Color this finding: curious (and consequently interesting).
Chinese researchers in Shanghai including Yu and colleagues at Fudan University published recent research findings in the December 2013 issue of the Journal of Gastrointestinal Surgery, the official periodical of the Society for Surgery of the Alimentary Tract. They reviewed the results of a number of potential serum tumor markers in 212 patients with confirmed pancreatic cancer (ductal adenocarcinoma of the pancreas).
The aim of the work was to establish which marker could be of best use in predicting which patients were found at an early enough stage of pancreatic cancer to be potentially eligible for surgery. The markers under study included alpha-fetoprotein (AFP), carcinoembryonic antigen CEA), CA19-9, CA50, CA125, CA242, and CA724.
Based on past work one might have predicted the superior marker to be CA 19-9. But in fact, CA125 (often elevated in ovarian cancer) proved superior for this specific task. The selected cut-off value was 19/7 U/mL, which gave a respectable Receiver Operating Characteristic (ROC) area of 0.81. (The ROC area of CA 19-9 with a cut-off of 289.4 U/mL was only 0.66).
We are not sure where to go with this result. But a first step would be to substantiate it. One might imagine that perhaps as a part of a panel – this could potentially be useful. It would be interesting to see how CA125 tracks with early and advanced stages of pancreatic cancer.
Dale O’Brien, MD
However counterintuitive, the association between saliva and the dental environment AND pancreatic cancer (ductal adenocarcinoma of the pancreas) continues to garner highly interesting research. One team lead by David T. Wong and colleagues at the Dental Research Institute of the UCLA School of Dentistry in Los Angeles, California first came to our attention per the Pancreatica blog on 6/23 of this year for a 2010 article in the journal Gastroenterology laying the basis for salivary biomarkers for cancer of the pancreas, and later for a 2012 article in the journal Gut postulating specific oral bacteria as associated with pancreatic cancer.
This UCLA team has now published an article in the September 13, 2013 issue of the Journal of Biological Chemistry that lays an intriguing and perhaps even likely possible predicate for the mechanism by which salivary fluid may be specifically affected by such apparently distal and unrelated diseases such as pancreatic cancer.
Before presenting the results of their research, we should discuss the concept of exosomes. Identified in the late 1980s, these are tiny (30 to 100 nanometers in diameter) durable vesicles or bubble-like structures that are found in most biological fluids. They have been found to contain proteins and other substances including messenger-RNA. In an over-simplistic statement, these structures appear to facilitate or at least affect such processes such as cell-to-cell communication throughout the body, coagulation, waste management, tumor invasion, and the immune response. The origin of exosomes is from within cells – and then in some cases, the plasma cell wall releases an exosome to extracellular space within which it can travel.
Wong and his fellow researchers in this present work, studied the role of exosomes that derived from pancreatic cancer tissue – and evaluated their presence and possible function in saliva in a mouse model. They developed a mouse that gave specific biomarkers for pancreatic cancer by implanting a pancreatic cancer cell line into the animal’s pancreas – and then identifying a selective panel of biomarkers and thereupon testing for these markers in the saliva of those mice with pancreatic cancer (which were found) as compared to those without (not found). Almost all of the components of this panel of seven gene-derived transcriptomic biomarkers were found in the affected mice tumor, serum, saliva, and exosomes.
Then the researchers used a modified tumor line that tended to suppress exosome production from the pancreatic cancer tissue. They then again looked at these mice tissues and found that almost none of the components of the seven biomarker panel were found in the saliva of these affected mice. This allowed the researchers to cautiously postulate a working theory that tumor-derived exosomes may be central to the pathway that establishes salivary biomarkers that appear to be specific for (in this case) pancreatic cancer. The authors call for further research to more fully explicate the precise course of the pathways in this process.
And we could ask for nothing more as a follow-on to this growing body of evidence from this clearly talented research team.
Dale O’Brien, MD
The move away from surgical diagnosis to radiographic criteria in many and now even most efforts at the staging of pancreatic cancer (ductal adenocarcinoma of the pancreas) carries a number of somewhat unspoken but profound consequences, one being efforts to find ways to downstage the diagnosis so as to profitably utilize surgery in locally advanced and borderline resectable pancreatic cancer. We have thus seen the rise of the use of chemotherapy alone or in combination with other modalities in induction neoadjuvant treatment in order to accomplish this.
But this is somewhat new territory. For example, it is not clear what the optimal duration of such neoadjuvant therapy should be. Thus, it comes with great interest that Donahue, Reber and colleagues at UCLA have reviewed their experience in this realm over the past two decades – with a rather startling finding: that prolonged duration of neoadjuvant therapy appears to confer a large benefit in many cases. This work has been published in the February 2014 issue of the journal JAMA Surgery (formerly Archives of Surgery).
The UCLA researchers reviewed patients treated at their institution from 1992 until 2011, identifying 49 patients who were Stage III / locally advanced or who were considered borderline resectable, AND who completed preoperative treatment – with a median duration of 7.1 months. A remarkable 75.5% of these patients were able to later undergo surgery. Most of these patients were lymph node negative at the time of surgery. The median overall survival duration of this studied group was 40.1 months.
Prolonged pre-surgical therapy appears to offer large benefit to select patients. This finding requires further study, but is highly encouraging.
Dale O’Brien, MD