Colon Cancer Symptoms

The elderly are not treated as aggressively for colon cancer as younger people, even though clinical trials show that the treatments are equally successful for them, researchers from Rand Corp. and UCLA reported Tuesday. However, there is not yet enough data available to show whether this reduced level of care affects survival, the researchers reported in the Journal of the American Medical Assn. The less aggressive therapy may be the result of a misguided compassion on the part of oncologists, who do not wish to subject older patients to the side effects associated with the most powerful treatments.

Colon and rectal cancer will strike an estimated 147,000 Americans this year, killing nearly 50,000. The most common treatment is surgical removal of the tumor, followed by chemotherapy with a combination of the drugs fluorouracil and leucovorin or levamisole. In clinical trials, those drugs produced a 24% reduction in deaths and a 32% decrease in recurrence among all age categories compared to surgery alone. Adding the more powerful drug oxaliplatin increases survival, but with an accompanying increase in severe side effects, which may include nerve damage at the extremities, anemia and other problems.

But the clinical trials of the cancer drugs have been conducted primarily in homogeneous groups of mostly younger patients, said Dr. Katherine L. Kahn of Rand and UCLA’s Jonsson Comprehensive Cancer Center. The question is how these findings from clinical trials are translated into treatment in the community and, particularly, how they are used on older patients. There are two questions that need to be asked, she said: Can older patients tolerate the therapy and is therapy beneficial? This report answers the first question with a yes.

Kahn and her colleagues studied the medical records of 675 patients with advanced colon cancer who underwent surgery at a cross-section of medical centers across the country from 2003 to 2005. They were monitored for as long as 15 months after their surgery.

Of the 202 patients who were 75 or older, only 101 received chemotherapy, compared with 87% of the 473 younger patients. Among those who did receive chemotherapy, only 14% of those over 75 received oxaliplatin, compared with 44% of younger patients. Among those who received chemotherapy, many did not complete the recommended six months of treatment: 40% of those over 65 had stopped by five months, compared with 25% of younger patients. And about 18% of patients received less than the recommended dosages of the drugs.

“We don’t know if there is a problem with underuse” of chemotherapy, Kahn said. “What we do know is the way doctors have decided to use chemotherapy is somewhat different than what is recommended in trials.” And, perhaps most important, the older patients subjected to chemotherapy did not suffer any more serious side effects than the younger patients.

Because most colon cancer recurrences happen during years two to five after the surgery, she added, the team will not be able to determine whether the chemotherapy was beneficial for another year and a half.

Biological differences may not be to blame for higher rates of colon cancer among African Americans. Instead, new research indicates the problem may be access to health care.

Researchers at the National Cancer Institute studied over 60,000 people who were told by their doctors they should be screened for colorectal cancer. They could not find a difference between blacks and whites when looking at the number of polyps and cancers found. However, African Americans were less likely to actually undergo the test. Such a lack of follow up can lead to a delayed diagnosis and treatment, as well as higher mortality rates.

The reasons for the disparity are unclear, but researchers speculate the costs of the follow up tests and lack of knowledge about cancer prevention could be to blame.

The study was published in the Journal of the National Cancer Institute.

Health researchers in Boston say Hispanics often live in areas where access to screening for colorectal cancer is limited.

Dr. Jennifer Haas, of the Brigham and Women’s Hospital and Harvard Medical School, said in a statement that she and her colleagues found that Hispanics tend to live in counties with less capacity for providing endoscopies than whites and African Americans.

Haas said a person’s use of colorectal screening increase modestly if he or she live in an area where the procedure is offered. She said that it is important that all areas of the country increase their capacity to provide colon cancer screening, and also increase education efforts to inform people of the importance of getting screened.

Haas’ study appears in the online edition of the American Cancer Society journal Cancer.

There is growing evidence that both local and systemic inflammatory responses play an important role in the progression of a variety of solid tumors. Colorectal cancer results from the cumulative effect of sequential genetic alterations, leading to the expression of tumor associated antigens possibly inducing a cellular anti-tumor immune response.

It is well recognized that cytotoxic lymphocytes constitute one of the most important effector mechanisms of anti-tumor-immunity. However, their potential prognostic influence in colorectal cancer remains controversial.

Aim of the study was to examine infiltration of CD3+ and CD8+ lymphocytes in colorectal cancer and their prognostic potential.Two-hundred-fifteen colorectal cancer cases, previously analyzed for microsatellite instability (MSI), were selected for immunohistochemical detection of CD3+, CD8+ infiltration and the expression of granzyme B. Prognostic relevance was assessed by survival analysis.

Results: Strong correlations were found between the infiltration of lymphocytes and several clinicopathological variables.

Survival analysis revealed that intra-epithelial infiltration of CD3+ and CD8+ T lymphocytes and stromal infiltration of CD3+ lymphocytes had a major impact on the patients’overall survival in the univariate analysis, however independent of their association with MSI-status. In addition, it was also demonstrated that there was an important disease specific survival advantage for patients with microsatellite stable (MSS) tumors containing intraepithelial CD8+ tumor infiltrating lymphocytes.

When samples were analyzed for colon cancer and rectal cancer separately, the results of the overall population were confirmed in colon cancer only. When entered into a multiple Cox regression analysis adjusting for other possible important confounding factors, the strong impact of lymphocyte infiltration on overall survival was not maintained.

Only early stage and young age (borderline significant for overall population only) were associated with a better overall survival (early disease with disease-free survival also).

Conclusions: In conclusion our results suggest a role for infiltrating CD3+ and CD8+ T lymphocytes in colorectal cancer whereby tumor infiltration could reflect a general principle of antitumor immunity, irrespective of the MSI-status.

Particular components of inflammasomes – protein complexes needed for generating immune responses to pathogens and cellular damage – lessen the severity of colitis and colitis-associated colon cancer in mice, according to a study published online this week in the Journal of Experimental Medicine.

Compared to healthy humans, patients with ulcerative colitis, a form of inflammatory bowel disease, have a higher risk of developing colorectal cancer. As the inflammasome is typically associated with activation of the immune system, Jenny Ting and co-workers suspected that mice lacking inflammasome components would be more resistant to colitis and associated colorectal cancer.

Unexpectedly, mice lacking some but not all inflammasome components developed more severe colitis and larger tumor burdens in the colon.

Additional work is needed to determine how specific inflammasome components protect against colitis in mice, and whether inflammasomes play similar roles in humans.

Millions of women stopped taking HRT when a Women’s Health Initiative study showed in 2002 that the hormones raised the risk of stroke, heart disease and breast cancer.

But the Women’s Health Initiative had also found that HRT protected against colon cancer. Some studies have also suggested that oral contraceptives might reduce the risk of the disease, while the fact that women are at lower risk of colon cancer than men also hints at a hormonal role in disease risk.

To investigate ties between HRT and colon cancer further, Dr. Millie D. Long of the University of North Carolina at Chapel Hill and her colleagues matched 443 women diagnosed between 2001 and 2006 with distal large bowel cancer (meaning tumors at the far end of the colon and the rectum) to 405 healthy control women. The average age of the study participants was around 63.

Long’s team found that women who had ever used HRT were at half the risk of this type of colon cancer compared to women who’d never used hormone replacement, and the longer a woman was on HRT, the lower the risk.

For example, women who used hormones for less than four years cut their colon cancer risk by about one-quarter; four to eight years of HRT cut risk by a third; nine to 14 years of use halved risk; and 15 years or more of HRT reduced risk by two-thirds. The effects were the same for African-American women and white women.

However, there was no relationship between oral contraceptive use and colon cancer risk, the study team reports in the American Journal of Gastroenterology.

Long-term hormone therapy is no longer recommended for postmenopausal women, Long and her team note, although it is still sometimes prescribed on a short-term basis to help women with menopausal symptoms such as hot flashes. The major drop off in distal large bowel cancer in recent years could have been related to widespread use of HRT, the researchers say.

More research is needed to determine if HRT’s protective effects persist after women stop taking hormones, the researchers add, or whether there might be a “rebound” effect with more pre-cancerous polyps developing after a woman halts HRT.

“It may become important in the future to tailor timing of women’s colorectal screening based on cessation of hormonal therapy,” Long and her colleagues conclude.

SOURCE: The American Journal of Gastroenterology, online March 30, 2010.

Obese people are known to have a higher risk of colon cancer. Now, a new study suggests they may have poorer long-term survival odds than their thinner counterparts if they do develop the disease.

The latest findings, reported in the journal Clinical Cancer Research, suggest that excess weight may particularly affect male survivors’ long-term prognosis.

In a study of nearly 4,400 U.S. adults treated for colon cancer, researchers at the Mayo Clinic in Rochester found that obese patients were one-quarter to one-third more likely to die over the next eight years than their normal-weight counterparts.

The relationship between obesity and survival appeared stronger among men — possibly, the researchers speculate, because men are more likely than women to have their excess body fat concentrated in the belly. Abdominal obesity is particularly linked to hormonal effects that, in theory, could contribute to colon cancer development or the cancer’s aggressiveness.

However, whether and how obesity, per se, affects colon cancer survival remains unclear. The current study points to a relationship between obesity and long-term survival, but does not prove that excess body fat directly affects a patient’s prognosis.

Still, the researchers say the findings suggest that people treated for colon cancer should try to maintain a body mass index lower than 30, the cutoff for obesity. Body mass index, or BMI, is a measure of weight in relation to height.

“People may think, ‘I already have cancer. What difference does my weight make?’ But this study suggests the cancer may behave more aggressively if you’re obese,” lead researcher Dr. Frank A. Sinicrope said in an interview.

Obese adults who’ve been treated for colon cancer can talk with their doctors about the best ways to safely lose weight, according to Sinicrope — though, he noted, it is unclear how receptive patients dealing with cancer may be to the prospect of losing weight.

Sinicrope and his colleagues based their findings on 4,381 U.S. adults who took part in any of seven clinical trials testing a chemotherapy regimen for colon cancer. All had stage II or III cancer, meaning the cancer had spread deeper into the colon wall or to nearby lymph nodes.

After eight years, the researchers found, 42 percent of the patients had died, and 36 percent had seen their cancer recur.

Among the 787 men who were normal-weight at the start of the study, 53 percent were alive eight years later. That compared with 42 percent of men who were very obese — having a BMI of 35 or higher.

When the researchers considered several other factors, including the patients’ age and stage of cancer, very obese men were 35 percent more likely than normal-weight men to die during the study period.

Among women, 61 percent of normal-weight patients were still alive after eight years, versus 55 percent of women who were moderately obese — having a BMI between 30 and 35. Fifty-nine percent of very obese women were still alive after eight years; when other factors were considered, very obese women did not have a significantly higher risk of death than normal-weight women.

Milder obesity, however, was linked to a 24 percent higher risk of death.

In theory, excess body fat could affect colon cancer aggressiveness, according to the researchers. Obesity, particularly abdominal obesity, is associated with higher levels of the hormones insulin and insulin-like growth-factor-1 (IGF-1), which have been shown in lab research to promote the growth and spread of colon cancer cells. Studies have also found that men and women with relatively high IGF-1 levels have a higher risk of developing colon cancer than those with lower levels of the hormone.

It’s not clear why more-severe obesity was not related to survival among women in this study. One possibility, Sinicrope said, is that the relationship is more complex in women owing to the effects of estrogen — which some research suggests is protective against colon cancer.

It’s possible, for instance, that very obese women were more likely to have been on hormone replacement therapy, Sinicrope noted. But the study did not have data on that.

The study also lacked information on patients’ diets and exercise habits — factors that could affect colon cancer prognosis or a person’s risk of death from other causes, like heart disease.

Further studies, the researchers conclude, are needed to show whether and why obesity affects colon cancer prognosis.

In a small study of patients with familial adenomatous polyposis, the free fatty acid form of eicosapentaenoic acid (EPA-FFA) reduced both the size and number of polyps.

“EPA-FFA should be considered for chemoprevention in patients with familial adenomatous polyposis,” and its potential against sporadic colorectal neoplasia should also be investigated, the researchers say.

According to the report in the March 18th Online First issue of Gut by Dr. Mark Hull, from St. James’s University Hospital, Leeds, UK, and his colleagues, eicosapentaenoic acid has shown anti-colorectal cancer activity in vitro and in animals.

To investigate its effects in humans, the authors randomized 55 patients to receive either an enteric-coated formulation of EPA-FFA (2 g/day) or placebo for 6 months. All of the patients had ileorectal anastomoses from previous colectomies. This study focused on changes in the rectal remnant.

On intent-to-treat analysis, EPA-FFA

reduced the number of polyps by an average of 22.4% compared to placebo (p = 0.012), and it reduced the sum of polyp diameters by 29.8% (p = 0.027). The global polyp burden worsened during the study in the placebo group but slightly improved in the EPA-FFA group, the authors report.

The treatment group had a 2.6-fold increase in mucosal EPA levels relative to the placebo group (p = 0.018).

EPA-FFA was comparable to placebo in terms of side effects and was well tolerated, the authors note.

“The selective cyclo-oxygenase-2 inhibitor celecoxib is licensed for use as an adjunct to endoscopic surveillance in familial adenomatous polyposis but has significant cardiovascular toxicity,” the researchers comment, adding, “The effect of EPA-FFA was similar in magnitude to that observed with celecoxib.”

The study was funded by SLA Pharma AG, which markets EPA-FFA capsules with the brand name ALFA.

A Canadian researcher suggests regulating intestinal inflammation may be key to preventing colon cancer
.

Dr. Maya Saleh of McGill University and McGill University Health Centre found the protein Caspase-1 plays a crucial role in inflammation regulation and intestinal tissue repair. However, if Caspase-12 — the protein that blocks Caspase-1– is absent, Saleh and colleagues found the inflammation mechanism caused by Caspase-1 can go out of control.

“If Caspase-1 is not eventually blocked, it could lead to appearance of tumors,” Saleh said in statement. “Our challenge at present is to further our research on the action of Caspases in the immune response and also to see whether they play a role in other types of cancer.”

The study, published in the journal Immunity, opens the door to a more targeted treatment strategy for dealing with inflammation, said Saleh.

Caspase-1 inhibitors were developed in the 1990s but inhibition of Caspase-1 seems to cause an intense inflammatory reaction, Saleh said.

LOUISVILLE, Ky. — Nearly 50,000 Americans died from colorectal cancer last year, yet, doctors say it’s one of the most detectable and, if found early enough, most treatable forms of cancer.

Members of the Kentucky Cancer Program said many people cringe at the idea of getting screened for colon cancer.

As part of National Colorectal Cancer Awareness month, Mayor Jerry Abramson’s wife, Madeline, is helping promote awareness about screening.

“Nobody expects to be told they found cancer,” colon cancer survivor Larry Kendall said.

That’s exactly what Kendall heard after his doctor received the results of his routine colonoscopy.

“They said it was stage one and they just did the surgery. They sectioned out 12 inches of the colon and no other treatments after that,” Kendall said.

“It is curable if it’s found in time, and that’s the sense of urgency we have here today,” Madeline Abramson said.

Abramson joined the Kentucky Cancer Program and a surgeon to talk about all the ways they’re spreading the word about the importance of getting screened, including asking the community to dress in blue on Friday.

“Colorectal screening has a very bad reputation. People are very embarrassed to go. They think it’s going to be a horrible exam, but it really isn’t,” said University of Louisville colorectal surgeon Dr. Susan Calandiuk.

“I’ve had my colonoscopy, and it is something that is not nearly as frightening as people would think that it is and it is a procedure that is very intimating to hear about, but not intimidating to go through. I can say that personally,” Abramson said.

“The actual procedure is nothing. It takes only 20 minutes and you don’t remember it anyway,” Kendall said.

Kendall said since there are no symptoms in the early stages, getting a colonoscopy saved his life.

“If it hadn’t been for the scope, we wouldn’t never known until it was too late,” Kendall said.

As part of Dress in Blue day on Friday to bring awareness to the importance of getting colonoscopies, Panera Bread on Dutchmans Lane will give away free pastry or bagels to anyone wearing blue from 5 a.m. to 9 a.m. The same free deal will be available at Panera Bread downtown on West Market Street from 7 a.m. to 9 a.m. on Friday.

Doctors say nine out of 10 colon cancers may be prevented or cured if detected early.

To learn more about Colon Cancer Awareness Promoted In March, click here.