Class Acts, Winter 2015

Herbert Zeh Rethinks Pancreatic Cancer
Winter 2015

Zeh performing a robotic Whipple at UPMC Presbyterian, one of only a handful of hospitals in the United States to offer the procedure.Surgical oncologist Herbert Zeh (MD ’94) says he isn’t a runner. And yet he signed up for the Pittsburgh, New York, and Dublin marathons. “It seemed like an interesting challenge,” says the Pitt associate professor of surgery, who completed every step of the 26.2 mile routes in New York and Pittsburgh. (And the Dublin finish line? “The pint of Guinness seemed more important,” he quips.)

And as a third-year medical student, Zeh signed up for a post in the laboratory of the University of Pittsburgh’s Michael Lotze, investigating the role of the immune system in cancer. The collaboration was so productive, Zeh took a year off from his coursework to author seven papers on their findings.

So don’t let that quip about the Guinness distract you—Zeh is tenacious. Consider his chosen field. He is chief of UPMC’s Gastrointestinal Surgical Oncology Division and codirector of the UPMC Pancreatic Cancer Program.

Typically identified late in its progression, pancreatic cancer kills 75 percent of patients in the first year after diagnosis. “Pancreas cancer was the highest mountain out there,” says Zeh, who also directs clinical research for UPCI’s Division of Surgical Oncology.

Prospects for survival are better for those who undergo the Whipple, a complex surgical procedure with an ominous reputation among surgeons and patients alike. During the operation, surgeons remove the head of the pancreas, the gallbladder, and portions of the small intestine, bile duct, and sometimes the stomach.

Then they replumb the whole system to excise pancreatic tumors and their blood supply while preserving gastrointestinal function.

Despite significant advances in the past 40 years, about 40 percent of patients experience significant postsurgical complications. Zeh mastered the procedure as a senior resident and fellow at Johns Hopkins Hospital, training at the elbow of John Cameron. “When Cameron started in the ’70s, patient mortality was 30 percent from the Whipple,” says Zeh. “By the time I graduated, only 1 to 3 percent of our patients died from the surgery. But we hadn’t made any progress on survival from the pancreatic cancer. Even if we did a successful surgery, 90 percent of the time, the cancer would come back.”

In 2002, Zeh joined the Pitt faculty and set about developing a robotic surgical program to further minimize the trauma and blood loss of the conventional Whipple and speed recovery. Recently, he partnered with assistant professors of surgery Melissa Hogg (Fel ’13) and Amer Zureikat (Fel ’10), to develop a surgical training program using the robotic techniques. “This approach gets more patients on to chemo, helps them return to health and work quicker, and they don’t have as much pain,” says Zeh. “The bottom line is that a complex operation like the Whipple can’t be done safely with the current [nonrobotic] laparoscopic technology,” because of the extremely fine dexterity required, he says.

Back at Pitt, Zeh also reconnected with Lotze, MD professor of surgery, immunology, and bioengineering and vice chair for research in the Department of Surgery, who had overseen Zeh’s foray into research as a med student. In 2003, they started work on a study that would be published in 2005 by the Journal of Immunotherapy, “Addicted to Death.”

“We suggested that cancer cells had learned to die in the wrong way, and [that] what we see as cancer is a consequence of their dying—a terrible, awful, crying out loud, blood-in-the streets kind of death,” says Lotze. “Virtually everything we imagined has come true.”

The two have since coauthored 56 papers, many on aspects of what is known as autophagy, a process that recycles damaged cellular components and returns a cell to useful service and, in cancer, appears to fuel a malignant cell’s survival.

In a series of ongoing investigations, Zeh, Lotze, and Daolin Tang, a PhD assistant professor of surgery, are testing tactics to interrupt autophagy in pancreatic cancer and elucidate the molecular mechanisms by which the cellular repair process runs off course. Promising data from clinical trials of a drug that halts autophagy in pancreatic cancer patients suggest the trio is on the right track. “Over the last two years, we’re starting to see changes that make me think we might get the rock up the hill,” says Zeh. “And I’m crazy enough to think the gods won’t push it back down.”

Photo courtesy of Herbert Zeh

 

Nicole Shirilla Upholds Life, and Death

BY LIBERTY FERDA

Nicole Shirilla (second from the right) and colleagues at St. Luke Hospital.Outside a hospital in Port-au-Prince, Haiti, in 2008, several Pitt med students huddle around a priest. “Poverty degrades people’s humanity, and it doesn’t end when they die,” Father Rick Frechette warns. They see what he means when they enter a morgue where the bodies of deceased patients—whose families do not have the means to bury them—have been placed. Together they honor the dead with a burial service.

Among the med students is Nicole Shirilla (MD ’11), who arranged this trip after learning of the St. Luke Foundation for Haiti, an organization that provides education, medical care, employment opportunities, and humanitarian outreach to Haiti’s most underserved. After inviting six other classmates to volunteer with her during spring break, Shirilla approached professor of emergency medicine Susan Dunmire (MD ’85), then-executive director of the Medical Alumni Association, to inquire about financial assistance.

“They were incredibly responsive and supportive,” Shirilla says.

With MAA’s green light, the group observed day-to-day life in Cité Soleil, a region near Port-au-Prince that, with 200,000 residents living without proper sanitation or infrastructure, is considered the largest slum in the Western Hemisphere. In Tabarre, Haiti, the students volunteered alongside Haitian doctors at St. Damien pediatric hospital, which successfully treats thousands of patients. At a nearby chapel, they paid tribute to those who died. This experience bolstered Shirilla’s desire to focus her life’s work on palliative care.

The 2010 earthquake magnified the area’s need, and Shirilla has maintained her connection to St. Luke, returning to Haiti when possible. Alongside the pediatric facility, a makeshift general hospital was erected; Shirilla has volunteered in its emergency department.

Now, as a hospice fellow at the University of California, Irvine, Shirilla remains committed to upholding the dignity of all, particularly those suffering from terminal illness or approaching the end of their lives. She often recalls those moments of honoring the dead in Haiti: “Your work doesn’t end when you can’t cure someone.”

Photo courtesy Nicole Shirilla