I want to speak about cancer of the pancreas. Cancer of the pancreas is maybe divided into some categories. We have primary cancer of the pancreas, which is the exocrine pancreatic cancer and that represents about 95% of cases. 2% of cases are neuroendocrine tumours; 2% are metastatic cancers to the pancreas from another organ and the rest are rare and very rare tumours like lymphoma and sarcoma. Pancreatic cancer is the ninth most common cancer in the United States and it’s the fourth cancer killing disease in the United States, it is the sixth in Europe. It kills about 200,000 people annually worldwide. This cancer is an epithelial cancer and it is mostly located in the head and neck, which is about 75%, 10% is in the body of the pancreas, 15% is in the tail and the rest involves the whole organ. There are specific risk factors, some of them are associated with low risk, some are associated with moderate risk and some are associated with high risk. These factors include obesity, they include some genetic diseases like BRCA1 mutations, BRCA2, blood sugar disease, then melanoma disease and mole syndrome, hereditary nonpolyposis colorectal cancer and chronic pancreatitis, cystic fibrosis and family history of pancreatic cancer.
The symptoms of pancreatic cancer, whether it’s in the head of the pancreas or in the body and tail, are very similar. These are constitutional symptoms like loss of weight and weakness and non-specific upper gastrointestinal symptoms like nausea, vomiting and abdominal pain. The only remarkable difference between these two sites in the organ is that jaundice is very common in the head of the pancreas and is rare in the body and tail of the pancreas cancer, for obvious reasons, because the tumour obstructs the common bile duct where it’s next to it in its vicinity. If there is jaundice in a patient who has cancer of the body and the tail it’s either because he has extensive metastatic disease in the liver or because he has portal lymphadenopathy that is causing obstruction of the common bile duct.
How do you investigate a patient with potential pancreatic cancer?
When we have patients suspected with pancreatic cancer we do the routine investigations and we do serum carbohydrate antigen 19-9 which is an antigen that is secreted by pancreatic cancer. The standard imaging test is a CT scan of the abdomen but an MRI and endoscopy are also helpful, and ultrasound. Endoscopic ultrasound can tell us about the size of the tumour as well as its consistency and the presence of lymph nodes and the status of the portal vein. In addition to this we usually do a laparoscopy for staging and before we embark on the operation.
Laparoscopy will show us very small metastases like subcentimetric metastases in the peritoneum or in the lymph nodes that may not be seen on CT scan. It will also give us the opportunity to do an endoscopic ultrasound, to do a biopsy and to do fluid collection for cytology. But laparoscopy is difficult when we are visualising retroperitoneal structures. There is also a very low but real risk of port site metastasis, especially if we handle the cancer tissue during the laparoscopy.
Now, the carbohydrate antigen has around 80% specificity and sensitivity and it correlates with the resectability so when it’s very high it’s more likely to be unresectable. This correlation is even stronger in the body and tail of the pancreas than in the head of the pancreas. We have to remember that carbohydrate antigen 19-9 is secreted by other malignancies of the pancreas and the liver, gynaecological and gastrointestinal malignancies and also in some benign conditions like cholangitis and cirrhosis.
Can you describe the staging of pancreatic cancer?
The staging of pancreatic cancer is based on the TNM classification which was developed by the American Joint Committee on Cancer. The T is for the tumour size from 1-3 and above and below 2cm and 4cm; the N is for lymph nodes and M is for metastasis. Stage 1 is usually T1, T2 lesions and stage 2 is T3 lesions or T1 and T2 with an N1 disease. Stage 3 is a T4, which is any size of lesion but with major vessels being involved or stage 3 can be an earlier T lesion but with N2 status, which means more than three lymph nodes are involved. Then stage 4 is metastasis. The staging correlates very well with prognosis as stage 1 have five year survival of about 40% while stage 3 has five year survival of about 10%.
How do surgeons classify pancreatic cancer?
The surgeons usually divide pancreatic cancer based on its resectability into resectable, which means there is no extra-pancreatic disease and there is no metastasis and there is a clear fat plane between the tumour and the major blood vessels. Then we have borderline resectable which means there is also no metastasis but there is partial involvement of blood vessels like the superior mesenteric vein and superior mesenteric artery but not exceeding more than 180o of the circumference of the wall of the blood vessel. Then we have unresectable which means either it’s metastatic or it is involving vital structures like the IVC or the aorta or if it is encasing the celiac artery and the superior mesenteric artery in a way that is unreconstructable.
What can you infer from CT scans?
We can predict from the CT scan the vascular invasion based on how much or what percentage of the circumference of the wall of the blood vessel is contiguous with the tumour, from 25% to 100%. The higher the percentage of the circumference of the blood vessel wall the more likely that invasion is there. So if there’s non-contiguity or the contiguity is less than 25% the chances are there is no invasion. If it’s more than 50% there is about a 50% chance of invasion and if it’s 75% there is about an 80% chance of invasion. If it is more than 75% almost all these cases have vascular invasion.
Another issue is also to look at how high or low the involvement of the superior mesenteric vein because if it is lower than the inferior border of the duodenum that makes it more unresectable. The veins are usually if there is a partial involvement and the tumour is wedged out from the vein and the patch of the internal jugular vein is used to close the defect. If the defect is through the whole vein then it has to be resected and then enteric anastomosis would be performed. Then if the segment is long then you may need to interpose an internal jugular vein graft between the superior mesenteric vein and the portal vein.
Are patients always prepared for surgery in the same way?
One controversial issue is the preparation of patients for surgery. Patients should have antibiotics prophylactically, anticoagulants, and they should have immunisation against encapsulated bacteria if a splenectomy is contemplated. The preoperative biliary drainage is controversial but these patients have coagulopathy sometimes and malnutrition. Although there is no significant difference in outcome between those that you would drain and those that you don’t drain, one study has shown that stenting is associated with more postoperative complications, especially infections, and a longer hospital stay. But usually we will do preoperative biliary draining selectively - those patients who are symptomatic and those who have significant hyperbilirubinemia and those who will undergo neoadjuvant chemotherapy.
The treatment for borderline resectable or locally advanced non-metastatic or unresectable is to give them chemotherapy, restage them, give them again another cycle of chemotherapy or radiotherapy and restage them and then reassess them and possibly some of them their tumour will shrink and they will be suitable for surgery.
Can you outline the operation?
The operation is a standard pancreaticoduodenectomy described by Whipple, which means you remove the distal stomach, duodenum and proximal duodenum and the common bile duct with the head of the pancreas, of course. If the patient has body anterior of the pancreas cancer then you do a distal pancreatectomy with a splenectomy. There are also lymph nodes around the area of the neck and tail of the pancreas that must be part of the specimen. When you are doing a pancreaticoduodenectomy the lymph nodes around the major vessels and the biliary tree should be excised. But the Japanese advocation of extended or radical lymphadenectomy in which the paraaortic lymph nodes are also involved is not widely accepted and doesn’t seem to have an impact on survival.
What are the procedures after the operation?
After the operation is done then you have to do three anastomoses which is stomach to you bring up Roux-en-Y jejunal loop and you anastomose it to the common hepatic duct and to the stump of the pancreas and to the stomach. The stump of the pancreas can be stitched either in two layers, mucosa to duct and then serosa to the aorta layer of the pancreas, or the pancreatic stump may be invaginated in the lumen and then closed with the stitching around it. This may be done in an end to end or end to side manner.
Are there any complications with these procedures?
Complications, well there is a mortality of about 1% in a highly specialised centre. You can have a post-operative intraabdominal abscess, wound infection, haemorrhage and post-operative leak, especially pancreatic leak. Of course recurrence as well. Recurrence usually occurs in the first three years and it’s most commonly in the liver and in the tumour bed area. Thank you.