Stomach Cancer

Dr. Arifa Malek PGY3 Dr. Mohamed Saleh PGY1

A 66Y/O AA Male With PMH of HTN, Dyslipidemia, Hypothyroidism presented in PCP office with C/O Dysphagia particularly with solids since July 2012.

WT Loss of 10-15 Lbs in 5 month Period.

Decreased oral intake for 1 month , Dysphagia getting Worse progressively.

PMH; HTN, Dyslipidemia

PSH; none

Meds; HCTZ, Norvasc, Simvastatin, Synthyroid

Allergies; None

FH; HTN

SH; Denies Smoking, Drugs, Alcohol

PT was seen in FMC in June 2012 with Epigastric pain, CT Abdomen and basic Lab work was done Results WNL.

F/U in Oct 2012 initially Barium Swallow study was odered and later EGD by Dr.Ferguson in Nov 2012.

Further workup and Treatment in Progress.

Final Diagnosis :

A-Stomach Cardia Biopsy: Adenocarcinoma Moderately Differentiated (intestinal type by Lauren classification ). (special stain negative for Helicobacter pylori).

B- Esophageal Biopsy:1-Minute fragment of Adenocarcinoma. 2-Additional Gastric glands with no Histologic Abnormalities.3-Squamous Epithelium with early reflux changes.

EpidemiologyEtiologySymptoms and signDiagnosisStagingTreatmentPrevention

•The overall incidence of gastric cancer in the United States has rapidly declined over the past 50 years.

•Gastric cancer is now 13th most common cause of cancer mortality in the United States.

•Estimated new cases and deaths from stomach cancer in the United States in 2012: New cases: 21,320 Deaths: 10,540

 

In developing countries, the incidence of gastric cancer is much higher and is second only to lung cancer in rates of mortality 

The typical patient with gastric cancer is male (male-to-female ratio, 1.7:1) and between 40 and 70 years of age (mean age, 65 years). Native Americans, Hispanic Americans, and Afro-Americans are twice as likely as Caucasian to have gastric carcinoma.

The overall declining incidence of gastric carcinoma is related to distal stomach tumors caused by Helicobacter pylori infection. Proximal stomach tumors of the cardiac region have actually increased in incidence in recent years.

This trend has been attributed to the increased incidence of Barrett’s esophagus and its direct correlation with the development of esophageal adenocarcinoma

Ninety-five percent of all malignant gastric tumors are adenocarcinomas.

The remaining 5 percent include lymphomas,  sarcomas, which involve the connective tissue (such as muscle, fat, or blood vessels)

Many risk factors have been associated with the development of gastric cancer, and the pathogenesis is most likely multifactorial.

1-Definite—surveillance suggested

Familial adenomatous polyposis

Gastric adenomas

Gastric biopsy revealing high-grade dysplasia

2-Definite

Chronic atrophic gastritis

Gastric metaplasia as a biopsy result.

Helicobacter pylori infection

Hereditary nonpolyposis colorectal cancer (LynchII)

3-Probable History of subtotal gastrectomy (> 20 years)

Pernicious anemia

Tobacco smoking (adenocarcinoma of cardia)

Excess alcohol ingestion Hamartomas High intake of salted, pickled, or smoked foods

Low intake of fruits and vegetables Ménétrier’s disease Peutz-Jeghers syndrome

Benign gastric ulcers

Fundic gland polyps

Hyperplastic polyps

These risk factors are most commonly related to the development of adenocarcinoma.

Etiologies other than Helicobacter pylori infection or chronic gastritis have been difficult to elucidate for mucosa-associated lymphoid tissue tumor.

The presenting symptoms of early gastric cancer are nonspecific. Patients may be

1-Asymptomatic 2-Dyspepsia 3- mild epigastric pain, 4- nausea, or anorexia. Given the high prevalence of dyspepsia in

the general population, many EGCs may be diagnosed incidentally.

The nonspecific nature of symptoms in EGC complicates optimal disease management strategies for patients presenting with dyspepsia. While the prevalence of gastric carcinoma among patients presenting with dyspepsia is low in the United States

There are no reliable clinical or laboratory features to distinguish patients with benign causes of dyspepsia from those with more serious underlying disease.

Warning (or alarm) symptoms suggestive of invasive disease in patients with EGC :

1- Anemia 5-15 % 2- Weight loss 4 to 40 % By comparison, weight loss occurs in more

than 60 percent of those with advanced gastric adenocarcinoma

1-Weight loss, 2-Abdominal pain,3-Nausea and vomiting4-Early satiety.5-Peptic ulcer symptoms .

1- A palpably enlarged stomach, 2- primary mass (rare),3- An enlarged liver4-Virchow’s node 5-Sister Mary Joseph’s nodule 6- Blumer’s shelf (metastatic tumor felt on rectal examination, with growth in the rectouterine/rectovesical space).

Assists in determining optimal therapy.

CBC identifies anemia ,with maybe caused by bleeding ,liver dysfunction, or poor nutrition.

15-20% have anemia .

Tumor markers :1-CEA :carcino-embryonic antigen2-CA19-9:carbohydrte Antigen3-CA724: carbohydrate Antigen

1- Double-contrast barium swallow, a cost-conscious, noninvasive, and readily available study, may be the initial step.

2- Esophagogastroduodenoscopy (EGD) is the diagnostic imaging procedure of choice in the work-up of gastric carcinoma.

EGD is a highly sensitive and specific diagnostic test, especially when combined with endoscopic biopsy. Multiple biopsy specimens should be obtained from any visually suspicious areas; this step involves repeated sampling at the same tissue site, so that each subsequent biopsy reaches deeper into the gastric wall.

After the initial diagnosis of gastric cancer is established, further evaluation for metastases is necessary to determine treatment options.

1- Computed tomographic (CT) scanning is a useful method of detecting liver metastases greater than 5 mm in diameter, perigastric involvement, peritoneal seeding, and involvement of other peritoneal structures (e.g., ovaries, rectal shelf).

CT scanning is unable to allow assessment of tumor spread to adjacent lymph nodes unless they are enlarged. In addition, it has not been shown to be effective in allowing determination of the depth of tumor invasion and cannot reliably support detection of solitary liver or lung metastases smaller than 5 mm in diameter.

Endoscopic ultrasonography (EUS) is a modality that allows for more accurate staging. In EUS, the transducer is placed directly next to the gastric wall, and high-frequency sound waves are used to determine the depth of tumor invasion and detect local lymph node involvement, which may be assessed by operative biopsy.

As with all types of cancer, the most important indicator of resectability and prognosis for gastric cancer is the clinicopathologic stage.

There are several similar staging classifications, but in the United States, the most commonly used system is the American Joint Committee on Cancer TNM (tumor, node, metastasis) staging system .

The two most important factors influencing survival in patients with resectable gastric cancer are

1- Depth of cancer invasion through the gastric wall

2- Number of lymph nodes involved.

1- Primary tumor (T) T0: No evidence of primary tumor Tis: Carcinoma in situ: intraepithelial tumor

without invasion of the lamina propria T1: Tumor invades lamina propria or

submucosa T2: Tumor invades the muscularis propria or

the subserosa* T3: Tumor penetrates the serosa (visceral

peritoneum) without invading adjacent structures.

T4: Tumor invades adjacent structures.

N0: No regional lymph node metastasis

N1: Metastasis in 1 to 6 regional lymph nodes

N2: Metastasis in 7 to 15 regional lymph nodes

N3: Metastasis in more than 15 regional lymph nodes

M0: No distant metastasis

M1: Distant metastasis

Stage 0 Tis, N0, M0

Stage IA T1, N0,M0 Stage IB T1, T2, M0 Stage II T1, N2, M0 T2, N1, M0 T3, N0, M0

Stage IIIA T2a, N2, M0 T3, N1, M0

T4, N0, M0

Stage IIIB T3, N2, M0

stage IV T4, N1, M0 T4, N2, M0 T4, N3, M0 T1, N3, M0 T2, N3, M0 T3, N3, M0 Any T, any N, M1

1. Surgery2. Chemotherapy3. Radiation therapy4. Chemoradiation5. Targeted therapy

Surgery is a common treatment of all stages of gastric cancer. The following types of surgery may be used:

Subtotal gastrectomy: nearby lymph nodes , and parts of other tissues and organs near the tumor. The spleen may be removed.

Total gastrectomy: Removal of the entire stomach, nearby lymph nodes, and parts of the esophagus, small intestine, and other tissues near the tumor. The spleen may be removed.

Chemotherapy drugs commonly used to treat stomach cancer include:

1.cisplatin 2.epirubicin 3.and fluorouracil (also called 5FU).

These drugs may be given together as the ECF regimen.

It may be used before surgery to reduce the size of the tumor , or after surgery to reduce the risk of cancer coming back after surgery.

It may also be used to try to slow down the cancer and improve quality of life if an operation to remove the cancer isn’t possible.

Chemotherapy is often a successful treatment for stomach cancer.

However, it doesn’t always shrink the cancer and may cause side effects without giving much benefit.

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation .

There are two types of radiation therapy. External radiation therapy and Internal radiation therapy uses a radioactive substance sealed in needles, seeds , wires, or catheters that are placed directly into or near the cancer.

studies have shown that patients receiving combined chemoradiation therapy have demonstrated improved disease-free survival and improved overall survival rates.

In one series,29 patients were randomized to receive postoperative radiotherapy and 5-fluorouracil chemotherapy or surgery alone. Results of this study demonstrated improved survival in the patients receiving adjuvant therapy compared with those who received surgery alone (52 percent three-year survival versus 41 percent, respectively).

.

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells.

Monoclonal antibody therapy is a type of targeted therapy used in the treatment of gastric cancer.

These antibodies can identify substances on cancer cells or normal substances that may help cancer cells grow. The antibodies attach to the substances and kill the cancer cells, block their growth, or keep them from spreading

A recombinant humanized monoclonal antibody directed against the human epidermal growth factor receptor 2 (HER2). After binding to HER2 on the tumor cell surface, trastuzumab induces an antibody-dependent cell-mediated cytotoxicity against tumor cells that overexpress HER2. HER2 is over expressed by many adenocarcinomas, particularly gastric and breast adenocarcinomas

Many patients present with distant metastases or direct invasion of organs, obviating the possibility of complete resection. In the palliative setting, radiotherapy may provide relief from bleeding, obstruction, and pain in patients with advanced disease, although the duration of palliation is short (mean, six to 18 months). Surgical procedures such as wide local excision, partial gastrectomy, total gastrectomy, or gastrointestinal bypass also are performed with palliative intent, to allow oral intake of food and alleviate pain.

The value of screening asymptomatic individuals for gastric cancer remains controversial

Mass screening programs have been implemented in some countries (eg, Japan, Venezuela, and Chile) where there continues to be a high incidence of gastric cancer By contrast, the relatively low incidence of gastric cancer in other regions (including the United States) makes this strategy costly and unwarranted.

In low risk regions case-finding rather than mass screening is the most appropriate approach for early detection.

Screening methods and intervals vary in different settings.

Population screening for gastric cancer in Japan, for example, is recommended for individuals older than 40 years.

In contrast, gastric cancer screening every two years via either upper gastrointestinal series or upper endoscopy has been recommended in Korea for individuals aged 40 years and older.

Screening has traditionally involved a simple Risk interview and barium studies.

The barium studies include the conventional double contrast barium x-ray with photofluorography or

The new double contrast barium x-ray with digital radiography.

An upper endoscopy is performed if any abnormality is detected

The new guidelines by the American College of Physicians (ACP) recommend against screening the general population with GERD this way, partly because the cancer is rare even in this at-risk group.

Although the ACP guidelines are similar to those of organizations such as the American Gastroenterological Association, they stand apart for specifically recommending against screening women with GERD for esophageal cancer.

The ACP guidelines do recommend screening men over 50 who have had GERD for more than five years and who have other risk factors for esophageal cancer, including smoking and being overweight, because this group faces elevated esophageal cancer risk.

The guidelines, based on a review of current research on GERD and the use of endoscopy, were published Dec. 4 in the Annals of Internal Medicine.

The guidelines point to two other groups that should receive an upper endoscopy. One is people who experience GERD along with symptoms including vomiting and difficulty swallowing, which can be signs of treatable conditions, such as narrowing of the esophagus.

Upper endoscopy is also recommended for those who continue to have heartburn despite medications.

Primary prevention with H. pylori eradication — The recognition of H. pylori as a gastric carcinogen has provided the opportunity to institute strategies aimed at primary prevention through its eradication. Emerging data point toward the effectiveness of such approaches .

Some of the most direct evidence was provided in a controlled trial from China in which 1630 healthy carriers of H. pylori infection were randomly assigned to H. pylori eradication or placebo precancerous lesions at baseline.

Routine screening for gastric cancer is not recommended outside of a few countries with a high gastric cancer burden that have already implemented screening programs. The effectiveness of these programs is unclear.

Eradication of H. pylori has the potential to reduce the burden of gastric cancer, Large scale studies are urgently needed to clarify the targeted population and cost effectiveness of mass screening of H. pylori and the subsequent eradication strategy in different populations with different gastric cancer incidences.

In populations with a low gastric cancer burden, the decision to recommend a screening program should be made on an individual patient basis. Periodic upper endoscopy (possibly with specialized techniques such as chromoendoscopy or magnification endoscopy) can be offered to patients who are considered to be at increased risk , although the benefits and risks of such an approach are unclear.

Questions ?ReferenceAAFP.Up to Date .National Cancer institute.Medscape .Myoclinic.com