02/10/12

Gastric Cancer:

Therapy

Gastric Cancer:
Therapy

Therapy

Overview There are essentially three modes of therapy for the treatment of gastric cancer. Curative resection, including endoscopic resection, appears the most effective. Surgical resection entails the removal of the primary tumor and regional lymph nodes with resection margins free of tumor. Gastric cancer has not been shown to respond successfully to radiation alone. Chemotherapy has demonstrated limited success with multi-drug regimens.

Surgical Therapy The prognosis following surgical resection depends on the stage at presentation. Early tumors confined to the stomach lining have higher cure rates than cases in which disease has already spread to distant sites or regional lymph nodes. Cure rates have improved in the past 30 years, particularly in Japan. These improvements can be attributed mainly to an increase in early detection rates. The type of surgery performed depends on the extent and location of tumor; therefore, preoperative evaluation is critical. Initial staging may be established by endoscopy with biopsy. Endoscopic ultrasound should follow. Endoscopic Ultrasound (EUS) has a sensitivity of 85% in assessing depth of tumor invasion and detecting nodal involvement prior to surgery. Laparoscopic staging prior to surgical resection is also advocated and has impacted preoperative treatment decisions. There are two principle types of gastric resectionthe subtotal gastrectomy and the total gastrectomy (Figure 20). Determination of the type of resection depends on various factors including: 1) the location of the tumor, 2) the size and the extent of the tumor, and 3) the histology pattern.

Figure 20. A, Total gastrectomy; B, subtotal gastrectomy.

In addition to removal of the stomach, resections with curative intent generally include lymphadenectomy, or removal of regional lymph nodes. Controversy remains as to the extent of the lymphadenectomy required. Some advocate removal of nodes adjacent to the stomach (D1 dissection, Figure 21), while some centers, particularly in Japan, advocate more radical lymphadenectomy (D2, Figure 21).

Figure 21. Surgical lymphadenectomy; D1 and D2 indicate the extent of lymph node removal.

Occasionally, adjacent organs may need to be removed, including the spleen, omentum and liver. Following gastrectomy, intestinal continuity is restored using a variety of reconstruction techniques. When only the distal stomach is removed, reconstruction can be achieved by a Billroth II gastrojejunostomy (Figure 22).

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Figure 22. A, Low subtotal gastrectomy; B, Billroth II anastomosis.

When all or most of the stomach is removed, typically a Roux-en-Y esophagojejunostomy (Figure 23, A and B) or gastrojejunostomy (Figure 24, A and B) is performed.

Figure 23. A, Total gastrectomy; B, Roux-en-Y esophagojejunostomy.

Figure 24. A, High subtotal gastrectomy; B, w ith Roux-en-Y gastrojejunostomy.

Endoscopic Therapy Therapeutic endoscopy may be curative for early gastric cancer or palliative for more advanced disease. The decision to use endoscopic treatment as opposed to surgical resection is affected by tumor stage, location, morphology, prognosis of the disease, risk factors, assessment of resectability versus cure, and the associated morbidity with each procedure. The role of adjuvant systemic or regional therapy is also of importance. EUS provides valuable information regarding the stage and the feasibility of endoscopic therapy. Patients with more superficial lesions may be candidates for endoscopic (or surgical) resection, while patients with more advanced disease may require palliative therapy. Tissue resection or ablation, dilation of strictures, stent placement, palliation of bleeding, and the placement of feeding or decompression tubes may all be accomplished endoscopically. Endoscopic Mucosal Resection Endoscopic mucosal resection has been advocated for early gastric cancers, those that are superficial and confined to the mucosa. Endoscopic mucosal resection may be attempted in patients without evidence of nodal or distant metastases, with differentiated tumors that are slightly raised and less than 2 cm in diameter, or in differentiated tumors that are ulcerated and less than 1 cm in diameter. The most commonly employed methods of endoscopic mucosal resection include strip biopsy, double-snare polypectomy, resection with combined use of highly concentrated saline and epinephrine, and resection using a cap. The prognosis after treatment is comparable to that of surgical resection for early gastric cancer. Five-year survival rates for individuals undergoing endoscopic

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prognosis after treatment is comparable to that of surgical resection for early gastric cancer. Five-year survival rates for individuals undergoing endoscopic mucosal resection of early gastric cancers have been reported to be as high as 95%. The strip biopsy method is performed with a double-channel endoscope equipped with grasping forceps and snare. After marking the lesion border with an electric coagulator, saline is injected into the submucosa below the lesion to separate the lesion from the muscle layer and force its protrusion (Figure 25A). The grasping forceps are passed through the snare loop. The mucosa surrounding the lesion is then grasped, lifted, strangulated (Figure 25B), and resected by electrocautery (Figure 25C).

Figure 25. Endoscopic mucosal resection of early gastric cancer; injection and snare technique.

The endoscopic double-snare polypectomy method is indicated for protruding lesions. Using a double-channel scope, the lesion is grasped and lifted by the first snare and strangulated (Figure 26A) with the second snare for complete resection. (Figure 26 B).

Figure 26. Double-snare technique for endoscopic mucosal resection of early gastric cancer.

Endoscopic resection with injection of concentrated saline and epinephrine is carried out using a double-channel scope. The lesion borders are marked with a coagulator. Highly concentrated saline and epinephrine are injected (1520 ml) into the submucosal layer to force the protrusion of the area containing the lesion and elucidate the markings (Figure 27A). The mucosa outside the demarcated border is excised using a high-frequency scalpel to the depth of the submucosa. The resected mucosa is lifted and grasped with forceps, trapping and strangulating the lesion with a snare (Figure 27B), and then resected by electrocautery (Figure 27C).

Figure 27. Endoscopic mucosal resection show ing injection, circumferential marking, snare excision, and removal of early gastric cancer.

A fourth method of endoscopic mucosal resection employs the use of a clear cap and prelooped snare positioned inside the cap. After insertion, the cap is placed on the lesion and the mucosa containing the lesion is drawn inside the cap by aspiration. The mucosa is caught by the snare, strangulated, and finally resected by electrocautery. Using this method, it is possible to retain the resected specimen in the cap for histological examination. The major complications of endoscopic mucosal resection include postoperative bleeding and perforation of the gastric wall. According to the Japanese Society of Gastroenterological Endoscopy, the complication rate is 0.382 percent. Bleeding is usually discovered several days after the procedure. During the procedure, an

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Gastroenterological Endoscopy, the complication rate is 0.382 percent. Bleeding is usually discovered several days after the procedure. During the procedure, an injection of 100,000 times diluted epinephrine into the muscular wall, along with high frequency coagulation or clipping, may be applied to the bleeding point for hemostasis. It is important to administer acid-reducing medications to prevent postoperative hemorrhage. Perforation of the gastric wall may be prevented with sufficient saline injection to raise the mucosa containing the lesion. The non-lifting sign and complaints of pain with snare strangulation of the lesion are contraindications to endoscopic mucosal resection. When perforation is recognized immediately after a procedure, clips should be applied to close the perforation, followed by abdominocentesis and aspiration of air from the abdominal cavity. Surgery should be considered in cases of endoscopic closure failure. Endoscopic Palliation Tumor ablation may be achieved by endoscopic resection of an exophytic mass or polyp using a diathermic snare, alcohol injection, or thermal or non-thermal destruction. Tumor traction and elevation from the wall with secondary snare resection using a double-channel endoscope has been proposed. Because the resected base is larger, there is a greater probability of obtaining clear margins. Thermal photodestruction may be induced by laser. The Nd:YAG laser (Figure 28), generating an infrared beam in a continuous or pulse mode, is applied through direct contact with tumor tissue or in a non-contact fashion. This method provides focal tumor destruction and is well suited for exophytic masses to regain lumen or to control bleeding. The Nd:YAG is best suited for soft, non-constricting, non-circumferential cancers; however, its use is limited because of expense and the need for frequent treatment sessions. Tumor destruction may also be achieved by non-thermal methods with photodynamic therapy (PDT). Following the oral or intravenous administration of a photosensitizing drug, the tumor area is exposed to low-power red light (dye laser emitting 630 nm). Currently, PDT is applied to small tumors 12 cm thick because penetration is only a few millimeters into the tissue. Moreover, PDT is associated with the risk of delayed hemorrhage following the partial necrosis of large lesions. PDT may also be used as complementary therapy with other techniques. For example, if the majority of a cancer is removed surgically, PDT may be used to destroy any remaining small areas. Thorough understanding of the biology involved is essential before the potential of PDT can be realized in treating gastrointestinal tumors.

Figure 28. Endoscopic palliative techniques.

Pure ethanol injection into a tumor induces immediate necrosis. Aliquots of 0.2 ml injection of pure alcohol are safe and effective. Care must be taken with regard to the amount of alcohol injected, because the depth of penetration is not predictable. Like laser therapy, over zealous treatment may result in perforation. Intratumoral injection of cytotoxic agents has also been used preoperatively or as palliative treatment. Injection with OK-432 causes degeneration of cancer tissue in carcinoma of the stomach. Studies have demonstrated that preoperative intratumoral injection of OK-432 improved five-year survival rates in patients with stage III cancer.

Chemotherapy Adenocarcinoma of the stomach is relatively sensitive to chemotherapy. Fluorouracil (5-FU) is the most commonly used drug in the treatment of gastric cancer, with a response rate around 21%. In an attempt to improve this rate, drug combinations have been tried; the most common is 5-FU, doxorubicin, and mitomycin C (FAM) with a response rate of 33% and an acceptable degree of toxicity. Other drug combinations have been tried, although the response duration and overall survival, when compared with 5-FU alone, were not significantly different. In addition, the combination groups had a higher toxicity rate. Newer investigational modalities employ tumor antigen-specific immunochemotherapy. Antibodies to tumor antigens are conjugated with chemotherapeutic drugs; in this way, the drugs can be delivered to the tumor directly.

Complications
Bleeding Bleeding may be controlled by endoscopic thermal techniques such as laser and multipolar electrocoagulation. After resuscitation and stabilization of the patient, endoscopy is the preferred procedure for treating hemorrhage . Gastric lavage is usually performed to remove blood from the stomach prior to endoscopy. The goal of endoscopic therapy is to stop the bleeding and/or oozing from the surface of the tumor. This may be achieved using laser, MPEC, or cauterization (Figure 29).

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Gastric Cancer:

Therapy

Figure 29. Laser palliation of a bleeding tumor.

Gastric Outlet Obstruction Gastric outlet obstruction is commonly associated with malignancy. CT scans and oral contrast radiographs are useful in diagnosis of this complication. The findings of a large gastric silhouette, gas bubble, and little or no air in the small intestine or the colon are consistent with gastric outlet obstruction. Surgery and/or endoscopy may be used for palliation of gastric outlet obstruction. Surgical procedures, especially for recurrent disease, carry a high risk of complications and have limited potential for long-term survival. Patients who have undergone tumor resection and then present with symptoms suggestive of recurrence should be evaluated endoscopically. Endoscopy is the best procedure for evaluating gastric outlet obstruction after a 1224 hour suctioning of the stomach. Non-surgical approaches should be the principal considerations in these patients. Endoscopic Therapy Endoscopic dilation of the gastric outlet obstruction is a reasonable palliative course. Balloon dilation can usually improve the acute problem by producing radial forces on the strictured segment. Through-the-scope balloons are usually the first choice (over guide wire balloons), using the largest balloon that can be safely passed into the segment. A well-lubricated balloon is passed through the endoscopic biopsy channel and carefully positioned in the stricture. The balloon is inflated with contrast, water, or air, and pressure is maintained for the desired time. Dilation may also be performed over a guide wire that is passed through the stricture. Sequential balloon dilation is performed with fluoroscopy and endoscopic evaluation. In the presence of a malignant gastric outlet obstruction, selfexpanding stents have been placed endoscopically for the treatment of obstruction (Figure 30).

Figure 30. Endoscopic palliation of gastric outlet obstruction w ith an expandable metal stent; A, gastric obstruction; B, placement of the stent; B, endoscopic view .

Good palliation of obstructive symptoms allows patients to consume liquid diets, preventing dehydration and frequent hospital admissions. Stent migration and occlusion are possible complications. These problems may be successfully resolved by implantation of a second stent or electrocoagulation of tumor overgrowth. Percutaneous endoscopic gastrostomy (PEG) has been used for decompression of gastrointestinal tract obstructions and most commonly for enteral feeding (Figure 31). In a study of 53 patients with gastric or small-bowel obstruction, endoscopic gastrostomies were performed for decompression. Decompression was

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(Figure 31). In a study of 53 patients with gastric or small-bowel obstruction, endoscopic gastrostomies were performed for decompression. Decompression was successful in 89% of these cases with low complication rates.

Figure 31. Technique for percutaneous endoscopic gastrostomy tube placement. (Click on the blue letters to view the consecutive images)

Surgical Therapy The goal of surgical therapy for the treatment of gastric outlet obstruction is to remove the obstruction. Gastric outlet obstruction resulting from gastric cancer should be resected by distal partial gastrectomy or subtotal gastrectomy with lymphadenectomy.

Figure 32. A, Subtotal gastrectomy w ith B, Billroth II gastrojejunostomy

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