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After a Whipple operation, about half of the patients are found to have deficiencies in both the endocrine and exocrine functions of the pancreas. Most people assume that the risk of these complications is greater in older individuals, but this isn’t always the case. 

Audrey was a single 29-year-old woman who had experienced a sequence of unusual medical conditions before she was finally found to harbor a pancreatic tumor. She had developed symptoms which seemed to have little connection to her pancreas, such as headache and dizziness, but when she complained of crampy abdominal pain, she finally underwent an abdominal CT scan and was found to have a cystic-appearing (fluid-filled) mass in the head of her pancreas. She had no history of pancreatitis – the cause of an inflammatory cyst known as a pseudocyst which is the most common cystic-appearing lesion of the pancreas. True cystic lesions of the pancreas range from serous cystadenomas, which are benign 96% of the time, to cystadenocarcinomas, which are cystic versions of the aggressive pancreatic ductal adenocarcinoma or PDAC, and therefore malignant 100% of the time. In between these ends of the spectrum are different types of tumors, including mucinous cysts, which contain mucus and have a distinct cellular lining, intraductal papillary mucinous neoplasms or IPMNs, which are not mucinous cysts at all but rather a cystic-appearing dilatation or swelling of the main pancreatic duct or the side branches of the pancreatic ductal system due to a mucus-producing growth on the lining of the duct, and papillary cystic tumors which are rare tumors filled with both solid and cystic areas that are mostly found in women of child-bearing age. Papillary-cystic tumors, IPMNs, and some mucinous tumors all have the potential to degenerate into invasive pancreatic cancer, so these are all candidates for removal.

Audrey’s tumor was examined by EUS, and the contents of a fine needle aspiration were interpreted as consistent with a benign serous cystadenoma. Because she had symptoms of crampy abdominal discomfort, she was advised to have the lesion removed. She saw another surgeon at a university medical center, who told her she needed to have a Whipple procedure. She searched for more information and discovered the work we had done on pancreas-sparing approaches to non-cancerous lesions of the pancreas. Despite the benign diagnosis, she wanted to have the lesion removed with as much sparing of her normal pancreas as possible so as to avoid the complications of pancreatic resection that she had learned about with much concern.  

When she came for her evaluation, I explained our procedure of performing an intra-operative ultrasound exam to verify that an excavation procedure could be performed and that if it could not be safely undertaken, a pylorus-preserving Whipple procedure would be required. At surgery, the ultra-sound examination revealed that the tumor was so close to the lower part of the common bile duct, which traverses through the head of the pancreas, that an attempt at excavation would likely injure this structure. This could create a devastating complication. After discussing this with her family in the waiting room, we proceeded with the Whipple procedure and completed it uneventfully. The pathologist who examined the lesion after its removal discovered that it was not a benign serous cystadenoma, as initially diagnosed, but was instead a papillary-cystic tumor. The entire tumor had been removed and did not harbor any invasive cancer.

Post-operative complications set in

Audrey did well for the first few days after surgery but was unable to resume a normal diet. When she was fed anything but clear liquids, she suffered nausea and vomiting due to failure of the stomach to empty. The condition of delayed gastric emptying is one of the most common complications of the Whipple procedure, and although distressful, usually resolves after a period of decompression with a naso-gastric tube passed through the nose into the stomach. Days went by, and despite several attempts to remove the tube, her lazy stomach refused to recover from its paralysis. Finally, she was able to tolerate a semi-liquid diet, then soft foods, and was finally able to eat about ten days after her surgery.  

Months after the surgery, she began to lose weight and feel ill and was found to have developed diabetes. The type of diabetes which occurs after removal of part or all of the pancreas is called pancreatogenic diabetes, or “type 3c diabetes” as it is a form of secondary diabetes due to diseases or removal of the pancreas. Initially, Audrey was able to control her blood sugar with diet and oral medication but eventually had to learn how to give herself insulin each day to keep her blood sugar under good control.

Then she began to develop abdominal pain after eating. A CT scan showed that she had developed a blockage of the connection from the remnant of her pancreas to the small intestine, due to scarring of the anastomosis, the seam between the pancreatic tissue and the intestine. A second operation was required to remove the scar and fashion a new connection of the pancreatic remnant to the intestine. Just as before, the recovery from her surgery was complicated by delayed gastric emptying which took days to resolve. Her symptoms of pain resolved, but the diabetes persisted, and she began to have multiple bowel movements each day, a sign of pancreatic enzyme deficiency, which required her to take enzyme replacement capsules with each meal. A few months later, she developed weakness and bulge in the area of her abdominal incision. This incisional hernia occurred due to poor healing of the primary incision and required yet a third operation to correct.

Audrey experienced virtually every late complication of the Whipple procedure possible. The delayed gastric emptying, called gastroparesis, is a frequent complication after the procedure that seems to occur paradoxically in young people more often than in older patients, and its cause is still debated. She had the miserable luck to have suffered from this delayed recovery in stomach function not once but twice, after both of her pancreatic procedures. The big Whipple operation disrupts the anatomy and nervous circuits of the upper gut, which are implicated in the cause of the condition. Her second operation involved almost no major dissection or disruption of these areas, so her development of the same problem after such a “limited” procedure remains mysterious in its cause.

Audrey’s diabetes was caused by removing half of her insulin-producing islet cells by the Whipple operation. She may have been destined to develop diabetes later in life anyway, and the operation may have simply sped up the time course for her to develop the condition, but about half of the patients who undergo the Whipple operation are found to be diabetic after surgery. Type 3c diabetes is different from either type 1 (juvenile-onset or insulin-dependent diabetes due to an auto-immune condition) or type 2 (adult-onset diabetes associated with obesity or aging). It frequently complicates diseases such as chronic pancreatitis and cystic fibrosis. Patients with type 3c diabetes usually require low-dose insulin treatment and must be followed for the same diabetes-related complications that occur with the more common type 1 and type 2 disease. Patients with type 3c diabetes always require pancreatic enzyme replacement, for life, as this helps to prevent osteoporosis and bone disease.

Audrey’s incisional hernia was no small matter for a young woman who had already undergone two abdominal operations. As many as 20% of Whipple patients suffer some kind of wound complication, which contributes to the difficulties patients have returning to normal activities. Over the past few years, an increasing number of surgeons skilled in minimally invasive or laparoscopic pancreatic surgery have found that the operation can be performed without the need for big incisions, which eliminates this complication. The “learning curve” for the laparoscopic Whipple procedure is steep, and although its benefits are significant, only a limited number of surgeons can perform the operation this way. Until more surgeons are trained in this method, only a small number of patients can benefit from it.

So Audrey was “cured” of her rare and potentially malignant pancreatic tumor, but suffered practically every complication associated with the surgery. Somehow, she retained her sense of humor and was able to adopt a philosophical attitude about the whole ordeal. Her course demonstrated why the diagnosis of pancreatic lesions is tricky – she was originally told that she had a benign tumor in error – and why pancreatic resection is never guaranteed to be uncomplicated even in a young, otherwise healthy patient. 

Curing her of a tumor which could have become aggressively malignant was a clear benefit but putting her at risk for the life-long complications of diabetes and enzyme deficiency tarnished this outcome.