Susan J. Stocker

A prospective single institution comparison of peri-operative outcomes for laparoscopic and open distal pancreatectomy

BACKGROUND Laparoscopic distal pancreatectomy (LP) is an emerging modality for managing benign and premalignant neoplasms of the pancreatic body and tail. The efficacy of LP has been examined in single and multi-institutional retrospective reviews but not compared prospectively to open distal pancreatectomy (ODP). METHODS We maintain a prospectively accruing database tracking peri-operative clinical parameters for all patients presenting to our tertiary care facility for treatment of pancreatic disease. We queried this database for patients undergoing LP or ODP between January 2003 and May 2008. Preoperative, operative, and postoperative characteristics were compared using standard statistical methods. RESULTS One-hundred twelve patients underwent distal pancreatectomy. Eighty-five underwent SDP. Twenty-eight LPs were attempted and 27 completed laparoscopically. One LP was converted to an open procedure because of bleeding and was excluded from study. In comparison to ODP, patients undergoing LP had statistically similar pre-operative demographics, disease comorbidities, tumor size, length of operation, rates of postoperative mortality, postoperative morbidity, and pancreatic fistula. Patients undergoing LP were less likely to have ductal adenocarcinoma and had fewer lymph nodes harvested in their resection but had a significantly shorter postoperative length of stay and significantly lower estimated blood loss than those undergoing ODP. CONCLUSION Laparoscopic distal pancreatectomy is a safe, effective modality for managing premalignant neoplasms of the pancreatic body and tail, providing a morbidity rate comparable to that for ODP and substantially shorter length of stay. Laparoscopic distal pancreatectomy fails to provide a lymphadenectomy comparable to ODP. This may limit the applicability of LP to the treatment of pancreatic adenocarcinoma.

Early National Experience with Laparoscopic Pancreaticoduodenectomy for Ductal Adenocarcinoma: A Comparison of Laparoscopic Pancreaticoduodenectomy and Open Pancreaticoduodenectomy from the National Cancer Data Base

BACKGROUND There is considerable debate about the safety and clinical equivalence of laparoscopic pancreaticoduodenectomy (LPD) and open pancreaticoduodenectomy (OPD) for pancreatic ductal adenocarcinoma (PDCA). STUDY DESIGN We queried the National Cancer Data Base to identify patients undergoing LPD and OPD for PDCA between 2010 and 2011. Chi-square and Students t-tests were used to evaluate differences between the 2 approaches. Multivariable logistic regression modeling was performed to identify patient, tumor, or facility factors associated with perioperative mortality. RESULTS Four thousand and thirty-seven (91%) patients underwent OPD. Three hundred and eighty-four (9%) patients underwent LPD. There were no statistical differences between the 2 surgical cohorts with regard to age, race, Charlson score, tumor size, grade, stage, or treatment with neoadjuvant chemoradiotherapy. Laparoscopic pancreaticoduodenectomy demonstrated a shorter length of stay (10 ± 8 days vs 12 ± 9.7 days; p < 0.0001) and lower rates of unplanned readmission (5% vs 9%; p = 0.027) than OPD. In an unadjusted comparison, there was no difference in 30-day mortality between the LPD and OPD cohorts (5.2% vs 3.7%; p = 0.163). Multivariable logistic regression modeling predicting perioperative mortality controlling for age, Charlson score, tumor size, nodal positivity, stage, facility type, and pancreaticoduodenectomy volume identified age (odds ratio [OR] = 1.05; p < 0.0001), positive margins (OR = 1.45; p = 0.030), and LPD (OR = 1.89; p = 0.009) as associated with an increased probability of 30-day mortality; higher hospital volume was associated with a lower risk of 30-day mortality (OR = 0.98; p < 0.0001). In institutions that performed ≥10 LPDs, the 30-day mortality rate of the laparoscopic approach was equal to that for the open approach (0.0% vs 0.7%; p = 1.00). CONCLUSIONS Laparoscopic pancreaticoduodenectomy is equivalent to OPD in length of stay, margin-positive resection, lymph node count, and readmission rate. There is a higher 30-day mortality rate with LPD, but this appears driven by a surmountable learning curve for the procedure.

Predicting aggressive behavior in nonfunctioning pancreatic neuroendocrine tumors

PURPOSE The biologic potential of nonfunctioning pancreatic neuroendocrine tumors (PNETs) is highly variable and difficult to predict before resection. This study was conducted to identify clinical and pathologic factors associated with malignant behavior and death in patients diagnosed with PNETs. METHODS We used International Classification of Diseases 9th edition codes to identify patients who underwent pancreatectomy for PNETs from 1998 to 2011 in the databases of 4 institutions. Functioning PNETs were excluded. Multivariate regression Cox proportional models were constructed to identify clinical and pathologic factors associated with distant metastasis and survival. RESULTS The study included 128 patients-57 females and 71 males. The age (mean ± standard deviation) was 55 ± 14 years. The body mass index was 28 ± 5 kg/m(2). Eighty-nine (70%) patients presented with symptoms, and 39 (30%) had tumors discovered incidentally. The tumor size was 3.3 ± 2 cm with 56 (44%) of the tumors measuring ≤2 cm. Seventy-three (57%) patients had grade 1 histology tumors, 37 (29%) had grade 2, and 18 (14%) had grade 3. Peripancreatic lymph node involvement was present in 31 patients (24%), absent in 75 (59%), and unknown in 22 (17%). Distant metastasis occurred in 18 patients (14%). There were 12 deaths, including 1 perioperative, 8 disease related, and 3 of unknown cause. With a median follow-up of 33 months, the overall 5-year survival was 75%. Multivariate Cox regression analysis identified age >55 (hazard ratio [HR], 5.89; 95% confidence interval [CI], 1.64-20.58), grade 3 histology (HR, 6.08; 95% CI, 1.32-30.2), and distant metastasis (HR, 8.79; 95% CI, 2.67-28.9) as risk factors associated with death (P < .05). Gender, race, body mass index, clinical symptoms, lymphovascular and perineural invasion, and tumor size were not related to metastasis or survival (P > .05). Three patients with tumors ≤2 cm developed distant metastasis resulting in 2 disease-related deaths. CONCLUSION Age >55 years, grade 3 histology, and distant metastasis predict a greater risk of death from nonfunctioning PNETs. Resection or short-term surveillance should be considered regardless of tumor size.

The laparoscopic approach to distal pancreatectomy for ductal adenocarcinoma results in shorter lengths of stay without compromising oncologic outcomes

BACKGROUND The oncologic equivalence of laparoscopic distal pancreatectomy (LDP) to open pancreatectomy (ODP) for ductal adenocarcinoma (DAC) is not established. METHODS The National Cancer Data Base was used to compare perioperative outcomes following LDP and ODP for DAC between 2010 and 2011. RESULTS One hundred forty-five patients underwent LDP; 625 underwent ODP. Compared with ODP, patients undergoing LDP were older (68 ± 10.1 vs 66 ± 10.5 years, P = .027), more likely treated in academic centers (70% vs 59%, P = .01), and had shorter hospital stays (6.8 ± 4.6 vs 8.9 ± 7.5 days, P < .001). Demographic data, lymph node count, 30-day unplanned readmission, and 30-day mortality were identical between groups. Multivariable regression identified a lower probability of prolonged length of stay with LDP (odds ratio .51, 95% confidence interval .327 to .785, P = .0023). There was no association between surgical approach and node count, readmission, or mortality. CONCLUSION LDP for DAC provides shorter postoperative lengths of stay and rates of readmission and 30-day mortality similar to OPD without compromising perioperative oncologic outcomes.

A multi-institutional comparison of perioperative outcomes of robotic and open pancreaticoduodenectomy

Objectives: Limited data exist comparing robotic and open approaches to pancreaticoduodenectomy (PD). We performed a multicenter comparison of perioperative outcomes of robotic PD (RPD) and open PD (OPD). Methods: Perioperative data for patients who underwent postlearning curve PD at 8 centers (8/2011–1/2015) were assessed. Univariate analyses of clinicopathologic and treatment factors were performed, and multivariable models were constructed to determine associations of operative approach (RPD or OPD) with perioperative outcomes. Results: Of the 1028 patients, 211 (20.5%) underwent RPD (4.7% conversions) and 817 (79.5%) underwent OPD. As compared with OPD, RPD patients had higher body mass index, rates of prior abdominal surgery, and softer pancreatic remnants, whereas OPD patients had a higher percentage of pancreatic ductal adenocarcinoma cases, and greater proportion of nondilated (<3 mm) pancreatic ducts. On multivariable analysis, as compared with OPD, RPD was associated with longer operative times [mean difference = 75.4 minutes, 95% confidence interval (CI) 17.5–133.3, P = 0.01], reduced blood loss (mean difference = −181 mL, 95% CI −355–(−7.7), P = 0.04) and reductions in major complications (odds ratio = 0.64, 95% CI 0.47–0.85, P = 0.003). No associations were demonstrated between operative approach and 90-day mortality, clinically relevant postoperative pancreatic fistula and wound infection, length of stay, or 90-day readmission. In the subset of 522 (51%) pancreatic ductal adenocarcinomas, operative approach was not a significant independent predictor of margin status or suboptimal lymphadenectomy (<12 lymph nodes harvested). Conclusions: Postlearning curve RPD can be performed with similar perioperative outcomes achieved with OPD. Further studies of cost, quality of life, and long-term oncologic outcomes are needed.

Adding days spent in readmission to the initial postoperative length of stay limits the perceived benefit of laparoscopic distal pancreatectomy when compared with open distal pancreatectomy

BACKGROUND Published comparisons of laparoscopic (laparoscopic distal pancreatectomy [LDP]) to open distal pancreatectomy (ODP) identify improved lengths of stay (LOS) after LDP but do not include data on readmissions. METHODS Demographic, operative, and postoperative outcomes data for patients undergoing LDP or ODP between August 2007 and December 2009 were culled from our prospectively accruing pancreatic database. Electronic medical records were reviewed to determine cause, treatment, and LOS for readmissions. RESULTS Patients undergoing LDP were statistically identical to those undergoing ODP in regard to age, presentation, demographic characteristics, comorbidities, operative times, tumor sizes, morbidity, mortality, and pancreatic fistula rates. The initial LOS was statistically shorter for those undergoing LDP (4.8 ± .1 days vs 8.7 ± .1 days, P < .001). The readmission rate for LDP was statistically higher than for ODP (25% vs 8%, P < .05). Overall LOS for LDP was 7.2 ± .3 days versus 9.3 ± .1 days for ODP (P = .2). CONCLUSIONS Adding readmission LOS to initial LOS eliminates the perceived effect of LDP to accelerate recovery.

Comparison of tumor markers for predicting outcomes after resection of nonfunctioning pancreatic neuroendocrine tumors

BACKGROUND This study compares the predictability of 5 tumor markers for distant metastasis and mortality in pancreatic neuroendocrine tumors (PNETs). METHODS A total of 128 patients who underwent pancreatectomy for nonfunctioning PNETs between 1998 and 2011 were evaluated. Tumor specimens were stained via immunochemistry for cytoplasmic and nuclear survivin, cytokeratin 19 (CK19), c-KIT, and Ki67. Univariate and multivariate regression analyses and receiver operating characteristics curve were used to evaluate the predictive value of these markers. RESULTS A total of 116 tumors (91%) were positive for cytoplasmic survivin, 95 (74%) for nuclear survivin, 85 (66.4%) for CK19, 3 for c-KIT, and 41 (32%) for Ki67 >3%. Twelve (9%) tumors expressed none of the markers. Survivin, CK19, and c-KIT had no substantial effect on distant metastasis or mortality. Age >55 years, grade 3 histology, distant metastasis, and Ki67 >3% were associated with mortality (P < .05). A cut-off of Ki67 >3% was the best predictor (83%) of mortality with an area under the curve of 0.85. Ki67 >3% also predicted occurrence of distant metastases with odds ratio of 9.22 and 95% confidence interval of 1.55-54.55 (P < .015). CONCLUSION Of the 5 markers studied, only Ki67 >3% was greatly associated with distant metastasis and death. Survivin, CK19, and c-KIT had no prognostic value in nonfunctioning PNETs.

Using a modification of the Clavien‐Dindo system accounting for readmissions and multiple interventions: Defining quality for pancreaticoduodenectomy

The Clavien‐Dindo system (CD) does not change the grade assigned a complication when multiple readmissions or interventions are required to manage a complication. We apply a modification of CD accounting for readmissions and interventions to pancreaticoduodenectomy (PD).

A semi-automated assessment of sarcopenia using psoas area and density predicts outcomes after pancreaticoduodenectomy for pancreatic malignancy

Background Sarcopenia has been associated with increased adverse outcomes after major abdominal surgery. Sarcopenia defined as decreased muscle volume or increased fatty infiltration may be a proxy for frailty. In conjunction with other preoperative clinical risk factors, radiographic measures of sarcopenia using both muscle size and density may enhance prediction of outcomes after pancreaticoduodenectomy (PD) for malignancy. Methods Preoperative computed tomography (CT) scans of patients undergoing PD for malignancy were analyzed from a prospective pancreatic surgery database. Sarcopenia was assessed both manually and with a semi-automated technique by measuring the total psoas area index (TPAI) and average Hounsfield units (HU) at the L3 lumbar level to estimate psoas muscle volume and density, respectively. Adjusting for known pre-operative risk factors, preoperative sarcopenia measurements were analyzed relative to perioperative outcomes. Results Sarcopenia assessments of 116 subjects demonstrated good correlation between the semi-automated and the manual techniques (P<0.0001). Lower TPAI (OR 0.34, P=0.009) and HU (OR 0.84, P=0.002) measurements were predictive of discharge to skilled nursing facility (SNF), but not major complications, length of stay, readmissions or recurrence on univariate analysis. Lower TPAI was protective against the risk of organ/space surgical site infection (SSI) including pancreatic fistula (OR 3.12, P=0.019). On multivariate analysis, the semi-automated measurements of TPAI and HU remained as independent predictors of organ/space SSI including pancreatic fistula (OR 4.23, P=0.014) and discharge to SNF (OR 0.79, P=0.019) respectively. Conclusions When combined with preoperative clinical assessments in patients with pancreatic malignancy, semi-automated sarcopenia metrics are a simple, reproducible method that may enhance prediction of outcomes after PD and help guide clinical management.

CA 19-9 nonproduction is associated with poor survival after resection of pancreatic adenocarcinoma

Background:Carbohydrate antigen (CA) 19-9 is the most common serum biomarker used in pancreatic adenocarcinoma (PC). Elevated preoperative levels have been shown to correlate with more advanced stage, greater risk of unresectability, and overall worse survival. The prognostic value of CA 19-9 nonproduction, which is present in an estimated 5% to 15% of the population, is unclear. We sought to determine whether CA 19-9 nonproduction was associated with worse survival after PC resection. Methods:We retrospectively reviewed our institution’s prospective pancreatic database for all PC patients with documented preoperative CA 19-9 values who underwent resection with curative intent from March 1992 to August 2009. After excluding 10 perioperative deaths, 200 patients remained for analysis. Results:Mean and median follow-up was 23.3 and 16.1 months, respectively. Median survival in months for patients with preoperative CA 19-9 levels in U/mL by category was as follows: normal (5.1 to 36.9): 32, nonproduction (⩽5): 21, mildly elevated (37 to 99.9): 35, highly elevated (100+): 16. Factors significantly associated with worse overall survival were: nonwhite race, nonproduction or highly elevated preoperative CA 19-9 (≥100 U/mL), estimated blood loss ≥1 L, tumor size (≥2 cm), lymph node-positivity, and advanced (3/4) histologic grade. On multivariate analysis, only CA 19-9 nonproduction or highly elevated production, estimated blood loss ≥1 L, advanced histologic grade, and node positivity remained significant in the final model. Conclusions:CA 19-9 nonproduction is not associated with improved survival after pancreatic cancer resection, as has previously been asserted, when compared with patients with normal and elevated levels.