insidesurgery

CONTENTS

BREAST CARE AT UCSF 1

LETTER FROM THE CHAIR 2

ENDOCRINE SURGERY 6Harnessing the power of informatics andmanagement sciences to advance thequality of breast cancer care is central toBCC Director Laura Esserman’s ongoingefforts to improve patient care. In recogni-tion of her work, Esserman, who also holdsan MBA from Stanford Graduate School ofBusiness, has recently been awarded a $7 million grant from the Department ofDefense Breast Cancer Research Programto create a national Center of Excellence(COE) in breast cancer care delivery. A pri-mary goal of the COE is to develop a proto-type clinical information system specificallydesigned to promote collaborative decisionmaking among physicians and patients.Conceptualized as a knowledge manage-ment system, it differs from current elec-

tronic medical record systems by empha-sizing the integration of standardized patientdata, routinely collected at the point of care,with information from other hospital andresearch databases. This will provide a plat-form that helps providers, in consultationwith patients, to tailor treatment to individualbiology and patient preference. It alsoallows providers to evaluate the impact ofclinical decisions based on outcomes gen-erated at both the BCC and other centersnationwide.

A second and equally important goal of theCOE is to develop tools for helping physi-cians scientifically assess and communicatea patient’s risk of cancer occurrence, recur-rence and death. These risk assessment

UCSF’s Carol Franc Buck Breast Care Center (BCC) offers women multidisciplinary

expertise in the diagnosis and treatment of a disease that ranks as the most preva-

lent malignancy among U.S. women.

Led by Laura Esserman, MD, a nationally recognized leader in breast cancer treat-

ment, the UCSF Mount Zion-based center, part of the UCSF Comprehensive Cancer

Center, combines high-quality, patient-centered care with rigorous scientific

research. Providers form a collaborative team of experts in surgical, medical and

radiation oncology, pathology, radiology, psychology and genetic counseling.

Additional staff offer psychosocial support, advice on nutrition and information

about complementary and alternative medicine.

VOLUME 1 NUMBER 4 FALL 2003

B R E A S T C A R E AT U C S F

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Using information science to improve patient care

L E T T E R F R O M T H E C H A I R

Two aspects of cancer care are showcased in this issue of Inside Surgery: the Carol FrancBuck Breast Care Center and the UCSF endocrine surgery program. Both are based at theComprehensive Cancer Center at UCSF/Mount Zion. Awarded the National Cancer Institute’shighest designation — “comprehensive” — for uniting innovative research and state-of-the-art patient care, the Center provides multidisciplinary evaluation and treatment for a varietyof types of cancer patients, all at one site. Oncologists, pathologists, surgeons, radiationoncologists and other specialists operate from adjacent offices in the Center. This physicalproximity streamlines the evaluation and treatment process, and fosters the interdisciplinarycollaboration that have for many years been hallmarks of the UCSF community.

I am also pleased to single out the hard work of UCSF surgeon Jeffrey Pearl, MD, whoserves as associate dean of the UCSF Medical School at Mount Zion. Dr. Pearl has workedtirelessly to involve the San Francisco community in this newly revitalized part of ourcampus. He has helped to oversee the complex movement of selected programs from themain campus to Mount Zion, and continues to champion this unique teaching and patientcare resource. His latest effort is the organization of a public lecture series on forensics,which will be held in the remodeled Herbst Hall auditorium at Mount Zion.

Community support is also evident in the level of financial assistance provided to UCSF pro-grams by outside groups. The Breast Care Center has been the grateful recipient of financialsupport provided by donors ranging from major corporations to private individuals.Endocrine research, which is highlighted in the story beginning on page 6, has also beengenerously supported by several individuals and family foundations. Their support keepsthese multifaceted programs vibrant and growing.

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Nancy L. Ascher, MD, PhDProfessor and Chair, Department of Surgery

models compare a patient’s profile to popu-lation-based statistics, integrating demo-graphics, tumor biology, treatment andoutcomes. Again, the goal is to develop sys-tems that support the ability to tailor treat-ments based on biology and risk.

The COE is currently developing and testingdecision-support models for patients whoare at high risk for developing breast cancer,for those who have been diagnosed withductal carcinoma in situ (DCIS), and forthose who are considering adjuvant therapyfollowing surgery for primary breast cancer.Although based at UCSF, the COE is aninternational effort, bringing together leadersfrom various fields and institutions.Participants include investigators from UCDavis, the Northern California CancerCenter, Stanford University Department ofManagement Science and Engineering,Harvard University School of Business, thePatient Safety Institute, University of TexasSouthwestern, Massachusetts General, theFoundation for Informed Decision Making,and the United Kingdom AdvancedComputation Laboratory.

Same-Day assessmentThe Center’s Same-Day Assessment pro-gram is an example of the care systemssupported by the COE grant. The programcoordinates provider schedules so thatpatients who require evaluation for a massor abnormal mammogram can undergo clin-ical examination, imaging and needle biopsyprocedures on the same day. This allowspatients to quickly learn whether they have aserious breast problem, allowing them toschedule treatment more rapidly than wouldordinarily be possible. The Center’s facilities,which include on-site diagnostic mammog-raphy, biopsy, and cytopathology, help facili-tate this process.

Two innovative clinical trials are associatedwith Same-Day Assessment. One is thedevelopment of a proteomics blood test(analysis of blood proteins) as an adjunct toscreening for breast cancer, either before orafter mammography. The second involvesidentifying patients with DCIS for novelstudies (see below).

Optimizing doctor-patient communicationThe Program for Collaborative Care usestrained facilitators to help patients preparefor consultations and to moderatedoctor/patient meetings. Its goal is toimprove the quality of treatment decisionsby helping physicians and patients commu-nicate more effectively. In a process calledconsultation planning, facilitators helppatients map out their questions and con-cerns before a meeting with a breast cancerspecialist. A printed flowchart, the consulta-tion plan, is created for each patient high-lighting questions, concerns, and issues.Both the patient and the physician receive acopy of the plan, which guides discussion oftreatment options.

A wide spectrum of researchOver the past five years, the number ofinvestigator-initiated trials originating at theBCC has increased significantly, and staffhave assumed leadership roles in large, mul-ticenter studies, including those sponsoredby national and international cooperativegroups. The Center’s clinical trials unit,under the direction of Hope Rugo, MD andLaura Esserman MD, is currently recruitingpatients for 30 open trials on topicsincluding breast cancer prevention, imaging,behavioral studies, biologically targetedtherapies and complementary/alternativemedicine. John Park, MD, PhD, is in chargeof innovative clinical translational researchbringing cutting-edge molecular therapeu-tics to patients at UCSF and elsewhere. TheCenter also collaborates with breast canceradvocates on the design and implementa-tion of new trials.

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Bringing mammography to under-served women

UCSF’s Mammovan, the only mobilemammography service in the SanFrancisco Bay Area and the only one inthe world equipped with the highest-quality digital screening technology,brings the expertise of UCSF clinicians towomen who would otherwise not receivebreast cancer screening. The Mammovantravels to 22 sites that comprise theCommunity Health Network of SanFrancisco, offering no-cost examinationsand counseling to underserved popula-tions. Working under the auspices of SanFrancisco General Hospital and under thedirection of Cheryl Ewing, MD, the UCSFMammovan screens 3,000 women a year.

For information, contact ShoshanaLevenberg at 415/353-7355.

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Karen Lane, MD John Park, MD

UCSF Mammovan staff

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Measuring tumor response with MRI

Studies of neoadjuvant chemotherapy, cur-rently standard treatment before breastcancer surgery, have shown that somepatients benefit greatly from it, while othersdo not. BCC director Laura Esserman, MD, isleading a multi-institutional study of womenundergoing neoadjuvant chemotherapy forstage II and stage III breast cancer. The aimis to identify biomarkers that would predictresponse to therapy. Participants’ responseto treatment is monitored with serial mag-netic resonance imaging (MRI) and corebiopsies. One goal of this study is to identifynon-responsive patients within approximatelya week of chemotherapy and then to identifynovel therapeutics most likely to succeed inthose patients.

In addition to UCSF, study sites include theUniversity of Pennsylvania, University ofNorth Carolina-Chapel Hill, University of

Alabama, Georgetown University, MemorialSloan-Kettering Cancer Center, University ofTexas Southwestern and University ofWashington, Seattle.

For more information, contact NnekaEmenyonu at 415/353-7606.

Tamoxifen v. letrozole in patientswith DCIS

One of the challenges in breast cancer careis determining how aggressively to treatductal carcinoma in situ (DCIS), the earliestform of the disease. A current BCC trialunder the direction of Shelley Hwang, MD, isstudying the effects of tamoxifen and thearomatase inhibitor letrozole administeredprior to lumpectomy on patients with DCIS,with the goal of identifying non-surgicaltreatments that may prevent the progressionof DCIS to invasive cancer. Patientsaccepted into the trial are placed on tamox-ifen or letrozole for three months prior tosurgery and are examined with a breast MRIbefore and after treatment to determine theeffect of these medications on DCIS. Thistrial uses the neoadjuvant approach toexamine how to best prevent or treat pro-gression from DCIS.

National randomized trials have shown thattamoxifen reduces the risk of breast cancerrecurrence, including recurrence of DCIS,after initial treatment with lumpectomy and

radiation. Aromatase inhibitors are a newclass of drugs found to be effective inreducing the risk of breast cancer recur-rence in postmenopausal women. Theyhave few adverse effects, and, unliketamoxifen, do not lead to an increased riskof endometrial cancer. Studies such as thisone may identify a role for these medica-tions as an alternative to surgery forpatients with DCIS.

For more information, contact Alex Herreraat 415/885-3849.

Immunotherapy for breast cancerA dendritic cell vaccine directed againstHER-2/neu, a genetic mutation associatedwith certain breast cancers, is currently

being tested in patients with advanced dis-ease. The concept of a HER-2 vaccine isbased on studies by Michael Campbell,PhD, and Laura Esserman, MD, showingthat vaccines have the potential to preventHER-2 tumors in transgenic mice.

The current patient trial, under the directionof John Park, MD, and Michelle Melisko,MD, is a collaboration with Dendreon Corp.Dendritic cells are removed from thepatient's blood, altered in the laboratory, andthen infused back into the body. Clinicaltrials at UCSF and elsewhere have shownexcellent T-cell responses following a den-dritic cell vaccine in prostate cancer.

For more information, contact JennaferCarlin at 415/885-7643.

Cheryl Ewing, MD Michael Campbell, PhD

Shelley Hwang, MD

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TARGET radiotherapy trialRegional radiotherapy techniques are beingstudied around the world. UCSF has joinedan international effort to test a single intra-operational dose of radiation as a replace-ment for a six-week course of externalradiotherapy. This study, scheduled to beginbefore the end of 2003, will be open towomen over 50 with stage I and II cancers.

Researchers led by surgeons Karen Lane,MD, and Shelley Hwang, MD, and radiationoncologists Alison Bevan, MD, andCatherine Park, MD, will examine which bio-logical characteristics predict a goodresponse to this treatment.

For more information, contact the clinicaltrials manager at 415/353-7213.

Preventing disease in high-risk womenThe Prevention Program at the UCSF BreastCare Center provides educational servicesand clinical trials for women at high risk forbreast cancer. Women eligible for preventiveprograms include those with a family historyof breast and/or ovarian cancer or BRCA 1/2mutation, personal history of breast canceror atypical hyperplasia, or other reproductiverisk factors such as late or no childbearingor early menarche. At the Center’s weeklyPrevention Clinic, patients receive breastcancer education, a thorough breast examand breast mapping, a personalized riskassessment and follow-up plan, an introduc-tion to breast cancer prevention clinical trialsand genetic counseling as needed.Providers are drawn from an expert team ofbreast surgeons, gynecologists andinternists, nurse practitioners, genetic coun-selors and researchers.

Tamoxifen is currently the only preventivemedical therapy approved for high-riskwomen, but many women are reluctant totake it because of potential side effects.Additional tests can be performed in thesewomen to assess both risk of breast cancerand likelihood of benefit from tamoxifen.These include testing for atypia with fineneedle aspirations or ductal lavage. Serum-estradiol levels can also be measured inpostmenopausal women.

Breast density is also being studied as apotential marker for breast cancer risk.Dense breast tissue has been linked to anincreased risk of developing breast cancer.Tamoxifen has been shown to reduce breastdensity, but again, many women may beunwilling to take this drug. A BCC pilotstudy (PREVENT), under the direction ofJeffrey Tice, MD, is examining whether soyprotein may be useful in reducing breastdensity in high-risk, premenopausal women.Women who are at high risk for breastcancer, based on a Gail Risk Factor >1.67%and breast density >50%, are eligible to par-ticipate in the study, in which they are ran-domly assigned to receive soy protein orplacebo. Participants are monitored over asix-month period with digital mammographyand blood tests for serum biomarkers.

For more information, contact NicoleGuthrie at 415/353-9739.

Postmenopausal high-risk women also havethe opportunity to participate in a multicenterclinical trial, the Study of Tamoxifen andRaloxifene (STAR). For more information, con-tact Rowena Mah at 415/476-4082, x156.

For more information about the PreventionProgram or to schedule an appointment,contact Caroline Annis at 415/353-7029.

Ductal papilloma as seen through ductscope

Laura Esserman, MD, with UCSF physician/author RachelNaomi Remen

Thyroid tumorsThyroid cancer, which is more common inwomen than in men, accounts for 1% of all can-cers diagnosed in the United States. Most thy-roid cancers grow slowly, but certain types canbe highly aggressive, making thyroid cancersecond only to ovarian cancer as a leading causeof death from endocrine cancers. UCSF offersthe full range of treatment options for thyroidcancer, including videoscopic and open opera-tion via small incisions, radioiodine treatment,external beam radiation and chemotherapy. Mostpatients can be cured of their disease with somecombination of these treatments.

Thyroidectomy is recommended in thyroidcancer patients, with total removal of the glandpreferred for tumors greater than 1.5 cm, whenthe procedure can be performed safely. Totalthyroidectomy is associated with a lower recur-rence rate and, in many reports, improved sur-vival. Serious complications such ashypoparathyroidism or recurrent laryngeal nerve

injuries occur in less than 0.5% of UCSFpatients undergoing thyroid operations.

In an effort to explore alternatives to thyroidec-tomy, UCSF surgeons will soon begin a study ofthe effectiveness of radiofrequency (RF) ablationfor some patients with either low-risk thyroidcancers or clinically benign thyroid nodules. Inthe first stage of the study, patients will betreated initially with RF ablation, then undergothyroidectomy to establish treatment response.

The UCSF group offers special expertise intreating inherited forms of thyroid cancer. Theseinclude familial medullary thyroid cancer, a raremalignancy of the parafollicular cells thatsecrete calcitonin, and familial papillary andHurthle cell cancers. Medullary thyroid cancersare commonly invasive, and both a total thy-roidectomy and meticulous, prophylactic bilat-eral central neck operation are necessary inthese patients to maximize the chance of acure. Genetic testing for RET point mutations isavailable to identify patients with the familial

S U R G I C A L M A N A G E M E N T O F E N D O C R I N E T U M O R S

Endocrine tumors can pose a complex treatment challenge, requiring the multidis-ciplinary expertise of an experienced health care team to assure the best possibleoutcome. At UCSF, expert treatment of thyroid, parathyroid and adrenal tumors isprovided by its internationally recognized Endocrine Surgery service. TheUCSF/Mount Zion–based endocrine program is the busiest of its kind in NorthernCalifornia. The surgical team, including Quan-Yang Duh, MD, Orlo H. Clark, MD,and Electron Kebebew, MD, performs more than 350 thyroid, 250 parathyroidand 40 adrenal operations each year. The high-volume program has very lowsurgical complication rates, in keeping with a pattern demonstrated in many out-come studies that complication rates fall as volumes increase.

Approximately 20% of patients treated surgically are referred to UCSF from other medical cen-ters because of persistent or recurrent disease. For many of these complex cases, the UCSFteam draws on the expertise of a multidisciplinary team of endocrinologists, nuclear medicinephysicians, radiologists, medical oncologists and radiation therapists to develop a treatmentplan tailored to each patient.

Teaching is an important component of the UCSF program. A highly regarded postgraduatetraining program is offered for general surgeons interested in academic endocrine surgery.Residents help to perform up to 40 operations each month; endocrine surgical oncology fel-lowships are offered in both clinical and basic science research.

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form of the disease, which may also be associ-ated with adrenal and parathyroid tumors. Totalthyroidectomy is recommended prior to age sixin children with a history of familial medullarythyroid cancer who are found to have a RETgerm line mutation. Familial papillary andHurthle cell cancer is less aggressive thanmedullary thyroid cancer, but is more aggressivethan sporadic forms of the disease. Identifyingthe gene(s) responsible for this form of familialthyroid cancer is a particular research interest ofthe UCSF endocrine surgical team.

Parathyroid tumors

Most studies, including substantial researchperformed at UCSF, show that treating patientswith primary hyperparathyroidism with parathy-roidectomy relieves symptoms, resolves mostrelated metabolic problems and improves sur-vival rates. UCSF has special expertise in initialand reoperative parathyroid surgery as well asin parathyroid cryopreservation and autotrans-plantation. The latter technique can prevent per-manent hypoparathyroidism in the small numberof patients who are hypocalcemic followingsubtotal or total parathyroidectomy or afterparathyroid reoperations.

For patients with primary sporadic hyperparathy-roidism, the UCSF team uses sestamibi scansand ultrasound to localize parathyroid tumorspreoperatively so that a minimally invasive sur-gical approach can be used. UCSF surgeonsalso routinely employ an intraoperative blood testto measure parathyroid hormone (PTH), whichhelps determine if the operation is complete.When the PTH level falls at least 50% from thehighest pre-removal level 10 minutes after exci-sion of the tumor, the operation is usually (=98%)successful, and the other parathyroid glands donot have to be identified. Use of this simpleblood test has made it possible to perform manyparathyroid operations through a small (2.5 cm)incision. The standard 4 cm incision is nowneeded only when the localization studies do notidentify a single parathyroid tumor or the patienthas familial hyperparathyroidism.

In a UCSF series of more than 1,000 patientsundergoing initial operations for primary hyper-parathyroidism using either a bilateral orfocused approach, there were no patients withpermanent hypoparathyroidism or recurrentlaryngeal nerve injury. These complicationsoccur in about 1.5% of patients undergoingreoperations at UCSF, a rate lower than thatreported at other medical centers.

Adrenal tumorsTreatment of patients with adrenal tumors haschanged markedly due to improved diagnosis,more precise localization and less invasive opera-tive procedures. Laparoscopic removal hasbecome the treatment of choice for most adrenaltumors less than 6 cm in size. Because few cen-ters have expertise in laparoscopic endocrinesurgery, UCSF is a major referral site, performing40 operations annually for these rare tumors.Laparoscopic removal of adrenal tumors hasshortened hospital stays, decreased postopera-tive pain and reduced recovery times.

Endocrine surgical oncology research The endocrine surgery team is involved in severalresearch projects exploring the pathogenesis andtreatment of thyroid cancers. The group includesprincipal investigators Drs. Clark, Duh andKebebew, laboratory director Mariwil G. Wong, aswell as one clinical science and two basic scienceresearch fellows.

Redifferentiation therapyCompared to well-differentiated tumors, poorly dif-ferentiated cancers are more likely to invade andmetastasize and are less responsive to radioiodinetherapy. Several UCSF studies attempting to redif-ferentiate thyroid cancers are currently under way.In vitro investigations have shown promisingresults inhibiting thyroid cancer growth with PPAR-gamma agonists, histone deacetylase inhibitorsand Cox 2 inhibitors. Treatment with some ofthese agents produced a thousandfold increase inradioiodine uptake. Growth of the thyroid cancersalso decreased with use of these agents, andcancer cell death (apoptosis) increased. Based onthese results, UCSF endocrine surgeons andendocrinologists are beginning a clinical trial inwhich patients will be given the PPAR-gammaagonist, rosiglitazone. This drug, used to treat dia-betes, resembles similar medications that havebeen shown by UCSF researchers to have rediffer-entiating effects on thyroid cancer cells. This treat-ment approach could help many patients whohave unresectable metastatic disease byincreasing tumor cells’ capacity to trap radioio-dine, and perhaps, by other mechanisms.

Genetic regulationThe UCSF team is also investigating the geneticsof familial nonmedullary thyroid cancer, usingcomparative genomic hybridization and linkageanalysis. They have identified chromosomal sitesthat appear to be associated with familial, papil-lary and Hurthle cell thyroid cancer. Subsequentinvestigations will explore the specific genes thatare responsible for these cancers.

C O N S U LTAT I O N S A N D R E F E R R A L S

For more information, please call 415/353-2161.

1: CT of a papillary thyroid cancer in right lobe with distant metastases to lung and brain. Primary tumor treated with thyroidectomy.

2,3: Ultrasound showing large left upper parathyroid tumors on longitudinal (Fig 3) and transverse (Fig 2)views. Transverse view also reveals a small cyst in thyroid gland.

4: Sestamibi scan (lateral view) in patient with recurrent secondary hyperparathyroidism two years afterremoval of 31/2 parathyroid glands. Scan shows tumor at site of remnant parathyroid gland at left lowerposition of neck and supernumerary tumor in the aortopulmonary window. 4

C A M P B E L L T O O V E R S E E S U R G I C A L E D U C AT I O N

Andre Campbell, MD, one of UCSF’s most honored medical educators,has been named Chair of Surgical Education, an endowed positionrecently created by the UCSF Academy of Medical Educators in conjunc-tion with the Department of Surgery. The Academy, one of only a fewsuch programs in the United States, was established in 2001 to advancethe teaching of medical students and provide moral and financial supportto talented teachers at UCSF. In his new position, Campbell will representteaching excellence in the Department of Surgery and work to promotethe highest standards of medical education throughout UCSF.

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A P P O I N T M E N T S

Vivian Ting, MDAssistant ProfessorPlastic & Reconstructive Surgery

Michael Mann, MDAssistant ProfessorCardiothoracic Surgery

Alden Harken, MDProfessorDirector, UCSF-East Bay SurgicalResidency Program

Distinguished medical educatorAlden Harken, MD, was nameddirector of the UCSF-East BaySurgical Residency Program inMay 2003. He comes to UCSFfrom the University of Colorado,where he chaired the Depart-ment of Surgery from 1983-2002. In addition to his notedcareer as a general and cardio-vascular surgeon and investi-gator, Harken has beenrecognized as an excellentteacher and mentor. The mostrecent of his many teachingawards was the Surgery FacultyTeacher of the Year Award fromthe University of Colorado. Paststudents consistently commenton his outstanding performanceas a mentor and role model,both in clinical practice and theresearch setting.

Dr. Harken's research has beenfocused on the cardiomyocellularresponse to ischemia/reperfu-sion and septic stress. He hasconducted clinical and basicresearch on electrophysiologicalstability, cardiomyocyte viability,and mechanical contractility.

Campbell, an Associate Professor in theDepartment of Surgery, has been repeatedlyhonored for distinction in the role of teacherand mentor. Earlier this year he was one offour recipients of the national Association forSurgical Education’s Outstanding TeacherAward, and he was nominated by UCSF med-ical students to receive the Henry J. KaiserExcellence in Teaching Award. He previouslyreceived the 1998-99 Distinction in TeachingAward from the UCSF Academic Senate.

Dr. Campbell’s appointment comes at a chal-lenging time for surgical education, as manystudents opt to specialize in other areas suchas emergency medicine, radiology and anes-thesia. “We have some of the best teachers in

the School of Medicine in our Department andI would like to make sure UCSF students getexposure to us,” said Campbell. “I am opti-mistic that we can increase the numbers ofstudents who are going into surgery in thefuture and inspire the next generation of sur-geons,” he said.

The establishment of endowed chairs willallow faculty to reduce their obligations inother areas to focus more attention onteaching and mentoring students and creatingtop-notch educational programs. UCSF plansto create 30 such chairs within the next fiveyears, eventually supporting up to 75 facultymembers per year through a combination ofchairs and program stipends.