Download Esoph and Gastr Cancer

Esophageal and Stomach
Cancers
Prof. Igor Y. Galaychuk, MD
Chief, Department of Oncology &
Radiology TSMU
Predisposing factors for esophageal cancer
Predisposing factors for squamous cell cancer
a. 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 esophagus
a. 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. Obesity
c. 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
Tis
T1
T2
T3
T4
No evidence of primary tumor
Carcinoma in situ
Tumor invades lamina propria or submucosa
Tumor invades muscularis propria
Tumor invades adventitia
Tumor invades adjacent structures
N - Regional lymph nodes
N0 No regional lymph node metastases
N1 Regional lymph node metastasis
M - Distant metastasis
M0 No distant metastasis
M1 Distant metastasis
Stage grouping
Stage 0
Stage I
Stage IIA
Stage IIB
Stage III
Stage IV
TisN0M0
T1N0M0
T2N0M0, T3N0M0
T1N1M0, T2N1M0
T3N1M0, T4 Any N M0
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
CT
X-ray
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.
Treatment
Surgery
A 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 treatment
Palliating 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 photosensitivity 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 Therapy
Photodynamic 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 adenocarcinoma of the thoracic esophagus, combined-modality treatment (5fiuorouracil [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
Tis
T1
T2
T3
T4
No evidence of primary tumor
Noninvasive carcinoma in situ
Extension to submucosa
Extension to serosa
Extension through serosa
Invasion of adjacent organs
N Regional lymph nodes
N0
N1
N2
N3
No regional nodal metastases
Metastases in 1 to 6 regional lymph nodes
Metastases in 7 to 15 regional lymph nodes
Metastases in more than 15 regional lymph nodes
M Distant metastases
M0
M1
No distant metastases
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!