Management of Gastric Polyposis/IM/Early Gastric Cancer

Jeffrey H. Lee, MD, MPH, FACG, FASGE, AGAFProfessor and Director, Advanced Therapeutic

Endoscopy Fellowship and TrainingMD Anderson Cancer Center

Gastric Lesions1. Gastric Polyposis

– Epithelial lesions• Fundic gland polyps• Hyperplastic polyps• Adenomas

– Subepithelial lesions• Carcinoids• Leiomyomas• Lipomas• Granular cell tumors • Gastrointestinal stromal tumors• Pancreatic rests• Linitis plastica

2. Gastric Intestinal Metaplasia3. Early Gastric Cancer

Diagnostic Tools

• EGD with biopsy• EUS

– Differentiate extramural from intramural growth– Determine layer of origin– Size the lesion– Evaluate for regional lymphadenopathy– Obtain tissue for diagnosis– Help determine appropriate management

• CT• MRI• CT-PET

Fundic Gland Polyps

Hyperplastic Polyps

Hyperplastic Polyps

Hyperplastic Polyp• Characteristics

– Frequency: 2nd most common gastric polyp– Increases between ages 60-80 years– Arise from mucosal damage due to chronic inflammation – Single, multiple, sessile, or pedunculated– Most commonly found in the antrum– H. pylori, pernicious anemia, chronic atrophic gastritis, adjacent to

ulcers, sites of gastroenterostomies, APC treatment of GAVE– CT: Multiple small, round, sessile polyps in the fundus or gastric body– EGD: Less than 1cm, smooth, dome- shaped, or stalked – Endoscopic finding of white opaque substance in a gastric

hyperplastic polyp is suggestive of neoplastic transformation

Dirschmid et al. Virchows Archiv 2006Park and Lauwers. Archives of pathol and lab med 2008Baudet et al. Endoscopy 2007

Hyperplastic Polyp• Symptoms

– Usually asymptomatic– Anemia, bleeding due to ulceration, dyspepsia, gastric outlet obstruction

• Malignant potential– 2 % malignant transformation– Mechanism of carcinogenesis is unknown

• Management– If polyp persists or dysplasia is present, polypectomy is recommended

with repeat EGD in one year – Although polyps greater than 2cm should be removed, carcinoma can

arise in polyps less than 2cm – No endoscopic guidelines for follow-up of hyperplastic gastric polyp

without dysplasiaDirschmid et al. Virchows Archiv 2006Park and Lauwers. Archives of pathol and lab med 2008Baudet et al. Endoscopy 2007

Adenoma with HGD

Adenoma with HGD

Adenoma with HGD

Adenoma with HGD

Adenoma with HGD

Adenoma with HGD

Gastric Adenoma• Characteristics

– Frequency: 6-10 % of gastric polyps in the western populations– Increases with age– Solitary– Commonly found in the antrum– Associated with atrophic gastritis and intestinal metaplasia– Tubular, tumbulovillous, villous– Villous >2cm: 28-40% increased risk of malignancy– Low or high grade dysplasia

• Based on degree of mitotic activity, cytoplasmic differentiation, nuclear crowding, hyperchromasia, stratification, architectural distortion

– FAP– CT may not be helpful

Vieth et al. Virchows Archiv 2003 Kamiya et al. Cancer 1982Iida et al. Cancer 1988

Gastric Adenoma• Symptoms

– Usually asymptomatic– Anemia, bleeding due to ulceration

• Malignant potential– High grade dysplasia predisposes to invasive cancer not only within

the polyp but also in synchronous areas of the stomach• Management

– Polypectomy– EMR– Follow-up

• For gastric adenoma after incomplete polypectomy or for high grade dysplasia; in 6 months

• For all other polyps; in 1 yearVieth et al. Virchows Archiv 2003 Kamiya et al. Cancer 1982Iida et al. Cancer 1988

Submucosal LesionsPathology Muscularis

mucosaSubmucosa Muscularis

propriaSerosa

GIST ✔ ✔Leiomyoma ✔ ✔

Lipoma ✔

Granular cell tumor

✔ ✔

Pancreatic rest ✔

Carcinoid ✔

Fibroid lesion ✔

Duplication cyst

✔ ✔ ✔ ✔

Varices ✔

Lymphangioma ✔

Schwannoma ✔ ✔

GIST• Characteristics

– Originates from the interstitial cells of Cajal – A gain of function mutation in the KIT gene that codes for the c-kit protein, a tyrosine kinase receptor– IHC stain: CD117 positive in nearly 95% of cases– EUS: Hypoechoic lesion arising from the MP layer– EUS FNA not sufficient for assessment of mitotic count

• Symptoms– Iron deficiency anemia– GI bleeding

• Malignant potential– Potential malignant transformation and distant metastasis– Size of the lesion– Number of cells undergoing mitosis at pathology

• Management– <2 cm: Observation with annual EGD and/or EUS, resection if growing per NCCN– >2 cm: Consider surgical resection

• Endoscopic resection only possible with full-thickness resection and suturing

– High risk lesions: Referral to medical oncology for consideration of adjuvant therapy with a tyrosine kinase inhibitor (e.g. Imatinib)

• A type of interstitial cells found in the GI

• Involved in the stimulation of smooth muscle cells

• Neurotransmitters act through them

Grotz and Donohue. Surgical Oncol 2011 Hirota et al. Science 1998Menon and Buscaglia. Ther Adv Gastroenterol 2014

GIST

Risk of malignancy Size Mitotic count

Very low <2 cm <5/50 HPF

Low 2-5 cm <5/50 HPF

Moderate <5cm 6-10/50 HPF

>5cm <5/50 HPF

High >5cm 6-10/50 HPF

Any size >10/50 HPF

Leiomyoma• Characteristics

– Originates from the muscular layer, commonly MP– Most commonly in mid or distal esophagus– IHC staining is negative for CD117, CD34, s100– IHC positive desmin, α-smooth muscle actin protein

• Symptoms– Usually asymptomatic– Bleeding

• Malignant potential– Malignant transformation to leiomyosarcoma is rare

• Management– > 1cm: EUS to confirm diagnosis– < 2cm: Surveillance EGD and/or EUS; if from MM layer, EMR

Lee et al. J Am Coll Surg 2004

Lipoma• Characteristics

– Originates from the submucosal layer– Most commonly in the gastric antrum and colon– Yellow hue– Soft when prodded with a biopsy forceps, ‘pillow’ sign

• 98% specificity

• Symptoms– Usually asymptomatic

• Malignant potential– Essentially no malignant potential

• Management– Jumbo biopsies reveal yellow adipose tissue– Bleeding after biopsy may require clipping– Once confirmed as lipoma, no surveillance is needed

Hwang et al. Gastrointest Endosc 2005

Granular Cell Tumors

• Characteristics– Subepithelial lesions of Schwann cell origin– Arise from the submucosal layer and grow toward the mucosa– Most occur within the esophagus

• Symptoms– Usually asymptomatic

• Malignant potential– Extremely low (one study, 2-4% and all were >4 cm)

• Management– <1 cm: Annual EGD surveillance– 1-2 cm: Annual surveillance vs. EMR– >2 cm: Surgical resection

Orlowska et al. Am J Gasgtroenterol 1993

Pancreatic Rest• Characteristics

– 1-2% of patients in autopsy series– Nearly all within the stomach (90%), most often in the antrum– Arises from the submucosal layer– Central area of umbilication– On deep biopsy, pancreatic acinar tissue

• Symptoms– Usually asymptomatic– Ulceration, pain, bleeding, acute pancreatitis, gastric outlet obstruction

• Malignant potential– Benign– Rare cases of malignant transformation

• Management– No surveillance or removal needed

Sadeghi et al. Gastroenterol and Hepatol 2008

Gastric Carcinoid

Gastric Carcinoid

Gastric Carcinoid

Carcinoid Tumors• Characteristics

– Slight female predominance (M:F; 1:1.6)– Gastric carcinoid tumors: 9% of all carcinoid tumors– Arise from the deep mucosal layer and penetrate into the submucosal layer – Type I: Atrophic gastritis, pernicious anemia, hypergastrinemia– Type II: hypergastrinemia due to ZE Syndrome or MEN-1– Type III: Sporadic, without hypergastrinemia

• Symptoms– Usually asymptomatic– Ulceration, pain, bleeding, acute pancreatitis, gastric outlet obstruction

• Malignant potential– Type I: Very low malignant potential; fewer than 2 % are metastatic– Type II: Intermediate malignant potential; metastasize in 30% of cases– Type III: High malignant potential; lymph node metastasis in 71% of cases

measuring more than 2 cmKulke et al. NCCN 2012Martinez-Ares et al. Rev Esp Enferm Dig 2004

Carcinoid Tumors

• Management– EUS can help in identifying the blood vessel near the carcinoid, which can

potentially help prevent bleeding during endoscopic resection – For type I and II

• <2 cm: EMR• >2 cm: Surgical resection

– Antrectomy to remove G cell mass burden – Fundectomy to remove ECL cell mass burden– Post-surgical resection: EGD q 6-12 months for 3 years and annually

thereafter– For type III

• Surgical resection with lymph node dissection• Follow-up EGD• Monitor chromogranin A, serum tumor marker, for recurrence• Monitor 5-HIAA, a metabolite of serotonin, for treatment response

Kulke et al. NCCN 2012Ramage et al. Gut 2005

Carcinoid Tumors

• Management– For hepatic metastasis

• Hepatic artery ligation or embolization– Decreases symptoms and improves survival

• Octreotide, Somatostatin analogue– Decreases the symptoms of carcinoid syndrome

– For Metastatic carcinoids• Chemotherapy

– Streptozocin, flurouracil, doxorubicin, cyclophosphamide

– Tumor response rate of 20-40%Kulke et al. NCCN 2012Ramage et al. Gut 2005

Gastric Carcinoid

Gastric Carcinoid

Linitus Plastica

Linitus Plastica

Linitus Plastica

Linitis Plastica• Characteristics

– Frequency: 3-19% of gastric adenocarcinoma– Diffuse type of gastric cancer characterized by diffuse thickening– Asymptomatic but symptomatic at advanced stage– Metastasis from breast should be excluded as infiltrative lobular breast cancer tends to

metastasize to stomach– CT scan findings: Thickened stomach wall, diffuse gastric wall thickening, perigastric

stranding, lung nodules, mediastinal lymphadenopathy, local lymphadenopathy and liver metastasis

– Usually the lower third of the mucosa; sometimes the biopsy of the mucosa can be negative as the mucosa is not infiltrated

– Multiple biopsies at the same site or diathermic snare– CT: Diffuse mural thickening with or without ulceration– EGD:

• Prominent gastric folds• Thickened area of irregular gastric mucosa at the greater curvature• Circumferential thickening of the proximal stomach

Hwang et al. Gastrointest Endosc 2005

Linitis Plastica• Symptoms

– Early satiety, abdominal discomfort, weight loss, dysphagia, dyspepsia, vomiting

– Most common; regurgitation of food due to decreasing volume of the stomach

• Malignant potential– Malignant– Peritoneal seeding, extension to surrounding organs and metastasis to

lymph nodes

• Management– Complete resection but only 20% benefit from total gastrectomy– Post-operative radiation with or without chemotherapy should be evaluated

in future studies since complete resection is not possible in the majority of cases

Hwang et al. Gastrointest Endosc 2005

Gastric Intestinal Metaplasia• Characteristics

– The most frequently encountered precancerous lesion – The sequence of gastric adenocarcinoma of intestinal type

• Nonatrophic gastritis • Multifocal atrophic gastritis• Metaplasia and dysplasia

– More common in populations at high risk for gastric cancer; Eastern Asia, Eastern Europe, and Andean Latin America (Bolivia, Columbia, Ecuador, and Peru)

– High-risk populations in US; African Americans, Native Americans, and immigrants from Asia and Latin America

– Risk factors: Helicobacter pylori infection, high salt intake, smoking, alcohol consumption, and chronic bile reflux

– Complete type IM • Contains the small bowel enzymes • Resemble small intestinal epithelium with eosinophil enterocytes, goblet cells, and paneth cells

– Incomplete IM • Contains no or little amount of small bowel enzymes • Resemble colonic epithelium with absent brush border

Lee et al. J Am Coll Surg 2004

Gastric Intestinal Metaplasia• Symptoms

– Usually asymptomatic– Nausea– Dyspepsia

• Malignant potential– Several studies showed that there is progression of IM to adenocarcinoma in

incomplete IM• Management

– Incomplete IM • Endoscopic mapping to identify multifocal areas of IM• Typically, biopsy is obtained from the antrum, corpus, incisura angularis,

and any visible lesion – Complete IM

• Endoscopic surveillance is not indicated unless there are other risk factors for gastric cancer

Lee et al. Am Coll Surg 2004

Early Gastric Cancer (EGC)

• Characteristics– Confined to the mucosa or submucosa regardless lymph

node metastasis– EGC accounts for 50 % of gastric cancer incidence in Japan– Paris classification– Kudo pit pattern– 5-year survival over 90 %

• Symptoms– Feeling bloated after eating– Nausea – Stomach pain

Saito et al. Surgical Endoscopy 2010 Minami et al. Gastrointestinal Endoscopy 2006 Takizawa et al. Endoscopy 2008Catalano et al. Surgical Endoscopy 2009 Oda et al. Digestive Endoscopy 2013 Ferlay et al. Int J Cancer 2010Maruyama et al. Gastric Cancer 1991 Ono et al. Gut 2001

Paris Classification

• Paris I: Protruded lesions

• Paris 2:– Paris 2a : Slightly

elevated, – Paris 2b: Completely flat– Paris 2c: Depressed

• Paris 3: Ulceration of the mucosa

Yada et al. Diagnostic and Therapeutic Endoscopy 2013

Kudo Pit Pattern

• Type 1: Round• Type 2: Stellar or papillary, nonneoplastic• Type 3: Tubular or small roundish• Type 4: Branch-like or gyrus-like• Type 5: Irregular or nonstructural pits, neoplastic

– Usually involves the submucosal layer and there is a high rate of lymph node metastasis

ESD Devices• Distal attachment

– Assorted size, transparent– Helps to open up the submucosal area by mechanical stretching technique

• Injection needle– Upper or lower case– Right gauge for easy injection

• Coag grasper– Used with soft coag setting to control bleeding– Can be used underwater

• Grounding pad– No metal such as plates, screws, or joint replacements– Across a large muscle area

• Electrical surgical unit– Generator providing modulated current options– Settings are different for different stages of the procedure and different models of

generators• ESD knives

Meta-analysis on EMR vs. ESD• 15 nonrandomized studies; 7 articles and 8 abstracts• ESD when compared with EMR

– Higher en bloc and curative resection rates for esophageal, gastric, and colorectal neoplasms and for lesions of size < 10 mm, 10mm – 20 mm, > 20 mm

– Lower local recurrent rate (OR 0.09, 95%CI 0.04-0.18)– More time-consuming

• Complications– Higher procedure-related bleeding and perforation rates than in general

procedures (OR 2.20, 95% CI 1.58-3.07; OR 4.09, 95%CI 2.47-6.80)– Bleeding: 93/1596 (6%) in EMR vs. 80/868 (9%) in ESD – Perforation: 19/1982 (1%) in EMR vs. 57/1255 (5%) in ESD

• Recurrence– Local recurrence: 118/2254 (5%) in EMR vs. 5/1484 (0.3%) in ESD

Cao Y et al. Endoscopy Lancet 2009;41:751-757

Early Gastric Cancer• Management

– EUS• To assess depth of invasion (T-stage)• To identify lymph node metastasis (N-stage)

– Endoscopic mucosal resection (EMR) – Endoscopic submucosal dissection (ESD)– Post EMR/ESD metachronous cancer; a 3-year cumulative incident rate of 5.9%

with average time until detection of 3.1 +1.7 years– Italian study of 45 patients

• En-bloc resection: 26/36(72%) in EMR and 11/12(92%) in ESD • Curative resection: 20/36(56%) in EMR vs. 11/12(92%) in ESD • No recurrence or distant metastasis in mean follow-up of 31 months• Complications of EMR vs. ESD

– Bleeding (8% vs. 8%)– Stenosis (3% vs. 0)– Perforation (0 vs. 8%)

Saito et al. Surgical Endoscopy 2010 Minami et al. Gastrointestinal Endoscopy 2006 Takizawa et al. Endoscopy 2008Catalano et al. Surgical Endoscopy 2009 Oda et al. Digestive Endoscopy 2013

Take-home Message

• Weigh the benefits and risks • Have a thorough discussion with the patient before the

planned procedure• For invasive procedures

– EMR/ESD team needed– Arrange surgical support

• Surveillance is important for some of the lesions