Amanda K. Arrington

Increasing Rates of Contralateral Prophylactic Mastectomy Among Patients With Ductal Carcinoma In Situ

PURPOSE Some women with unilateral ductal carcinoma in situ (DCIS) undergo contralateral prophylactic mastectomy (CPM) to prevent cancer in the opposite breast. The use and trends of CPM for DCIS in the United States have not previously been reported. METHODS We used the Surveillance, Epidemiology, and End Results database to analyze the initial treatment (within 6 months) of patients with unilateral DCIS diagnosed from 1998 through 2005. We determined the CPM rate as a proportion of all surgically treated patients and as a proportion of all patients who underwent mastectomy. We compared demographic and tumor variables in women with unilateral DCIS who underwent surgical treatment. RESULTS We identified 51,030 patients with DCIS; 2,072 patients chose CPM. The CPM rate was 4.1% for all surgically treated patients and 13.5% for patients undergoing mastectomy. Among all surgically treated patients (including breast-conserving surgery), the CPM rate increased by 148% from 1998 (2.1%) to 2005 (5.2%). Among patients who underwent mastectomy to treat DCIS (excluding patients undergoing breast-conserving surgery), the CPM rate increased by 188% from 1998 (6.4%) to 2005 (18.4%). Young patient age, white race, recent year of diagnosis, and the presence of lobular carcinoma in situ were significantly associated with higher CPM rates among all surgically treated patients and all patients undergoing mastectomy. Large tumor size and higher grade were significantly associated with increased CPM rates among all surgically treated patients but lower CPM rates among patients undergoing mastectomy. CONCLUSION The use of CPM for DCIS in the United States markedly increased from 1998 through 2005.

The Increasing Use of Prophylactic Mastectomy in the Prevention of Breast Cancer

Selected high-risk women without breast cancer choose to undergo bilateral prophylactic mastectomy (BPM) to reduce their risk of developing the disease. Several studies have reported that BPM significantly reduces, but does not eliminate, breast cancer risk. Few studies have reported rates or trends of BPM use. Patients with unilateral breast cancer are at increased risk for developing cancer in the normal contralateral breast. Some breast cancer patients choose contralateral prophylactic mastectomy (CPM) to prevent cancer in the contralateral breast. The risk of contralateral breast cancer is significantly reduced after CPM. Recent studies reported that CPM rates have markedly increased in recent years in the United States. Alternatives to CPM include surveillance with clinical breast examination, mammography, and, potentially, breast MRI. Endocrine therapy with tamoxifen or aromatase inhibitors significantly reduces the risk of contralateral breast cancer and may be more acceptable than CPM for some patients.

Milan Criteria and UCSF Criteria: A Preliminary Comparative Study of Liver Transplantation Outcomes in the United States.

The application of orthotopic liver transplantation (OLT) for patients with hepatocellular cancer (HCC) necessitates highly selective criteria to maximize survival and to optimize allocation of a scarce resource. The objective of this study was to compare the outcomes of OLT for HCC in patients transplanted under Milan and UCSF criteria. The United Network of Organ Sharing (UNOS) database was queried for patients who had undergone OLT for HCC from 2002 to 2007, and 1,972 patients (Milan criteria, n = 1, 913; UCSF criteria, n = 59) were identified. Patients were stratified by pretransplant criteria (Milan versus UCSF), and clinical and pathologic factors and overall survival were compared. There were no differences in age, gender, diabetes mellitus, body mass index, and hepatitis B, or C status between the two groups. Overall survival was similar between the Milan and UCSF cohorts (1-, 2-, 3-, and 4-year survival rates: 88%, 81%, 76%, and 72% versus 91%, 80%, 68% and 51%, respectively, P = 0.21). Although the number of patients within UCSF criteria was small, our results nevertheless suggest that patients with HCC may have equivalent survival when transplanted under Milan and UCSF criteria. Long-term followup may better determine whether UCSF criteria should be widely adopted.

Ninety-day mortality and major complications are not affected by use of lung allocation score.

BACKGROUND In May 2005 the Organ Procurement Transplant Network (OPTN) and United Network for Organ Sharing (UNOS) implemented the donor lung allocation score (LAS) system to prioritize organ allocation among prospective transplant recipients. The purpose of our study was to determine the impact of LAS implementation on 90-day survival, early complications and incidence of severe primary graft dysfunction (PGD) after the transplant procedure. METHODS Early outcomes among 78 patients receiving transplants after the initiation of the scoring system were compared with those of the 78 previous patients. Survival rates at 90 days and 1 year were the primary end-points of the study. Arterial blood-gas measurements were collected for all patients at the time of ICU arrival and at 12, 24 and 48 hours after surgery to determine the distribution of International Society of Heart and Lung Transplant (ISHLT) PGD grade. Major complications within 30 days post-transplant were recorded. RESULTS We found a small but significant 1-year survival advantage among post-LAS implementation patients, which was largely due to decreased early mortality in comparison to the control cohort. The incidence of ISHLT Grade 3 PGD measured within the first 24 hours after transplant did not differ between groups, nor was there an increase in the rate of major post-operative complications. CONCLUSIONS Implementation of the LAS system has not been associated with an increase in early mortality, immediate PGD or major complications.

Targeted therapies in colorectal cancer: surgical considerations

Colorectal cancer (CRC) is a leading worldwide health concern that is responsible for thousands of deaths each year. The primary source of mortality for patients with CRC is the development and subsequent progression of metastatic disease. The most common site for distant metastatic disease is the liver. Although patients with metastatic disease to the liver have several effective treatment options, the only one for cure remains surgical resection of the liver metastases. Historically, most patients with liver metastases have had unresectable disease, and only a small percentage of patients have undergone complete curative resection. However, improved systemic therapies have led to an evolution in strategies to treat metastatic CRC to the liver. Under most conditions the management of these patients remains complex; and as chemotherapy options and new targeted therapies continue to improve outcomes, it is clear that a multidisciplinary approach must be the foundation on which advanced surgical and medical techniques are employed. Here, in this review, we highlight the role of targeted therapies in the surgical management of patients with metastatic CRC to the liver.

Timing of chemotherapy and survival in patients with resectable gastric adenocarcinoma

AIM To evaluate the timing of chemotherapy in gastric cancer by comparing survival outcomes in treatment groups. METHODS Patients with surgically resected gastric adenocarcinoma from 1988 to 2006 were identified from the Los Angeles County Cancer Surveillance Program. To evaluate the population most likely to receive and/or benefit from adjunct chemotherapy, inclusion criteria consisted of Stage II or III gastric cancer patients > 18 years of age who underwent curative-intent surgical resection. Patients were categorized into three groups according to the receipt of chemotherapy: (1) no chemotherapy; (2) preoperative chemotherapy; or (3) postoperative chemotherapy. Clinical and pathologic characteristics were compared across the different treatment arms. RESULTS Of 1518 patients with surgically resected gastric cancer, 327 (21.5%) received perioperative chemotherapy. The majority of these 327 patients were male (68%) with a mean age of 61.5 years; and they were significantly younger than non-chemotherapy patients (mean age, 70.7; P < 0.001). Most patients had tumors frequently located in the distal stomach (34.5%). Preoperative chemotherapy was administered to 11.3% of patients (n = 37) and postoperative therapy to 88.7% of patients (n = 290). An overall survival benefit according to timing of chemotherapy was not observed on univariate or multivariate analysis. Similar results were observed with stage-specific survival analyses (5-year overall survival: Stage II, 25% vs 30%, respectively; Stage III, 14% vs 11%, respectively). Therefore, our results do not identify a survival advantage for specific timing of chemotherapy in locally advanced gastric cancer. CONCLUSION This study supports the implementation of a randomized trial comparing the timing of perioperative therapy in patients with locally advanced gastric cancer.

Generation of a novel, cyclooxygenase-2-targeted, interferon-expressing, conditionally replicative adenovirus for pancreatic cancer therapy

BACKGROUND Oncolytic adenoviruses provide a promising alternative for cancer treatment. Recently, adjuvant interferon (IFN)-alfa has shown significant survival benefits for pancreatic cancer, yet was impeded by systemic toxicity. To circumvent these problems adenovirus with high-level targeted IFN-alfa expression can be generated. METHODS Conditionally replicative adenoviruses (CRAds) with improved virulence and selectivity for pancreatic cancer were generated. The vectors were tested in vitro, in vivo, and in human pancreatic cancer and normal tissue specimens. RESULTS Adenoviral death protein and fiber modifications significantly improved oncolysis. CRAds selectively replicated in vitro, in vivo and showed persistent spread in cancer xenografts. They showed high-level replication in human pancreatic cancer specimens, but not in normal tissues. Improved IFN-CRAd oncolytic efficiency was shown. CONCLUSIONS Optimized cyclooxygenase-2 CRAds show highly favorable effects in vitro and in vivo. We report a pancreatic cancer-specific, highly virulent, IFN-expressing CRAd, and we believe that adenovirus-based IFN therapy offers a new treatment opportunity for pancreatic cancer patients.

ERBB2 suppression decreases cell growth via apoptosis in gastrointestinal adenocarcinomas

BACKGROUND Although the incidence of adenocarcinoma of the esophageal and gastroesophageal junction has increased at an alarming rate in the past 30 years, little improvement has been made in treatment strategies. Previous studies have demonstrated that many upper gastrointestinal (GI) adenocarcinomas exhibit ERBB2 amplification. In cancers proven to have similar amplification, such as breast, ERBB2-targeted therapies have dramatically improved overall survival and disease-free rates of survival. This study uses siRNA to knockdown ERBB2 in GI adenocarcinoma cell lines to evaluate cell viability, apoptosis, and changes in cell cycle. METHODS A cell line with a baseline amount of ERBB2 (Seg-1) and 2 upper GI adenocarcinoma cell lines with known amplification of ERBB2 (esophageal [OE19] and gastric [MKN45]) were treated with 120 pmol of 1 of 2 independent ERBB2 siRNAs or control siRNA for 6 hours. RESULTS We demonstrate that knockdown of ERBB2 in esophageal and gastric cancer cell lines with known ERBB2 amplification effectively decreases ERBB2 protein levels and decreases cell viability mainly via apoptotic pathways. CONCLUSION ERBB-directed therapy may be of benefit in the subset of patients with GI adenocarcinomas exhibiting amplification of ERBB2.

A randomized, placebo-controlled trial of aprotinin to reduce primary graft dysfunction following lung transplantation

Herrington CS, Prekker ME, Arrington AK, Susanto D, Baltzell JW, Studenski LL, Radosevich DM, Kelly RF, Shumway SJ, Hertz MI, Bittner HB, Dahlberg PS. A randomized, placebo‐controlled trial of aprotinin to reduce primary graft dysfunction following lung transplantation.
Clin Transplant 2011: 25: 90–96.

Impact of medical and surgical intervention on survival in patients with cholangiocarcinoma

AIM To examine surgical and medical outcomes for patients with cholangiocarcinoma using a population-based cancer registry. METHODS Using the California Cancer Registrys Cancer Surveillance Program, patients with intrahepatic cholangiocarcinoma treated in Los Angeles County from 1988 to 2006 were identified and evaluated for clinical and pathologic factors and therapies received (surgery, radiation, and chemotherapy). The surgical cohort was further categorized into three treatment groups: patients who received adjuvant chemotherapy, adjuvant chemoradiation, or underwent surgery alone (no chemotherapy or radiation administered). Survival was assessed by Kaplan-Meier method; and Cox proportional hazard modeling was used in multivariate analysis. RESULTS Of 825 patients, 60.2% received no treatment. Of the remaining 328 patients, 18.5% chemotherapy only, 7.4% chemoradiation, and 13.8% underwent surgery. More male patients underwent surgical resection (P = 0.004). Surgical patients were younger than the patients receiving chemotherapy or chemoradiation (P < 0.001). Of the surgical cohort (n = 114), 60.5% underwent surgery alone while 39.5% underwent surgery plus adjuvant therapy (chemotherapy, n = 20; chemoradiation, n = 21) (P < 0.001). Median survival for all patients in the study was 6.6 mo. Median survival was highest for patients who underwent surgery (23 mo), whereas both chemotherapy (9 mo) and chemoradiation (8 mo) alone were each less effective (P < 0.001). By multivariate analysis, extent of disease, receipt of surgery, and administration of chemotherapy (with/without surgery) were independent predictors of overall survival. CONCLUSION This study demonstrates that surgery is a critical treatment modality. Multimodality treatment has yet to be standardized, but play a role in optimal therapy for cholangiocarcinoma.