The authors have no acknowledgments.

The patient gave written and oral informed consent to use medical data and the operative video for education and scientific purposes. This research was performed in compliance with all institutional, national and international guidelines for human welfare. Written informed consent was obtained from the patient for publication of this manuscript and any accompanying images.
1. Positioning
<ol>
	<li>Place the patient on a vacuum mattress in a supine French position (legs split). Lower the right arm alongside the body on an arm support and extend the left arm. Tilt the operating table 10-20&#176; in anti-Trendelenburg and 5-10&#176; to the left.</li>
</ol>
2. Robot docking
<ol>
	<li>After Verres needle insufflation on Palmers&#39; point, introduce four 8 mm robot trocars (R1-4) in a semi-curved line just above the umbilicus. The distance between the trocars is 6-7 cm: R1 in the right anterior axillary line, R2 in the right midclavicular line, R3 just right and above the umbilicus (camera) and R4 just medial in the left midclavicular line.</li>
	<li>Introduce two assistant 5 mm trocars 3-4 cm below to the left (vessel sealing device) and right of the umbilicus.</li>
</ol>
3. Mobilization
<ol>
	<li>Mobilize the hepatic flexure of the colon using robotic diathermia or laparoscopic sealing device.</li>
	<li>Introduce the liver retractor from the left and retract the liver from segment III and IV. This enables optimal exposure of the surgical site. Optionally, it could suspend the stomach.</li>
	<li>Identify the gastrocolic ligament and divide it with the vessel sealing device, hence opening the lesser sac.</li>
	<li>Continue the mobilization from lateral to medial until the hepatic flexor of the colon is freed.</li>
	<li>Perform Kocher&#39;s maneuver until the left renal vein is identified. Hereafter, dissect the right gastroepiploic vein free and ligate using a vessel sealer. Both steps are optional but improve exposure and control which may be useful in case of bleeding from the pancreatic head.</li>
	<li>Retract the pancreas and duodenum with the third robotic arm to entirely expose the abdominal aorta and inferior vena cava.</li>
	<li>Identify the right gastroepiploic vein and divide it with the laparoscopic sealing device and clips.</li>
	<li>Mobilize the pancreatic head using the cautery hook.</li>
</ol>
4. Intraoperative ultrasonography
<ol>
	<li>Introduce the ultrasonography probe and identify the trajectory of the pancreatic duct and the intra-pancreatic lesion.</li>
	<li>Demarcate the lesion with the cautery hook, with help of the ultrasonography probe.</li>
</ol>
5. Dissection
<ol>
	<li>Place a traction suture through the lesion.</li>
	<li>Lift the lesion up with the traction suture and enucleate the lesion circumferentially with the diathermic scissors.</li>
	<li>Cut a finger from a sterile surgical glove and introduce it into the abdominal cavity. Put the enucleated tissue in the finger and extract the specimen. The roof of the pancreatic duct is visible at the bottom of the enucleation site.</li>
	<li>Cut a finger from a sterile surgical glove and insert a dry sealant patch. Introduce the finger into the abdominal cavity. Position the sealant patch on the defect in the pancreatic parenchyma. Place two wet 10 x 10 cm gauzes on top and remove the gauzes after 3-5 minutes, the sealant patch remains on the pancreatic head. 
	NOTE: The sealant patch should not be made wet before positioning. Placement of a patch is optional; studies did not demonstrate its effectiveness in reducing the risk of pancreatic fistulas.</li>
</ol>
6. Drain placement
<ol>
	<li>Introduce a 18-20 French drain from the right side of the patient and advance it over the pancreatic head.</li>
	<li>Test produced drain fluids for amylase levels on the first and third postoperative day postoperatively to test for post-operative fistula. Consider placement of a stent in the pancreatic duct if the amylase level consistently exceeds 3 times the upper limit of the institutions normal serum amylase9.</li>
</ol>

<ol><li>Falconi, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((ENETS+Consensus+Guidelines+Update+for+the+Management+of+Patients+with+Functional+Pancreatic+Neuroendocrine+Tumors+and+Non-Functional+Pancreatic+Neuroendocrine+Tumors%5BTitle%5D)+AND+%22Neuroendocrinology%22%5BJournal%5D)">ENETS Consensus Guidelines Update for the Management of Patients with Functional Pancreatic Neuroendocrine Tumors and Non-Functional Pancreatic Neuroendocrine Tumors.</a> Neuroendocrinology. 103 (2), 153-171 (2016).</li>
<li>Su, A. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Is+laparoscopic+approach+for+pancreatic+insulinomas+safe%3F+Results+of+a+systematic+review+and+meta-analysis%5BTitle%5D)+AND+%22Journal+of+Surgical+Research%22%5BJournal%5D)">Is laparoscopic approach for pancreatic insulinomas safe? Results of a systematic review and meta-analysis.</a> Journal of Surgical Research. 186 (1), 126-134 (2014).</li>
<li>Shi, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Pancreatic+enucleation+using+the+da+Vinci+robotic+surgical+system%3A+a+report+of+26+cases%5BTitle%5D)+AND+%22The+International+Journal+of+Medical+Robotics%22%5BJournal%5D)">Pancreatic enucleation using the da Vinci robotic surgical system: a report of 26 cases.</a> The International Journal of Medical Robotics. 12 (4), 751-757 (2016).</li>
<li>Tian, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Propensity+score-matched+analysis+of+robotic+versus+open+surgical+enucleation+for+small+pancreatic+neuroendocrine+tumours%5BTitle%5D)+AND+%22British+Journal+of+Surgery%22%5BJournal%5D)">Propensity score-matched analysis of robotic versus open surgical enucleation for small pancreatic neuroendocrine tumours.</a> British Journal of Surgery. 103 (10), 1358-1364 (2016).</li>
<li>Zhang, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Enucleation+of+pancreatic+lesions%3A+indications%2C+outcomes%2C+and+risk+factors+for+clinical+pancreatic+fistula%5BTitle%5D)+AND+%22Journal+of+Gastrointestinal+Surgery%22%5BJournal%5D)">Enucleation of pancreatic lesions: indications, outcomes, and risk factors for clinical pancreatic fistula.</a> Journal of Gastrointestinal Surgery. 17 (12), 2099-2104 (2013).</li>
<li>Liang, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Robotic+enucleation+for+pediatric+insulinoma+with+MEN1+syndrome%3A+a+case+report+and+literature+review%5BTitle%5D)+AND+%22BMC+Surgery%22%5BJournal%5D)">Robotic enucleation for pediatric insulinoma with MEN1 syndrome: a case report and literature review.</a> BMC Surgery. 18 (1), 44(2018).</li>
<li>Ore, A. S., Barrows, C. E., Solis-Velasco, M., Shaker, J., Moser, A. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Robotic+enucleation+of+benign+pancreatic+tumors%5BTitle%5D)+AND+%22Journal+of+Visualized+Surgery%22%5BJournal%5D)">Robotic enucleation of benign pancreatic tumors.</a> Journal of Visualized Surgery. 3 (10), (2017).</li>
<li>Jin, J. B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Robotic+Enucleation+for+Benign+or+Borderline+Tumours+of+the+Pancreas%3A+A+Retrospective+Analysis+and+Comparison+from+a+High-Volume+Centre+in+Asia%5BTitle%5D)+AND+%22World+Journal+of+Surgery%22%5BJournal%5D)">Robotic Enucleation for Benign or Borderline Tumours of the Pancreas: A Retrospective Analysis and Comparison from a High-Volume Centre in Asia.</a> World Journal of Surgery. 40 (12), 3009-3020 (2016).</li>
<li>Bassi, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((The+2016+update+of+the+International+Study+Group+%28ISGPS%29+definition+and+grading+of+postoperative+pancreatic+fistula%3A+11+Years+After%5BTitle%5D)+AND+%22Surgery%22%5BJournal%5D)">The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 Years After.</a> Surgery. 161 (3), 584-591 (2017).</li>
<li>Boone, B. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Assessment+of+quality+outcomes+for+robotic+pancreaticoduodenectomy%3A+identification+of+the+learning+curve%5BTitle%5D)+AND+%22JAMA+Surgery%22%5BJournal%5D)">Assessment of quality outcomes for robotic pancreaticoduodenectomy: identification of the learning curve.</a> JAMA Surgery. 150 (5), 416-422 (2015).</li>
<li>Zureikat, A. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((250+robotic+pancreatic+resections%3A+safety+and+feasibility%5BTitle%5D)+AND+%22Annals+of+Surgery%22%5BJournal%5D)">250 robotic pancreatic resections: safety and feasibility.</a> Annals of Surgery. 258 (4), 559-562 (2013).</li>
<li>Jilesen, A. P. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Postoperative+Outcomes+of+Enucleation+and+Standard+Resections+in+Patients+with+a+Pancreatic+Neuroendocrine+Tumor%5BTitle%5D)+AND+%22World+Journal+of+Surgery%22%5BJournal%5D)">Postoperative Outcomes of Enucleation and Standard Resections in Patients with a Pancreatic Neuroendocrine Tumor.</a> World Journal of Surgery. 40 (3), 715-728 (2016).</li>
<li>Crippa, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Surgical+Management+of+Insulinomas%3A+Short-+and+Long-term+Outcomes+After+Enucleations+and+Pancreatic+Resections%5BTitle%5D)+AND+%22JAMA+Surgery%22%5BJournal%5D)">Surgical Management of Insulinomas: Short- and Long-term Outcomes After Enucleations and Pancreatic Resections.</a> JAMA Surgery. 147 (3), 261-266 (2012).</li>
<li>Li, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Laparoscopic+ultrasound+enhances+diagnosis+and+localization+of+insulinoma+in+pancreatic+head+and+neck+for+laparoscopic+surgery+with+satisfactory+postsurgical+outcomes%5BTitle%5D)+AND+%22Ultrasound+in+Medicine+and+Biology%22%5BJournal%5D)">Laparoscopic ultrasound enhances diagnosis and localization of insulinoma in pancreatic head and neck for laparoscopic surgery with satisfactory postsurgical outcomes.</a> Ultrasound in Medicine and Biology. 37 (7), 1017-1023 (2011).</li>
<li>Lu, W. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Enucleation+of+benign+or+borderline+pancreatic+head+tumors+adjacent+to+the+common+pancreatic+duct%5BTitle%5D)+AND+%22Pancreas%22%5BJournal%5D)">Enucleation of benign or borderline pancreatic head tumors adjacent to the common pancreatic duct.</a> Pancreas. 41 (2), 336-337 (2012).</li>
<li>Zhang, X. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Margin+status+and+long-term+prognosis+of+primary+pancreatic+neuroendocrine+tumor+after+curative+resection%3A+Results+from+the+US+Neuroendocrine+Tumor+Study+Group%5BTitle%5D)+AND+%22Surgery%22%5BJournal%5D)">Margin status and long-term prognosis of primary pancreatic neuroendocrine tumor after curative resection: Results from the US Neuroendocrine Tumor Study Group.</a> Surgery. 165 (3), 548-556 (2019).</li>
<li>Gkegkes, I. D., Mamais, I. A., Iavazzo, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Robotics+in+general+surgery%3A+A+systematic+cost+assessment%5BTitle%5D)+AND+%22Journal+of+Minimal+Access+Surgery%22%5BJournal%5D)">Robotics in general surgery: A systematic cost assessment.</a> Journal of Minimal Access Surgery. 13 (4), 243-255 (2017).</li>
</ol>

The authors have nothing to disclose.

There are six critical steps highlighted here: positioning and robot docking, mobilization, intraoperative ultrasonography, traction suture, dissection, and drain placement. Conversion to laparotomy should be performed in case of uncontrollable intraoperative bleeding or in case the tumor is not adequately located with ultrasound.
A liver retractor is useful to expose the surgical site. Intraoperative ultrasonography plays an important role in enabling a parenchyma-sparing enucleation. Preferably, a (interventional) radiologist should identify the lesion and especially its relationship with the pancreatic duct14. Applying a traction suture through the lesion eases the dissection, especially in a parenchyma-sparing resection.
Besides general complications of surgery, pancreatic fistula should be closely monitored after this procedure15. As shown here, the lesion had a close relationship with the pancreatic duct with only 1-2 mm distance between the insulinoma and the pancreatic duct. Because of this risk, a retro pancreatic drain was positioned and monitored at least during the first postoperative days9.
A microscopically margin-positive (R1) resection was obtained. Although microscopically margin-negative (R0) resection would be preferably, this is not deemed necessary, as this is not associated with improved long-term overall survival in pancreatic neuroendocrine tumors16.
Limitations of robotic surgery are the availability of the robotic system, the need for specific training, lack of tactile feedback and high costs17. The added degrees of freedom obtained by the robotic system may be useful for enucleation of insulinomas, especially in case of a close proximity to the pancreatic duct, as in this demonstrated case.
Robotic enucleation of insulinomas seems feasible; still, future prospective studies should confirm this suggestion. We believe that the described technique, with adequate ultrasonography guided localization of the lesion, could be a valuable alternative for open enucleation as stated in guidelines1. Further studies are needed to compare short- and long-term outcomes after robotic, open, and laparoscopic enucleation.

Insulinoma is the most prevalent functioning pancreatic neuroendocrine tumor (F-PNET) with an annual incidence of 1-32/100,000 patients1. Pancreas-sparing surgery (i.e., enucleation) is mostly indicated for single lesions as pancreatic resections could be needed in multifocal or more extensive lesions1. General advantages of parenchymal-sparing enucleation over pancreatoduodenectomy or distal pancreatectomy include function preservation (both exocrine and endocrine), less blood loss, shorter operative time, and the absence of high risk anastomoses as required after pancreatoduodenectomy and central pancreatectomy.
A minimally invasive surgical approach aims to shorten the time to functional recovery with comparable oncologic outcomes1,2. Compared to open enucleation, robotic enucleation is associated with a shorter operative time and lower blood loss with a similar risk of postoperative pancreatic fistulas and major postoperative complications3,4. Compared to laparoscopic enucleation, robotic enucleation seems to be associated with less intraoperative blood loss, which could be related to the additional degrees of freedom during dissection that could lead to more accurate dissection5.
Three studies have so far addressed robotic enucleation of pancreatic neoplasms, one of which describes the technique to enucleate an insulinoma in the pediatric setting, the others describe techniques to enucleate benign pancreatic lesions6,7,8. In this study, we present a technique for robotic enucleation of an insulinoma originating from the pancreas. We fully acknowledge that many variations are possible to nearly every step. Accurate identification and meticulous dissection, especially with regards to the main pancreatic duct, are crucial.
This case shown here involves a 42-year old woman who presented with sweating, tremor and episodes of hypoglycemia. A fasting test confirmed endogenic insulin overproduction. CT and MRI were inconclusive; therefore, an endoscopic ultrasound of the pancreatic head was made. Endoscopic ultrasonography showed a non-bulging, hypoechoic lesion, which was fully embedded within the pancreatic head at 1-2 mm distance from the main pancreatic duct. The patient was consented for both a robotic pancreatoduodenectomy procedure and a robotic enucleation. Intraoperatively, the final decision was made to perform an enucleation.

<table><tbody><tr><td>Arietta V70 Ultrasound</td><td>Hitachi</td><td>-</td><td>The ultrasound system.</td></tr><tr><td>Cobra Liver Retractor Diamond-Flex</td><td>CareFusion</td><td>89-6216</td><td>Retracting the liver for optimal exposure of the surgical site.</td></tr><tr><td>da Vinci Surgeon Console</td><td>Intuitive Surgical</td><td>SS999</td><td>Used to control the surgical robot.</td></tr><tr><td>da Vinci Vision Cart</td><td>Intuitive Surgical</td><td>VS999</td><td>The vision cart houses advanced vision and energy technologies and provides communications across da Vinci system components.</td></tr><tr><td>da Vinci Xi</td><td>Intuitive Surgical</td><td>K131861</td><td>The surgical robot: &#039;patient side-cart&#039;.</td></tr><tr><td>da Vinci Xi Endoscope with Camera, 8 mm, 30&amp;deg;</td><td>Intuitive Surgical</td><td>470027</td><td>The camera of the da Vinci robot.</td></tr><tr><td>ENDOEYE Rigid Video Laparoscope, 10 mm, 30&amp;deg;</td><td>Olympus</td><td>WA50042A</td><td>To see within the intra-abdominal cavity.</td></tr><tr><td>ENDOWRIST Fenestrated Bipolar Forceps</td><td>Intuitive Surgical</td><td>470205</td><td>Used for dissection and coagulation.</td></tr><tr><td>ENDOWRIST HOT SHEARS</td><td>Intuitive Surgical</td><td>470179</td><td>Used for cutting and coagulation.</td></tr><tr><td>ENDOWRIST Mega SutureCut Needle Driver</td><td>Intuitive Surgical</td><td>470309</td><td>Used as a needle driver.</td></tr><tr><td>ENDOWRIST Permanent Cautery Hook</td><td>Intuitive Surgical</td><td>470183</td><td>Used for coagulation.</td></tr><tr><td>ENDOWRIST PROGrasp Forceps</td><td>Intuitive Surgical</td><td>470093</td><td>Used for dissection.</td></tr><tr><td>LigaSure Dolphin Tip 37cm</td><td>Medtronic</td><td>LS1500</td><td>Used for vessel sealing and dividing.</td></tr><tr><td>Robotic ultrasonography transducer</td><td>Hitachi</td><td>L43K</td><td>Used for intraoperative laparoscopic ultrasonography.</td></tr><tr><td>TachoSil 4.8 cm x 4.8 cm</td><td>Baxter Healthcare Corporation</td><td>1144923</td><td>Used for coagulation.</td></tr></tbody></table>

robotic enucleation of an intra-pancreatic insulinoma in the pancreatic head

Pancreatic parenchyma sparing surgery for insulinomas avoids the risk of endocrine and exocrine insufficiency, and potential high-risk anastomoses associated with pancreatic resection. Robotic surgery may be used as an alternative for open pancreatic enucleation without compromising dexterity and 3D-vision.
We present the case of a 42-year old woman who presented with sweating, tremor and episodes of hypoglycemia. A fasting test confirmed endogenic insulin overproduction. After inconclusive CT- and MRI imaging, endoscopic ultrasonography showed a hypoechoic lesion, which was fully within the pancreatic head. Although consent was obtained for pancreatoduodenectomy, robotic enucleation seemed feasible. After mobilization, intraoperative ultrasonography was used to identify the lesion and its relation with the pancreatic duct. Dissection was performed using a traction suture, hot shears and bipolar diathermia. A sealant patch was applied for hemostasis and a drain placed. The patient developed a grade B pancreatic fistula for which endoscopic sphincterotomy was performed; the surgical drain could be removed in the outpatient clinic after 20 days. Prospective studies should confirm the short- and long-term benefits of robotic enucleation of insulinomas.

Total operation time was 180 minutes with a blood loss of 5 mL. At the third postoperative day, drain amylase levels were still elevated. We therefore decided to attempt a stent placement in the pancreatic duct. During ERCP, this was technically not feasible, thus a pancreatic sphincterotomy was performed. This was classified as a grade B postoperative pancreatic fistula, due to the ERCP intervention9. The patient was discharged on postoperative day 7. After drain amylase had normalized, the drain could be removed in the outpatient clinic on postoperative day 20.
Histopathological examination revealed a grade 1 (mitotic index &#60;2/mm2 and Ki67 &#60;3%) well-differentiated neuroendocrine tumor measuring 1.5 cm with positive insulin staining (see Figure 1). Tumor cells were microscopically present at the resection margin (R1).
Comparable results from literature 
In general, a robotic docking time of 5-10 min has been described10 as well as an operative time of 206 &#177; 67 min, operative blood loss 43 ml (IQR 27-98)11 and a median tumor size of pancreatic neuroendocrine tumours of 16 mm (IQR 11-22)12. The expected postoperative hospital stay is 5 days (IQR 3-12)11, major morbidity rate 30%11, with a very low in hospital mortality rate (0%)12,13. The rate of clinically relevant pancreatic fistula rate is reported to be 30-40%11,12 and the delayed gastric emptying rate 0-26%12,13.
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/60290/60290fig1a.jpg" /> 
Figure 1: Specimen. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/60290/60290fig1large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>

Watch this Scientific Journal Video about Robotic Enucleation of an Intra-Pancreatic Insulinoma in the Pancreatic Head at JoVE.com

Robotic Enucleation of an Intra-Pancreatic Insulinoma in the Pancreatic Head

Here, we present a robotic approach to enucleate an insulinoma in the pancreatic head.

Pancreatic parenchyma sparing surgery for insulinomas avoids the risk of endocrine and exocrine insufficiency, and potential high-risk anastomoses ...

robotic-enucleation-an-intra-pancreatic-insulinoma-pancreatic

Nanyang Technological University

Research

JoVE Journal

Medicine

8.1K Views.  University of Amsterdam. Dit videovignet illustreert een robotachtige benadering van het insuclereren van een intra-alvleeskliersyleeroom in de alvleesklierkop. Deze zaak gaat om een 42-jarige vrouw die gepresenteerd met zweten, tremor en episodes van hypoglykemie. Een vastentest bevestigde endogene insulineoverproductie.Endoscopische ultrasonografie toonde een niet-uitpuilende, hypoechoïsche laesie die volledig in de alvleesklierkop zat. De patiënt werd gediagnosticeerd met een intra-alvleesklier insulinoma...

Video: Robotic Enucleation of an Intra-Pancreatic Insulinoma in the Pancreatic Head

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 ...

Cancer Research

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), ...

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.

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 ...

Application of End-to-end Anastomosis in Robotic Central Pancreatectomy

Central pancreatectomy is carried out for the treatment of benign or low-malignant potential tumors located in the pancreatic neck or proximal part of pancreatic body. With technological development, the robotic surgical system has shown its advantage in minimally invasive surgery and been increasingly applied in central pancreatectomy. However, reconstruction of the continuity of pancreas with end-to-end anastomosis after robotic central pancreatectomy has not been applied. In this study, we report surgical techniques for robotic central pancreatectomy with end-to-end anastomosis. The pancreas is reconstructed by duct-to-duct anastomosis of the pancreatic duct with a pancreatic stent inserted in the two stumps of pancreatic duct, and by end-to-end anastomosis of the pancreatic parenchyma. Compared with traditional central pancreatectomy with pancreaticoenteric anastomosis, this approach decreases the operative injury to the patient, and also conserves the integrity and continuity of the digestive duct and pancreatic duct. The robotic surgical system integrated with multiple instruments with flexible and precise movement is particularly suitable for the dissection and reconstruction of the pancreatic duct. We found that robotic central pancreatectomy with end-to-end anastomosis is safe and feasible, and we need more experience to evaluate its best indications and long-term outcomes.

The robotic central pancreatectomy with end-to-end anastomosis is feasible and safe for tumor in the pancreatic neck and proximal portion of pancreatic body. The operative techniques of this operation are presented.

Central pancreatectomy is carried out for the treatment of benign or low-malignant potential tumors located in the pancreatic neck or proximal part of ...

Technical Detail for Robot Assisted Pancreaticoduodenectomy

Since its first report in 2003, robotic pancreaticoduodenectomy (RPD) has gained popularity among pancreatic surgeons. Inherent advantages of the robotic platform, including three-dimensional vision, wristed instruments, and improved ergonomics, allow the surgeon to recapitulate the principles of open pancreatoduodenectomy allowing safe oncologic dissection, hemostasis, and meticulous reconstruction. Over the course of the past decade, significant strides have been achieved in outlining the safety, feasibility, and learning curve of the robotic Whipple. When performed by high volume pancreatic surgeons experienced in RPD, recent comparative effectiveness studies show potential advantages compared to the open technique, including reductions in hospital stay and morbidity. National data also show reductions in conversion rates compared to its laparoscopic counterpart. Although long-term oncologic data are still needed, short-term oncologic surrogates of margin resection and lymph node harvest suggest no compromise in oncologic outcomes. As pancreatic surgeons increasingly integrate robotics into their practice, proficiency-based training and credentialing will be necessary for the safe application and dissemination of RPD. Here, we provide the detailed steps of a robotic pancreaticoduodenectomy performed at the University of Pittsburgh Medical Center.&#160;

The following manuscript details a stepwise approach to the robot-assisted pancreaticoduodenectomy performed at the University of Pittsburgh Medical Center.

Since its first report in 2003, robotic pancreaticoduodenectomy (RPD) has gained popularity among pancreatic surgeons. Inherent advantages of the robotic ...

Robotic Central Pancreatectomy with Roux-en-Y Pancreaticojejunostomy

Central pancreatectomy is a parenchyma-sparing alternative to distal pancreatectomy in patients with a benign or low-grade malignant tumor in the body of the pancreas. The aim of central pancreatectomy is to prevent postoperative life-long endocrine and exocrine insufficiency. The downside of central pancreatectomy is the high rate of postoperative pancreatic fistula, which is the main reason that many surgeons do not routinely use central pancreatectomy in eligible patients. Most studies report open or laparoscopic central pancreatectomy with a pancreatico-gastrostomy anastomosis in adults. This is the first description of a standardized approach to robotic central pancreatectomy with Roux-en-Y pancreaticojejunostomy reconstruction in an adolescent (16-year-old boy) with a pseudopapillary tumor in the body of the pancreas. The operation time was 248 min with 20 mL of blood loss. The postoperative course was uneventful except for the short-term medical treatment for a grade B pancreatic fistula. Robotic central pancreatectomy can be safely applied in selected patients in experienced centers.

Robotic central pancreatectomy may be used in selected patients in experienced centers. This protocol presents all steps and the feasibility of a robotic central pancreatectomy with Roux-en-Y pancreaticojejunostomy in a 16-year-old adolescent patient.

Central pancreatectomy is a parenchyma-sparing alternative to distal pancreatectomy in patients with a benign or low-grade malignant tumor in the body of ...

Laparoscopic Pancreatoduodenectomy for Pancreatic Cancer Using In-Situ No-Touch Isolation Technique

Laparoscopic pancreatoduodenectomy (LPD) is a standard radical operation for pancreatic head malignant tumors by now. Due to the complex laparoscopic resection and reconstruction techniques, it is difficult to perform LPD for patients with locally advanced pancreatic head cancer after neoadjuvant therapy. Our team initiates LPD using the in-situ No-Touch isolation technique. The innovation and optimization of this modified No-Touch isolation technique emphasize exploring the distal section of superior mesenteric vein&#160;(SMV) and the left side of the superior mesenteric artery (SMA) prior to evaluating the resectability by subcolonic mesenteric approach, which is an ideal exploring approach. After that, we use the median-anterior, and left-posterior of SMA approaches to cut off the blood flow of the pancreatic head to make the tumor isolated intact, then move and dissect the tumor. It is a process fitting the surgical principle of tumor-free. This article aims to demonstrate the feasibility and safety of performing LPD using the in-situ No-Touch isolation technique, which might elevate the R0 resection rate. It is an oncological ideal operation process.

Laparoscopic Pancreatoduodenectomy for Pancreatic Cancer Using In-Situ No-Touch Isolation Technique

No-Touch isolation procedures might prevent the dissemination of cancer cells from the primary tumor. However, these techniques are not widely accepted in laparoscopic pancreatoduodenectomy (LPD) by now. We herein present in-situ No-Touch isolation LPD with partial resection and reconstruction of the superior mesenteric vein (SMV) for pancreatic cancer after neoadjuvant therapy.

Laparoscopic pancreatoduodenectomy (LPD) is a standard radical operation for pancreatic head malignant tumors by now. Due to the complex laparoscopic ...

Laparoscopic Duodenum-Preserving Pancreatic Head Resection via Inferior Infracolic Approach: A Surgical Approach for Benign Lesions

Minimally invasive pancreatic resections are gaining popularity despite being technically demanding. However, in contrast to laparoscopic pancreatoduodenectomy (LPD), laparoscopic duodenum-preserving pancreatic head resection (LDPPHR) has not yet obtained wide acceptance. This could be attributed to the technical challenges involved in preserving the blood supply of the duodenum and bile duct.
This study describes and demonstrates all the steps of LDPPHR. A 48-year-old woman was diagnosed with a 3.0 cm x 2.5 cm pancreatic head cystic mass, which was detected unexpectedly. The surgery was performed using the 3D laparoscopy via an inferior infracolic approach. The operation lasted approximately 310 min with 100 mL of blood loss. Postoperatively, the patient experienced no complications and was discharged 5 days later. Pathology revealed intraductal papillary mucinous neoplasms.
LDPPHR via an inferior infracolic approach is feasible and safe when performed by experienced surgeons in selected patients with thin mesenteric fat layers. The described technique for LDPPHR via inferior infracolic approach should be well standardized and performed at high-volume centers with experienced surgeons in both open and laparoscopic pancreatology.

This article provides a whole technical process of laparoscopic duodenum-preserving pancreatic head resection via an inferior infracolic approach. This is a surgical approach for benign tumors without intraoperative fluorescence image guidance.

Minimally invasive pancreatic resections are gaining popularity despite being technically demanding. However, in contrast to laparoscopic ...

Robotic Spleen-Preserving Distal Pancreatectomy: The Warshaw and Kimura Techniques

Spleen-preserving distal pancreatectomy offers an alternative surgical approach to the traditional distal pancreatectomy combined with splenectomy for removing benign and low-grade malignant lesions in the distal pancreas, avoiding complications associated with splenectomy. This procedure can be accomplished either by resecting and ligating the splenic vessels (Warshaw technique) or by preserving them (Kimura technique). Currently, the widespread use of minimally invasive surgery has established laparoscopic and robotic approaches for spleen-preserving distal pancreatectomy as valid and safe options for treating such conditions. Our protocol aims to describe how the Warshaw and Kimura techniques of spleen-preserving distal pancreatectomy can be performed robotically. The first patient is a 36-year-old female with a neuroendocrine tumor (NET) in the pancreatic body who underwent a spleen-preserving distal pancreatectomy with the ligation of the splenic vessels (WT). The second patient is a 76-year-old male with chronic pancreatitis presenting with a dilated main pancreatic duct in the tail of the pancreas who underwent a spleen-preserving distal pancreatectomy with a vessel-preserving approach (KT).

Here, we present a step-by-step protocol of robotic spleen preserving distal pancreatectomy, with and without preserving the splenic vessels (i.e., the Kimura and Warshaw techniques, respectively).

Spleen-preserving distal pancreatectomy offers an alternative surgical approach to the traditional distal pancreatectomy combined with splenectomy for ...

Robotic Enucleation of an Intra-Pancreatic Insulinoma in the Pancreatic Head

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