The American Journal of Surgery (2015) 209, 557-563
Midwest Surgical Association
The laparoscopic approach to distal pancreatectomy for ductal adenocarcinoma results in shorter lengths of stay without compromising oncologic outcomes Susan M. Sharpe, M.D.a, Mark S. Talamonti, M.D.b, Edward Wang, Ph.D.b, David J. Bentrem, M.D.c, Kevin K. Roggin, M.D.a, Richard A. Prinz, M.D.b, Robert D. W. Marsh, M.D.b, Susan J. Stocker, C.C.R.P.b, David J. Winchester, M.D.b, Marshall S. Baker, M.D., M.B.A.b,* a
Department of Surgery, Pritzker School of Medicine, University of Chicago, Chicago, IL, USA; Department of Surgery, NorthShore University HealthSystems, Evanston, IL, USA; cDepartment of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
b
KEYWORDS: Laparoscopy; Open; Distal; Pancreatectomy; Adenocarcinoma
Abstract 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 6 10.1 vs 66 6 10.5 years, P 5 .027), more likely treated in academic centers (70% vs 59%, P 5 .01), and had shorter hospital stays (6.8 6 4.6 vs 8.9 6 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 5 .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. Ó 2015 Elsevier Inc. All rights reserved.
The authors declare no conflicts of interest. * Corresponding author. Tel.: 11-847-570-1327; fax: 11-847-5702930. E-mail address: [email protected] Manuscript received July 21, 2014; revised manuscript October 31, 2014 0002-9610/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjsurg.2014.11.001
The laparoscopic approach for distal pancreatectomy has gained widespread acceptance as an effective treatment modality for benign or premalignant lesions of the pancreatic body and tail. Multiple, single institutional, prospective studies and several larger multi-institutional retrospective reviews have examined perioperative outcomes following laparoscopic and open distal pancreatectomy.1–5 In general,
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these studies demonstrate that laparoscopic pancreatectomy is associated with a shorter hospital stay and less intraoperative blood loss than the open approach. There has, to date, been one multi-institutional examination of laparoscopic distal pancreatectomy specifically for cancer.2 This study examined perioperative outcomes for 23 laparoscopic distal pancreatectomies and compared them with 189 contemporaneous open distal pancreatectomies. There have been no well-powered studies investigating the use of laparoscopic distal pancreatectomy compared with open resection for ductal adenocarcinoma with regard to perioperative oncologic outcomes and the oncologic equivalence of laparoscopic distal pancreatectomy to open distal pancreatectomy has not been demonstrated. In this study, we use a large National Cancer Data Base (NCDB) to determine the potential difference in perioperative outcomes between laparoscopic and open approaches for the management of pancreatic cancer in the body and tail of the pancreas. We hypothesize that the laparoscopic group would have a shorter length of stay, but that there would be no difference between the laparoscopic and open approaches in rates of readmission and postoperative mortality, and several perioperative oncologic outcomes, including lymph node count and rates of margin negative resection.
Native, and Other. Insurance status was examined as private, Medicaid, Medicare, and uninsured/unknown. Facility type included Community Cancer Program, Comprehensive Community Cancer Program, and Academic/ Research/National Cancer Institute Program and are distinguished according to the number of newly diagnosed cancer patients treated and if postgraduate medical education is offered. Specifically, Community Cancer Programs treat between 100 and 500 newly diagnosed cancer patients each year; Comprehensive Community Cancer Programs treat more than 500 cases a year. Academic/research facilities treat more than 500 new cancer cases and offer postgraduate medical education and are grouped with NCI-designated cancer centers. Facility location was categorized into the following regions as defined in the 2010 United States Census: New England (CT, MA, ME, NH, RI, VT), Middle Atlantic (NJ, NY, PA), South Atlantic (DC, DE, FL, GA, MD, NC, SC, VA, WV), East North Central (IL, IN, MI, OH, WI), East South Central (AL, KY, MS, TN), West North Central (IA, KS, MN, MO, ND, NE, SD), West South Central (AR, LA, OK, TX), Mountain (AZ, CO, ID, MT, NM, NV, UT, WY), and Pacific (AK, CA, HI, OR, WA).
Patients and Methods
Statistical analyses were performed using SAS version 9.4 (SAS institute, Inc, Cary, NC). P values less than or equal to .05 were considered statistically significant. Age, demographic factors, comorbid condition (Charlson score), facility factors (type and location), pathologic features (tumor size, number of positive lymph nodes, grade, and stage), treatment factors (neoadjuvant chemotherapy or radiation therapy), and perioperative outcomes (number of lymph nodes examined, margin status, length of stay, 30-day readmission rate, and 30-day mortality rate) for patients who underwent laparoscopic resection were compared with those for patients undergoing open resection. Data for overall survival are available only if a patient was diagnosed 5 years or earlier; therefore, the most recent year that provides for survival is 2006 and thus, in this study, the difference in overall survival between the 2 groups was not investigated. Diseasespecific survival is not captured by the database at this time and that outcome was not evaluated. Comparisons among groups were performed using the Student t-test for continuous variables or chi-square or Fisher’s exact test for categorical variables as appropriate. Patient, tumor, and facility factors were analyzed in multivariable logistic regression models to identify variables associated with length of stay longer than the median of 7 days, lymph node count greater than the median of 12, positive margin status, 30-day unplanned readmission, and 30-day mortality.
Data source The NCDB is a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society; it captures information from approximately 1,500 Commission on Cancer-accredited hospitals and greater than 70% of all newly diagnosed malignancies in the United States. It contains specific details about patient demographics, facility type and location, tumor characteristics, treatment course, and outcomes. All data within the NCDB are deidentified of specific patient factors and are compliant with the Health Insurance Portability and Accountability Act; this study is therefore exempt from approval from our Institutional Review Board.
Study population The NCDB was queried to identify all patients greater than or equal to 18 years old diagnosed with pancreatic adenocarcinoma who underwent a laparoscopic or open partial pancreatectomy between 2010 and 2011. Tumor histology was classified according to the International Classification of Disease for Oncology, Third Edition. Patients were excluded if they had metastatic disease or concomitant cancer diagnoses. Patient age at diagnosis was analyzed as younger than 45, between ages 45 and 64, and 65 years or older. The race of each patient was categorized into White, Black, Hispanic, Asian/Pacific Islander, Native American/Alaskan
Statistical analysis
Results A total of 769 patients underwent distal pancreatectomy for ductal adenocarcinoma: 625 (81%) had an open
S.M. Sharpe et al. Table 1
Laparoscopic open distal pancreatectomy
559
Comparison of open and laparoscopic distal pancreatectomy for adenocarcinoma
Age (years) Mean 6 SD Median %65 66–74 R75 Race White Black Hispanic Asian/Pacific Islander Native American/Alaska Native Other/unknown Charlson/Deyo score 0 1 2 Income ($) ,30,000 30,000–34,999 35,000–45,999 R46,000 Insurance status Uninsured Private insurance Medicaid Medicare Unknown Facility type Community Cancer Program Comprehensive Community Cancer Program Academic/Research/NCI Other Facility location New England Middle Atlantic South Atlantic East North Central East South Central West North Central West South Central Mountain Pacific Tumor size (cm) Mean 6 SD Median %2 .2 Unknown Lymph nodes examined Mean 6 SD Median Lymph nodes positive Negative
Open distal n 5 625 (81%)
Laparoscopic distal n 5 144 (19%)
n (%)
n (%)
65.6 6 10.5 66 297 (48) 184 (29) 144 (23)
67.7 6 10.1 68 55 (38) 47 (33) 42 (29)
474 89 29 19 4 10
120 17 2 4 1 0
P value
.027 .105
.228 (76) (14) (5) (3) (1) (2)
(83) (12) (1) (3) (1) (0) .194
383 (61) 190 (30) 52 (8)
83 (58) 42 (29) 19 (13)
84 108 148 237
(13) (17) (24) (38)
18 22 43 48
(13) (15) (30) (33)
17 284 307 12 5
(3) (45) (49) (2) (1)
3 51 88 1 1
(2) (35) (61) (1) (1)
25 231 368 1
(4) (37) (59) (.2)
1 41 101 1
(1) (29) (70) (1)
29 123 138 116 35 45 55 28 56
(5) (20) (22) (19) (6) (7) (9) (5) (9)
6 31 38 24 8 15 11 1 10
(4) (22) (26) (17) (6) (10) (8) (1) (7)
.437
.124
.010
.417
4.2 6 3.2 3.6 94 (15) 519 (83) 12 (2)
3.7 6 1.9 3.5 30 (21) 111 (77) 3 (2)
13.3 6 9.9 12
14.9 6 10.0 13
.018 .213
.085
.906 286 (46)
69 (48) (continued on next page)
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Table 1
(continued )
Open distal n 5 625 (81%) Positive Unknown Grade Well-differentiated Moderately differentiated Poorly/undifferentiated Unknown Stage I II III Unknown Margin status Negative Positive Unknown Length of stay (days) Mean 6 SD Median 30-day readmission No readmission Unplanned Neoadjuvant chemotherapy No Yes Unknown Neoadjuvant radiation No Yes Unknown 30-day mortality Alive Dead
Laparoscopic distal n 5 144 (19%)
304 (49) 35 (6)
68 (47) 7 (5)
63 310 194 58
(10) (50) (31) (9)
10 85 46 3
(7) (59) (32) (2)
149 444 21 11
(24) (71) (3) (2)
30 107 6 1
(21) (74) (4) (1)
P value
.006
.694
.042 489 (78) 127 (20) 9 (1)
125 (87) 17 (12) 2 (1)
8.9 6 7.5 7
6.8 6 4.6 5
559 (89) 53 (9)
133 (92) 10 (7)
518 (83) 69 (11) 38 (6)
127 (88) 3 (2) 14 (10)
585 (94) 38 (6) 2 (.3)
139 (97) 3 (2) 2 (1)
615 (98) 10 (2)
144 (100) 0 (0)
,.001 .616
,.001
.049
.222
NCI 5 National Cancer Institute; SD 5 standard deviation.
resection and 144 (19%) underwent a laparoscopic resection. Table 1 lists the patient, tumor, facility, and treatment demographics. There were no statistical differences between laparoscopic and open pancreatectomy with regard to race, Charlson score, income, insurance status, or facility location. Patients in the laparoscopic group were older than those in the open group (67.7 6 10.1 vs 65.6 6 10.5 years, P 5 .027). A higher proportion of patients undergoing a laparoscopic distal pancreatectomy were treated at academic/research institutions (70% vs 59%, P 5 .01). More patients in the open group received neoadjuvant chemotherapy (11% vs 2%, P , .001) or radiation (6% vs 2%, P 5.049). Patients in the open group had larger tumors than those in the laparoscopic group (4.2 6 3.2 vs 3.7 6 1.9 cm, P 5 .018); however, the proportion of small and large tumors was not different between the 2 groups (P 5 .213). A larger proportion of patients who underwent open resection had positive margins following pancreatectomy (20% vs 12%, P 5 .042). There were no differences between the 2 groups with regard to the number of lymph
nodes examined, the number of positive lymph nodes, or stage. Length of stay was shorter in the laparoscopic resection group compared with the open group (6.8 6 4.6 vs 8.9 6 7.5, P , .001). The rates of 30-day readmission and 30day mortality were similar between groups. We performed 5 separate multivariable logistic regression analyses predicting lymph node count greater than the median of 12, positive margin status, 30-day unplanned readmission, 30-day mortality, and length of stay greater than the median of 7 days. Each regression controlled for age, Charlson score, facility type and location, tumor size, stage, grade, margin status (except for the regression predicting positive margins), number of lymph nodes examined (except for the regression predicting lymph node count greater than the median), lymph node positivity, neoadjuvant chemotherapy, neoadjuvant radiation, and surgical approach. In the multivariable regression for lymph node count, the variables associated with lymph node assessment greater than the median of 12 were age (odds ratio [OR] .98, 95%
S.M. Sharpe et al.
Laparoscopic open distal pancreatectomy
561
Table 2 Multivariable logistic regression for prolonged length of stay after distal pancreatectomy for adenocarcinoma (median length of stay 5 7 days) Age (years) Charlson/Deyo score 0 1 2 Facility type Community Cancer Program Comprehensive Community Cancer Program Academic/Research/NCI Other Facility location New England Middle Atlantic South Atlantic East North Central East South Central West North Central West South Central Mountain Pacific Tumor size (cm) %2 .2 Unknown Grade Well-differentiated Moderately differentiated Poorly/undifferentiated Unknown Stage I II III Unknown Margin status Negative Positive Number of lymph nodes examined Positive lymph nodes Negative Positive Unknown Neoadjuvant chemotherapy No Yes Unknown Neoadjuvant radiation No Yes Unknown Surgical approach Open distal Laparoscopic distal
Odds ratio (95% CI)
P value
1.03 (1.014–1.046)
.0003
Reference 1.50 (1.055–2.125) 1.43 (.812–2.500)
Reference .024 .217
Reference .91 (.363–2.292) .88 (.349–2.193) 1.87 (.094–37.379)
Reference .845 .775 .682
Reference .92 (.394–2.132) 1.48 (.626–3.347) 1.67 (.701–3.964) 1.02 (.367–2.821) 1.34 (.518–3.466) 1.30 (.500–3.379) .92 (.301–2.821) 1.57 (.603–4.111)
Reference .841 .388 .248 .972 .547 .591 .886 .354
Reference 1.28 (.814–2.011) .81 (.187–3.513)
Reference .285 .779
Reference 1.49 (.845–2.640) 1.07 (.583–1.971) .71 (.307–1.655)
Reference .167 .823 .431
Reference .79 (.508–1.237) .89 (.342–2.328) .90 (.231–3.509)
Reference .306 .815 .879
Reference 1.35 (.898–2.034) 1.00 (.981–1.017)
Reference .149 .928
Reference 1.12 (.770–1.641) 1.62 (.732–3.567)
Reference .543 .235
Reference .87 (.383–1.970) .43 (.204–.902)
Reference .736 .026
Reference 2.62 (.913–7.510) 4.08 (.418–39.837)
Reference .073 .227
Reference .51 (.327–.785)
Reference .002
Odds ratio .1 indicates increased chance of having a hospital length of stay longer than the median (7 days). CI 5 confidence interval; NCI 5 National Cancer Institute.
562 confidence interval [CI] .965 to .996, P 5 .0155), lymph node positivity (OR 2.13, 95% CI 1.463 to 3.085, P , .0001), and treatment in an academic/research institution compared with a Community Cancer Program (OR 3.86, 95% CI 1.326 to 11.223, P 5 .0132) (data not shown). Surgical approach (laparoscopic distal pancreatectomy versus open) was not associated with achieving a lymph node count greater than 12 (OR 1.19, 95% CI .785 to 1.816, P 5 .408) (data not shown). Higher stages when compared with Stage I predicted positive margins in the multivariable regression: Stage II (OR 3.62, 95% CI 1.800 to 7.260, P 5 .0003) and Stage III (OR 10.00, 95% CI 3.289 to 30.375, P , .0001); there was a trend for positive margins with lymph node positivity (OR 1.56, 95% CI .989 to 2.462, P 5 .0558) (data not shown). Laparoscopic distal pancreatectomy was associated with a decreased risk of having positive margins (OR .54, 95% CI .302 to .960, P 5 .0358) (data not shown). The only factor that predicted an increased risk of a 30-day unplanned readmission was older age (OR 1.03, 95% CI 1.002 to 1.064, P 5 .0361); surgical approach was not associated with an increased risk of readmission (OR .83, 95% CI .374 to 1.827, P 5 .637) (data not shown). There were no factors associated with an increased risk of perioperative mortality, including surgical approach (OR .30, 95% CI .049 to 1.786, P 5 .185) (data not shown). Table 2 shows the multivariable regression model for length of stay. The laparoscopic group was half as likely as the open group to have a hospital stay longer than the median of 7 days (OR .51, 95% CI .327 to .785, P 5 .0023). Age (OR 1.03, 95% CI 1.014 to 1.046, P 5 .0003) and Charlson score of 1 (OR 1.50, 95% CI 1.055 to 2.125, P 5 .0237) were associated with a hospital stay longer than 7 days.
Comments There have been relatively few prior studies comparing the perioperative outcomes following laparoscopic distal pancreatectomy with those for open distal pancreatectomy. The largest series was a multi-institutional retrospective comparison of laparoscopic and open distal pancreatectomy4 and included 142 patients in the laparoscopic group. The laparoscopic cohort in this series had shorter lengths of stay than those in the open cohort. This study was not specific for adenocarcinoma and included both benign and malignant tumors. The largest series examining outcomes specifically in cancer patients was a multi-institutional review of 212 patients, of which 23 patients underwent laparoscopic distal pancreatectomy. The patients who had laparoscopic distal pancreatectomy had shorter lengths of stay. There was no difference between laparoscopic and open approaches in operative characteristics (eg, blood loss, operative time, lymph node count, margin status) or perioperative mortality.2 This study evaluates outcomes for 769 patients and confirms that patients who have laparoscopic distal pancreatectomy were in the hospital a median of 2 days fewer and
The American Journal of Surgery, Vol 209, No 3, March 2015 half as likely to have a hospital stay longer than 7 days than those in the open resection group. Our study further demonstrates that the laparoscopic approach provides equivalent numbers of lymph nodes examined and that laparoscopic pancreatectomy patients were less likely to have positive margins than the patients with an open resection, while controlling for age, facility type, tumor size, grade, stage, and neoadjuvant therapy. Our study has several limitations. It is a retrospective review of a national database and has the potential for omitted variable bias. There are no operation-specific data such as blood loss or operative time, nor morbidity data such as pancreatic fistula rate, surgical site infection rate, or overall morbidity rate recorded in the NCDB. Thus, a comparison of the morbidity between the 2 approaches is not possible. There is also undoubtedly some effect of selection bias. The patients who were chosen for laparoscopic resection were older, had smaller tumors, and were more likely to have their operations at academic/research institutions. There are likely additional reasons for the type of procedure chosen that are not captured in the NCDB. Such potential for selection bias cannot be completely avoided when using this database for the comparison. The fact that tumor size was different may impact the improved rates of margin negative resection with laparoscopic pancreatectomy. Other studies have not found a difference in margin status between laparoscopic and open resections, but this may be due to underpowering or other patient or tumor factors.2–4 Additionally, the NCDB does not capture recurrence data in the participant user file available to the public; similarly, the NCDB began collecting information on surgical approach in 2010. However, the latest year for which overall survival data are available is 2006 (5 years earlier than the date of the participant user file used for this study). Therefore, we were unable to compare any differences between the laparoscopic and open approaches with regard to these fundamental oncologic outcomes. Because the number of patients with distal pancreas adenocarcinoma who are eligible for resection is low, a randomized trial comparing the laparoscopic and open approaches with resection, as has been performed in other malignant diseases, is logistically difficult to pursue. Investigations for perioperative outcomes with these methods will likely be limited to retrospective reviews and single institutional prospective studies. To our knowledge, this study represents the largest series evaluating perioperative outcomes between laparoscopic and open distal pancreatectomy for adenocarcinoma. Our study showed no difference between the laparoscopic and open groups regarding number of lymph nodes examined, 30-day readmission rate, and 30-day mortality rate, but noted a decrease in hospital stay and margin positivity rate. Laparoscopic distal pancreatectomy for adenocarcinoma is a safe procedure and does not compromise oncologic outcomes, while, at the same time, provides the established benefits of laparoscopy.
S.M. Sharpe et al.
Laparoscopic open distal pancreatectomy
References 1. Baker MS, Bentrem DJ, Ujiki MB, et al. A prospective single institution comparison of peri-operative outcomes for laparoscopic and open distal pancreatectomy. Surgery 2009;146:635–45. 2. Kooby DA, Hawkins WG, Schmidt M, et al. A multicenter analysis of distal pancreatectomy for adenocarcinoma: is laparoscopic resection appropriate? J Am Coll Surg 2010;210:779–85. 3. Vijan SS, Ahmed KA, Harmsen WS, et al. Laparoscopic vs open distal pancreatectomy: a single-institution comparative study. Arch Surg 2010;145:616–21. 4. Kooby DA, Gillespie T, Bentrem D, et al. Left-sided pancreatectomy: a multicenter comparison of laparoscopic and open approaches. Ann Surg 2008;248:438–46. 5. Kim SC, Park KT, Hwang JW, et al. Comparative analysis of clinical outcomes for laparoscopic distal pancreatic resection and open distal pancreatic resection at a single institution. Surg Endosc 2008;22:2261–8.
Discussion Dr Margo C. Shoup (Warrenville, IL). I didn’t see any mention of any other organs that were resected. I don’t know if you had any of those done laparoscopically in your database. Also, do you have any long-term survival data? Regarding the database, how confident are you that you were able to really select out those patients that had laparoscopic versus open. There is no CPT code for laparoscopic distal pancreatectomy. And then, finally, how many patients had their laparoscopic procedures converted to open and if you analyze those patients with the laparoscopic group, do your results change? Dr Sharpe: Your first question was if other organs were resected. Right now the NCDB does not specify if other
563 organs outside of the pancreas are resected, so we could not make those comparisons between the two surgical approaches. Your second question was whether or not we had long-term survival data. The NCDB only reports 5 year overall survival data. Disease-specific survival is not reported. The date range examined in this study is too recent to have a report on overall survival. Your other question was on the confidence of our selection for laparoscopic or open. Hospitals reporting to the NCDB must have designated NCDB registrars who populate specified data fields. These individuals are required to review the medical records for patients being entered into the NCDB. The data for each patient on exact procedure performed are extracted from operative notes and not determined by CPT codes. And then for your final question regarding why do we exclude those who were converted to open, we thought it provided a more meaningful comparison of laparoscopic and open approaches. We felt that reporting the conversions with the laparoscopic group would obscure the benefit of a successful laparoscopic procedure and thus hide the potential value of the approach. Including conversions in the open cohort could unduly make the open group appear to have poorer results. There were a total of 57 conversions (7% of the total population, 28% of all laparoscopic cases). In data not shown, we have included these on an intent-to-treat basis with the laparoscopic group. In this analysis, there was no longer a difference in the rate of margin negative resection but the laparoscopic cohort continued to demonstrate a decreased length of stay and short-term oncologic results comparable to those for the open cohort.
Midwest Surgical Association
The laparoscopic approach to distal pancreatectomy for ductal adenocarcinoma results in shorter lengths of stay without compromising oncologic outcomes Susan M. Sharpe, M.D.a, Mark S. Talamonti, M.D.b, Edward Wang, Ph.D.b, David J. Bentrem, M.D.c, Kevin K. Roggin, M.D.a, Richard A. Prinz, M.D.b, Robert D. W. Marsh, M.D.b, Susan J. Stocker, C.C.R.P.b, David J. Winchester, M.D.b, Marshall S. Baker, M.D., M.B.A.b,* a
Department of Surgery, Pritzker School of Medicine, University of Chicago, Chicago, IL, USA; Department of Surgery, NorthShore University HealthSystems, Evanston, IL, USA; cDepartment of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
b
KEYWORDS: Laparoscopy; Open; Distal; Pancreatectomy; Adenocarcinoma
Abstract 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 6 10.1 vs 66 6 10.5 years, P 5 .027), more likely treated in academic centers (70% vs 59%, P 5 .01), and had shorter hospital stays (6.8 6 4.6 vs 8.9 6 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 5 .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. Ó 2015 Elsevier Inc. All rights reserved.
The authors declare no conflicts of interest. * Corresponding author. Tel.: 11-847-570-1327; fax: 11-847-5702930. E-mail address: [email protected] Manuscript received July 21, 2014; revised manuscript October 31, 2014 0002-9610/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjsurg.2014.11.001
The laparoscopic approach for distal pancreatectomy has gained widespread acceptance as an effective treatment modality for benign or premalignant lesions of the pancreatic body and tail. Multiple, single institutional, prospective studies and several larger multi-institutional retrospective reviews have examined perioperative outcomes following laparoscopic and open distal pancreatectomy.1–5 In general,
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The American Journal of Surgery, Vol 209, No 3, March 2015
these studies demonstrate that laparoscopic pancreatectomy is associated with a shorter hospital stay and less intraoperative blood loss than the open approach. There has, to date, been one multi-institutional examination of laparoscopic distal pancreatectomy specifically for cancer.2 This study examined perioperative outcomes for 23 laparoscopic distal pancreatectomies and compared them with 189 contemporaneous open distal pancreatectomies. There have been no well-powered studies investigating the use of laparoscopic distal pancreatectomy compared with open resection for ductal adenocarcinoma with regard to perioperative oncologic outcomes and the oncologic equivalence of laparoscopic distal pancreatectomy to open distal pancreatectomy has not been demonstrated. In this study, we use a large National Cancer Data Base (NCDB) to determine the potential difference in perioperative outcomes between laparoscopic and open approaches for the management of pancreatic cancer in the body and tail of the pancreas. We hypothesize that the laparoscopic group would have a shorter length of stay, but that there would be no difference between the laparoscopic and open approaches in rates of readmission and postoperative mortality, and several perioperative oncologic outcomes, including lymph node count and rates of margin negative resection.
Native, and Other. Insurance status was examined as private, Medicaid, Medicare, and uninsured/unknown. Facility type included Community Cancer Program, Comprehensive Community Cancer Program, and Academic/ Research/National Cancer Institute Program and are distinguished according to the number of newly diagnosed cancer patients treated and if postgraduate medical education is offered. Specifically, Community Cancer Programs treat between 100 and 500 newly diagnosed cancer patients each year; Comprehensive Community Cancer Programs treat more than 500 cases a year. Academic/research facilities treat more than 500 new cancer cases and offer postgraduate medical education and are grouped with NCI-designated cancer centers. Facility location was categorized into the following regions as defined in the 2010 United States Census: New England (CT, MA, ME, NH, RI, VT), Middle Atlantic (NJ, NY, PA), South Atlantic (DC, DE, FL, GA, MD, NC, SC, VA, WV), East North Central (IL, IN, MI, OH, WI), East South Central (AL, KY, MS, TN), West North Central (IA, KS, MN, MO, ND, NE, SD), West South Central (AR, LA, OK, TX), Mountain (AZ, CO, ID, MT, NM, NV, UT, WY), and Pacific (AK, CA, HI, OR, WA).
Patients and Methods
Statistical analyses were performed using SAS version 9.4 (SAS institute, Inc, Cary, NC). P values less than or equal to .05 were considered statistically significant. Age, demographic factors, comorbid condition (Charlson score), facility factors (type and location), pathologic features (tumor size, number of positive lymph nodes, grade, and stage), treatment factors (neoadjuvant chemotherapy or radiation therapy), and perioperative outcomes (number of lymph nodes examined, margin status, length of stay, 30-day readmission rate, and 30-day mortality rate) for patients who underwent laparoscopic resection were compared with those for patients undergoing open resection. Data for overall survival are available only if a patient was diagnosed 5 years or earlier; therefore, the most recent year that provides for survival is 2006 and thus, in this study, the difference in overall survival between the 2 groups was not investigated. Diseasespecific survival is not captured by the database at this time and that outcome was not evaluated. Comparisons among groups were performed using the Student t-test for continuous variables or chi-square or Fisher’s exact test for categorical variables as appropriate. Patient, tumor, and facility factors were analyzed in multivariable logistic regression models to identify variables associated with length of stay longer than the median of 7 days, lymph node count greater than the median of 12, positive margin status, 30-day unplanned readmission, and 30-day mortality.
Data source The NCDB is a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society; it captures information from approximately 1,500 Commission on Cancer-accredited hospitals and greater than 70% of all newly diagnosed malignancies in the United States. It contains specific details about patient demographics, facility type and location, tumor characteristics, treatment course, and outcomes. All data within the NCDB are deidentified of specific patient factors and are compliant with the Health Insurance Portability and Accountability Act; this study is therefore exempt from approval from our Institutional Review Board.
Study population The NCDB was queried to identify all patients greater than or equal to 18 years old diagnosed with pancreatic adenocarcinoma who underwent a laparoscopic or open partial pancreatectomy between 2010 and 2011. Tumor histology was classified according to the International Classification of Disease for Oncology, Third Edition. Patients were excluded if they had metastatic disease or concomitant cancer diagnoses. Patient age at diagnosis was analyzed as younger than 45, between ages 45 and 64, and 65 years or older. The race of each patient was categorized into White, Black, Hispanic, Asian/Pacific Islander, Native American/Alaskan
Statistical analysis
Results A total of 769 patients underwent distal pancreatectomy for ductal adenocarcinoma: 625 (81%) had an open
S.M. Sharpe et al. Table 1
Laparoscopic open distal pancreatectomy
559
Comparison of open and laparoscopic distal pancreatectomy for adenocarcinoma
Age (years) Mean 6 SD Median %65 66–74 R75 Race White Black Hispanic Asian/Pacific Islander Native American/Alaska Native Other/unknown Charlson/Deyo score 0 1 2 Income ($) ,30,000 30,000–34,999 35,000–45,999 R46,000 Insurance status Uninsured Private insurance Medicaid Medicare Unknown Facility type Community Cancer Program Comprehensive Community Cancer Program Academic/Research/NCI Other Facility location New England Middle Atlantic South Atlantic East North Central East South Central West North Central West South Central Mountain Pacific Tumor size (cm) Mean 6 SD Median %2 .2 Unknown Lymph nodes examined Mean 6 SD Median Lymph nodes positive Negative
Open distal n 5 625 (81%)
Laparoscopic distal n 5 144 (19%)
n (%)
n (%)
65.6 6 10.5 66 297 (48) 184 (29) 144 (23)
67.7 6 10.1 68 55 (38) 47 (33) 42 (29)
474 89 29 19 4 10
120 17 2 4 1 0
P value
.027 .105
.228 (76) (14) (5) (3) (1) (2)
(83) (12) (1) (3) (1) (0) .194
383 (61) 190 (30) 52 (8)
83 (58) 42 (29) 19 (13)
84 108 148 237
(13) (17) (24) (38)
18 22 43 48
(13) (15) (30) (33)
17 284 307 12 5
(3) (45) (49) (2) (1)
3 51 88 1 1
(2) (35) (61) (1) (1)
25 231 368 1
(4) (37) (59) (.2)
1 41 101 1
(1) (29) (70) (1)
29 123 138 116 35 45 55 28 56
(5) (20) (22) (19) (6) (7) (9) (5) (9)
6 31 38 24 8 15 11 1 10
(4) (22) (26) (17) (6) (10) (8) (1) (7)
.437
.124
.010
.417
4.2 6 3.2 3.6 94 (15) 519 (83) 12 (2)
3.7 6 1.9 3.5 30 (21) 111 (77) 3 (2)
13.3 6 9.9 12
14.9 6 10.0 13
.018 .213
.085
.906 286 (46)
69 (48) (continued on next page)
560
The American Journal of Surgery, Vol 209, No 3, March 2015
Table 1
(continued )
Open distal n 5 625 (81%) Positive Unknown Grade Well-differentiated Moderately differentiated Poorly/undifferentiated Unknown Stage I II III Unknown Margin status Negative Positive Unknown Length of stay (days) Mean 6 SD Median 30-day readmission No readmission Unplanned Neoadjuvant chemotherapy No Yes Unknown Neoadjuvant radiation No Yes Unknown 30-day mortality Alive Dead
Laparoscopic distal n 5 144 (19%)
304 (49) 35 (6)
68 (47) 7 (5)
63 310 194 58
(10) (50) (31) (9)
10 85 46 3
(7) (59) (32) (2)
149 444 21 11
(24) (71) (3) (2)
30 107 6 1
(21) (74) (4) (1)
P value
.006
.694
.042 489 (78) 127 (20) 9 (1)
125 (87) 17 (12) 2 (1)
8.9 6 7.5 7
6.8 6 4.6 5
559 (89) 53 (9)
133 (92) 10 (7)
518 (83) 69 (11) 38 (6)
127 (88) 3 (2) 14 (10)
585 (94) 38 (6) 2 (.3)
139 (97) 3 (2) 2 (1)
615 (98) 10 (2)
144 (100) 0 (0)
,.001 .616
,.001
.049
.222
NCI 5 National Cancer Institute; SD 5 standard deviation.
resection and 144 (19%) underwent a laparoscopic resection. Table 1 lists the patient, tumor, facility, and treatment demographics. There were no statistical differences between laparoscopic and open pancreatectomy with regard to race, Charlson score, income, insurance status, or facility location. Patients in the laparoscopic group were older than those in the open group (67.7 6 10.1 vs 65.6 6 10.5 years, P 5 .027). A higher proportion of patients undergoing a laparoscopic distal pancreatectomy were treated at academic/research institutions (70% vs 59%, P 5 .01). More patients in the open group received neoadjuvant chemotherapy (11% vs 2%, P , .001) or radiation (6% vs 2%, P 5.049). Patients in the open group had larger tumors than those in the laparoscopic group (4.2 6 3.2 vs 3.7 6 1.9 cm, P 5 .018); however, the proportion of small and large tumors was not different between the 2 groups (P 5 .213). A larger proportion of patients who underwent open resection had positive margins following pancreatectomy (20% vs 12%, P 5 .042). There were no differences between the 2 groups with regard to the number of lymph
nodes examined, the number of positive lymph nodes, or stage. Length of stay was shorter in the laparoscopic resection group compared with the open group (6.8 6 4.6 vs 8.9 6 7.5, P , .001). The rates of 30-day readmission and 30day mortality were similar between groups. We performed 5 separate multivariable logistic regression analyses predicting lymph node count greater than the median of 12, positive margin status, 30-day unplanned readmission, 30-day mortality, and length of stay greater than the median of 7 days. Each regression controlled for age, Charlson score, facility type and location, tumor size, stage, grade, margin status (except for the regression predicting positive margins), number of lymph nodes examined (except for the regression predicting lymph node count greater than the median), lymph node positivity, neoadjuvant chemotherapy, neoadjuvant radiation, and surgical approach. In the multivariable regression for lymph node count, the variables associated with lymph node assessment greater than the median of 12 were age (odds ratio [OR] .98, 95%
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561
Table 2 Multivariable logistic regression for prolonged length of stay after distal pancreatectomy for adenocarcinoma (median length of stay 5 7 days) Age (years) Charlson/Deyo score 0 1 2 Facility type Community Cancer Program Comprehensive Community Cancer Program Academic/Research/NCI Other Facility location New England Middle Atlantic South Atlantic East North Central East South Central West North Central West South Central Mountain Pacific Tumor size (cm) %2 .2 Unknown Grade Well-differentiated Moderately differentiated Poorly/undifferentiated Unknown Stage I II III Unknown Margin status Negative Positive Number of lymph nodes examined Positive lymph nodes Negative Positive Unknown Neoadjuvant chemotherapy No Yes Unknown Neoadjuvant radiation No Yes Unknown Surgical approach Open distal Laparoscopic distal
Odds ratio (95% CI)
P value
1.03 (1.014–1.046)
.0003
Reference 1.50 (1.055–2.125) 1.43 (.812–2.500)
Reference .024 .217
Reference .91 (.363–2.292) .88 (.349–2.193) 1.87 (.094–37.379)
Reference .845 .775 .682
Reference .92 (.394–2.132) 1.48 (.626–3.347) 1.67 (.701–3.964) 1.02 (.367–2.821) 1.34 (.518–3.466) 1.30 (.500–3.379) .92 (.301–2.821) 1.57 (.603–4.111)
Reference .841 .388 .248 .972 .547 .591 .886 .354
Reference 1.28 (.814–2.011) .81 (.187–3.513)
Reference .285 .779
Reference 1.49 (.845–2.640) 1.07 (.583–1.971) .71 (.307–1.655)
Reference .167 .823 .431
Reference .79 (.508–1.237) .89 (.342–2.328) .90 (.231–3.509)
Reference .306 .815 .879
Reference 1.35 (.898–2.034) 1.00 (.981–1.017)
Reference .149 .928
Reference 1.12 (.770–1.641) 1.62 (.732–3.567)
Reference .543 .235
Reference .87 (.383–1.970) .43 (.204–.902)
Reference .736 .026
Reference 2.62 (.913–7.510) 4.08 (.418–39.837)
Reference .073 .227
Reference .51 (.327–.785)
Reference .002
Odds ratio .1 indicates increased chance of having a hospital length of stay longer than the median (7 days). CI 5 confidence interval; NCI 5 National Cancer Institute.
562 confidence interval [CI] .965 to .996, P 5 .0155), lymph node positivity (OR 2.13, 95% CI 1.463 to 3.085, P , .0001), and treatment in an academic/research institution compared with a Community Cancer Program (OR 3.86, 95% CI 1.326 to 11.223, P 5 .0132) (data not shown). Surgical approach (laparoscopic distal pancreatectomy versus open) was not associated with achieving a lymph node count greater than 12 (OR 1.19, 95% CI .785 to 1.816, P 5 .408) (data not shown). Higher stages when compared with Stage I predicted positive margins in the multivariable regression: Stage II (OR 3.62, 95% CI 1.800 to 7.260, P 5 .0003) and Stage III (OR 10.00, 95% CI 3.289 to 30.375, P , .0001); there was a trend for positive margins with lymph node positivity (OR 1.56, 95% CI .989 to 2.462, P 5 .0558) (data not shown). Laparoscopic distal pancreatectomy was associated with a decreased risk of having positive margins (OR .54, 95% CI .302 to .960, P 5 .0358) (data not shown). The only factor that predicted an increased risk of a 30-day unplanned readmission was older age (OR 1.03, 95% CI 1.002 to 1.064, P 5 .0361); surgical approach was not associated with an increased risk of readmission (OR .83, 95% CI .374 to 1.827, P 5 .637) (data not shown). There were no factors associated with an increased risk of perioperative mortality, including surgical approach (OR .30, 95% CI .049 to 1.786, P 5 .185) (data not shown). Table 2 shows the multivariable regression model for length of stay. The laparoscopic group was half as likely as the open group to have a hospital stay longer than the median of 7 days (OR .51, 95% CI .327 to .785, P 5 .0023). Age (OR 1.03, 95% CI 1.014 to 1.046, P 5 .0003) and Charlson score of 1 (OR 1.50, 95% CI 1.055 to 2.125, P 5 .0237) were associated with a hospital stay longer than 7 days.
Comments There have been relatively few prior studies comparing the perioperative outcomes following laparoscopic distal pancreatectomy with those for open distal pancreatectomy. The largest series was a multi-institutional retrospective comparison of laparoscopic and open distal pancreatectomy4 and included 142 patients in the laparoscopic group. The laparoscopic cohort in this series had shorter lengths of stay than those in the open cohort. This study was not specific for adenocarcinoma and included both benign and malignant tumors. The largest series examining outcomes specifically in cancer patients was a multi-institutional review of 212 patients, of which 23 patients underwent laparoscopic distal pancreatectomy. The patients who had laparoscopic distal pancreatectomy had shorter lengths of stay. There was no difference between laparoscopic and open approaches in operative characteristics (eg, blood loss, operative time, lymph node count, margin status) or perioperative mortality.2 This study evaluates outcomes for 769 patients and confirms that patients who have laparoscopic distal pancreatectomy were in the hospital a median of 2 days fewer and
The American Journal of Surgery, Vol 209, No 3, March 2015 half as likely to have a hospital stay longer than 7 days than those in the open resection group. Our study further demonstrates that the laparoscopic approach provides equivalent numbers of lymph nodes examined and that laparoscopic pancreatectomy patients were less likely to have positive margins than the patients with an open resection, while controlling for age, facility type, tumor size, grade, stage, and neoadjuvant therapy. Our study has several limitations. It is a retrospective review of a national database and has the potential for omitted variable bias. There are no operation-specific data such as blood loss or operative time, nor morbidity data such as pancreatic fistula rate, surgical site infection rate, or overall morbidity rate recorded in the NCDB. Thus, a comparison of the morbidity between the 2 approaches is not possible. There is also undoubtedly some effect of selection bias. The patients who were chosen for laparoscopic resection were older, had smaller tumors, and were more likely to have their operations at academic/research institutions. There are likely additional reasons for the type of procedure chosen that are not captured in the NCDB. Such potential for selection bias cannot be completely avoided when using this database for the comparison. The fact that tumor size was different may impact the improved rates of margin negative resection with laparoscopic pancreatectomy. Other studies have not found a difference in margin status between laparoscopic and open resections, but this may be due to underpowering or other patient or tumor factors.2–4 Additionally, the NCDB does not capture recurrence data in the participant user file available to the public; similarly, the NCDB began collecting information on surgical approach in 2010. However, the latest year for which overall survival data are available is 2006 (5 years earlier than the date of the participant user file used for this study). Therefore, we were unable to compare any differences between the laparoscopic and open approaches with regard to these fundamental oncologic outcomes. Because the number of patients with distal pancreas adenocarcinoma who are eligible for resection is low, a randomized trial comparing the laparoscopic and open approaches with resection, as has been performed in other malignant diseases, is logistically difficult to pursue. Investigations for perioperative outcomes with these methods will likely be limited to retrospective reviews and single institutional prospective studies. To our knowledge, this study represents the largest series evaluating perioperative outcomes between laparoscopic and open distal pancreatectomy for adenocarcinoma. Our study showed no difference between the laparoscopic and open groups regarding number of lymph nodes examined, 30-day readmission rate, and 30-day mortality rate, but noted a decrease in hospital stay and margin positivity rate. Laparoscopic distal pancreatectomy for adenocarcinoma is a safe procedure and does not compromise oncologic outcomes, while, at the same time, provides the established benefits of laparoscopy.
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References 1. Baker MS, Bentrem DJ, Ujiki MB, et al. A prospective single institution comparison of peri-operative outcomes for laparoscopic and open distal pancreatectomy. Surgery 2009;146:635–45. 2. Kooby DA, Hawkins WG, Schmidt M, et al. A multicenter analysis of distal pancreatectomy for adenocarcinoma: is laparoscopic resection appropriate? J Am Coll Surg 2010;210:779–85. 3. Vijan SS, Ahmed KA, Harmsen WS, et al. Laparoscopic vs open distal pancreatectomy: a single-institution comparative study. Arch Surg 2010;145:616–21. 4. Kooby DA, Gillespie T, Bentrem D, et al. Left-sided pancreatectomy: a multicenter comparison of laparoscopic and open approaches. Ann Surg 2008;248:438–46. 5. Kim SC, Park KT, Hwang JW, et al. Comparative analysis of clinical outcomes for laparoscopic distal pancreatic resection and open distal pancreatic resection at a single institution. Surg Endosc 2008;22:2261–8.
Discussion Dr Margo C. Shoup (Warrenville, IL). I didn’t see any mention of any other organs that were resected. I don’t know if you had any of those done laparoscopically in your database. Also, do you have any long-term survival data? Regarding the database, how confident are you that you were able to really select out those patients that had laparoscopic versus open. There is no CPT code for laparoscopic distal pancreatectomy. And then, finally, how many patients had their laparoscopic procedures converted to open and if you analyze those patients with the laparoscopic group, do your results change? Dr Sharpe: Your first question was if other organs were resected. Right now the NCDB does not specify if other
563 organs outside of the pancreas are resected, so we could not make those comparisons between the two surgical approaches. Your second question was whether or not we had long-term survival data. The NCDB only reports 5 year overall survival data. Disease-specific survival is not reported. The date range examined in this study is too recent to have a report on overall survival. Your other question was on the confidence of our selection for laparoscopic or open. Hospitals reporting to the NCDB must have designated NCDB registrars who populate specified data fields. These individuals are required to review the medical records for patients being entered into the NCDB. The data for each patient on exact procedure performed are extracted from operative notes and not determined by CPT codes. And then for your final question regarding why do we exclude those who were converted to open, we thought it provided a more meaningful comparison of laparoscopic and open approaches. We felt that reporting the conversions with the laparoscopic group would obscure the benefit of a successful laparoscopic procedure and thus hide the potential value of the approach. Including conversions in the open cohort could unduly make the open group appear to have poorer results. There were a total of 57 conversions (7% of the total population, 28% of all laparoscopic cases). In data not shown, we have included these on an intent-to-treat basis with the laparoscopic group. In this analysis, there was no longer a difference in the rate of margin negative resection but the laparoscopic cohort continued to demonstrate a decreased length of stay and short-term oncologic results comparable to those for the open cohort.
