Faculty Bibliography

Pancreatic cancer has a dismal prognosis. A technically perfect surgical operation may still not provide a survival advantage for patients with technically resectable pancreatic cancer. Appropriate selection of patients for surgical resections is an imminent issue. Recent studies have provided an important clue on what serum biomarkers may be used to select out the patients who would unlikely benefit from the surgical resection.

Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded.

BACKGROUND:The widespread use of diagnostic imaging has led to an increase in the incidence and diagnosis of benign liver tumors. The objective of this study was to define the overall use and temporal trends of operative procedures for benign liver tumors using a nationally representative cohort. METHODS:All patients who underwent liver surgery for benign liver tumors between 2000 and 2011 were identified from the Nationwide Inpatient Sample database. Trends in annual volume of liver procedures were analyzed using the average annual percent change (AAPC) assessed by joinpoint analysis. RESULTS:There were 2,489 open (94.5%) and 144 (5.5%) minimally invasive surgical (MIS) procedures. Partial hepatectomy accounted for 43.8% of all cases (n = 1,153). Surgery for patients with benign liver tumors increased from 156 in 2000 to 272 in 2011 (AAPC, 5.8%; 95% CI, 3.2-8.6%). There was decline in the relative use of open operative procedures from 98.1% in 2000 to 92.3% in 2011 (AAPC, -0.4%; 95% CI, -0.7 to -0.1%). In contrast, the proportion of MIS procedures increased from 1.9% in 2000 to 7.7% in 2011 (AAPC, 7.4%; 95% CI, 1.9-13.3%). The median duration of stay among all patients was 5 days (interquartile range, 4-7; 5 days [open] vs 3 days [MIS]; P < .001). Inpatient mortality was 0.6% (n = 15 [open] vs n = 0 [MIS]; P = .43) and did not change during the study period (P > .05). CONCLUSION/CONCLUSIONS:Overall volume of surgical management of benign liver tumors has increased substantially over the past decade. There has been a relative shift away from open procedures toward MIS procedures.

About a third of patients with pancreatic cancer present with locally advanced disease that is not amenable to resection. Because these patients have localized disease, conventional ablative therapies (thermal ablation and cryoablation) have the potential to be beneficial, but their use is inherently limited in the pancreas. These limitations could be overcome by irreversible electroporation-a novel, non-thermal ablative method that is gaining popularity for the treatment of many soft tissue tumors, including those of the pancreas. This review summarizes the status of this technique in the treatment of locally advanced pancreatic cancer. Most of the evidence on efficacy and safety is based on non-randomized prospective series, which show that irreversible electroporation may improve overall survival and pain control in locally advanced pancreatic cancer. As experience with this procedure increases, randomized controlled trials are needed to document its efficacy in locally advanced pancreatic cancer more precisely.

BACKGROUND:Postoperative readmissions have been proposed by Medicare as a quality metric and can impact provider reimbursement. Because readmission after pancreatectomy is common, we sought to identify factors associated with readmission to establish a predictive risk scoring system. STUDY DESIGN/METHODS:A retrospective analysis of 2,360 pancreatectomies performed at 9 high-volume pancreatic centers between 2005 and 2011 was performed. Forty-five factors strongly associated with readmission were identified. To derive and validate a risk scoring system, the population was randomly divided into 2 cohorts in a 4:1 fashion. A multivariable logistic regression model was constructed and scores were assigned based on the relative odds ratio (OR) of each independent predictor. A composite Readmission after Pancreatectomy (RAP) score was generated and then stratified to create risk groups. RESULTS:Overall, 464 (19.7%) patients were readmitted within 90 days. Eight pre- and postoperative factors, including earlier MI (OR = 2.03), American Society of Anesthesiologists class ≥ 3 (OR = 1.34), dementia (OR = 6.22), hemorrhage (OR = 1.81), delayed gastric emptying (OR = 1.78), surgical site infection (OR = 3.31), sepsis (OR = 3.10), and short length of stay (OR = 1.51) were independently predictive of readmission. The 32-point RAP score generated from the derivation cohort was highly predictive of readmission in the validation cohort (area under the receiver operating curve = 0.72). The low-risk (0 to 3), intermediate-risk (4 to 7), and high-risk (>7) groups correlated with 11.7%, 17.5%, and 45.4% observed readmission rates, respectively (p < 0.001). CONCLUSIONS:The RAP score is a novel and clinically useful risk scoring system for readmission after pancreatectomy. Identification of patients with increased risk of readmission using the RAP score will allow efficient resource allocation aimed to attenuate readmission rates. It also has potential to serve as a new metric for comparative research and quality assessment.

BACKGROUND:Pancreatic adenosquamous carcinoma (PASC) accounts for only 1-4% of all exocrine pancreatic cancers and carries a particularly poor prognosis. This retrospective study was performed to determine whether inclusion of a platinum agent as part of adjuvant therapy is associated with improved survival in patients with resected PASC. METHODS:Records of all patients who underwent pancreatic resection at Johns Hopkins Hospital from 1986 to 2012 were reviewed to identify those with PASC. Multivariable Cox proportional hazards modeling was used to assess for significant associations between patient characteristics and survival. RESULTS:In total, 62 patients (1.1%) with resected PASC were identified among 5,627 cases. Median age was 68 [interquartile range (IQR), 57-77] and 44% were female. Multivariate analysis revealed that, among all patients (n=62), the following factors were independently predictive of poor survival: lack of adjuvant therapy [hazard ratio (HR) =3.6; 95% confidence interval (CI), 1.8-7.0; P<0.001], margin-positive resection (HR =3.5; 95% CI, 1.8-6.8; P<0.001), lymph node involvement (HR =3.5; 95% CI, 1.5-8.2; P=0.004), and age (HR =1.0; 95% CI, 1.0-1.1; P=0.035). There were no significant differences between patients who did and did not receive adjuvant therapy following resection (all P>0.05). A second multivariable model included only those patients who received adjuvant therapy (n=39). Lack of inclusion of a platinum agent in the adjuvant regimen (HR =2.4; 95% CI, 1.0-5.8; P=0.040) and larger tumor diameter (HR =1.3; 95% CI, 1.0-1.6; P=0.047) were independent predictors of inferior survival. CONCLUSIONS:Addition of a platinum agent to adjuvant regimens for resected PASC may improve survival among these high-risk patients, though collaborative prospective investigation is needed.

BACKGROUND:While sarcopenia is typically defined using total psoas area (TPA), characterizing sarcopenia using only a single axial cross-sectional image may be inadequate. We sought to evaluate total psoas volume (TPV) as a new tool to define sarcopenia and compare patient outcomes relative to TPA and TPV. METHOD/METHODS:Sarcopenia was assessed in 763 patients who underwent pancreatectomy for pancreatic adenocarcinoma between 1996 and 2014. It was defined as the TPA and TPV in the lowest sex-specific quartile. The impact of sarcopenia defined by TPA and TPV on overall morbidity and mortality was assessed using multivariable analysis. RESULT/RESULTS:Median TPA and TPV were both lower in women versus men (both P < 0.001). TPA identified 192 (25.1%) patients as sarcopenic, while TPV identified 152 patients (19.9%). Three hundred sixty-nine (48.4%) patients experienced a postoperative complication. While TPA-sarcopenia was not associated with higher risk of postoperative complications (OR 1.06; P = 0.72), sarcopenia defined by TPV was associated with morbidity (OR 1.79; P = 0.002). On multivariable analysis, TPV-sarcopenia remained independently associated with an increased risk of postoperative complications (OR 1.69; P = 0.006), as well as long-term survival (HR 1.46; P = 0.006). CONCLUSION/CONCLUSIONS:The use of TPV to define sarcopenia was associated with both short- and long-term outcomes following resection of pancreatic cancer. Assessment of the entire volume of the psoas muscle (TPV) may be a better means to define sarcopenia rather than a single axial image.

OBJECTIVE:Vascular reconstruction can facilitate pancreas tumor resection, but optimal methods of reconstruction are not well studied. We report our results for portal vein reconstruction (PVR) for pancreatic resection and determinants of postoperative patency. METHODS:We identified 173 patients with PVR in a prospective database of 6522 patients who underwent pancreatic resection at our hospital from 1970 to 2014. There were 128 patients who had >1 year of follow-up with computed tomography imaging. Preoperative, intraoperative, and postoperative factors were recorded. Patients with and without postoperative PVR thrombosis were compared by univariable, multivariable, and receiver operating characteristic curve analyses. RESULTS:The survival of patients was 100% at 1 month, 88% at 6 months, 66% at 1 year, and 39% on overall median follow-up of 310 days (interquartile range, 417 days). Median survival was 15.5 months (interquartile range, 25 months); 86% of resections were for cancer. Four types of PVR techniques were used: 83% of PVRs were performed by primary repair, 8.7% with interposition vein graft, 4.7% with interposition prosthetic graft, and 4.7% with patch. PVR patency was 100% at 1 day, 98% at 1 month, 91% at 6 months, and 83% at 1 year. Patients with PVR thrombosis were not significantly different from patients with patent PVR in age, survival, preoperative comorbidities, tumor characteristics, perioperative blood loss or transfusion, or postoperative complications. They were more likely to have had preoperative chemotherapy (53% vs 9%; P < .0001), radiation therapy (35% vs 2%; P < .0001), and prolonged operative time (618 ± 57 vs 424 ± 20 minutes; P = .002) and to develop postoperative ascites (76% vs 22%; P < .001). Among patients who developed ascites, 38% of those with PVR thrombosis did so in the setting of tumor recurrence at the porta detected on imaging, whereas among patients with patent PVR, 50% did so (P = .73). Patients with PVR thrombosis were more likely to have had prosthetic graft placement compared with patients with patent PVRs (18% vs 2.7%; P = .03; odds ratio [OR], 7.7; 95% confidence interval [CI], 1.4-42). PVR patency overall was significantly worse for patients who had an interposition prosthetic graft reconstruction (log-rank, P = .04). On multivariable analysis, operative time (OR, 1.01; 95% CI, 1.01-1.02) and prosthetic graft placement (OR, 8.12; 95% CI, 1.1-74) were independent predictors of PVR thrombosis (C statistic = 0.88). CONCLUSIONS:Long operative times and use of prosthetic grafts for reconstruction are risk factors for postoperative portal vein thrombosis. Primary repair, patch, or vein interposition should be preferentially used for PVR in the setting of pancreatic resection.

BACKGROUND:It is estimated that approximately 10% of pancreatic cancers have a familial component. Many inheritable genetic syndromes are associated with increased risk of pancreatic cancer, such as Peutz-Jeghers syndrome, hereditary breast-ovarian cancer and familial atypical multiple mole melanoma, but these conditions account for only a minority of familial pancreatic cancers. Previous studies have identified an increased prevalence of noninvasive precursor lesions, including pancreatic intraepithelial neoplasia, in the pancreata of patients with a strong family history of pancreatic cancer. A detailed investigation of the histopathology of invasive familial pancreatic cancer could provide insights into the mechanisms responsible for familial pancreatic cancer, as well as aid early detection and treatment strategies. METHODS:We have conducted a blinded review of the pathology of 519 familial and 651 sporadic pancreatic cancers within the National Familial Pancreas Tumor Registry. Patients with familial pancreatic cancer were defined as individuals from families in which at least a pair of first-degree relatives have been diagnosed with pancreatic cancer. RESULTS:Overall, there were no statistically significant differences in histologic subtypes between familial and sporadic pancreatic cancers (p > 0.05). In addition, among surgical resection specimens within the study cohort, no statistically significant differences in mean tumor size, location, perineural invasion, angiolymphatic invasion, lymph node metastasis and pathologic stage were identified (p > 0.05). CONCLUSIONS:Similar to sporadic pancreatic cancer, familial pancreatic cancer is morphologically and prognostically a heterogeneous disease.