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Bacterial Involvement in Pseudomyxoma Peritonei?

Bacterial Involvement in Pseudomyxoma Peritonei?

on Sep 24, 2016

PMP Pals is always amazed at how families support PMP patients in their time of need, and how they often remain engaged in our tight-knit community. This blog explores the exciting work being done by some of those people, like the Microbiome Team determining the role bacteria plays in the development of PMP, and how antibiotics might play a role in its treatment.

This story begins in 2003 when Professor Thomas McAvoy’s wife Jesse was diagnosed with PMP. Their search for the right diagnosis and treatment eventually brought them to Dr. Armando Sardi, who has treated PMP since 1994, and Dr. Andre Dubois, who did research on infectious and gastrointestinal diseases. Thus began the formation of a team testing a hunch that bacteria play a role in PMP.

Through Dr. McAvoy’s persistence the team has grown to include Microbiologists Dr. Traci Testerman and Dr. Scott Merrell, as well as Biologist (and PMP patient caregiver) Dr. Jessica Metcalf. PMP Pals has been proud to partner with the ACPMP Research Foundation and engage Dr. Laura Lambert, Dr. Edward Levine and others in our clinical community to advance this research.

Although Jesse McAvoy succumbed to PMP in 2004, we’re grateful for the work the Microbiome Team continues to deliver, and the potential advancement it offers for the treatment of PMP. To read more about the humble beginnings of this research and the McAvoys’ journey, we encourage you to read Jesse’s Miracle, which you can purchase here: www.pmpcure.org/product/jessies-miracle-book.

Bacterial Involvement in Pseudomyxoma Peritonei

by Dr. Thomas McAvoy

bacteria cancerStarting in 2004 Dr. Armando Sardi, Dr. Andre Dubois, and I began collaborative research on my hypothesis that bacteria might be involved in PMP. This research has resulted in several papers 1-4, and is ongoing.  This article summarizes key results of our research. Paper1 was published in 2008 and it is dedicated to my wife, Jessie, who passed away from PMP in 2004.  In paper1 we noted that H. pylori, a bacterium that can cause stomach cancer and other bacteria were found in PMP tumors. We hypothesized that pre- and post-op­erative antibiotic treatment may enhance the efficacy of cytoreductive surgery with HIPEC. A single blind study was initiated in 2007 to explore antibiotic co-treatment. The study continued until 2009, at which time the IRB raised questions about why we were not conducting a double blind study with ½ of patients given a placebo.  Due to the difficulty of setting up such a study it was decided not to resubmit a revised protocol. Our antibiotic pilot project was stopped after 21 patients had been treated, but it was reactivated by Dr. Sardi in February, 2015.

In 2009 Doctor Dubois and his lab director, Dr. Semino Mora, expanded our research to study the β-catenin protein. Normally β-catenin resides in cell membranes and it helps cells adhere to one another. When β-catenin migrates inside cells it is easier for cells to metastasize, and increased levels of intracellular β-catenin are an indicator of cancer.  The β-catenin study compared 14 antibiotic treated patients to 34 not receiving antibiotics, and it also included a comparison of bacterial densities in tumors from these two groups2. Bacteria, including H. pylori, were detected in 83% of PMP tumors. PMCA patients treated with antibiotics had a significantly lower bacterial density and decreased β-catenin levels inside cells. Conversely, there was a non-significant effect of antibiotics in DPAM patients. Cell membrane β-catenin was significantly increased in both DPAM and PMCA patients receiving antibiotics. This last result indicated that the tendency for metastasis was decreased in the antibiotic patients.

In another paper3 we gave very preliminary, but statistically non-significant results that patient survival  in lymph node negative patients, who constitute over ½ of PMP patients, appears to be enhanced when antibiotics are given pre- and post-operatively. In lymph node positive patients disease has metastasized.  En masse, our data suggest that in addition to cytoreductive surgery with HIPEC, antibiotic treatment of lymph node negative patients may affect the carcinogenic pathway indicated by β-catenin and may serve as a novel co-treatment of PMP.  We have also studied the microbiome of PMP patients3, been able to culture bacteria from tumors4, and are initiating a study through the American Gut Project to assess any differences between the gut microbiomes of PMP patients and those of healthy people. Through our research the link between bacteria and PMP has been established, but whether bacteria cause the disease or take advantage of it, and pre- and post-operative antibiotics help have not yet been determined.

References:

  1. Semino-Mora, C., et al, Ann Surg Oncol 2008 15, 1414-23, 2008. p. 197.
  2. Semino-Mora C, et al, Clin Cancer Res. 2013 Jul 15;19(14):3966-76.
  3. Gilbreath J, et al, Orphanet J Rare Dis. 2013 Jul 12;8:105.
  4. Lo A, et al, genome A. in press 2015.