Leading by Example – A Journey of Innovation for Pancreatic Cancer Surgery

The incidence of pancreatic cancer is increasing worldwide and currently almost half a million people are diagnosed with this disease each year. For most patients with a pancreatic cancer, the tumor is located in the pancreatic head. The complex ‘Whipple’ (i.e. pancreatoduodenectomy) procedure is the most common surgical procedure performed to remove this cancer in the head of the pancreas and improve the life expectancy of patients.

During Whipple surgery, a localized tumor is removed to restore the flow of pancreatic digestive fluids and bile from the liver into the digestive tract. It is a complex surgery in which the head of the pancreas, the first region of the small intestine (i.e. duodenum), and the gallbladder with the distal bile duct are removed, while preserving major blood vessels in the area. Importantly, the three-way junction between the remaining organs needs to be restored carefully to support normal digestion and prevent complications such as leakage of digestive fluids into the abdominal cavity.

Over recent years, significant progress has been made to improve the quality and safety of the Whipple procedure, thanks to formidable efforts by collaborative surgical clinical research. A considerable contribution to this research was initiated in the Netherlands by the Dutch Pancreatic Cancer Group (DPCG). The DPCG is a national multidisciplinary collaboration that brings various experts together, including surgeons, oncologists, radiologists, pathologists, and scientists. The hepato, pancreatic, and biliary (HPB) surgical team at Cancer Center Amsterdam – Amsterdam UMC is also part of the DPCG.

How Are New Surgical Techniques Implemented?

Long gone are the days when new surgical techniques were introduced in an operating theater on a whim, after watching a surgical video or even a one-day course. “Compare it to traveling by plane,” Marc Besselink, Professor of Pancreatic and Hepatobiliary Surgery, starts off. “When you board, you expect the pilots, crew, and ground staff to be properly trained and certified. The same holds true for what patients can expect from surgeons and the teams running the operating room. The patient is trusting you with their life. Obviously, the facilities and staff should be highly trained, experienced, and top notch.”

Over the last decade, Prof. Besselink has been a leader in a large national and international consortium of experts on minimally invasive pancreatic and hepatobiliary surgery. Through careful planning and the implementation of programs involving surgical quality review, knowledge exchange, training, and mentoring (see below ‘Training Programs and Randomized Trials’ ), their work has helped transform standard ‘open’ pancreas surgery into a minimally invasive ‘keyhole’ procedures, mostly assisted by highly sophisticated surgical robots. These innovative technique benefits patients, who typically have fewer complications, a reduction in blood loss, less pain and discomfort, and shorter recovery times.

Beyond the ‘one-size-fits-all’ approach

“We are passionate about our mission to keep pushing boundaries to improve patient care. This starts with careful and objective evaluation of techniques and outcomes to see how the surgery can be improved. We also look at treatment modality. For example, can pretreatment with chemotherapy allow more patients to be helped by the Whipple procedure? How can we tailor this particular surgery to the needs of each patient?” says Prof. Besselink.

Volume Matters

Several studies from research groups in the United States clearly highlighted that minimally invasive Whipple surgery only improves outcomes when performed at least 20 times per medical center per year. If performed less, outcomes were generally worse compared to the traditional, open surgical approach.

Prof. Besselink: “This finding really opened our eyes and led directly to new guidelines. The Miami guidelines, in which the Dutch team was closely involved, now states that minimally invasive Whipple surgery should be limited to hospitals that perform at least a total of 50 Whipples procedures (open and/or minimally invasive) each year.” This advice excludes roughly 80% of the hospitals in Europe and has accelerated centralization of these complex surgeries in select expertise centers, including Amsterdam UMC.

This guideline is essential for good clinical practice, according to Prof. Besselink: In Germany – without centralization of complex care – the surgery-associated mortality following the days and weeks after a Whipple procedure exceeds 10%. In the United States, over 80% of surgeons performing Whipple surgery perform less than two of these operations per year, resulting in unacceptable outcomes.

In the Netherlands, the current minimum volume requirement for Whipple surgery is 20 procedures per center per year. Since the implementation of the new guidelines, the mortality following Whipple surgery has dropped to 3 percent. This result is also supported by recent nationwide research of the Dutch Pancreatic Cancer Group. At Amsterdam UMC, following the merger between AMC and VUmc hospitals, over 140 of these procedures are now performed annually, leading to enhanced care pathways and highly specialized teams resulting in a further reduction in mortality.

Robot-assisted Whipple: The Pittsburgh Connection

Eight of the 16 hospitals performing pancreatic surgery in the Netherlands also met the new guideline-based volume requirement for participation in LEALAPS-3. The objective of this study was to assess feasibility and safety of a multicenter training program in robot-assisted pancreatoduodenectomy based on techniques developed by surgeons in Pittsburgh, Pennsylvania.

From left to right: Prof.Marc Besselink - Shirley Sussenbach - Maurice Zwart - Dr. Melissa Hogg (Pittsburgh, currently Chicago), and Prof. Olivier Busch.

The intensive training program involved 100 hours of surgical videos followed by training on a robotic virtual simulator, in which participating surgeons had to achieve a quality score of 95% in 20 robot-assisted surgical exercises. This was followed by comprehensive simulation exercises with plastic-silicone mockups to practice suturing. Only then were trainees allowed to operate under supervision on patients using the surgical robotic system.

Prof. Besselink: “Three Pittsburgh-based surgeons came to the Netherlands to instruct us.Following that, our PhD student tra velled with them to all participating pancreatic centers in the Netherlands to train surgeons there. Thanks to the Pittsburgh training program, we had a very quick - and most importantly - safe dissemination of knowledge and skills that resulted in multiple medical centers gaining solid expertise in robot-assisted Whipple surgeries. Currently the use of robotic Whipple surgery in the Netherlands is the highest in the world, exceeding 25%.”

To further evaluate the new procedure, a randomized controlled trial called ‘DIPLOMA-2’ is ongoing that includes 288 patients, two-third of these patients are randomly selected for robot-assisted Whipple surgery versus one-third for standard open Whipple. “The study aims to confirm the safety of this approach and objectify potential benefits. Thirteen centers in the Netherlands, Italy, Belgium, Germany, and Sweden are participating, and the trial is well ahead of schedule. At this time, over 90% of patients have been included over 17 months, and results are expected by the end of this year:” says Prof. Besselink.

Passing it on! EU-wide Training Program

Following the successful introduction of the robot-assisted Whipple procedure at Cancer Center Amsterdam and select hospitals in the Netherlands, countries across Europe started to take notice. “It was time to pass on the expertise we had gained,” says Marc. Thus, the European LEARNBOT program was launched.

This training program is endorsed by the European-African Hepato-Pancreato-Biliary Association (E-AHPBA), a ‘prime interdisciplinary organization for HPB-related surgical science and scholarship in the Europe-Africa-Middle-East region’ (see below ‘Prof. Marc Besselink Appointed President’). Eligible hospitals were invited to join the training program free of charge. The only requirement is that surgical parameters are submitted to the European surgical ‘E-MIPS’ quality audit to monitor quality and give feedback.

Inspiring International Experiences in the Operation Theater

“The LEARNBOT experiences are truly enthralling and a wonderful boost for all the members of our operation room team at Amsterdam UMC and other centers involved,” Prof. Besselink says enthusiastically. “For instance, every Monday here at Cancer Center Amsterdam, we start a robotic Whipple surgery procedure with two operating pancreatic surgeons. Next to myself Prof.Olivier Busch, Dr.Sebastiaan Festen (OLVG, HPB-Amsterdam collaboration), and Dr.Freek Daams." For the majority of procedures, this involves a training session with a different international team of surgeons sometimes accompanied by their ‘scrub’ nurses. Already, 50 teams from leading medical centers such as Milan, Stockholm, Heidelberg, Paris, Berlin, and Copenhagen - have visited us.”

Each Monday, the operation room is filled with anticipation, who will visit this week? “We have welcomed surgeons from across Europe, including Finland, the Czech Republic, Poland, but also China, Malaysia, and the United States. And in many of these occasions, we actually learn from each other with new surgical concepts and ‘technical tricks’ being discussed afterwards over a cup of soup. It is very inspiring to us all, knowing that patients with pancreatic cancer all over Europe, and even further away, can rely on their surgeons following dedicated training programs and sharing experiences and knowledge. As an operation room team, it inspires us greatly. Our guests show great appreciation for the good atmosphere, smooth teamwork team, and communication between anesthetists, ‘scrub’ nurses and surgeons.”

After participating in the LEARNBOT program and having performed 10 robot-assisted pancreatoduodenectomies, it was really valuable to visit Professor Besselink and his team at Amsterdam UMC. The visit reinforced us in that we are on the right track with our program, and we look forward to continuing to offer our patients minimally invasive pancreatic surgery

Ernesto Sparrelid, M.D., Ph.D.

Associate Professor, Chair of the Department for Upper Abdominal Diseases, Karolinska Comprehensive Cancer Center, Stockholm, Sweden.

Next Steps in Robot-Assisted Surgery

At Amsterdam UMC, work is ongoing to add a fourth robot to the three existing Da Vinci Intuitive robots. The expansion will support further implementation of robot-assisted operations in other disciplines like pulmonary, colorectal, gynecological, esophageal, and gastric surgery. Recently, new robotic systems from different manufacturers have become available which allows for comparison of important aspects like costs and sustainability.

In the meantime, PhD students at Cancer Center Amsterdam, who also work in Brescia, Italy, for the “European Consortium on Minimally Invasive Pancreatic Surgery” (E-MIPS) are analyzing data from over 4000 surgeries included in the E-MIPS European quality registry. Prof. Besselink: “Just because you become an expert in the latest state-of-the-art technique doesn’t mean you are done. You have to continue to push those boundaries. That is why we require teams we train to submit all data to the audit for quality monitoring. It is vital to complete the quality cycle to spot whether clinical practice is in agreement with clinical trial results, and to evaluate where the next improvements can be made that will help our patients.”

For more information, contact Prof. Marc Besselink.

People involved at Amsterdam UMC – Cancer Center Amsterdam

Prof. Olivier Busch, HPB surgery

Prof. Geert Kazemier, HPB surgery

Dr. Freek Daams, HPB surgery

Dr. Sebastiaan Festen, HPB Surgery (also: OLVG, HPB-Amsterdam)

Dr. Babs Zonderhuis, HPB surgery

Dr. Joris Erdmann, HPB surgery

Dr. Rutger-Jan Swijnenburg HPB surgery and proctor robotic liver surgery

Annuska Schoorlemmer, nurse specialist HPB surgery

Andre Sterk, nurse specialist HPB surgery

Dr. Rogier Voermans, gastroenterology HPB

Dr. Roy van Wanrooij, gastroenterology HPB

Dr. Thijs Wielenga, gastroenterology HPB

Dr. Maarten Jacobs, gastroenterology HPG

Prof. Paul Fockens, gastroenterology HPB

Irma Post-Hoekstra nurse specialist HPB gastroenterology

Prof. Hanneke Wilmink, medical oncology pancreas

Dr. Heinz-Josef Klumpen, medical oncology liver

Mariette Weterman, nurse specialist HPB oncology

Prof. Otto van Delden, interventional radiology HPB

Prof. Martijn Meijerink, interventional radiology HPB

Dr. Janneke van den Bergh, radiology HPB

Prof. Jaap Stoker, radiology HPB

Prof. Joanne Verheij, pathology HPB

Dr. Arantza Farina, pathology HPG

Fritz de Graaf, lead operating team robotic surgery HPB

Els Jagtenberg, lead operation planning

Marie-Jose Hendriks, lead patient ward 6B

Chris Bakker, lead patient ward 6C

Drs. Maurice Zwart, PhD Student LAELAPS-3

Dr. Jony van Hilst, post-doc LAELAPS, DIPLOMA

Drs. Leia Jones, PhD student LEARNBOT

Drs. Anouk Emmen, PhD student DIPLOMA-2

Drs. Nine de Graaf, PhD student DIPLOMA-2

Text by Henri van de Vrugt.

_{This article was created for Cancer Center Amsterdam.}

_{© 2023 NHBC– All rights reserved.}