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Primary Therapy: Surgical Method—Gastric Cancer
Surgical excision has traditionally been the first treatment for gastric carcinoma. Because many patients have occult distant metastases at presentation and improved results have been demonstrated with preoperative chemotherapy61,62, neoadjuvant treatment is appropriate when preoperative staging is consistent with ≥T3 primary tumors and/or ≥N1 disease. The increasing prevalence of proximal gastric cancers, especially in the developed world, has resulted in more operations encompassing a thoracic component of resection to obtain an adequate proximal margin and remove intrathoracic lymph nodes at risk for metastasis.
Surgical excision of the gastric and nodal components of disease remains the primary therapy for all potentially curable gastric carcinomas. Based on pathological findings, the Japanese Research Society for Gastric Cancer has defined four categories of surgical resection: (1) absolute curative (no peritoneal or hepatic metastases, no serosal involvement, and a level of lymph nodes removed beyond those involved); (2) relative curative (same as category 1 but nodal involvement to the level excised); (3) relative noncurative (complete gross tumor excision but curative criteria not met); and (4) absolute noncurative (residual cancer).50 Most curable tumors can be removed with adequate margins by subtotal gastrectomy; total gastrectomy is used when mandated by proximal cancer location or disease extent. Routine total gastrectomy does not improve survival by providing wider margins and eliminating multicentric disease but it may increase the rates of patient morbidity and mortality. A randomized study63 showed similar survival rates with subtotal and total gastrectomy. Surgical resection alone, including endoscopic mucosal resection in selected patients,64 is an excellent treatment for gastric carcinomas limited to the mucosa or submucosa without nodal involvement (TIS or T1N0M0). These early gastric cancers now occur with an incidence of more than 30% in Japan but still less than 5% in the United States and other Western countries. At least one Japanese report showed similar excellent results for T2 cancers if lymph nodes were uninvolved.65 For the more invasive gastric carcinomas, curative or palliative resection is indicated for 50% to 60% of patients at the time of disease presentation, but only 25% to 40% of these patients will have potentially curative surgical procedures.
Increasingly, subtotal66 and total67 laparoscopic gastrectomies are being performed safely and without apparent compromise of patient outcome. Laparoscopic gastrectomy has reduced morbidity and mortality in controlled trials compared with open resection of mostly clinical early gastric cancers (pathological T1/T2, N0 cancers). Longterm results comparing patient survivals and large controlled trials comparing laparoscopic and open gastrectomy in advanced gastric cancers have yet to be reported.
Only one prospective randomized trial63 exists with regard to the extent of gastric resection, but extensive experience exists with various different surgical procedures, and appropriate generalizations can be made. The preferred treatment for lesions arising in the body or antrum of the stomach is a radical distal subtotal resection (Fig. 75-2). This procedure removes approximately 80% of the stomach along with the first portion of the duodenum, the gastrohepatic and gastrocolic omenta, and the nodal tissue adjacent to the three branches of the celiac axis. Extensive or proximal cancers will require a total gastrectomy to achieve an adequate proximal gastric margin (Fig. 75-3). Total gastrectomy provides no advantage when subtotal gastrectomy will provide a 5-cm clearance of the gross tumor. The propensity for gastric carcinoma to spread via submucosal and subserosal lymphatics dictates the need for a 5-cm surgical resection margin of normal stomach beyond the visible tumor. It may be necessary to extend the resection to include some (or additional) esophagus or duodenum if frozen-section pathological evaluation of the surgical margins fails to confirm the adequacy of proximal and distal resection margins. If total gastrectomy is necessary, a splenectomy is sometimes performed, particularly in gastric cancers of the proximal third of the stomach, and tumors of the body near the greater curvature. These cancers are more apt to metastasize to lymph nodes in the splenic hilum that cannot be completely excised without a splenectomy. Routine splenectomy is no longer practiced because of the increased complications found in randomized controlled68,69 and retrospective studies. A splenectomy should be performed when worrisome, palpable nodes are present in the splenic hilum.
Direct spread beyond the gastric wall should be treated with en bloc extended resection to achieve negative margins of resection, if a curative resection is contemplated.70,71 These extended resections are potentially curative but increase perioperative morbidity and mortality. Common examples of local tumor extension include involvement of the body or tail of the pancreas (treated by distal pancreatectomy and splenectomy), invasion of the transverse mesocolon (often requires transverse colectomy), and involvement of the spleen (splenectomy) or left lobe of the liver (usually requires wedge resection with a 1-cm or wider clearance).
The optimal extent of lymph node dissection for gastric cancer remains controversial. The presence and extent of lymph node metastasis correlate with the depth of primary tumor invasion.72 Japanese surgeons universally advocate regional lymph node removal for all but in situ or intestinal mucosal tumors as a means to improve both local control and survival.73 Because more distal nodes can be involved with metastasis in 11% of patients with negative perigastric nodes, a wider regional nodal dissection is deemed necessary for cure.72 A recent study of sentinel lymph node biopsies in gastric cancer patients in Japan74 demonstrated that 37% of tumors drained to N2 nodes, either in combination with N1 sentinel nodes (32%) or as the sole site of lymphatic drainage (5%). When a radical subtotal gastrectomy and omentectomy is performed, all perigastric (D1) lymph nodes along the lesser curvature and those on the greater curvature distal to the site of transection should be removed. In many major cancer centers, the lymph nodes adjacent to the celiac axis and its branches (D2) are also resected with a limited increase in postoperative morbidity (D2 dissection; see E-Fig. 75-2 regarding D2 dissection; N1, perigastric nodes; N2, nodes along the left gastric, common hepatic, celiac, and splenic arteries). Some surgeons in Japan routinely remove N3 lymph nodes (D3 dissection, usually portal and retropancreatic). A more recent randomized trial comparing a Japan D2 versus extended D2 resections75 shows a very low operative mortality and low morbidity with no significant increase in complications, nor as yet, any improvement in patient survival.
Thus far, randomized trials76,77 have not demonstrated either disease-free or overall survival (OS) advantage for extended lymphadenectomy (D2 dissection). A large multicenter phase III study that accrued 711 curable gastric cancer patients in the Netherlands76 noted significantly higher morbidity and mortality rates with the more extensive nodal dissection (Table 75-3). A randomized study from the United Kingdom that included 400 patients with gastric adenocarcinoma also demonstrated higher morbidity and mortality rates in the extended lymphadenectomy cohort (see Table 75-3).77 Neither the Dutch76 nor the British trial77 demonstrated any improvement in overall or disease-free survival (see Table 75-3). In the Dutch study,76 patients who did not undergo a splenectomy or distal pancreatectomy had an improvement in relapse-free survival ([RFS] 71% vs. 59% at 5 years, P = 0.02). Splenectomy and pancreatectomy had significant adverse impact on survival in both trials.76,77 Preliminary data from a Japanese trial comparing D2 and extended D2/D3 resections75 and an Italian study comparing D1 and D2 resections78 did not show increased morbidity with extended lymphadenectomy. Results for disease-free and long-term OS are not yet available from either study.
Any potential survival benefit seen with the extended node dissection performed in Japan may be due to the phenomenon of a stage migration rather than superior surgical therapy.79 In Japan and the United States, gastric resection specimens are handled quite differently.80 Japanese pathologists evaluated an average of 62 nodes in subtotal gastrectomy specimens and as many as 100 in total gastrectomy cases, including lymph nodes less than 3 mm in diameter.81 This number compares with an average of 12 and 13 nodes examined after subtotal and total gastrectomy, respectively, at Memorial SloanKettering.82 Patient survival after a curative operation significantly improves when more than 15 lymph nodes are pathologically examined.83,84 Failure to evaluate an adequate number of regional lymph nodes probably results in the understaging of many gastric cancer patients. N2 nodes cannot be defined as positive if they are not resected and examined; involvement of resected N1 nodes cannot be assessed if the specimen is not thoroughly evaluated by the pathologist. Most patients with more than six lymph node metastases or with lymph node metastasis not adjacent to the primary tumor still have a very poor outcome.16 Extended lymph node dissection seems reasonable for experienced surgeons who can perform this procedure without significantly increased surgical morbidity or mortality, because it improves pathological staging.75,78,85
Endoscopic laser surgery has been used in selected individuals with early gastric cancer.64,86 Small lesions (≤3 cm) that are not ulcerated, do not involve the submucosa, and are well differentiated infrequently have lymph node metastasis (<5%). As many as 75% of these select tumors can be completely removed endoscopically. Although early gastric cancer may have a long natural history before progression, standard surgical resection rather than endoscopic removal is still preferable for most Western patients.