Faculty Bibliography

BACKGROUND:Non-invasive intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia and IPMN-associated invasive pancreatic ductal adenocarcinoma (PDAC) are frequently included under the term "malignancy". The goal of this study is to clarify the difference between these two entities. METHODS:From 1996 to 2013, data of 616 patients who underwent pancreatic resection for an IPMN were reviewed. RESULTS:The median overall survival for patients with IPMN with high-grade dysplasia (92 months) was similar to survival for patients with IPMN with low/intermediate-grade dysplasia (118 months, p = 0.081), and superior to that of patients with IPMN-associated PDAC (29 months, p < 0.001). IPMN-associated PDAC had lymph node metastasis in 53%, perineural invasion in 58%, and vascular invasion in 33%. In contrast, no lymph node metastasis, perineural or vascular invasion was observed with high-grade dysplasia. None of the patients with IPMN with high-grade dysplasia developed recurrence outside the remnant pancreas. In stark contrast 58% of patients with IPMN-associated PDAC recurred outside the remnant pancreas. The rate of progression within the remnant pancreas was significant in patients with IPMN with high-grade (24%) and with low/intermediate dysplasia (22%, p = 0.816). CONCLUSION/CONCLUSIONS:Non-invasive IPMN with high-grade dysplasia should not be considered a malignant entity. Compared to patients with IPMN with low/intermediate-grade dysplasia, those with high-grade dysplasia have an increased risk of subsequent development of PDAC in the remnant pancreas.

OBJECTIVE:The aim of this study was to evaluate the feasibility and reproducibility of diffusion-weighted imaging in distinguishing between mucin-producing and serous pancreatic cysts. METHODS:Forty-four pancreatic cysts (43 patients, 27 women; mean age, 57 years; 26 mucin-producing cysts, 18 serous cysts) that underwent histological examination or cyst analysis after diffusion-weighted magnetic resonance imaging were retrospectively reviewed. Three blinded readers independently evaluated signal intensity and apparent diffusion coefficient (ADC). Intraobserver and interobserver agreements were calculated. Fisher exact test and Welch t test were used to compare signal intensity and ADC values, respectively, with pathological results. Receiver operating characteristic analysis was used to determine diagnostic accuracy of various thresholds for ADC. A P value less than 0.05 was considered statistically significant. RESULTS:Mean ADC values of the mucin-producing cysts were 3.26 × 10, 3.27 × 10, and 3.35 × 10 mm/s for the 3 readers, respectively. Mean ADC values of the serous cysts were 2.86 × 10, 2.85 × 10, and 2.85 × 10 mm/s for the 3 readers, respectively. Differences in ADC values between the 2 cyst groups were 12.4%, 12.9%, and 14.8% for the 3 readers, respectively (P < 0.001). Intraobserver and interobserver agreement was excellent. A threshold ADC of 3 × 10 mm/s resulted in correct identification of cysts in 77% to 81% of cases, with sensitivity and specificity ranging between 84% and 88% and 66% and 72%, respectively. CONCLUSIONS:Diffusion-weighted imaging may be a helpful tool in distinguishing between mucin-producing and serous pancreatic cysts.

BACKGROUND:Retroperitoneal sarcomas are connective tissue tumors arising in the retroperitoneum. Surgical resection is the mainstay of treatment. Debate has arisen over extent of resection, changes in histological classification/grading, and interest in incorporating radiotherapy. Therefore, we reviewed our institution's experience to evaluate prognostic factors. METHODS:Retrospective chart review of all primary RPS patients at Johns Hopkins Hospital from 1994 to 2010. Histologic diagnosis and grading were re-evaluated with current criteria. Prognostic factors for survival, and recurrence were assessed. RESULTS:One hundred thirty-one primary RPS patients met inclusion criteria. Median survival for patients who undergo en-bloc resection to negative margins (R0/R1) is 81.7 months. Surgical margins and grade were the most important factors for survival along with age, gender, presence of metastases and resection of ≥5 organs. Five-year survival for R0/R1 resection was 60%, similar to compartmental resection. Radiotherapy significantly decreased local recurrence (P = 0.026) on multivariate analysis. Grade in leiomyosarcomas and dedifferentiation in liposarcomas dictated patterns of local versus distal recurrence. CONCLUSIONS:En bloc surgical resection to R0/R1 margins remains the cornerstone of therapy and provides comparable outcomes to compartmental resections. Grade remains important for prognosis, and histology dictates recurrence patterns. Radiotherapy appears promising for local control and warrants further investigation. J. Surg. Oncol. 2016;114:56-64. © 2016 Wiley Periodicals, Inc.

Recognition and management of aberrant hepatic arterial anatomy for patients undergoing pancreaticoduodenectomy (PD) are critical to ensure safe completion of the operation. When the common hepatic artery (CHA) is noted to emanate from the superior mesenteric artery (Michels' type 9 variant), it is vulnerable to injury during the dissection required for PD. While this anatomy does not preclude an operation, care must be taken to avoid injury, often by identifying the CHA throughout its entire course before beginning the dissection of the portal venous structures. The oncologic principle that cautions against resection of a pancreatic cancer when it involves the CHA in its standard position may not universally apply to tumors that focally involve the CHA in the type 9 anatomic variant. In highly selected patients, surgical resection may be entertained as disease biology may be analogous to local involvement of the gastroduodenal artery in a patient with standard anatomy. Here, we review the indications, techniques, and outcomes associated with arterial resection and reconstruction during pancreatectomy among patients with a pancreatic tumor involving a common hepatic artery arising from the superior mesenteric artery.

OBJECTIVE:Total pancreatectomy (TP) may be considered for diffuse disease of the pancreas. However, the quality of life (QOL) implications of TP have not been well studied in the contemporary era. We report the QOL and cause of death after TP. METHODS:186 patients underwent TP between 2000 and 2013. The 100 who were still alive at last follow-up were sent a questionnaire including the Short Form-36 (SF-36), the Audit of Diabetes Dependent QoL (ADD QoL), and the European Organization for Research and Treatment in Cancer Pancreas 26 (EORTC-PAN-26). The cause of death was determined for the 86 patients who were dead at last follow-up. RESULTS:While the majority of deaths of the 86 patients were cancer related (n = 65), only one patient died of diabetes complications. Among the 100 surviving patients, the median follow-up was 5.9 years. Among the 36 patients who responded to the survey, every patient required pancreatic enzymes and insulin; four patients required seven total hospitalizations for hypoglycemia. The SF-36 survey indicated a worse QOL in six domains compared with a national population matched with age and gender. However, only physical and emotional domains were decreased compared with self-matched preoperative state (p < 0.01 and p < 0.05, respectively). The ADD QoL survey showed an overall decrease in diabetes-related QoL (p < 0.01). When compared to other types of insulin-dependent diabetes, no significant difference in QoL were found in 14 of 19 domains. The EORTC-PAN-26 survey demonstrated that more than 50 % of patients had moderate to severe changes in three of seven domains. CONCLUSIONS:Mortality from diabetic complications following TP is uncommon. The decreasing QoL after TP is comparable to self-matched preoperative assessment or insulin-dependent diabetes from other causes. Accounting for the overall health changes, TP should be considered in carefully selected patients.

Intraductal papillary mucinous neoplasms (IPMN) are cystic precursors to pancreatic cancer believed to arise within a widespread neoplastic field defect. The tendency for some patients to present with multifocal disease and/or develop additional lesions over time argues in favor of a field defect and complicates surgical management decisions. Surgery usually consists of partial pancreatic resection, which leaves behind a pancreatic remnant at risk for recurrent disease and progression to cancer. As an alternative, total pancreatectomy (TP) provides the most complete oncologic resection, but postoperative morbidity and quality of life (QoL) issues have generally limited its use to only the highest risk patients. Significant progress has been made in the management of the post-TP apancreatic state and studies now show less morbidity with acceptable QoL comparable to type 1 diabetic and post-pancreaticoduodenectomy patients. These improvements do not yet justify the routine use of TP, but they have opened the door for expansion to additional subsets of non-invasive IPMN. Here, we have identified several groups of patients that we believe would benefit from TP over partial resection based on the most current literature.

PURPOSE/OBJECTIVE:Pancreatic cysts frequently pose clinical dilemmas. On one hand, cysts with high-grade dysplasia offer opportunities for cure, on the other hand, those with low-grade dysplasia are easily over treated. Cyst fluid markers have the potential to improve the evaluation of these cysts. Because telomerase activity is commonly activated in malignant cells, we evaluated the diagnostic performance of cyst fluid telomerase activity measurements for predicting histologic grade. EXPERIMENTAL DESIGN/METHODS:Telomerase activity was measured using telomerase repeat amplification with digital-droplet PCR in surgically aspirated cyst fluid samples from 219 patients who underwent pancreatic resection for a cystic lesion (184 discovery, 35 validation) and 36 patients who underwent endoscopic ultrasound fine-needle aspiration. Methodologic and clinical factors associated with telomerase activity were examined. RESULTS:Telomerase activity was reduced in samples that had undergone prior thawing. Among 119 samples not previously thawed, surgical cyst fluids from cystic neoplasms with high-grade dysplasia ± associated invasive cancer had higher telomerase activity [median (interquartile range), 1,158 (295.9-13,033)] copies/μL of cyst fluid than those without [19.74 (2.58-233.6) copies/μL; P < 0.001)]. Elevated cyst fluid telomerase activity had a diagnostic accuracy for invasive cancer/high-grade dysplasia of 88.1% (discovery), 88.6% (validation), and 88.2% (merged). Among cysts classified preoperatively as having "worrisome features," cyst fluid telomerase activity had high diagnostic performance (sensitivity 73.7%, specificity 90.6%, accuracy, 86.1%). In multivariate analysis, telomerase activity independently predicted the presence of invasive cancer/high-grade dysplasia. CONCLUSIONS:Cyst fluid telomerase activity can be a useful predictor of the neoplastic grade of pancreatic cysts. Clin Cancer Res; 22(20); 5141-51. ©2016 AACRSee related commentary by Allen et al., p. 4966.

BACKGROUND:With improved neoadjuvant regimens, more aggressive surgical resections may be warranted for patients with locally advanced pancreatic cancer (LAPC) with focal encasement of the celiac axis (CA) and proximal common hepatic artery (HA). We sought to investigate the clinicopathological features and outcomes of the modified Appleby procedure (DP-CAR) in light of improved neoadjuvant therapies. METHODS:A prospectively maintained database of all pancreatectomies performed at Johns Hopkins Hospital, Baltimore, MD, USA, was reviewed to identify all patients who underwent DP-CAR for pancreatic ductal adenocarcinoma (PDAC) between 2004 and 2016. A 3:1 match for patients undergoing distal pancreatectomy (DP) versus DP-CAR was performed on the basis of their clinicopathological features. RESULTS:Seventeen patients who underwent DP-CAR were matched to 51 patients who underwent DP for resection of PDAC. Prior to DP-CAR, 15 (88.2 %) patients received neoadjuvant therapy, and the most frequently used regimen was FOLFIRINOX (80.0 %). DP-CAR was associated with longer operative time (404 vs. 309 min; p = 0.003) and elevated postoperative liver transaminases compared with DP. No difference was observed in estimated blood loss and length of hospitalization. R0 resection was achieved in 82.4 % of DP-CAR patients versus 92.2 % of DP patients (p = 0.355). No difference was observed in postoperative outcomes, including overall complications, pancreatic fistula, readmission, and mortality. Median survival for DP-CAR was 20 versus 19 months in the DP group (p = 0.757). CONCLUSION:In light of improved neoadjuvant therapeutic regimens, the modified Appleby procedure is a feasible and safe treatment option for patients with LAPC involving the CA, with morbidity and mortality similar to patients undergoing classic DP.

PURPOSE/OBJECTIVE:Pancreatic neoplasms are uncommon in children. This study sought to analyze the clinical and pathological features of surgically resected pancreatic tumors in children and discuss management strategies. METHODS:We conducted a retrospective review of patients ≤21 years with pancreatic neoplasms who underwent surgery at a single institution between 1995 and 2015. RESULTS:Nineteen patients were identified with a median age at operation of 16.6 years (IQR 13.5-18.9). The most common histology was solid pseudopapillary neoplasm (SPN) (n = 13), followed by pancreatic neuroendocrine tumor (n = 3), serous cystadenoma (n = 2) and pancreatoblastoma (n = 1). Operative procedures included formal pancreatectomy (n = 17), enucleation (n = 1) and central pancreatectomy (n = 1). SPNs were noninvasive in all but one case with perineural, vascular and lymph node involvement. Seventeen patients (89.5 %) are currently alive and disease free at a median follow-up of 5.7 (IQR 3.7-10.9) years. Two patients died: one with metastatic insulinoma and another with SPN who developed peritoneal carcinomatosis secondary to a concurrent rectal adenocarcinoma. CONCLUSIONS:Pediatric pancreatic tumors are a heterogeneous group of neoplastic lesions for which surgery can be curative. SPN is the most common histology, is characterized by low malignant potential and in selected cases can be safely and effectively treated with a tissue-sparing resection and minimally invasive approach.

BACKGROUND:Retroperitoneal sarcomas are rare tumors that can be locally aggressive with high rates of recurrence. Given that data on survival in patients with retroperitoneal sarcomas are conflicting, we sought to use a nationwide cancer database to identify factors associated with survival in patients with retroperitoneal sarcomas. METHODS:The Surveillance, Epidemiology, and End Results database was utilized to identify patients with retroperitoneal sarcomas from 2002 to 2012. Univariable and multivariable survival analysis was performed using a generalized gamma parametric survival function. RESULTS:A total of 2,920 patients were included; overall 5- and 10-year survivals were 58.4% and 45.3%, respectively. On multivariable survival analysis, age, histologic type, grade, size, local extension, lymph node, and distant metastasis were associated with decreased survival (all P < .05). Patients undergoing operative resection survived 2.5 times longer (95% confidence interval: 2.0-3.0, P < .001) and those receiving radiation therapy 1.3 times longer (95% confidence interval: 1.1-1.6, P = .001), respectively. CONCLUSION:During the past decade, retroperitoneal sarcoma patients treated with radiation demonstrate longer survival compared with patients who did not receive radiation. Further study is needed to fully elucidate the mechanisms that underlie the radiation-related survival benefit observed in this study.