LITTLE FALLS, N.J., July 15 — A pill that contains an endoscope and two cameras provided good visualization of the colon, but had less sensitivity for detecting lesions than traditional colonoscopy, researchers say.

• Explain that capsule endoscopy provided good images of the colon, although sensitivity was not as good as that of traditional colonoscopy.
• Note, however, that sensitivity of capsule endoscopy increased as colon cleanliness improved.
• Point out that the capsule has not been cleared for sale in the U.S. but is actively marketed in Europe and sold for $1,150.

Sensitivity and specificity for detecting polyps that were 6 mm or larger were 64% and 84%, respectively, with capsule endoscopy, Andre Van Gossum, MD, of University Libre de Bruxelles in Belgium, and colleagues reported in the July 16 issue of the New England Journal of Medicine.

However, the sensitivity of the pill camera increased with the cleanliness of the colon, the researchers said.

“Efforts should be made,” they said, “to improve the colon-preparation regimen for capsule endoscopy.”

There’s a need for a less invasive method of detecting lesions in the colon, the researchers said, especially one that would complement colonoscopy for those who’ve had an incomplete examination.

The PillCam capsule endoscope used in the study is an ingestible pill that consists of an endoscope with a video camera at both ends and measures 31 mm by 11 mm and has been proven safe in pilot studies.

To compare capsule endoscopy with optical colonoscopy, the researchers conducted a prospective, multicenter study, enrolling 328 patients with known or suspected colonic disease.

Different physicians interpreted the colonoscopy — which was done for comparison — and the capsule endoscopy.

Colon cleanliness was also assessed. Bowel preparation for capsule endoscopy was more extensive than typical colonoscopy because a residual clear liquid is needed to aid the capsule in its travel through the gastrointestinal tract.

So oral sodium phosphate and water were given two hours after ingestion of the pill, with an additional dose in the early afternoon.

The capsule was excreted within 10 hours of ingestion and before the end of the camera’s battery lifetime in 92.8% of patients. Natural excretion was accomplished for all patients within 16 hours of ingestion.

For detecting advanced adenoma, sensitivity and specificity were 73% (95% CI 61 to 83) and 79% (95% CI 77 to 81), respectively.

Of 19 cancers detected by colonoscopy, 14 were also detected by capsule endoscopy (sensitivity 74%, 95% CI 52 to 88).

The researchers said that the sensitivity of capsule endoscopy was significantly higher in patients with good or excellent colon cleanliness than in those with poor or fair cleanliness, although cleanliness had only a limited effect on specificity.

Adverse events occurred in 7.9% of patients and were primarily related to colon preparation. They included abdominal discomfort, nausea, vomiting, and headache, but most were mild-to-moderate and resolved within 48 hours.

The researchers noted that the study sample was not representative of a typical screening population because the patients were known or suspected to have colonic disease.

“This study shows that capsule endoscopy is a safe method of visualizing the colonic mucosa through colon fluids without the need for sedation or insufflation,” they said. “However, the sensitivity of capsule endoscopy for detecting colonic polyps, advanced adenomas, and colorectal cancer was relatively low in comparison with colonoscopy.”

In an accompanying editorial, Michael Bretthauer, MD, PhD, of Oslo University Hospital, said that since the size of colorectal lesions is a predictor of the development of cancer, “the relatively low sensitivity of capsule endoscopy is cause for concern.”

However, he said, “the sensitivity of both colonoscopy and CT colonography are better for the detection of large lesions than small lesions.”

He stated that in light of the sensitivity, the requirement for more extensive bowel-cleansing regimens, and its high cost ($1,150), “colon capsule endoscopy cannot be recommended at this time.”

He noted that detection rates for polyps and cancer are only surrogates for the ability to reduce associated mortality. All three procedures — colonoscopy, CT colonography, and capsule endoscopy — Dr. Bretthauer said, “should be tested in randomized, comparative trials that allow valid and precise quantification of their effect on colorectal cancer incidence and mortality.”

The study was supported by Given Imaging, maker of the PillCam capsules. The authors reported financial relationships with Given Imaging, Norgine, Cook Endoscopy, Merckle Recordati, Boston Scientific, Olympus, Satiety, and Astra Zeneca.

Primary source: New England Journal of Medicine

Source reference:

Van Gossum A, et al “Capsule endoscopy versus colonoscopy for the detection of polyps and cancer” N Engl J Med 2009; 361: 264-70.

HOUSTON, July 15 — Metastasis of pediatric cancers may have its origin in activities related to circulating endothelial progenitor cells, according to investigators who identified the association.

• Explain to patients that higher levels of a type of cell produced in the bone marrow have been associated with metastatic disease in pediatric cancer patients.
• Whether treatment that lowers levels of the cells improves patient outcomes has yet to be studied.

Levels of the cells were significantly higher in children with metastatic cancers compared with those who had localized disease and with healthy controls (P<0.001), French investigators reported in the July 15 issue of Clinical Cancer Research.

The findings provided the first confirmation of preclinical studies showing that circulating endothelial cells and progenitor cells have a pivotal role in the initiation and progression of metastasis.

“This implies that these endothelial cells most likely play a role in the development of cancer in children,” Françoise Farace, PhD, of Institut Gustave Roussy, in Villejuif, said in a statement. “We also observed a large range of cell levels in patients with various tumor types. In some cases, very high levels were observed, which means that their role may be very important.”

The findings could lead to better understanding of the biology of tumor neovascularity in pediatric cancers, she added.

Pediatric cancer patients generally have more favorable outcomes and survival compared with adult cancer patients. However, the prognosis remains grim for pediatric patients with metastatic or relapsed solid malignancies.

Novel approaches to treatment of metastatic/relapsed pediatric cancers have included examination of the role of angiogenesis.

“Although most clinical studies have focused on adult malignancies, antiangiogenesis represents an appealing therapeutic strategy in pediatric oncology, as well,” the authors said.

James L. Abbruzzese, MD, editor of Clinical Cancer Research, said the study might point toward more effective therapeutic strategies for pediatric solid malignancies.

“Understanding these vascular precursor cells and seeing the changes over time may represent a real strategy for helping to identify drugs that might work in the pediatric population,” Dr. Abbruzzese, of the University of Texas M.D. Anderson Cancer Center in Houston, said in a statement.

“Insights as to which patients are likely to develop metastases may help us to identify a subset of patients that require more extensive therapy.”

Tumor neovascularization depends on the availability of mature endothelial cells and on recruitment of mobilized bone marrow-derived endothelial progenitor cells.

Studies have shown that rare circulating bone marrow derived endothelial progenitors contribute to tumor neovascularity in animals and adults with cancer. However, a role for these cells in pediatric cancers had not been demonstrated, the authors said.

Extending the investigation of the role of endothelial cells and progenitors in cancer, investigators drew blood samples from 23 pediatric patients with localized cancer, 22 with metastatic disease, and 20 healthy children.

Subsets of circulating vascular endothelial growth factor receptor (VEGFR) 2⁺-bone marrow-derived progenitor cells were measured in progenitor-enriched fractions by flow cytometry. Levels of circulating mature endothelial cells were measured in whole blood.

Levels of a subset of the bone marrow-derived progenitor cells (known as CD45^-CD34⁺VEGFR2⁺7AAD^-) were significantly elevated in cancer patients compared with the healthy controls (1.5% versus 0.3% of circulating progenitors, P<0.0001).

Moreover, the same subset of progenitor cells was elevated in patients with metastatic disease compared with those who had localized cancer (2.9% versus 0.7%, P<0.001).

Median values for circulating endothelial cells did not differ significantly among the groups.

The authors disclosed no potential conflicts of interest.

Primary source: Clinical Cancer Research

Source reference:

Taylor M, et al “High levels of circulating VEGFR2⁺ bone marrow-derived progenitor cells correlate with metastatic disease in patients with pediatric solid malignancies” Clin Cancer Res. 2009; 15(14): 4561-71.

HOUSTON, July 20 — Retrieving more lymph nodes during colorectal cancer resection does not improve detection of stage III disease or identify more patients with positive nodes, data from a large case series showed.

In fact, the proportion of patients with stage III diagnoses actually tended to decline as the number of lymph nodes retrieved increased, Tina Hieken, MD, of Rush Medical College in Chicago, and colleagues reported in the July issue of Archives of Surgery.

The distribution of N1 and N2 disease also did not change significantly with increased lymph-node retrieval.

“Our data suggest that harvest of at least 12 lymph nodes as a quality or performance measure appears unfounded,” the authors concluded.

• Explain to patients that the study showed no advantages to examining 12 or more lymph nodes in patients with colorectal cancer.

In 1990 participants in the World Congress of Gastroenterology introduced the concept that identification of at least 12 lymph nodes as the minimum acceptable number for patients undergoing resection of colorectal cancer.

Subsequently, other organizations adopted the benchmark, including the American College of Surgeons, the American Society of Clinical Oncology, and several insurers.

However, recent population-based studies have suggested that in a majority of patients with operable colorectal cancer, doctors do not retrieve at least 12 lymph nodes, the authors said.

Studies evaluating the benefits of increased lymph-node retrieval have yielded mixed results, as some studies showed improved detection of metastatic disease and others did not.

Most studies have focused on surgeon-related variables influencing lymph-node retrieval. In a previous study, the authors found that the variability extended beyond surgeon-specific factors and included the individual pathologist, patient age, comorbid illness, and tumor stage and location.

“These findings prompted us to formulate an institutional initiative to increase reported lymph node counts with colorectal cancer resections,” they said.

The current study focused on results of a multidisciplinary approach to increase lymph node counts and to determine the effect on diagnosis of stage III disease or the number of positive nodes per case.

The initiative included a program aimed at increasing institutional awareness of the issues.

Additionally, institutional pathologists modified their approach to lymph node assessment. Pathologists used a formalin-based fat-clearing solution to improve lymph node yield. If fewer than 12 nodes were identified, the blocks were routinely reevaluated.

The study included 701 consecutive colorectal cancer patients, 553 of whom had surgery before the initiative and 148 patients who had surgery after the program began.

The mean lymph-node count increased from 12.8 before the initiative to 17.3 afterward (P<0.001).

The number of resections with at least 12 nodes retrieved increased from 53% to 71.6% (P<0.001).

The proportion of patients with stage III disease tended to decrease from 36.9% prior to the institutional initiative to 32.4% for the later patient group (P=0.31).

Among patients with positive lymph nodes, the distribution of N1 and N2 disease was unchanged (early, 50.5% N1 and 49.5% N2; late, 54.2% N1 and 45.8% N2; P=0.54).

In an invited discussion that followed the article, University of Louisville surgeon Charles Scoggins, MD, said the study demonstrated a phenomenon common to many hospitals.

“When I am not satisfied with the number of nodes reported, I simply call the pathologist and order more nodes,” he said. “Magically, they are able to find more.

“This point serves as the main stratification variable in this paper: they ‘ordered’ more nodes and the pathologists responded. This has not, however, led to stage migration or the distribution of N1 and N2 disease. This is simply an observation and appears not to have affected patient care in any meaningful way.

“In essence, no more patients are eligible for adjuvant chemotherapy because of this change in policy at their hospital.”

Neither the authors nor Dr. Scoggins reported any financial disclosures.

Primary source: Archives of Surgery

Source reference:
Kukreja S et al. “Increased lymph node evaluation with colorectal cancer resection.” Arch Surg. 2009;144(7):612-617.