Faculty Bibliography

BACKGROUND/OBJECTIVES/OBJECTIVE:Mucinous cystic neoplasms (MCNs) are rare pancreas tumors distinguished from intraductal papillary mucinous neoplasms (IPMNs) by the presence of ovarian-type stroma. Historical outcomes for MCNs vary due to previously ambiguous diagnostic criteria resulting in confusion with IPMNs. This study seeks to characterize and clarify the clinical features and long-term outcomes of MCNs versus IPMNs in the largest single-institution series of pathology-confirmed MCNs to date. METHODS:We compared 142 MCNs and 746 IPMNs resected at a single institution. MCNs were reviewed for confirmation of ovarian-type stroma and reclassified according to current WHO guidelines. RESULTS:MCNs presented almost exclusively in middle-aged women (median 47.5 years, 96.5% female) as solitary (100%), macrocystic (94.2%) lesions in the distal pancreas (92.1%). IPMNs were distributed equally by sex in an older population (median 69.0 years, 49.6% female) and favored the proximal pancreas (67.6%). Compared with IPMNs, MCNs were larger (4.2 cm vs 2.5 cm) and more often low-grade (71.1% vs 13.8%). Associated invasive carcinoma was less common in MCNs than in IPMNs (9.9% vs 32.4%). Surgical resection was curative for 100% of noninvasive MCNs. Patients with an MCN-associated invasive carcinoma had a much better prognosis than did patients with an IPMN-associated invasive carcinoma with 10-year disease-specific survival of 79.6% versus 27.2%, respectively. CONCLUSION/CONCLUSIONS:MCNs have a stereotypical clinical profile that is readily distinguishable from IPMNs based on demographic features, imaging, and pathology. Most MCNs are noninvasive and curable with surgical resection. Prognosis remains excellent even for invasive disease with 10-year survival approaching 80% following resection.

BACKGROUND:The current staging system for pancreatic ductal adenocarcinoma (PDAC) includes information about size and local extension of the primary tumor (T stage). The value of incorporating any local tumor extension into pancreatic staging systems has been questioned because it often is difficult to evaluate tumor extension to the peri-pancreatic soft tissues and because most carcinomas of the head of the pancreas infiltrate the intra-pancreatic common bile duct. This study sought to evaluate the prognostic implications of having PDAC with local tumor extension. METHODS:A single-institution, prospectively collected database of 1128 patients who underwent surgical resection for PDAC was queried to examine the prognostic significance of extra-pancreatic tumor involvement ("no involvement," "duodenal involvement," and "extensive involvement"; e.g., gastric, colon or major vein involvement). RESULTS:The median overall survival for the patients without extra-pancreatic involvement was 26 months versus 19 months for the patients with duodenal involvement and 16 months for the patients with extensive involvement (p < 0.001). In the multivariable analysis, duodenal and extensive involvement independently predicted increased risk of death compared with no involvement (hazard ratio [HR] 1.30; 95% confidence interval [CI] 1.08-1.57 and 1.78; 95% CI 1.25-2.55, respectively). A multivariable model combining duodenal and extensive extra-pancreatic involvement, tumor grade, lymph node ratio, and other prognostic features had the highest c-index (0.67). CONCLUSIONS:Inclusion of duodenal involvement in the staging of PDAC adds independent prognostic information.

BACKGROUND:Underutilization of potential curative surgical treatment remains a problem in the management of hepatocellular carcinoma (HCC). Demographic and socioeconomic disparities continue to be important factors impacting utilization patterns, and exact mechanisms underlying these disparities remain largely unclarified. Focusing on these mechanisms provides us with a potential approach to improve survival of HCC patients. METHODS:We performed a retrospective cohort study using the Surveillance, Epidemiology, and End Results Database to assess patients with early stage HCC diagnosed between January 2004 and December 2012. Demographic and socioeconomic factors were analyzed to assess associations with utilization of treatment, stage of presentation, and disease-specific survival by means of multinominal and Cox regression. RESULTS:A total of 13,694 patients were included in the analysis of which only 6239 (45.6%) underwent surgical treatment for early stage HCC. Surgical treatment options consisted of 1445 liver resections (10.6%), 2121 liver transplantations (15.5%), and 2673 liver ablations (19.5%). The rate of surgical treatment fell from 56.1% in 2004 to 37.8% in 2012. Compared with no surgical therapy, African Americans were less likely to undergo liver transplantation (relative risk ratio [RRR] = 0.54; 95% confidence interval [CI], 0.36-0.79) than Caucasian patients and more likely to undergo surgical resection (RRR = 1.67; 95% CI, 1.13-2.48). Patients from the Pacific West were less likely to be transplanted versus patients from the Southeast (RRR = 0.68; 95% CI, 0.50-0.93). Also, patients who were married (RRR = 2.44; 95% CI, 1.96-3.04) or had health insurance (RRR = 4.74; 95% CI, 1.66-13.6) were more likely to receive liver transplantation. Young age (hazard ratio = 1.02; 95% CI, 1.00-1.03; P = 0.025) and positive marital status (hazard ratio = 0.71; 95% CI, 0.55-0.92; P = 0.010) both were independently associated with increased disease-specific survival. CONCLUSIONS:An increasing proportion of patients with early stage HCC did not undergo surgical therapy between 2004 and 2012. Demographic and socioeconomic factors were associated with different treatment modality utilization after controlling for available confounders. Of these factors, age and marital status were independently associated with increased disease-specific survival.

BACKGROUND:Recently, a tumor-burden "metro ticket" score (TBS) based on final pathology was proposed to predict outcome following resection of colorectal liver metastasis (CRLM). We sought to validate the TBS prognostic tool using preoperative radiologic cross-sectional imaging. METHODS:Imaging TBS was defined on a Cartesian plane that incorporated both maximum tumor size (x-axis) and lesion number (y-axis) assessed by pre-operative imaging. The discriminatory power (area under the curve [AUC]) and goodness-of-fit (Harrel's C statistic and Somer's D statistics) of the imaging TBS model was assessed. RESULTS:Imaging and pathologic TBS correlated strongly (r = 0.76, P < 0.01). Among patients treated with neoadjuvant therapy, the correlation was strongest among patients with progressive disease/stable disease (PD/SD) (r = 0.81). Discriminatory power of the imaging-based versus pathology-based TBS models were comparable (AUC 0.64 vs. 0.67, respectively P > 0.05). An incremental worsening of long-term survival was noted as the imaging TBS increased (5-year OS: Zone1, Zone2, and Zone3-61.3%, 46.7%, and 38.5%, respectively; P = 0.03). The imaging-based TBS model outperformed the "classic" pathology-based Fong score (Harrel's C-index: imaging TBS-0.56 vs. Fong score-0.53; Somers'D-index: imaging TBS-012 vs. Fong score-0.06). CONCLUSIONS:Imaging-based TBS was superior to traditional tumor size and number and was comparable to pathology-based TBS. Imaging-based TBS may have the potential to facilitate improved preoperative risk stratification of patients with CRLM.

BACKGROUND:Rates of superficial surgical site infection (SSI) following pancreaticoduodenectomy remain high. Following resection for cancer, complications such as SSI impact adjuvant therapy delivery and portend worse survival. An incisional negative pressure dressing (iVAC) has been demonstrated to reduce SSI in other high-risk cohorts. METHODS:Following a comprehensive effort to identify patients at high risk for SSI, the practice patterns at a single academic center shifted and iVAC use increased. SSI rates were tracked in a prospectively maintained database and are reported. RESULTS:394 patients underwent pancreaticoduodenectomy over 21 months. 120 patients (30.5%) had an iVAC applied. The overall rate of SSI was 19.8%. On multivariate analysis, increased risk for SSI was associated with neoadjuvant therapy, preoperative biliary interventions and prior abdominal surgery. iVAC use decreased the rate of SSI (OR 0.45, p = 0.015). In the highest-risk patients, SSI rate declined from 50% in patients without an iVAC to 19.1% with iVAC use (p = 0.015). CONCLUSION:The use of an iVAC following pancreaticoduodenectomy is associated with decreased SSI rates. This is particularly true for patients at highest risk as defined by a previously established risk scoring system in patients undergoing open pancreaticoduodenectomy.

BACKGROUND:Although experimental data strongly support the pro-tumorigenic role of postoperative liver regeneration, this hypothesis has not been clinically investigated. We aimed to examine the impact of liver regeneration determined by volumetric imaging on recurrence following resection of colorectal liver metastasis (CRLM). METHODS:). Early and late kinetic growth rates (KGR) were defined as the postoperative increases in liver volume within 2-3 and 8-10 months from surgery, respectively, divided by the corresponding time interval. RESULTS:Median early and late KGR was 2.6%/month (IQR: -0.9 to 12.3) and 1.0%/month (IQR: -0.64 to 2.91), respectively. Late KGR predicted intrahepatic recurrence after 1 year from surgery (AUC 0.677, P = 0.011). Specifically, patients with a late KGR ≥1% had a higher cumulative risk of recurrence compared with patients with a KGR <1% (P = 0.038). In multivariate analysis, KGR ≥1% independently predicted recurrence (P = 0.027). DISCUSSION:A KGR ≥1% during the late regeneration phase was associated with increased risk of intrahepatic recurrence. These data may inform the timing of adjuvant therapy administration and focus surveillance strategies for high-risk patients.

Background and Objectives Despite routine inclusion of lymphovascular invasion (LVI) status in pathologic reports of resected pancreatic ductal adenocarcinomas (PDA), the clinical implications of LVI have not been well characterized. Methods This study is a retrospective review of 2640 patients who underwent a pancreatectomy for PDA at Thomas Jefferson University Hospital, Massachusetts General Hospital, or Johns Hopkins Hospital (2003-2014). Clinical and pathologic records were extracted from institutional databases. Results The median post-resection survival for the total cohort was 19.2 months with a 5-year survival rate of 15.2%. In a multivariate Cox proportional hazards model including conventional pathologic features, LVI was an independent predictor of survival (HR = 1.14, P = 0.017). In a stratified Kaplan-Meier survival analysis, patients with N0, LVI- PDA had a significantly improved overall survival compared to those with N0, LVI+ PDA (median 31 vs 24 mo, P = 0.020). Similarly, patients with N1, LVI- PDA had superior survival to patients with N1, LVI+ disease (18.6 vs 16.5 mo, P = 0.001). Conclusions As the first large scale study focused on the clinical impact of LVI status in PDA, these data indicate that this routinely reported pathologic feature is a bona fide and independent adverse prognostic factor.

The use of neoadjuvant chemotherapy or radiation for borderline resectable pancreatic adenocarcinoma (BL-PDAC) is increasing. However, the impact of neoadjuvant chemotherapy and radiation therapy on the outcome of BL-PDAC remains to be elucidated. We performed a retrospective analysis of 93 consecutive patients who were diagnosed with BL-PDAC and primarily followed at Johns Hopkins Hospital between February 2007 and December 2012. Among 93 patients, 62% received upfront neoadjuvant chemotherapy followed by chemoradiation, whereas 20% received neoadjuvant chemoradiation alone and 15% neoadjuvant chemotherapy alone. Resectability following all neoadjuvant therapy was 44%. Patients who underwent resection with a curative intent had a median overall survival (mOS) of 25.8 months, whereas those who did not undergo surgery had a mOS of 11.9 months. However, resectability and overall survival were not significantly different between the three types of neoadjuvant therapy. Nevertheless, 22% (95% CI, 0.13-0.36) of the 58 patients who received upfront chemotherapy followed by chemoradiation remained alive for a minimum of 48 months compared to none of the 19 patients who received upfront chemoradiation. Among patients who underwent curative surgical resection, 32% (95% CI, 0.19-0.55) of those who received upfront chemotherapy remained disease free at least 48 months following surgical resection, whereas none of the eight patients who received upfront chemoradiation remained disease free beyond 24 months following surgical resection. Neoadjuvant therapy with upfront chemotherapy may result in long-term survival in a subpopulation of patients with BL-PDAC.

BACKGROUND:Patients with pancreatic ductal adenocarcinoma (PDAC) are frequently referred to tertiary centers after unsuccessful attempted resections at other institutions. The outcome of these patients who are ultimately resected is not well understood. METHODS:We performed a retrospective review of patients with PDAC who underwent re-exploration between 1995 and 2013 at a single high volume tertiary care institution. We aimed to evaluate the association of neoadjuvant therapy prior to re-exploration on pathologic findings and clinical outcome in previously explored patients with PDAC. RESULTS:10 months, P<0.001). CONCLUSIONS:Patients with PDAC deemed unresectable may warrant re-exploration. Treatment with neoadjuvant therapy between operations is associated with improved pathological stage and survival. In this highly selected group of patients, successful resection is associated with improved survival compared to R2 resections.