We would like to acknowledge Amer Zureikat, Melissa Hogg, Olivier Saint-Marc, Ugo Boggi, and Herbert Zeh III who supported and trained us in robotic pancreatic surgery in the Dutch Pancreatic Cancer Group - LAELAPS-3 program.

<ol>
	<li>Torphy, R. J., Fujiwara, Y., Schulick, R. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pancreatic+cancer+treatment:+better,+but+a+long+way+to+go.">Pancreatic cancer treatment: better, but a long way to go.</a> Surgery Today. 50 (10), 1117-1125 (2020).</li><li>Asbun, H. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Miami+International+Evidence-based+Guidelines+on+Minimally+Invasive+Pancreas+Resection.">The Miami International Evidence-based Guidelines on Minimally Invasive Pancreas Resection.</a> Annals of Surgery. 271 (1), 1-14 (2020).</li><li>Boone, B. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessment+of+Quality+Outcomes+for+Robotic+Pancreaticoduodenectomy.">Assessment of Quality Outcomes for Robotic Pancreaticoduodenectomy.</a> JAMA Surgery. 150 (5), 416 (2015).</li><li>Cai, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Robotic+Pancreaticoduodenectomy+Is+Associated+with+Decreased+Clinically+Relevant+Pancreatic+Fistulas:+a+Propensity-Matched+Analysis.">Robotic Pancreaticoduodenectomy Is Associated with Decreased Clinically Relevant Pancreatic Fistulas: a Propensity-Matched Analysis.</a> Journal of Gastrointestinal Surgery. 24 (5), 1111-1118 (2020).</li><li>Zureikat, A. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=500+Minimally+Invasive+Robotic+Pancreatoduodenectomies.">500 Minimally Invasive Robotic Pancreatoduodenectomies.</a> Annals of Surgery. 273 (5), 966-972 (2019).</li><li>Jones, L. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Robotic+Pancreatoduodenectomy:+Patient+Selection,+Volume+Criteria,+and+Training+Programs.">Robotic Pancreatoduodenectomy: Patient Selection, Volume Criteria, and Training Programs.</a> Scandinavian Journal of Surgery. 109 (1), 29-33 (2020).</li><li>Zwart, M. J. W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Outcomes+of+a+Multicenter+Training+Program+in+Robotic+Pancreatoduodenectomy+(LAELAPS-3).">Outcomes of a Multicenter Training Program in Robotic Pancreatoduodenectomy (LAELAPS-3).</a> Annals of Surgery. 269 (2), 344-350 (2021).</li><li>Balzan, S. M. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prevalence+of+hepatic+arterial+variations+with+implications+in+pancreatoduodenectomy.">Prevalence of hepatic arterial variations with implications in pancreatoduodenectomy.</a> Arquivos Brasileiros de Cirurgia Digestiva. 32 (3), 1455 (2019).</li><li>Nguyen, T. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Robotic+pancreaticoduodenectomy+in+the+presence+of+aberrant+or+anomalous+hepatic+arterial+anatomy:+safety+and+oncologic+outcomes.">Robotic pancreaticoduodenectomy in the presence of aberrant or anomalous hepatic arterial anatomy: safety and oncologic outcomes.</a> HPB. 17 (7), 594-599 (2015).</li><li>Kim, J. H., Gonzalez-Heredia, R., Daskalaki, D., Rashdan, M., Masrur, M., Giulianotti, P. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Totally+replaced+right+hepatic+artery+in+pancreaticoduodenectomy:+is+this+anatomical+condition+a+contraindication+to+minimally+invasive+surgery.">Totally replaced right hepatic artery in pancreaticoduodenectomy: is this anatomical condition a contraindication to minimally invasive surgery.</a> HPB. 18 (7), 580-585 (2016).</li><li>Lee, J. -. M., Lee, Y. -. J., Kim, C. -. W., Moon, K. -. M., Kim, M. -. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+Implications+of+an+Aberrant+Right+Hepatic+Artery+in+Patients+Undergoing+Pancreaticoduodenectomy.">Clinical Implications of an Aberrant Right Hepatic Artery in Patients Undergoing Pancreaticoduodenectomy.</a> World Journal of Surgery. 33 (8), 1727-1732 (2009).</li><li>MacKenzie, S., Kosari, K., Sielaff, T., Johnson, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+robotic+Whipple:+operative+strategy+and+technical+considerations.">The robotic Whipple: operative strategy and technical considerations.</a> Journal of Robotic Surgery. 5 (1), 3-9 (2011).</li><li>Stauffer, J. A., Bridges, M. D., Turan, N., Nguyen, J. H., Martin, J. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Aberrant+right+hepatic+arterial+anatomy+and+pancreaticoduodenectomy:+recognition,+prevalence+and+management.">Aberrant right hepatic arterial anatomy and pancreaticoduodenectomy: recognition, prevalence and management.</a> HPB. 11 (2), 161-165 (2009).</li><li>Abdullah, S. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Anatomical+variations+of+the+hepatic+artery:+study+of+932+cases+in+liver+transplantation.">Anatomical variations of the hepatic artery: study of 932 cases in liver transplantation.</a> Surgical and Radiologic Anatomy. 28 (5), 468-473 (2006).</li><li>Kowalsky, S. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Combination+of+Robotic+Approach+and+ERAS+Pathway+Optimizes+Outcomes+and+Cost+for+Pancreatoduodenectomy.">A Combination of Robotic Approach and ERAS Pathway Optimizes Outcomes and Cost for Pancreatoduodenectomy.</a> Annals of Surgery. 269 (6), 1138-1145 (2019).</li><li>Klotz, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evaluation+of+robotic+versus+open+partial+pancreatoduodenectomy-study+protocol+for+a+randomised+controlled+pilot+trial+(EUROPA,+DRKS00020407).">Evaluation of robotic versus open partial pancreatoduodenectomy-study protocol for a randomised controlled pilot trial (EUROPA, DRKS00020407).</a> Trials. 22 (1), 40 (2021).</li><li>Baimas-George, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Robotic+pancreaticoduodenectomy+may+offer+improved+oncologic+outcomes+over+open+surgery:+a+propensity-matched+single-institution+study.">Robotic pancreaticoduodenectomy may offer improved oncologic outcomes over open surgery: a propensity-matched single-institution study.</a> Surgical Endoscopy. 34 (8), 3644-3649 (2020).</li></ol>

M.J.W Zwart, L.R. Jones and M.G. Besselink received funding from Intuitive for the European LEARNBOT training program for robotic pancreatoduodenectomy. (Grant Reference&#42889; Impact of a European training program for robot pancreatoduodenectomy using a video databank, da Vinci simulator and robot biotissue anastomoses on clinical outcomes (LEARNBOT): a pan-European prospective study) and MEH received funding from Intuitive for studies on safe implementation of robot-assisted pancreatic surgery.
J.A.M.G. Tol, M. Abu Hilal, F. Daams, S. Festen&#160;and O.R. Buschhave no conflict of interest or financial ties to disclose.

This case report shows that RPD is feasible to perform in case of a replaced right hepatic artery when performed in selected patients by trained surgeons in high-volume centers with an annual volume of at least 20 RPD procedures per center, following the Miami guidelines2. RPD combines the benefits of a minimal invasive approach with enhanced 3D vision and the use of articulating instruments and therefore the inherent possibility of wrist movements. Moreover, the large external movements of the surgeon are scaled down to limited internal movements of the &#34;robotic hands&#34;. This improves ergonomics that results in higher precision and greater ability of the surgeon to perform technically difficult procedures in a limited space.
Aberrant vasculature, most commonly a replaced right hepatic artery, can increase the technical difficulty of the resection phase of RPD8. A replaced right hepatic artery can make it more challenging to dissect the pancreatic head and perform an adequate lymph node dissection. Damage to an aberrant hepatic artery can induce bile duct and liver ischemia13,14. The safety of RPD in patients with a replaced right hepatic artery has been shown by several studies9,10. Adequate description of the preoperative imaging is essential to identify aberrant vascularization such as a replaced hepatic artery or other arterial abnormalities such as a celiac trunk stenosis. It is crucial during surgery to identify the replaced right hepatic artery early, and to circle and retract the artery using a vessel loop to facilitate safe dissection of the pancreatic head and lymph node harvesting.
One of the limitations of the robotic approach compared to the open approach is the loss of haptic feedback2. Furthermore, the robotic approach is a more costly approach, although improved time to functional recovery and shortened hospital stay can partly compensate for this15. Lastly, no randomized trials have been conducted to date, to suggest superiority of RPD as compared to the open approach. The potential improved clinical and oncological outcomes of RPD vs OPD should be researched in future randomized trials such as in two ongoing trials in Heidelberg16 and Johns Hopkins Medical Institutes and by the European Consortium on Minimally Invasive Pancreatic Surgery (E-MIPS)4,5,17.
This case report shows a RPD for pancreatic head cancer in a patient with a replaced right hepatic artery and described the surgical technique in detail. In conclusion, RPD for pancreatic head cancer is a feasible procedure in case of a replaced right hepatic artery when performed by experienced surgeons (after overcoming the first learning phase after 22 cases7) in high volume centers, based on the Miami guidelines advice of 20 annual procedures per center per year2.

The combination of surgery and systemic therapy provides the most effective way of prolonging life expectancy in patients with resectable pancreatic cancer1. In recent years, interest in minimally invasive pancreatoduodenectomy has increased, aiming to decrease the impact of surgery and thereby enhancing postoperative recovery2.
Robotic pancreatoduodenectomy (RPD) aims to overcome compromises made by laparoscopy, by the ability of wrist movements, scaled down movements, and enhanced 3D vision combined with benefits of the minimally invasive approach for more precision and improved surgical ability. RPD is associated with a learning curve3,4; an experienced single center study reported that the learning curve based on operative time was overcome after 80 RPD procedures5. A dedicated training program can have a positive impact on this learning curve6. The University of Pittsburgh Medical Center (UPMC) group found improved outcomes after the implementation of a training program for RPD5. In the Netherlands, the LAELAPS-3 multicenter training program for RPD was started by the Dutch Pancreatic Cancer Group (DPCG) in collaboration with the UPMC team and demonstrated good results, including a learning curve based on operative time that was overcome after 22 RPD procedures7. Currently, this is being followed by the European LEARNBOT multicenter training program for RPD.
Aberrant hepatic vasculature is present in 15-20% of patients undergoing RPD, most commonly a replaced right hepatic artery, which may complicate the resection phase8. Currently, specific teaching material for RPD in patients with a replaced right hepatic artery is lacking. Detailed descriptions are crucial to prepare an optimal surgical strategy, also highlighting the importance of preoperative imaging for detecting any aberrant vasculature. The safety of RPD with aberrant hepatic vasculature was confirmed by several studies as long as these procedures are performed by specifically trained and experienced surgeons, working in high volume centers6,8,9,10,11,12.
This case report describes and shows a step-by-step technical approach to RPD in case of a replaced right hepatic artery performed in the Netherlands, aimed to facilitate ongoing (i.e., LEARNBOT) and future training programs. The Amsterdam UMC currently performs &#62;40 RPD procedures per year and therefore conforms to the Miami guidelines volume cut-off of &#62;20 RPD procedures2, as do all Dutch centers that participated in the LAELAPS-3 program. The described technique was standardized after 32 procedures (since November 2019) and a total of 115 procedures have been performed (until February 2022).
The described approach is reproducible and compatible for both normal and aberrant anatomy and includes additional steps for a replaced right hepatic artery.
A 58-year-old woman presented with an incidental finding of a 1.7 cm pancreatic head mass suspect for pancreatic ductal adenocarcinoma. No distant metastases and lymph node involvement was identified on the preoperative CT-scan. However, the CT-scan revealed a replaced right hepatic artery originating from the superior mesenteric artery (SMA) (Figure 1). Patient had a history of cholecystectomy, body mass index 30 kg/m2, and was ASA 1. The pancreatic duct measured 3 mm at the neck of the pancreas, and the hepatic duct measured 7 mm at the intended transection plane. The patient did not receive neoadjuvant chemotherapy, as no definitive preoperative histological diagnosis of pancreatic ductal adenocarcinoma could be made. The patient appeared suitable for a minimally invasive approach.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Sutures:</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Internal pancreatic duct stent (12cm)&#160;4 Fr Hobbs stent</td>
			<td>Hobbs medical</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>PDS, RB-1, 8cm 5-0 x6; Z320: taper point. &#189; circle 13/17mm</td>
			<td>Ethicon</td>
			<td>Z320</td>
			<td></td>
		</tr>
		<tr>
			<td>Silk, SH, 18cm 2-0 x5; C016D: taper point, &#189; circle 26mm</td>
			<td>Ethicon</td>
			<td>C016D</td>
			<td></td>
		</tr>
		<tr>
			<td>Straight needle Monocryl</td>
			<td>Ethicon</td>
			<td>Y523H</td>
			<td>For retraction lig. teres</td>
		</tr>
		<tr>
			<td>Vicryl suture without needle 60cm</td>
			<td>Ethicon</td>
			<td>e.g. D7818</td>
			<td>For measuring distance HJ-G</td>
		</tr>
		<tr>
			<td>V-loc L0803: taper point, &#189; circle 17mm, CV-23, 15cm 4-0</td>
			<td>Medtronic</td>
			<td>L0803</td>
			<td>In case of thick wall, dilated bile duct x2</td>
		</tr>
		<tr>
			<td>Instruments laparoscopy:</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Autosuture Endo Clip applier 5 mm</td>
			<td>Covidien</td>
			<td>176620</td>
			<td></td>
		</tr>
		<tr>
			<td>ECHELON FLEX ENDOPATH 60mm Stapler</td>
			<td>Ethicon</td>
			<td></td>
			<td>Powered surgical stapler with gripping surface technology</td>
		</tr>
		<tr>
			<td>o&#160;&#160; White filling 60mm x2 (for transection of jejunum, gastroduodenal artery)</td>
			<td>Ethicon</td>
			<td>GST60W</td>
			<td></td>
		</tr>
		<tr>
			<td>o&#160;&#160; Black filling 60mm (for transection of stomach)</td>
			<td>Ethicon</td>
			<td>GST60T</td>
			<td></td>
		</tr>
		<tr>
			<td>Endo Catch II Pouch 15mm</td>
			<td>Covidien</td>
			<td>173049</td>
			<td>Bag for specimen extraction. For single lymph node extractions a cut off finger surgical glove can be used.</td>
		</tr>
		<tr>
			<td>LigaSure Dolphin Tip Laparoscopic Sealer/Divider</td>
			<td>Medtronic</td>
			<td>LS1500</td>
			<td>Dolphin-nose tip sealer and divider, 37 cm shaft</td>
		</tr>
		<tr>
			<td>Mediflex retractor liver</td>
			<td>Mediflex</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Set of laparoscopic bulldog clamps</td>
			<td>Aesculap</td>
			<td></td>
			<td>This set consists of several bulldog clamps (of different shape and size) with dedicated laparoscopic instruments to be used to apply and remove the clamps</td>
		</tr>
		<tr>
			<td>Instruments robot:</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Cadiere x2 (470049)</td>
			<td>Intuitive Surgical</td>
			<td>470049</td>
			<td></td>
		</tr>
		<tr>
			<td>&#160;&#160;&#160;&#160;&#160; Endoscope 30&#186; (470026)</td>
			<td>Intuitive Surgical</td>
			<td>470026</td>
			<td></td>
		</tr>
		<tr>
			<td>Fenestrated Bipolar Forceps (470205)</td>
			<td>Intuitive Surgical</td>
			<td>470205</td>
			<td></td>
		</tr>
		<tr>
			<td>Hot Shears, Monopolar Curved Scissors (470179)</td>
			<td>Intuitive Surgical</td>
			<td>470179</td>
			<td></td>
		</tr>
		<tr>
			<td>Large Needle Driver x 1 (470006)</td>
			<td>Intuitive Surgical</td>
			<td>470006</td>
			<td></td>
		</tr>
		<tr>
			<td>&#160;&#160;&#160;&#160;&#160; Medium hem-o-lok Clip applier</td>
			<td>Intuitive Surgical</td>
			<td>470327</td>
			<td></td>
		</tr>
		<tr>
			<td>Permanent Cautery Hook (470183)</td>
			<td>Intuitive Surgical</td>
			<td>470183</td>
			<td></td>
		</tr>
		<tr>
			<td>Suture Cut Needle Driver x1 (470296)</td>
			<td>Intuitive Surgical</td>
			<td>470296</td>
			<td></td>
		</tr>
		<tr>
			<td>Other:</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Hem-o-lok Clips MLX</td>
			<td>Weck Surgical Instuments, Teleflex Medical, Durham, NC</td>
			<td>544230</td>
			<td>Vascular clip 3mm - 10mm Size Range</td>
		</tr>
		<tr>
			<td>Hem-o-lok Clips XI</td>
			<td>Weck Surgical Instuments, Teleflex Medical, Durham, NC</td>
			<td>544250</td>
			<td>Vascular clip 7mm - 16mm Size Range</td>
		</tr>
		<tr>
			<td>Medium extraction port (double ring)</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Vessel loops</td>
			<td>Omnia Drains</td>
			<td>NVMR61</td>
			<td>Disposible silicon rubber stripes, typically used to tag relevant anatomical structures</td>
		</tr>
	</tbody>
</table>

robotic pancreatoduodenectomy for pancreatic head cancer: a case report of a standardized technique

Robotic pancreatoduodenectomy (RPD) for pancreatic cancer is a challenging procedure. Aberrant vasculature may increase the technical difficulty. Several studies have described the safety of RPD in case of a replaced or aberrant right hepatic artery, but detailed video descriptions of the approach are lacking. This case report describes a step-&#173;by-&#173;step technical video in case of a replaced right hepatic artery. A 58-year-old woman presented with an incidental finding of a 1.7 cm pancreatic head mass. RPD was performed using the da Vinci Xi system and involves a robotic-assisted pancreatico- and hepatico-jejunostomy and open gastro-jejunostomy at the specimen extraction site. The operation time was 410 min with 220 mL of blood loss. The patient had an uncomplicated postoperative course and was discharged after 5 days. Pathology revealed a pancreatic head cancer. RPD is a feasible and safe procedure in case of a replaced hepatic artery when performed in selected patients in high-volume centers by experienced surgeons.

During routine work-up, the pancreatic CT-scan revealed a replaced right hepatic artery originating from the superior mesenteric artery (SMA) (Figure 1). Vessel loops used in the hepatic ligament, including the replaced right hepatic artery, are shown in Figure 3.
The sequence of instruments during each operative step are shown in Table 1 and specified in the Table of Materials.
Representative results are shown in Table 2. The operation time was 410 min (including 15 min break between the resection and anastomotic phase) with 220 mL of measured intraoperative blood loss. The postoperative course was unremarkable, with a total postoperative hospital stay of five days without complications. Oral intake was possible after two days with normal diet at day four. Patient started walking on the first postoperative day and expanded this to 200 m on day three. On the early morning of postoperative day three, drain amylase was low (86 U/L)and the drain was removed. The patient was discharged two days later on postoperative day five.
Pathology assessment revealed a 1.7 cm adenocarcinoma of the head cancer. The resection margins were microscopically radical (R0) with &#62;3 mm margin and five of 17 retrieved lymph nodes were positive for tumor. Patient started with adjuvant chemotherapy capecitabine as part of a randomized trial.
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/62863/62863fig01.jpg" /> 
Figure 1: 3D reconstruction of hepatic vasculature including replaced right hepatic artery <a href="https://www.jove.com/files/ftp_upload/62863/62863fig01large.jpg" target="_blank">Please click here to view a larger version of this figure.</a> 
Red: Arterial system 
Translucent yellow: Pancreatic duct 
Translucent green: Biliary system 
Translucent blue/purple: Portal system 
Translucent white: Pancreatic tissue
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/62863/62863fig02.jpg" /> 
Figure 2: Port placement <a href="https://www.jove.com/files/ftp_upload/62863/62863fig02large.jpg" target="_blank">Please click here to view a larger version of this figure.</a> 
Blue: 8 mm robotic ports 
Red: 12 mm laparoscopic ports 
Green: 5 mm port for liver retractor 
Arrow: Umbilicus
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/62863/62863fig03.jpg" /> 
Figure 3: Vessel loops hepatic ligament <a href="https://www.jove.com/files/ftp_upload/62863/62863fig03large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td colspan="2"></td>
			<td colspan="4">Instruments Used</td>
		</tr>
		<tr>
			<td colspan="2" rowspan="2"></td>
			<td colspan="3">Robotic</td>
			<td>Laparoscopic</td>
		</tr>
		<tr>
			<td colspan="3">(console surgeon)</td>
			<td>(assistant surgeon)</td>
		</tr>
		<tr>
			<td colspan="2">Operative steps</td>
			<td>Arm 1</td>
			<td>Arm 2</td>
			<td>Arm 4</td>
			<td></td>
		</tr>
		<tr>
			<td colspan="2">2.5 Mobilization</td>
			<td>Cadiere forceps</td>
			<td>Fenestrated bipolar forceps</td>
			<td>Permanent cautery hook</td>
			<td>Sealing device, suction, clip-applier, stapler</td>
		</tr>
		<tr>
			<td colspan="2">3.10 Portal dissection</td>
			<td>Cadiere forceps</td>
			<td>Fenestrated bipolar forceps</td>
			<td>Permanent cautery hook</td>
			<td>Sealing device, suction, clip-applier, stapler</td>
		</tr>
		<tr>
			<td colspan="2">3.17 Pancreatic neck transection</td>
			<td>Cadiere forceps</td>
			<td>Fenestrated bipolar forceps</td>
			<td>Monopolar curved scissors</td>
			<td>Sealing device, suction, clip-applier</td>
		</tr>
		<tr>
			<td colspan="2">2.18-2.23 Pancreatic head dissection</td>
			<td>Cadiere forceps</td>
			<td>Fenestrated bipolar forceps</td>
			<td>Cadiere forceps</td>
			<td>Sealing device, suction, clip-applier</td>
		</tr>
		<tr>
			<td colspan="2">4.1 Drain placement</td>
			<td>Cadiere forceps</td>
			<td>Fenestrated bipolar forceps</td>
			<td>Cadiere forceps</td>
			<td>Fenestrated grasper</td>
		</tr>
		<tr>
			<td>4.4-4.5 PJ and HJ</td>
			<td>PJ</td>
			<td>Cadiere forceps</td>
			<td>Large needle driver</td>
			<td>Large needle driver with suture cut</td>
			<td>Fenestrated grasper</td>
		</tr>
		<tr>
			<td></td>
			<td>HJ</td>
			<td>Cadiere forceps</td>
			<td>Large needle driver</td>
			<td>Large needle driver with suture cut</td>
			<td>Fenestrated grasper</td>
		</tr>
		<tr>
			<td>4.10 Specimen extraction</td>
			<td>GJ preparation</td>
			<td>Cadiere forceps</td>
			<td>Large needle driver</td>
			<td>Cadiere forceps</td>
			<td>Fenestrated grasper</td>
		</tr>
	</tbody>
</table>
Table 1: Sequence of instruments during each operative step
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Variable</td>
			<td>Outcome</td>
		</tr>
		<tr>
			<td>Intraoperative</td>
			<td></td>
		</tr>
		<tr>
			<td>Operative time, minutes</td>
			<td>410</td>
		</tr>
		<tr>
			<td>Resection, minutes</td>
			<td>202</td>
		</tr>
		<tr>
			<td>Reconstruction, minutes</td>
			<td>179</td>
		</tr>
		<tr>
			<td>Estimated intraoperative blood loss, mL</td>
			<td>220</td>
		</tr>
		<tr>
			<td>Postoperative</td>
			<td></td>
		</tr>
		<tr>
			<td>Clavien-Dindo complication grade</td>
			<td>0</td>
		</tr>
		<tr>
			<td>Drain removal, postoperative day</td>
			<td>3</td>
		</tr>
		<tr>
			<td>Postoperative hospital stay, days</td>
			<td>5</td>
		</tr>
		<tr>
			<td>Pathological diagnosis</td>
			<td>Adenocarcinoma of the head cancer</td>
		</tr>
		<tr>
			<td colspan="2">Legend: Operative time comprises steps 2.3-5.3, Resection comprises steps 3-3.25, reconstruction comprises steps 4-4.13</td>
		</tr>
	</tbody>
</table>
Table 2: Representative results

Watch this Scientific Journal Video about Robotic Pancreatoduodenectomy for Pancreatic Head Cancer: a Case Report of a Standardized Technique at JoVE.com

Robotic Pancreatoduodenectomy for Pancreatic Head Cancer: a Case Report of a Standardized Technique

Robotic pancreatoduodenctomy (RPD) has been highly standardized in recent years and may be used in selected patients with pancreatic head cancer, including those with a replaced right hepatic artery. This case report describes a standardized and reproducible technique for RPD, which includes the approach of the Dutch LAELAPS-3 training program to an aberrant vasculature.

Robotic pancreatoduodenectomy (RPD) for pancreatic cancer is a challenging procedure. Aberrant vasculature may increase the technical difficulty. Several ...

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5.0K Views.  Amsterdam UMC, location University of Amsterdam. Robotic pancreatoduodenctomy (RPD) has been highly standardized in recent years and may be used in selected patients with pancreatic head cancer, including those with a replaced right hepatic artery. This case report describes a standardized and reproducible technique for RPD, which includes the approach of the Dutch LAELAPS-3 training program to an aberrant vasculature.

Video: Robotic Pancreatoduodenectomy for Pancreatic Head Cancer: a Case Report of a Standardized Technique

Fluorescent Orthotopic Mouse Model of Pancreatic Cancer

Pancreatic cancer remains one of the cancers for which survival has not improved substantially in the last few decades. Only 7% of diagnosed patients will survive longer than five years. In order to understand and mimic the microenvironment of pancreatic tumors, we utilized a murine orthotopic model of pancreatic cancer that allows non-invasive imaging of tumor progression in real time. Pancreatic cancer cells expressing green fluorescent protein (PANC-1 GFP) were suspended in basement membrane matrix, high concentration, (e.g., Matrigel HC) with serum-free media and then injected into the tail of the pancreas via laparotomy. The cell suspension in the high concentration basement membrane matrix becomes a gel-like substance once it reaches room temperature; therefore, it gels when it comes in contact with the pancreas, creating a seal at the injection site and preventing any cell leakage. Tumor growth and metastasis to other organs are monitored in live animals by using fluorescence. It is critical to use the appropriate filters for excitation and emission of GFP. The steps for the orthotopic implantation are detailed in this article so researchers can easily replicate the procedure in nude mice. The main steps of this protocol are preparation of the cell suspension, surgical implantation, and whole body fluorescent in vivo imaging. This orthotopic model is designed to investigate the efficacy of novel therapeutics on primary and metastatic tumors.

A procedure to implant green fluorescent protein-expressing pancreatic cancer cells (PANC-1 GFP) orthotopically into the pancreas of Balb-c Ola Hsd-Fox1nu mice to assess tumor progression and metastasis is presented here.

Pancreatic cancer remains one of the cancers for which survival has not improved substantially in the last few decades. Only 7% of diagnosed patients will ...

A Model for Perineural Invasion in Head and Neck Squamous Cell Carcinoma

Perineural invasion (PNI) is found in approximately 40% of head and neck squamous cell carcinomas (HNSCC). Despite multimodal treatment with surgery, radiation, and chemotherapy, locoregional recurrences and distant metastases occur at higher rates, and overall survival is decreased by 40% compared to HNSCC without PNI. In vitro studies of the pathways involved in HNSCC PNI have historically been challenging given the lack of a consistent, reproducible assay. Described here is the adaptation of the dorsal root ganglion (DRG) assay for the examination of PNI in HNSCC. In this model, DRG are harvested from the spinal column of a sacrificed nude mouse and placed within a semisolid matrix. Over the subsequent days, neurites are generated and grow in a radial pattern from the cell bodies of the DRG. HNSCC cell lines are then placed peripherally around the matrix and invade preferentially along the neurites toward the DRG. This method allows for rapid evaluation of multiple treatment conditions, with very high assay success rates and reproducibility.

Perineural invasion (PNI) is a common feature of head and neck squamous cell carcinoma (HNSCC), conferring lower survival rates. Its mechanisms are poorly understood. Utilizing neurites generated from murine dorsal root ganglia confined to a semisolid matrix, the pathways involved in the PNI of HNSCC cell lines can be investigated.

Perineural invasion (PNI) is found in approximately 40% of head and neck squamous cell carcinomas (HNSCC). Despite multimodal treatment with surgery, ...

Flow Cytometry-based Drug Screening System for the Identification of Small Molecules That Promote Cellular Differentiation of Glioblastoma Stem Cells

Glioblastoma (GBM) is the most common and most lethal primary brain tumor in adults, causing roughly 14,000 deaths each year in the U.S. alone. Median survival following diagnosis is less than 15 months with maximal surgical resection, radiation, and temozolomide chemotherapy. The challenges inherent in developing more effective GBM treatments have become increasingly clear, and include its unyielding invasiveness, its resistance to standard treatments, its genetic complexity and molecular adaptability, and subpopulations of GBM cells with phenotypic similarities to normal stem cells, herein referred to as glioblastoma stem cells (GSCs). Because GSCs are required for tumor growth and progression, differentiation-based therapy represents a viable treatment modality for these incurable neoplasms. 
The following protocol describes a collection of procedures to establish a high throughput screening platform aimed at the identification of small molecules that promote GSC astroglial differentiation. At the core of the system is a glial fibrillary acidic protein (GFAP) differentiation reporter-construct. The protocol contains the following general procedures: (1) establishing GSC differentiation reporter lines; (2) testing/validating the relevance of the reporter to GSC self-renewal/clonogenic capacity; and (3) high-capacity flow-cytometry based drug screening. 
The screening platform provides a straightforward and inexpensive approach to identify small molecules that promote GSCs differentiation. Furthermore, utilization of libraries of FDA-approved drugs holds the potential for the identification of agents that can be repurposed more rapidly. Also, therapies that promote cancer stem cell differentiation are expected to work synergistically with current "standard of care" therapies that have been shown to target and eliminate primarily more differentiated cancer cells.

An efficient screening protocol is presented for the identification of small molecules that promote astroglial differentiation in glioblastoma stem cells (GSCs). The assay is based on a stem cell differentiation reporter whereby the expression of the enhanced GFP (eGFP) is driven by the human GFAP promoter.

Glioblastoma (GBM) is the most common and most lethal primary brain tumor in adults, causing roughly 14,000 deaths each year in the U.S. alone. Median ...

Laparoscopic Pancreatoduodenectomy With Modified Blumgart Pancreaticojejunostomy

Minimally invasive pancreatic resections are technically demanding but rapidly increasing in popularity. In contrast to laparoscopic distal pancreatectomy, laparoscopic pancreatoduodenectomy (LPD) has not yet obtained wide acceptance, probably due to technical challenges, especially regarding the pancreatic anastomosis.
The study describes and demonstrates all steps of LPD, including the modified Blumgart pancreaticojejunostomy. Indications for LPD are all pancreatic and peri-ampullary tumors without vascular involvement. Relative contra-indications are body mass index &#62;35 kg/m2, chronic pancreatitis, mid-cholangiocarcinomas and large duodenal cancers.
The patient is in French position, 6 trocars are placed, and dissection is performed using an (articulating) sealing device. A modified Blumgart end-to-side pancreaticojejunostomy is performed with 4 large needles (3/0) barbed trans-pancreatic sutures and 4 to 6 duct-to-mucosa sutures using 5/0 absorbable multifilament combined with a 12 cm, 6 or 8 Fr internal stent using 3D laparoscopy. Two surgical drains are placed alongside the pancreaticojejunostomy.
The described technique for LPD including a modified Blumgart pancreatico-jejunostomy is well standardized, and its merits are currently studied in the randomized controlled multicenter trial. This complex operation should be performed at high-volume centers where surgeons have extensive experience in both open pancreatic surgery and advanced laparoscopic gastro-intestinal surgery.

Laparoscopic pancreatoduodenctomy (LPD) may offer advantages over open pancreatoduodenectomy, including early postoperative mobilization, less delayed gastric emptying and a shorter hospital stay. However, LPD is technically challenging and not well-standardized, especially regarding the pancreatic anastomosis. We describe a standardized technique for the pancreatic anastomosis during LPD: modified Blumgart pancreaticojejunostomy.

Minimally invasive pancreatic resections are technically demanding but rapidly increasing in popularity. In contrast to laparoscopic distal ...

A Syngeneic Pancreatic Cancer Mouse Model to Study the Effects of Irreversible Electroporation

Pancreatic cancer (PC), a disease which kills approximately 40,000 patients each year in the US, has successfully evaded several therapeutic approaches including the promising immunotherapeutic strategies. Irreversible electroporation (IRE) is a non-thermal ablation technique that induces tumor cell death without destruction of adjacent collagenous structures, thus enabling the procedure to be performed in tumors very close to blood vessels. Unlike thermal ablation techniques, IRE results in gradual apoptotic cell death, along with immediate ablation induced necrosis, and is currently in clinical use for selected patients with locally advanced PC. An ablative, non-target specific procedure like IRE can induce a myriad of responses in the tumor microenvironment. A few studies have addressed the effects of IRE on tumor growth in other tumor types, but none have focused on PC. We have developed a syngeneic mouse model of PC in which subcutaneous (SQ) and orthotopic tumors can be successfully treated with IRE in a highly controlled setting, facilitating various longitudinal studies post procedure. This animal model serves as a robust system to study the effects of IRE and ways to improve the clinical efficacy of IRE.

Irreversible electroporation (IRE) is a non-thermal ablation technique used for the treatment of locally advanced pancreatic cancer. Being a relatively new technique, the effects of IRE on the tumor growth are poorly understood. We have developed a syngeneic mouse model that facilitates studying the effects of IRE on pancreatic cancer.

Pancreatic cancer (PC), a disease which kills approximately 40,000 patients each year in the US, has successfully evaded several therapeutic approaches ...

Ultrasound-Guided Orthotopic Implantation of Murine Pancreatic Ductal Adenocarcinoma

The recent success of immune checkpoint blockade in melanoma and lung adenocarcinoma has galvanized the field of immuno-oncology as well as revealed the limitations of current treatments, as the majority of patients do not respond to immunotherapy. Development of accurate preclinical models to quickly identify novel and effective therapeutic combinations are critical to address this unmet clinical need. Pancreatic ductal adenocarcinoma (PDA) is a canonical example of an immune checkpoint blockade resistant tumor with only 2% of patients responding to immunotherapy. The genetically engineered KrasG12D+/-;Trp53R172H+/-;Pdx-1 Cre (KPC) mouse model of PDA recapitulates human disease and is a valuable tool for assessing therapies for immunotherapy resistant in the preclinical setting, but time to tumor onset is highly variable. Surgical orthotopic tumor implantation models of PDA maintain the immunobiological hallmarks of the KPC tissue-specific tumor microenvironment (TME) but require a time-intensive procedure and introduce aberrant inflammation. Here, we use an ultrasound-guided orthotopic tumor implantation model (UG-OTIM) to non-invasively inject KPC-derived PDA cell lines directly into the mouse pancreas. UG-OTIM tumors grow in the endogenous tissue site, faithfully recapitulate histological features of the PDA TME, and reach enrollment-sized tumors for preclinical studies by four weeks after injection with minimal seeding on the peritoneal wall. The UG-OTIM system described here is a rapid and reproducible tumor model that may allow for high throughput analysis of novel therapeutic combinations in the murine PDA TME.

We describe a protocol for the ultrasound guided implantation of murine-derived pancreatic ductal adenocarcinoma cell lines directly into the native tumor site. This approach resulted in pancreatic tumors detectable by ultrasound scanning within 2-4 weeks of injection, and significantly reduced the proportion tumor cell seeding on the peritoneal wall as compared to surgical orthotopic implantation.

The recent success of immune checkpoint blockade in melanoma and lung adenocarcinoma has galvanized the field of immuno-oncology as well as revealed the ...

Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity

In vivo models of pancreatic cancer provide invaluable tools for studying disease dynamics, immune infiltration and new therapeutic strategies. The orthotopic murine model can be performed on large cohorts of immunocompetent mice simultaneously, is relatively inexpensive and preserves the cognate tissue microenvironment. The quantification of T cell infiltration and cytotoxic activity within orthotopic tumors provides a useful indicator of an antitumoral response.
This protocol describes the methodology for surgical generation of orthotopic pancreatic tumors by injection of a low number of syngeneic tumor cells resuspended in 5 &#181;L basement membrane directly into the pancreas. Mice bearing orthotopic tumors take approximately 30 days to reach endpoint, at which point tumors can be harvested and processed for characterization of tumor-infiltrating T cell activity. Rapid enzymatic digestion using collagenase and DNase allows a single-cell suspension to be extracted from tumors. The viability and cell surface markers of immune cells extracted from the tumor are preserved; therefore, it is appropriate for multiple downstream applications, including flow-assisted cell sorting of immune cells for culture or RNA extraction, flow cytometry analysis of immune cell populations. Here, we describe the ex vivo stimulation of T cell populations for intracellular cytokine quantification (IFN&#947; and TNF&#945;) and degranulation activity (CD107a) as a measure of overall cytotoxicity. Whole-tumor digests were stimulated with phorbol myristate acetate and ionomycin for 5 h, in the presence of anti-CD107a antibody in order to upregulate cytokine production and degranulation. The addition of brefeldin A and monensin for the final 4 h was performed to block extracellular transport and maximize cytokine detection. Extra- and intra-cellular staining of cells was then performed for flow cytometry analysis, where the proportion of IFN&#947;+, TNF&#945;+ and CD107a+ CD4+ and CD8+ T cells was quantified.
This method provides a starting base to perform comprehensive analysis of the tumor microenvironment.

Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity

This protocol describes the surgical generation of orthotopic pancreatic tumors and the rapid digestion of freshly isolated murine pancreatic tumors. Following digestion, viable immune cell populations can be used for further downstream analysis, including ex vivo stimulation of T cells for intracellular cytokine detection by flow cytometry.

In vivo models of pancreatic cancer provide invaluable tools for studying disease dynamics, immune infiltration and new therapeutic strategies. The ...

Enhanced Viability for Ex vivo 3D Hydrogel Cultures of Patient-Derived Xenografts in a Perfused Microfluidic Platform

Patient-derived xenografts (PDX), generated when resected patient tumor tissue is engrafted directly into immunocompromised mice, remain biologically stable, thereby preserving molecular, genetic, and histological features, as well as heterogeneity of the original tumor. However, using these models to perform a multitude of experiments, including drug screening, is prohibitive both in terms of cost and time. Three-dimensional (3D) culture systems are widely viewed as platforms in which cancer cells retain their biological integrity through biochemical interactions, morphology, and architecture. Our team has extensive experience culturing PDX cells in vitro using 3D matrices composed of hyaluronic acid (HA). In order to separate mouse fibroblast stromal cells associated with PDXs, we use rotation culture, where stromal cells adhere to the surface of tissue culture-treated plates while dissociated PDX tumor cells float and self-associate into multicellular clusters. Also floating in the supernatant are single, often dead cells, which present a challenge in collecting viable PDX clusters for downstream encapsulation into hydrogels for 3D cell culture. In order to separate these single cells from live cell clusters, we have employed density step gradient centrifugation. The protocol described here allows for the depletion of non-viable single cells from the healthy population of cell clusters that will be used for further in vitro experimentation. In our studies, we incorporate the 3D cultures in microfluidic plates which allow for media perfusion during culture. After assessing the resultant cultures using a fluorescent image-based viability assay of purified versus non-purified cells, our results show that this additional separation step substantially reduced the number of non-viable cells from our cultures.

This protocol demonstrates methods to enable extended in vitro culture of patient-derived xenografts (PDX). One step enhances overall viability of multicellular cluster cultures in 3D hydrogels, through straightforward removal of non-viable single cells. A secondary step demonstrates best practices for PDX culture in a perfused microfluidic platform.

Patient-derived xenografts (PDX), generated when resected patient tumor tissue is engrafted directly into immunocompromised mice, remain biologically ...

An Orthotopic Resectional Mouse Model of Pancreatic Cancer

There is a lack of satisfactory animal models to study adjuvant and/or neoadjuvant therapy in patients being considered for surgery of pancreatic cancer (PC). To address this deficiency, we describe a mouse model involving orthotopic implantation of PC followed by distal pancreatectomy and splenectomy. The model has been demonstrated to be safe and suitably flexible for the study of various therapeutic approaches in adjuvant and neo adjuvant settings.
In this model, a pancreatic tumor is first generated by implanting a mixture of human pancreatic cancer cells (luciferase-tagged AsPC-1) and human cancer associated pancreatic stellate cells into the distal pancreas of Balb/c athymic nude mice. After three weeks, the cancer is resected by re-laparotomy, distal pancreatectomy and splenectomy. In this model, bioluminescence imaging can be used to follow the progress of cancer development and effects of resection/treatments. Following resection, adjuvant therapy can be given. Alternatively, neoadjuvant treatment can be given prior to resection.
Representative data from 45 mice are presented. All mice underwent successful distal pancreatectomy/splenectomy with no issues of hemostasis. A macroscopic proximal pancreatic margin greater than 5 mm was achieved in 43 (96%) mice. The technical success rate of pancreatic resection was 100%, with 0% early mortality and morbidity. None of the animals died during the week after resection.
In summary, we describe a robust and reproducible technique for a surgical resection model of pancreatic cancer in mice which mimics the clinical scenario. The model may be useful for the testing of both adjuvant and neoadjuvant treatments.

In the clinical context, patients with localized pancreatic cancer will undergo pancreatectomy followed by adjuvant treatment. This protocol reported here aims to establish a safe and effective method of modelling this clinical scenario in nude mice, through orthotopic implantation of pancreatic cancer followed by distal pancreatectomy and splenectomy.

There is a lack of satisfactory animal models to study adjuvant and/or neoadjuvant therapy in patients being considered for surgery of pancreatic cancer ...

Robot Assisted Distal Pancreatectomy with Celiac Axis Resection (DP-CAR) for Pancreatic Cancer: Surgical Planning and Technique

Malignant pancreatic tumors involving the celiac artery can be resected with a distal pancreatectomy, splenectomy and celiac axis resection (DP-CAR), relying on collateral flow to the liver through the gastroduodenal artery (GDA). In the current manuscript, the technical conduct of robotic DP-CAR is outlined. The greater curve of the stomach is mobilized with care to avoid sacrificing the gastroepiploic vessels. The stomach and liver are retracted cephalad to facilitate dissection of the porta hepatis. The hepatic artery (HA) is dissected and encircled with a vessel loop. The gastroduodenal artery (GDA) is carefully preserved. The common HA is clamped and triphasic flow in the proper HA via the GDA is confirmed using intra-operative ultrasound. A retropancreatic tunnel is made over the superior mesenteric vein (SMV). The pancreas is divided with an endovascular stapler at the neck. The inferior mesenteric vein (IMV) and splenic vein are ligated. The HA is stapled proximal to the GDA. The entire specimen is retracted laterally with further dissection cephalad to expose the superior mesenteric artery (SMA). The SMA is then traced back to the aorta. The dissection continues cephalad along the aorta with the bipolar energy device used to divide the crural fibers and celiac nerve plexus. The specimen is mobilized from the patient's right to left until the origin of the celiac axis is identified and oriented towards the left. The trunk is circumferentially dissected and stapled. Additional dissection with hook cautery and the bipolar energy device fully mobilizes the pancreatic tail and spleen. The specimen is removed from the left lower quadrant extraction site and one drain is left in the resection bed. A final intra-operative ultrasound of the proper HA confirms pulsatile, triphasic flow in the artery and liver parenchyma. The stomach is inspected for evidence of ischemia. Robotic DP-CAR is safe, feasible and when used in conjunction with multi-modality therapy, offers potential for long-term survival in selected patients.

Robot Assisted Distal Pancreatectomy with Celiac Axis Resection DP-CAR for Pancreatic Cancer: Surgical Planning and Technique

We present our operative approach to robot assisted distal pancreatectomy, splenectomy, and celiac axis resection (DP-CAR), demonstrating that the procedure is safe and feasible with proper planning, patient selection, and surgeon experience.

Malignant pancreatic tumors involving the celiac artery can be resected with a distal pancreatectomy, splenectomy and celiac axis resection (DP-CAR), ...