Results in pancreatic cancer surgery: Are we offering the best possible care to these patients?

In 2012, Sasha Muller from Switzerland published a review article in the Recent Results in Cancer Research*  (Please click on the * for references) on the bird's eye view of developments in pancreatic cancer surgery. We want our reader to recognise that the fact that surgery is the mainstay of curative treatment in pancreatic cancer, while at the same time recognise the limits of such an unimodal approach.

In a country with accessible health for most of the population, 40% of patients with resectable disease were not offered surgery*. We do not have similar statistics with regard to the situation in India, but we believe that situation may be worse from additional factors like affordability.

At best, the 5 year probability of surviving pancreatic cancer remains at a dismal 10%*. The fact that the survival has reached double digits has been a source of joy for the pancreatic surgical community.  If we look at the SEER database 1998 - 2003, the drop in the proportion of survivors even in localised disease is at 60% within the first year*. We do find that drop in the proportion of survivors alarming. 

We were looking at the standardisation of Whipple's operation and the perioperative care of patients who undergo pancreatic surgery. The standards of Whipple operation is very variable even among established surgical departments. There are several issues that came up: inadequate retroperitoneal margins (The distance between the tumour margin and the cut margin at the level of the superior mesenteric artery), inadequate lymph node margins are the twin challenges that we wanted to eliminate at the root.

KV Menon and Verbeke, from Leeds, UK using detailed pathological examination showed that the pancreatic cancer surgery had a very high risk of inadequate surgery in their now classic paper. They found that 85% of the patients had R1 resections, which means microscopic tumour was found at the surgical cut margin*. This seminal work was known since 2009 in the pancreatic community. The challenge was to find a solution to the margin problem.

The second major issue was the adequacy of LN clearance from the tissues around the pancreas. Neoptolemos published in 1999, the international consensus definition of a standard Kausch Whipple operation and the standard lymph node removal template*. For pancreas head cancers which straddle the space between two major visceral blood vessels, getting all the needed lymph nodes for treatment and prognostication is a challenge. 

Today, we look at possible solutions that the pancreatic community has produced for these 2 key problems that prevent us from getting the appropriate results in pancreatic cancer surgery.

Margin adequacy at the retroperitoneal margin is the first challenge. The pancreas wraps around the main intestinal blood vessels like a 'C' encasing partially on the right side. The lower end of the C is attached to the superior mesenteric artery and has a variable thickness. Pancreas surgeons have traditionally approached these lesions from the right side of the curve and ended up leaving some tissue on the artery. For a long time, I used a lateral roll method to get to the site where the tissue is the thinnest and provided a long margin. This portion also completely removes the uncinate process of the pancreas and gives a thin fibrous tissue with very few blood vessels running across. This provided the twin benefits of low incidence of post pancreatic surgery bleeds and longer surgical margins. Even this was not adequate in certain tumours of the pancreas head, by virtue of mere position or sometimes due to advanced stage and large size.

The next level that was done to get good margins was developed for a completely different surgical reason, which nevertheless has become accepted for greater margin clearance. One of the key arteries in pancreatic cancer surgery is the inferior pancreatico duodenal artery, which can arise independently from the superior mesenteric artery or take off along with the first jejunal artery. This portion lies behind the portal vein (vein that takes all the digested material to the liver by draining blood from all over the intestine) and is very critical for good pancreas surgery. Taking this blood vessel though multiple approaches has been called the artery first dissection. Today this ligation is called the LV2 approach by the Japanese surgeons.

The blood vessel from which the inferior pancreaticoduodenal vessels take off is called the superior mesenteric artery. This artery is wrapped around by a fat layer which contains a plexus of nerves. These neural elements can be involved in pancreas cancers. LV 3 dissection removes up to complete 180 degrees of the neural elements on the right side of the artery. Since we took up this research component as a part of our practice, we found slightly increased diarrhea, but definitely better margin clearance. It is this technique that allows us to treat larger tumours, with lesser morbidity, giving us near 100% survival at 1 year. We continue to advocate this slightly technically difficult operation for better results.

Once this is achieved at 1 year, we believe that we are on the road to a better survival for our patients with pancreatic cancer.

The second challenge is the adequacy of LN clearance. Despite the fact that clearing lymph nodes may not increase survival, we believe that it gives us better prognostication on long term survival. There are 5 pairs of lymph node stations* that are removed in pancreatic cancer: 12a, 12 b, 12p on the liver hilum, 8 a and 8p along the liver artery, 13 a and 13 b on the posterior surface of the pancreas, 17 a and 17b on the anterior surface of the pancreas, 14p and 14 d on the right side of the superior mesenteric artery. Together, these constitute a standard lymph node package of a Whipple operation.

From the Japanese Pancreas Society classification, we simplified the application template to enable standardisation, which I have used for 10 years. Our template is based on arteries around the pancreas: We use 3 arteries to get all the lymph node packets - Hepatic artery - proximal and distal (Station 12 and 8 packets), Gastroduodenal arery (Station 13a, 17 a) and the inferior pancreaticoduodenal artery (Station 13 b, 17 b,14 p and 14 d). This simplification for application has provided the global surgical template for pancreas head cancer surgery with adequate cancer clearance goals in our program.

I am not saying that all the challenges of pancreatic cancer are overcome, but we believe that the first step is to reduce the steep drop in survivors within the first year of treatment must be reduced by adequate surgery. That it may be working, is the inference that we draw from our current experience.

Reading time: 13 minutes