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Cancer Outcomes


Morphea of the Breast - An Uncommon Cause of Breast Erythema

Breast-associated morphea (BAM) can mimic benign and malignant inflammatory breast disorders. The aim of the current study was to document our experience with this rare sclerosing dermatologic disorder. We conducted a retrospective study of all Virginia Mason patients who had pathological diagnosis of morphea between January 1995 and October 2007. We identified 15 patients with pathological evidence of morphea infvolving the breast. Two-thirds of these patients were initially misdiagnosed with inflammatory breast cancer or breast infections. While two patients had previous exposure to external beam radiation, the remaining patients had no identifiable predisposing risk factors. BAM resulted in limited morbidity and did not result in significant disfiguration. Treatment included topical steroids, topical calcineurin inhibitor, and surgical excision.

Our experience with BAM emphasizes the benefit of early tissue biopsy in patients with unexplained breast erythema to confirm a clinical diagnosis and thus guide subsequent therapeutic interventions.

Source: Clark CJ, Wechter D. Am J Surg 2010;200:173-176.

Incidence of Precancerous Lesions in Breast Reduction Tissue: A Pathologic Review of 562 Consecutive Patients
Reduction mammoplasty is the 5th most common reconstructive surgical procedure in the U.S. In 2007, 105,706 women underwent breast reduction, nearly a threefold increase from 39,639 patients in 1992. Three main indications for breast reduction are congenital breast asymmetry, macromastia, and to obtain symmetry after an operation for breast cancer. Macromastia is a benign condition of breast hypertrophy resulting in back and shoulder pain, kyphosis (outward curvature of the upper back), excoriation from bra straps, and chronic intertrigo (chafing rash) in breast skin folds. Severe breast hypertrophy can limit exercise and daily activities.

At Virginia Mason, a total of 562 patients underwent breast reduction over a 5-year period from 2001 to 2005. In this study, the authors conducted a retrospective chart review on these patients, examining the incidence of benign and precancerous lesions in breast reduction specimens. No invasive breast carcinoma was identified during pathologic analysis of breast reduction specimens but over 50 percent of breast tissue examined contained benign or precancerous breast lesions. Understanding the incidence of precancerous breast lesions in breast reduction patients can help plastic surgeons in the perioperative setting, not only in the preoperative evaluation and counseling of patients, but also in the postoperative management of patients found to have an increased risk of breast cancer.

Source: Clark CJ, Whang S, Paige KT. Plast Reconstru Surg 2009;124(4):1033-1039.

Screening Mammography
Research has shown that breast cancers detected early have the highest likelihood of cure.  Many early-stage tumors can be detected by screening mammography years before they can be felt by manual exam, affording the opportunity to treat them before the cancer grows or spreads. Virginia Mason's mammography screening results exceed national benchmarks.  Nearly 79% of cancers detected by screening mammography at Virginia Mason in 2006-2007 were early-stage (0 or 1) tumors (compared with 76% nationally), and 42% of the invasive cancers identified by screening mammography were small (<10mm; compared with 37.2% nationally).
Virginia Mason Data:  Virginia Mason Cancer Registry. 
National benchmarks:  Rosenberg RD, Yankaskas BC, Abraham LA, et al.  Performance Benchmarks for Screening MammographyRadiology 2006;241(1):55-66.

Mammography Screening
Screening mammography is used worldwide to detect early stage breast cancer. Published data from randomized clinical trials show that the use of mammography to screen healthy women decreases mortality from breast cancer by 25%-30%, because the cancers are detected early, when they tend to be most responsive to treatment. Since 2006, of women who had at least two primary care visits at a Virginia Mason location with mammography facilities, nearly 74% received one or more screening mammograms each year.

Source:  Kerlikowske K, et al. Efficacy of screening mammography: a meta-analysisJAMA 1995;273(2):149-154.

Intraductal Papillomas without Atypia on Breast Core Needle Biopsy (CNB): Surgical Excision is Advisable
How best to manage patients who have a breast core biopsy containing an intraductal papilloma without atypia is currently a matter of intense debate. Often these patients are observed conservatively. Virginia Mason physicians reviewed 38 consecutive cases that had surgical excision instead of observation. They found that 8 percent of patients had DCIS (ductal carcinoma in-situ) and 8 percent had ADH (atypical ductal hyperplasia). Our findings suggest that surgical excision remains prudent for all patients with intraductal papilloma without atypia on core needle biopsy due to the risk of more significant pathology occurring in the targeted lesion.

Source: Jacobs TW, Guinee DG, Holden J, Hashimoto B, Wechter D. Pathology, Virginia Mason, Seattle, WA and Pathology, University of Utah, Salt Lake City, UT

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ACG Practice Guidelines: 
Role of Esophageal Stents in Benign and Malignant Diseases
Virginia Mason's Dr. Richard Kozarek and co-author Dr. Prateek Sharma (Veterans Affairs Medical Center and University of Kansas School of Medicine, Kansas City, MO), recently developed recommendations to provide an evidence-based approach to the role of esophageal stents in the management of benign and malignant diseases. The guidelines, intended for use by health care providers, are based on a critical review of the available scientific literature on the topic identified in Medline and PubMed (January 1992-December 2008) using search terms that included stents, self-expandable metal stents, self-expandable plastic stents, esophageal cancer, esophageal adenocarcinoma, esophageal squamous cell carcinoma, esophageal stricture, perforations, anastomotic leaks, tracheoesophageal fistula, and achalasia. As with other practice guidelines, they are not intended to replace clinical judgment but rather to provide general guidelines applicable to the majority of patients. They are intended to be flexible, in contrast to standards of care, which are inflexible policies designed to be followed in every case. These guidelines were produced in collaboration with the Practice Parameters Committee of the American College of Gastroenterology, whose members provided peer review.

The quality of evidence and strength of recommendations have been assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system - a system which has been adopted by multiple national and international societies. GRADE is based on a sequential assessment of quality of evidence, followed by assessment of the balance between benefits vs. downsides (harms, burden, and costs) and subsequent judgment regarding the strength of recommendation. These evidence-based guidelines have been selected by both European and some Asian GI Societies as the [current] definitive paper on the topic.

Source:  Sharma P, Kozarek R. Role of Esophageal Stents in Benign and Malignant Diseases. Am J Gastroenterol 2010;105:258-273.

Acquired Risk Factors for Colorectal Cancer
The risk of developing colorectal cancer (CRC) is influenced by several acquired risk factors, including environmental exposures and comorbid medical conditions that are partially genetic in nature. These risk factors are based on data almost exclusively derived from observational studies. Because of the possibility of bias due to confounding, these acquired risk factors should not be automatically assumed to be causative, and in fact some may not be truly independent risk factors. Acquired risk factors include the following categories: 1) dietary factors, 2) lifestyle factors, 3) side-effects of medical interventions, and 4) comorbid medical conditions.

Dietary factors that potentially increase the risk of CRC include low fruit, vegetable, or fiber intake, high red meat or saturated fat consumption, and exposure to caffeine or alcohol. Of these factors, the significance of low fruit, vegetable, and fiber intake has been called into question because of contradictory results from large observational studies and negative results from randomized trials. The association of high red meat or saturated fat consumption with increased CRC risk is supported by the preponderance of observational data. Lifestyle factors include lack of exercise and smoking. These risk factors are supported by observational data of moderate quality.

Source: Lin OS. M. Verma (ed) Methods of Molecular Biology, Cancer Epidemiology, vol. 472, chapter 16. 2009 Humana Press, Totowa NJ

Assessment of Criteria and Clinical Significance of Circumferential Resection Margins in Esophageal Cancer
The hallmark of successful cancer surgery is to provide surgical margins which are negative for malignancy. At the time of publication, there were two international criteria for assessing circumferential resection margins in esophageal malignancy. North America and much of Europe use the system promoted by the American College of Pathologists (CAP) in which positive resection margins involve finding cancer cells at the cut surgical margin. In the United Kingdom, much of Asia and Australia, the system of the Royal College of Pathology (RCP) is utilized which defines positive resection margins as tumor cells within 1mm of the cut margin. This difference in classification has made comparison of international outcomes and coordination of recommendations for adjuvant therapy difficult or impossible.

The purpose of the study was to carry out a prospective controlled comparison of outcomes between the CAP and RCP criteria. A prospective IRB-approved single-surgeon Virginia Mason database was interrogated to identify 135 consecutive patients presenting with pathologic T3 esophageal and esophagogastric tumors between 1991 and 2006. Only T3 tumors were included because this group is the most likely population to have positive circumferential resection margins. All patients with T3 tumors had their original pathologic slides reassessed by a single gastrointestinal pathologist (RD). 

Operative mortality was 0.7% in the entire series and mean follow up was 3.1 years. Follow up was completed in 81% of patients. Positive resection margins were identified in 16 cases in the CAP group and 83 cases in the RCP group. Five year Kaplan-Meier survival curves in the CAP group demonstrated a significant (p < 0.001) difference in survival whereas the RCP group showed no difference (p = 0.20). In direct comparisons of patients with negative versus positive margins respectively, median survival in the CAP group was 29.8 months versus 8.3 months in the RCP group. Univariate and multivariate analysis identified only R1 margins in the CAP group and lymph node ratio as being directly linked to survival.

We concluded that positive circumferential resection margins are prognostically important and the CAP criteria provide a more clinically meaningful assessment. Universal adoption of a CAP system can improve interpretation of international clinical trials and allow for a more uniform system for recommendations of adjuvant therapy and comparison of international outcomes.

Source: Deeter M, Dorer R, Kuppusamy M, Koehler R, Low DE. Assessment of Criteria and Clinical Significance of Circumferential Resection Margins in Esophageal Cancer. Arch Surg 2009;144(7):618-624.

Endotherapy for Barrett's Esophagus with High-Grade Dysplasia and Intramucosal Carcinoma
The incidence of adenocarcinoma of the esophagus related to Barrett's esophagus in the United States appears to be rising rapidly. High-grade dysplasia (HGD) is the immediate precursor of esophageal cancer and represents the endpoint of current Barrett's surveillance programs. Once HGD has been found, management has included close endoscopic surveillance, esophagectomy, and more recently, endoscopic ablative therapies (ET). ET has included photodynamic therapy (PDT), endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESMD), radiofrequency ablation (RFA) and cryotherapy, as well as a variety of thermal treatments such as argon plasma coagulation (APC).

Endoscopic surveillance of HGD has largely fallen out of favor and currently the question of whether to treat these patients surgically or by ET remains a point of controversy in many tertiary care centers in industrial countries. In many centers, esophagectomy remains the standard intervention for these patients, provided they are fit for surgery. However, ET has become more popular as experience with the techniques and evidence of efficacy has accumulated. Public demand for less invasive therapies has also spurred a growth in these treatments. 

HGD and IMC are, by definition, mucosal processes. It follows then that if the diseased mucosa can be removed or destroyed and replaced by normal or non-dysplastic mucosa, the progression from dysplasia to invasive cancer will be prevented. HGD has no ability to metastasize or invade. IMC - cancer that does not invade beyond the mucsularis mucosa - while technically a cancer with the potential to metastasize, rarely does. In 1993, two landmark papers were published showing that if the mucosa in Barrett's esophagus is destroyed endoscopically and intra-esophageal acid is controlled by high-dose proton pump inhibiters, non-dysplastic squamous tissue tends to regrow in the treatment area. Numerous studies over the last decade have demonstrated the effectiveness of a variety of endoscopic therapies for BE with dysplasia. Many earlier reports described treatment with PDT, while subsequent reports include EMR with PDT or even EMR alone. The most recent series describe results with RFA and cryotherapy. ET studies have been criticized for a lack of consistency regarding protocols, outcome measures and randomization as well as small numbers and short follow-up periods. However, several series now report patients followed out over 5 years and a cumulative experience of over 600 ET patients exists in the literature. Unfortunately, given the great differences between ET and surgery, it appears very unlikely that a randomized trial of the two therapies will occur.

ET was compared with esophagectomy in two medium sized retrospective series from US medical centers. In a Mayo Clinic study, 129 patients with BE and HGD who had been treated with PDT with or without EMR were compared to 70 patients with similar histology who had undergone esophagectomy over a 10 year period. Groups were comparable, although the ET group was older and less healthy than the surgical group. Both groups were followed for a median of 60 months. Outcomes in terms of cancer-free survival were similar at 5 years and overall survival was virtually identical. No patient in either group died of esophageal cancer. Similar results were seen at Virginia Mason where 61 patients underwent ET and 32 had esophagectomy for BE with HGD or IMC over a 7 year period. In this series, ET patients were 6 years older on average than surgical patients and had slightly higher ASA scores. Overall survival was similar, with no patient in either group succumbing to esophageal cancer. Reviewing the same studies of ET reveals that the procedures are safe, with only one mortality reported among 541 patients treated (<0.2%). Major complications, such as perforation, bleeding or prolonged hospitalization occurred in about 4% of patients (range 0% to 12%). In contrast, although mortality among surgical series was far less than the 4-17% commonly cited for esophagectomy series, surgical deaths still occurred on average 1.5% (range 0-3%) and the incidence of serious morbitidy, including anastamotic leak, pulmonary embolus, and wound infection was 36% (range 11% to 57%). Further, surgery appears to cost up to 50% more than ET, at least for initial treatment.

At Virginia Mason, all patients referred with BE and HGD or IMC get a surgical and GI consultation. All patients undergo endoscopy with endscopic ultrasound and if no obvious invasive disease is detected, EMR of any nodular or ulcerated areas. An attempt is made to present all patients at thoracic tumor board to discuss findings and treatment options.  The results of tumor board discussions are then shared with the patient and his or her family as well as with the referring physician. We often recommend ET for patients with short segment BE, a single nodule of IMC, those at high surgical risk and to those who express a preference for ET. We reserve esophagectomy as a first line treatment for those with long segment BE, generally over 10 cm, those with multi-focal high-grade or nodular disease, those at high risk for non-compliance or an inability to submit to frequent endoscopic follow-up at our institution, those with a heightened level of anxiety, and those with a preference for up-front surgical therapy. We have found that a medical center that offers both ET and esophagectomy in a collaborative manner can produce excellent outcomes in both areas and experience high levels of patient and referring physician satisfaction.

Source:  Schembre DB. J Gastrointest Surg (2009);13(7):1172-1178

Squamous Cell Carcinoma Arising within a Choledochal Cyst
Choledochal cysts (CDCs) are rare congenital or acquired anomalies of the biliary ductal system.  CDCs are more prevalent in females than in males and in Asian than in Western countries.  The cause of cyst formation is unknown however the ducts dilate or weaken into a cyst-like structure that allows stasis of bile, inflammation, and scarring.  Most CDCs are diagnosed in the first decade of life, but 20-30% of individuals remain undiagnosed until adulthood.  Individuals may experience intermittent abdominal pain, episodes of jaundice, or other biliary tract symptoms.

We reported a case of a 41-year-old female with a long standing history of gallstones and presence of a large CDC, without surgical intervention, who presented ten years later with flu-like symptoms, jaundice, and weight loss.  She was found to have a rare case of squamous cell carcinoma arising within the CDC that was unresectable.  This patient accentuates the need for early diagnosis, proper treatment, and palliation with biliary stent placement and chemotherapy.

Early identification of individuals with CDCs is important because the risk of development of cancer is 10-14%.  Ultrasound is the test of choice for diagnosis, although computed tomography (CT), magnetic resonance imaging (MRI), or magnetic resonance cholangiopancreatography (MRCP) are also useful, non-invasive techniques to diagnose and classify cysts.  Though invasive, endoscopic retrograde cholangiopancreatography (ERCP) is the definitive method of diagnosis.  Cyst removal is strongly recommended although the extent of resection remains controversial.  Drainage of cysts is ineffective in preventing pancreatic complications and development of cancer; however cyst drainage endoscopically or in conjunction with interventional radiology may play a role in palliation of jaundice.  Even after complete surgical cyst removal, patients will require life-long follow-up because a few cases of biliary malignancy have been reported after several years.

Source: Price L, Kozarek R, Agoff N. Dig Dis Sci 2008;53(10):2822-2825. 

Colon Cancer Screening
Deaths from colorectal cancer can be reduced if abnormal growths are detected before they become cancerous and if cancers are detected and treated in the early stages. Abnormal growths in the colon can often be identified years before invasive cancer develops. When colorectal cancer is detected and treated early, five-year survival is as high as 90 percent. Still, colorectal screening remains underused in the United States. Findings from the National Health Interview Survey, which is administered by the Centers for Disease Control (CDC), indicate that in 2000, only 43% of U.S. adults age 50 or older had undergone colon cancer screening as recommended by national guidelines. Since 2006 at Virginia Mason, the colon cancer screening rate for eligible patients has been about 48%, regularly exceeding the national average documented by the CDC. This is good, but we can do better. As many as 60 percent of deaths from colorectal cancer could be prevented if everyone age 50 and older were screened regularly. Our goal at Virginia Mason is to make colorectal cancer screening readily available, and to actively encourage people age 50 or older, and those with risk factors for colorectal cancer, to talk to their physician about being screened.

Esophagectomy - it's not just about mortality anymore
Surgical treatment of esophageal cancer (esophagectomy) has a well-earned reputation as a technically demanding operation association with significant complications and high death rates. Multiple recent analyses in the medical literature demonstrate that surgical outcomes for this procedure are linked to the number of procedures performed by individual surgeons and medical centers. In the Medicare population in the United States, mortality rates have ranged from 10% in high-volume centers to as high as 20% in low-volume centers.

Virginia Mason currently performs the highest volume of esophageal resections in the Pacific Northwest. A recent article published in the Journal of Gastrointestinal Surgery highlighting the results of surgical management of esophageal cancer at Virginia Mason, won the award for Best Paper published in that journal in 2007. This article highlighted the utilization of standardized, perioperative clinical pathways and their role in improving outcomes, including complication and mortality rates and 5-year survival rates in patients treated with esophageal cancer. This paper demonstrated a mortality rate in over 350 patients treated over 15 years of 0.3%. It also demonstrated dramatically improved results in 5-year survival in Stage 1, 2, and 3 patients treated at Virginia Mason. The standardized clinical pathways have also set new targets for optimizing a wider range of procedural outcomes, including blood transfusion requirements, early mobilization of patients, and nutritional goals.

Source: Low DE, Kunz S, Schembre D, Otero H, Malpass T, Hsi A, Song G, Hinke R, Kozarek RA. Esophagectomy--it's not just about mortality anymore: standardized perioperative clinical pathways improve outcomes in patients with esophageal cancer. J Gastrointest Surg 2007 Nov;11(11):1395-402; discussion 1402. Epub 2007 Aug.

Treatment of Barrett’s esophagus with early neoplasia: a comparison of endoscopic therapy and esophagectomy .
Esophageal cancer is one of the fastest-growing malignancies currently in the United States . There is now a clear link between chronic gastroesophageal reflux disease (heartburn) and the development of Barrett’s esophagus. The most common type of esophageal cancer originates in a small proportion of patients with Barrett’s esophagus. Patients who are found to have Barrett’s are routinely followed with endoscopic assessment. When patients are found to have high-grade dysplasia or intra-mucosal cancer, they have historically been recommended to undergone esophagectomy. In the past, mortality rates for esophagectomy in the United States have ranged from 8 percent to 20 percent.  More recently, mortality rates in high-volume esophagectomy centers have been shown to be between 0 percent and 2 percent. An alternative approach to esophagectomy is endoscopic therapy. This treatment approach can involve much lower risk than esophagectomy but the effectiveness of these treatments long-term is not completely known. Virginia Mason physicians compared the outcomes of 94 patients who were treated with either esophagectomy or endoscopic therapy between May 1998 and November 2005. The study shows that both therapies are appropriate and can be performed safely and effectively.  Virginia Mason’s experience demonstrates that esophagectomies performed at high-volume centers, like Virginia Mason, result in few to no deaths and lower risk for complications – far below the national and international averages for the procedure.

Source: Schembre DB, Huang JL, Lin OS, Cantone N, Low DE . Treatment of Barrett’s esophagus with early neoplasia: a comparison of endoscopic therapy and esophagectomy. Gastrointes Endos 2008;67(4):595-601.

Barrett Esophagus:  Outcomes and Health-Related Quality of Life After Esophagectomy
An individual with Barrett Esophagus (BE) has a 30 to 125 times higher risk of developing esophageal cancer than those in the general population.  The risk is even greater if the individual has both BE and high-grade dysplasia (HGD).  Although a variety of treatments are being evaluated for patients with BE and HGD, suitable patients have historically undergone esophagectomy because the procedure offers a high expectation of surgical cure.  Unfortunately, many physicians and patients have the perception that esophagectomy is routinely associated with severe adverse effects and the inability of patients to resume a normal lifestyle and eating pattern after surgery.  As a result, some elect to pursue less invasive therapies which are not as reliable with respect to eliminating the Barrett’s and involve a long-term commitment to frequent, rigorous endoscopies, repeated biopsies, and the associated emotional toll of continuing to live with a condition that has a high propensity for the development of cancer. 

Doctors at Virginia Mason have demonstrated convincingly that surgical outcomes associated with esophagectomy are directly linked with hospital and surgeon experience in performing the procedure.  Specifically, their research has shown that esophagectomy can be accomplished with minimal morbidity and mortality approaching zero in medical centers, such as Virginia Mason, where a high volume of these procedures are performed.  In addition, research shows that patients treated at high-volume centers report minimal and generally well-tolerated post-operative symptoms; the vast majority (85 percent) of BE patients who undergo esophagectomy at Virginia Mason report normal, or near-normal dietary intake following surgery, and a health-related quality of life comparable with people of similar age in the general population.  These results demonstrate that esophagectomy performed at a high-volume center remains the best – and potentially curative – treatment for patients with BE and HGD.

Source:  Moraca RJ and Low DE.  Outcomes and health-related quality of life after esophagectomy for high-grade dysplasia and intramucosal cancer.  Arch Surg 2006;141(6):545-551.

Colonoscopy Complication Rates
Compared to data from national studies, Virginia Mason has above average results with a completion rate of 99 percent and a complication rate of less than 0.05 percent. A completed colonoscopy is important to ensure all areas of the colon are examined and the risk of missing a malignancy is minimized.

Useful Benchmarks to Evaluate Outcomes after Esophagectomy and Pancreaticoduodenectomy
Donald Low, MD, and L. William Traverso, MD, have generated prospective databases for outcomes of Esophagectomies (EG) and Pancreaticoduodenectomies (PD) respectively. These two operations are currently among the most carefully scrutinized procedures in the United States due to increasing evidence that morbidity and mortality is directly linked to the volume of these cases performed by individual hospitals and surgeons. These surgeons practice in a multi-specialty clinic within a tertiary-referral, resident-training hospital. From January 1996 to December 2002, 174 consecutive patients underwent EG performed by Dr. Low and 232 consecutive patients underwent PD by Dr. Traverso. These outcomes are compared with those recently published EG and PD series.

Virginia Mason’s mortality rate for both operations is zero. For the EG series, the estimated blood loss was 204mL compared with recent published literature of 964mL. Transfusion rate was 3.5 percent versus 34 percent, length of hospital stay was 11.1 days versus 16.6, and an anastomotic leak occurred in 2.9 percent of the cases versus 9.1 percent. For the PD series, the estimated blood loss was 382mL compared to 1183mL, length of hospital stay was 11.2 days versus 17.8 and an anastomotic leak occurred in 6.5 percent of cases versus 9.9 percent. The re-operation rate is 0.4 percent compared to 3.8 percent.

These two series demonstrate some of the best results ever reported by individual surgeons and potential additional benchmarks to help better define acceptable outcomes after EG and PD.

Source: Traverso LW, Shinchi H, Low DE (2004). Useful Benchmarks to Evaluate Outcomes after Esophagectomy and Pancreaticoduodenectomy. American Journal of Surgery 187: 604-608

Advanced Pre-Cancerous Lesions Detected By Screening Colonoscopies
In 2003, Virginia Mason gastroenterologists performed more than 3,400 screening colonoscopies. All of these patients were completely asymptomatic with no complaints. Twenty-one percent (705) of patients were found to have had pre-cancerous lesions. Out of those 705 patients, 24 percent (166) had advanced pre-cancerous lesions that if they had gone undetected would have turned into cancer within a few years.

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Development of a Diagnostic Microarray Assay to Assess the Risk of Recurrence of Prostate Cancer Based on PITX2 DNA Methylation
Prostate cancer is among the most common cancers. Although it has a relatively good prognosis, 15 to 30% of men with prostate cancer experience a relapse after radical prostatectomy. Identifying patients with an aggressive tumor will therefore help to improve prostate cancer management. DNA methylation of PITX2 has been established in several studies as a prognostic biomarker for breast and prostate cancer. These case control studies were conducted using research assay components; to facilitate its use in a diagnostic setting, the PITX2 biomarker was transferred to a validated diagnostic platform, the Affymetrix GeneChip System. A customized microarray (Epichip PITX2) was designed using features in high redundancy to ensure a robust determination of the methylation state of the PITX2 promoter. The developed method allowed for accurate assessment of prognosis in prostate cancer patients who underwent radical prostatectomy. Determination of PITX2 methylation in formalin-fixed and paraffin-embedded tissue samples from a cohort of 157 prostatectomy patients resulted in an excellent level of concordance of the clinical classification, as well as the measured output between the research assay and the Epichip PITX2. These analytical performance results describe the Epichip PITX2 as a robust and reliable diagnostic tool for assessing the methylation status of PITX2, enabling an improved outcome prediction in cancer patients following radical prostatectomy.

Source: Schatz P, Dietrich D, Koenig T, Burger M, Lukas A, Fuhrmann I, Kristiansen G, Stoehr R, Schuster M, Lesche R, Weiss G, Corman J, Hartmann A. J Mol Diagn 2010;12(3):345-353

DNA Methylation of the PITX2 Gene Promoter a Strong Prognostic Marker
Patients diagnosed with localized prostate cancer who have a life expectancy of longer than 10 years are commonly treated with radical prostatectomy. Historically, recurrence, defined by PSA relapse, can affect up to 35% of men. Current prognostic indicators cannot sufficiently detect who is at risk for biochemical recurrence. Numerous reports provide evidence that DNA methylation of specific gene loci contains diagnostic or prognostic information about prostate cancer. (DNA methylation is a type of chemical modification of DNA that can be inherited and subsequently removed without changing the original DNA sequence.)

The study involved 605 patients who underwent a prostatectomy at Virginia Mason, Baylor College of Medicine or Stanford University. We evaluated DNA methylation markers for prostate cancer prognosis by analyzing tissue specimens. Of the markers analyzed, PITX2 methylation was the strongest predictor of biochemical recurrence. This in combination with other prognostic variables (pathologic stage, tumor grade, patient age, PSA) was especially useful in predicting which patients with intermediate risk prostate cancer are at highest risk of disease recurrence. Patients with greater than median PITX2 methylation in the tumors were four times more likely to experience biochemical recurrence within eight years after surgery than patients with less than average methylation. The prognostic potential of the PITX2 biomarker may provide the patient with better knowledge about the expected clinical course and guide the physician in counseling. In particular, more accurate risk prediction may help identify patients who might benefit from more aggressive treatment immediately following prostatectomy.

Source:  Weiss G, Conttrell S, Distler J, Schatz P, Kristiansen G, Ittmann M, Haefliger C, Lesche R, Hartmann A, Corman J, Wheeler T. DNA methylation of the PITX2 gene promoter region is a strong independent prognostic marker of biochemical recurrence in patients with prostate cancer after radical prostatectomy. J Urol 2009;181(4):1678-1685.

Neoadjuvant Docetaxel and Gefitinib Followed by Radical Prostatectomy for High-Risk, Locally Advanced Prostate Cancer
Prostate cancer trials investigating neoadjuvant hormonal therapy, followed by surgery, have demonstrated that elimination of all tumor cells from the primary site is rare. The authors report a phase 2 trial assessing the efficacy and toxicity of docetaxel and gefitinib in patients with high-risk localized prostate cancer as neoadjuvant therapy before radical prostatectomy (RP).

Thirty-one patients with high-risk prostate cancer were treated with docetaxel and gefitinib for 2 months before RP. All patients met the criteria of clinical stage T2b-3 or serum prostate-specific antigen (PSA) level >20 ng/mL, or Gleason score of 8 to 10. The primary endpoint was pathologic complete response. Secondary objectives included clinical response. The median age of the patients was 60 years, the median pretreatment PSA level was 7.43 ng/mL, and the median Gleason score was 8. Clinical staging prior to treatment consisted of: T1 in 4 patients, T2 in 17 patients, and T3 in 10 patients. Thirty patients received all scheduled therapies including RP. Grade 3 toxicities included asymptomatic liver function test elevation in 4 (13%) patients, diarrhea in 1 (3%) patient, and fatigue in 1 (3%) patient. Twenty-nine (94%) patients achieved a clinical partial response, including 35% of patients who demonstrated radiographic improvement on eMRI.

No pathologic complete response was noted in 31 patients treated with docetaxel and gefitinib. This combination was well tolerated, and did not result in increased surgical morbidity.

Source: Vuky J, Porter C, Isacson C, Vaughan M, Kozlowski P, Picozzi V, Corman J. Phase II Trial of Neoadjuvant Docetaxel and Gefitinib Followed by Radical Prostatectomy in Patients with High-Risk, Locally Advanced Prostate Cancer. Cancer 2009;115(4):784-791.

Establishing an Anal Dysplasia Clinic for HIV-Infected Men: Initial Experience
Anal dysplasia is a precursor lesion to squamous cell carcinoma of the anus (SCCA).  This malignancy disproportionally impacts HIV-infected individuals due to co-infection of high-risk strains of human papilloma virus (HPV), which causes dysplastic changes in the perianal area and the anal canal.  Individuals with compromised immune systems are unable to clear HPV, which places them at particular risk for this cancer at a rate of 70-80 per 100,000, compared to 1 per 100,000 in the general population (Gypsyamber, et al, 2008).  With the advent of anti-retroviral therapy to treat HIV infection, it is proposed that the incidence of SCCA will increase given the improved life span and prolonged exposure to HPV.

The purpose of creating an anal dysplasia clinic is to identify pre-cancerous anal lesions and early stage SCCA in order to offer early treatment, which is associated with reduced mortality and morbidity and hence cost associated with this malignancy (Chiao, et al, 2006).  The article describes our initial experience in assessing the frequency and severity of anal intraepithelial neoplasia (AIN) in our anal dysplasia clinic in Seattle (opened in November 2007).  During a 7-month period, 150 HIV-positive men were evaluated by anal cytology in addition to digital rectal exam and high-resolution anoscopy (HRA).  Forty-seven of the 122 patients who underwent biopsy (39%) had biopsy-identified low-grade AIN, and 47 (39%) had high-grad AIN (HGAIN).  Two patients with HGAIN were referred for surgical treatment and were further noted to have micro-invasive SCCA. No patient reported significant post-HRA complications (e.g., bleeding, pain or infection).  Patient tolerance and acceptance of AIN screening was good, and the majority of those who underwent screening have been adherent to recommended follow-up exams and treatment. 

The clinic is expanding rapidly, with excellent community and provider support.  We now offer Infrared Coagulator therapy to precancerous anal lesions as part of the service line in the dysplasia clinic.  We anticipate that the anal dysplasia clinic will enable our institution to participate in emerging HIV-and HPV-related AIN clinical trials.

Source: Siekas LL, Aboulafia DM. Establishing an anal dysplasia clinic for HIV-infected men: initial experience. AIDS Reader 2009;19(5):178-186.

Immunotherapy for Metastatic Hormone-Refractory Prostate Cancer
Ongoing research in immunology has resulted in agents that stimulate the patient's immune system to destroy cancer cells.  This article details a multicenter clinical trial evaluating multiple dose levels of immunotherapy based on the GVAX platform in the treatment of metastatic hormone-refractory prostate cancer (HRPC). The GVAX platform involves injection of whole, irradiated tumor cells to provoke an immune response to multiple antigens.  The injected cells also have been genetically modified to secrete granulocyte-macrophage-colony-stimulating factor (GM-CSF), an immune stimulant.

Eighty men between 49-90 years old (median age 69) were treated. Dose levels varied and were based on earlier trials of GVAX platform-based immunotherapies.  Patients were treated for up to six months and followed for one year from the start of treatment or until they started a new treatment for prostate cancer; all were followed annually for life for potential late toxicities.  The most common adverse effect was injection-site erythema.  Overall, the therapy was well tolerated, with median survival time 35 months in the high-dose group, 20 months in the mid-dose group, and 23.1 months in the low-dose group.

Source:  Higano CS, Corman JM, Smith DC, et al. Phase 1/2 Dose-Escalation Study of a GM-CSF-Secreting, Allogeneic, Cellular Immunotherapy for Metastatic Hormone-Refractory Prostate Cancer. Cancer 2008;113:975-984.

Predicting Recurrence after Radical Prostatectomy
Doctors and scientists turn to measures like "distant metastatic-free survival" to help them determine the effectiveness of treatments.  In the case of radical prostatectomy (RP), survival rates that measure biochemical relapse are the best indicators of whether the treatment was successful, both in terms of destroying the existing disease as well as preventing a recurrence.  The more precisely these survival rates are calculated, the more likely it is that doctors will be able to know whether RP, which has been observed to be effective men who have already been treated, will also be effective in men who have not yet undergone treatment. 

Until now, the very best models have only been able to predict biochemical recurrence of prostate cancer for up to 10 years following radical prostatectomy.  Recently, however, Virginia Mason physicians Christopher Porter, Koichi Kodama, Robert Gibbons and Roy Correa, together with colleagues from the US, Canada, Italy and Germany, have described a model capable of accurately predicting an individual's risk of developing metastatic disease for up to 20 years after surgery.  This enhanced model makes it possible for doctors and patients to better understand the effectiveness of RP as an approach to treating prostate cancer.

Porter CR, Suardi N, Kodama K, Capitanio U, Gibbons RP, Correa R, Jeldress C, Perrotte P, Montorsi F, Karakiewica PI.  A nomogram predicting metastatic progression after radical prostatectomyIntl J of Urol 2008;15:889-894.

Suardi N, Porter CR, Reuther AM, Walz J, Kodama K, Gibbons RP,Correa R, Montorsi F, Graefen M, Huland H, Klein EA, Karakiewicz PI.  A nomogram predicting long-term biochemical recurrence after radical prostatectomyCancer 2008;112:1254-63.

Sorafenib for Older Patients with Renal Cell Carcinoma
The perception that older cancer patients may be at higher risk than younger patients of toxic effects from cancer therapy, but may also obtain less clinical benefit from therapy may be based on the under-representation of older patients in clinical trials.  Because older patients tend not to be included in clinical trials, it is not generally known how they respond to targeted therapies. Results of the study showed that the clinical benefits of sorafenib therapy were similar in older and younger patients.  Adverse effects of the therapy were predictable and manageable regardless of age.  Further, the study showed that sorafenib treatment delayed the time to self-reported health status deterioration in young and old alike, and improved quality of life over that time as well.  The authors concluded that, among patients with advanced renal cell carcinoma receiving sorafenib treatment, the outcomes of patients age 70 or older were similar to those of patients age 70 or below.

Source:  Eisen T, Oudard S, Szczylik C, Gravis G, Heinzer H, Middleton, R, Cihon F, Anderson S, Shah S, Bukowski R, Escudier B, for the TARGET Study Group.  Sorafenib for older patients with renal cell carcinoma:  subset analysis from a randomized trial.  J Natl Cancer Inst 2008;100(20):1454-1463.

Kidney Cancer Survival
The Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute is an authoritative source of information on cancer incidence and survival in the United States.  The Program is considered the standard for quality among cancer registries around the world.  Virginia Mason contributes data to the SEER registry and, in return, periodic reports are generated which allow us to compare the results of patients we have treated with results obtained for similar patients treated elsewhere in the region.  For the period 2001-2006 (the most recent for which data are available), SEER registry data show that survival among kidney cancer patients treated at Virginia Mason was as good or better than the average for the rest of the 13-county Puget Sound region.

Source:  National Cancer Institute's SEER Registry.  Report date:  Feb 1, 2008.  Data covers 2001-2006, Virginia Mason vs. all institutions in the Puget Sound region.

Successfully Adapting Stereotactic Radiotherapy to Treat Prostate Cancer
Stereotactic radiotherapy (SRT) uses sophisticated computerized imaging to target an X-ray beam with pinpoint accuracy, making it possible to destroy small tumors or close down abnormal blood vessels.  The technique, which is accurate to one millimeter or less, does not require surgery.  SRT is commonly used to treat patients with conditions such as brain tumors and special tumors of the head and neck regions.  Now, though, doctors at Virginia Mason have taken the essentials of their intracranial SRT experience and adapted it for treatment of prostate tumors.  They call the technique "stereotactic hypofractionated accurate radiotherapy of the prostate", or SHARP.  In the first clinical trial of the SHARP approach, these investigators demonstrated that with careful treatment planning technique and precise targeting, it is, indeed, feasible to use hypofractionated radiotherapy to treat tumors of the prostate, with minimal toxicity.  Their findings are reported in the International Journal of Radiation Oncology, Biology, Physics.

Source:  Madsen BL, Hsi RA, Pham HT, Fowler JF, Esagui L, Corman J.  Stereotactic hypofractionated accurate radiotherapy of the prostate (SHARP), 33.5 Gy in five fractions for localized disease: first clinical trial results.  Int J Radiat Oncol Biol Phys 2007;67(4):1099-1105.

PSA Predicts Prostate Cancer in Black, but not White American Men
More than a million prostate biopsies are performed annually in the United States. Several recent studies have shown that black men have a higher incidence of prostate cancer than white men, and recently race has been suggested as a predictor of prostate cancer detection among men who undergo biopsy. To explore the question, doctors at Virginia Mason and Stony Brook Medical Centers reviewed the records of 914 consecutive patients who had prostate biopsy, concluding that PSA statistically is an independent predictor of a positive prostate biopsy in black, but not in white American men. The findings are reported in The Journal of Urology. Virginia Mason co-author Christopher Porter, MD, notes that these results certainly need further confirmation in large, multiethnic databases, but that "this kind of pre-biopsy parameter may help us better educate and counsel patients as they present for possible prostate cancer evaluation."

Source:  Latchamsetty KC, Kim J, Porter CR. Prostate specific antigen remains an independent predictor of cancer at prostate biopsy in black American men but not in white men: Results from a consecutive series of 914 men. The Journal of Urology (2006) 175:913-917.

HIV-Associated Prostate Cancer
HIV-positive men being treated with highly active antiretroviral therapy (HAART) are living longer and, as a result, are more likely to develop cancers such as prostate cancer. Thus, the number of HIV-positive men with prostate cancer is increasing, and there is interest in better understanding how to identify and treat prostate cancer in this patient population. Dr. David Aboulafia of Virginia Mason recently collaborated with investigators from Tufts University School of Medicine, Harvard Medical School and Rush University to explore some of these questions. Their effort – which produced the largest combined case series investigation of this topic to date – concluded that neither the detection, treatment, nor outcomes of treatment for prostate cancer are influenced dramatically by HIV status. Their findings suggest that patients with prostate cancer and well-controlled HIV can be managed similarly to their HIV-negative counterparts, and can expect to achieve comparable clinical results of therapy.

Source:  Pantanowitz L, Bohac G, Cooley TP, Aboulafia D, Dezube BJ.  Human immunodeficiency virus-associated prostate cancer:  clinicopathological findings and outcome in a multi-institutional study. BJU Int 2008 Jun;101(12):1519-23. Epub 2008 Apr 2.

Avoiding Erectile Dysfunction After Radical Prostatectomy
Radical prostatectomy is a gold standard therapy for localized prostate cancer, with a 10-year disease free survival rate of 70-85 percent.  The primary treatment goal for these patients is to maximize survival while minimizing the impact of therapy on continence and potency.  Technical advancements in the past decade have enabled surgeons to perform radical prostatectomy with less impact on patients’ quality of life; still, erectile dysfunction remains a common concern for most patients.  With relatively new nerve-sparing techniques, however, many patients undergoing radical prostatectomy are able to avoid the problem.  Building on a technique used commonly in orthopedics, neurosurgery and otolaryngology, urologists have shown that grafting peripheral nerves during surgery allows those nerve fibers to regenerate and recover function.  A recent study published by surgeons at Virginia Mason demonstrated successful erectile function in 72 percent of men undergoing unilateral nerve grafts following radical prostatectomy at Virginia Mason, results which meet or exceed those published by other investigators.  These data confirm that nerve grafting is a feasible and well-tolerated approach for many men needing radical prostatectomy, allowing them to avoid the reduction in quality of life that would result from loss of sexual potency following surgery.

Source:  Hanson GR, Borden LS Jr, Backous DD, Bayles SW, Corman JM.  Erectile function following unilateral cavernosal nerve replacement.  The Canadian Journal of Urology;15(2); April 2008:3910-3913.

25-Year Prostate Cancer Control And Survival
Men with localized prostate cancer have many treatment options, ranging from radical prostatectomy (RP) to watchful waiting.  Data from randomized clinical trials comparing the long-term (more than 10-year) outcomes among men who have undergone different treatments for prostate cancer are unavailable.  This lack of data makes it difficult for newly diagnosed patients to make an informed choice among treatment options.  To address this limitation, our doctors analyzed and reported the long-term outcomes of 752 consecutive RPs performed between 1954 and 1994 at Virginia Mason.  This analysis, representing 40-years of experience with RP, is the most mature of the large case series published as of 2006.  Its results suggest that about half of the men who have undergone RP are at risk of biochemical (elevated PSA) recurrence at 25 years after surgery.  However, the analysis also demonstrates that RP provides excellent control of local and distant cancer recurrences, and minimal cancer-specific mortality even 25 years after surgery.

Source:  Porter CR, Kodama K, Gibbons RP, Correa Jr. R, Chun FKH, Perrotte P and Karakiewica PI. 25-Year Prostate Cancer Control And Survival Outcomes:  A 40-Year Radical Prostatectomy Single Institution Series. J Urol 2006;176:569-574.

Prostate Cancer
At Virginia Mason, nearly 300 patients are diagnosed with prostate cancer each year. More than 240 radical prostatectomies (removal of all of the prostate gland) were performed in 2007 for treatment of prostate cancer. As of 2007, ten-year survival rate for patients treated at Virginia Mason is 9 percent better than the Northwest regional data contained within the national database – Surveillance, Epidemiology and End Results (SEER) Registry. Twenty-year survival demonstrates a 60 percent advantage for patients treated at Virginia Mason.

Surveillance, Epidemiology and End Results (SEER) is a program of the National Cancer Institute. The SEER Regional data represents 13 county areas in Northwest Washington.

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Cervical Cancer Screening Rate
According to the 2010 Puget Sound Health Alliance Community Checkup, Virginia Mason's performance in cervical cancer screening is statistically above the regional average. Virginia Mason's results for the percentage of women between the ages of 21 to 64 who had at least one Pap test during the three-year measurement period was 76.8 percent. More information is available on the PSHA Community Checkup website.

Intraperitoneal Therapy in Ovarian Cancer
Ovarian carcinoma usually presents with stage 3 disease and unfortunately often (> 80%) relapse after standard surgery and chemotherapy. There has been a resurgence of interest in the intraperitoneal route of administration of chemotherapy in the last 3 years. Intraperitoneal therapy with a platinum agent is now considered the standard of care for patients who have had optimal surgery. This recent paper shows the feasibility of intraperitoneal topotecan which sets the stage for further study of this drug and route of administration in a phase 3 study.

Source:  Muntz HG, Malpass TW, McGonigle KF, Robertson MD, Weiden PL. Phase 2 Study of Intraperitoneal Topotecan as Consolidation Chemotherapy in Ovarian and Primary Peritoneal Carcinoma. Cancer 2008;113(3):490-496.

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The Triangular Intermuscular Space as a Site of Lymph Node Metastasis in Melanoma of the Back

The importance of an accurate sentinel lymph node biopsy as part of melanoma staging cannot be overemphasized. Lymphoscintigraphy is a key element of surgical planning for SLNB in melanoma, but one weakness of the technique lies in its focus on traditional lymph node basins. Intransit, or interval lymph nodes, are lymph nodes found along routes of lymphatic drainage between the primary tumor site and a conventional nodal basin. In-transit nodes may be involved with tumor, and therefore represent the site of the true sentinel node.

The Triangular Intermuscular Space is defined by borders of the teres major, teres minor, and long head of the triceps. Through this space pass the descending circumflex scapular artery, vena comitants, and lymphatics. We report 3 patients with truncal melanoma, presenting with recurrent disease in the TIS. These cases suggest that in patients with melanoma of the back, the Triangular Intermuscular Space, as the gateway to the axilla, may be an important site of metastatic disease.

Virginia Mason is presently evaluating fused lymphoscintigraphic/computed tomographic imaging with data retrieved from detectors at multiple angles around the patient. As it is unknown whether this will better illustrate in-transit basins, we recommend examining the triangular intermuscular space with the gamma probe in all SLNB performed on primary melanoma of the back. These measures may improve the accuracy of staging, and consequently optimize treatment for melanoma patients.

Source:  Herbert GS, Beshlian KM. Ann Plast Surg 2010;64(1):52-54.
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Assessment of Pancreatic Cancer Quality Indicators
Pancreatic cancer outcomes vary considerably among hospitals. Assessing pancreatic cancer care by using quality indicators could help reduce this variability. However, valid quality indicators are not currently available for pancreatic cancer management, and a composite assessment of the quality of pancreatic cancer care in the US has not been done.

Potential quality indicators were identified from the literature, consensus guidelines, and interviews with experts. To identify such indicators, a panel of 20 pancreatic cancer experts, including Virginia Mason's Dr. Vincent Picozzi, ranked potential quality indicators for validity based on the RAND/UCLA Appropriateness Methodology, rating each at high or moderate validity or not valid. Adherence with the indicators at both the patient and hospital levels was assessed using data from the National Cancer Data Base of the American College of Surgeons (2004-2005) for almost 50,000 patients treated at 1,134 hospitals in the US. The panel identified 43 valid indicators, which assessed structural factors, clinical processes of care, treatment appropriateness, efficiency, and outcomes. Patient-level adherence with indicators ranged from 49.6% to 97.2%, whereas hospital-level adherence ranged from 6.8% to 99.9%. Of the 10 component indicators that were used to develop a composite score, most hospitals were adherent with fewer than half of the indicators.

Based on the quality indicators developed in this study, there is considerable variability in the quality of pancreatic cancer care in the US. Hospitals can use these indicators to evaluate the care they provide and to identify potential quality improvement opportunities.

Source: Bilimoria KY, Bentrem DJ, Lillemoe KD, et al, on behalf of the American College of Surgeons' Pancreatic Cancer Quality Indicator Development Expert Panel. Assessment of pancreatic cancer care in the United States based on formally developed quality indicators. J Natl Cancer Inst 2009;101(12):848-859.

Combined Modality Treatment of Resectable and Borderline Resectable Pancreas Cancer
In the U.S., approximately 5,000 patients annually undergo resection (removal) of pancreatic cancer with curative intent. Despite concerted international efforts, especially over the past 20 years, survival statistics for such patients have changed little and remain disappointing. Reported 2- and 5-year overall survival rates for patients with resected pancreas cancer are 40-50% and 15-20% respectively, and rates of local and systemic recurrence also remain high (35-60% and 80-90% respectively).

Efforts to increase the number of long-term survivors after curative-intent pancreas cancer resection have centered on one of four areas: 1) neoadjuvant therapy (before surgery); 2) adjuvant (after surgery) chemotherapy; 3) whether or not to include radiation treatment; and 4) the extension of potentially curative treatment to patients with borderline resectable disease. The article then goes on to discuss the controversies, complexities and rationales associated with each of the four areas, as well as the limitations of available data. Working consensus statements are articulated for each area to provide focus for future study and express present levels of agreement.

Source:  Abrams RA, Lowy AM, O'Reilly EM, Wolff RA, Picozzi VJ, Pisters PWT. Combined Modality Treatment of Resectable and Borderline Resectable Pancreas Cancer: Expert Consensus Statement. Ann Surg Oncol 2009;16(7):1751-1756.

Adjuvant Therapy for Resected Pancreatic Cancer
Pancreatic cancer remains one of the greatest challenges within oncology. Over 37,000 people in the USA were diagnosed with pancreatic cancer in 2005; only 2-3% can expect to live 5 years using present treatment techniques. Virtually all long-term survivors come from among the approximately 5,000 people who will undergo definitive surgical resection of their pancreatic cancer this year. However, 5-year survival even for this relatively favored group of patients is typically only 10-25%. Among eight major randomized trials for resected pancreas cancer, five (GITSG, EORTC, ESPAC-1, RTOG 9704, and CONKO-1), containing a total of over 1,200 patients, have shaped world opinion on this subject. These trials have many significant methodological differences. Major conclusions that can be drawn from these trials in composite are (1) adjuvant chemotherapy is superior to observation following pancreaticoduodenectomy for pancreatic cancer, (2) gemcitabine is superior to 5-FU as adjuvant chemotherapy, and (3) the benefit of adjuvant chemoradiation is uncertain. Additional randomized trials are needed to address significant areas of controversy within available data.

Source: Picozzi VJ, Pisters PWT, Vickers SM, Strasberg SM. Strength of the Evidence: Adjuvant Therapy for Resected Pancreatic Cancer. J Gastrointest Surg 2008;12(4):657-661.

Improving Survival Among Patients With Locally Advanced Pancreatic Cancer
Pancreas cancer has the lowest overall survival of any major cancer.  Overall survival among patients with locally advanced pancreatic cancer (LAPC) is estimated in the medical literature to be 9 to 14 months, and only 10-15% of patients with LAPC survive two years.  Outcomes at Virginia Mason are well ahead of these estimates:  for the 99 LAPC patients treated at Virginia Mason between the years 2001-2007, two-year overall survival was 35%, about three-times that generally expected among patients in this clinically difficult population.

Source:  Picozzi VJ, Picozzi BV, Neil NJ.  Six-month progression-free survival (PFS) predicts superior overall survival in locally advanced pancreas cancer (LAPC)  Abstract submitted to ASCO Gastrointestinal Cancers Symposium, September 2008.

Pancreas Cancer:  Targeting Therapy, Improving Survival
Nearly 100 patients with locally advanced pancreas cancer (LAPC) were treated at Virginia Mason between the years 2001-2007.  Although two-year overall survival among LAPC patients treated at Virginia Mason is higher (35%) than estimates found in the medical literature (15%), pancreas cancer has the lowest overall survival of any major cancer and the prognosis in this group is poor.  Surgery and/or radiation therapy are often considered in an attempt to control the spread of LAPC, but these treatments are associated with significant side effects and, in some cases, do not improve survival.  At Virginia Mason, we made it our goal to try to identify ahead of time which patients would be most likely to benefit from these interventions.  Looking back over our considerable experience treating LAPC, we were able to determine that patients whose disease does not progress for 6 months following initial treatment are the ones who have the highest potential for long-term survival (two-year survival of about 48%).  These patients may be the ones most likely to benefit from additional surgical and/or radiation therapy to control the progression of disease.

Source:  Picozzi VJ, Picozzi BV, Neil NJ.  Six-month progression-free survival (PFS) predicts superior overall survival in locally advanced pancreas cancer (LAPC)  Abstract submitted to ASCO Gastrointestinal Cancers Symposium, September 2008.

Pancreaticobiliary Cancer: Long-term Survivorship
Patients with resectable pancreas cancer have a poor prognostic outlook with long-term survivorship being just 10 to 20 percent.

As a result of its unique surgical expertise in pancreaticoduodenectomy, physicians at Virginia Mason developed the “Virginia Mason methodology” (as it has come to be known) for treating resected pancreas cancer. Using standard treatment, half of the patients are alive at 18 to 20 months after treatment. Using the “Virginia Mason methodology” more than half of the patients are alive at 32 months follow-up after treatment. Our one-year survival rate was 95 percent; at two years it was 64 percent. Long-term (5 year) survival is estimated to be 50 to 60 percent.
The “Virginia Mason methodology” for treating resected pancreas cancer is now being employed at centers such as MD Anderson and Washington St. Louis (Barnes Hospital), and is the focus of an NCI-sponsored trial through the auspices of the American College of Surgeons Oncology Group (ASCOG) that began in November 2003.

Source: Picozzi VJ, Kozarek RA, Traverso LW. Interferon-based adjuvant chemoradiation therapy after pancreaticoduodenectomy for pancreatic adenocarcinoma. Am J Surg 2003;185:476-480.

Pancreaticobiliary Cancer: Operative Mortality
In the April 11, 2002, issue of the New England Journal of Medicine, Dr. Birkmeyer and colleagues from Dartmouth University, Vermont, report their analysis of surgical mortality in the United States (N Engl J Med 2002 Apr 11;346(15):1128-37). Using information from the national Medicare claims database, they examined the relationship between hospital volume (total number of procedures performed per year) and mortality (death in hospital or within 30 days) for a variety of surgical procedures. The mortality rate for Whipple procedures (pancreaticoduodenectomy) at low-volume centers (16.3 percent) was much greater than the mortality rate at high-volume centers (3.8 percent). (Low volume = <1 case/year; high volume = >16 cases/year.)

With an annual case volume that exceeds 60 cases per year, operative mortality at Virginia Mason for Whipple procedures has been zero for more than a decade.

Surviving Metastatic Pancreas Cancer
It is reported in the medical literature that patients with metastatic pancreas cancer have a median survivorship of four to five months. Using newly available treatments, doctors at Virginia Mason have achieved median survivorship roughly double that figure for this clinically difficult patient population.

Source: Clinical Decision Support

Pancreatic Resection Volumes
According to leading health care quality experts like those at the Leapfrog Group, institutions performing a minimum number of pancreatic surgical resections become more proficient at the complex procedure, thus reducing the number of complications and deaths. As reported in the 2004 Leapfrog Group survey, Virginia Mason performed five times the Leapfrog Group recommended minimum number of pancreatic surgeries, more than any other health care institutions in Washington. The total number of pancreatic cases performed by Virginia Mason reported by Leapfrog Group is 55.

Source: Leapfrog and Clinical Decision Support

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A Plan for Life
The number of cancer survivors in the US has more than tripled in the last 30 years, from 3 million individuals in 1971 to approximately 10 million individuals in 2002.  Because of the commitment demonstrated by those who work to improve the care and outcomes of patients with cancer, survival rates continue to improve. This good news brings new challenges, among them the need to develop evidence-based best practices for the long-term care of adult cancer survivors. 

Most adult cancer survivors in the United States are followed by their oncologists with a focus on monitoring for cancer recurrence and any persistent or late-toxicities of cancer therapies.  But survivors of adult cancers may also face other long-term and/or lifetime health risks that will vary depending upon their particular cancer, cancer treatment exposures, other existing health conditions, genetic predispositions and lifestyle behaviors.  The key to caring for these survivors—and maximizing the likelihood that they will remain survivors—is building comprehensive, proactive systems for ongoing surveillance and prevention based on each patient’s individual risks.  Unfortunately, a report published in 2005 by the Institute of Medicine (From Cancer Patient to Cancer Survivor:  Lost in Transition) concluded that this kind of specialized care system to support cancer survivors in the United States is the exception rather than the norm.

It doesn’t have to be this way, and it isn’t at Virginia Mason.  Our Cancer Survivorship Program teams patients who have completed active cancer treatment with a dedicated survivorship nurse.  The nurse begins by working together with the patient, the patient’s oncologist, primary care physician and any specialists who may be part of the clinical care team.  The goal is to create a Survivorship Care Plan tailored to each patient’s specific needs and situation.  Each care plan includes a comprehensive summary of the patient’s clinical experience with cancer, detailed information about potential long-term or late effects that might be caused by his or her cancer treatments, and evidence-based recommendations for ongoing cancer screening and other preventive health care.  Each patient also receives a list of lifestyle, behavioral and nutritional guidelines that may decrease his or her risk of disease recurrence.  The survivorship nurse is able to make specialist referrals for patients experiencing physical or emotional problems following cancer treatment, and able to recommend appropriate resources for patients who may have other special needs.  Perhaps most importantly, the survivorship nurse serves as an central resource and active partner to help patients lead healthy, active lives after cancer. 

Source:  Oeffinger KC and McCabe MS.  Models for Delivering Survivorship Care.   J Clin Oncol 2006;24:5117-5124

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Therapy-Related Acute Myeloid Leukemia Following HIV-Associated Lymphoma
In the highly active antiretroviral therapy era, an increasingly large number of HIV-infected patients are developing non-AIDS-defining cancers (NADCs). As patients survive longer, long-term therapy-related complications take on greater importance.

Herein, we describe a patient with AIDS who presented to medical attention with pancytopenia 48 months postchemotherapy with etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (R-EPOCH) for diffuse large B-cell lymphoma. Bone marrow biopsy showed a moderately hypocellular marrow; 51% of the nucleated cells were blasts with myelomonocytic differentiation. Cytogenetic studies revealed an abnormal karyotype with deletion of the long arm of chromosome 11 (11q21) and 2 additional copies of the MLL gene attached to the short arms of chromosome 10 in 80% of the metaphase cells examined. With the diagnosis of therapy-related acute myeloid leukemia (AML) secured, he began induction chemotherapy with idarubicin and cytarabine. Two weeks later, he died of fungal septicemia and multiorgan failure. 

Through a literature search, we were able to identify 4 additional cases of therapy-related AML in AIDS patients following chemotherapy for lymphomas. The median age of these patients at the time of AML diagnosis was 39 years (range, 33-59 years), the median time from the treatment of lymphoma to AML was 18 months (range, 11-48 months), and the median survival following induction chemotherapy was 4 weeks (range, 2-16 weeks). With many HIV-infected patients surviving alkylator and topoisomerase inhibitor-based treatment and radiation therapy for AIDSdefining cancers and NADCs, long-term follow-up for therapy-related complications assumes greater importance.

Source:  Mani D, Dorer RK, Aboulafia DM. Therapy-related acute myeloid leukemia following HIV-associated lymphoma. Clinical Lymphoma & Myeloma 2009;9(4):316-319

Certified Oncology Nursing Staff
Superior cancer nursing is a priority at Virginia Mason. Approximately 75 percent of Virginia Mason cancer nurses are certified for oncology nursing, compared to about 30 percent nationwide.

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Pre-2004 Publications by Virginia Mason Providers:

Ludwig DJ, Thirlby RC, Low DE (2001). A prospective evaluation of dietary status and symptoms after near-total esophagectomy without gastric emptying procedure. American Journal of Surgery, 181(5):454-458.

Low DE, Kozarek RA (2003). Removal of Esophageal Expandable Metal Stents. Surgical Endoscopy; 17: 990-996

Madsen BL, Hsi RA, Pham HT, Corman J, Myers L, (2003). Intrafractional Stability of the Prostate Using A Stereotactic Radiotherapy Technique. Radiation Oncology Biology and Physics: 57; 1285-1291

Porter CR (2004). Low AUA Symptom Score Independently Predicts Positive Prostate Needle Biopsy: Results from a Racially Diverse Series of 411 Patients: Urology: 63; 90-94

Aboulafia DM, Evans DL, Pantanowitz L, Dezube BJ (2002). Breast Enlargement in 13 Men Who Were Seropositive for Human Immunodeficiency Virus. Clinical Infectious Diseases; 35; 1113-1119

Corman JM, McClure D, Pritchett TR, Kozlowski P, Hampson NB (2003). Treatment of Radiation Induced Hemorrhagic Cystitis with Hyperbaric Oxygen. The Journal of Urology; 169; 2200-2202

Neal JM, Wilcox RT, Allen HW, Low DE (2003). Near Total Esophagectomy: The Influence of Standardized Multimodal Management and Intraoperative Fluid Restriction. Regional Anesthesia and Pain Medicine; 28, No 4: 328-334

Muntz HG, Goff BA, McGonigle K, Isacson C (2002). The Significance of Psammoma Bodies in Screening Cervical Cytologic Smears. Presented at the Sixty-Ninth Annual Meeting of the Pacific Coast Obstetrical and Gynecological Society, October 22-27, 2002, Rancho Mirage, California.

Moonka R, Beyer T (2003). Normal Mammography and Ultrasonography in the Setting of Palpable Breast Cancer. The American Journal of Surgery; 185: 416-419

Corman JM, Porter CR. Percent Carcinoma in Prostatectomy Specimen is Associated with The Presence of Extracapsular Disease. Presented at the Northwest Urologic Annual Meeting, Vancouver, BC, December 2004

Porter CR, Bhalla RS, Corman JM. Intraoperative Identification of Extraprostatic Disease in High Risk Patients: Is Frozen Section Warranted? Abstract presented at Western Society American Urological Association.

Hansman, Ryan, Holmes, Hogan, Lee, Kramer, Biehl (2001). Management and longterm follow-up of hepatic cysts. The American Journal of Surgery; 181:404-410.

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