Faculty Bibliography

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.

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.

Importance/UNASSIGNED:While laparoscopic pancreaticoduodenectomy (LPD) is being adopted with increasing enthusiasm worldwide, it is still challenging for both technical and anatomical reasons. Currently, there is no consensus on the technical standards for LPD. Objective/UNASSIGNED:The aim of this consensus statement is to guide the continued safe progression and adoption of LPD. Evidence Review/UNASSIGNED:Summit on Minimally Invasive Pancreatico-Biliary Surgery in Wuhan, China. Findings/UNASSIGNED:Twenty-eight international experts from 8 countries constructed the expert panel. Sixteen statements were produced by the members of the expert panel. At least 80% of responders agreed with the majority (80%) of statements. Other than three randomized controlled trials published to date, most evidences were based on level 3 or 4 studies according to the AGREE II-GRS Instrument. Conclusions and Relevance/UNASSIGNED:The Wuhan international expert consensus meeting on LPD has produced a set of clinical practice statements for the safe development and progression of LPD. LPD is currently in its development and exploration stages, as defined by the international IDEAL framework for surgical innovation. More robust randomized controlled trial and registry study are essential to proceed with the assessment of LPD.

OBJECTIVE:PDAC patients who undergo surgical resection and receive effective chemotherapy have the best chance of long-term survival. Unfortunately, we lack predictive biomarkers to guide optimal systemic treatment. Ex-vivo generation of PDO for pharmacotyping may serve as predictive biomarkers in PDAC. The goal of the current study was to demonstrate the clinical feasibility of a PDO-guided precision medicine framework of care. METHODS:PDO cultures were established from surgical specimens and endoscopic biopsies, expanded in Matrigel, and used for high-throughput drug testing (pharmacotyping). Efficacy of standard-of-care chemotherapeutics was assessed by measuring cell viability after drug exposure. RESULTS:A framework for rapid pharmacotyping of PDOs was established across a multi-institutional consortium of academic medical centers. Specimens obtained remotely and shipped to a central biorepository maintain viability and allowed generation of PDOs with 77% success. Early cultures maintain the clonal heterogeneity seen in PDAC with similar phenotypes (cystic-solid). Late cultures exhibit a dominant clone with a pharmacotyping profile similar to early passages. The biomass required for accurate pharmacotyping can be minimized by leveraging a high-throughput technology. Twenty-nine cultures were pharmacotyped to derive a population distribution of chemotherapeutic sensitivity at our center. Pharmacotyping rapidly-expanded PDOs was completed in a median of 48 (range 18-102) days. CONCLUSIONS:Rapid development of PDOs from patients undergoing surgery for PDAC is eminently feasible within the perioperative recovery period, enabling the potential for pharmacotyping to guide postoperative adjuvant chemotherapeutic selection. Studies validating PDOs as a promising predictive biomarker are ongoing.

BACKGROUND:Solid pseudopapillary tumors (SPTs) are rare, benign tumors of the pancreas that present as heterogeneous masses. We sought to evaluate the short- and long-term outcomes of surgical resected SPTs. Patients managed via initial surveillance were compared to those who underwent upfront resection. METHODS:A prospectively maintained institutional database was used to identify patients who underwent surgical resection for a SPT between 1988 and 2018. Data on clinicopathological features and outcomes were collected and analyzed. RESULTS:Seventy-eight patients underwent surgical resection for SPT during the study period. The mean age was 34.0 ± 14.6 years and a majority were female (N = 67, 85.9%) and white (N = 46, 58.9%). Thirty patients (37.9%) were diagnosed incidentally. Imaging-based presumed diagnosis was SPT in 49 patients (62.8%). A majority were located in the body or tail of the pancreas (N = 47, 60.3%), and 48 patients (61.5%) underwent a distal pancreatectomy. The median tumor size was 4.0 cm (IQR, 3.0-6.0), nodal disease was present in three patients (3.9%), and R0 resection was performed in all patients. No difference was observed in clinicopathological features and outcomes between patients who were initially managed via surveillance and those who underwent upfront resection. None of the patients under surveillance had nodal disease or metastasis at the time of resection; however, one of them developed recurrence of disease 95.1 months after resection. At a median follow-up of 36.1 months (IQR, 8.1-62.1), 77 (%) patients were alive and one patient (1.3%) had a recurrence of disease at 95.1 months after resection and subsequently died due to disease. CONCLUSIONS:SPTs are rare pancreatic tumors that are diagnosed most frequently in young females. While a majority are benign and have an indolent course, malignant behavior has been observed. Surgical resection can result in exceptional outcomes.