early gastric cancer

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DR. DEEPESH R.SHARMA DATE- 08/08/15 Early Gastric Cancer (EGC)

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Page 1: Early gastric cancer

DR. DEEPESH R.SHARMA

DATE- 08/08/15

Early Gastric Cancer (EGC)

Page 2: Early gastric cancer

Introduction Gastric cancer - second leading cause of cancer mortality

Regional differences –Asia (Japan and Korea) has higher incidence compared to West

Gastric cancer is now being detected more often in the asymptomatic stages

In Japan, 50% of the cases of gastric cancer currently treated in early stage

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Early gastric carcinoma (EGC)

Lesion confined to the mucosa and/or submucosa, regardless of the lymph node metastatic status

Japanese Gastric Cancer Association, “Japanese classification of gastric carcinoma—2nd English edition,” Gastric Cancer, vol. 1, no. 1, pp. 10–24, 1998.

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The incidence of EGC has gradually increased with advances in diagnostic techniques and equipment

West 4 - 16% of all gastric carcinoma cases,

Japan is approximately 30 - 50%

Borie, F et al Arch Surg., 135, 1218-1223.

Page 5: Early gastric cancer

EGC

Good prognosis

Can be cured by minimally invasive approaches

5-year survival rates of EGC:

99% when limited to the mucosa

96% when the submucosa is invaded

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Classification of Early Gastric Cancer

Macroscopic classifications: Three macroscopic types (0-I, 0-II, and 0-III)

0-II is subclassified into 0-IIa 0-IIb 0-IIc

The most common type - 0-IIc

Japanese Gastric Cancer Association, “Japanese Classification of Gastric Carcinoma,” Gastric Cancer, Vol. 1, 1998, pp. 10-24.

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• 0-I

• 0-II

• 0-III

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Considerable controversy between Japanese and Western

pathologists

Western countries- if the tumor has invaded the submucosa or muscularis mucosae, at least deeper than the lamina propria

Japan- based on cellular atypia or structural atypia, regardless of the extent of invasion

Vienna classification was proposed to lessen this discripency

Microscopic classification

Page 9: Early gastric cancer

Vienna classification of gastrointestinal epithelial neoplasia

Category 1 Negative for neoplasia/dysplasia

Category 2 Indefinite for neoplasia/dysplasia

Category 3 Non-invasive low grade neoplasia (low grade adenoma/dysplasia)

Category 4 Non-invasive high grade neoplasia4.1 High grade adenoma/dysplasia4.2 Non-invasive carcinoma (carcinoma

in situ)*

4.3 Suspicion of invasive carcinoma

Category 5 Invasive neoplasia5.1 Intramucosal carcinoma5.2 Submucosal carcinoma or beyond

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Endoscopic Diagnosis

White light endoscopy

Chromoendoscopy

Narrow band imaging (NBI)

Endoscopic ultrasonography (EUS)

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White Light Endoscopy

The American Gastroenterological Association (AGA) recommendation:

1. Patients > 55 years with new-onset dyspepsia

2. Patients < 55 years who have “alarm” symptoms (weight loss, recurrent vomiting, dysphagia, evidence of bleeding, anemia)

3. Dyspeptic patients in whom an empirical trial of PPIs and eradication of Hp do not relieve symptoms

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The accuracy of WLE in the diagnosis of EGC was 68.9% Easily missed by WLE

J. Zhang et al. BMC Gastroenterology, Vol. 11, 2011, pp. 135-141.

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Important points :

1. Slight color changes in the mucosa (pale redness or fading of color)

2. loss of visibility of underlying submucosal vessels

3. Thinning of and interruptions in mucosal folds

4. Spontaneous bleeding

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Chromoendoscopy or chromoscopy

Refers to the topical application of stains or dyes at the time of endoscopy

Effort to enhance tissue characterization, differentiation, or diagnosis

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STAINSAbsorptive stains Main applicationsLugol’s solution (iodine þ potassiumiodide)

Esophageal squamous cell cancer anddysplasiaBarrett’s esophagus

Methylene blue Barrett’s esophagusGastric intestinal metaplasia and cancerChronic ulcerative colitis

Toluidine blue Oral and esophageal squamous cell cancer

Crystal violet Barrett’s esophagusColonic neoplasms

Contrast stainsIndigo carmine Colonic neoplasms, Gastric cancer

Chronic ulcerative colitisReactive stainsCongo red Ectopic gastric mucosa

Gastric cancerAdequacy of vagotomy

Phenol red H pylori infection

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Gastric neoplasia

Methylene blue staining with magnification endoscopy- 84% accurate.

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Contd…

Indigo carmine stain- EGCs as ‘‘bleached’’ areas of mucosa.

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Advantages:

 Widely available

The techniques are simple, quick, inexpensive, and safe

Limitations: Time consuming

The interpretation of the findings is not always

straightforward

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€€€

A study published in Korea showed that the rate of recognizing

tumor borders with the help of acetic acid indigo carmine

chromoendoscopy was 84 versus 67% with conventional white light

endoscopy (WLE)

Lee BE et al. BMC Gastroenterology 2010

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NBI(Narrow Band Imaging)

Using narrow-bandwidth filters in a red-green-blue (R/G/B) sequential illumination system

Increases the contrast between the epithelial surface and the

subjacent vascular pattern.

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Technical background

Carried out in the usual way

No special requirements for preparation and sedation of the patient

After endoscopic detection of a lesion, magnification imaging and then NBI are used

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B GR

Narrow Band Imaging

BLUE - Superficial mucous layers .GREEN - Capillary network of the deeper submucosal layer RED - Image of large, deep collecting vessels .

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Small round pits, surrounded by honeycomb-like SECNs and interspersed with spider-like CVs

Coiled or wavy SECNs surrounded by linear or reticular pits are observed and CVs are invisible

Normal gastric corpus Normal gastric antrum

Page 24: Early gastric cancer

Gastritis in the antrum with intestinal metaplasia

The mucosa (black arrow) demonstrates ridged to villoussurface structure fringed by a fine blue-white line, that is, light blue-crest (LBC). (the light blue crest sign)

Page 25: Early gastric cancer

Magnifying NBI endoscopic diagnosis of early gastric cancer

Three criteria for the detection of superficial gastric cancer:

The disappearance of fine mucosal structure,

Microvascular dilation

Heterogeneity in shape of vessels

Kaise M et al. Endoscopy 2009

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VS classification system: To differentiate between cancerous and noncancerous

lesions

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Accordingly, set the criteria for making a diagnosis of gastric cancer as follows:

1) An irregular microvascular pattern with a demarcation line

2) An irregular microsurface pattern with a demarcation line

If the endoscopic findings fulfill either or both – cancer,

non-cancer if neither is fulfilled

97% of early gastric cancers fit the above criteria

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Page 29: Early gastric cancer

The fine network pattern, appearing as mesh microvesselswell differentiated adenocarcinoma,

The corkscrew pattern, with isolated and tortuous microvessels, Undifferentiated adenocarcinoma

To different histologic types of cancer

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Evaluation of the depth of submucosal invasion of the carcinoma

The blurry mucosal pattern (BMP) The irregular mesh vascular pattern (IMP)

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Therapeutic

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NBI superior to chromoendoscopy & conventional endoscopy

The accuracy of WLE - 68.9%

chromoendoscopy – 91 %

NBI – 93.6 %

J. Zhang et al.BMC Gastroenterology, Vol. 11, 2011, pp. 135-141.

NBI Vs WLE Vs Chromoendoscopy

Page 33: Early gastric cancer

UGIE enhancement techniques

Confocal Laser Endoscopy :

Obtaining High-resolution optical images with depth selectivity

Real-time microscopic Images of mucosa and submucosal 250um

Confocal fluorescent microscope integrated into the tip of an endoscope, or a miniprobe passed throughout the working channel of a regular endoscope

Li WB et al. Gut 2011

Page 34: Early gastric cancer

Li et al. (1) compared WLE and CLE for differentiation of noncancerous lesions and cancer/high-grade intraepithelial neoplasia lesions.

Sensitivity : 88.9 vs 72.2 specificity, : 99.3 vs 95.1 positive predictive values : 99.5 vs 92

Expensive & time consuming

Page 35: Early gastric cancer

Endoscopic Ultrasonography (EUS)

20 MHz catheter-based

miniprobes- High frequency

(instead of 12 Mhz)

Diagnosing invasion depth

Preoperatively to assess the submucosal vasculature in order to predict intraoperative bleeding

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Limitations :

The layers do not always correspond to the histologic layers ; additional layers are caused by echoes produced by the interfaces between the histologic layers

Cannot assess full extent of tumors with to high-grade strictures

The possibility of over staging and under staging of tumors - due to discrepancy resulting from additional echoes

Limited usefulness in the overall assessment of distant metastases

Dependent on operator experience

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EUS

Sensitivity Specificity Accuracy

Overall T staging T1 T2 T3 T4

88.1%82.73%89.7%99.2%

65-92.1%

Serosal involvement

77.8-100% 67.9-100%

N staging EUS FNA

Esp low for N2/3

92%98%

30% (upto 66%)1)Kwee RM et al.J Clin Oncol 20072)Hwang SW et al. J Gastroenterol Hepatol 2010

Page 38: Early gastric cancer

CT abdomen

MDCT is considered the best modality for the staging of GC assessment of local extension of tumor nodal disease metastases

Accuracy for overall T staging : 77% to 89%

Kim HJ et al. Radiology 2005

Page 39: Early gastric cancer

Endoscopic Therapy

The frequency of LN metastasis in EGC:

3% for intramucosal carcinoma

20% for submucosal carcinoma

Indications:

Lesions where lymph node metastasis can be disregarded

M.Sasako et al 139–146,1993.

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Endoscopic Therapy

EMR (Endoscopic Mucosal Repair)

Strip biopsy method (two-channel method)- 1984

Endoscopic Resection With A Cap-fitted Panendoscope

(EMRC)

ESD (Endoscopic Submucosal Dissection)

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Indications

A differentiated elevated intramucosal cancer <2 cm in

size

A differentiated depressed intramucosal cancer <1 cm in

size without ulcer findings

Invasion limited to mucosa on the basis of EUS

No lymphatic/vascular involvement

Page 42: Early gastric cancer

Standard EMR procedure

Soetikno et al, Gastrointest Endosc, 2003

Polypectomy; Deyhle et al., Endoscopy, 1973

Strip Biopsy; Tada et al., Gastroenterol Endosc, 1984

EMR-C; Inoue et al., Gastrointest Endosc, 1993

EMR-L; Akiyama et al., Gastrointest Endosc, 1997

With A Cap-fitted Panendoscope

Page 43: Early gastric cancer

Endoscopic devices for conventional EMR

Hard and soft hood for EMR-C

EMR-L using pneumo-activated EVL device

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Strip Biopsy method

Identification of lesion

CuttingGrasping of lesion with forcep passed through snair

Injection of physiological solutionMargin- chromoendoscopy

Principle: “inject-and-cut” technique

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EMR

Disadvantage:

Large tumors (>1.5cm) cannot be resected en bloc

Piecemeal resection - difficult to assess completion/

curability

Increased incidence of residual tumor- 2.3 to 35 %

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Endoscopic resection by conventional EMR

One piece resection Piecemeal resection

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Histological assessment

1: assess the lateral margin

2: assess submucosal penetration3: assess lymphatic vascular involvement

cut every 2mm

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ESD

dissecting along the submucosal layer directly using a high-frequency knife

Indications:

Differentiated intramucosal cancers without ulcer findings, irrespective of

size

Differentiated intramucosal cancers < 3 cm in size with ulcer

Differentiated minute invasive submucosal SM1 (< 500 μm below the

muscularis mucosa) cancers < 3 cm

Undifferentiated intramucosal cancers < 2 cm in size without ulcer

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ESD

Page 50: Early gastric cancer

ESD- procedure

Page 51: Early gastric cancer

ESDIncreased instances of bleeding Endoscopic closure by

metallic clips

Perforation

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Management, Surveillance Postendoscopic Resection

EMR: annual endoscopic surveillance to ensure early detection of metachronous cancer (5.9%)

ESD: annual endoscopic surveillance + half-yearly abdominal CT or EUS, for at least 3 years in order to detect lymph node or distant metastasis

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EMR vs ESD

A meta-analysis comparing outcomes of EMR and ESD

9 nonrandomized studies 2410 patients and 4237 treated lesions

In a retrospective review of 177 patients treated endoscopically for EGC.(2)

overall, en-bloc resection rate was 94.3% with ESD vs 53.8% with EMR;

complete resection rates were 92.6 and 37.5%

5-year recurrence-free rate was 100 versus 82.5%.

For tumors < 5mm in size, there was no difference in complete or en-bloc

resection rates between the two techniques

Cao Y, Liao C, Tan A, et al. Endoscopy 2009

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Limited surgical resection

Gastrotomy with full-thickness mural excision (to allow accurate pathologic assessment of T status)

Aided by intraoperative gastroscopy for tumor localization

Formal lymph node dissection is not required in these patients

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Gastrectomy

Lower, upper or total gastrectomy with D1 or D2 LN dissection

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Conclusion Early detection and early treatment are vital, improving the

prognosis of gastric cancer Endoscopic examination plays an important role in the early

detection of gastric cancer Endoscopist must acquire the necessary skills and knowledge to

identify lesions on conventional white light endoscopy Combined use of chromoendoscopy and image-enhanced endoscopy

is expected to further improve diagnostic precision Minimally invasive methods of treatment are currently the preferred

treatment option At present,ESD is rapidly becoming favored in many countries -

greater potential for a complete cure

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Thank You

Page 58: Early gastric cancer

Lymph node dissection D1 : limited dissection of only the perigastric lymph nodes. D2 : D1 + removal of nodes along the hepatic, left gastric, celiac

and splenic arteries as well as those in the splenic hilum (stations 1-11).

D3 : D2 + removal of nodes within the porta hepatis and periaortic regions (stations 1-16), some say D2 + periaortic nodal dissection alone.

Japanese surgeons routinely perform extended lymphadenectomy accounts for the better survival rates in Asian as compared to

Western series(1) removing a larger number of nodes more accurately stages

disease extent failure to remove these nodes leaves behind disease which would

be a potentially fatal event in as many as one-third of patients (2)

Wagner PK,et al. Br J Surg 1991; 78:825.

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TNM staging (primary tumor T)

Tx Primary tumor cannot be assessedT0 No evidence of primary tumorTis Carcinoma in situ: intraepithelial tumor without invasion of

lamina propriaT1 T1a T1b

Tumor invades mucosa or submucosaTumor invades muscularis mucosaTumor invades submucosa

T2 Tumor invades muscularis propriaT3 Tumor invades subserosal connective tissuesT4 T4a T4b

Tumor invades serosa(visceral peritoneum) or adjacent structuresTumor invades serosa(visceral peritoneum)Tumor invades adjacent structures(spleen, transverse colon, liver, diaphragm, pancreas, abdominal wall, adrenal gland, kidney, small intestine and retroperitoneum)

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TNM staging(regional lymph nodes N)

NX Regional lymph node(s) cannot be assessed

N0 No regional lymph node metastasis

N1 Metastasis in 1-2 regional lymph nodes

N2 Metastasis in 3-6 regional lymph nodes

N3 N3a N3b

Metastasis in seven or more regional lymph nodesMetastasis in 7-15 regional lymph nodesMetastasis in 16 or more regional lymph nodes

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TNM staging (Distant metastasis M)

M0 No distant metastasisM1 Distant metastasis