Applied Molecular Medicine

The USC Center for Applied Molecular Medicine uses proteomic and molecular technologies to better understand cancer and develop personalized therapies. The Center is funded by the National Cancer Institute as part of the Center for Cancer Nanotechnology Excellence and by private foundations to develop and apply technology to patients with advanced cancer.

USC Norris Westside Cancer Center

Located in Beverly Hills, the USC Norris Westside Cancer Center is a multi-disciplinary cancer clinic and clinical trials center. We work to provide care for patients with prostate and other genito-urinary cancers and bring innovative therapies to patients through clinical trials. Our goal is to make the most exciting and promising molecular targeted therapeutics available for our patients. Our team is comprised of medical oncologists, radiologists, radiation therapists and urologists.

Center for Applied Molecular Medicine (CAMM) Laboratory

Our CAMM team works to pioneer and apply technology to further develop new targeted therapeutics for genito-urinary cancers and to manage patients with cancer.

The principle goal of our center is the development, validation and application of proteomics technologies for the diagnosis and management of disease. (Patients will have biopsies of their tumor, and/or blood/plasma samples interrogated by quantitative protein profiling techniques to discover and establish initial panels of markers of response to a given therapy.) Once an initial panel has been constructed, it will direct the treatment course for patients. Samples from these patients may then be used to iteratively refine the existing marker panel and potentially to inform cancer biology and aid in the identification of new targets for the development of novel therapeutic agents. Toward this vision, we are actively applying existing proteomics techniques to clinical and biological samples to better understand the biology of cancer and other diseases. In addition, we are developing new technologies that will allow us to extract more information reproducibly from biological and clinical samples.

 

Early Complications After Cystectomy Following High Dose Pelvic Radiation

Authors: Manuel S. Eisenberg, Ryan P. Dorin, Georg Bartsch, Jie Cai, Gus Miranda, Eila C. Skinner

USC Institute of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

PURPOSE: Radical cystectomy in patients with a history of pelvic radiation therapy (RT) is an often challenging and morbid procedure. We report early complication rates in patients undergoing cystectomy and urinary diversion (UD) after high dose pelvic radiation.

MATERIALS AND METHODS: From 1983 to 2008, 2629 patients underwent cystectomy with UD at a single institution.  Of these, 148 received ≥60 Gy pelvic RT  prior to surgery. Each patient’s medical record was retrospectively reviewed and any complication within 90 days of surgery was graded using the Clavien-Dindo system.

RESULTS: The median age was 74 years old, with a median ASA score of 3.  Patients received a median 70 Gy pelvic RT a median 2.3 years prior to surgery.  UD performed were ileal conduit in 65 (43.9%), continent cutaneous pouch in 35 (23.6%), and orthotopic neobladder in 48 (32.4%).  A total of 335 early complications were identified.  The highest grade complication was: none in 23%, grade 1 in 12.2%, grade 2 in 32.4%, grade 3 in 18.9%, grade 4 in 7.4%, and grade 5 in 6.1%.  Age >65 and ASA were statistically significant predictors of postoperative complications (p=0.0264 and p=0.0252, respectively). Type of UD did not significantly affect the grade distribution or number of early complications per patient (p=0.7444 and p=0.1807, respectively).

CONCLUSIONS: The early complication rate using a standardized reporting system in patients undergoing post-RT radical cystectomy is higher than previously published in non-irradiated subjects.  Age and ASA, but not urinary diversion type, are associated with early complications in this population.

Table 2: Patient clinical characteristics

Characteristic Median (% or IQR)
n 148
Age, years 74 (69-78)
Male 120 (81.1%)
ASA (n=122) 3 (3-3)
Radiation to surgery interval (years) 2.3 (1-9)
Total radiation dose 70 (65-100)
Indication for radiation therapy
   bladder cancer 79 (53.4%)
   prostate cancer 55 (37.2%)
   other* 14 (9.5%)
Previous abdominal or pelvic surgery (n=147) 95 (64.6%)
Preoperative systemic chemotherapy 39 (26.4%)
IQR, inter-quartile range; ASA, American Society of Anesthesiologists score*other indications for radiation therapy include cervical cancer, endometrial cancer, lymphoma, and carcinoma not otherwise specified

 

Table 6: Complication categories and types

Category Complication type (incidence*) n* % of total
Gastrointestinal Ileus† (29), dehydration (22), diarrhea (13), fistula / anastamotic bowel leak (9), failure to thrive (9), gastrointestinal bleeding (6), liver insufficiency/elevated LFT’s (4), emesis (3), dysphagia (3), small bowel obstruction (2) constipation‡ (2), large bowel obstruction (1) 103 30.7%
Infectious Sepsis (15), urinary tract infection (11), fever of unknown origin (7), urosepsis (6), C. difficile infection (5), abscess (4), oral candidiasis (2), cholecystitis (1), pyelonephritis (1) 51 15.2%
Bleeding Anemia requiring transfusion (28), internal hemorrhage (3), hematoma (2) 33 9.9%
Cardiac Arrhythmia (17), angina (4), myocardial infarction (3), congestive heart failure (3), hypertension (3), hypotension (1) 31 9.3%
Genitourinary (GU) / Diversion Urinary leak (7), renal insufficiency (4), urinary fistula (3), stomal incontinence (3), stomal ischemia/necrosis (3), acute tubular necrosis (2), ureteral obstruction (1), hematuria (1), renal failure (1), low urine output (1) 26 7.8%
Miscellaneous Edema (4), depression (4), electrolyte abnormality (3), rash (3), decubitus ulcer (2), other rare complications (10) 26 7.8%
Neurologic Altered mental status (18), neuropraxia (4), neuropathy (1), loss of consciousness (1) 24 7.2%
Pulmonary Respiratory distress (8), respiratory failure (6), atelectasis (4), pneumonia (2) 20 6.0%
Wound Seroma (10), superficial infection (6), fascial dehiscence (2) 18 5.4%
Thromboembolic Deep venous thrombosis (2), pulmonary embolus (1) 3 0.9%
LFTs, Liver function tests*Patients experiencing multiple complications are counted more than once†Ileus is defined as post-operative nausea or vomiting requiring the cessation of oral intake and/or nasogastric tube placement, or the intolerance of any oral intake by postoperative day 5.

‡Constipation is defined as the inability to have a bowel movement by postoperative day 5 without signs of ileus or bowel obstruction

 

Table 7: Complication categories by grade

Low Grade (n = 264) High Grade (n = 71)
Category n (%) Category n (%)
Gastrointestinal 81 (30.7%) Gastrointestinal 22 (31.0%)
Infectious 43 (16.3%) GU / Diversion 16 (22.5%)
Bleeding 30 (11.4%) Pulmonary 10 (14.1%)
Cardiac 26 (9.8%) Infectious 8 (11.3%)
Neurologic 23 (8.7%) Cardiac 5 (7.0%)
Miscellaneous 23 (8.7%) Bleeding 3 (4.2%)
Wound 16 (6.1%) Miscellaneous 3 (4.2%)
GU / Diversion 10 (3.8%) Wound 2 (2.8%)
Pulmonary 10 (3.8% Thromboembolic 1 (1.4%)
Thromboembolic 2 (0.8%) Neurologic 1 (1.4%)

 

Table 8: Statistical analysis of early complications (≤ 90days)

Univariate variable No Complications Any Grade 1-5 complication P value
n 34 114
Male 25 (73.5%) 95 (83.3%) 0.2002
Age >65yrs 24 (70.6%) 99 (86.8%) 0.0264
ASA (n=122) 0.0252
   1 2 (7.1%) 0 (0%)
   2 5 (17.9%) 17 (18.1%)
   3 20 (71.4%) 62 (66.0%)
   4 1 (3.6%) 15 (16.0%)
RT to RC interval (yrs, median) (IQR) 2 (1-10) 2 (1-8) 0.7035
RT dose (Gy, median) (IQR) 71 (65-100) 70 (65-136) 0.8925
Indication for XRT 0.8587
   bladder cancer 17 (50.0%) 62 (54.4%)
   prostate cancer 14 (41.2%) 41 (36.0%)
   Other 3 (8.8%) 11 (9.6%)
Prior abdominal or pelvic sugery (n=147) 22 (66.7%) 73 (64.0%) 0.7807
Prior neoadjuvant chemotherapy 9 (26.5%) 30 (26.3%) 0.9857
Extent of lymphadenectomy 0.3129
   Not performed 14 (41.2%) 35 (30.7%)
   <15 6 (17.7%) 34 (29.8%)
   ≥15 14 (41.2%) 45 (39.5%)
Diversion type 0.5681
   Ileal conduit 15 (44.1%) 50 (43.9%)
   Continent cutaneous 6 (17.7%) 29 (25.4%)
   Orthotopic neobladder 13 (38.2%) 35 (30.7%)
Operative time (hr, median) (IQR) 5 (5.0-6.0) 6 (5.0-7.0) 0.3238
EBL (ml, median) (IQR) 700 (600-1200) 1000 (700-1500) 0.1796