Minimally invasive left pancreatectomy for pancreatic ductal adenocarcinoma: review of the current literature
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Abstract
The minimally invasive approach has gained popularity in the last decades, even in complex abdominal surgery such as pancreatic resections. Currently, many meta-analyses focus on the benefits and advantages of the minimally invasive approach compared to open surgery, especially during left pancreatectomy (LP). Limited data on the oncological outcomes are available. The review aims to describe the surgical and oncological outcomes of the minimally invasive left pancreatectomy (MILP). The search terms were based on the final histological pathology (pancreatic adenocarcinoma) and the comparison of different surgical approaches (open vs. minimally invasive). The search strategy was constructed in PubMed and adapted to run across other database platforms, focusing on studies published until 2022. A total of 2,878 studies were selected and duplicates were removed. After title and abstract screening, 109 articles remained for full-text assessment, of which 28 met the eligibility criteria for this systematic review. Considering the study design, the studies were divided into retrospective (n = 15), prospective (n = 4), and 13 propensity score-matched (n = 9). The present review of the literature suggests that MILP is technically feasible and safe for treating body and tail pancreatic ductal adenocarcinoma (PDAC). MILP did not have any impact on the major complications, reducing hospitalization. Regarding the oncological outcomes, the surgical technique did not have an impact on the R0 resection rate, lymph node harvested rate, use of adjuvant chemotherapy, and overall survival. Further prospective randomized trials remain indicated to assess the oncological impact of the MILP in patients with PDAC.
Keywords
INTRODUCTION
The minimally invasive approach to the left-side pancreatic lesions is, actually, considered safe, feasible, and quite easy in expert hands. However, no consensus and robust data in the literature are obtained regarding the use of the minimally invasive approach in the treatment of pancreatic cancer [pancreatic ductal adenocarcinoma (PDAC)]. Since the first report by Gagner in 1996[1], the laparoscopic approach to left pancreatectomy (LP) has gained popularity worldwide, becoming the gold-standard approach for benign and low-grade malignancy lesions of the pancreatic body-tail. The introduction of robotic platforms for performing LP in 2002 contributed to the widespread adoption of minimally invasive pancreatic surgery (MIPS)[2].
After an initial phase where the studies primarily focused on evaluating the safety and feasibility of MIPS on benign or pre-neoplastic lesions, the main effort of the scientific community forthwith changed to try to assess the adequacy and safety of the oncological treatment of PDAC[3]. Although the 2019 Miami guidelines encouraged adopting the minimally invasive approach for all left-side pancreatic lesions, skepticism persisted within the surgical community[4]. This skepticism was highlighted in two recent international surveys, where 19% to 31% of surgeons believed minimally invasive left pancreatectomy (MILP) to be inferior to open LP (OLP) in patients with PDAC[5,6].
Several studies comparing the MILP to OLP consider short-term or surgical outcomes. Few studies focused on the oncological results. However, most of them reported data about all the malignant pancreatic lesions without focusing on PDAC. A large Cochrane review tried to analyze the MILP series on PDAC. The report included 12 studies, demonstrating that different surgical techniques did not have any impact on oncological outcomes, such as tumor negative resection margins (R0), recurrence, and survival. However, all included studies were of very low quality[7].
Recently, data of the literature improved in quality due to the publication of large multicenter or propensity-matched cohort studies. This systematic review aims to compare the short-term and oncological outcomes of patients who underwent minimally invasive vs. open left pancreatic resections.
METHODS
This systematic review was conducted following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines [Figure 1] and the Cochrane Handbook for Systematic Reviews of Interventions[8,9].
Figure 1. The PRISMA study selection flowchart. PRISMA: Preferred reporting items for systematic reviews and meta-analyses.
Literature search
The search terms were derived from the final histological pathology (PDAC) and a comparison of different surgical approaches (open vs. minimally invasive). The search strategy was designed in PubMed and adapted for Ovid and Web of Science databases, focusing on studies published until 2022. The PubMed research was as follows:
((((((“Pancreatic Neoplasms”[Mesh]) OR pancreatic adenocarcinom* [tiab]) OR malignan* [tiab]) OR tumo* [tiab])) AND (((((“Pancreatectomy”[Mesh]) OR distal pancreatectom* [tiab]) OR left pancreatectom* [tiab]) OR spleno pancreatectom* [tiab]) OR pancreatosplenectom* [tiab])) AND ((((“Laparoscopy”[Mesh]) OR laparoscop* [tiab]) OR robot* [tiab]) OR minimally invasive* [tiab]).
Eligibility criteria
Studies must report a comparison of different surgical approaches, such as minimally invasive surgery (laparoscopic or robotic) versus open surgery for the treatment of PDAC in the distal pancreas. Non-English studies, duplicates, editorials, animal studies, and studies involving children were excluded. If the outcomes of interest were not reported or indirectly inferable, the study was also excluded. Small case series (< 10 cases per surgical approach) were not selected for the review. Studies reporting data extracted from national or international databases were screened and only the most recent study was included.
Study selection
Two reviewers (MDP and AC) independently screened the research results based on titles and abstracts, followed by full-text evaluation for eligibility. The full-text eligibility selection was conducted independently by MDP and AC following the Scottish intercollegiate guidelines network (SIGN) methodology[10,11]. Any conflicts were resolved using discussion until a consensus was reached.
Risk of bias
Two independent reviewers (MDP and AC) assessed the study quality according to the Newcastle Ottawa Scale (NOS) for all studies since no randomized controlled trials (RCTs) were expected to be included. The NOS checklist consisted of three different quality parameters: comparability of groups, selected population, and assessment of either the exposure or outcome of interest for case-control or cohort studies. A final score was assigned to each study, ranging from 0 to 9. Studies with a score of 7 or higher were considered high-quality.
Inclusion criteria
The studies included must be written in English, report a study population of more than 20 patients who underwent LP for PDAC, and describe intra-, postoperative, and oncological parameters. To avoid data overlap, the most informative or recent article was considered if the data provided came from the same Institution’s database.
Exclusion criteria
Abstracts, case series, no comparing analysis, review articles, partial or incomplete data reporting, case reports, animal studies, studies involving children, or non-English manuscripts were excluded from the systematic review.
Data extraction
Two different reviewers (MDP and AC) extracted data following a predefined evidence table. Data consisted of study design, study period, country, sample size, type of surgical approach, demographic information [age, body mass index (BMI), American Society of Anesthesiology (ASA) score, neoadjuvant therapy], intraoperative characteristics (operative time, estimated blood loss, vascular resection, multi-visceral resection, and conversion rate), postoperative outcomes (postoperative major complications classified by Clavien-Dindo[12], postoperative pancreatic fistula, post pancreatectomy hemorrhage, delayed gastric empty, and length of hospital stay), and oncological outcomes (R0 resection, harvested lymph nodes, adjuvant chemotherapy, and survival). All pancreas-specific complications were classified by the International Study Group of Pancreatic Surgery (ISGPS) definitions[13-15].
RESULTS
Search results
The literature research resulted in 2,878 studies identified, removing the duplicates. After screening titles and abstracts, 109 articles remained for full-text assessment, of which 28 met the eligibility criteria for this systematic review[3,16-42]. Based on the study design, the papers were categorized as retrospective (n = 14), prospective (n = 4), and propensity score-matched (n = 10) studies. Figure 1 illustrates the PRISMA study selection flowchart.
Methodological quality
As shown in Table 1, most included studies were of moderate to high quality (NOS ≥ 6). Only four studies were designed as prospective analyses. Ten studies used propensity score-matched analysis to compare the surgical approaches. Half of the studies were conducted in the Western Countries. Laparoscopy was the most common minimally invasive approach used. Seven articles reported both, laparoscopic and robotic, surgical procedures, while only a recent Chinese paper compared robotic and OLPs.
Methodological quality of the manuscripts
| Author | Study period | Country | Study design | N of patients | Details of MIS | Quality | |
| MILP | OLP | ||||||
| Retrospective studies | |||||||
| Anderson | 2010-2012 | USA | Retrospective | 505 | 1,302 | LLP (51)/RLP (454) | 8 |
| Chopra | 2008-2019 | USA | Retrospective | 105 | 41 | LLP (17)/RLP (88) | 6 |
| Hao | 2013-2017 | China | Retrospective | 41 | 46 | LLP | 6 |
| Huang | 2014-2018 | China | Retrospective | 20 | 31 | LLP | 5 |
| Hu | 2007-2011 | China | Retrospective | 11 | 23 | LLP | 8 |
| Hirashita | 2007-2019 | Japan | Retrospective | 19 | 31 | LLP | 5 |
| Kantor | 2010-2013 | USA | Retrospective | 349 | 1,205 | LLP | 6 |
| Kooby | 2000-2008 | USA | Retrospective | 23 | 70 | LLP | 7 |
| Magge | 2002-2010 | USA | Retrospective | 28 | 34 | LLP (20)/RLP (8) | 8 |
| Sharpe | 2010-2011 | USA | Retrospective | 144 | 625 | LLP | 7 |
| Sulpice | 2007-2012 | France | Retrospective | 347 | 2,406 | LLP | 8 |
| Zhang | 2003-2013 | China | Retrospective | 17 | 34 | LLP | 7 |
| Zhang | 2012-2018 | China | Retrospective | 25 | 23 | LLP | 6 |
| Zhang | 2010-2014 | China | Retrospective | 22 | 76 | LLP | 6 |
| Prospective studies | |||||||
| Bauman | 2005-2014 | USA | Prospective | 33 | 46 | LLP (28)/RLP (5) | 7 |
| Plotkin | 2011-2014 | USA | Prospective | 166 | 335 | LLP (130)/RLP (36) | 7 |
| Shin | 2006-2013 | Korea | Prospective | 70 | 80 | LLP | 8 |
| Stauffer | 1995-2014 | USA | Prospective | 44 | 28 | LLP | 7 |
| Propensity score matching studies | |||||||
| Balduzzi | 2007-2015 | Italy | Propensity score matching | 44 | 44 | LLP | 8 |
| Chen | 2004-2020 | China | Propensity score matching | 86 | 86 | LLP | 6 |
| Chen | 2010-2019 | China | Propensity score matching | 66 | 66 | LLP | 7 |
| Kwon | 2010-2017 | Korea | Propensity score matching | 156 | 156 | \ | 7 |
| Lee | 2007-2010 | Korea | Propensity score matching | 10 | 40 | LLP (8)/RLP (4) | 8 |
| Lee | 2009-2017 | Korea | Propensity score matching | 35 | 105 | LLP | 7 |
| Raoof | 2010-2013 | USA | Propensity score matching | 563 | 563 | LLP | 8 |
| Van Hilst | 2007-2015 | Dutch | Propensity score matching | 340 | 340 | LLP (324)/RLP (16) | 8 |
| Watson | 2010-2016 | USA | Propensity score matching | 805 | 805 | \ | 8 |
| Weng | 2011-2019 | China | Propensity score matching | 170 | 166 | RLP | 8 |
Minimally invasive left pancreatectomy vs. open left pancreatectomy
A total of 28 studies on MILP vs. OLP were included in the systematic review. Overall, 4,254 and 8,807 patients were submitted to MILP and OLP, respectively. The growth of the minimally invasive approach is evidenced by the increased use of robotic platforms, with 660 robotic procedures reported in studies published after 2010, compared to 125 robotic distal pancreatectomies before 2010.
Few data were reported about the baseline and demographic characteristics of the patients [Supplementary Table 1]. Most studies reported no significant differences between the groups in terms of age, BMI, and ASA score. The open approach was preferred for surgical exploration post-chemotherapy, as reported in a large series by Sharpe et al. and Plotkin et al. Conversion rate had a high variation across the studies ranging from 0% to 40%[25,31] [Supplementary Table 2]. Table 2 and Supplementary Table 2 summarize the intraoperative outcomes. Since the first study, the minimally invasive approach reported an improvement in the operating time and estimated blood loss. A recent propensity score-matching study from Weng et al. reported a significant reduction in the median operative time (120 vs. 180 min, P < 0.001) comparing the robotic approach to the OLP[43]. The better results were more evident in analyzing the estimated blood loss. Almost all the studies reported a decrease in blood loss during the MIDP across the study period. Indeed, considering two large propensity score-matching studies by Van Hilst et al. and Chen et al., both reported significant improvements in the intraoperative bleeding control (200 vs. 300 mL, P < 0.001; 195 vs. 210 mL, P < 0.01, respectively)[35,40]. Major vessel resections were poorly described and, most of the time, involved venous resection and an open approach.
Intraoperative and postoperative outcomes
| Author | Procedure | Operation time | P value | Blood loss | P value | CD > 2 complications | P value | Postoperative hospital stay | P value |
| Retrospective studies | |||||||||
| Anderson | MIS 505 Open 1,302 | N.A. | \ | N.A. | \ | N.A. | \ | 6 (5-8) 7 (6-10) | < 0.001 |
| Chopra | MIS 105 Open 41 | 280 (174-416) 248 (181-334) | 0.001 | 181 (50-606) 200 (100-450) | 0.119 | 23% 10% | 0.414 | 6 (5-8) 7 (5.5-7) | 0.695 |
| Hao | LAP 41 Open 46 | 411.0 ± 106.2 355.8 ± 72.7 | NS | 294.4 ± 247.5 338.6 ± 230.0 | 0.410 | 3% 2% | 0.500 | 7.9 ± 1.4 11.5 ± 2.7 | < 0.001 |
| Huang | LAP 20 Open 31 | 273.8 ± 90.3 264.3 ± 77.1 | 0.692 | 252.5 ± 198.3 472.6 ± 428.0 | 0.037 | 5% 3% | 0.263 | 19.0 ± 9.9 19.6 ± 16.8 | 0.876 |
| Hu | LAP 11 Open23 | 150.0 ± 54.0 160.0 ± 48.0 | 0.445 | 100 (50-400) 150 (50-350) | 0.678 | N.A. | \ | 5.2 ± 2.5 8.6 ± 3.9 | 0.010 |
| Hirashita | LAP 19 Open 31 | 397.0 ± 78.0 319.0 ± 80.0 | 0.001 | 299.0 ± 237.0 576.0 ± 78.0 | 0.034 | N.A. | \ | 21.5 ± 10.5 29.4 ± 23.3 | 0.171 |
| Kantor | MIS 349 Open 1,205 | N.A. | \ | N.A. | \ | N.A. | \ | 7.1 ± 6.0 8.7 ± 7.3 | < 0.001 |
| Kooby | LAP 23 Open 189 | 238.4 ± 68.1 230.4 ± 80.4 | 0.065 | 422.0 ± 473.0 790.0 ± 828.0 | 0.040 | N.A. | \ | 7.4 ± 3.4 10.7 ± 6.3 | 0.030 |
| Magge | MIS 28 Open 34 | 317.0 ± 23.0 294.0 ± 24.0 | NS | 290.0 ± 60.0 570.0 ± 80.0 | 0.006 | 0% 9% | 0.730 | 6 (IQR: 3) 8 (IQR: 2.75) | 0.030 |
| Sharpe | LAP 144 Open 625 | N.A. | \ | N.A. | \ | N.A. | \ | 6.8 ± 4.6 8.9 ± 7.5 | < 0.001 |
| Sulpice | LAP 347 Open 2,406 | N.A. | \ | N.A. | \ | 7% 10% | 0.028 | 14.9 ± 8.9 19.6 ± 14.6 | < 0.001 |
| Zhang | LAP 25 Open 23 | 212.2 ± 66.3 203.1 ± 39.7 | 0.572 | 402.0 ± 258.8 506.5 ± 418.4 | 0.119 | N.A. | \ | 11.7 ± 5.2 12.9 ± 5.0 | 0.425 |
| Zhang | LAP 22 Open 76 | 188.0 ± 39.0 160.0 ± 35.0 | 0.060 | 210.0 ± 130.0 240.0 ± 120.0 | 0.240 | N.A. | \ | N.A. | \ |
| Zhang | LAP 17 Open 34 | 190 (100-390) 245 (155-420) | 0.064 | 50 (30-500) 400 (100-3,900) | < 0.001 | 0% 9% | 0.754 | 13 (4-23) 15.5 (6-40) | 0.022 |
| Prospective studies | |||||||||
| Bauman | LAP 33 Open 46 | 234.0 ± 12.0 252.0 ± 12.0 | 0.360 | 310.0 ± 68.0 597.0 ± 95.0 | 0.016 | 15% 22% | 0.100 | 7.6 ± 1.4 9.0 ± 0.7 | 0.440 |
| Plotkin | MIS 166 Open 355 | 239.0 ± 9.0 250.0 ± 6.2 | 0.311 | N.A. | \ | 10% 15% | 0.024 | 5.0 ± 0.31 7.0 ± 0.51 | 0.009 |
| Shin | LAP 70 Open 80 | 239 (125-397) 254 (115-573) | 0.320 | N.A. | \ | 20% 26% | 0.310 | 9 (5-29) 12 (7-87) | < 0.001 |
| Stauffer | LAP 44 Open 28 | 254 (99-521) 266 (131-543) | 0.596 | 322 (10-2650) 874 (150-3,400) | 0.001 | 14% 25% | 0.346 | 5.1 (2-17) 9.4 (4-36) | < 0.001 |
| Propensity score matching studies | |||||||||
| Balduzzi | LAP 44 Open 44 | 240 (195-322) 280 (222-379) | 0.107 | 290 (70-650) 333 (130-700) | 0.495 | 25% 34% | 0.350 | 9 (6-13) 13 (8-23) | 0.005 |
| Chen | LAP 66 Open 66 | 193.6 ± 49.6 217.5 ± 61.0 | 0.020 | 195 (80-800) 210 (80-800) | < 0.01 | 6% 12% | 0.500 | 12 (4-34) 15 (7-42) | < 0.01 |
| Chen | LAP 86 Open 86 | 189.1 ± 45.2 213.3 ± 54.4 | < 0.01 | 180 (80-600) 220 (120-800) | < 0.01 | 5% 11% | 0.330 | 9 (4-34) 13 (7-42) | < 0.01 |
| Kwon | MIS 156 Open 156 | 217 ± 56 222 ± 81 | 0.500 | N.A. | \ | 6% 3% | 0.190 | 10.0 ± 5.1 13.4 ± 7.9 | < 0.001 |
| Lee | MIS 10 Open 40 | 330.0 ± 168.2 253.3 ± 124.7 | 0.112 | 440.0 ± 328.0 625.0 ± 879.0 | 0.366 | N.A. | \ | 12.7 ± 7.1 22.1 ± 27.1 | 0.050 |
| Lee | LAP 35 Open 105 | 128.0 ± 40.0 170.0 ± 64.0 | 0.001 | 235.0 ± 240.0 252.0 ± 229.0 | 0.718 | 11% 15% | 0.782 | 11.1 ± 6.7 14.4 ± 7.7 | 0.026 |
| Raoof | LAP 563 Open 563 | N.A. | \ | N.A. | \ | N.A. | \ | 6 (5-8) 7 (5-9) | < 0.001 |
| Van Hilst | MIS 340 Open 340 | 240 (180-295) 230 (178-286) | 0.626 | 200 (60-400) 300 (150-500) | < 0.001 | 18% 21% | 0.431 | 8 (6-12) 9 (7-14) | < 0.001 |
| Watson | MIS 805 Open 805 | N.A. | \ | N.A. | \ | N.A. | \ | 6.8 ± 5.5 8.5 ± 7.3 | < 0.001 |
| Weng | Robotic 170 Open 166 | 120 (110-180) 180 (150-234) | < 0.001 | 100 (50-200) 200 (100-350) | < 0.001 | N.A. | \ | 14 (10-21) 17 (12-24) | 0.001 |
Regarding the postoperative outcomes, the use of the minimally invasive approach did not have any impact on the occurrence of major complications when compared to the OLP. Only large series, such as those by Sulpice et al. and Plotkin et al., reported a favorable outcome in the minimally invasive group (6.6% vs. 10.4%, P = 0.028; 31.0% vs. 42.0%, P = 0.024, respectively)[26,31]. Pancreas-specific complications such as pancreatic fistula, post-pancreatectomy hemorrhage, and delayed gastric emptying were not affected by the surgical approach [Supplementary Table 3].
However, almost the entire cohorts reported in the literature recorded a lower hospital length of stay in the minimally invasive group across all the study designs and periods analyzed. Different minimally invasive approaches, whether laparoscopic or robotic, did not influence the reduction in hospitalization, as demonstrated by large series such as those by Kantor et al. (7.1 ± 6.0 vs. 8.7 ± 7.3 days, P < 0.001), and Weng et al. [14 (10-21) vs. 17 (12-24) days, P = 0.001][22,43].
Table 3 shows the oncological outcomes. The minimally invasive approach was not inferior when compared to OLP regarding the radical resection status. Furthermore, MILP appeared superior to OLP in achieving R0 status. Anderson et al. described a significant increase in the surgical margin disease-free of the minimally invasive resections compared to the open group (85.9% vs. 79.0%, P < 0.001)[16]. Overall, the harvested lymph node rate resulted appropriated, even higher in the minimally invasive group as described by Stauffer et al. (26 vs. 13, P < 0.001)[3]. Two studies by Van Hilst et al. and Weng et al. reported a significant decrease in the number of harvested lymph nodes during MILP (14 vs. 22, P < 0.001; 9 vs. 12, P = 0.003, respectively)[40,43].
Oncological outcomes
| Author | Procedure | R0 status | P value | Harvested LN | P value | Adjuvant chemotherapy | P value | Overall survival | P value |
| Retrospective studies | |||||||||
| Anderson | MIS 505 Open 1,302 | 85.9% 79.0% | < 0.001 | 12 (7-19) 12 (7-19) | 0.350 | 57.8% 53.8% | 0.110 | 3 years 55% 3 years 52% | 0.420 |
| Chopra | MIS 105 Open 41 | 69.5% 65.9% | 0.538 | 24 (10-56) 20 (9-48) | 0.077 | 77.0% 70.7% | 0.628 | 33.5 months 28.4 months | 0.914 |
| Hao | LAP 41 Open 46 | 88.9% 81.8% | 0.760 | 8.7 ± 6 8.4 ± 5.8 | 0.830 | N.A. | \ | 24.0 months 21.0 months | 0.090 |
| Huang | LAP 20 Open 31 | 100.0% 97.0% | 0.315 | 9.6 ± 6.4 12.8 ± 5.8 | 0.203 | 70.0% 80.6% | 0.382 | 2 years 50.2% 2 years 38.3% | 0.411 |
| Hu | LAP 11 Open23 | 100.0% 100.0% | NS | 14.8 ± 4.5 16.1 ± 5.7 | 0.875 | N.A. | \ | 42.0 months 54.0 months | NS |
| Hirashita | LAP 19 Open 31 | N.A. | \ | 14.0 ± 17.0 19.0 ± 18.0 | 0.845 | 68.0% 68.0% | NS | N.A. | 0.084* |
| Kantor | MIS 349 Open 1,205 | 82.2% 75.1% | < 0.001 | 14.0 ± 11.7 14.8 ± 12.0 | 0.310 | 67.9% 61.8% | 0.050 | 29.9 months 24.0 months | 0.090 |
| Kooby | LAP 23 Open 189 | 74.0% 73.0% | 0.098 | 13.8 ± 8.4 12.5 ± 8.5 | 0.470 | 57.0% 70.0% | 0.230 | 11.0 months 11.0 months | 0.710 |
| Magge | MIS 28 Open 34 | 86.0% 88.0% | NS | 11 (8-20) 12 (6-19) | 0.750 | N.A. | \ | N.A. | 0.800* |
| Sharpe | LAP 144 Open 625 | 87.0% 78.0% | 0.042 | 14.9 ± 10.0 13.3 ± 9.9 | 0.085 | N.A. | \ | N.A. | \ |
| Sulpice | LAP 347 Open 2,406 | N.A. | \ | N.A. | \ | N.A. | \ | 62.5 months 36.7 months | < 0.001 |
| Zhang | LAP 25 Open 23 | 92.0% 95.6% | 0.663 | 15.8 ± 6.7 18.2 ± 7.9 | 0.268 | 92.0% 82.6% | 0.716 | 24.5 months 28.7 months | 0.633 |
| Zhang | LAP 22 Open 76 | 91.0% 87.0% | 0.610 | 11.2 ± 4.6 14.4 ± 5.5 | 0.440 | N.A. | \ | 29.6 months 27.6 months | 0.340 |
| Zhang | LAP 17 Open 34 | 94.1% 85.3% | 0.650 | 9 (5-15) 8 (2-22) | 0.534 | 76.5% 76.5% | NS | 14.0 months 14.0 months | 0.802 |
| Prospective studies | |||||||||
| Bauman | LAP 33 Open 46 | 77.0% 87.0% | 0.530 | 14.5 ± 1.1 17.5 ± 1.2 | 0.070 | 61.0% 63.0% | 0.830 | 17.9 months 15.1 months | NS |
| Plotkin | MIS 166 Open 355 | N.A. | \ | N.A. | \ | N.A. | \ | N.A. | \ |
| Shin | LAP 70 Open 80 | 75.7% 83.8% | 0.220 | 12 (1-34) 10 (1-64) | 0.130 | 78.6% 68.8% | 0.180 | 33.4 months 29.1 months | 0.250 |
| Stauffer | LAP 44 Open 28 | 95.5% 82.1% | 0.101 | 26 (5-48) 13 (1-45) | < 0.001 | 75.6% 75.0% | NS | 26.6 months 26.4 months | 0.851 |
| Propensity score matching studies | |||||||||
| Balduzzi | LAP 44 Open 44 | 67.0% 48.0% | 0.063 | 11 (6-22) 19 (11-30) | 0.023 | 71.0% 79.0% | 0.758 | 19 months 20 months | 0.571 |
| Chen | LAP 66 Open 66 | 97.0% 89.4% | 0.008 | 13.4 ± 5.4 11.7 ± 5.1 | 0.006 | 71.2% 65.2% | 0.460 | 19.0 months 17.0 months | 0.330 |
| Chen | LAP 86 Open 86 | 96.5% 90.7% | 0.120 | 14.4 ± 5.2 12.7 ± 5.0 | 0.030 | 70.9% 66.3% | 0.510 | N.A. | 0.500 |
| Kwon | MIS 156 Open 156 | 76.3% 64.1% | 0.019 | 14.1 ± 8.7 15.6 ± 9.7 | 0.150 | 66.7% 66.4% | NS | 34.9 months 24.5 months | 0.012 |
| Lee | MIS 10 Open 40 | 100.0% 87.5% | 0.426 | 11.7 ± 7.2 12.1 ± 8.1 | 0.887 | 70.0% 65.0% | 0.765 | N.A. | 0.053* |
| Lee | LAP 35 Open 105 | 94.3% 90.5% | 0.730 | 12.6 ± 8.1 14.3 ± 10.0 | 0.380 | N.A. | \ | N.A. | \ |
| Raoof | LAP 563 Open 563 | 85.1% 81.5% | 0.110 | 12 (7-18) 11 (6-18.5) | 0.759 | N.A. | \ | 3 years 41.6% 3 years 36.0% | 0.457 |
| Van Hilst | MIS 340 Open 340 | 67.0% 58.0% | 0.019 | 14 (8-22) 22 (14-31) | < 0.001 | 76.0% 73.0% | 0.561 | 28.0 months 31.0 months | 0.774 |
| Watson | MIS 805 Open 805 | 83.1% 80.0% | 0.605 | 13.8 ± 10.3 14.2 ± 10.1 | 0.524 | 53.4% 51.6% | 0.454 | 28.0 months 21.0 months | 0.006 |
| Weng | Robotic 170 Open 166 | 92.9% 89.2% | 0.224 | 9 (4-14) 12 (7-17) | 0.003 | 61.8% 67.5% | 0.274 | 31.0 months 27.0 months | 0.070 |
The adjuvant treatment rate reported was surprisingly inferior to expectation. The different surgical approaches did not have any impact on this result, even if positive postoperative outcomes have been reported in the minimally invasive group. Comparable results were recorded for the overall postoperative survival. Overall, the surgical approach did not affect the patient’s survival. However, a large series reported some long-term benefits of the MILP. Sulpice et al. analyzed 347 laparoscopic LP, describing a significant improvement in survival in the minimally invasive group (62.5 vs. 36.7 months, P < 0.001)[26]. These data were confirmed by two recent large series by Kwon et al. and Watson et al. that reported a higher overall survival rate of the MILP when compared to OLP (34.9 vs. 24.5 months, P = 0.012; 28.0 vs. 21.0 months, P = 0.006, respectively)[36,41].
DISCUSSION
Despite advances in surgical techniques and the widespread use of minimally invasive approaches for resecting benign and pre-malignant pancreatic tumors, pancreatic resection for adenocarcinoma remains a challenge, even in experienced hands[44].
The results of this systematic review have revealed that MILP was safe and feasible even in the treatment of PDAC. The minimally invasive approach appears to be at least as effective as the open approach in terms of intra- and postoperative outcomes. Furthermore, the minimally invasive technique appeared to reduce both estimated blood loss and hospital length of stay. Regarding oncological outcomes, MILP again proved to be non-inferior when compared to OLP. Particularly, the MILP reached at least the same accuracy as the OLP in the lymphadenectomy and R0 resection.
Since the introduction of MIPS, there has been significant skepticism regarding its short- and long-term outcomes, especially compared to open surgery[45]. Nevertheless, this review clearly demonstrates a growing interest in MIPS over time. Increased use, standardization, and technological advancements have led to improved MIPS outcomes. Indeed, MILP, even when used in treating PDAC, showed advantages over open surgery, including reduced estimated blood loss (11/19 studies), shorter hospital stays (22/27 studies), comparable operative time (14/20 studies), and lower rates of major postoperative complications (15/18 studies).
For left-sided PDAC, the recommended oncological treatment includes resection of the spleen, Gerota’s fascia, and appropriate lymphadenectomy (at least 11 lymph nodes with resection of stations 10, 11, and 18 for pancreatic tail tumors, also adding stations 8 and 9 in case of pancreatic body tumors)[46,47]. In a recent multicenter study involving 1,200 patients from 34 centers, resection of Gerota’s fascia (P = 0.019), R0 resection (P = 0.006), and a decreased lymph node ratio (P < 0.001) were identified as positive prognostic factors for overall survival[46]. Furthermore, two systematic reviews involving PDAC patients who underwent MILP analyzed these oncological outcomes[48,49]. These studies were significantly small, including only 5 and 12 studies with a total of 261 and 1,506 patients, respectively. However, the surgical free resection margin rate and survival reported were similar between the two surgical approaches, though the evidence available was of low quality. In the present study, after reviewing 28 studies, both R0 resection and survival rates were comparable between MILP and OLP (no difference in 19/28 and 22/28 studies, respectively). Additionally, similar results were found when considering the lymph node harvest rate (no difference in 20/28 studies). These findings were supported by the results of the latest RCT on the oncological safety and feasibility of the MILP[50]. The DIPLOMA trial is an international multicenter study that provided the best evidence of the non-inferiority of MILP for radical resection margin rate compared to OLP[50]. Furthermore, the study assessed that the harvested lymph node rate was similar in both groups. MILP was correlated to longer operative times but provided better aesthetic results one year postoperatively. In line with the results of this review, the surgical approach did not affect other postoperative outcomes. However, the authors did not record any benefits for time to functional recovery, estimated blood loss, and length of hospital stay from MILP as has been described in previous RCT performed for all indications[51,52]. To date, three RCTs are ongoing to compare MILP vs. OLP in patients with PDAC: (1) the LAPAN study, promoted by the Japan Clinical Oncology Group study (jRCT 1031220705)[53]; (2) the NCT03792932 trial performed by the Fudan University in China; and (3) the NCT03957135 trial performed by the Seoul National University Hospital in Korea.
Oncological outcomes may be closely linked to surgical outcomes. Indeed, we can assume that a short length of stay and a short time to return to normal activity are associated with a higher adjuvant chemotherapy treatment rate. It is widely recognized that completing adjuvant chemotherapy after PDAC resection is associated with improved overall survival. Recently, a study on 2,440 patients treated with upfront surgery for PDAC, showed that at least 65% of patients did not receive chemotherapy after surgery. Only 7% of the patients completed the adjuvant chemotherapy, while 28% received incomplete treatment[54]. The results of this review underlined the shorter hospitalization of the patients submitted to MILP compared to OLP, recording the same major complication rate. However, no significant difference in adjuvant treatment was reported between the two approaches. This could be explained by the possibility that the MIPS series included smaller tumors in the minimally invasive arm, which may not require adjuvant treatment after neoadjuvant chemotherapy.
The present results should be read carefully due to several limitations and potential selection bias of the included studies. Indeed, the selection criteria for candidates undergoing MIDP varied across studies and are commonly linked to postoperative outcomes. Young patients, with low BMI, small lesions at the first stage, no vascular involvement, and without previous abdominal surgery are more often selected for MILP. The availability of robotic platforms may also contribute to selection bias. Third, the robotic procedures could be performed only in high-volume centers by expert surgeons. Fourth, a clear definition of free surgical margin or R0 resection is unavailable. The heterogeneity of the definitions could affect the oncological data, especially the patient’s survival, as previously reported[55]. Fifth, only one RCT was available. Despite efforts to report more comparable data, using a registry, prospective database, or propensity score matching studies, RCTs remain mandatory to assess the real benefit of MILP in patients affected by PDAC.
CONCLUSIONS
This literature review suggests that MILP is technically feasible and safe for treating pancreatic adenocarcinoma of the body and tail. MILP did not affect major complications but reduced hospitalization time. In terms of oncological outcomes, free surgical resection margin rate, lymph node harvested rate, use of adjuvant chemotherapy, and overall survival were not influenced by the surgical technique. Further prospective randomized trials are warranted to assess the oncological benefit of MILP in patients affected by PDAC.
DECLARATIONS
Authors’ contributions
Conception and design: De Pastena M, Coppola A
Administrative support: De Pastena M, Coppola A
Provision of study materials or patients: De Pastena M, Coppola A
Collection and assembly of data: De Pastena M, Coppola A, Esposito A, Casciani F, Tufo A, Salvia R
Data analysis and interpretation: De Pastena M, Coppola A, Esposito A, Casciani F, Tufo A, Salvia R
Manuscript writing: De Pastena M, Coppola A, Esposito A, Casciani F, Tufo A, Salvia R
Final approval of manuscript: De Pastena M, Coppola A, Esposito A, Casciani F, Tufo A, Salvia R
Availability of data and materials
Not Applicable.
Financial support and sponsorship
None.
Conflicts of interest
All authors declared that there are no conflicts of interest.
Ethical approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Copyright
© The Author(s) 2024.
Supplementary Materials
REFERENCES
1. Gagner M, Pomp A, Herrera MF. Early experience with laparoscopic resections of islet cell tumors. Surgery 1996;120:1051-4.
2. Melvin WS, Needleman BJ, Krause KR, et al. Computer-enhanced robotic telesurgery. Initial experience in foregut surgery. Surg Endosc 2002;16:1790-2.
3. Stauffer JA, Coppola A, Mody K, Asbun HJ. Laparoscopic versus open distal pancreatectomy for pancreatic adenocarcinoma. World J Surg 2016;40:1477-84.
4. Ann Surg 2020. pp. 1-14. Asbun HJ, Moekotte AL, Vissers FL, et al; International Study Group on Minimally Invasive Pancreas Surgery (I-MIPS). The Miami international evidence-based guidelines on minimally invasive pancreas resection. Ann Surg 2020;271:1-14.
5. de Rooij T, Besselink MG, Shamali A, et al; DIPLOMA trial group. Pan-European survey on the implementation of minimally invasive pancreatic surgery with emphasis on cancer. HPB 2016;18:170-6.
6. van Hilst J, de Rooij T, Abu Hilal M, et al. Worldwide survey on opinions and use of minimally invasive pancreatic resection. HPB 2017;19:190-204.
7. Riviere D, Gurusamy KS, Kooby DA, et al. Laparoscopic versus open distal pancreatectomy for pancreatic cancer. Cochrane Database Syst Rev 2016;4:CD011391.
8. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009;6:e1000097.
9. Cumpston M, Li T, Page MJ, et al. Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Database Syst Rev 2019;10:ED000142.
10. Vernooij RWM, Alonso-Coello P, Brouwers M, Martínez García L. CheckUp Panel. Reporting items for updated clinical guidelines: checklist for the reporting of updated guidelines (CheckUp). PLoS Med 2017;14:e1002207.
11. Gagliardi AR, Marshall C, Huckson S, James R, Moore V. Developing a checklist for guideline implementation planning: review and synthesis of guideline development and implementation advice. Implement Sci 2015;10:19.
12. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004;240:205-13.
13. Bassi C, Marchegiani G, Dervenis C, et al; International Study Group on Pancreatic Surgery (ISGPS). The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 years after. Surgery 2017;161:584-91.
14. Wente MN, Veit JA, Bassi C, et al. Postpancreatectomy hemorrhage (PPH): an International Study Group of Pancreatic Surgery (ISGPS) definition. Surgery 2007;142:20-5.
15. Wente MN, Bassi C, Dervenis C, et al. Delayed gastric emptying (DGE) after pancreatic surgery: a suggested definition by the International Study Group of Pancreatic Surgery (ISGPS). Surgery 2007;142:761-8.
16. Anderson KL Jr, Adam MA, Thomas S, Roman SA, Sosa JA. Impact of minimally invasive vs. open distal pancreatectomy on use of adjuvant chemoradiation for pancreatic adenocarcinoma. Am J Surg 2017;213:601-5.
17. Chopra A, Nassour I, Zureikat A, Paniccia A. Perioperative and oncologic outcomes of open, laparoscopic, and robotic distal pancreatectomy for pancreatic adenocarcinoma. Updates Surg 2021;73:947-53.
18. Hao T, Shiming J, Yong C. Analysis of safety and efficacy of laparoscopic distal pancreatectomy in the treatment of left pancreatic malignant tumors. J Int Med Res 2021;49:3000605211063098.
19. Huang J, Xiong C, Sheng Y, Zhou X, Lu CD, Cai X. Laparoscopic versus open radical antegrade modular pancreatosplenectomy for pancreatic cancer: a single-institution comparative study. Gland Surg 2021;10:1057-66.
20. Hu M, Zhao G, Wang F, Zhao Z, Li C, Liu R. Laparoscopic versus open distal splenopancreatectomy for the treatment of pancreatic body and tail cancer: a retrospective, mid-term follow-up study at a single academic tertiary care institution. Surg Endosc 2014;28:2584-91.
21. Hirashita T, Iwashita Y, Fujinaga A, et al. Surgical and oncological outcomes of laparoscopic versus open radical antegrade modular pancreatosplenectomy for pancreatic ductal adenocarcinoma. Surg Today 2022;52:224-30.
22. Kantor O, Bryan DS, Talamonti MS, et al. Laparoscopic distal pancreatectomy for cancer provides oncologic outcomes and overall survival identical to open distal pancreatectomy. J Gastrointest Surg 2017;21:1620-5.
23. Kooby DA, Hawkins WG, Schmidt CM, et al. A multicenter analysis of distal pancreatectomy for adenocarcinoma: is laparoscopic resection appropriate? J Am Coll Surg 2010;210:779-87.
24. Magge D, Gooding W, Choudry H, et al. Comparative effectiveness of minimally invasive and open distal pancreatectomy for ductal adenocarcinoma. JAMA Surg 2013;148:525-31.
25. Sharpe SM, Talamonti MS, Wang E, et al. The laparoscopic approach to distal pancreatectomy for ductal adenocarcinoma results in shorter lengths of stay without compromising oncologic outcomes. Am J Surg 2015;209:557-63.
26. Sulpice L, Farges O, Goutte N, et al; ACHBT French Pancreatectomy Study Group. Laparoscopic distal pancreatectomy for pancreatic ductal adenocarcinoma: time for a randomized controlled trial? Results of an all-inclusive national observational study. Ann Surg 2015;262:868-73; discussion 873-4.
27. Zhang H, Li Y, Liao Q, et al. Comparison of minimal invasive versus open radical antegrade modular pancreatosplenectomy (RAMPS) for pancreatic ductal adenocarcinoma: a single center retrospective study. Surg Endosc 2021;35:3763-73.
28. Zhang M, Fang R, Mou Y, et al. LDP vs ODP for pancreatic adenocarcinoma: a case matched study from a single-institution. BMC Gastroenterol 2015;15:182.
29. Zhang AB, Wang Y, Hu C, Shen Y, Zheng SS. Laparoscopic versus open distal pancreatectomy for pancreatic ductal adenocarcinoma: a single-center experience. J Zhejiang Univ Sci B 2017;18:532-8.
30. Bauman MD, Becerra DG, Kilbane EM, et al. Laparoscopic distal pancreatectomy for pancreatic cancer is safe and effective. Surg Endosc 2018;32:53-61.
31. Plotkin A, Ceppa EP, Zarzaur BL, Kilbane EM, Riall TS, Pitt HA. Reduced morbidity with minimally invasive distal pancreatectomy for pancreatic adenocarcinoma. HPB 2017;19:279-85.
32. Shin SH, Kim SC, Song KB, et al. A comparative study of laparoscopic vs. open distal pancreatectomy for left-sided ductal adenocarcinoma: a propensity score-matched analysis. J Am Coll Surg 2015;220:177-85.
33. Balduzzi A, van Hilst J, Korrel M, et al; European Consortium on Minimally Invasive Pancreatic Surgery (E- MIPS). Laparoscopic versus open extended radical left pancreatectomy for pancreatic ductal adenocarcinoma: an international propensity-score matched study. Surg Endosc 2021;35:6949-59.
34. Chen K, Tong Q, Yan JF, et al. Laparoscopic versus open distal pancreatectomy for pancreatic ductal adenocarcinoma: a single-center propensity score matching study. Updates Surg 2020;72:387-97.
35. Chen K, Pan Y, Huang CJ, et al. Laparoscopic versus open pancreatic resection for ductal adenocarcinoma: separate propensity score matching analyses of distal pancreatectomy and pancreaticoduodenectomy. BMC Cancer 2021;21:382.
36. Kwon J, Park SY, Park Y, et al. A comparison of minimally invasive vs open distal pancreatectomy for resectable pancreatic ductal adenocarcinoma: propensity score matching analysis. J Hepatobiliary Pancreat Sci 2021;28:967-82.
37. Lee SH, Kang CM, Hwang HK, Choi SH, Lee WJ, Chi HS. Minimally invasive RAMPS in well-selected left-sided pancreatic cancer within Yonsei criteria: long-term (>median 3 years) oncologic outcomes. Surg Endosc 2014;28:2848-55.
38. Lee JM, Kim H, Kang JS, et al. Comparison of perioperative short-term outcomes and oncologic long-term outcomes between open and laparoscopic distal pancreatectomy in patients with pancreatic ductal adenocarcinoma. Ann Surg Treat Res 2021;100:320-8.
39. Raoof M, Ituarte PHG, Woo Y, et al. Propensity score-matched comparison of oncological outcomes between laparoscopic and open distal pancreatic resection. Br J Surg 2018;105:578-86.
40. van Hilst J, de Rooij T, Klompmaker S, et al; European Consortium on Minimally Invasive Pancreatic Surgery (E-MIPS). Minimally invasive versus open distal pancreatectomy for ductal adenocarcinoma (DIPLOMA): a pan-european propensity score matched study. Ann Surg 2019;269:10-7.
41. Watson MD, Baimas-George MR, Thompson KJ, et al. Improved oncologic outcomes for minimally invasive left pancreatectomy: propensity-score matched analysis of the National Cancer Database. J Surg Oncol 2020;122:1383-92.
42. Chen H, Shen Z, Ying X, et al. Robotic distal pancreatectomy reduces pancreatic fistula in patients without visceral obesity as compared to open distal pancreatectomy: a propensity score matching retrospective cohort study. Int J Surg 2021;90:105960.
43. Weng Y, Shen Z, Gemenetzis G, et al. Oncological outcomes of robotic pancreatectomy in patients with pancreatic cancer who receive adjuvant chemotherapy: a propensity score-matched retrospective cohort study. Int J Surg 2022;104:106801.
44. Ohtsuka T, Nagakawa Y, Toyama H, et al. A multicenter prospective registration study on laparoscopic pancreatectomy in Japan: report on the assessment of 1,429 patients. J Hepatobiliary Pancreat Sci 2020;27:47-55.
45. de Rooij T, Klompmaker S, Abu Hilal M, Kendrick ML, Busch OR, Besselink MG. Laparoscopic pancreatic surgery for benign and malignant disease. Nat Rev Gastroenterol Hepatol 2016;13:227-38.
46. Korrel M, Lof S, van Hilst J, et al; European Consortium on Minimally Invasive Pancreatic Surgery (E-MIPS). Predictors for survival in an international cohort of patients undergoing distal pancreatectomy for pancreatic ductal adenocarcinoma. Ann Surg Oncol 2021;28:1079-87.
47. Tol JA, Gouma DJ, Bassi C, et al; International Study Group on Pancreatic Surgery. Definition of a standard lymphadenectomy in surgery for pancreatic ductal adenocarcinoma: a consensus statement by the International Study Group on Pancreatic Surgery (ISGPS). Surgery 2014;156:591-600.
48. Ricci C, Casadei R, Taffurelli G, et al. Laparoscopic versus open distal pancreatectomy for ductal adenocarcinoma: a systematic review and meta-analysis. J Gastrointest Surg 2015;19:770-81.
49. van Hilst J, Korrel M, de Rooij T, et al; DIPLOMA study group. Oncologic outcomes of minimally invasive versus open distal pancreatectomy for pancreatic ductal adenocarcinoma: a systematic review and meta-analysis. Eur J Surg Oncol 2019;45:719-27.
50. Korrel M, Jones LR, van Hilst J, et al; European Consortium on Minimally Invasive Pancreatic Surgery (E-MIPS). Minimally invasive versus open distal pancreatectomy for resectable pancreatic cancer (DIPLOMA): an international randomised non-inferiority trial. Lancet Reg Health Eur 2023;31:100673.
51. de Rooij T, van Hilst J, van Santvoort H, et al; Dutch Pancreatic Cancer Group. Minimally invasive versus open distal pancreatectomy (LEOPARD): a multicenter patient-blinded randomized controlled trial. Ann Surg 2019;269:2-9.
52. Björnsson B, Larsson AL, Hjalmarsson C, Gasslander T, Sandström P. Comparison of the duration of hospital stay after laparoscopic or open distal pancreatectomy: randomized controlled trial. Br J Surg 2020;107:1281-8.
53. Ikenaga N, Hashimoto T, Mizusawa J, et al; on behalf of the Hepatobiliary and Pancreatic Oncology Group in Japan Clinical Oncology Group. A multi-institutional randomized phase III study comparing minimally invasive distal pancreatectomy versus open distal pancreatectomy for pancreatic cancer; Japan Clinical Oncology Group study JCOG2202 (LAPAN study). BMC Cancer 2024;24:231.
54. Altman AM, Wirth K, Marmor S, et al. Completion of adjuvant chemotherapy after upfront surgical resection for pancreatic cancer is uncommon yet associated with improved survival. Ann Surg Oncol 2019;26:4108-16.
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De, Pastena M.; Coppola A.; Esposito A.; Casciani F.; Tufo A.; Salvia R. Minimally invasive left pancreatectomy for pancreatic ductal adenocarcinoma: review of the current literature. Mini-invasive. Surg. 2024, 8, 20. http://dx.doi.org/10.20517/2574-1225.2023.123
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