Esophageal and Stomach Cancers

Prof. Igor Y. Galaychuk, MD

Chief, Department of Oncology & Radiology TSMU

Predisposing factors for esophageal cancerPredisposing factors for squamous cell cancera. Howel-Evans syndrome or tylosis (hyperkeratosis of the palms and soles) is a rare genetic

disease that is transmitted as a mendelian-dominant trait (nearly 40% develop esophageal cancer).

b. Lye stricture (up to 30%), c. Esophageal achalasia (30%)d. Esophageal web (20%)e. Plummer-Vinson syndrome (iron-deficiency anemia, dysphagia from an esophageal web, and

glossitis, 10%)f. Short esophagus (5%), g. Peptic esophagitis (1%)h. Other conditions associated with squamous cell esophageal cancer(1) Patients with head and neck cancer (Field's cancerization theory)(2) Patients with celiac disease(3) Chronic esophagitis without Barrett's esophagus (4) Thermal injury to the esophagus because of drinking boiling hot tea or coffee (Russia,

China, and Middle East)Predisposing factors for adenocarcinoma of the esophagusa. Barrett’s esophagus is metaplastic replacement of squamous with intestinalized columnar

epithelium.(1) Adenocarcinomas associated with Barrett's esophagus constitute the cancer whose

incidence is most rapidly increasing worldwide, but particularly in white men.(2) In the United States, the incidence of adenocarcinoma of the esophagus has increased 6- to

7-fold since 1970. Patients with Barrett's esophagus have a 30- to 125-fold increased risk for esophageal adenocarcinoma compared with the average U.S. population.

b. Obesityc. Reflux esophagitis

Anatomy and parts of Esophagus

1. Cervical esophagus (end at 18 cm from the upper incisor teeth)

2.   Intrathoracic esophagus:

the upper thoracic portion (18 - 24 cm)

the mid-thoracic portion (24 - 32 cm)

the lower thoracic portion (32 - 36 cm).

3.Abdominal esophagus (36 - 40)

Structure of the esophageal wall:

Mucosa

Submucosa

Muscularis propria

Adventitia

Regional Lymph Nodes

Cervical esophagus:- Scalene, Internal jugular, Upper and lower cervical- Periesophageal, Supraclavicular

Intrathoracic esophagus:- Upper periesophageal, Subcarinal,- Lower periesophageal (below the azygous vein)- Mediastinal- Perigastric

Location of cancer in the esophagus

Cervical: 10%

Upper thoracic: 40%

Lower thoracic: 50%

Рак грудного відділу стравоходу

TNM Clinical Classification

T - Primary tumor T0 No evidence of primary tumorTis Carcinoma in situT1 Tumor invades lamina propria or submucosaT2 Tumor invades muscularis propriaT3 Tumor invades adventitiaT4 Tumor invades adjacent structures

N - Regional lymph nodesN0 No regional lymph node metastasesN1 Regional lymph node metastasis

M - Distant metastasisM0 No distant metastasisM1 Distant metastasis

Stage grouping

Stage 0 TisN0M0

Stage I T1N0M0

Stage IIA T2N0M0, T3N0M0

Stage IIB T1N1M0, T2N1M0

Stage III T3N1M0, T4 Any N M0

Stage IV Any T Any N M1

Symptoms and signs

Dysphagia is the most common complaint. Patients become unable to swallow solid foods and eventually liquids. Symptoms rarely develop until the esophageal lumen is greatly narrowed and metastases have occurred. Pain may or may not be present. Physical findings: cachexia, palpable supraclavicular lymph nodes, or hepatomegaly.

Diagnostic studies Esophagoscopy with tumor biopsy, barium esophagogram, chest radiograph, abdomen ultrasound Computed tomography (CT) scan staging predicts invasion or metastases with an accuracy rate of more than 90% for the aorta, tracheobronchial tree, pericardium, liver, and adrenal glands; 85% for abdominal nodes; and 50% for paraesophageal nodes.Endoscopic ultrasound (EUS) is more accurate than CT in assessing tumor depth and paraesophageal nodes. Transesophageal biopsy to sample enlarged lymph nodes is possible under EUS guidance.Laparoscopy allows assessment of subdiaphragmatic, peritoneal, liver, and lymph node metastases. Bronchoscopy for tumors of the upper or middle esophagus can diagnose direct tumor extension into the tracheobroncheal tree

Esophageal Carcinoma

The carcinoma is shown as a mass around the lumen of the oesophagus (arrow). Subcarinal nodes (N) are also present. Ao, descending aorta; RPA, right pulmonary artery . There is an irregular stricture with shouldering (arrow) at the upper end.

CT X-ray

TreatmentSurgeryA standard esophagectomy for cancer includes resection of the esophagus with at least a 5-cm margin of normal esophagus above the most proximal gross extent of tumor, the surrounding soft tissues and lymph nodes, and the proximal stomach including lesser curve lymph nodes. Concerns about the incidence of persistent disease and local recurrence in patients with esophageal cancer prompted the development of more extensive resections of the primary tumor and regional lymph nodes in the late 1960s, termed radical en bloc esophagectomy. The extent of an en bloc esophagectomy varies among surgeons. In the case of tumors adjacent to the esophageal hiatus, a rim of diaphragm is removed. An attempt is made to establish proximal and distal margins of resection at least 10 cm from the extent of gross tumor. In the case of tumors of the cardia, some surgeons recommend total gastrectomy as part of the en bloc dissection. A true en bloc dissection is only possible for neoplasms of the middle and lower thoracic esophagus and the cardia. The surgical procedures employed in esophagectomy depend on the location and preference of the surgeon and include principally transhiatal esophagectomy or the Ivor-Lewis procedure, which requires both thoracotomy and laparotomy. In the 25% to 30% of patients in whom complete resection is possible, 5-year survival rates of 15% to 30% are reported.

Treatment

Surgery for Cervical Esophageal Cancer.Neoplasms of the cervical esophagus pose special problems with regard to surgical therapy. To obtain adequate surgical margins in tumors that extend to the cricopharyngeus muscle or invade the proximal trachea, it is necessary to include a laryngectomy as part of the resection, which adds substantial long-term morbidity to what is often a palliative procedure. As a result, a higher percentage of patients with cervical esophageal cancer are treated nonsurgically than is the case for patients with cancers in other locations. Resection provides good palliation for dysphagia but does not appear to substantially influence long-term survival. Combined chemoradiotherapy with or without surgery currently is being explored as a means to better control local disease

Subtotal resection

Reconstruction after Esophagectomy

Re-establishing alimentary tract continuity after esophageal resection in a manner that permits ingestion of a normal diet is an important component of surgery for esophageal cancer. Options for reconstruction include using the stomach as a substitute or interposing a segment of colon or jejunum between the proximal esophageal remnant and the stomach (or duodenum after total gastrectomy). The use of the stomach for reconstruction is by far the most common technique because the stomach has the most reliable blood supply among any of the reconstructive options and because only a single anastomosis is required, compared with the three anastomoses necessary for bowel interposition. Cervical anastomoses are favored by many surgeons because they decrease the incidence of acid reflux into the esophageal remnant and because anastomotic leaks are usually easily managed by simple cervical drainage. The disadvantages of cervical anastomoses are a higher incidence of recurrent laryngeal nerve injury and more frequent anastomotic leaks. Whether the additional tumor-free proximal margin provided by a cervical anastomosis offers a survival advantage has not been proven. Use of the posterior mediastinum (esophageal bed) for reconstruction optimizes emptying of the reconstructive organ but may predispose to tumor infiltration if a complete resection is not performed.

Reconstruction of esophagus

Esophageal resection

Variant of esophageal reconstruction

Palliative treatmentPalliating an obstructed esophagus can be accomplished by several

procedures and permits enteral nutrition.1. Laser therapy may relieve obstruction and bleeding. Endoscopic laser

therapy has less than a 1% mortality rate but may require prior mechanical dilation. Although successful laser therapy may require multiple endoscopic sessions, it can be done on an outpatient basis, and its overall cost is still much lower than the cost of palliative surgery. Photosensitization of esophageal tumors using an injectable porphyrin derivative can increase the laser energy absorbed by the tumor with palliative benefit but is associated with generalized dermal photo-sensitivity to sunlight lasting 4 to 6 weeks.

2. Esophageal stenting. At least 17 devices are available for esophageal intubation. About 15% of patients with malignant esophageal obstruction are candidates for tube placement. The tube may be introduced with a pusher tube, which is loaded either onto a bougie or over an endoscope and expands after placement. The latter method permits visualization of the obstructed lumen. The success rate is 90% to 97%.

3. Feeding gastrostomy is not advisable because it does not palliate dysphagia, which forces patients with complete or nearly complete esophageal obstruction to expectorate saliva and secretions, does not increase life expectancy, and has its own morbidity and mortality.

Gastrostomy

Palliative treatment

4. Photodynamic TherapyPhotodynamic therapy (PDT) is emerging as an option for treating patients with carcinoma in situ or superficial cancers who are unable to tolerate or who refuse resection. PDT is performed by first systemically administering a photosensitive compound, and after its uptake in tumor, strong areas of concern are endoscopically treated with low-level laser light to activate the compound, causing selective cell death through release of toxic oxygen metabolites. The complete response rate of 75 to 80% endures for several years, suggesting that some patients may be cured with this therapy. PDT also is being investigated as one of several techniques, including laser photocoagulation, argon beam cautery, and electrocautery, for ablating Barrett's muscosa as a means of preventing the development of adenocarcinoma. Current staging techniques are relatively inaccurate, and up to 50% of patients who undergo resection for high-grade dysplasia in Barrett's esophagus have invasive cancer.These data suggest that such endoscopic therapies should remain investigational or relegated as therapy for patients who are not candidates for resection.

Chemotherapy & Radiotherapy

Primary therapy without surgery. In patients not planning to undergo esophageal surgery because of co-morbid disease or patient or physician choice, combined chemotherapy and radiation can lead to long-term survival in some, as compared with surgery alone. In a prospective, randomized trial of patients with squamous cell or adeno-carcinoma of the thoracic esophagus, combined-modality treatment (5-fiuorouracil [5-FU] plus cisplatin plus 5000 cGy) resulted in improved median survival (9 months versus 12.5 months) when compared with RT alone (6400 cGy). The 2-year survival rate for patients randomized to combined chemotherapy and radiation was 38%, compared with 10% for those randomized to radiation alone. The patients receiving the combined-modality treatment experienced decreased local and distant recurrences but significantly more toxicity, much of which was serious or life-threatening. Only half of these patients received all the planned cycles of chemotherapy.

Chemotherapy and surgery. Response rate to multiagent neoadjuvant chemotherapy can be as high as 40% to 50%, and up to 25% of treated patients may have apparent pathologic complete remissions. Preoperative chemotherapy with cisplatin and 5-FU, however, did not improve overall survival when compared with surgery alone in a randomized trial of 440 patients with squamous esophageal cancer.

Radiation Therapy

External-beam irradiation or endoluminal brachytherapy can result in tumor regression with palliation in some cases. Up to 70% to 80% of patients with dysphagia may note improved swallowing after external-beam irradiation. Endoluminal brachytherapy can be useful in previously irradiated patients with local tumor regrowth causing dysphagia.Radiotherapy to a dose of 6000 cGy resulted in 1, 2, 3- and 5-year survival rates of 33%, 12%, 8%, and 7% of patients treated on the radiation arm of a randomized trial in which responding patients were permitted to go on to resection at physician discretion.

Stomach Cancer

Stomach Cancer

In Ukraine (2002) there were 14,015 (29.1 per 100,000) new cases of stomach cancers. Of these 8,456 (37.9 per 100,000) were diagnosed in men and 5,559 (21.4 per 100,000) in women. The death rates caused by stomach cancers were in men 31.0 and in women 17.0 per 100,000.

Mortality from gastric cancer is highest in Costa Rica (61 deaths per 100,000 population) and East Asia (Hong Kong, Japan and Singapore) and lowest in the United States (5 deaths per 100,000).

Risk factors

- Diet

- Helyc. pylori infection

- Heredity and race. African, Asian, and Hispanic Americans have a higher risk for gastric cancer than whites.

- Pernicious anemia, achlorhydria, and atrophic gastritis.

- Previous gastric resection

- Mucosal dysplasia

- Gastric polyps and Chronic gastritis

Location of cancers

Distal location: 40% Proximal: 35% Body: 25%

Histology. About 95% of gastric cancers are adenocarcinomas; 5% are leiomyosarcomas, lymphomas, carcinoids, squamous cancers, or other rare types

Anatomic location of stomach

TNM Staging of Gastric Cancer T Primary tumor

T0 No evidence of primary tumorTis Noninvasive carcinoma in situT1 Extension to submucosaT2 Extension to serosaT3 Extension through serosaT4 Invasion of adjacent organs

N Regional lymph nodesN0 No regional nodal metastasesN1 Metastases in 1 to 6 regional lymph nodesN2 Metastases in 7 to 15 regional lymph nodesN3 Metastases in more than 15 regional lymph nodes

M Distant metastasesM0 No distant metastasesM1 Distant metastases present

Symptoms and signs. Gastric cancer often progresses to an advanced stage before symptoms and signs develop. Symptoms of advanced disease include anorexia, early satiety, distaste for meat, weakness, and dysphagia. Abdominal pain is present in about 60% of patients, weight loss in 50%, nausea and vomiting in 40%, anemia in 40%, and a palpable abdominal mass in 30%. The abdominal pain is similar to ulcer pain, is gnawing in nature, and may respond initially to antacid treatment but remains unremitting. Hematemesis or melena occurs in 25% and, when present, is seen more often with gastric sarcomas.

Diagnostic studies

Preliminary studies include CBC, LFTs, esophagogastroduodenoscopy (EGD) or upper GI barium studies, and chest radiographs.

Endoscopy. The combination of flexible upper GI endoscopy with biopsy of visible lesions, exfoliative cytology, and brush biopsy is able to detect more than 95% of gastric cancers. Biopsy of a stomach lesion alone is accurate in only 80% of cases. Positive gastric cytology with no endoscopic or radiographic abnormalities indicates superficial spreading gastric cancer.

EUS is up to six times more accurate in staging the primary gastric tumors than CT, but differentiation between benign and malignant changes in the wall is often difficult. EUS is useful in imaging the cardia, which may be difficult to evaluate by CT. Lymph node biopsy can also be obtained by EUS guidance.

CT and US of the abdomen is useful for assessing the extent of disease. At laparotomy, however, half of patients are found to have more extensive disease than predicted by CT. Laparoscopy can identify patients with regionally advanced or disseminated disease who are not candidates for immediate potentially curative surgical intervention

Early noninvasive gastric carcinoma

Japanese Endoscopic Society Classification:

Type I – polypoid or masslike

Type II – flat, minimally elevated, or depressed

Type III – cancer associated with true ulcer

Early cancer: endoscopy

Type І Type ІІа+ІІс

Chromogastroscopy

Metastases of Gastric Cancer

Gastric carcinoma spreads by the lymphatic system and blood vessels, by direct extension, and by seeding of peritoneal surfaces. The ulcerative and polypoid types spread through the gastric wall and involve the serosa and draining lymph nodes. The scirrhous type spreads through the submucosa and muscularis, encasing the stomach, and in some instances spreading to the entire bowel. Often, the physical examination is normal.Widespread metastatic disease may affect any organ, especially the liver (40%), lung (may be lymphangitic, 40%), peritoneum (10%), supraclavicular lymph nodes (Virchow's node), left axillary lymph nodes (Irish's node), and umbilicus (Sister Joseph nodule). Sclerotic bone metastases, carcinomatous meningitis, and metastasis to the ovary in women (Krukenberg's tumor) or rectal shelf in men (Blumer's shelf) may also occur.

Gastric outlet obstruction. A carcinoma is causing narrowing of the antrum (arrow). The speckled appearance in the fundus of the

enlarged stomach is due to food residues

Рак антрального відділу шлунка

Malignant ulcer. The ulcer (arrow) does not project from the lumen of the stomach. Note how the mucosal folds do not reach

the ulcer crater. The stomach is narrowed by an extensive carcinoma converting it to a rigid tube with obliteration of

mucosal folds

Carcinoma. There are a number of large filling defects in the antrum and body of the stomach

Treatment The goal of a potentially curative operation is to remove all visible disease

en bloc. Although the impact of nodal metastasis is clearly important, there are many patients with gastric cancer who are cured of disease by surgery alone.

The various types of procedure to achieve gastrectomy include (1) subtotal gastrectomy (used for a tumor of the antrum or distal body), (2) total gastrectomy, and (3) proximal subtotal gastrectomy or esophagogastrectomy performed either with a transperitoneal approach or combined with a transthoracic approach. For proximal tumors, controversy concerning the benefits of a proximal subtotal versus a total gastrectomy notwithstanding, most data suggest that a total gastrectomy is the operation of choice. In most series that examine the relative survivals of patients undergoing an R0 resection, survival has been better for patients who have had a total gastrectomy. One possible explanation for this would be the complete removal of lesser curvature nodes. Althought some surgeons advocate a total gastrectomy for all procedures, the data do not support this as a routine practice. Nutritionally, patients who have a subtotal gastrectomy tend to fare somewhat better than those who have a total gastrectomy. Widespread or infiltrating tumors may require total gastrectomy.

Total Gastrectomy

Types of anastomoses after gastrectomy

Subtotal distant gastrectomy (Bilrot ІІ)

Gastro-enteroanastomose (Bilrot ІІ)

Subtotal proximal gastrectomy

Chemotherapy

Perioperatively. Intraperitoneal mitomycin (50 mg) given in one trial from Japan was associated with significantly higher patient survival than was noted in untreated patients. Side effects were mild and well tolerated.

Postoperatively. Intraperitoneal cisplatin and 5-FU followed by systemic 5-FU or 5-FU and mitomycin is being evaluated. Side effects are mainly neutropenia and sclerosing encapsulating peritonitis (are toxicity)

Chemotherapy for advanced disease. Single agents produce low response rates. Combination regimens produce higher response rates but are more toxic and more costly. Cisplatin has been increasingly used in new combinations that also yield higher response rates, but the incidence of important toxic events exceeds 10%. The reported response rates are about 20% for 5-FU alone and 10% to 50% for combination chemotherapy; the median survival times range from 5 to 11 months. After nearly two decades of using combination chemotherapy, including mitomycin, doxorubicin, epidoxorubicin, etoposide, methotrexate, nitrosoureas, irinotecan, or cisplatin, there is no regimen considered standard in the setting of advanced disease.

Radiation therapy Localized disease. RT alone has not proved useful for treating

gastric cancer. RT (4000 cGy in 4 weeks) in combination with 5-FU (15 mg/kg IV on the first 3 days of RT), however, appears to improve survival over RT alone in patients with localized but unresectable cancers. Intraoperative radiation (IORT) allows high doses of radiation to the tumor bed or residual disease while permitting the exclusion of mobile radiosensitive normal tissues from the area irradiated. Trials are limited to single institutional experiences; therefore, generalizing from such trials is difficult. Selected patients may benefit from IORT, particularly when combined with supplemental external-beam radiation and chemotherapy. Long-term survival has been reported in some patients treated in this fashion for residual disease after surgery.

Advanced disease. Gastric adenocarcinoma is relatively radioresistant and requires high doses of radiation with attendant toxic effects to surrounding organs. RT may be useful for palliating pain, vomiting due to obstruction, gastric hemorrhage, and metastases to bone and brain.

Thank you for your attention!