Clostridium difficile (c.diff.) is a bacterial infection in the gastrointestinal tract which causes severe diarrhea, fever, and  abdominal pain.  Although c.difficile is often associated with hospitalization,, recent outbreaks have been found in community settings.  Antibiotic use has also been associated with the disease.

Researchers at McGill University in Montreal have found the risk of c.difficile infection is more than three and a half times more likely in people who have been taking heartburn medications known as proton pump inhibitors    There was no increased risk of c.difficile infection among patients treated with a different antacid — an H₂-receptor antagonist.

Patients in the study were located using a primary care data base in the United Kingdom, identifying those who had received a prescription for oral vancomycin as having community-acquired clostridium difficile associated disease (CDAD).  Since CDAD is the only indication for oral vancomycin, this provided a good way to accurately identify community cases of CDAD.

The research team identified 317 cases of community-acquired CDAD between 1994 and 2004 along with 3167 controls close in age and from the same medical practices who had not been hospitalized and had no sign of CDAD.  Patients with CDAD were 3.5 times more likely to be using a proton pump inhbitor drug than the controls.

The strongest association between CDAD and drug treatment was for antibiotic use during the three months prior to diagnosis.  CDAD patients were more than eight times as likely to have been taking an antibiotic.  However, nearly half (45%) of CDAD patients had not been on antibiotic treatment.

There was also an increased risk of CDAD among patients who also had other illnesses including renal failure, cancer, inflammatory bowel disease, and infections that were resistant to multiple antibiotics.

Proton pump inhibitors include brand names Prilosec, Prevacid, Nexium, Protonix, and Aciphex, some of which are available as over-the-counter drugs in the United States.  The H₂-receptor antagonists, which were not associated with CDAD, include brand names such as Tagamet, Pepcid, Zantac, and Axid, which are also available as non-prescription drugs.

Writing in the September 26, 2006 Canadian Medical Association Journal, Dr. Sandra Dial and her colleagues at McGill in Montreal conclude:

Proton pump inhibitor use was associated with an increased risk of community-acquired CDAD, when cases were defined by receipt of prescription for oral vancomycin therapy. Prior antibiotic exposure was also a significant risk factor, but a significant proportion of the patients with community-acquired CDAD had no such exposure.

When colon or rectal cancer has spread to the lungs only, removing them surgically can lead to long-term remissions and, in some cases, cures. Reviewing patients who had lung metastases surgically resected, surgeons in Japan identified four factors that led to a better prognosis.

Favorable factors included:

• Three or fewer tumors in the lung
• No spread to hilar and/or mediastinal lymph nodes
• Lung mets occuring later than original colon or rectal tumor
• Normal carcinoembryonic antigen (CEA) before surgery

The research team studied 58 patients who had surgery for lung metastases.  Overall, the five-year survival rate was 29% with a median survival time of 27 months.  Sixteen patients had all four favorable features and had a five-year survival of 67%, significantly better than patients without the characteristics.  Median survival time for these patients was 86 months.

Thirteen patients had a repeat surgery for lung mets.  They had a five-year survival rate of 37% with a median survival time of 32 months.

The team headed by Rintaro Koga concluded:

The four factors selected in our multivariate analysis appear to be favourable factors for the practical identification of those patients who are most likely to benefit from surgical resection. Repeated pulmonary resection for lung-only recurrence may benefit carefully selected patients.

Koga et. al. Japanese Journal of Clinical Oncology published early online on August 25, 2006.

If current colorectal cancer screening methods were maximized and existing chemotherapy used by all age groups, deaths from colon and rectal cancer in the United States could be reduced by 50% by the year 2020.

Researchers used a microsimulation model (MSCAN-COLON) to simulate the 2000 U.S. population with respect to risk factors for colon and rectal cancer, use of colorectal cancer screening, and treatment use. Using this data, they were able to project deaths from colorectal cancer in the year 2020 under three different scenarios:

• No changes in risk factor prevalence, screening use, and treatment use.
• Contining the trends in the three factors during the period from 1995-2000.
• Risk factors are reduced, screening is increased to 70% of the population, and treatment use is extended to all age groups

The simulation model projected:

• If there is no change, mortality from colorectal cancer will decrease by 17% by 2020.
• If the current 1995-2000 trends continue, mortality will decrease by 36%.
• If risk factors are reduced, screening rates increased, and treatment use expanded, deaths will be reduced by 49%.

The team led by Iris Vogelaar and her colleagues in the Netherlands and at Memorial Sloan Kettering in New York wrote in the October 2006 issue of Cancer:

Currently available interventions for risk-factor modification, screening, and treatment have the potential to reduce CRC mortality by almost 50% by the Year 2020. However, without action now to further increase the uptake of current effective interventions, the reduction in CRC mortality may be only 17%

Vogelaar et. al. Cancer Volume 107, Issue 7 Pages 1624 – 1633

While adding chemotherapy to radiation treatment given before surgery for rectal cancer did not improve overall survival, it did significantly reduce cancer returning locally at the surgical site.

In a clinical trial reported in the September 14, 2006 New England Journal of Medicine researchers randomly assigned rectal cancer patients who were receiving preoperative radiotherapy to:

• preoperative radiotherapy without any chemotherapy
• preoperative radiotherapy with chemotherapy before surgery
• preoperative radiotherapy with chemotherapy after surgery
• preoperative radiotherapy with chemotherapy both before and after surgery

Radiotherapy was delivered over 5 weeks before surgery.  Chemotherapy consisted of cycles of 5FU (fluorouracil) and leucovorin given for 5 days per cycle.  Preoperative chemotherapy was given for two cycles; postoperative chemo treatment was four cycles.

Over 1000 patients with T3 or T4 surgically resectable rectal cancers were entered in the trial.  There was no significant difference in overall survival among the four groups — chemotherapy, whether given before or after surgery or not given at all had no impact on survival at five years.  The combined five-year survival rate was 62.5%.

However, there was a significant difference in cancer returning to the original site in the rectum where it had been removed — local recurrence.  Local recurrence rates for preoperative chemotherapy, postoperative chemotherapy, or both pre-and-postoperative chemo were 8.7%, 9.6%, and 7.6% respectively. For patients who received no chemotherapy in addition to their radiation treatment, local recurrence incidence was 17.1%.

Jean-Francois Bosset M.D. and his colleagues concluded:

In patients with rectal cancer who receive preoperative radiotherapy, adding fluorouracil-based chemotherapy preoperatively or postoperatively has no significant effect on survival. Chemotherapy, regardless of whether it is administered before or after surgery, confers a significant benefit with respect to local control.

Bosset et. al. New England Journal of Medicine, September 14, 2006, Volume 355:1114-1123

 More information about the study is available from Medpage Today.

Dr. John Marshall narrates webcast slide presentation of key colorectal cancer research abstracts which were presented at the June 2006 ASCO meeting in Atlanta.

• Research discussed includes:
• Giving metastatic colorectal cancer patients chemo holidays  or breaks from chemotherapy. 
• Optimal regimen for giving 5FU for first line treatment of metastatic colorectal cancer — infusional, bolus, or oral. 
• Combining all three chemotherapy drugs (FOLFOXIRI vs. FOLFIRI) as first line therapy analyzed for both effectiveness and side effects.
• Erbitux (Cetuximab) combined with chemotherapy for first-line treatment of metastatic colorectal cancer.
• Managing side effects of chemotherapy — neurotoxicity.
• Benefits and toxicity for colorectal cancer treatment for elderly patients.
• Gene expression analysis of risk and benefit for chemotherapy for early stage patients.
• Identifying patients with potentially surgically resectable liver metastases.

While designed as a continuing medical education program for health professionals, Dr. Marshall’s presentation can be understood by lay people interested in colorectal cancer research as well.  Registration is required to view the PowerPoint slides and audio.