Faculty Bibliography

OBJECTIVE:The purpose of this study is to determine preoperative factors that are predictive of malignancy in patients undergoing pancreatic resection for intraductal papillary mucinous neoplasms (IPMN). SUMMARY BACKGROUND DATA:IPMN of the pancreas may be precursor lesions to pancreatic cancer (PC) and represent a target for early diagnosis or prevention. While there has been much effort to define preoperative risk factors for malignant pathology, guidelines are ever-changing and controversy remains surrounding which patients would benefit most from resection. METHODS:We performed a retrospective analysis of 901 consecutive patients obtained from two tertiary referral centers who underwent pancreatic resection for histologically proven IPMN between 2004 and 2017. Collected data included patient demographic characteristics, preoperative symptoms, radiological findings, and laboratory data. RESULTS:Main pancreatic duct (MPD) dilatation was the only variable that was significantly associated with increased probability of malignancy (defined high-dysplasia or invasion) on both univariate and multivariate analysis. Even middle-range MPD dilatation from 5 mm to 9.9 mm (n = 286) was associated with increased odds of HG-IPMN (OR = 2.74; 95% CI = 1.80-4.16) and invasion (OR = 4.42; 95% CI = 2.55-7.66). MPD dilatation >10 mm (n = 150) had even greater odds of HG-IPMN (OR = 6.57; 95% CI = 3.94-10.98) and invasion (OR = 15.07; 95% CI = 8.21-27.65). A cutoff of 5 to 7 mm MPD diameter was determined to be the best predictor to discriminate between malignant and benign lesions. CONCLUSIONS:In agreement with current IPMN management guidelines, we found MPD dilatation, even low levels from 5 mm to 9.9 mm, to be the single best predictor of HG-IPMN or invasion, highlighting the critical role that MPD plays in the selection of surgical candidates.

BACKGROUND:In pancreatic cancer, extensive tumor involvement of the mesenteric venous system poses formidable challenges to operative resection. Such involvement can result from cavernous collateral veins leading to increased intraoperative blood loss or long-segment vascular defects of not only just the superior mesenteric vein but also even jejunal/ileal branches. Strategies to facilitate margin-free resection and safe vascular reconstruction in pancreatic surgery are important, particularly because systemic control of the tumor is improving with multi-agent chemotherapy regimens. METHODS:We describe a systematic, multidisciplinary assessment for patients with pancreatic cancer that involves the superior mesenteric vein, as well as the preoperative planning of those undergoing operative resection. In addition, detailed descriptions of operative approaches and technical strategies, which evolved with increasing experience at a high-volume center, are presented. RESULTS:For the preoperative evaluation of tumor-free, vascular locations for potential reconstruction and collateralization, computed tomographic imaging with high-resolution of vascular structures (used with 3-dimensional or cinematic rendering) allows a precise calibration of radiographic data with intraoperative findings. From an operative perspective, we identified 5 potential strategies to consider for resection: collateral preservation, mesoportal bypass (preresection), mesoportal interposition graft (postresection), mesocaval shunt, and various combinations of these strategies. Many of these techniques use interposition grafts, making it essential to assess autologous veins (preferred conduit for reconstruction) or to prepare cryopreserved vascular allografts (an alternative conduit, which must be thawed and should be matched for size and blood type). CONCLUSION/CONCLUSIONS:Herein we share operative strategies to overcome involvement of the superior mesenteric vein in pancreatic cancer. Improvements in preoperative planning and operative technique can address common barriers to resection with curative intent.

Importance/UNASSIGNED:In patients who undergo surgery for colorectal cancer liver metastases (CRLM), a number of somatic mutations have been associated with worse overall (OS) and recurrence-free survival (RFS). Although useful, an association with prognosis does not necessarily equate to an impact on surgical management. Objective/UNASSIGNED:The aim of this review was to investigate whether the best-studied somatic mutations impact surgical management of CRLM by informing: (I) post-hepatectomy surveillance; (II) selection of surgical technique; (III) selection of optimal margin width; and (IV) selection of patients for surgery. Lastly, we discuss the refinement of genetic data from overall mutation status to specific variants, as well as lesser studied somatic mutations. Evidence Review/UNASSIGNED:We conducted a computerized search using PubMed and Google Scholar for reports published so far, using mesh headings and keywords related to genetic data and CRLM. Findings/UNASSIGNED:Genetic data may impact surgical management of CRLM in three ways. Firstly, KRAS mutations can predict lung recurrences. Secondly, KRAS mutations may help tailor margin width. Thirdly, KRAS mutations may help tailor surgical technique. Conclusions/UNASSIGNED:Although genetic data may impact post-hepatectomy surveillance, selection of surgical technique and optimal margin width, their use to guide surgical selection remains elusive, as the data cannot support denying surgery to patients according to their somatic mutation profile.

BACKGROUND AND AIMS/OBJECTIVE:Single-cell next-generation sequencing (scNGS) technology has been widely used in genomic profiling, which relies on whole-genome amplification (WGA). However, WGA introduces errors and is especially less accurate when applied to single nucleotide variant (SNV) analysis. Targeted scNGS for SNV without WGA has not been described. We aimed to develop a method to detect circulating tumor cells (CTCs) with DNA SNVs. METHODS:We tested this targeted scNGS method with three driver mutant genes (KRAS/TP53/SMAD4) on one pancreatic cancer cell line AsPC-1 and then applied it to patients with metastatic PDAC for the validation. RESULTS:All single-cell of AsPC-1 and spiked-in AsPC-1 cells in healthy donor blood, which were isolated by the filtration with size or by flow cytometry, were detected by targeted scNGS method. All blood samples from six patients with metastatic PDAC, for the validation of target scNGS method, showed CTCs with SNVs of KRAS/TP53/SMAD4 and the positive confirmation of immunofluorescent stainings with Pan-CK/Vimentin/CD45. Four patients with early stage disease, one patient with benign pancreatic cyst and a healthy control sample all showed concordant results between targeted scNGS and CTC enumeration. CONCLUSIONS:The novel technique of targeted scNGS for SNV analysis, without pre-amplification, is a promising method for identifying and characterizing circulating tumor cells.

PURPOSE/OBJECTIVE:We assessed the feasibility and safety of placing a radiopaque hydrogel in the pancreaticoduodenal groove via endoscopic ultrasound guidance in patients with borderline resectable/locally advanced pancreatic cancer (BR/LAPC). METHODS AND MATERIALS/METHODS:Hydrogel injections were done at time of fiducial placement to form blebs in the pancreaticoduodenal groove. Patients subsequently underwent simulation computed tomography (sim-CT) followed by hypofractionated stereotactic body radiotherapy (SBRT; 33 Gy in 5 fractions). Four to 8 weeks after SBRT, patients underwent CT re-evaluation for surgical candidacy and assessment of hydrogel location and size. Hydrogel placement was considered successful if identified in the pancreaticoduodenal groove on sim-CT scan. Stability was evaluated using equivalence testing analyses, with a null hypothesis of the presence of a ≥20% mean percentage change in volume and ≥2 mm change in the median and mean interbleb surface distance with a P value <.05 required to reject the null hypothesis and conclude equivalence. For patients undergoing pancreaticoduodenectomy, hydrogel sites were histologically examined for location and local inflammatory reactions. RESULTS:Hydrogel placement was successful in 6 of the 6 evaluable patients. The average changes in median and mean interbleb distances were -0.43 mm and -0.35 mm, respectively, with P < .05. The average change in volume from sim-CT to post-SBRT CT was -1.0%, with P < .05. One patient experienced grade 3 nausea after fiducial/hydrogel placement, with no other adverse events to date. CONCLUSIONS:These data demonstrate feasibility and safety of injecting a hydrogel marker in the pancreaticoduodenal groove in patients with BR/LAPC and set the stage for a follow-up clinical trial to place hydrogel as a spacer between the pancreatic tumor and dose-limiting, radiosensitive duodenum.

BACKGROUND:The burden of surgical disease in refugee and internally displaced person (IDP) populations has not been well defined. Populations fleeing conflict are mobile, limiting the effectiveness of traditional sampling methods. We employed novel sampling and survey techniques to conduct a population-based surgical needs assessment amongst IDPs in Kerenik, West Darfur, Sudan, over 4 weeks in 2008. METHODS:Satellite imagery was used to identify man-made structures. Ground teams were guided by GPS to randomly selected households. A newly created surgical needs survey was administered by surgeons to household members. One randomly selected individual answered demographic and medical history questions pertaining to themselves and first-degree blood relatives. All household members were offered a physical examination looking for surgical disease. FINDINGS:There were 780 study participants; 82% were IDPs. A history since displacement of surgical and potentially surgical conditions was reported in 38% of respondents and by 73% of respondents in first-degree blood relatives. Surgical histories included trauma (gunshots, stabbings, assaults) (5% respondents; 27% relatives), burns (6% respondents; 14% relatives), and obstetrical problems (5% female respondents; 11% relatives). 1485 individuals agreed to physical examinations. Untreated surgical and potentially surgical disease was identified in 25% of participants. INTERPRETATION:We identified and characterized a high burden of surgical and potentially surgical disease in an IDP population in West Darfur. Our study is unique in its direct assessment of a traumatized, mobile, vulnerable population. Health officials and agencies charged with the care of IDP and refugee populations should be aware of the high prevalence of surgical and potentially surgical conditions in these communities. This study adds to the growing body of evidence that investment in surgical resources may address a significant portion of the overall burden of disease in marginalized populations.

Background/UNASSIGNED:Prolonged survival of patients after pancreaticoduodenectomy can be associated with late complications due to altered gastrointestinal anatomy. The incidence of gastric cancer is increasingly reported. We set out to examine our experience with gastric cancer as a late complication after pancreaticoduodenectomy with a focus on incidence, risk factors, and outcomes. Methods/UNASSIGNED:We queried our prospectively collected institutional database for patients that developed gastric cancer after pancreaticoduodenectomy and conducted a systematic review of the literature. Results/UNASSIGNED:Our database revealed 6 patients who developed gastric cancer following pancreaticoduodenectomy, presenting with a mean age of 62.2 years and an even sex distribution. All of those patients underwent pancreaticoduodenectomy for malignant indications with an average time to development of metachronous gastric cancer of 8.3 years. Four patients complained of gastrointestinal discomfort prior to diagnosis of secondary malignancy. All of these cancers were poorly differentiated and were discovered at an advanced T stage (≥ 3). Only half developed at the gastrointestinal anastomosis. Four underwent surgery with a curative intent, and 2 patients are currently alive (mean postgastrectomy survival = 25.5 months). In accordance with previous literature, biliopancreatic reflux from pancreaticoduodenectomy reconstruction, underlying genetic susceptibility, and adjuvant therapy may play a causative role in later development of gastric cancer. Conclusion/UNASSIGNED:Long-term survivors after pancreaticoduodenectomy who develop nonspecific gastrointestinal complaints should be evaluated carefully for complications including gastric malignancy. This may serve as an opportunity to intervene on tumors that typically present at an advanced stage and with aggressive histology.

PURPOSE/OBJECTIVE:To study the perioperative CT angiography (CTA) findings of modified Appleby procedure candidates for the surgical feasibility in patients with locally advanced distal pancreatic cancer (LAPC) and to assess CTA performance. MATERIALS AND METHODS/METHODS:This retrospective study evaluated CTA of patients with distal LAPC who underwent modified Appleby procedure between March 2004 and October 2017. Preoperative CT scans performed within up to three months prior to the surgery and postoperative scans, at least one of which was within one month of surgery, were reviewed. Data was collected reporting tumor size, relation to vessels, changes from neoadjuvant chemoradiation, modifications to the surgery and complications. The CTA findings were correlated with operative notes and surgical pathology. Statistical analysis was performed using binary classification method to evaluate CTA performance. RESULTS:Consecutive 20 patients underwent modified Appleby procedure in the study period. In 18/20 patients who received neoadjuvant chemoradiation, mean pancreatic mass size significantly reduced from 4.58 + 1.17 cm to 3.55 + 0.84 cm (p = 0.002). The celiac axis (CA) was encased in all, whereas none of the patients had encasement of the superior mesenteric artery (SMA) or involvement of gastroduodenal artery (GDA). The CTA had 88.89% sensitivity, 100% specificity, and 90% accuracy for evaluating the arterial involvement. CONCLUSION/CONCLUSIONS:Distal LAPC patients, in particular those who have significant size reduction after neoadjuvant chemoradiation, with encasement of CA and without encasement of SMA and GDA can undergo a technically successful modified Appleby procedure. CTA offers accurate and valuable perioperative assessment of the surgical candidates.