Oral Microbiota Mouth Off in Cystic Pancreatic Tumors

Article reposted from Genetic Engineering & Biotechnology News March 15, 2019.

Scientists at the Karolinska Institutet report that the presence of oral bacteria in cystic pancreatic tumors is associated with the severity of the tumor. The team, whose study (“Enrichment of oral microbiota in early cystic precursors to invasive pancreatic cancer”) appears in Gut, hopes the results can help to improve the diagnosis and treatment of pancreatic cancer.

“Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic cysts that can progress to invasive pancreatic cancer. Associations between oncogenesis and oral microbiome alterations have been reported. This study aims to investigate a potential intracystic pancreatic microbiome in a pancreatic cystic neoplasm (PCN) surgery patient cohort.

“Paired cyst fluid and plasma were collected at pancreatic surgery from patients with suspected PCN (n=105). Quantitative and qualitative assessment of bacterial DNA by qPCR, PacBio sequencing (n=35), and interleukin (IL)-1β quantification was performed. The data were correlated to diagnosis, lesion severity, and clinical and laboratory profile, including proton-pump inhibitor (PPI) usage and history of invasive endoscopy procedures,” the investigators wrote.

“Intracystic bacterial 16S DNA copy number and IL-1β protein quantity were significantly higher in IPMN with high-grade dysplasia and IPMN with cancer compared with non-IPMN PCNs. Despite high interpersonal variation of intracystic microbiota composition, bacterial network and linear discriminant analysis effect size analyses demonstrated co-occurrence and enrichment of oral bacterial taxa including Fusobacterium nucleatum and Granulicatella adiacens in cyst fluid from IPMN with high-grade dysplasia. The elevated intracystic bacterial DNA is associated with, but not limited to, prior exposure to invasive endoscopic procedures, and is independent from the use of PPI and antibiotics.

“Collectively, these findings warrant further investigation into the role of oral bacteria in cystic precursors to pancreatic cancer and have added values on the etiopathology as well as the management of pancreatic cysts.”

Pancreatic cancer is one of the most lethal cancers in the west. The disease is often discovered late, which means that in most cases the prognosis is poor. But not all pancreatic tumors are cancerous. For instance, there are cystic pancreatic tumors (pancreatic cysts), many of which are benign. A few can, however, become cancerous.

It is currently difficult to differentiate between these tumors. To rule out cancer, many patients therefore undergo surgery, which puts a strain both on the patient and on the healthcare services. Now, however, researchers at Karolinska Institutet have found that the presence of bacteria inside the cystic tumors is linked to how severe the tumor is.

“We find most bacteria at the stage where the cysts are starting to show signs of cancer,” said corresponding author Margaret Sällberg Chen, DDS, PhD, docent and senior lecturer at the department of dental medicine, Karolinska Institutet. “What we hope is that this can be used as a biomarker for the early identification of the cancerous cysts that need to be surgically removed to cure cancer, this will in turn also reduce the amount of unnecessary surgery of benignant tumors. But first, studies will be needed to corroborate our findings.”

The researchers examined the presence of bacterial DNA in fluid from pancreatic cysts in 105 patients and compared the type and severity of the tumors. Doing this they found that the fluid from the cysts with high-grade dysplasia and cancer contained much more bacterial DNA than that from benign cysts.

To identify the bacteria, the researchers sequenced the DNA of 35 of the samples that had high amounts of bacterial DNA. They found large variations in the bacterial composition between different individuals, but also a greater presence of certain oral bacteria in fluid and tissue from cysts with high-grade dysplasia and cancer.

“We were surprised to find oral bacteria in the pancreas, but it wasn’t totally unexpected,” said Sällberg Chen. “The bacteria we identified has already been shown in an earlier, smaller study to be higher in the saliva of patients with pancreatic cancer.”

The results can help to reappraise the role of bacteria in the development of pancreatic cysts, she noted. If further studies show that the bacteria actually affect the pathological process it could lead to new therapeutic strategies using antibacterial agents.

The researchers also studied different factors that could conceivably affect the amount of bacterial DNA in the tumor fluid. They found that the presence of bacterial DNA was higher in patients who had undergone invasive pancreas endoscopy, a procedure that involves the insertion of a flexible tube into the mouth to examine and treat pancreatic conditions thus the possible transfer of oral bacteria into the pancreas.

“The results were not completely unequivocal, so the endoscopy can’t be the whole answer to why the bacteria is there,” Sällberg Chen continued. “But maybe we can reduce the risk of transferring oral bacteria to the pancreas by rinsing the mouth with an antibacterial agent and ensuring good oral hygiene prior to examination. That would be an interesting clinical study.”

After Neoadjuvant Therapy, Imaging No Longer Provides a Clear Answer

The following summary comes the article by Dr. Cristina Ferrone and was published in the International Journal of Radiation Oncology, Biology, Physics. The full article can be found here.

Image credit: Ferrone CR, Marchegiani G, Hong TS, et al. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg. 2015;261(1):12-7.

Patients with a presumed diagnosis of pancreatic cancer are initially evaluated by radiological imaging (Pancreas protocol CT-scan). Imaging provides a great deal of information regarding the tumor including tumor size, involvement of nearby blood vessels and organs, and distant spread of disease. Patients with tumors that involve nearby blood vessels may not be a candidate for a surgery-first approach and have been shown to benefit from upfront chemotherapy followed by potential surgical resection (see October blog post, Outcome of Patients with Borderline Resectable Pancreatic Cancer in the Contemporary Era of Neoadjuvant Chemotherapy for more information on vessel involvement).

Given the improvements in chemotherapy a majority of patients with pancreatic cancer are now managed via a neoadjuvant-first approach even when diagnosed at a resectable stage, given that systemic disease dictates long term outcomes. With this change in practice, a majority of patients initially receive chemo/chemoradiation therapy followed by a repeat scan (re-staging scan), and a potential surgical resection. Recently, it has become evident that post-neoadjuvant CT scans might not provide accurate assessment of disease. At Massachusetts General Hospital in Boston, MA, researchers have theorized that preoperative chemoradiation may cause tumors to appear worse on CT scans than before therapy. With this in mind, this group sought to find patients who received neoadjuvant therapy and had unfavorable imaging after the neoadjuvant therapy, but did have a good performance status and a decrease in pancreatic cancer tumor markers (CA19-9). These patients were taken to the operating room for surgical exploration to evaluate the true extent of disease. Promisingly, 92% of the first 40 patients underwent R0 resection margins, meaning there was no tumor seen at the resection plane (see August blog post, “The Importance of Resection Margin Status in Pancreatic Surgery” for more information on resection margins). What was observed on the CT-scans of these patients was most likely dead tissue with scarring that was mimicking living tumor.

In conclusion, patients with good performance status and decreasing tumor markers after neoadjuvant therapy should be considered for surgical exploration, even if CT scans demonstrate persistent tumor.

A special thanks for this summary by Michael Wright, Department of Surgery, Johns Hopkins School of Medicine and to Dr. Ammar Javed for his support.

FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer

Article reposted from The New England Journal of Medicine, December 20, 2018.

Abstract

BACKGROUND

Among patients with metastatic pancreatic cancer, combination chemotherapy with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) leads to longer overall survival than gemcitabine therapy. We compared the efficacy and safety of a modified FOLFIRINOX regimen with gemcitabine as adjuvant therapy in patients with resected pancreatic cancer.

METHODS

We randomly assigned 493 patients with resected pancreatic ductal adenocarcinoma to receive a modified FOLFIRINOX regimen (oxaliplatin [85 mg per square meter of body-surface area], irinotecan [180 mg per square meter, reduced to 150 mg per square meter after a protocol-specified safety analysis], leucovorin [400 mg per square meter], and fluorouracil [2400 mg per square meter] every 2 weeks) or gemcitabine (1000 mg per square meter on days 1, 8, and 15 every 4 weeks) for 24 weeks. The primary end point was disease-free survival. Secondary end points included overall survival and safety.

RESULTS

At a median follow-up of 33.6 months, the median disease-free survival was 21.6 months in the modified-FOLFIRINOX group and 12.8 months in the gemcitabine group (stratified hazard ratio for cancer-related event, second cancer, or death, 0.58; 95% confidence interval [CI], 0.46 to 0.73; P<0.001). The disease-free survival rate at 3 years was 39.7% in the modified-FOLFIRINOX group and 21.4% in the gemcitabine group. The median overall survival was 54.4 months in the modified-FOLFIRINOX group and 35.0 months in the gemcitabine group (stratified hazard ratio for death, 0.64; 95% CI, 0.48 to 0.86; P=0.003). The overall survival rate at 3 years was 63.4% in the modified-FOLFIRINOX group and 48.6% in the gemcitabine group. Adverse events of grade 3 or 4 occurred in 75.9% of the patients in the modified-FOLFIRINOX group and in 52.9% of those in the gemcitabine group. One patient in the gemcitabine group died from toxic effects (interstitial pneumonitis).

CONCLUSIONS

Adjuvant therapy with a modified FOLFIRINOX regimen led to significantly longer survival than gemcitabine among patients with resected pancreatic cancer, at the expense of a higher incidence of toxic effects. (Funded by R&D Unicancer and others; ClinicalTrials.gov number, NCT01526135; EudraCT number, 2011-002026-52.)

Article by: Thierry Conroy, M.D., Pascal Hammel, M.D., Ph.D., Mohamed Hebbar, M.D., Ph.D., Meher Ben Abdelghani, M.D., Alice C. Wei, M.D., C.M., Jean-Luc Raoul, M.D., Ph.D., Laurence Choné, M.D., Eric Francois, M.D., Pascal Artru, M.D., James J. Biagi, M.D., Thierry Lecomte, M.D., Ph.D., Eric Assenat, M.D., Ph.D., for the Canadian Cancer Trials Group and the Unicancer-GI–PRODIGE Group

An Activist and Survivor Shares Her Story

Lisa Eidelberg has been integral in raising funds for Nikki Mitchell Foundation’s “Country Boots Cancer” show, which is donating 100% of the proceeds to the future Pancreatic Cancer Precision Medicine Program at Johns Hopkins Medicine.

The pancreatic cancer activist and survivor shares her story: 

Lisa and her sons

“Peace Out Johns Hopkins”

Rhonda Miles, Jamey Johnson, Lisa Eidelberg

 

 

 

 

 

 

 

 

I am a very lucky four-year pancreatic cancer survivor!!

This journey began on Saturday June 7, 2014 when I woke up, looked in the mirror and thought, “Mmm, I look a little yellow!”  A friend had stopped by, looked at me and confirmed what I didn’t want to believe; I was indeed yellow!  My husband Marc and I went to the emergency room of a local hospital where I was told I would simply need my gall bladder out, even as I was becoming increasingly yellow! Fortunately, the doctors in my family had me moved to another hospital where I would have an ERCP the next day.  Coming out of anesthesia, Marc had the most difficult task of delivering the bad news……I had pancreatic cancer.  We were all shocked!  I was 54 at the time, healthy, had no family history of it, was active and had two 19-year-old sons who still needed me!  In the four months prior to diagnosis, I had an endoscopy, colonoscopy, two ultrasounds and blood work (just six weeks before diagnosis) which were all normal!

Luckily for me, I got an appointment with Dr. Wolfgang and team at Johns Hopkins Hospital, which I was told was the premiere pancreatic cancer team. Boy is that true!  On Saturday June 14, 2014, I had a successful Whipple surgery.  Recovery was so much more pleasant because of the caring staff at JHH!  Aftercare with this surgery is almost as important as the surgery itself!   Following recovery, I had 10 rounds of Folfirinox and radiation at Overlook Hospital in Summit, NJ where again, I was fortunate to receive compassionate, quality care.

At a post-surgical visit with Dr. Wolfgang and Lindsey Manos, they urged me to reach out to the Nikki Mitchell Foundation founder Rhonda Miles.  Somehow, they got a vibe that I resembled Nikki in spirit and attitude, although we were completely different people in the way we lived our lives.  My attitude was always positive, but I made it my business NOT to read the sad stories of this dreaded disease, so why would I reach out to Rhonda? Nikki had sadly and bravely lost her battle with this demon.  However, I’m so glad I did!  It’s enlightened me to the fact that this disease does not discriminate.  There is no “stereotypical” person who is affected by this many time fatal disease.  It’s brought about a renewed outlook on life and others.  Just as pancreatic cancer doesn’t judge, I don’t either.

It is my privilege to work with both the Nikki Mitchell Foundation and Johns Hopkins Hospital to raise funds for the new Pancreatic Cancer Precision Medicine program which will enhance the patient’s experience.  This will be THE place, for competent, caring, compassionate and cohesive treatment for those afflicted by this ugly disease!

I personally look forward to celebrating many more survival anniversaries but look forward to having a lot more company in the future!!

Donations for this event can be made HERE and select the campaign “Country Boots Cancer.”

How Do We Make a Difference?

We love the fact Nikki Mitchell Foundation has opportunities to plan amazing concerts with big-time talent! You might think we spend all our time producing concerts and an annual golf tournament, right? As our events bring in funds and our revenue grows, so do our expenses. More money coming in means more going out, so more funds mean we are able to increase patient assistance and fund promising research.

On the flip side, sometimes days can be rough in the office.

This week, we took a pancreatic cancer patient client off of our active financial aid roster and moved them to our “closed file.” You can guess what that means…she wasn’t cured, and she fought her disease until she couldn’t fight anymore. This woman was someone we connected with on a personal level, Rhonda spoke with her on the phone and listened to her stories, fears, needs and hopes. She figured out her financial needs and sent her gas and grocery cards, paid co-pays and financed a second opinion at UCLA through our Bridge of Wings program. Rhonda became her cheerleader and supporter.

We then called the first name on our waiting list. The family requested assistance with their mortgage payment. The patient was unable to talk, and his wife was at work, so their 17-year-old son took charge and was organized, thankful, and on top of their needs.

After the first phone call, the realization hit…this teenager should be hanging with his friends, playing sports or just acting like a 17-year-old. Instead, five minutes after hanging up, he emailed us their mortgage information, followed up with a phone call, thanked us and told us to have a blessed day. This kid is having to grow up too fast and take care of things most kids never even think about, like how can house payments be made or what would happen if they lose their home as his dad is suffering from pancreatic cancer.

We keep 40 clients on the active list and 40 times a month, we ask them: what do you need, what can we do to help? As we help our patients and plan our events, we constantly think – what do we do if we run out of funds? What if this event doesn’t bring in enough to support the Bridge of Wings program? The foundation doesn’t just help patients one time and then leave them to figure out finances as their disease worsens. We help these patients every month, as long as they are in need. Forty patients a month is all we are able to financially handle at this time and all we are able to manage with our small office.

How do we do it? How do we make a difference? We do it through YOU, and through our events sponsors, our faithful donors, event attendees and our online auctions. Our mission and goal is bigger than these events, bigger than the foundation, bigger than each individual. It’s about making a difference for this 17-year-old kid who sent his parent’s mortgage information. It’s about helping patients who are fighting this horrific disease. It’s about awareness and finding a cure.

Let’s make the difference in someone’s pancreatic cancer battle and let’s honor Nikki Mitchell while we do this.

Please consider donating today.

Outcomes After Minimally-Invasive Versus Open Pancreatoduodenectomy

 

 

 

The following summary comes from the Annals of Surgery, a leading source of peer-reviewed surgical literature. Original article can be found here.

Outcomes after minimally-invasive versus open pancreatoduodenectomy.

Klompmaker, S., van Hilst, J., Wellner, U.F. et al.

Annals of Surgery, June 2018

The Dutch Pancreatic Cancer Group is a coalition of medical centers in the Netherlands that collaborate and share data to improve the overall quality of care of pancreatic disease. In 2018, this group lead a collaboration of 14 experienced medical centers in Europe to determine the outcomes in patients undergoing Whipple operations with either an open approach or a minimally invasive approach (i.e. laparoscopic or robotic). In this study, patients were matched by similarity to eliminate selection bias. A total of 1,458 patients were included (729 open and 729 minimally invasive).

This study found that there were no differences in the following:
– major postoperative complications
– postoperative mortality
– need for post-operative drain placements
– need for re-operations
– length of hospital stay

Significant differences were found in:
Postoperative pancreatic fistula (leaking fluid from the pancreas where it is reconnected to the small intestine). The authors suggest this may be due to the learning curve associated with this part of the operation. This complication was higher in the minimally invasive group, but no differences were found between laparoscopic vs. robotic.

Additionally, laparoscopic approaches were more likely to be converted to an open procedure as compared to robotic approaches.

In summary, minimally invasive approaches are appropriate choices for the right patients when performed at experienced medical centers. Proper patient selection is the product of multiple factors and should be discussed between the patient and their medical team. As more centers gain experience with minimally invasive surgery, these procedures will most likely become safer and available at more medical centers.

Summary written by Michael Wright

Department of Surgery, Johns Hopkins School of Medicine.

David’s Story

In August of 2017, at age 55, I was diagnosed with pancreatic cancer. Five years earlier my mom passed away from the disease so I knew what lay ahead of me.

When I met with my oncologist he said, “We’re talking cure, not life extension.” My surgeon at Johns Hopkins said, “We got this.” I knew the statistics but after hearing how optimistic my care team was…how could I not be?!

Over the next few months, as I went through the chemo, radiation and all the side effects, I remained absolutely optimistic and positive. I refused to allow negativity, anger or sorrow into my thought process….as these were counter-productive to my desired outcome. Along with a great care team, and just as essential, I had amazing support from my wife, kids and community (near and far), providing me with a lot of comfort.

March 16, 2018 I had my Whipple surgery. Everything went smoothly and as of now I’ve made a rapid recovery. I take great pride in saying that I am a survivor of pancreatic cancer….something too few people get to say.

What has become abundantly clear is that the past is past. The future is not here yet and all we have this moment. I am very much living in the moment and every day find something to appreciate or amaze me.

By, David Sokoloff

Palliative Care: Myths vs. Facts

I just returned from the Pancreas Club 2018 conference in Washington D.C., where I listened to 63 oral abstracts regarding ongoing research. It was a lot to sit through! The final presentation on the second and last day was titled “Utilization of palliative care services among patients with pancreatic cancer.”

I find it ironic that palliative care was recommended to Nikki very near the end of her life and the conference pushed this presentation to the very end as well. Nikki and I spoke many times about the need for palliative care early in a cancer diagnosis. Why not utilize all avenues to strengthen and improve your quality of life and build up a support system? I believe doctors and patients lack education on this extremely important and helpful type of care.

So, what is Palliative Care?  PALLIATIVE CARE IS “NOT” HOSPICE CARE.

Palliative care is specialized medical care for people with serious illness. This type of care is focused on providing relief from the symptoms and stress of a serious illness. The goal is to improve quality of life for both the patient and the family. Palliative care is provided by a specially-trained team of doctors, nurses and other specialists who work together with a patient’s other doctors to provide an extra layer of support. It is appropriate at any age and at any stage in a serious illness, and it can be provided along with curative treatment.

5 Myths and Facts of Palliative Care

  1. Myth: Palliative care hastens death. 
    Fact:
     Palliative care does not hasten death. It provides comfort and the best quality of life from diagnosis of an advanced illness until end of life.
  2. Myth:Palliative care is only for people dying of cancer.
    Fact: Palliative care can benefit patients and their families from the time of diagnosis of any illness that may shorten life.
  3. Myth: Palliative care is only provided in a hospital.
    Fact:Palliative care can be provided wherever the patient lives: home, long-term care facility, hospice or hospital. 
  4. Myth:Taking pain medications in palliative care leads to addiction. 
    Fact: 
    Keeping people comfortable often requires increased doses of pain medication. This is a result of tolerance to medication as the body adjusts, not addiction. 
  5. Myth:Palliative care means my doctor has given up and there is no hope for me.
    Fact: Palliative care ensures the best quality of life for those who have been diagnosed with an advanced illness.

The last myth is a big pet peeve of mine. I have heard people comment, “If your doctor mentions palliative care, then get a new doctor.” They think this means the doctor has given up on them, but this is flat out incorrect. If a doctor recommends palliative care, then you have a progressive doctor seeking to treat the whole person and ultimately, their loved ones. That is the kind of forward-thinking doctor I’d want for myself.

This type of care treats pain, depression, shortness of breath, fatigue, constipation, nausea, loss of appetite, difficulty sleeping, anxiety and any other symptoms that may be causing distress. The doctor will help you gain the strength to carry on with daily life and improve your quality of life.

Nikki’s first visit with her palliative care doctor was amazing! He sat and listened to her for a very long time, asked many questions and listened to her answers. He then formulated a plan specifically for her and gave her the tools she needed to move forward. When she felt better, physically and mentally, she wasn’t a cancer patient, she was just Nikki…

For more information on palliative care, click HERE (scroll to the end) and HERE.

Post by Rhonda Miles

Exosomes may be a key in diagnosing and treating pancreatic cancer

Exosomes, once thought to be only cell waste, play an important role in cell-to-cell communication, and could help treat pancreatic cancer patients or detect pancreatic cancer at an earlier stage.

Read more about these virus-sized molecules here: Q&A: What are exosomes, exactly?

Modifying exosomes to treat tumors

Valerie LeBleu, assistant professor of cancer biology at the University of Texas MD Anderson Cancer Center is leading a team that is working on modifying exosomes to target genes associated with pancreatic cancer, delivering molecules that can destroy tumors. Using the technique in mice, they were able to stop tumor growth and therefore extend life.

Read the full article here: What Was Once Considered Cell Waste Could Now Treat Pancreatic Cancer

Additional articles: Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancerInnovative therapy strategy for pancreatic cancer uses engineered exosomes targeting mutated KRAS gene

Early detection of pancreatic cancer

In addition to treatment, exosomes could detect pancreatic cancer before it becomes untreatable.   Read the article here: Exosomes as a platform for ‘liquid biopsy’ in pancreatic cancer

Cancer Treatment Gift Guide

 

Want to do something for a loved one who’s undergoing chemotherapy but don’t know what to do, what to get, or even what to say? I recently struggled with these questions when a friend who lives out of state told me she has cancer and has been on chemo for the last few months. This is just the beginning for her, as she has multiple surgeries scheduled for when she recovers from the infusions.

I chose get well gifts tailored to combat the effects of chemo and make her more comfortable during the treatment. Since my friend has surgeries after chemo, I hoped some of the items could help in her recovery as well.

Gift ideas:

Robe and slippers – To wear when feeling sick after chemo or surgery. Robes with pockets can hold drains if the patient will have them.

Ginger candies or butterscotch – Both help combat dry mouth as well as the metallic taste chemo leaves in the mouth.

Peppermint tea, nausea drops or queasy pops – Most people are nauseous during and after chemotherapy.

Head scarves, beanies, hat – This one is obvious, but when chemo patients lose their hair, they are frequently cold. A pashmina wrap can double as a headscarf or shoulder wrap.

Ways to pass the time – Treatments can take up to 8 hours and can be very boring sitting in the same room for that long. Items like magazines, audiobooks, crosswords or playing cards can help pass the time and distract the patient. If the person is crafty or hands-on, think about an embroidery kit, knitting supplies or an adult coloring book with markers or colored pencils.

Notebooks and notepads – Many patients get “chemo brain” (see article about that here) and their memories are foggy and they become forgetful. Writing things down will help them remember and give them more control over their daily lives.

Eye mask, earplugs, neck pillow, blanket, socks, slippers – Feel comfortable and for naps in the chemo chair and block out other patients who make them uncomfortable (i.e. snorers).

Unscented lotions – Chemo can lead to dry and itchy skin. Choose unscented lotions and creams, as patients can be sensitive to smells.

What are your thoughts on gifts for cancer patients? We’d love to hear your ideas, so feel free to leave them in the comments section.