The Sol Goldman Pancreatic Cancer Research Center

What's New 1999

Mucinous Cystic Tumors of the Pancreas
November 19, 1999

Mucinous cystic tumors are rare neoplasms of the pancreas characterized by the presence of large cysts (fluid filled cavities) lined by mucin producing cells. Some investigators have suggested that all mucinous cystic neoplasms are malignant (capable of spreading to other organs) and that all mucinous cystic tumors should therefore be designated as cancers "mucinous cystadenocarcinomas."

Investigators at Johns Hopkins studied over 60 of these rare tumors and found that with careful examination they could accurately separate mucinous cystic tumors into two groups those that are entirely benign (the tumors never recurred) if completly resected ("mucinous cystadenomas") and those that had a malignant or cancerous potential ("mucinous cystadenocarcinomas"). This study by Dr. Robb Wilentz is reported in the November issue of the American Journal of Surgical Pathology (volume 23, pages 1320-1327). Importantly, two-thirds of the mucinous cystic tumors in Dr. Wilentzs study fell into the entirely benign group. This means that simply lumping all mucinous cystic tumors into the malignant category would have incorrectly labeled two-thirds of the patients as having cancer when they didnt!

The study is also important because it highlights the impact private donations can have on research. Dr. Wilentz conducted this research during a research fellowship year he spent in the laboratory of Dr. S. Kern and this fellowship was supported by the Helen S. Heller and Daniel Kim Memorial Funds for pancreatic cancer research at Hopkins. Without this private support, Dr. Wilentz would not have been able to do his study. Private giving makes a difference!

Wilentz RE, Albores-Saavedra J, Zahurak M, Talamini MA, Yeo CJ, Cameron JL, Hruban RH. Pathologic examination accurately predicts prognosis in mucinous cystic neoplasms of the pancreas. Am J Surg Pathol 23(11):1320-1327, 1999.

Peutz-Jeghers Gene Shown To Play a Role in the Development of Pancreas Cancer
June 23, 1999

Twelve years ago doctors at Johns Hopkins reported that patients with a rare syndrome, called "The Peutz-Jeghers Syndrome," had an increased risk of developing pancreatic cancer.1 The reason for this increased risk remained a mystery until now.

The Peutz-Jeghers Syndrome is a rare inherited syndrome in which affected patients develop dark pigmented spots on their lips ("mucocutaneous melanin macules") and polyps in their intestinal tract ("hamartomas"). These patients have an increased risk of cancer, especially pancreatic cancer. In the June 1999 issue of the American Journal of Pathology, Gloria Su, Ph.D. and colleagues from Johns Hopkins explain this association.2

The STK11/LKB1 gene in chromosome 19 is responsible for the Peutz-Jeghers Syndrome. Gloria Su and colleagues examined the status of the STK11/LKB1 gene in a large series of pancreatic cancers and in pancreatic cancer resected from patients with the Peutz-Jeghers Syndrome. They found that the STK11/LKB1 gene was inactivated in 4-6% of the pancreatic cancers. While the inactivation of this gene plays a role in only a small percentage of pancreatic cancers, Gloria Su and colleagues made a second, quite remarkable discovery. They found that the inactivation of the STK11/LKB1 gene in patients with the Peutz-Jeghers Syndrome explained the development of pancreatic cancer in these patients. Thus, a long-standing mystery was solved. The inheritance of a defective copy of the STK11/LKB1 gene causes the Peutz-Jeghers Syndrome and the inactivation of this gene in these patients explains their increased risk of pancreatic cancer.

Giardello FM, Welsh SB, Hamilton SR, Offerhaus GJA, Gittelsohn AM, Booker SV, Krush AJ, Yardley JH, Luk GD: Increased risk of cancer in the Peutz-Jeghers syndrome. N Engl J Med 1987, 316:1511-1514.

Su GH, Hruban RH, Bansal RK, Bova GS, Tang DT, Shekher MC, Westerman AM, Entius MM, Goggins M, Yeo CJ, Kern SE. Germline and somatic mutations of the STK11/LKB1 Peutz-Jeghers gene in pancreatic and biliary cancers. Am J Pathol 154(6):1835-1840, 1999.


Standard vs. Radical Whipple
May 28, 1999

Surgical resection is currently the most effective treatment for cancer of the pancreas. The extent of the surgery which should be performed is, however, controversial. Some have argued that the standard pancreaticoduodenectomy (Whipple procedure) should be extended to include the removal of the distal stomach (distal gastrectomy) as well as the removal of additional lymph nodes (retroperitoneal lymphadenectomy). The more extended surgery is called a "radical pancreaticoduodenectomy". The controversy over standard versus radical Whipple has been difficult to resolve, because most centers do one surgery or the other and data between institutions may not be comparable.

In the May 1999 issue of the Annals of Surgery, Drs. Yeo, Cameron and colleagues from Johns Hopkins report a study that may finally help resolve this controversy. They report a randomized single-institution trial in which patients were randomized to receive either a standard or a radical Whipple. Of the 114 patients randomized, 56 underwent a standard Whipple and 58 a radical Whipple. Dr. Yeo and colleagues found that the two procedures can be performed with similar morbidity and mortality. Importantly, the one-year survival rate for both groups was similar (~80%).

This important study will continue and the patients enrolled will be followed to determine if there are any long-term benefits to doing a radical Whipple. For now, part of the controversy in the radical versus standard Whipple debate has been answered. Both can be performed with equal morbidity and mortality, but the radical Whipple does not provide any improvement in survival at one year.

Yeo CJ, Cameron JL, Sohn TA, Coleman J, Sauter PK, Hruban RH, Pitt HA, Lillemoe KD. Pancreaticoduodenectomy with or without extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma. Comparison of morbidity and mortality and short-term outcome. Annals of Surgery 1999; 229: 613- 624.


Robb Wilentz Wins an Award
March 26, 1999

Robb Wilentz, one of the pancreas cancer research fellows at Johns Hopkins, won the 1999 Gastrointestinal Pathology Society Award for best presentation by a resident or fellow at the 1999 meetings of the United States and Canadian Academy of Pathology. Robb won the award for his presentation entitled "Morphology Accurately Predicts Behavior of Mucinous Cystic Neoplasms of the Pancreas" (Modern Pathology, Volume 12, 1999, Page 169A). This work is important because it has been previously suggested that all cystic tumors of the pancreas which produce mucin (so called mucinous cystic neoplasms) are malignant (cancerous). Robb showed that a careful microscopic examination of these tumors can be used to separate them into two groups: those patients who are completely cured if their tumors are removed surgically and those patients who need additional therapy. Using the techniques Robb outlined a group of patients with these tumors can be told that they are cured while other patients will receive the benefit of additional therapies. Our congratulations go out to Robb for a job well done.

Wilentz et al. Morphology Accurately Predicts Behavior of Mucinous Cystic Neoplasms of the Pancreas. Modern Pathol 12(1):169A, 1999.


More on "What's Broke in Pancreatic Cancer?"
March 1, 1999

A few months ago here in the What's New pages, we introduced an analogy. We noted that we get televisions fixed when only a single small part breaks. The same holds for cars, houses, and bicycles. Maybe if we knew just what was broken in a cancer cell, we could fix it.

We continue to make progress in figuring out "What's Broke." In a study published recently (Cancer Research 58:9329), additional clues implicate an important tumor suppressor system. This study was led by Michael Goggins, a postdoctoral fellow in the Kern laboratory and now a new faculty member (see below for the establishment of his new laboratory dedicated to developing screening techniques for the early diagnosis of pancreatic cancer). He discovered that some pancreatic and biliary cancers have mutations or deletions of certain genes that produce proteins for the surface of the pancreatic cells. One of the most well-studied proteins in cancer research is one called TGF-beta. TGF-beta exists outside of cells, in tissue and circulating in blood, but can bind to receptors on a cell's surface. When this happens, the cell is instructed to slow its growth, or to become a more mature type of cells (called "differentiation"), or even for the cell to cease living (called "apoptosis", from a Greek word that refers to the falling off of leaves from trees in the fall). Cancer cells are notoriously poor in responding normally to TGF-beta's suppressive effect, but exactly why has been difficult to figure out. Mutations in the receptors are only rarely found. Dr. Goggins' study was the first ever to show that cancers can genetically inactivate both of the major types of TGF-beta receptors. This study also provided the first concrete evidence that pancreatic cancers arise, in part, because they acquire the ability to evade the normal control of TGF-beta.

In a related discovery published last month (Proc Natl Acad Sci USA96:1427), Dr. Jiale Dai, another postdoctoral fellow in the Kern laboratory, helped us understand the role of another tumor-suppressor of pancreatic cancer. The DPC4 gene is mutated or is deleted in just over half of pancreatic cancers. No other tumor type has as many alterations in DPC4 as does pancreatic cancer, suggesting that the study of DPC4 may hold some important lessons for pancreatic cancer. Dr. Dai discovered that if he took cells that made no DPC4, and then genetically engineered them so they would produce DPC4, the cells grew much slower. This is what you might expect for a tumor-suppressor gene. He then expanded on these findings in a clever way. He made a special form of DPC4 where he could control its activity at will. Upon adding a certain chemical, he could make the DPC4 go from an inactive form to an active form within minutes. By doing this type of comparison, he found that active DPC4 could kill the cancer cells, and it seemed that this may have been the major way by which DPC4 acts as a suppressor gene. When he studied a mutant form of DPC4 found in a patient's cancer, the opposite results were found. Now instead of suppressing growth and causing cell death, growth was stimulated and the cancer cells were protected from death.

Due to Dr. Dai's work, we now have a clearer understanding of just how pancreas cancer cells come to misbehave. Now that he knows the overall effects of DPC4, Dr. Dai is currently refining his studies to understand the exact mechanism by which DPC4 accomplishes it all.

These and future research efforts should help us to understand "What's Broke" in pancreatic cancer. Only then will we be empowered to fix it.


New Laboratory Established at Hopkins for the Early Detection of Pancreatic Cancer
February 2, 1999

All too often patients with pancreas cancer do not come for medical attention until after the disease has spread beyond the pancreas. We urgently need a new test for the early diagnosis of pancreatic cancer, so that these cancers can be detected at their earliest stages while they are still curable. Johns Hopkins is therefore pleased to announce that on February 1, 1999 we opened a new laboratory dedicated to finding new methods to detect early pancreatic cancer. Dr. Michael Goggins will head this laboratory. Remarkably, the creation of this lab was made possible by funds raised from the November 8th, 1998 Pancreatic Cancer Fundraiser held in California, and by generosity of users of this Web page! The creation of this lab shows what "people power" can accomplish.

Number one on the list of goals for this laboratory is to develop a screening test for early pancreatic cancer. Screening tests for breast cancer, colon cancer, and prostate cancer already exist and have helped save lives. Dr. Goggins has dedicated his laboratory effort to finding the "PSA test for pancreatic cancer."

Although we were able to raise enough funds to open this exciting new laboratory, we have only raised approximately $100,000 of the $400,000 needed to operate the laboratory over the next three years.

Left to right: Mike Goggins, Jessa Jones, Gloria Su, Judy M., Ralph Hruban, Marsha G.
Left to right: Mike Goggins, Jessa Jones, Gloria Su, Judy M., Ralph Hruban, Marsha G.