Period from 1/2016 through 6/2016

The group held conference calls on 2/19, 4/15, and 5/27.

Feb. 19. In the February call a case where both a mother and her daughter had contracted PMP was discussed. This case was unusual since PMP is not considered to be an hereditary disease. It was decided that these two patients should be included in AGP study to see if there was any difference in their gut microbiomes. Our group also discussed how we could involve more PMP surgery centers to participate in our research by sending specimens to us for analysis. Dr. Laura Lambert from UMASS had already agreed to participate and she sent specimens from 10 patients. Chris Piekarski, who is President of the PMP Pals support group, volunteered to help with recruiting additional surgeons.

April 15. In November 2015 we submitted a major proposal to NIH to fund our research. In March, 2016 we got the results of the NIH review. Unfortunately our proposal was not recommended for funding, but it was scored which was a good sign. During the April conference call the group discussed the NIH referees’ comments in detail. The referees felt that our PMP model justification was good but the overall proposal was too ambitious. The referees were not enthusiastic about the metabolomics part of the proposal. Our group discussed cutting down the proposal aims from 4 to 3.  The referees also felt that the proposal needed to address more fundamental issues such as pathways and etiology. It was decided that we rewrite the proposal to answer the referees’ criticisms and resubmit the proposal. After the April conference call Dr. Merrell talked with Phil Daschner of NIH. Phil had sat in on the panel review of our proposal and we wanted to get his feedback. Drs. Merrell, Metcalf, and Testerman then held a conference call about how to respond to the referees and Phil Daschner’s comments and how to edit the NIH proposal for resubmission in November, 2016.  Phil Daschner suggested that the annual budget be cut to about $300k/year and that the original proposal was too ambitious.

May 27. During the May conference call Dr. Merrell mentioned that his new postdoc Faith Blum had completed an inventory of PMP specimens available at USUHS. Prior to the conference call he emailed the group a spreadsheet giving the inventory. Dr. Merrell asked the group for suggestions on how to proceed with microbiome sequencing the available samples since all 592 samples cannot be sequenced; about 100 samples will be used for sequencing. Dr. Merrell would like to choose samples wisely for the next sequencing round. Of the 100 samples to be sequenced 10 will be reserved for the UMASS specimens from Dr. Lambert. The specimens from the mother daughter pair discussed above will be included in the 90 remaining specimens to be sequenced. USUHS had samples from 15 patients who had more than 1 PMP surgery. The group thought that it would be interesting to compare sequencing results for some of these 15 patients to see if changes occurred between their surgeries. Dr. Testerman suggested that looking at how patients did long term and comparing microbiomes between patients who did well and those who did not could yield useful information. The group also felt that it would also be interesting to sequence samples for DPAM patients and compare results to PMCA patients.

As of the end of May 16 patients had been recruited into the new pre- and post-operative antibiotics protocol at Mercy Medical. Two of these patients had not yet had surgery. Seven of the remaining 14 patients had undergone both the pre- and post-operative antibiotics courses.

Period from 7/2016 through 12/2016

The group held conference calls on 7/8, 9/9, 10/14 and 12/2.

July 8. In July Dr. Merrell informed the group that he had received an email from Dr. Pocard of INSERM, in Paris. Dr. Marc Pocard is the Head of the Digestive and Cancer Surgical Unit, and has developed an animal model for PMP.  Dr. Picard read our microbiome paper and emailed Dr. Merrell about potential collaboration. Dr. Pocard will be in Washington D.C. in November for the 10th International Congress on Peritoneal Surface Malignancies and Dr. Merrell indicated the he could meet in person then.

Sept. 9. In September Dr. McAvoy mentioned that he had scheduled a conference call in mid-August among Drs. Testerman, Merrell, Metcalf and himself. The goal of the call was to discuss how the NIH proposal could be revised and to develop a timeline for rewriting it. During the call it was agreed to set Sept. 15 as a date for rewriting the Aims and sub-Aims for the proposal. The number of Aims will be cut down to 3 from 4 following the referees’ suggestion that the original proposal was too ambitious. Dr. Merrell mentioned that the re-submission date is Nov. 4. Drs. Testerman, Merrell, and Metcalf will work on revising and rewriting the original proposal along the lines discussed in the August conference call.

In September Dr. Testerman reported that she has gotten her animal protocol approved. She has been in contact with NCI about obtaining immune-deficient mice. They will donate 20 mice to her, which she can use for her PMP studies. She will be able to purchase additional mice in the future at an approximately 40% discount (~$60/mouse). Her student is currently working on cell lines that can be transplanted into the mice to study tumor growth.  Dr. Testerman has also been continuing her culturing work on PMP tumors and some of the cells she has cultured have been very slow growing. Growth has taken several months. Dr. Testerman described the cultured cells as being weird and strange. Some of them look similar to what she has seen in PMP tumors.

Oct. 14. In October Dr. Merrell mentioned that he had been in contact with Chris Piekarski about sending out an email seeking additional surgeon involvement in our microbiome research. He said that a positive response was received from Dr. Arias from Columbia, and he would like to contribute specimens to our study. In addition Dr. Abad from Northwestern and Dr. Alexander from the University of Maryland responded.

Dec. 2. Drs. Sardi, Merrell, and McAvoy met with Dr. Pocard on Nov. 17 at the 10th International Congress on Peritoneal Surface Malignancies in Washington, D.C. Dr. Pocard has harvested PMP tumors from PMP patients and has been able to grow them in mice. Once tumors have been grown they have been transplanted from one mouse to another so that Dr. Pocard now has 8 tumor strains alive, 7 PMCA and 1 DPAM. Dr. Pocard was very enthusiastic about the possibility of collaborating with us on PMP research. He volunteered to send tumor specimens from patients and mice to Dr. Merrell to see if the bacteria in each are the same. Dr. Merrell is working on modifying his PMP IRB protocol at USUHS so that he can accept specimens from Dr. Pocard. He also will need an import permit to have samples shipped to him from France. Dr. Merrell will also modify his protocol so that specimens can be accepted from surgeons contacted by PMP pals who have agreed to submit tumor specimens to him for analysis.

In December Dr. Metcalf reported that the specimens from the mother daughter PMP pair had been set up for AGP sequencing.  A total of 24 PMP patients will have fecal specimens analyzed through the AGP. Twelve of the patients will be taken from those in our antibiotics protocol, and the remaining 12 will be non-antibiotic treated patients. As of December 18 patients had been enrolled in the antibiotics protocol at Mercy Medical.