-two MDCT scans were performed on 256 patients who underwent exploration for pancreatic adenocarcinoma. The patients had a median age of 67 years (range, 30-95 years), and 51.6% (132/256) were male. The median time between MDCT and surgical exploration was 15.5 days (range, 1-198 days). MDCT correctly predicted the absence of metastatic disease at surgery in 233 of 274 (85.0%) studies. MDCT was more accurate in predicting the absence of metastatic disease if the study was performed within 25 days of surgery than it was if the study was performed within more than 25 days of surgery (89.3% vs 77.0%; p = 0.0097). Furthermore, regression models showed that the negative predictive value of a given MDCT significantly decreased after approximately 4 weeks. CONCLUSION. MDCT is an accurate method to stage patients with pancreatic cancer, but its accuracy in excluding distant metastatic disease depreciates over time. Patients should undergo a repeat MDCT within 25 days of any planned definitive operative intervention for pancreatic cancer to avoid unexpectedly finding metastatic disease at surgery.
American Journal of Roentgenology 01/2015; 204(1):W37-42. DOI:10.2214/AJR.13.12439 · 2.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Readmission after pancreatectomy is common, but few data compare patterns of readmission to index and nonindex hospitals.
To evaluate the rate of readmission to index and nonindex institutions following pancreatectomy at a tertiary high-volume institution and to identify patient-level factors predictive of those readmissions.
Retrospective analysis of a prospectively collected institutional database linked to statewide data of patients who underwent pancreatectomy at a tertiary care referral center between January 1, 2005, and December 2, 2010.
The primary outcome was unplanned 30-day readmission to index or nonindex hospitals. Risk factors and reasons for readmission were measured and compared by site using univariable and multivariable analyses.
Among all 623 patients who underwent pancreatectomy during the study period, 134 (21.5%) were readmitted to our institution (105 [78.4%]) or to an outside institution (29 [21.6%]). Fifty-six patients (41.8%) were readmitted because of a gastrointestinal or nutritional problem related to surgery and 42 patients (31.3%) because of a postoperative infection. On multivariable analysis, factors independently associated with readmission included age 65 years or older (odds ratio [OR], 1.80; 95% CI, 1.19-2.71), preexisting liver disease (OR, 2.28; 95% CI, 1.23-4.24), distal pancreatectomy (OR, 1.77; 95% CI, 1.11-2.84), and postoperative drain placement (OR, 2.81; 95% CI, 1.00-7.14).
In total, 21.5% of patients required early readmission after pancreatectomy. Even in the setting of a tertiary care referral center, 21.6% of these readmissions were to nonindex institutions. Specific patient-level factors were associated with an increased risk of readmission.
[Show abstract][Hide abstract] ABSTRACT: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are precursor lesions that progress to invasive cancer through progressively worsening dysplasia. Although smoking is an established risk factor for pancreatic adenocarcinoma, potential associations with IPMN grade of dysplasia remain unclear.
Pancreatic resections for IPMN from 1995 to 2013 were retrospectively reviewed. A total of 446 patients in which the smoking status was documented were identified.
Smoking history was positive in 47 % of patients. Of smokers, 50 % had branch-duct, 14 % had main-duct, and 36 % had mixed-type IPMN. Patients with main-duct IPMN were more commonly smokers (65 %), compared to smoking history in 46 % with mixed and 44 % with branch-duct IPMN (p = 0.03). High-grade dysplasia occurred in 25 % of smokers and 21 % of nonsmokers (p = 0.32), and invasive carcinoma in 25 % of smokers and 25 % nonsmokers (p = 0.95). On multivariate analysis, duct size was independently associated with high-grade dysplasia (OR = 3.17, 95 %CI = 1.79-5.64, p < 0.001). Presence of mural nodules (OR = 3.34, 95 %CI = 1.82-6.12, p < 0.001), duct size (OR = 3.87, 95 %CI = 2.21-6.75, p < 0.001), and symptoms (OR = 7.10, 95 %CI = 3.80-13.08, p < 0.001), but not smoking history (OR = 1.10, 95 %CI = 0.64-1.88, p = 0.73), were independent predictors of invasive carcinoma. Median overall survival was 70 months for smokers and 88 months for nonsmokers (p = 0.68).
Positive smoking history correlated with duct type classification but does not appear to be a risk factor for harboring high-grade dysplasia or invasive carcinoma in IPMNs.
Journal of Gastrointestinal Surgery 12/2014; 19(4). DOI:10.1007/s11605-014-2714-y · 2.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Data on the effect of bile duct injuries (BDI) on health-related quality of life (HRQOL) are not well defined. We sought to assess long-term HRQOL after BDI repair in a large cohort of patients spanning a 23-year period.
Journal of the American College of Surgeons 06/2014; 219(5). DOI:10.1016/j.jamcollsurg.2014.04.024 · 4.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
The impact of postoperative complications on the administration of adjuvant therapy following pancreaticoduodenectomy (PD) for adenocarcinoma is still unclear.
A retrospective review of all patients undergoing PD at our institution between 1995 and 2011 was performed. Clinicopathological data, including Clavien–Dindo complication grade, time to adjuvant therapy (TTA), and survival, were analyzed.
A total of 1,144 patients underwent PD for adenocarcinoma between 1995 and 2011. The overall complication rate was 49.1 % and clinically severe complications (≥IIIb) occurred in 4.2 %. Overall, 621 patients (54.3 %) were known to have received adjuvant therapy. The median TTA was 60 days. Although the presence of a complication was associated with a delay in TTA (p = 0.002), the grade of complication was not (p = 0.112). On multivariate analysis, only age > 68 years (p 9 days (p = 0.002) correlated with no adjuvant therapy. Patients with postoperative complications were more likely to receive single adjuvant chemotherapy or radiation therapy (31.4 %) than were patients without complications (17.1 %; p
[Show abstract][Hide abstract] ABSTRACT: Background: The determination of the primary tumor origin of patients with neuroendocrine tumor liver metastases (NELM) can pose a significant management challenge. Recent studies have shown that the alternative lengthening of telomeres (ALT) is prevalent in some human tumors, including pancreatic neuroendocrine tumors (PanNET), and can be useful in predicting tumor biology. In this study, we aimed to evaluate the utility of ALT as a biomarker in patients with NELM, in particular to predict the site of origin of the metastases.
Methods: Tissue Microarrays (TMAs) were constructed using tumor tissue from NELM patients undergoing liver resection between 1998-2010. These included 43 PanNET and 47 gastrointestinal carcinoid tumors. The TMAs were tested for ALT using telomere-specific fluorescent in-situ hybridization. The association between ALT positivity and clinicopathologic features and long-term outcome was investigated.
Results: ALT was positive (ALT+) in 26 (29%) of the 90 tumors included in the TMAs. PanNET were ALT+ in 56% of cases, compared to only 4% ALT+ among gastrointestinal carcinoid tumors (p<0.001). The specificity of ALT for detecting pancreatic origin was 96% and the positive predictive value 92%, while the sensitivity was 56% and the negative predictive value 70%. Additionally, ALT was associated with the pattern of metastatic disease: ALT+ NELM were more likely to have oligometastases (p=0.001) and less likely to be bilateral in distribution (p=0.05) than were ALT- tumors. Furthermore, ALT+ was associated with improved prognosis in the PanNET patient population.
Conclusions: ALT was found to be a useful biomarker in patients with NELM. This marker may be helpful in guiding therapy by identifying the site of origin in patients in whom the primary site is unknown.
Journal of the American College of Surgeons 04/2014; 218(4). DOI:10.1016/j.jamcollsurg.2014.01.001 · 4.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The development of noninvasive methods to detect and monitor tumors continues to be a major challenge in oncology. We used digital polymerase chain reaction-based technologies to evaluate the ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types. We found that ctDNA was detectable in >75% of patients with advanced pancreatic, ovarian, colorectal, bladder, gastroesophageal, breast, melanoma, hepatocellular, and head and neck cancers, but in less than 50% of primary brain, renal, prostate, or thyroid cancers. In patients with localized tumors, ctDNA was detected in 73, 57, 48, and 50% of patients with colorectal cancer, gastroesophageal cancer, pancreatic cancer, and breast adenocarcinoma, respectively. ctDNA was often present in patients without detectable circulating tumor cells, suggesting that these two biomarkers are distinct entities. In a separate panel of 206 patients with metastatic colorectal cancers, we showed that the sensitivity of ctDNA for detection of clinically relevant KRAS gene mutations was 87.2% and its specificity was 99.2%. Finally, we assessed whether ctDNA could provide clues into the mechanisms underlying resistance to epidermal growth factor receptor blockade in 24 patients who objectively responded to therapy but subsequently relapsed. Twenty-three (96%) of these patients developed one or more mutations in genes involved in the mitogen-activated protein kinase pathway. Together, these data suggest that ctDNA is a broadly applicable, sensitive, and specific biomarker that can be used for a variety of clinical and research purposes in patients with multiple different types of cancer.
Science translational medicine 02/2014; 6(224):224ra24. DOI:10.1126/scitranslmed.3007094 · 14.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patient-specific factors impacting the need for possible perioperative blood transfusions have not been examined in patients undergoing hepatopancreatobiliary (HPB) procedures. We sought to define the overall utilization of blood transfusions for HPB surgery stratified by procedure type, as well as identify patient-level risk factors for transfusion.
Hepatic and pancreatic resections were selected from the 2005-2011 American College of Surgeons National Surgical Quality Improvement Program's public use files. Transfusion utilization, risk factors, temporal trends, and outcomes were assessed using regression models. Missing data were addressed using multiple imputation.
Twenty-six thousand eight hundred twenty-seven patients met the inclusion criteria. There were 16,953 pancreas cases (distal pancreatectomy (31.2 %), pancreaticoduodenectomy (65.8 %), total pancreatectomy (3.0 %)), and 9,874 liver cases (wedge resection (60.0 %), hemi-hepatectomy (30.1 %), trisegmentectomy (9.9 %)). Overall, 25.7 % patients received a perioperative transfusion. Transfusion rates varied by operation type (hepatic wedge resection 18.7 %, lobectomy 31.3 %, trisegmentectomy 39.8 %, distal pancreatectomy 19.8 %, Whipple 28.7 %, total pancreatectomy 43.6 %, p < 0.001). On multivariate analysis, several patient-level factors were strongly associated with the risk of transfusion: preoperative hematocrit <36 % (risk ratios (RR) 1.99, 95 % CI 1.91-2.08), preoperative albumin <3.0 g/dL (RR 1.25, 95 % CI 1.19-1.31), American Society of Anesthesiologists (ASA) class IV (RR 1.24, 95 % CI 1.16-1.33), and anticoagulation/bleeding disorder (RR 1.26, 95 % CI 1.15-1.38) (all p < 0.001). Patients with any one of these high-risk factors had an over twofold increased risk of perioperative transfusion (RR 2.31, 95 % CI 2.21-2.40, p < 0.001).
There are large differences in the incidence of transfusion among patients undergoing HPB procedures. While the type of HPB procedure was associated with the risk of transfusion, patient-level factors-including preoperative hematocrit and albumin, ASA classification, and history of anticoagulation/bleeding disorder-were as important.
Journal of Gastrointestinal Surgery 12/2013; 18(4). DOI:10.1007/s11605-013-2417-9 · 2.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Neoadjuvant therapy increases rates of margin-negative resection of borderline resectable pancreatic ductal adenocarcinoma (BL-PDAC). Criteria for BL-PDAC resection following neoadjuvant chemotherapy and radiation therapy (NCRT) have not been clearly defined.
Fifty consecutive patients with BL-PDAC who received NCRT from 2007 to 2012 were identified. Computed tomography (CT) scans pre- and post-treatment were centrally reviewed.
Twenty-nine patients (58 %) underwent resection following NCRT, while 21 (42 %) remained unresected. Patients selected for and successfully undergoing resection were more likely to have better performance status and absence of the following features on pre- and post-treatment CT: superior mesenteric vein/portal vein encasement, superior mesenteric artery involvement, tumor involvement of two or more vessels, and questionable/overt metastases (all p <0.05). Tumor volume and degree of tumor-vessel involvement did not significantly change in both groups after NCRT (all p > 0.05). The median overall survival was 22.9 months in resected versus 13.0 months in unresected patients (p < 0.001). Of patients undergoing resection, 93 % were margin-negative, 72 % were node-negative, and 54 % demonstrated moderate pathologic response to NCRT.
Apparent radiographic extent of vascular involvement does not change significantly after NCRT. Patients without metastatic disease should be chosen for surgical exploration based on adequate performance status and lack of disease progression.
[Show abstract][Hide abstract] ABSTRACT: To generate a map of local recurrences after pancreaticoduodenectomy (PD) for patients with resectable pancreatic ductal adenocarcinoma (PDA) and to model an adjuvant radiation therapy planning treatment volume (PTV) that encompasses a majority of local recurrences.
Consecutive patients with resectable PDA undergoing PD and 1 or more computed tomography (CT) scans more than 60 days after PD at our institution were reviewed. Patients were divided into 3 groups: no adjuvant treatment (NA), chemotherapy alone (CTA), or chemoradiation (CRT). Cross-sectional scans were centrally reviewed, and local recurrences were plotted to scale with respect to the celiac axis (CA), superior mesenteric artery (SMA), and renal veins on 1 CT scan of a template post-PD patient. An adjuvant clinical treatment volume comprising 90% of local failures based on standard expansions of the CA and SMA was created and simulated on 3 post-PD CT scans to assess the feasibility of this planning approach.
Of the 202 patients in the study, 40 (20%), 34 (17%), and 128 (63%) received NA, CTA, and CRT adjuvant therapy, respectively. The rate of margin-positive resections was greater in CRT patients than in CTA patients (28% vs 9%, P=.023). Local recurrence occurred in 90 of the 202 patients overall (45%) and in 19 (48%), 22 (65%), and 49 (38%) in the NA, CTA, and CRT groups, respectively. Ninety percent of recurrences were within a 3.0-cm right-lateral, 2.0-cm left-lateral, 1.5-cm anterior, 1.0-cm posterior, 1.0-cm superior, and 2.0-cm inferior expansion of the combined CA and SMA contours. Three simulated radiation treatment plans using these expansions with adjustments to avoid nearby structures were created to demonstrate the use of this treatment volume.
Modified PTVs targeting high-risk areas may improve local control while minimizing toxicities, allowing dose escalation with intensity-modulated or stereotactic body radiation therapy.
International journal of radiation oncology, biology, physics 12/2013; 87(5):1007-1015. DOI:10.1016/j.ijrobp.2013.09.005 · 4.18 Impact Factor