early gastric cancer
TRANSCRIPT
DR. DEEPESH R.SHARMA
DATE- 08/08/15
Early Gastric Cancer (EGC)
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
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.
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.
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
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.
• 0-I
• 0-II
• 0-III
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
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
Endoscopic Diagnosis
White light endoscopy
Chromoendoscopy
Narrow band imaging (NBI)
Endoscopic ultrasonography (EUS)
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
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.
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
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
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
Gastric neoplasia
Methylene blue staining with magnification endoscopy- 84% accurate.
Contd…
Indigo carmine stain- EGCs as ‘‘bleached’’ areas of mucosa.
Advantages:
Widely available
The techniques are simple, quick, inexpensive, and safe
Limitations: Time consuming
The interpretation of the findings is not always
straightforward
€€€
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
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.
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
B GR
Narrow Band Imaging
BLUE - Superficial mucous layers .GREEN - Capillary network of the deeper submucosal layer RED - Image of large, deep collecting vessels .
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
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)
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
VS classification system: To differentiate between cancerous and noncancerous
lesions
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
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
Evaluation of the depth of submucosal invasion of the carcinoma
The blurry mucosal pattern (BMP) The irregular mesh vascular pattern (IMP)
Therapeutic
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
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
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
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
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
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
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
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.
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)
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
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
Endoscopic devices for conventional EMR
Hard and soft hood for EMR-C
EMR-L using pneumo-activated EVL device
Strip Biopsy method
Identification of lesion
CuttingGrasping of lesion with forcep passed through snair
Injection of physiological solutionMargin- chromoendoscopy
Principle: “inject-and-cut” technique
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 %
Endoscopic resection by conventional EMR
One piece resection Piecemeal resection
Histological assessment
1: assess the lateral margin
2: assess submucosal penetration3: assess lymphatic vascular involvement
cut every 2mm
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
ESD
ESD- procedure
ESDIncreased instances of bleeding Endoscopic closure by
metallic clips
Perforation
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
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
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
Gastrectomy
Lower, upper or total gastrectomy with D1 or D2 LN dissection
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
Thank You
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.
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)
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
TNM staging (Distant metastasis M)
M0 No distant metastasisM1 Distant metastasis