Pancreatic cancer:
In patients with localised disease the relation of the tumour to the surrounding arteries (celiac trunc, sup. mes. artery) and veins (superior mesenteric-portal vein) is crucial
Resection of pancreatic cancer is difficult and should preferably be done in high volume centers
The main intraoperative morbidity arises from vascular problems, the major postoperative morbidity is associated with pancreatic fistula
Chronic pancreatitis:
In patients with intractable pain and local complications such as bile duct or duodenal obstruction, a surgical approach is the preferred treatment
Duodenum preserving procedures (Berne-, Beger- or Frey procedure) are the preferred procedures if malignancy is ruled out
Pancreatic cancer is the eighth most common cancer in the United States and Europe. Five-year survival rate is only around 6%, which makes it the fourth cause of cancer-related death. Over 95% of pancreatic cancers develop from the exocrine part of the pancreas, in 80% as ductal adenocarcinoma. Acinar cell carcinoma, cystadenocarcinoma, mucinous carcinoma, and endocrine tumors, which arise from hormone-producing cells, are rare entities. Harboring 75% of tumors, the pancreatic head is the predominant site.
Pancreatic cancer is a very aggressive tumor as shown by a 1-year survival of only around 18% for all stages. The disease is often diagnosed in a locally advanced stage or with distant metastases already present. Metastases are mainly located in the liver, the peritoneum, and the lungs.1 Complete resection remains the backbone of treatment in patients with locally limited disease and offers the only chance for cure and prolonged survival. Pancreatic cancer is found in an early stage, which qualifies the patients for surgery, in as little as 10% to 15% of cases. Five-year survival rates for these patients rise to 25%. Oncological surgery with R0 resection is an important factor determining the outcome in patients with pancreatic cancer. However, more recent data based on clearly defined histopathological specimen analysis revealed many earlier studies dealing with R0 resection as possibly having been based on incorrect baseline figures.2 In addition, resections are termed R1 according to the seventh edition of the TNM classification of the Union for International Cancer Control if a tumor is located within 1 mm from the resection margin. This is particularly important in the area around the mesentericoportal vein when no invasion of the vessel wall is present. Despite the R1 status of these patients, no data support resection of the vein.
The role of preoperative chemotherapy or radiochemotherapy is analyzed in several recent studies, especially in locally advanced tumors but not (yet) used routinely.3
The selection of patients who qualify for pancreatic surgery can be more difficult than the operation itself. Apart from the local situation, a good nutritional status and sufficient hepatic and renal function are crucial factors for the prevention of complications. Preoperative feeding has become very important in the last 10 years. The level of physical and mental fitness has an influence on postoperative recovery too, and should be determined and if possible improved preoperatively. Pancreatic cancer is a disease of the elderly patient. Age itself, however, is not a contraindication for pancreatic surgery.4 Both morbidity and mortality rates following pancreatic resection increase with age. Also elderly patients have a higher need for an extended-care facility following hospital discharge. However, overall the risk is not associated with age by itself but with the effect of patient comorbidities, cognitive status, preoperative functional status, and frailty that cause the postoperative problems in the elderly patient and therefore need to guide the surgeon when selecting candidates for pancreatic cancer resection.
When planning a pancreatic resection, a contrast enhanced computed tomography (CT) scan (1-3 mm layers) not older than 4 weeks is crucial. Alternatively MRI can be done instead of a CT. Importantly, there is no general need to perform both CT and MRI for assessing the pancreas, surrounding tissues, and vessels, and planning surgical resection. Such a policy is supported by the German S3 guidelines; the American Joint Committee on Cancer (AJCC) staging manual of pancreatic cancer supports the use of CT.
On the other hand, for surgical candidates, diffusion-weighted MR imaging has proven to be superior in detecting liver metastases5 and therefore is recommended in many centers for this group of patients in addition to multidetector contrast-enhanced CT.
For tumors smaller than 2 cm, additional endoscopic ultrasound can be helpful for detecting the primary lesion. In many cases, pancreatic head cancer is suspected in the presence of indirect signs such as dilatation of the common bile duct and main pancreatic duct and atrophy of the left-sided pancreas. In such cases, performing a resection in a patient with a solid mass without histology is correct.6 However, with the more widespread use of neoadjuvant treatment, histology is mandatory prior to starting treatment.
Preoperative criteria for borderline resection and unresectability are given in several guidelines and are nicely summarized in a recent consensus statement by the International Study Group of Pancreatic Surgery.7 See Table 12.1.
| Location of the Tumor | Borderline Resectable | Unresectable |
|---|---|---|
Tumor in the pancreatic head |
|
|
Tumor in the pancreatic body and tail | Abutment of the SMA not to exceed 180° of the circumference of the vessel wall. | Celiac encasement of greater than 180°. |
Current evidence justifies portomesenteric resections in patients with pancreatic cancer.8 The portal vein and the superior mesenteric vein should be open or, at least, show an open, accessible segment proximal and distal of the tumor for safe reconstruction.8
Of course, suspicious, possibly metastatic, lesions should be worked up before proceeding with an extensive resection. All kinds and localizations of metastases are contraindications for resectional surgery, whereas lymphadenopathy is not.
For cancer located in the pancreatic body or tail, again, the situations around the celiac trunk and superior mesenteric artery are key elements to assess local resectability. Formal arterial resections are not recommended. However, in exceptional circumstances, individual therapeutic approaches may be evaluated.8
It is not only the tumor and its relation to veins and arteries that is of interest but also the celiac trunk, common hepatic artery, and the trunk of the superior mesenteric artery that need to be assessed in detail on the preoperative CT scan. If the proximal segment of one of these arteries is stenosed, dilatation or stenting may be necessary prior to planning pancreaticoduodenectomy.
Traditionally oncological pancreatic resections are done by open technique. During the last years some data indicate that both pancreatic left resection and duodenopancreatectomy can be done by minimally invasive techniques. However, an increased 30-day mortality as recently published for duodenopancreatectomy is certainly not acceptable.9 In cases of suspected advanced disease with possible peritoneal metastases that are notoriously difficult to detect on cross-sectional imaging, diagnostic laparoscopy prior to open resection is the best way to avoid unnecessary laparotomies.
The surgical approach is based on localization and size of the tumor within the pancreas.
For an oncological resection, pancreaticoduodenectomy is needed. In terms of oncological outcome, the pylorus-preserving technique is as good as the classical Whipple procedure, which includes a distal stomach resection. Today the classical Whipple resection, its modification with an only minimal gastric resection (so-called subtotal stomach-preserving pancreaticoduodenectomy), and the pylorus-preserving version are all established techniques.10
The bursa omentalis is opened and the hepatic flexure of the colon is mobilized. A wide Kocher maneuver is done. The plane between uncinate process and mesocolon is dissected.
Now the tumor can be palpated and the relationship of the tumor to the superior mesenteric vein is assessed. If the superior mesenteric vein is infiltrated by the tumor and no distal segment can be found for a venous reconstruction, a pancreaticoduodenectomy is not appropriate. Otherwise the hepaticoduodenal ligament is dissected and its structures are identified. Cholecystectomy should be made for a safe biliodigestive anastomosis. Usually the bile duct is transected proximal to the insertion of the cystic duct. The gastroduodenal artery is ligated and cut only after temporary clamping and verification of persistent good arterial liver perfusion. This is important because in the presence of a stenosis at the level of the celiac trunk or the common hepatic artery, arterial hepatic perfusion may be dependent on flow via the gastroduodenal artery. If this is the case, simple ligation of the gastroduodenal artery without restoring sufficient arterial blood flow to the liver will result in postoperative liver failure, with considerably elevated morbidity and mortality.
After transection of the gastroduodenal artery, access to the portal vein at the superior margin of the pancreas is free. The pancreas is now ready for being transected above the superior-portal vein. Prior to this being done, the very proximal jejunum is transected and mobilized under the mesocolon. The uncinate process is further dissected from the superior mesenteric vein (if this has not already been completely done by an uncinate-process-first approach).11 Now the pancreas is transected over the mesenterico-portal vein.
Surgical Bail-Out Strategies
If the arterial liver perfusion is significantly dependent on the gastroduodenal artery and the latter has nevertheless been ligated and cut…
❍ First, the common hepatic artery and the celiac trunk need to be exposed and the arcuate ligament divided. If this does not improve the liver perfusion, 1 of the following steps becomes necessary:
❍ If the pancreaticoduodenectomy is done and the surgeon realizes the insufficient arterial blood flow to the liver (persisting after ligamentum arcuatum division), a graft from the splenic artery (if this vessel is not affected by the stenosis) or directly from the aorta is a possible alternative to restore arterial hepatic blood flow.
❍ Depending on the situation at the celiac trunk and the local expertise in-house, a catheter-guided revascularization of the common hepatic artery may be another option to restore hepatic arterial blood flow.
❍ If the gastroduodenal artery is a significant inflow vessel for the liver, its diameter is often more than 3 or 4 mm. Technically dissection of both ends and a repair using a saphenous vein interposition or a short PTFE graft are possible, but the tumor then remains in place and pancreaticoduodenectomy is not performed. However, the patient will not suffer from acute liver failure.
❍ If the impaired liver perfusion is not realized during pancreaticoduodenectomy but later due to a steep increase in liver enzymes, a liver duplex sonography combined with an angiography allow for assessment of the arterial liver perfusion. These investigations then are needed in order to plan the revascularization, either catheter-guided or by open surgery.
Importantly, such vascular problems are best dealt with together with experienced vascular surgeons and not done by GI surgeons themselves.
If the vein is not infiltrated, the pancreatic head is then mobilized from the vein and the right side of the superior mesenteric artery. With this step, the pancreaticoduodenectomy specimen is completely detached.
In the so-called artery-first approach, dissection parallel to the superior mesenteric artery is done before dissection along the vein is performed.12 This technique is similar to the mesopancreas-first dissection.13
If infiltration of the superior mesenteric or portal vein is present, the transection of the pancreas is done further to the left after taking down small branches draining the pancreatic neck and adhesions to the splenic vein. Also the inferior mesenteric vein joins the venous confluence in this area and it should be preserved. The next step is dissection from behind, similar to the artery-first approach or mesopancreas-first dissection.13,14 This allows for mobilizing the pancreatic head leaving only the tumor-related adherence and/or infiltration to the mesenterico-portal vein. As a last step, the portal, splenic, and superior mesenteric vein are clamped and cut whereby the pancreaticoduodenectomy specimen is complete. Together with the retroperitoneal lymph nodes, the tumor package is removed.
The easiest way of restoration of the venous drainage is done by direct anastomosis of the mesenterico-portal axis and ligation of the splenic vein. This however is merely possible if only a short segment (usually less than 2 cm) has been resected. Alternatively, a PTFE graft can be used, or in case of only partial venous resection, continuity can be achieved by using a vein or synthetic patch.
Surgical Bail-Out Strategies
If there is severe venous bleeding from the mesenterico-portal vein and/or splenic vein before the transection of the pancreas has been done, putting a clamp in this situation is difficult because the severe bleeding prevents a clear view on the anatomical situation and putting the clamp blindly may harm the vein, thereby causing even more bleeding.
❍ Digital compression combined with suction enables the surgeon to continue dissection and transection of the pancreas. This allows for better access to the superior mesenteric, splenic, and portal vein. Consequently, these can now be clamped in a controlled way.
❍ The hole or tear in the vein is repaired by direct suture even if this results in a certain narrowing. Nevertheless, this restores venous backflow to the liver and reduces venous congestion in the small intestine.
❍ Now oncological resection can be completed and then the venous repair has to be controlled and improved until any stenosis is eliminated. This can be done by direct suture, patch enlargement, or graft interposition, depending on the local situation.
Pancreatic and bile duct resection margins, as well as the retropancreatic margins (tissue to the right of or behind the superior mesenteric artery), are sent for frozen section histology.12
Surgical Bail-Out Strategies
If the vascular involvement is more extensive than suspected according to the preoperative imaging…
❍ The preparation is done from different sides in order to mobilize the specimen as well as possible. For accessing the superior mesenteric artery (SMA), this means combining the uncinate process first approach and the mesopancreas first dissection. In order to access the left and dorsal side of the mesenterico-portal vein, the splenic vein is ligated left to the (possible) tumor infiltration also opening the window to dissect from above towards the SMA. If short segment infiltration of the SMA is confirmed and resection is continued, arterial reconstruction may either be performed by graft interposition or by transposition of the splenic artery to the outflow segment of the SMA.
❍ If the common hepatic artery is infiltrated and needs short segment resection, there are several options to repair arterial hepatic blood flow. This may be done by direct suture in an end-end technique, by transposition of the splenic artery (when total pancreatectomy with splenectomy is done), or by a bypass from the aorta to the proper hepatic artery.
In cases with arterial or even both venous and arterial anastomoses in the area of the future pancreatic anastomosis there remains an increased risk for postoperative hemorrhage in case of a postoperative anastomotic leak. Therefore the option of eliminating a pancreatic anastomosis by performing a total pancreatectomy may has to be taken.
Reconstruction is performed after standard lymphadenectomy (see below). Superiority of pancreaticogastrostomy to pancreaticojejunostomy could not be proven uniformly, so the technique of the pancreatic anastomosis is surgeon-dependent. A well-documented and widely used technique is the pancreaticojejunostomy as a 2-layer anastomosis with mucosa-to-mucosa stitches. The end-to-side hepaticojejunostomy is usually a 1-layered, mucosa-to-mucosa anastomosis, done as a running suture or with interrupted stitches, which depends mostly on the diameter of the bile duct and again on the surgeon’s preferences. At the end the gastro- or duodeno-pars I-jejunostomy is performed.
Positioning of the last anastomosis antecolic or retrocolic may have an influence on the incidence of postoperative delayed gastric emptying (DGE), with the antecolic route being associated with fewer cases of DGE.15 A nasojejunal tube or a percutaneous feeding jejunostomy is implanted in all of our patients with a nutritional risk score of > 3 allowing a start of enteral nutrition as early as 6 hours postoperatively, which has been shown to enhance recovery.16
Left-sided tumors are treated with pancreatic tail resection, which is combined with a splenectomy in cancer patients allowing for adequate local lymph node clearance. The ideal closure technique of the pancreatic remnant after distal pancreatectomy is unknown: In a randomized, controlled multicenter trial, hand-sewn closure and stapler closure were compared with no difference in the fistula rate being found.17 Single series describe other procedural methods such as adding a pancreaticojejunostomy or coverage of the pancreatic resection margin by autologous tissue to prevent pancreatic fistula.
Depending on the intraoperative situs (tumor localization and size), extended pancreatic tail resection or total pancreaticoduodenectomy may have to be performed. Often the middle colic artery is infiltrated and indication for ongoing resection (with resection of the transverse colon) has to be carefully evaluated.
The lymph node status of patients with resectable pancreatic ductal adenocarcinoma is a key predictor of survival. Also, lymphadenectomy is important for adequate nodal staging. Extended lymphadenectomy including resection of lymph nodes along the left side of the superior mesenteric artery and around the celiac trunk, splenic artery, or left gastric artery showed no survival benefit compared with a standard lymphadenectomy.18 See Table 12.2.
Figure 12.1 indicates the number and location of the relevant lymph node stations.19
Sometimes total pancreatectomy is necessary for complete tumor resection. Multivisceral resections including spleen or transverse colon might be considered in single cases. In case of large tumors or ascites, a laparoscopy for exclusion of peritoneal carcinosis or hepatic metastasis should be done prior to performing laparotomy.
In a nonresectable cancer situation, treatments of biliary and/or duodenal obstruction are important to maintain the best possible quality of life (QoL). Obstructive jaundice limits QoL by its symptoms of refractory pruritus, nausea, and malnutrition. Relief of biliary obstruction therefore is of utmost importance and should primarily be attempted by endoscopic techniques.20 A biliodigestive bypass, mostly done by hepaticojejunostomy can be performed with a low complication rate in cases where irresectability has been found only at surgical exploration.
A gastric outflow obstruction occurs if the tumor infiltrates the distal stomach or the duodenum and in about 25% of patients such an obstruction becomes problematic. In these patients, endoscopic stent placement is a first choice. Unfortunately in the duodenum, stents are often not applicable due to technical or anatomical difficulties. Then a laparoscopic gastroenterostomy is the next best option to treat recurrent vomiting and aspiration due to duodenal obstruction.21
PITFALLS AND PEARLS
Anatomy of the upper abdomen is demanding and many vascular varieties are known. Different intraoperative surgical tactics may be required to deal with the individual anatomy and to perform the oncological tumor resection both radically and safely.
✓ Prior to starting resection, peritoneal dissemination or undetected liver metastases need to be ruled out. The liver and peritoneum have to be inspected and—if in doubt—intraoperative ultrasound can clarify suspicious intrahepatic lesions. Frozen section histology must be available. If hepatic metastases or peritoneal carcinosis is proven, the prognosis of the patient decreases markedly and extended surgical resection is not appropriate. Depending on the leading symptoms of the patient, palliative surgical intervention should be evaluated.
✓ An underdiagnosed and mistakenly ligated accessory right hepatic artery may lead to (transient) postoperative liver failure.
✓ A high-grade stenosis of the celiac trunk or superior mesenteric artery may be compensated by internal bypass circulation via the gastroduodenal artery. If this is not recognized and the gastroduodenal artery is clipped (as part of the standard procedure), this may lead to insufficient liver or intestinal perfusion associated with a steep increase in postoperative mortality.
✓ Nutritional status: Preoperatively as well as postoperatively, a sufficient nutrition is important for favorable patient rehabilitation. A nasojejunal tube or a feeding jejunostomy allows early enteral feeding. However, these catheters are associated with surprisingly high morbidity rates especially in those who are malnourished.22
✓ Exocrine pancreatic insufficiency is possible and should be searched for and treated by oral pancreatic enzymes.
✓ The anastomosis to the pancreatic remnant is the most critical one. Pancreatic leaks are correlated with morbidity and mortality. Leakage may lead to septic consequences or arrosion of blood vessels sutured or ligated during pancreaticoduodenectomy, thereby causing severe acute bleeding. Placing one or two drains around this anastomosis may help to recognize a pancreatic fistula earlier, allowing for intervention without delay.
✓ Performing a pancreatic anastomosis is easier in cases of a dilated and centrally located main duct and fibrosed pancreatic tissue. One possibility to deal with soft pancreatic tissue and a narrow main duct is to place a drain in the main duct (stenting of the anastomosis). However, there is no evidence that this decreases the rate of pancreatic fistula in this situation.
✓ Pancreatic tissue is extremely sensitive. The potential to develop severe inflammation in the postoperative course obliges the surgeon to handle with care and to avoid any additional squeezing or touching the organ.
✓ It is crucial to recognize a possible complication early. One reason why pancreatic surgery is safer if performed in high-volume centers lies in the fact that the whole team, including residents and nursing staff, is more familiar with this kind of surgery and realizes faster if the postoperative course is delayed.
✓ Septic and hypovolemic shock are the two most severe complications of pancreatic anastomotic leakage. In both cases, emergency intervention is key for the outcome in a single patient.
✓ Insufficiency of the hepaticojejunostomy is often caused by local hypoperfusion and necrosis of the bile duct. It is important not to do an enhanced preparation and denudation of the bile duct thereby destroying sufficient arterial perfusion.
✓ Conservative management of a well-drained anastomotic leakage of the hepaticojejunostomy is reasonable if the patient is stable and the amount of bile in the drainage is decreasing. Surgical revision is needed in case of sepsis and/or persisting secretion of bile.
✓ Because of the very good vascularization, gastric anastomotic leakage is rare and technical error should be considered. In some cases, an insufficiency is a result of an obstruction distal to the anastomosis.
✓ Postoperative DGE is a frequent problem after pancreaticoduodenectomy (about 20%). The incidence is increased significantly if additional problems such as pancreatic fistula occur. The pathophysiology is not yet sufficiently understood. Some risk factors are known.23
Related posts:
Shared Decision Making—the “Holy Grail” of Informed Consent? Implications for Surgical Practice
Safety in Surgery Beyond the Checklist: The Team Approach to Keep Patients Safe
Surgical Safety Checklists—Pitfalls and Pearls
When Things Go Wrong in the Operating Room: Intraoperative “Rescue” Strategies
Failure to Plan is Planning to Fail: How to Prevent Intraoperative Complications in Orthopedic Surgery
Technical Errors and Bail-Out Strategies in Abdominal Surgery
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