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Lymph Node Surgery for Neuroendocrine Tumors ?

Hawkins and colleagues at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis, Missouri E-published an article on November 19, 2013 in the journal Annals of Surgery  which examined regional lymph node status and the medical disposition of 136 of their patients who had received surgery for pancreatic neuroendocrine tumors from 1994 through 2012.

In this retrospective study the authors found that lymph node metastases were associated with bigger tumors.  They also found increased regional lymph node presence in those tumors that were found in the head of the pancreas (not in the tail, for instance), those with high Ki-67 levels, and those with lymphatic vascular invasion.  But perhaps the key finding was that at a p < 0.0001 level, the median survival was lower for those patients who evidenced lymph node metastases. The median survival duration for those without these metastases was 14.6 years versus 4.5 years for those with metastases.

The researchers conclude that these data suggest that regional lymphadenectomy may be an important additional step for patients with pancreatic neuroendocrine tumors who undergo pancreatic resection.

This research contains the inherent limitations of retrospective studies in general, and the primary conclusion (that lyphadenectomy may significantly prolong survival) does not necessarily strictly translate.  Nevertheless, it is an interesting finding that may well be true.  Thus, it is deserving of further inquiry  – including perhaps a prospective study.


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Dale O’Brien, MD

Plerixafor Inhibits Chemokine Ligand 12 (of CXCR4): Biological Therapy in Pancreatic Cancer

The physical size of the structural aspect of pancreatic cancer (ductal adenocarcinoma of the pancreas) can be misleading as perhaps 90% of the tumor bulk is actually the somewhat inert – and not completely understood – stromal tissue that the “surrounds” the malignant aspect of pancreatic cancer. One practical effect of the stromal tissue is that it may physically, through mediating immunosuppression, and otherwise tend to block the effects of standard treatment modalities – including immunotherapy.

Researcher Fearon and colleagues from Cambridge University UK recently published findings in the December 10, 2013 issue of the Proceedings of
the National Academy of Sciences of the United States of America
detailing their work in attempting to account for and defeat the effects
of the tumor-protective stromal tissue utilizing a mouse model in the experimental treatment of pancreatic cancer.

The authors employed the immune-stimulant drug-agent plerixafor (also known as AMD3100) that is in use in the U.S. for such matters as stem
cell transplantation, and the treatment of AIDS (past usage), lymphoma and multiple myeloma. Typically, the combination of G-CSF and plerixafor
increases stem cell mobilization in peripheral blood. Also, as another aspect of its mechanisms of action, plerixafor in the immune system is a
partial antagonist of ligand 12 of the alpha chemokine receptor CXCR4 that depletes the stroma-supporting carcinoma-associated fibroblasts
that express fibroblast activation protein.

On administering plerixafor, the researchers were able to determine that the agent greatly diminished the mouse pancreatic cancer cells and
rapidly increased local T-cell accumulation. Further and importantly, the authors through this study have given credence to the gate-keeper
aspect that carcinoma-associated fibroblasts may be exerting through stroma – that tends to defeat standard therapy in pancreatic cancer (and
other adenocarcinomas). By teasing out the mechanism of this process, the authors are moving us closer to improved treatment options for
pancreatic cancer.

This is highly interesting early work that is deserving of confirmation and more complete explication.

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Dale O’Brien, MD

Do Women Respond More Favorably Than Men to the FOLFIRINOX Regimen in Advanced Pancreatic Cancer ?

We have come across an interesting recent finding from researchers in Austria.

Greil and colleagues from the Paracelsus Medical University in Salzburg, have published the results of their work in the January 2014 issue of the International Journal of Oncology. These findings appear to suggest that the female gender may be a predictor of a positive response to the four-drug regimen known as FOLFIRINOX in the treatment of advanced pancreatic cancer (ductal adenocarcinoma of the pancreas).

The researchers undertook a retrospective analysis of 49 patients with unresectable cancer of the pancreas who were treated with FOLFIRINOX.  This included 24 females and 25 males. Although the overall median survival duration of women in this study was not found to be significantly different than the men (15 months vs. 12 months) the women’s progression-free survival, response rates and disease control rates in pancreatic cancer were significantly improved over their male counterparts.  This was a surprising finding.

The demographics of the females appeared fairly well matched compared that of the males, although the women showed higher levels of CA 19-9, CEA, Ki-67 and mutated p53 cells.  Also perhaps significantly, the women demonstrated more stage 3 tumors and many less stage 4 then the men.   Finally, the authors point to the increased number of non-metastatic locally advanced tumors in the male patients versus the females (6 vs. 0) with the idea that these may have nullified the advantage conferred by women having a higher response rate.

Still, this is an intriguing result worthy of further inquiry.

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Dale O’Brien, MD

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