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Mistletoe for Pancreatic Cancer

Viscum Album is a kind of mistletoe that is native to many European and Asian countries. Members of the mistletoe family have been used as an “alternative” or complementary treatment for any number of maladies including pancreatic cancer (ductal adenocarcinoma of the pancreas). As we have mentioned before, the Pancreatica Blog appreciates alternative therapies for cancer of the pancreas that have been subjected to the scientific method. We like these studies as so many patients who we encounter seem to be interested in alternative or complementary therapy for their pancreatic cancer. It seems like a service to offer up information on ones in which serious study has been undertaken.

Mistletoe has been studied more scientifically for the past two decades for pancreatic cancer.  One of our Pancreatica Science Board members participated in a research study almost twenty years ago that found no substantive survival advantage of mistletoe in pancreatic cancer (yet interestingly, it appeared to demonstrate improved quality of life).  It seems as if it is mostly German researchers who have been exploring this area.

Troger and colleagues from Germany and Serbia published the results of their Phase III study involving 220 patients in the December 2013 issue of the European Journal of Cancer whereby the authors reviewed the effects of a dose escalating subcutaneously given regimen of Viscum album offered to patients with advanced and locally advanced adenocarcinoma of the pancreas VERSUS no antineoplastic therapy given for an evenly randomized control group.

The median overall survival in the mistletoe treated group was 4.8 months, and 2.7 months for the control group (p<0.0001).  There were no adverse side-effects due to the Viscum album noted.

This is intriguing of course. There are potential problems with the study including the Stages mix and selection bias. One cringes a bit that the control group did not receive standard of care chemotherapy. The survival advantage seems fairly small.  But it is a finding – and likely worthy of further inquiry.

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Dale O’Brien, MD

Adding Grade Status to Staging Improves Prognostic Capability in Pancreatic Cancer

The pancreatic cancer surgical (and oncology) team at UCLA developed a new experimental staging method such that the tumor’s grade was added to the standard (TNM) AJCC staging criteria, whereby a high-grade tumor increased the pancreatic cancer stage (ductal adenocarcinoma of the pancreas) to the next higher level than would have been otherwise indicated.

Published in the December issue of the Annals of Surgical Oncology, the study at hand is essentially an attempt at a proof of this concept related to these novel pancreatic cancer stages.  In passing, one might remark that these UCLA researchers must be utilizing Big Data, as many of the team are the same as on another recent intriguing large concept study that the Pancreatica Blog commented on involving prolonged neoadjuvant therapy for pancreatic cancer.

The authors reviewed the records and pathology results of patients who underwent pancreatic cancer resection at UCLA from 1990 until 2006, identifying 256 individuals. These patients’ disease were then re-staged using the new staging schema, and the disease outcomes were examined.

The authors found that low-grade tumors gave about a 13 month median survival advantage as compared to high-grade tumors.  They found that adding grade to the traditional TMN criteria in the staging of pancreatic cancer gave a more precise and discriminatory survival element to the staging system.

The researchers suggest that the addition of tumor grade to the staging of pancreatic cancer be considered.

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Dale O’Brien, MD

DNA Found in Exosomes in Pancreatic Cancer – with Characteristic Mutations !

We recently commented (here) on the interesting properties of exosomes that were explored as possible messengers within the body including saliva in the context specifically of biomarkers in pancreatic cancer (ductal adenocarcinoma of the pancreas) by Wong and dental colleagues at UCLA.

Exosomes are tiny bubble type structures found in most biological fluids that contain proteins and other substances including messenger-RNA. Apart from other functions, exosomes appear to be involved in cell-to-cell communication within the body.  This makes exosomes a promising target for possible use as diagnostic or screening biomarkers for any number of diseases including pancreatic cancer.

The question of whether exosomes carry full DNA has been unknown, though there have been isolated discoveries of mitochondrial and single strand DNA.

Now comes what seems to be a rather important finding by Kalluri and colleagues from MD Anderson Cancer Center in Houston, together with German colleagues in an article E-published on January 7, 2014 in the Journal of Biological Chemistry, the official publication of The American Society for Biochemistry and Molecular Biology. The researchers studied exosomes that were isolated from two pancreatic cancer cell lines, in addition to exosomes from the serum of patients with pancreatic cancer and those of healthy human controls.

They looked for and were able to find large fragments of double-stranded DNA in these exosomes involved in pancreatic cancer. This appears to be a breakthrough.  Additionally, they found that the entire patient DNA was represented in the pancreatic cancer related exosome samples. And further, critically, that the DNA in the exosomes from the serum of patients with pancreatic cancer showed mutations involving two of the most common mutated genes in pancreatic cancer: K-Ras and p53.

This appears to be a rather startling discovery.  It needs replication and further research; these are early days.  But this line of inquiry may represent a key way station on the route to an effective diagnostic and even screening biomarker for pancreatic cancer.

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Dale O’Brien, MD

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