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Advances in Oncology and Gastroenterology

Advancements in Cancer Surveillance Provide Earlier Diagnoses of GI Malignancies

Early detection and diagnosis of cancer can be critical as it drives treatment decisions and affects survival rates. Advancements in cancer surveillance and treatment--such as probebased confocal laser endomicroscopy (pCLE) and the use of molecular markers--are helping NewYork-Presbyterian Hospital physicians and surgeons to provide early and accurate diagnoses, comprehensive therapeutic interventions, and robust patient care.

The use of pCLE in advanced endoscopy is changing the way Michel Kahaleh, MD, Chief of Endoscopy, NewYork-Presbyterian/Weill Cornell Medical Center, diagnoses and treats malignancies of the digestive tract, specifi cally those located within the pancreatic and bile ducts. pCLE is an innovative tool for in vivo imaging of the gastrointestinal tract. pCLE uses light that is funneled through a confocal opening, which reduces scattered outside light. Because only one spot (ie, the confocal) can be imaged at a time, all other light spots located on either vertical or horizontal planes must be scanned in order to produce dynamic images. A contrast agent (eg, fl uorescein) can be injected to create high-contrast images.

Michel Kahaleh, MD
Michel Kahaleh, MD

pCLE allows real-time evaluations of tissue at the cellular level, so cancerous or precancerous tissue can be quickly identified. After an injection of fluorescein, the area without adequate uptake will appear darker while the normal area will appear lighter, permitting mapping of the duct that is being investigated. Physicians are then able to remove or treat the diseased tissue. "Confocal imaging is basically a live biopsy--you look at the cell itself," said Dr. Kahaleh. The identification of diseased tissue provides the map required for the clinician to offer the appropriate intervention.

Currently, the Center for Advanced Digestive Care at NewYork-Presbyterian/Weill Cornell is one of only a handful of US hospitals that actively uses pCLE technology. In fact, Dr. Kahaleh was one of the fi rst physicians to use this technology and had a primary role in developing the inflammatory criteria by which pCLE images are interpreted. To address the limitations of the Miami classification, Dr. Kahaleh and colleagues developed descriptive criteria for benign inflammatory strictures: vascular congestion, dark granular patterns with scales, thickened reticular structures, and increased space between scales. The new criteria, called the Paris classification, improved the accuracy of pCLE for determining malignant versus benign strictures.

Dr. Kahaleh recently contributed to a key study that compared the feasibility and benefits of real-time pCLE of the pancreatic duct with cytologic and histologic results. In this study, 5 patients with pancreatic ductal disease who underwent endoscopic retrograde cholangiopancreatography and pCLE were analyzed. Realtime confocal images were analyzed based on the Miami classification criteria. The criteria included thick white or dark bands, presence of epithelium or dark clumps, interstitial fluorescein leakage, and vascular congestion.1

A Confocal imaging of a patient with sclerosing cholangitis; and a confocal imaging of an abnormal pancreatic duct lesion.
A) Confocal imaging of a patient with sclerosing cholangitis; and B) confocal imaging of an abnormal pancreatic duct lesion.

The investigators found that in 3 of the cases, thick dark bands or epithelium were present, indicating malignancy, whereas the other 2 cases indicated benign strictures. One patient with thick dark bands subsequently underwent a Whipple procedure, which revealed a main duct intraductal papillary mucinous neoplasm with severe dysplasia. The other 2 patients with thick dark bands were started on a chemotherapy regimen for pancreatic adenocarcinoma.

Overall, the study results showed that pCLE might be an effective tool for diagnosing indeterminate pancreatic duct strictures and for surveying abnormal pancreatic ducts while planning surgical interventions.

This technology expedites the patient's entire experience, combining the initial diagnostic visit with the possibility for immediate treatment or removal of the diseased tissue. pCLE can be used in the pancreatic duct as well as the bile duct, esophagus, rectum, colon, and stomach. It also can provide more incentives to the surgeon to resect a suspicious lesion and provides the oncologist with more data to start chemotherapy.

pCLE provides real-time histology and may be effective for detecting and classifying biliary and pancreatic strictures. The pCLE device is small enough to access the small biliary tree and durable enough to withstand precise placement or adjustments to the probe tip. In terms of biliary imaging, the probe is maneuvered through a side-viewing endoscope and into the biliary tree using a rotatable catheter or cholangioscope.

At the Center for Advanced Digestive Care, cutting-edge technology like the pCLE is combined with patient-centric care. The use of innovative tools and collaborations between the medical and surgical teams enables the Center to offer comprehensive, effective patient care.

Molecular Markers and Endoscopic Techniques

Tamas A. Gonda, MD, Assistant Attending Physician, NewYork-Presbyterian/Columbia University Medical Center, also emphasizes the importance of early detection and treatment of gastrointestinal malignancies. He uses endoscopic techniques along with molecular markers to detect these abnormalities.

Within the scope of early detection and early diagnosis, Dr. Gonda's research focuses on cancers of the pancreas and esophagus, Barrett's esophagus, and pancreatic cyst surveillance. In several of these conditions, molecular markers may provide the opportunity to identify cancerous transformation before it is detectable by either imaging or histology.

"In the biliary tract, there are some diseases--notably, primary sclerosing cholangitis--which are high-risk conditions for progression to biliary malignancies. Molecular markers, especially fluorescent in situ hybridization or FISH, already play a signifi can't role in identifying those patients who have developed cancer or precancerous lesions, "Dr. Gonda explained.

Recently, Dr. Gonda investigated the additional benefi t of detecting mutations in the cell-free component of bile duct biopsies and the potential advantage of adding this modality to FISH and brush cytology. The mutational analysis used 17 markers, including KRAS point mutation and loss of heterozygosity at multiple loci.

The results showed that residual supernatant fluid from cytology brushes can be used to secure adequate amounts of DNA for mutational analysis. The study also demonstrated that mutational analyses on cell-free DNA specimens might contribute to the diagnostic yield, especially in cases where brush specimens have low cellularity, which is a common problem encountered in biliary diagnostics.2

Pancreatic cystic neoplasms are another area where a combination of molecular markers and endoscopic imaging may play a significant role in identifying patients at the highest risk. At the Pancreas Center of NewYork-Presbyterian/Columbia the goal of several screening programs and protocols is to detect patients who have not yet developed pancreatic cancer but who carry a high risk for developing it. This early detection may offer an opportunity for prevention of pancreatic cancer in this population of patients.

Endoscopic biopsies may also increasingly influence treatment decisions in pancreatic cancer. Dr. Gonda noted that research is moving toward targeted therapies and the use of molecular markers to identify the best possible treatment options. "One of our goals is to try to provide targeted or tailored therapy based on molecular profi les of the tumors. Identifying certain mutations, such as KRAS or BRCA-1 or -2, and others, will hopefully drive treatment decisions once the diagnosis of cancer has been established," Dr. Gonda said.

"NewYork-Presbyterian/Columbia is unique in our very comprehensive approach, from expert diagnostic modalities--such as endoscopy, therapeutic endoscopy, and molecular diagnosis--to therapeutic expertise in both oncology and surgery. This approach can bring significant improvement in the diagnosis and treatment of esophageal, gastric, and biliary diseases," said Dr. Gonda.

References

1. Turner BG, Bezak KB, Sarkaria S, et al. Probe-based confocal laser endomicroscopy in the pancreatic duct provides direct visualization of ductal structures and aids in clinical management. Presented at: American College of Gastroenterology 2012 Annual Scientifi c Meeting; October 19-24, 2012; Las Vegas, NV. Poster P652.

2. Gonda TA, Sethi A, Poneros JM, et al. Mo1318 mutational analysis from cellfree DNA in the diagnosis of biliary strictures. Gastrointest Endosc. 2012;75(suppl 4):AB387.

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