Briefly

Patients with diabetes aren’t any more likely to develop neuropathy in hands and feet when treated with oxaliplatin.

Learn more about  current colorectal cancer prevention and treatment at a Memorial Sloan Kettering CancerSmart workshop on November 12.  NIH has a downloaded booklet on palliative care, and Oncology on Canvas is looking for artwork from cancer patients and their families and caregivers.

Research Reports

• Diabetic patients have no more risk of developing peripheral sensory neuropathy when they are treated with oxaliplatin than do patients without diabetes.  A pooled analysis looked at three studies totalling almost 1,600 patients.  Of those, 135 or 8.5 percent had diabetes.  The percentage of patients without diabetes and with diabetes who developed neuropathy was almost identical for each grade:  45.0%/46.7% (grade 1), 28.6%/26.7% (grade 2), and 13.0%/12.6% (grade 3).   Diabetic patients who had neuropathy before beginning treatment with oxaliplatin were not included in the study.  R. K. Ramanathan reported results from clinical trials for first and second line metastatic colorectal cancer and the adjuvant MOSAIC trial in the Annals of Oncology Advance Access, November 3, 2009.

Other Headlines

• Memorial Sloan Kettering Cancer Center offers An Update on Colorectal Cancer next Thursday, November 12, from 6:00 to 7:30 pm. Oncologist Leonard Saltz, MD,  surgeon José Guillem, MD, MPH,  and radiation oncologist Karyn Goodman, MD will discuss up-to-date information on screening and treatment for colorectal cancer.  Part of MSK’s CancerSmart, the program will be held at the MSKCC Rockefeller Research Laboratories, 430 East 67th Street in New York City.  Call 212-639-3074 for more information.
• The National Institute of Nursing Research has a booklet for patients and families that can be downloaded: Palliative Care: The Relief You Need When You’re Experiencing the Symptoms of Serious Illness. In explaining that palliative care is different from hospice care, the booklet says, “Palliative care is available to you at any time during your illness. remember that you can receive palliative care at the same time you receive treatments that are meant to cure your illness. its availability does not depend upon whether or not your condition can be cured. The goal is to make you as comfortable as possible and improve your quality of life.”
• Oncology on Canvas provides a way for people affected by cancer to express their experiences through art.  The 2010 competition is now open.  Registration must be submitted by June 10, 2010 and artwork completed by June 30, 2010.  Work in watercolor, oil, pastel, photography, acrylic or mixed media is acceptable.  Artists must be someone diagnosed with cancer, or a family member, friend, caregiver or healthcare provider of a person diagnosed with cancer.

A study from Memorial Sloan Kettering recently showed that patients who have stage IV disease, which means spread to other organs, don’t need to undergo surgery immediately. If the tumor does not cause problems such as obstruction or bleeding, patients appear to do better to start with chemotherapy right away without delay because of the surgery.

Over 230 patients were studied with metastatic colon cancer. and the data showed that patients did very well when started with chemotherapy without surgery for the primary tumor. Only 7 percent required surgery for symptoms during chemotherapy.

Usually, in the conventional approach to treating stage IV disease, patients underwent colon surgery immediately following their diagnosis and would typically start chemotherapy treatments three to six weeks later. The rationale for immediate colon resection was to prevent future symptoms and complications from the primary tumor. It was assumed that the majority of colorectal cancers would have little response to chemotherapy.

However we have now more effective and less toxic chemotherapy  which can shrink both colon tumors and the metastases. We need to caution that of course there are individual exceptions and each of these decisions needs to discuss with the surgeons and medical oncologists.

ACG Annual Meeting 2009 Brief Reports

The American College of Gastroenterology held its Annual Scientific Meeting in San Diego from October 23 – 28, 2009 in San Diego.  Research reported during the meeting included how videorecordings of colonoscopy improved quality tests, the effectiveness of a drug that reduces constipation from opiate drugs, and support for guidelines that call for screening colonoscopy beginning at age 40 for people with a family history of colorectal cancer.

Videos Improve Colonoscopy Performance

When endoscopists knew that their colonoscopies were being recorded on video, their overall performance increased significantly.  They spent more time on each exam and average quality judged on a 1 to 5 scale improved from 2.9 to 3.8.

In a quality improvement program, experienced doctors were not told at first that their colonoscopies were being taped, but digital recordings were made of 8 to 10 tests.  After being told they would be recorded another 10 cases were taped. Both sets of “pre” and “post” awareness tapes were randomly shuffled, reviewed and scored by an expert endoscopist who didn’t know which gastroenterologist did the exam or whether the doctor was aware of not of being recorded.

In reporting the study at the ACG meeting, Douglas Rex, MD, FACG, from Indiana University, concluded,

Videorecording of colonoscopy dramatically changed process quality indicators of colonoscopist behavior toward longer examination time and better technique. Systematic videorecording of colonoscopy may support quality performance of colonoscopy.

ACG Abstract 11, Rex et al. Videorecording Impacts Colonoscopy Performance

Experimental Medicine Helps with Opiate-Induced Constipation

In a randomized, placebo-controlled clinical trial, NKTR-118 increased the number of spontaneous bowel movements in patients with constipation caused by opioid pain medicines.  In addition, the time before the first bowel movement was much shorter than with a placebo. Time before a bowel movement for 25 mg NKTR-118 was 6.6 hours compared to 48.6 hours for placebo and  and 2.9 hours for the 50 mg dose compared to 44.9 with placebo.

NKTR-118 blocks opioid receptors in the gut but does not affect receptors in the central nervous system where opiates work to reduce pain.  There were no opiate withdrawal symptoms or lack of pain relief at any point during NKTR use.

Lynn Webster, MD and colleagues concluded,

In conclusion, the results of this study show that oral NKTR-118 is an effective and safe therapy to normalize GI function in patients with opiate-induced constipation without reversing analgesia.

ACG Abstract 26: Webster et al., Efficacy, Safety and Pharmacokinetics of Oral NKTR-118 in Patients with Opioid-Induced Constipation

Screening Finds Polyps in People from 40 to 49 with a Family History of Colon Cancer

Current ACG guidelines call for screening people with a first-degree relative (parents, brothers, sisters) with colorectal cancer to have screening colonoscopies beginning at age 40.  Doctors at the University of Michigan  reviewed colonoscopies done only for screening in their patients from 40 to 49 who had a first-degree relative with colorectal cancer.  They found adenomatous polyps in 1 in 5, and advanced adenomas in 4 out of 100.

There was no significant difference in either polyps or advanced adenomas depending on whether the relative had been diagnosed with colorectal cancer before or after the age of 60.  However, diabetes did have a significant impact on finding polyps.

Dr. Akshay Gupta and team concluded,

Based upon 21.7% prevalence of adenomas and 3.6% prevalence of advanced adenomas, our data supports current guideline recommendations to begin screening colonoscopy at age 40 among individuals with a family history of colorectal cancer.

ACG Abstract 16A: Gupta et al, Prevalence and Risk Factors for Adenomas in 40-49 Year Old Individuals with a Family History of Colon Cancer

For years we have known that alcohol consumption is one of the risk factors in developing colon cancer particular in women. This week an interesting article was published by Dr. Christopher Forsyth from Rush University Medical Center suggesting that if you have colon cancer and you drink alcohol that colon cancer may spread easier.

Alcohol may play a role in the process of transition from the origin of the colon cancer into the surrounding tissue and spread through the blood system. Alcohol seems to turn on signals allowing this way of spreading called EMT (epithelial–to–mesenchymal transition).

Many research groups are working on understanding better how this process works, particularly what tools the tumor cells have to make the different steps successfully from moving from its original space called epithelial to the surrounding tissue called mesenchym, which is the reason the process is called epithelial mesenchymal transition (EMT). If we could understand the exact steps better, we might find treatments to stop the process or even reverse it.

This study published in Alcoholism: Clinical and Experimental Research is the first giving suggestions that our diet may influence that process.

Laboratory tests showed that alcohol activated characteristic of the epithelial-to-mesenchymal transition and demonstrated that the alcohol-treated cells had lost their tight junctions with adjacent cells, a preparation for migrating, as metastatic cells do.

Dr. Regina Benjamin (AP Photo)

The  Senate unanimously confirmed the nomination of Regina Benjamin, MD as Surgeon General of the United States on October 28, 2009.

Dr. Benjamin is the founder and CEO of the Bayou La Batre Rural Health Clinic in Alabama, where she often provides care for the poor at no cost.

She has won a number of awards including a MacArthur Genius award, the Nelson Mandala Award for Health and Human Rights, and the 2000 National Caring Award which was inspired by Mother Teresa.

In 1995 she was elected to the American Medical Association Board of Trustees , the first physician under age 40 and the first African-American woman on the AMA Board.

Sgt. Joshua T. Rose and Iron (Photo by Tina Susman)

Briefly: Pancreatic cancer occurs in about on in five Lynch syndrome families, increasing risk for the cancer substantially.

Colorectal cancer patients whose tumors don’t have EGFR on immunohistochemical testing can still benefit from Erbitux treatment.

Patients learn more and like medical consultations better when doctors sit side-by-side with them to view tests.

Gastroenterologists deployed in Iraq are using their skills to help military working dogs.

Research Reports

• Among families with Lynch syndrome, one in five had at least one person with pancreatic cancer.  Data from 6,342 individuals in 147 families in familial cancer registries at Dana-Farber Cancer Institute in Boston and University of Michigan Comprehensive Cancer Center in Ann Arbor included 47 cases of pancreatic cancer in Lynch families, evenly spread between men and women.  There was a 3.68 percent risk of having pancreatic cancer before age 70, almost nine times the risk in the general population. Fay Kastrinos, MD, MPH and her team reported their study results in the October 28, 2009 issue of the Journal of the American Medical Association.
• Some colorectal cancer patients whose tumors did not express the epidermal growth factor receptor (EGFR) when tested with immunohistochemical staining still responded to treatment with Erbitux© (cetuximab), when given as a single drug (monotherapy). Seven of 85 patients (8.2 percent) had tumors shrink.  For the group, median time to cancer progression was 2.1 months with median overall survival of 10 months.  About 40 percent of patients were alive one year after treatment began.  Study results were similar to other clinical trials of cetuximab monotherapy restricted to patients with EGFR positive tumors.Rafal Wierzbicki and colleagues published their phase II clinical trial results in Investigational New Drugs, online October 15, 2009.

Other Headlines

• When doctors and patients sat side by side at a semicircular table facing a computer screen during a consultation, they shared more information and patients said they were more satisfied with the visit than in a conventional office.  The computer displayed the patient’s electronic medical record, test results, and Internet pages with other health information.  Watch Dr. Victor Montori of the Mayo Clinic who led the randomized Space and Interaction Trial (SIT) discuss the results.
• Gastroenterologists in Iraq are using their skills — and their colonoscopes — to help military working dogs return to duty.  Deployed in Iraq, the doctors removed buttons, tacks, and rocks swallowed by the dogs.  They also stemmed bleeding, found fungal infections, and discovered a large cancer in one dog, who died.  Leon Kundrotas, MD, FACG and Timothy Cassidy, DO presented their work with military dogs in a poster at the American College of Gastroenterology Annual Meeting in San Diego last week.

Disclosure: C3 has accepted funding for projects and educational programs from Bristol-Myers Squibb and ImClone Systems in the form of unrestricted educational grants. C3 has ultimate authority over website content.

People with cancer are at higher risk for complications from both the H1N1 flu and seasonal flu, according to the Centers for Disease Control.

Talk to your doctor before you or your family gets the flu about how you should manage it.  Your oncologist may want you to stay home and not come into the office if you have symptoms or may want to see you when other patients aren’t in the office.

You may also want to avoid emergency rooms when there is a lot of flu in your community.  Discuss how you should handle non-flu medical emergencies or complications from your cancer treatment during the flu season to avoid contact with flu patients.  Your doctor may advise you to call first before going to the hospital or an emergency room.

The CDC has recommendations for what to do if you get sick with the flu.

Patients with severe symptoms should get urgent medical care.  Call your doctor and get medical care right away if you or a family member has one of the emergency warning signs:

• Difficulty breathing or shortness of breath
• Pain or pressure in the chest or abdomen
• Sudden dizziness
• Confusion
• Severe or persistent vomiting

Emergency warning signs in children include:

• Fast breathing or trouble breathing
• Bluish skin color
• Not drinking enough fluids
• Not waking up or not interacting
• Being so irritable that the child does not want to be held
• Flu-like symptoms improve but then return with fever and worse cough
• Fever with a rash

According to the CDC, people with compromised immune systems should not get vaccine that contains live virus such as the nasal spray H1N1 vaccine. Talk to your doctor about getting flu shots with killed virus for both H1N1 and seasonal flu.

People from 25 through 64 years of age with certain chronic medical conditions or a weakened immune system are among those prioritized to receive H1N1 flu shots first.

Dr. Joe Bresee, with CDC’s Influenza Division, describes the symptoms of swine flu and warning signs to look for that indicate the need for urgent medical attention.

Patients who have had one operation to remove lung tumors that have spread from cancer in their colon or rectum can have good outcomes with a second and even third lung surgery.

Surgeons in Seoul, South Korea reviewed outcomes for 202 patients who had surgery to remove a colorectal cancer metastasis in their lungs (pulmonary metastasectomy).

After a median follow-up of 28.9 months, 48 patients had a second lung surgery.  Of those, 28 patients had cancer return in their lungs again, and 10 had a third operation to remove lung tumors.

• For the 48 patients who had a second lung surgery, overall survival at five years was 79 percent, with 49 percent of patients having no sign of cancer at that time.
• For the 10 patients with a third surgery, overall survival five years later was 78 percent.

Writing in the Annals of Oncology, J.S. Park and colleagues concluded,

Repeated resection after initial metastasectomy can be carried out safely and provides long-term survival in patients with recurrent pulmonary metastasis from colorectal cancer. Our findings indicate that close follow-up for the early detection of recurrence and parenchyma-saving resection can improve the results after repeated resection.

SOURCE: Park et al., Annals of Oncology, Advance Access, October 27, 2009.

Despite considerable controversy over the use of Diprivan® (propofol) for endoscopies without an anesthesiologist present, there were few serious problems in almost 650,000 procedures where trained registered nurses administered the sedation under the direction of the doctor performing the exam.

Only 11 patients needed a tube inserted in their throats to help them breathe, and there were 4 deaths, all of them during upper endoscopies in seriously ill patients.  There were no permanent neurological injuries.

Costs for using an anesthesiologist or nurse-anesthetist for all of the studied procedures would have reached nearly $185 million.

The FDA-approved labeling for Ditropan calls for a it to be administered only by “persons trained in the administration of general anesthesia and not involved in the conduct of the surgical/diagnostic procedure.” However, it is increasingly being used during upper endoscopies and colonoscopies when doctors doing the test supervise registered nurses specially trained in giving the drug.

Douglas Rex, MD, FACG and his team reviewed safety information from all  223,656 published cases of endoscopist-directed propofol (EDP).  In addition, they surveyed 28 centers in 17 countries that had prospectively kept records of the use of EDP and its safety and found another 422,424 cases.

In all those cases there were four deaths and no instances of permanent neurological damage.  Eleven patients needed a breathing tube inserted.

The four deaths all occurred during upper endoscopies.  Two were in patients with advanced pancreatic cancer, one patient was severely mentally retarded, and the fourth patient who died had advanced heart disease and a history of substance abuse.  The death rate for all patients in the study was 1 in 161,515 cases.

The research team also reviewed published safety studies for the more common sedation used for endoscopy and found death rates of 1 in 1,000 to 1 in 11,000.  The most recent safety study included  information from 324,737 cases where opioids and benzodiazepines were used for gastrointestinal endoscopy and found 39 deaths or 11 per 100,000, including 28 cardiac deaths.

Using the average cost of an anesthesia specialist to deliver propofol sedation of $286, it would had cost $184,778,880 if specialists had been necessary for all 646,080 procedures.  The researchers estimated that the cost per life year saved would have been over $2.6 million.  Even if the anesthesia specialists had only been used in the most serious cases, the cost per life year saved would have been over half a million dollars.

In addition to the 11 patients who needed a breathing tube, another 489 required an oxygen mask and bag ventilation during their exam.  Mask-bag ventilation was necessary ten times as often during upper endoscopies as colonoscopies.  Only 20 patients needed the mask-bag assistance during a colonoscopy.

Dr. Rex and his colleagues concluded,

In conclusion, EDP is as safe or safer than endoscopist administered opioids and benzodiazepines, based on the available literature. Further, our findings on the safety of endoscopist-administered sedation show that the use of anesthesiologists for sedation for endoscopic procedures is costly.

However, they added,

We recommend that all individuals involved in the administration of propofol sedation receive appropriate training before using propofol.

SOURCE: Rex et al., Gastroenterology, Volume 147, Issue 4, October 2009.

Listen to Dr. Rex describe the study:

One of the questions I often get is if colon cancer has traveled to the liver is it then liver cancer or is it still colon cancer.

The answer is very easy. It is still colon cancer but the consequences of it being in the liver or any other organ are getting more and more important.

The scientists call it the tumor environment. We have known for years from animal experiments that if we take a tumor from its original site and put it into the liver or lung, the tumor changes its sensitivity to drugs significantly not because the tumor changed but because the environment is important  to whether the tumor can grow or even metastasize. Only in recent years have we gained much better understanding about the interactions between the tumor and its environment.

For example, we know that tumor blood vessel formation is induced by the environment. The host of the patient plays an important role in the way tumors can grow and the way the tumor responds to chemotherapy. The tumor can take advantage of the environment for nutrition or blood supply, for example.

It is our job to take advantage of the tumor’s advantage.

What do I mean?  We know, for example, the liver has everything the tumor needs– food and oxygen. One of the driving pathways of growth in the tumor is the EGFR pathway. In the clinic we have seen when Erbitux is combined with chemotherapy there is a higher response rates for tumors in the liver than tumors outside the liver.

Patients with liver- limited disease are being looked at to be able to convert them to resectability and a chance of cure.  Particularly in these patients we need to get the treatment right because it can make a difference between death and life. We are seeing an increasing number of patients who present with metastatic disease in liver and lung which we were able to cure.

We will do even better in the future because of new, more effective drugs, but we will also know what drugs are more likely to work. All our new trials use drugs which are targeted to specific markers present only in the tumor. We need to test tumors to see if this specific marker is in the tumor to be treated.

It is an exciting time for new treatments and hopefully curing more and more patients with metastatic disease.