Improving Clinical Outcomes for Borderline Resectable and Locally Advanced Pancreatic Cancer

By Assoc Prof Chan Chung Yip (Head & Senior Consultant), Dr Koh Ye Xin (Consultant), Dr Chua Weiquan Darren (Associate Consultant), Dept of Hepato-pancreato-biliary and Transplant Surgery, Singapore General Hospital

7/5/2021 2:15:00 PM | Defining Med;Medical News

The article is contributed/written by Singapore General Hospital

With recent advancements in chemotherapeutics and surgical techniques, more patients with borderline resectable and locally advanced pancreatic cancers can now be considered for curative surgery. Find out the latest state-of-the-art clinical developments for borderline resectable and locally advanced pancreatic cancer.

EPIDEMIOLOGY OF PANCREATIC CANCER

Pancreatic cancer is currently the fourth leading cause of cancer-related death in the United States and among the top ten most common causes of cancerrelated death among Singaporeans.

It is estimated that only 20% of patients are eligible for upfront curative resection at the time of presentation. The larger group of borderline resectable and locally advanced pancreatic cancers had a much poorer outlook in the past.

Over the years, improvements have been made to the chemotherapy regimens and surgical approach for the treatment of pancreatic cancer such that more of these patients now have a chance of cure of the disease.

National Comprehensive Cancer Network guidelines on resectability criteria - Singapore General Hospital

DEFINITION OF BORDERLINE RESECTABLE AND LOCALLY ADVANCED PANCREATIC CANCER

Traditionally, borderline resectable and locally advanced pancreatic cancers, as defined by the International Study Group of Pancreatic Surgery and National Comprehensive Cancer Network (NCCN) to have varying degrees of vascular involvement, were deemed unresectable.

However, patients with borderline resectable and locally advanced lesions can now be considered for curative surgery.

WHO WILL BENEFIT FROM THE SURGERY?

The evolution of multimodality treatment, including chemotherapeutic agents coupled with advanced surgical techniques, have rendered a select group of patients amenable to curative surgery for borderline resectable and locally advanced cancer.

These patients would have undergone > 6 months of neoadjuvant chemotherapy with radiological evidence of stable disease. In addition, patients with favourable improvement of CA 19-9 and preserved functional status will stand to benefit from surgery.

WHAT DOES THE SURGERY ENTAIL?

This surgery is possible with advanced extended lymphadenectomy (i.e., periadventitial lymphadenectomy and the TRIANGLE operation [clearance of the celiac artery, superior mesenteric artery and portal vein triangle]), en bloc resection of involved vascular structures and advanced vascular reconstruction techniques.

With continual refinements in surgical techniques and chemotherapeutics, patients with borderline resectable or locally advanced disease can look forward to treatment with potentially curative intent.

CASE EXAMPLES
The following case examples depict how advancements in surgical techniques have made curative surgery possible for borderline resectable and locally advanced pancreatic cancer for more patients. CASE A Accessory right hepatic artery arising from the superior mesenteric artery (SMA). Tumour involvement of accessory anatomy was previously deemed unresectable. In this setting, periadventitial dissection was necessary to achieve negative margins. Portal vein pictured is slung with a blue vessel loop. *Figure 1* CASE B Total pancreatectomy procedure with control of the superior mesenteric vein (SMV), portal vein (PV) and a major venous branch. The pancreatic adenocarcinoma was noted to have a segmental involvement of the SMV which was subsequently resected en bloc. Segmental reconstruction was performed using a synthetic graft with reimplantation of the splenic vein. An alternative conduit for reconstruction involves harvesting an autologous deep femoral vein *(see Figure 3).* *Figure 2* CASE C Operative view after extended lymphadenectomy (TRIANGLE operation). Reconstruction performed with autologous deep femoral vein panel graft (top) prepared for an interposition venous graft (bottom). TRIANGLE depicts the borders: portal vein (PV), celiac axis (CA), superior mesenteric artery (SMA). *Figure 3* CASE D Multifocal pancreatic adenocarcinoma of the head and the tail with common hepatic artery encasement *(Figure 4, top).* This patient underwent neoadjuvant chemotherapy, curative total pancreatectomy, and extended lymphadenectomy (TRIANGLE operation) segmental portal vein resection. These tumours often elicit a desmoplastic (fibrotic) response that renders dissection challenging. Periadventitial vascular dissection and radical lymphadenectomy is necessary to achieve negative margins *(Figure 4, bottom).* *Figure 4*
LEGEND CA: celiac axis, CHA: common hepatic artery, GDA: gastroduodenal artery, LHA: left hepatic artery, PHA: proper hepatic artery, PV: portal vein, RHA: right hepatic artery, rRHA: replaced right hepatic artery, SA: splenic artery, SMA: superior mesenteric artery, SMV: superior mesenteric vein

CASE EXAMPLES

The following case examples depict how advancements in surgical techniques have made curative surgery possible for borderline resectable and locally advanced pancreatic cancer for more patients.

CASE A

Accessory right hepatic artery arising from the superior mesenteric artery (SMA). Tumour involvement of accessory anatomy was previously deemed unresectable.

In this setting, periadventitial dissection was necessary to achieve negative margins. Portal vein pictured is slung with a blue vessel loop.

Figure 1

CASE B

Total pancreatectomy procedure with control of the superior mesenteric vein (SMV), portal vein (PV) and a major venous branch. The pancreatic adenocarcinoma was noted to have a segmental involvement of the SMV which was subsequently resected en bloc.

Segmental reconstruction was performed using a synthetic graft with reimplantation of the splenic vein. An alternative
conduit for reconstruction involves harvesting an autologous deep femoral vein (see Figure 3).

Case B - Singapore General Hospital

Figure 2

CASE C

Operative view after extended lymphadenectomy (TRIANGLE operation). Reconstruction performed with autologous deep femoral vein panel graft (top) prepared for an interposition venous graft (bottom). TRIANGLE depicts the borders: portal vein (PV), celiac axis (CA), superior mesenteric artery (SMA).

Case C - Singapore General Hospital

Figure 3

CASE D

Multifocal pancreatic adenocarcinoma of the head and the tail with common hepatic artery encasement (Figure 4, top).

This patient underwent neoadjuvant chemotherapy, curative total pancreatectomy, and extended lymphadenectomy (TRIANGLE operation) segmental portal vein resection.

These tumours often elicit a desmoplastic (fibrotic) response that renders dissection challenging. Periadventitial vascular dissection and radical lymphadenectomy is necessary to achieve negative margins (Figure 4, bottom).

Case D - Singapore General Hospital

Figure 4

LEGEND
CA: celiac axis, CHA: common hepatic artery, GDA: gastroduodenal artery, LHA: left hepatic artery,
PHA: proper hepatic artery, PV: portal vein, RHA: right hepatic artery, rRHA: replaced right hepatic artery,
SA: splenic artery, SMA: superior mesenteric artery, SMV: superior mesenteric vein

Associate Professor Chan Chung Yip is a Senior Consultant Surgeon and is the current Head of Department. He graduated from the Faculty of Medicine at the National University of Singapore in 1997. He completed his training in General Surgery in 2006 and received further training in liver surgery and transplantation in Kaohsiung, Taiwan as well as in laparoscopic hepatobiliary and pancreatic surgery in Seoul, Korea. He is a pioneer in laparoscopic surgery of the liver, pancreas and bile duct in Singapore, and is a leader in its adoption amongst other surgeons in the country and region. He is a Ministry of Health-gazetted liver transplant surgeon, and is a lead surgeon of the living donor liver transplant programme in the hospital.

Dr Koh Ye Xin is a Consultant at the Department of Hepato-pancreato-biliary and Transplant Surgery in Singapore General Hospital and a member of the Singapore Hepato-Pancreato-Biliary Association (HPBA-S). Dr Koh serves as the Co-Chairman of the Quality Improvement Committee of the Surgery Academic Clinical Programme. Dr Koh graduated from the SingHealth General Surgery Residency Programme and the Singapore Chief Residency Programme from the Healthcare Leadership College. Dr Koh is a Fellow of the Royal College of Surgeons, Edinburgh and holds a Master of Medicine (Surgery). He was the Asia-Pacific awardee of the Japan Hepato-Pancreato-Biliary Society observership to Hokkaido University for training in advanced hepato-pancreato-biliary malignancy. He was a senior clinical fellow in Abdominal Transplantation at Cambridge University, Addenbrookes hospital, focusing on multivisceral and intestinal transplantation.

Dr Darren Chua is an Associate Consultant at the Department of Hepato-pancreato-biliary and Transplant Surgery at Singapore General Hospital. He obtained his MBBS (Hons) from the Yong Loo Lin School of Medicine, National University Singapore (NUS) in 2015 and completed his training with the SingHealth General Surgery Residency Programme in 2020. During his training, he also obtained his Masters of Medicine (Surgery) from NUS and was admitted as a fellow to the Royal College of Surgeons, Edinburgh. Dr Chua is an aspiring researcher and will embark on his Master of Clinical Investigation at NUS. He hopes to be able to pursue a PhD someday.

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