DDW 2016: Stem Cells Help Heal Perianal Fistulas, Increasing Rates of Colorectal Cancer in Younger Individuals, and Agents Effective Against HCV Genotypes 1–6

Researchers reported important findings on a variety of gastrointestinal and hepatic disorders at Digestive Disease Week in San Diego.

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– A small, phase 1 study reported that a bioprosthesis plug soaked in autologous mesenchymal stem cells helped heal refractory perianal fistulas that commonly occur in patients with Crohn’s disease.

Amy Lightner (Mayo Clinic, Rochester, MN) reported that in 11 patients who received the plug, 9 achieved complete healing that lasted at least 1 year. According to MedPage Today, the 2 patients who had not achieved complete healing should be considered as patients with slower-healing fistulas.

In the trial, mesenchymal stem cells were collected from the patients’ own adipose tissue and expanded. A plug is soaked in the cells was then sutured in place at the fistula. Lightner explained that the cells then incorporated into the patients’ tissue.

MedPage Today reported that all 11 patients with Crohn’s disease (4 women and 7 men) had the fistulas for an average of more than 4 years and had, on average, 7 prior surgeries.

There are various surgical treatments for perianal fistulas, but these reduce quality of life.

Complete cessation of drainage and characteristics of healed fistulas were defined by serial magnetic resonance imaging. Lightner said that after 2 to 4 weeks, patients say they have improvement in their condition.

Placement of the stem cell-coated fistula plug was not associated with adverse events and there were no findings of plug migration. To date, there have been no fistula recurrences in these patients, said MedPage Today.

Lightner cautioned that these are findings from a small study population. In addition, this is an expensive procedure and not ready for prime-time.

“It is very fair to characterize this as promising,” said Neil Hyman (University of Chicago) told MedPage Today. But he noted that surgeons who treat perianal fistulas are skeptical of new procedures because others have failed in the past.

“In previous studies using these types of techniques, the outcomes have been plagued by recurrence,” he said. “We really don’t know all the mechanisms of how this works, and therefore we don’t know the optimal way to apply these stem cells.”

-Rates of colorectal cancer are increasing among individuals younger than 50, Elie Sutton (Mount Sinai West Hospital in New York City) reported (abstract Tu1812) from an analysis of the National Cancer Database.

Sutton et all found that from 2004 through 2013, the number of young-onset cases of colorectal cancer increased by 11.4%—an average increase of approximately 1.28%, or 136 new cases, each year.

MedPage Today explained that, in contrast, the number of cases during that time period in patients over 50 decreased by 2.5%.

“The healthcare system has done a great deal to address colorectal cancer, with heightened patient awareness and increased screening, which have contributed to the overall decline in colorectal cancer diagnoses in recent years. However, these efforts have focused on people who are over 50,” Sutton said.

The researchers analyzed 1,010,530 cases of colorectal cancer (70.5% in the colon, 20.9% in the rectum, and 7.6% considered recto-sigmoid).

Patients under 50 years also had a higher incidence of more advanced cancers than older patients. In the young-onset group, 30.6% were stage 3 at the time of diagnosis compared with 25.1% in the older group, whereas stage 4 cancer was found in 25.6% of younger patients compared with 18.2% of older patients. Liver metastases were more prevalent in the young-onset group (19.4% vs 13.8% in the older group).

MedPage Today reported that hospitalization and survival rates also differed between the young-onset and older-onset patients. A total of 56.6% of the younger-onset group were discharged within 5 days compared with 43.3% of the older-onset group. The 30-day mortality rates were 0.6% for older vs 3.5% for younger patients, and 90-day mortality values were 1.6% vs 6.4%.

MedPage Today explained that studies of colorectal cancer conducted about 5 years made similar observations about young-onset colorectal cancer, which means that we still have not adequately addressed the risk of young-onset colorectal cancer. “It’s critical that we reverse this trend so that we are able to reduce, and hopefully eliminate it in all populations, regardless of age,” Sutton said.

Sutton is not sure why more colorectal cancers are being detected in younger patients. “I don’t know if anybody knows,” he told Medpage Today. He said that it might be associated with the increasing incidence of inflammatory bowel disease.

He also noted that a possible explanation for these young-onset cancers being detected at later stages is the delay in diagnosis. This could be because when a patient younger than age 50 presents with a change in bowel habits or rectal bleeding, the first instinct of the clinician isn’t to run and do a colonoscopy, Sutton said.

-A combination of 2 investigative agents produces sustained viral responses 12 weeks after treatment (SVR12) in patients infected with hepatitis C virus (HCV) genotypes 1–6, researchers reported.

MedPage Today reported no cases of virologic failure among patients infected with HCV genotypes 1, 2, or 3 and cirrhosis who were given an 8 week course of ABT-493 plus ABT-530, or among patients with HCV genotypes 4, 5, or 6 who were given a 12 week course.

The only patients in all the studies who did not achieve SVR12s were those who did not complete their regimens. None of these patients, however, had quantifiable levels of circulating HCV at the time they left the study.

ABT-493 is an NS3/4A protease inhibitor and ABT-530 is an NS5a inhibitor. The regimens did not contain ribavirin or interferon.

In one study (abstract 752), treatment-naïve patients with HCV genotypes 1 or 2 without cirrhosis or those who had not responded to treatment with pegylated interferon and ribavirin received once-daily ABT-493 (300 mg) and ABT-530 (120 mg) for 8 weeks.

Tarek I. Hassanein reported that in 34 patients diagnosed with HCV genotype 1, 33 patients achieved an SVR12 after 8 weeks of treatment with the agents. In the modified intention-to-treat protocol, 33 of 33 patients achieved SVR12.

Of the 54 patients with HCV genotype 2, 53 achieved an SVR12 after 8 weeks of treatment, and all the patients in the modified intention-to-treat protocol achieved SVR12s.

In a separate study (abstract 753), treatment-naïve patients with HCV genotype 3 infection without cirrhosis were given once-daily ABT-493 (300 mg) and ABT-530 (120 mg) for 8 weeks.

David Wyles reported that of the 29 patients, 28 achieved an SVR12 after 8 weeks of treatment. In the modified intention-to-treat protocol, all patients achieved SVR12.

In a study (abstract 755) of treatment-naïve or pegylated interferon/ribavirin treatment-experienced patients with HCV genotypes 4, 5, or 6, the participants were given once-daily ABT-493 (300 mg) and ABT-530 (120 mg) for 12 weeks.

All 11 patients with HCV genotype 4 achieved an SVR12 after a 12-week treatment regimen, Hassanein reported. One patient with HCV genotype 5 achieved an SVR12 after the 12 week regimen, and all 22 patients with HCV genotype 6 achieved an SVR12 after the 12 week regimen, he said.

Phase 3 studies are evaluating ABT-493 and ABT-530 in patients with and without cirrhosis, infected with all 6 major HCV genotypes, including 8 week duration treatments,” Hassanein said. Wyles and Hassanein reported few adverse events.

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