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Презентация на тему Gastric cancer

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Gastric cancer encompasses a heterogeneous collection of etiologic and histologic subtypes associated with a variety of known and unknown environmental and genetic factors. It is a global public health concern, accounting for 700,000 annual deaths worldwide,
Gastric cancerValeriya Semenisty, MD Gastric cancer encompasses a heterogeneous collection of etiologic and histologic subtypes associated Approximately 3% to 5% of gastric cancers are associated with a hereditary Gastric cancer has traditionally been subtyped pathologically according to Lauren’s1 classification published More clinically relevant, the majority of gastric cancers can be subdivided into ETIOLOGY  Environmental Risk Factors      diet and More than 70% of cases occur in developing countries, and men have PATHOLOGY AND TUMOR BIOLOGY  Approximately 95% of all gastric cancers are adenocarcinomas. PATTERNS OF SPREAD  Carcinomas of the stomach can spread by local CLINICAL PRESENTATION AND PRETREATMENT EVALUATION  Because of the vague, nonspecific symptoms Up to 25% of the patients have history/symptoms of peptic ulcer disease. PRETREATMENT STAGING  Tumor markers – CEA, CA19-9,CA125EUSCTMRIPET-CTStaging Laparoscopy and Peritoneal Cytology STAGING, CLASSIFICATION, AND PROGNOSIS TREATMENT OF LOCALIZED DISEASE  Stage I Disease (Early Gastric Cancer) Endoscopic Stage II and Stage III Disease  GASTRECTOMY Adjuvant Therapy  Adjuvant therapy indicates administration of a treatment following a There are several theoretical reasons for beginning adjuvant therapy soon after operation Neoadjuvant chemotherapy has a dual goal: allowing a higher rate of R0 D1 vs D2 Lymphadenectomy Rationale for Preoperative Therapy in Proximal Gastric Cancer Studies demonstrating benefit of Importance of Preoperative Staging When Considering Neoadjuvant TherapyAccuracy of predicting nodal involvement Rationale for Up Front Surgery in Patients With Gastric Cancer Pathologic staging Algorithm for Management of Gastric Cancer* *ESMO-ESSO- Post-Operative Chemo vs Chemoradiation:ARTIST TrialLee et al. JCO Jan 2012Samsung University458 patient Recurrence-Free SurvivalP=0.029Post-Operative Chemo vs Chemoradiation:Nanjing University380 patientsRandomized trialAll D2 gastrectomy~10% GE junctionPostoperative Impact of Extent of Surgery and Postop Chemoradiation:Dutch Gastric Cancer Group TrialDikken MacDonald et al. NEJM 2001Chemoradiation After Surgery Versus Surgery Alone for Gastric PreoperativeChemotherapy3x ECC q 3 wksPreoperativeChemotherapy3x ECC q 3 wksD1+ SurgeryD1+ Surgery3x ECC SummaryAdjuvant Therapy for Proximal Gastric CancerWhile preoperative therapy may be preferred in Metastatic gastric cancer
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Gastric cancer encompasses a heterogeneous collection of etiologic

Gastric cancer encompasses a heterogeneous collection of etiologic and histologic subtypes

and histologic subtypes associated with a variety of known

and unknown environmental and genetic factors.
It is a global public health concern, accounting for 700,000 annual deaths worldwide, and currently ranks as the fourth leading cause of cancer mortality, with a 5-year survival of only 20%.
The incidence and prevalence of gastric cancer vary widely, with Asian/Pacific regions bearing the highest rates of disease.


Слайд 3
Approximately 3% to 5% of gastric cancers are

Approximately 3% to 5% of gastric cancers are associated with a

associated with a hereditary predisposition, including a variety of

Mendelian genetic conditions and complex genetic traits.


Слайд 4
Gastric cancer has traditionally been subtyped pathologically according

Gastric cancer has traditionally been subtyped pathologically according to Lauren’s1 classification

to Lauren’s1 classification published in 1965 and revised by

Carneiro et al.2 in 1995.
The four histologic categories include:
(1) glandular/intestinal,
(2) border foveal hyperplasia,
(3) mixed intestinal/diffuse, and
(4) solid/undifferentiated.


Слайд 5
More clinically relevant, the majority of gastric cancers

More clinically relevant, the majority of gastric cancers can be subdivided

can be subdivided into intestinal type or diffuse type.


Diffuse gastric tumors frequently feature signet ring cells
The intestinal subtype is seen more commonly in older patients, whereas the diffuse type affects younger patients and has a more aggressive clinical course.


Слайд 6 ETIOLOGY
Environmental Risk Factors

ETIOLOGY Environmental Risk Factors   diet and lifestyle variables. Infectious

diet and lifestyle variables.

Infectious Risk Factors

H. pylori infection
Epstein-Barr virus
Genetics



Слайд 7
More than 70% of cases occur in developing

More than 70% of cases occur in developing countries, and men

countries, and men have roughly twice the risk of

women.
In 2008, estimates of gastric cancer burden in the United States were 21,500 cases (13,190 men and 8,310 women) and 10,880 deaths. The median age at diagnosis for gastric cancer is 71 years, and 5-year survival is approximately 25%.
Only 24% of stomach cancers are localized at the time of diagnosis, 30% have lymph node involvement, and another 30% have metastatic disease. Survival rates are predictably higher for those with localized disease, with corresponding 5-year survival rates of 60%.


Слайд 8 PATHOLOGY AND TUMOR BIOLOGY


Approximately 95% of all

PATHOLOGY AND TUMOR BIOLOGY Approximately 95% of all gastric cancers are adenocarcinomas.

gastric cancers are adenocarcinomas.



Слайд 9 PATTERNS OF SPREAD
Carcinomas of the stomach can

PATTERNS OF SPREAD Carcinomas of the stomach can spread by local

spread by local extension to involve adjacent structures and

can develop lymphatic metastases, peritoneal metastases, and distant metastases.
These extensions can occur by the local invasive properties of the tumor, lymphatic spread, or hematogenous dissemination.


Слайд 10 CLINICAL PRESENTATION AND PRETREATMENT EVALUATION
Because of the

CLINICAL PRESENTATION AND PRETREATMENT EVALUATION Because of the vague, nonspecific symptoms

vague, nonspecific symptoms that characterize gastric cancer, many patients

are diagnosed with advanced-stage disease.
Patients may have a combination of signs and symptoms such as weight loss (22% to 61%)37; anorexia (5% to 40%); fatigue, epigastric discomfort, or pain (62% to 91%); and postprandial fullness, heart burn, indigestion, nausea, and vomiting (6% to 40%). None of these unequivocally indicates gastric cancer. In addition, patients may be asymptomatic (4% to 17%). Weight loss and abdominal pain are the most common presenting symptoms at initial encounter. Weight loss is a common symptom, and its clinical significance should not be underestimated.
Dewys et al. found that in 179 patients with advanced gastric cancer, >80% of patients had a >10% decrease in body weight before diagnosis. Furthermore, patients with weight loss had a significantly shorter survival than did those without weight loss


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Up to 25% of the patients have history/symptoms

Up to 25% of the patients have history/symptoms of peptic ulcer

of peptic ulcer disease. A history of dysphagia or

pseudoachalasia may indicate the presence of a tumor in the cardia with extension through the gastroesophageal junction. Early satiety is an infrequent symptom of gastric cancer but is indicative of a diffusely infiltrative tumor that has resulted in loss of distensibility of the gastric wall.
Delayed satiety and vomiting may indicate pyloric involvement. Significant gastrointestinal bleeding is uncommon with gastric cancer; however, hematemesis does occur in approximately 10% to 15% of patients, and anemia in 1% to 12% of patients. Signs and symptoms at presentation are often related to spread of disease.

Ascites, jaundice, or a palpable mass indicate incurable disease. The transverse colon is a potential site of malignant fistulization and obstruction from a gastric primary tumor. Diffuse peritoneal spread of disease frequently produces other sites of intestinal obstruction.

A large ovarian mass (Krukenberg’s tumor) or a large peritoneal implant in the pelvis (Blumer’s shelf), which can produce symptoms of rectal obstruction, may be palpable on pelvic or rectal examination.

Nodular metastases in the subcutaneous tissue around the umbilicus (Sister Mary Joseph’s node) or in peripheral lymph nodes such as in the supraclavicular area (Virchow’s node) or axillary region (Irish’s node) represent areas in which a tissue diagnosis can be established with minimal morbidity. There is no symptom complex that occurs early in the evolution of gastric cancer that can identify individuals for further diagnostic measures. However, alarming symptoms (dysphagia, weight loss, and palpable abdominal mass) are independently associated with survival;

increased number and the specific symptom is associated with mortality.

Слайд 12 PRETREATMENT STAGING
Tumor markers – CEA, CA19-9,CA125
EUS
CT
MRI
PET-CT
Staging Laparoscopy

PRETREATMENT STAGING Tumor markers – CEA, CA19-9,CA125EUSCTMRIPET-CTStaging Laparoscopy and Peritoneal Cytology

and Peritoneal Cytology


Слайд 13 STAGING, CLASSIFICATION, AND PROGNOSIS




STAGING, CLASSIFICATION, AND PROGNOSIS

Слайд 14 TREATMENT OF LOCALIZED DISEASE
Stage I Disease (Early

TREATMENT OF LOCALIZED DISEASE Stage I Disease (Early Gastric Cancer) Endoscopic

Gastric Cancer)
Endoscopic Mucosal Resection
Limited Surgical Resection
Gastrectomy




Слайд 15 Stage II and Stage III Disease
GASTRECTOMY

Stage II and Stage III Disease GASTRECTOMY

Слайд 16 Adjuvant Therapy
Adjuvant therapy indicates administration of a

Adjuvant Therapy Adjuvant therapy indicates administration of a treatment following a

treatment following a potential curative resection of the primary

tumor and regional lymph nodes.
Therapy after resections that leave microscopic or gross disease are not adjuvant treatment, but rather therapy for known disease, which is palliative in nature.
Neoadjuvant chemotherapy involves the use of systemic treatment before potentially curative surgery.


Слайд 17
There are several theoretical reasons for beginning adjuvant

There are several theoretical reasons for beginning adjuvant therapy soon after

therapy soon after operation (perioperative chemotherapy). Studies have shown

a rapid increase in cell growth of metastases after a primary tumor has been removed related to a decline in certain circulating factors, which serve to inhibit angiogenesis or other cell-cycle promotors, once the primary tumor is removed.
Perioperative or neoadjuvant chemotherapy has been studied because the ability to perform a R0 resection in gastric cancer is difficult. In addition, a substantial number of patients undergoing gastrectomy have prolonged recovery.

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Neoadjuvant chemotherapy has a dual goal: allowing a

Neoadjuvant chemotherapy has a dual goal: allowing a higher rate of

higher rate of R0 resections and treatment of micrometastatic

disease early in the course of treatment.


Слайд 19 D1 vs D2 Lymphadenectomy

D1 vs D2 Lymphadenectomy

Слайд 20 Rationale for Preoperative Therapy in Proximal Gastric Cancer

Rationale for Preoperative Therapy in Proximal Gastric Cancer Studies demonstrating benefit


Studies demonstrating benefit of preoperative chemotherapy over surgery alone1


Evidence of role of induction chemoradiation therapy in distal esophageal CA2

1MAGIC Trial. Cunningham et al. Radiother Oncol 104 (2012)
2CROSS Trial. van Hagen et al. NEJM (2012)


Слайд 21 Importance of Preoperative Staging When Considering Neoadjuvant Therapy
Accuracy

Importance of Preoperative Staging When Considering Neoadjuvant TherapyAccuracy of predicting nodal

of predicting nodal involvement is 60-80%
Surgery alone may be

sufficient for Stage II disease
Neoadjuvant therapy may be overtreating some patients


Слайд 22 Rationale for Up Front Surgery in Patients With

Rationale for Up Front Surgery in Patients With Gastric Cancer Pathologic

Gastric Cancer
Pathologic staging may result in more appropriate

choice of adjuvant therapy (accurate stage II vs III, D1 vs D2, margins).
Symptomatic patients may require initial surgery.
In reality, gastrectomy is often performed before MDT consultation.

Слайд 23 Algorithm for Management of Gastric Cancer*
*ESMO-ESSO-

Algorithm for Management of Gastric Cancer* *ESMO-ESSO-

Слайд 24 Post-Operative Chemo vs Chemoradiation:
ARTIST Trial
Lee et al. JCO

Post-Operative Chemo vs Chemoradiation:ARTIST TrialLee et al. JCO Jan 2012Samsung University458

Jan 2012
Samsung University
458 patient RCT
D2 gastrectomy
~5% proximal CA

Postoperative adjuvant

Cap-Cis ± RT

No difference in DFS
No difference in locoregional rec




Слайд 25 Recurrence-Free Survival
P=0.029
Post-Operative Chemo vs Chemoradiation:
Nanjing University
380 patients
Randomized trial
All

Recurrence-Free SurvivalP=0.029Post-Operative Chemo vs Chemoradiation:Nanjing University380 patientsRandomized trialAll D2 gastrectomy~10% GE

D2 gastrectomy
~10% GE junction

Postoperative adjuvant 5FU-LV ± IMRT

Improved RFS

with IMRT (50 vs 32 mo)
No difference in OS



Zhu et al. Radiother Oncol 104 (2012)


Слайд 26 Impact of Extent of Surgery and Postop Chemoradiation:
Dutch

Impact of Extent of Surgery and Postop Chemoradiation:Dutch Gastric Cancer Group

Gastric Cancer Group Trial
Dikken et al. JCO May 2010


Слайд 27 MacDonald et al. NEJM 2001
Chemoradiation After Surgery Versus

MacDonald et al. NEJM 2001Chemoradiation After Surgery Versus Surgery Alone for

Surgery Alone for Gastric and GEJ Adenocarcinoma
20% GE Junction
Criticized

for inadequate surgical radicality

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Preoperative
Chemotherapy

3x ECC q 3 wks
Preoperative
Chemotherapy

3x ECC q 3

PreoperativeChemotherapy3x ECC q 3 wksPreoperativeChemotherapy3x ECC q 3 wksD1+ SurgeryD1+ Surgery3x

wks
D1+ Surgery
D1+ Surgery
3x ECC q 3 wks
Chemoradiotherapy

45 Gy/25 fx
+

capecitabine
+ cisplatin

R

Within 4-12 weeks

3-6 weeks

2 weeks

CRITICS Study


Слайд 29 Summary
Adjuvant Therapy for Proximal Gastric Cancer
While preoperative therapy

SummaryAdjuvant Therapy for Proximal Gastric CancerWhile preoperative therapy may be preferred

may be preferred in most cases, initial gastrectomy is

being commonly performed.
While R0 gastrectomy with D2 lymphadenectomy is recommended, less radical surgery is common.
Chemoradiation appears to have a role in reducing local recurrence.
Postoperative chemoradiation should be considered when managing a post-op patient, particularly when

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