Standardized Approach to Superior Mesenteric Artery Resection for Locally Advanced Pancreatic Cancer

Summary

Superior mesenteric artery (SMA) resections are increasingly reported for the treatment of locally advanced pancreatic cancer (LAPC) with involvement of the superior mesenteric vessels in pancreatic ductal adenocarcinoma. Here, we describe an approach for SMA resections and reconstructions in LAPC with SMA encasement and excellent response to neoadjuvant treatment.

Abstract

Novel multimodal treatment strategies might enable curative-intent resection of locally advanced pancreatic cancer (LAPC). While venous resections are routinely performed, arterial resections remain part of individualized treatment strategies in a few expert centers. Historically, SMA involvement, by definition, precluded resectability. However, in selected patients with excellent response to preoperative treatment, arterial resection has been associated with satisfactory outcomes in high-volume centers with significant experience in extended and vascular resections. Even though arterial divestment is increasingly performed if technically possible, arterial resection is still required when the arterial wall cannot be preserved to achieve macroscopically complete resection, especially if the SMA is encased along with its branches in SMA segment 2. Usually, the SMV is also encased in these tumors, and combined arterial and venous resections are necessary. Here, we describe our approach to SMA resection and reconstruction after neoadjuvant treatment in a 64-year-old female patient with locally advanced pancreatic ductal adenocarcinoma (PDAC) and complete encasement of the SMA in segment 2. Critical steps in this situation are assessing the feasibility of SMA and SMV resection using an infracolic artery first approach, performing a wide Kocher maneuver to access the SMA from the right, and the Cattell-Braasch maneuver to enable tension-free direct end-to-end anastomoses.

Introduction

Surgery remains the only treatment option with curative potential for PDAC. However, only 20%-30% of patients qualify for upfront surgery, while 30% present with LAPC and the remaining ones with distant metastasis¹. Recent advances in surgical techniques, multimodal treatments, and perioperative care have led to an increased number of patients with tumors initially staged as locally advanced and unresectable that are reconsidered for curative-intent resection after neoadjuvant therapy. Retrospective data suggests successful resection of initially unresectable LAPC in up to 60% of cases with FOLFIRINOX-based induction chemotherapy².

Importantly, R0 resection is an independent prognostic factor for overall and disease-free survival after PDAC resection, independent from tumor stage^3,4. With the goal of achieving tumor-free margins, vascular resections are increasingly performed in cases with excellent response after preoperative treatment. While venous resections, including portal vein resections, have become routine and are supported by current ESMO and NCCN guidelines, arterial resections remain limited to expert centers as individualized treatment approaches due to high morbidity and mortality rates of up to 15%^5,6,7,8.

Arterial resections were initially performed by Joseph Fortner in the 1970s at Memorial Sloan Kettering Cancer Center as part of en-bloc resections of PDAC of the pancreatic head⁶. Yet, due to the high morbidity and mortality, this practice was soon abandoned. Alternatively, to achieve tumor clearance, arterial divestment has been proposed^7,8. Importantly, this has been associated with lower morbidity and mortality than arterial resections^7,8,9. Due to the rotation of nerve fibers around the SMA, clearance of ≥180° is necessary to achieve clear margins in PDAC with perineural invasion¹⁰. However, this is technically frequently impossible in cases of SMA segment 2 involvement and thus carries a high risk of incomplete surgical radicality. In recent years, there has been an increasing number of retrospective reports on arterial resections in PDAC. The aim of this article is to describe a standardized approach to resection and reconstruction of the SMA in PDAC in selected cases of SMA involvement without the option of arterial divestment.

Case Presentation:
The case is a 64-year-old female who presented with nonspecific back pain and weight loss without a family history of PDAC. An abdominal CT scan revealed a mass in the pancreatic head, suspicious of PDAC, with involvement of the SMA and portal vein. Baseline CA19-9 was 597 IU/mL, and total bilirubin was 18 mg/dL, while CEA was within normal limits. An MRI with hepatocyte-specific contrast agent did not show any evidence of liver metastasis, confirming LAPC. Based on the involvement of major upper abdominal vessels and an ECOG status of zero, the multidisciplinary team recommended induction chemotherapy after histological verification of diagnosis. A biliary stent was placed, and endoscopic biopsy confirmed the diagnosis of PDAC. Subsequently, neoadjuvant treatment was initiated with FOLFIRINOX. In total, the patient received six cycles of FOLFIRINOX. Based on partial response on imaging and >50% of baseline CA19-9, the multidisciplinary tumor board decided to recommend exploration with potential vascular resection.

Protocol

The present protocol follows the ethics guidelines of the Medical University of Vienna, and informed consent was obtained from the patient for this article and video.

The appropriate consent for surgical exploration and potential extended resection with vascular resection is obtained from the patient after extensive discussion of the risks and potential benefits associated with this procedure. The patient needs to be aware that no high-quality evidence currently supports arterial resections in PDAC.

1. Preoperative management

1. Perform a high-quality contrast-enhanced triple-phase CT scan to assess vascular anatomy and involvement. This includes sagittal and coronal CT planes or 3D reconstructions to assess the exact location of venous and arterial involvement and suitable vessels for reconstruction, especially in the mesentery below the tumor.
2. Obtain an MRI of the liver with hepatocyte-specific contrast agent to rule out liver metastases. Additionally, carry out a multidisciplinary tumor board discussion (mandatory).
3. Perform a fine needle biopsy to obtain a histological diagnosis for initiation of preoperative treatment¹¹. In cases of jaundice, place a self-expandable metal stent in the common bile duct.
4. Administer preoperative chemotherapy with FOLFIRINOX or Gemcitabine Nab-Paclitaxel. When a biochemical response and response on CT scans are confirmed, consider surgery¹².
5. Check the preoperative CT scan, and if it shows evidence of involvement of the first two jejunal branches (J1 and J2 in SMA segment 2, respectively), divestment will not achieve appropriate margins.
   NOTE: On CT imaging, a halo sign indicates the possibility of divestment, showing an encased but fully patent SMA¹³. In contrast, the string sign points to a true invasion of the SMA with narrowing or segmental stenosis on CT imaging, precluding the possibility of divestment. In cases of SMA encasement, the superior mesenteric vein is almost always also involved, and usually a combined SMA and SMV resection is necessary.

2. Operative setting

1. Place the patient in a supine position with the right arm in ≤ 90° abduction. The surgeon is on the patient's right side while the first assistant is on the left side.
2. Administer perioperative antibiotics with piperacillin-tazobactam. If a preoperative bile duct stent was placed, continue piperacillin-tazobactam for 5 days. In cases of signs of postoperative infections, tailor the antibiotic therapy to the intraoperative bile swabs.

3. Exploration phase

1. Perform a median laparotomy from the xiphoid to below the umbilicus to gain adequate exposure to the critical structures. Preserve the falciform ligament to be used as a cover for the arterial anastomosis.
2. Confirm the absence of detectable liver metastasis and peritoneal carcinomatosis, and then proceed with an inframesocolic artery first approach (mesenteric approach)¹⁴.
3. Elevate the omentum and the transverse colon cranially and perform an oblique incision approximately 10 cm in size below the mesocolon from the ligament of Treitz to the right mesocolon to expose the SMA and SMV within the mesenteric root below the palpable tumor border.
4. Dissect the mesenteric fatty and lymphatic tissue using ligatures and clips for small blood and lymphatic vessels until the SMA is completely exposed and secure it with a vessel loop. Send a specimen from the nerve plexus around the SMA for frozen section analysis.
   NOTE: Typically, the proximal SMA (segment 1) directly at the aorta is free of cancer. If there is evidence of tumor involvement at the origin of the SMA from the aorta, the surgical strategy needs to be adapted with the addition of an artery-first approach and frozen sections at the SMA origin at this stage of exploration. Arterial divestment can be considered as an alternative in selected cases of SMA resections, but involvement of SMA segment 2 and the intestinal branches at their origin carry a high risk of pseudoaneurysm or incomplete surgical radicality, and therefore, divestment may not be the preferred option.
5. Ensure that the venous axis is reconstructible by exposure of the SMV and its branches. One of the main SMV branches is usually sufficient for venous reconstruction and adequate venous drainage of the intestine. Suitability for venous reconstruction of the portal vein in the hepatoduodenal ligament is usually given.
   NOTE: Frequently, prehepatic hypertension due to stenosis of the portal vein or its tributaries in LAPC leads to cavernous transformation. In these cases, reconstructability of the portal vein is assessed in the porta hepatis by a right posterior approach to the portal vein without division of the bile duct and venous collaterals. Then, we place a (temporary) mesenterico-portal shunt using a ring-enforced, heparinized 8-10 mm polytetrafluoroethylene GORE-TEX prosthesis, depending on the size of the SMV or its tributary¹⁵. At the end of the reconstruction phase, the prosthesis can be either removed completely and an end-to-end veno-venous anastomosis is then performed, or length can be tailored so that kinking of the reconstructed SMA is avoided.

4. Resection phase

1. After confirming the feasibility of SMA and SMV reconstruction, enter the lesser sac and perform an extended Kocher maneuver with mobilization of the duodenum and exposure of the left renal vein. Then, proceed with a right-sided artery first approach to the proximal SMA (Segment S1) at its origin from the aorta¹⁶.
2. Transect the superior mesenteric plexus near the origin of the SMA and send a specimen to frozen section analysis.
3. Subsequently, continue the resection with a cholecystectomy and dissection of the hepatoduodenal ligament.
4. Perform a lymphadenectomy of lymph nodes 8, 9, and 12 (according to the Japanese Gastric Cancer Association) along the hepatic artery and the celiac artery using bipolar forceps, monopolar electrocautery, or sealing devices.
5. Secure the common hepatic artery and the celiac trunk with vessel loops. Divide the common bile duct and secure the portal vein with a vessel loop.
   NOTE: Adjust antibiotic therapy based on the microbial swab from the common bile duct postoperatively in cases where continued antibiotic treatment is indicated.
6. Ligate the right gastric, the gastroduodenal, and the right gastroepiploic arteries. Transect the postpyloric duodenum or the prepyloric antrum using a linear stapler, depending on the exact tumor location.
7. Place the (remnant) stomach in the upper left quadrant to achieve better exposure of the superior pancreatic margin.
8. Transect the transverse mesocolon with the middle colic vessels below the marginal vessels until the left side of the ligament of Treitz.
9. Transect the second jejunal loop and resect the mesentery, including the first and second jejunal branches.
10. Completely divide all mesenteric tissue except for the SMV and SMA, on the left side of the SMA from the looped segment towards the ligament of Treitz. Clip or ligate all arterial and venous tributaries and lymphatic vessels.
11. Dissect the lower pancreatic margin and tunnel the pancreatic neck and subsequently divide the pancreas with a scalpel. Submit the transection margin for frozen section analysis.
12. Identify the splenic vein and secure it with a vessel loop. In cases of tumor infiltration at the confluence, divide the splenic vein. If there is evidence of left-sided portal hypertension, create a splenorenal shunt by end-to-side anastomosis of the splenic vein to the left renal vein to relieve left-sided portal venous pressure and ensure venous drainage of the stomach, pancreas, and spleen¹⁷.
13. Loop the splenic artery and perform a lymphadenectomy along the splenic artery at the superior border of the pancreas.
14. Completely dissect all tissue between the celiac trunk and the SMA (the triangle tissue between the SMA caudally, the portal vein anteriorly, and the celiac trunk cranially¹⁸), so that the aortic segment is fully exposed. Now, the specimen is only attached to the mesenteric artery, the SMV, and the portal vein.

5. Vascular resection and reconstruction

1. Perform a Cattel-Braasch maneuver with wide mobilization of the small bowel, mesentery, and right-sided hemicolon. Leave just one medio-caudal peritoneal strip to avoid twisting without compromising exposure and mobility for later tension-free vascular end-to-end anastomosis.
2. Clamp the SMA close to its origin from the aorta as well as below the tumor. Prior to clamping, administer 1000-2500 IU heparin systemically depending on the patient's body weight.
3. Clamp the SMV in the mesentery and the portal vein. In case of cavernous transformation, and use of a mesenterico-portal shunt, this step is dispensable.
4. Transect the vein and perform a venous anastomosis using monofilament non-resorbable 6-0 running sutures with a growth factor to avoid a subsequent stenosis of the vein. In case of size mismatch, release the inflow from the SMV before the suture is knotted to ensure adequate distension of the venous anastomosis.
   NOTE: In case of cavernous transformation and use of a mesenterico-portal shunt, the latter two steps are dispensable. The extensive mobilization of the small bowel and mesentery usually allows direct end-to-end anastomosis without tension.
   1. Take great care to ensure correct rotation and avoid twisting of the SMV. Alternatively, mark the ventral surface of the veins with a pen before transection to ensure correct orientation.
5. Reconstruct the SMA using a direct end-to-end anastomosis with non-resorbable monofil 6-0 sutures. For the posterior wall, use a parachute technique, while for the anterior wall, perform reconstruction using non-resorbable monofilament 6-0 running or interrupted sutures.
6. Release the venous clamp. Release the arterial clamp.
7. Afterwards, proceed with single-loop reconstruction as described previously¹⁹. Usually, we do not perform planned total pancreatectomy in the context of SMA resection and reconstruction.
8. Wrap the arterial anastomosis with a falciform patch or omental flap to protect it against potential pancreatic secretions. Place a Robinson drain behind the vascular anastomoses and place two Easy-Flow drains at the hepaticojejunostomy and the pancreaticojejunostomy.

6. Postoperative phase

1. Keep the patient in the intensive care unit for 1-2 days, depending on the postoperative course.
2. Initiate prophylactic anticoagulation with low molecular weight heparin (LMWH) beginning 6 h postoperatively in cases of unsuspicious drain fluid. In cases of venous prothesis or complex venous reconstructions, administer LMWH adjusted to body weight, and initiate anticoagulation with a non-vitamin K antagonist initiated during hospital stay.
3. Initiate lifelong antiplatelet therapy with aspirin. Do not administer routine postoperative antibiotic therapy.
4. Initiate liquid oral food intake on the 1^st postoperative day. Mobilize the patient on the 1^st postoperative day with assistance.
5. Perform a CT angiography routinely within the 1^st week even if the postoperative course is uneventful.
6. Initiate early diagnostic measures if there are any signs of postoperative complications.
7. Carry out oncologic follow-up based on a standard approach after resection of PDAC, which involves CT scan, tumor markers, and clinical examination every 3 months for the first 2 years and every 6 months thereafter until 5 years after surgery.

Results

The case is a 64-year-old female who was diagnosed with locally advanced PDAC of the pancreatic head with encasement of the SMA (Figure 1). The surgery lasted 7 h and 35 min with an estimated blood loss of 950 mL. The intraoperative situs is depicted in Figure 2. A pylorus-resecting pancreatoduodenectomy was performed with resection and reconstruction of the SMA and SMV. The postoperative course was uneventful. We initiated proph...

Discussion

This article describes our approach at the Medical University of Vienna for SMA resections and reconstructions in LAPC following neoadjuvant treatment. High-quality preoperative diagnostics, careful selection of surgical candidates, and preoperative planning of the resection strategy are essential for arterial resections in PDAC surgery. However, in cases of stable disease on imaging and biochemical response, we go for exploration, as CT scans are well known to be unreliable in assessing tumor burden after neoadjuvant tr...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Computed Tomography	Canon medical systems
MRI	Siemens
Folfirinox	Adcock ingram
piperacillin	Pfizer
tazobactam	Pfizer
low molecular weight heparin	Merck