Liver / GI / GU

 

 

LIVER / GI / GU

 

 

Liver / GI / GU includes research in the following areas:

Colorectal Research
Liver Research
Prostate Research

 

 

COLORECTAL RESEARCH

 


Initiated in 2009, the Colorectal Research Program was developed with three main areas of focus:

Colorectal Cancer Risk

 

Colorectal cancer is the third most common malignancy among both men and women in the United States and represents the second leading cause of cancer death. In addition to known genetic syndromes that increase risk of cancer, there are a variety of risk factors in the general population for developing colorectal cancer. These risk factors include consumption of red meat and especially processed meats, obesity, and a sedentary lifestyle.

 

The molecular pathways that transform a benign colorectal polyp into cancer may include genetic mutations and epigenetic phenomena that turn genes on and off. The colorectal cancer research program at HMRI currently focuses on the role of increased body mass index on epigenetic changes that occur in the colon.

 

Pelvic Floor Disorders

 

By age 50, one half of women will develop clinical problems related to pelvic floor relaxation. While not life-threatening, these disorders which include incontinence, obstruction, pelvic organ prolapse, and pain have a significant impact on quality of life. These problems can cause progressive dysfunction, and by age 80, 11% of women in the United States will undergo surgery for incontinence or pelvic organ prolapse.

 

Our research program seeks to understand age-related changes in the pelvic floor with aging and obesity utilizing state-of-the-art MRI technology. Moreover, Dr. Kaufman was one of 16 international investigators who studied the effect of sacral nerve stimulation on bowel control. This therapy was recently approved by the FDA for the treatment of fecal incontinence and is currently available to patients at the Huntington Hospital. The pelvic floor research program is intimately related to our clinical efforts in the multidisciplinary treatment of pelvic floor disorders at the Huntington Hospital.

 

Patient Safety and Quality in Colorectal Surgery

 

This program focuses upon improving outcomes in colorectal surgery patients. Our goal is not only to track the clinical outcomes of patients with colorectal disorders treated at the Huntington Hospital, but to utilize validated outcomes based databases towards understanding risk and improving care for patients undergoing surgery for colorectal diseases.

References:

 

Chung DC. The genetic basis of colorectal cancer: insights into critical pathways of tumorigenesis. Gastroenterology. 2000 Sep;119(3):854-65.

Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB, Issa JP. CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci 1999;96(15):8681-6.

Wexner SD, Coller JA, Devroede G, Hull T, McCallum R, Chan M, Ayscue JM, Shobeiri AS, Margolin D, England M, Kaufman H, Snape WJ, Mutlu E, Chua H, Pettit P, Nagle D, Madoff RD, Lerew DR, Mellgren A. Sacral nerve stimulation for fecal incontinence: Results of a 120-patient prospective multi-center study. Ann Surg. 2010; 251:441-449.

 

Research in Progress

 

  • Evaluation of the role dynamic MR imaging in the management of pelvic floor disorders
  • Prospective RCT of the use of sacral nerve stimulation in the treatment of fecal incontinence
  • Prospective evaluations of epigenetic profiles in colon mucosa in patients with polyps, obese individuals
  • Prospective evaluations of epigenetic profiles in serum and plasma or patients with and without colorectal neoplasia
  • Safety and quality process implementation in colorectal and pelvic floor surgery
  • The use of anastomotic buttresses in colorectal surgery

 

Major Areas of Research Interest

 

  • Diagnosis and management of pelvic floor disorders
  • Advanced treatments for fecal incontinence
  • Multimodality treatment of rectal cancer, other pelvic malignancies
  • Adhesion prevention following colorectal surgery
  • The effects of morbid obesity on pelvic floor function
  • The effects of morbid obesity on colon cancer risk
  • Epigenetic markers in colorectal cancer
  • Anastomotic buttressing in colorectal surgery
  • Safety and quality processes in general, colorectal, and pelvic floor surgery

 

Huntington Hospital General Surgery Residency Program

 

  • Lectures on colorectal diseases, pelvic floor disorders, patient safety and quality 2006-present
  • Daily informal teaching of residents, fellows, and medical students in operating room, clinic, endoscopy suite, 2004-present
  • Full-time teaching faculty, 2009-present
  • Curriculum committee, 2009-present
  • Advisor to categorical residents, 2009-present

 

Specific Administrative Responsibilities

 

  • Medical Director, Cancer Services, Huntington Hospital 2007-present
  • Chair, Cancer Committee, Huntington Hospital, 2007-present
  • Surgical Quality Committee, Huntington Hospital, 2008-present
  • Value Analysis Committee, Huntington Hospital, 2009-present

 

Committee Memberships

 

  • Board of Directors, Southern California Chapter of American College of Surgeons, 2006-present
  • Governor at large, American College of Surgeons

 

Awards

 

  • Top Docs in San Gabriel Valley, Pasadena Magazine 2008 to 2011
  • Southern California Super Doctor 2012

 

Office Address

 

  • HMH Radiation Oncology Dept
    100 W. California Blvd.
    Pasadena CA 91105
  • www. hmri.org or http://howardkaufmanmd.com/
  • Office: 626.397.5896
    Fax: 626.397.5899
    Mon: 8:30AM-5:00PM
    Tue: 8:30AM-5:00PM
    Wed: 8:30AM-5:00PM
    Thu: 8:30AM-5:00PM
    Fri: 8:30AM-5:00PM
    Sat: Closed
    Sun: Closed

 


Liver Research Program

 

The HMRI Liver Center’s clinical research programs are directly related to our customized patient-centered care and treatment. The HMRI Liver Center’s research focuses on the natural history and clinical course of viral and autoimmune diseases affecting the liver and has authored more than 230 peer-reviewed articles in these areas. Our participation in multi-centered clinical research trials using the most advanced drugs, allows us to deliver medical care on the cutting-edge of medical and pharmaceutical technologies. These multi-centered clinical trials have led to FDA approval of medications which have dramatically impacted the length and quality of life for patients living with chronic liver diseases.

 

The HMRI Liver Center hepatocellular research studies have elucidated the pathogenesis of chronic viral infections and the role it plays in the development of hepatocellular carcinoma (HCC). Together with leading clinicians and research collaboration with UCLA, the HMRI Liver Center utilizes medical treatments which have significantly prolonged the lives of patients with hepatobiliary malignancies. In addition, HMRI is continuing to search for liver cancer molecular markers which will enhance early detection and future treatment modalities for patients afflicted with this highly fatal cancer.

 

 


Prostate Research

 

 

Achievements:

 

  1. Established cell lines for human prostate cancer: the Pasadena Cell Lines
  2. Development of the patented endo rectal coil for prostatic magnetic resonance imagery
  3. Discovery of a novel agent for hormone-refractory prostate cancer
  4. Development of a prostate research information network for patients in all stages of prostate cancer

 

Collaborative Studies:

 

  1. Huntington Medical Research Institutes

 

The Prostate Research Program and the Molecular Pathology Program have been evaluating the expression of functional androgen receptor (AR) as a potential prognostic biomarker for the development of castration resistant prostate cancer (CRPC).  The presently available markers have not been shown to be effective in predicting the development of CRPC.  The results have demonstrated the presence of functional AR in both primary cancer cells and metastatic cancer cells with significantly higher levels present in metastatic cancer cells.  Cases that had undergone castration and hormone therapy still showed continued AR expression indicating that prior therapy did not prevent the development of castrate resistance. This has never been demonstrated in human tissue.  According to publications, this has only been done in rodent models.

 

Publications:

 

Zon, G., Barker, M.A., Kaur, P., Groshen, S., Jones, L.W., Imam, S.A., Boyd, V.L. Formamide as a Denaturant for Bisulfite Conversion of Genomic DNA: Bisulfite Sequencing of the GSTPi and RARb2 Genes of 43 Formalin-Fixed Paraffin-Embedded Prostate Cancer Specimens. Anal Biochem, 392(2):117-125 (2009). PMID: 19505431

 

Baisakhi, S., Arase, A., Imam, S.S., Tsao-Wei, D., Naritoku, W.Y., Groshen, S., Jones, L.W., Imam, S.A. Overexpression of E-Cadherin and ß-Cartenin Proteins in Metastatic Prostate Cancer Cells in Bone. Prostate. 68(1): 78-84 (2008). PMID: 18008331

 

Baisakhi, S., Kaur, P., Tsao-Wei, D., Naritoku, W.Y., Groshen, S., Datar, R.H., Jones, L.W., Imam, S.A. Unmethylated E-Cadherin Gene Expression is Significantly Associated with Metastatic Human Prostate Cancer Cells in Bone. Prostate. 68(15):1681-1688 (2008). PMID: 18712716

 

 

  1. Cedars Sinai Medical Center

 

Our collaborative study with Dr. Lelund Chung and Dr. Haiyen Zhau from Cedars Sinai Medical Center was designed to test the hypothesis that novel, biologically relevant, noninvasive techniques of assessing changes in risk related metabolic products will improve risk assessment for treatment initiation versus continued surveillance for management of prostate cancer.

 

We reported that the activation of RANK and c-Met signaling components in both experimental mouse models and human prostate cancer (PC) specimens predicts bone metastatic potential and PC patient survival. In this study, we tested the hypothesis that a population of metastasis-initiating cells (MICs), known to express stronger RANKL, phosphorylated c-Met (p-c-Met), and neuropilin-1 (NPR1) signaling than bystander or dormant cells (DCs), can be detected in primary PC specimens and that the relative abundance of MICs compared to DCs could predict the survival of PC patients. We employed a multiplexed quantum-dot labeling protocol to detect the co-expression of RANK and c-Met signaling components at the single cell level. We observed PC cells with MIC and DC phenotypes in primary formalin fixed paraffin embedded (FFPE) PC tissue specimens and the relative abundance of MICs compared to DCs in primary PC correlated with PC patient survival.

 

Publication:
Li, Qin, Li, Qua, Nuccio, J., Liu, C., Duan, P., Wang, R., Jones, L.W., Chung, L.W.K., Zhau, H.E. Metastasis Initiating Cells in Primary Prostate Cancer Tissues From Transurethral Resection of the Prostate (TURP) Predicts Castration-Resistant Progression and Survival of Prostate Cancer Patients. Prostate. 10.1002/pros 23011 (2015). PMID 25990623