Current and Future Role of the Gastroenterologist in GI Cancer Management

Abstract

With advances in technology, advances in the understanding of biology of cancer, and the advent of improved and novel therapies, the role of the gastroenterologist has been modified greatly over the past 2 decades, and continues to be shaped by the knowledge, skill, and opportunity to capitalize on the unique position that gastroenterologists hold in the patient care continuum. The gastroenterologist is evolving from a “pure” diagnostician to an endoscopic surgeon, a geneticist, a nutritionist, an immunologist and chemotherapist, and palliative care physician.

Introduction

Gastroenterologists use a combination of endoscopic procedures and radiologic imaging techniques to be the major diagnosticians of gastrointestinal cancers for patients. Specialized endoscopists, often called advanced endoscopists because of additional training, use techniques with technology to remove or sample lesions that routine endoscopists cannot perform in a relatively safe manner. Endoscopists contribute relatively passively to palliation for patients at present, largely utilizing techniques to maintain luminal patency and/or to create a means for nutrition delivery to the stomach or intestine. Gastroenterologists help prevent cancer through screening endoscopy as well as through the advocacy of HBV vaccination, as examples. I will briefly highlight these current roles of the gastroenterologist, which provide largely intermittent rather than long-term care patient interactions, followed by a description of the evolving role of the gastroenterologist from a pure diagnostician to an endoscopic surgeon, a geneticist, a nutritionist, an immunologist and chemotherapist, and palliative care physician. Many of these new roles will create a more long-term interaction with the patient that minimizes physician hand offs for care and will likely strengthen the gastroenterologist-patient relationship.

Present Roles and GI Diagnostic Tools Used by Gastroenterologists

One of the major tools that a gastroenterologist utilizes is the endoscope (gastroscope, colonoscope, side-viewing endoscope, enteroscope), and this tool serves as the major evaluative mechanism to screen and discover and sample cancer in the luminal GI tract, be it esophageal, stomach, small intestinal, biliary, pancreatic, colon or rectal neoplasia. In the United States, colonoscopy is the most common diagnostic endoscopic procedure, and in the screening population where a polyp may be encountered, polypectomy is the most common therapeutic procedure performed. Thus, colonoscopy can be diagnostic and therapeutic. Furthermore, colonoscopy is the recommended test for surveillance of known high-risk individuals for colorectal cancer. Enteroscopy has evolved recently, with double balloon enteroscopy becoming the standard deep bowel small intestinal tool for evaluation. Enteroscopy has been enhanced with the utilization of diagnostic capsule endoscopy for pre-evaluation of the small intestine.

Radiography (plain abdominal or chest x-ray, abdominal and/or thoracic CT and CT enterography, MRI) is another tool used by gastroenterologists and hepatologists to assist in screening and surveillance of GI organs, particularly the liver (hepatocellular carcinoma), pancreas, biliary tree, and parts of the luminal GI tract. CT colonography, developed to enhance the detection of polyps or cancer for colorectal cancer screening, is just as effective as colonoscopy in detecting large polyps. If CT colonography becomes commonplace as a tool for colorectal cancer screening in the United States, colonoscopy will be relegated from being both a diagnostic and therapeutic procedure to being only a therapeutic procedure for colorectal cancer screening. Combinatory use of technologies, such as done with endoscopic retrograde cholangiopancreatography (use of a side-viewing duodenoscope combined with fluoroscopy in real time) allows the advanced endoscopist to diagnose and treat pancreaticobiliary disorders. Diagnostic MRI cholangiopancreatography (MRCP) has largely negated the need for a diagnostic ERCPs; however, ERCPs are not only therapeutically useful, but can also aid in diagnosis with brushings and biopsies of biliary or pancreatic ductal lesions. Endoscopic ultrasound (EUS) is another combination endoscopic and radiologic tool to diagnose, sample, and stage cancers of the GI tract, and can convey prognosis and surgical resectability.

Therapeutic tools and techniques utilized during endoscopy, such as narrow-band imaging, chromoendoscopy, and endomicroscopy along with improved trans-channel tools to sample and completely remove appropriate lesions has allowed the development of “endoscopic surgeons”. These advanced endoscopists can treat and cure some cancers via endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), and in some cases with surgeons, perform natural orifice transluminal endoscopic surgery (NOTES). However, NOTES appears to be more aligned with surgery training with the need in some cases to perform traditional surgery as an adjunct. These techniques have allowed the endoscopist to remove larger and more complex lesions, delegating some surgical cures from the operating room to the endoscopic suite. Indeed, even some perforations after lesion removal, if recognized quickly, can be treated via endoscopic-assisted closure. Palliation through placement of percutaneous endoscopic gastrostomies (PEG) or feeding tubes for nutritional support, and luminal, biliary, esophageal, intestinal and pancreatic stents to relieve obstruction have become the norm for gastroenterologists in advanced endoscopic centers (1-3).

Developing and Future Roles for Gastroenterologists

There are at least two additional areas that will expand the realm of gastroenterologists for the future in addition to further utilizing enhanced endoscopic tools: an understanding and implications of genetics of GI tract tumors, and more direct role of chemical and biological treatment of cancers. In many cases, the genetics and treatment of certain cancers will go hand-in-hand in the approach to patient care. In regards to enhanced endoscopic tools, bioengineers and gastroenterologists will continue to refine and innovate endoscopy, and gastroenterologists will become permanent fixtures to multidisciplinary tumor boards that address care for complex gastrointestinal cancer patients. Gastroenterologists will be utilized for complex procedures in certain patients, removing larger tumors for potential cure or even debulking. In other words, gastroenterologists will not only diagnose cancers, but be a larger part of the multidisciplinary approach in managing certain cancers.

The improved understanding of the genetics and epigenetics of sporadic colon cancer outlined by the Cancer Genome Atlas Network (4) will direct diagnostic, preventive, prognosis, and therapeutic approaches for colon cancer for the foreseeable future. These include diagnostic fecal DNA tests and blood–based tests that might replace the use of diagnostic endoscopy for some cases, the prognostic use of genetic information that is predictive of outcome beyond staging information, such as DNA mismatch repair gene status (5,6) and prevention of recurrent cancer with aspirin knowing the PI3 kinase mutational status of the patient's tumor (7). The gastroenterologist will need to become more familiar with the rapid increase in knowledge of cancer-prone familial syndromes of the GI tract (such as Lynch syndrome and PTEN Hamartoma syndrome), and the implications for screening, surveillance, genetic counseling, genetic testing, and approach to care. The present approach to genetic testing is through single gene mutational assessment (8), but with whole genome and exome sequencing, knowledge of secondary findings from sequencing the genome may need to be passed from the gastroenterologist to the patient and their family. Genetic counselors will be part of this dissemination, and are a key part of practices with growing populations at high risk for familial cancer.

Treatment for GI cancers has extended into the realm of targeted biological therapy based on the genetics and biological behavior discovered at the molecular level within tumors. The approach to care is multidisciplinary, often through tumor board mechanisms that considers a thoughtful, coordinated, informed, and practical approach to care for the cancer patient. For the gastroenterologist, this will include endoscopic approaches that go beyond stent palliation or EMR. The gastroenterologist may perform direct endoscopic injection of chemoimmunomodulatory therapy into a tumor, which occurs in some centers on a clinical trial basis. Brachytherapy can also be administered endoscopically. With appropriate training, gastroenterologists may administer chemotherapy and targeted therapy to the patient (Table 1), participating in the continued care of the patient beyond endoscopic diagnosis and endoscopic treatment. Many of these therapies will eventually become oral-based making them easier to administer, and much like the gastroenterologist or hepatologist who direct chemoembolization of the hepatic artery for hepatocellular carcinoma, or treat patients with immune drugs for post liver transplant patients, or treat inflammatory bowel disease patients with anti-TNF-alpha or other immunomodulatory medications (Table 2). Drug treatment for GI cancer care, at least in part, may eventually fall into the realm of the gastroenterologist's practice (9).

Table 1.

Some drugs used for gastrointestinal cancers. Some of these could be prescribed by gastroenterologists in the future with appropriate oncological training.

Esophageal	Gastric	Liver/Biliary	Pancreatic	Colon
Cisplatin	Adriamycin	Adriamycin	Gemcitabine	Irinotecan
5FU	5FU	5FU	5FU	5FU
Docetaxel	Docetaxel	Cisplatin	Erlotinib	Oxaliplatin
Epirubicin	Doxorubicin	Sorafenib (Nexavar)		Cetuximab
Irinotecan	Trastuzumab (Herceptin)			Panitumab
Mitomycin C	Mitomycin C			Bevacizimab
Paclitaxel
Vindesine
Vinorelbine

Table 2.

Examples of toxic therapies that gastroenterologists administers or directs usage of in the United States.

Therapy	Drug Type	Disease	GI's Role
Corticosteroids	Anti-inflammatory, immunomodulatory	IBD, OLT	Administers
Infliximab/others	Anti-TNF alpha	IBD	Administers
Azathioprine/6-MP	immunomodulatory	IBD	Administers
Cyclosporin A	Immunomodulatory	UC, OLT	Administers
Tacrolimus/FK506	Immunomodulatory	OLT	Administers
Mycophenylate mofitil	Immunomodulatory	OLT	Administers
Antibiotics, various	Antibiotic	IBD, MALT Lymphoma, other infections	Administers
TACE	Antiproliferative chemotherapies	HCC	Directs (with IR/oncologist)
Direct tumor injection	Sclerosants, chemotherapy	Esophageal, gastric, pancreatic, HCC	Directs (with IR/oncologist) or administers (via endoscopy or EUS/FNA)
Imatinib	Tyrosine Kinase Inhibitor	GIST	Directs or administers
Interferons	Immunomodulatory	HBV, HCV, HDV	Administers
Ribavirin	Antiviral	HCV	Administers
Telaprevir/boceprivir	Antiviral	HCV	Administers
Lamivudine/adefovir/entacavir/telbivudine/tenofovir	Antiviral	HBV, HDV	Administers
Botulinum toxin	Ach release inhibitor	Achalasia	Administers
Ethanolamine	Sclerosant	Esophageal varices	Administers
NSAIDs	Anti-inflammatory, chemopreventive	FAP post colectomy	Administers
Octreotide	Somatostatin analog	Symptomatic endocrine neoplasias, varices	Administers
Sorafenib	TKI	HCC	Administers

In summary, the role of the gastroenterologist for cancer care is evolving from pure diagnostician to that of active cancer management after diagnosis (Table 3). This is a welcome feature for patients who can continue to have relationships with familiar physicians after their GI cancer diagnosis. Endoscopic approaches and innovations will continue to enhance patient care. Genetics will influence the approach to care, and the gastroenterologist will utilize that knowledge to provide competent and precise care. Chemotherapy may be administered with appropriate training. This transformation allows the gastroenterologist to be a larger part of the continuum of care for cancer patients.

Table 3.

Evolving and future roles of gastroenterologists in cancer care.

Old or Current Roles	Evolving or Future Roles
Endoscopic diagnostician	Endoscopic surgeon
Luminal palliation	Luminal and neurologic palliative care and nutrition
Prevention and screening	Prevention and screening
	Geneticist
	Chemotherapy prescription and delivery
	Direct medical treatment of cancers (e.g. direct injection of compounds into tumors endoscopically)

Abbreviations used

HBV

hepatitis B virus

GI

gastrointestinal

CT

computed tomography scan

MRI

magnetic resonance imaging

ERCP

endoscopic retrograde cholangiopancreatogrpahy

MRCP

Magnetic resonance cholangiopancreatogrpahy

EUS

endoscopic ultrasound

NOTES

natural orifice transluminal endoscopic surgery

EMR

endoscopic mucosal resection (EMR)

ESD

endoscopic submucosal dissection

PEG

percutaneous endoscopic gastrostomy