Surgical Considerations in the Treatment of Gastric Cancer




Gastric cancer is one of the most common malignancies in the world and is a leading cause of cancer death. Surgical treatment remains the best treatment option for potential cure and can be beneficial in the palliation of advanced disease. Several neoadjuvant chemotherapy regimens have been recently evaluated as potential adjuncts to surgery. This review describes the current role of surgical therapy in staging, resection, and palliation of gastric cancer.


Key points








  • Surgical resection remains the only potentially curative treatment of gastric cancer.



  • Newer staging modalities aid in minimizing unnecessary laparotomy in noncurative disease.



  • Adequate lymphadenectomy may improve outcomes, similar to selective resection of adjacent organs based on tumor invasion.



  • Lymph node involvement and positive surgical margins are associated with poorer overall survival.



  • Neoadjuvant chemotherapy may downstage responsive tumors and may improve survival even with extensive lymphatic disease.



  • Palliative surgery for advanced gastric cancer remains important in providing symptom relief in appropriately selected patients.






Introduction


Despite steady declines in the incidence and mortality, gastric cancer is the 5th most common malignancy diagnosed in developed countries in both men and women, with more than 270,000 new diagnoses in 2011. More than 180,000 deaths from gastric cancer were reported for the same year, reflecting a high cancer-related mortality rate. Fatality rates are high in most countries (overall mortality approximately 70%–90%) except in Japan (40%), and stomach cancer ranks 2nd as a cause of cancer-related death. Surgical resection remains the treatment of choice for gastric cancer. Improvements in multimodal chemotherapy and radiotherapy, however, have influenced clinical decision making and treatment algorithms. The largest reported experience in the surgical treatment of gastric cancer originates from the East Asia, especially Japan and Korea. New data from Western centers have reproduced many of these findings. This review aims to evaluate the role of surgery in the staging, resection, and palliation of gastric cancer.




Introduction


Despite steady declines in the incidence and mortality, gastric cancer is the 5th most common malignancy diagnosed in developed countries in both men and women, with more than 270,000 new diagnoses in 2011. More than 180,000 deaths from gastric cancer were reported for the same year, reflecting a high cancer-related mortality rate. Fatality rates are high in most countries (overall mortality approximately 70%–90%) except in Japan (40%), and stomach cancer ranks 2nd as a cause of cancer-related death. Surgical resection remains the treatment of choice for gastric cancer. Improvements in multimodal chemotherapy and radiotherapy, however, have influenced clinical decision making and treatment algorithms. The largest reported experience in the surgical treatment of gastric cancer originates from the East Asia, especially Japan and Korea. New data from Western centers have reproduced many of these findings. This review aims to evaluate the role of surgery in the staging, resection, and palliation of gastric cancer.




Gastric cancer staging


Histologic Staging


Staging of gastric cancer is according to depth of invasion (T stage), number of lymph node metastases (N stage), and presence of distant disease (M stage). Starting January 1, 2010, newly diagnosed gastric cancers were to be staged using the 7th edition of the TNM staging system ( Table 1 ). The differences between the 6th and 7th editions specifically regarding gastric cancer pertain mostly to depth of tumor invasion, including




  • T1 subdivided to delineate mucosal versus submucosal lesions



  • T2a and T2b changed to T2 and T3 to represent muscularis propria and subserosa invasion, respectively



  • T3 and T4 changed to T4a and T4b to represent serosal perforation and invasion of adjacent structures, respectively



Table 1

TNM staging classification, 7th edition; stages 0 to IIIC are M0




























T Stage N Stage Stage
Tis: carcinoma in situ N1: 1–2 nodes Stage 0: TisN0
T1a: lamina propria
T1b: submucosa
N2: 3–6 nodes Stage IA: T1N0
Stage IB: T2N0, T1N1
T2: muscularis propria N3a: 7–15 nodes
N3b: >15 nodes
Stage IIA: T3N0, T2N1, T1N2
Stage IIB: T4aN0, T3N1, T2N2, T1N3
T3: subserosa Stage IIIA: T4aN1, T3N2, T2N3
Stage IIIB: T4bN0, T4bN1, T4aN2, T3N3
Stage IIIC: T4bN2, T4bN3, T4aN3
T4a: perforates serosa
T4b: invades adjacent structures
Stage IV: any T, any N, M1


  • Positive cytology is M1 disease



Historically, the Siewert criteria published in 1998 have been used to classify adenocarcinomas arising at or near the gastroesophageal junction (GEJ) :




  • Type I: lesion of the distal esophagus, 1–5 cm proximal to the GEJ



  • Type II: lesion arising within the GEJ, within 1 cm proximal and 2 cm distal to the GEJ



  • Type III: Lesion arising 2 cm to 5 cm distal to the GEJ with invasion into the esophagus



As part of the 7th edition of the TNM staging system, GEJ adenocarcinomas were also reclassified as follows:




  • A lesion with its center within 5 cm of the GEJ and with extension into the esophagus is staged using esophageal carcinoma criteria.



  • A lesion with its center within 5 cm of the GEJ but without extension into the esophagus, and a lesion with its center greater than 5 cm away from the GEJ are staged using gastric carcinoma criteria.



To evaluate the clinical effects of the new TNM staging system, Suh and colleagues retrospectively reviewed adenocarcinoma of the GEJ in 497 patients operated on with curative intent based on Siewert classification, from 2003 to 2009. On analysis of staging, 11 of 230 (4.6%) lesions that before would have been classified as TNM stage I under gastric guidelines were upstaged to TNM stage II esophageal lesions. The 5-year survival rates of gastric TNM stage I and esophageal TNM stage II in this study were 92.1% and 90.6%, respectively. Meanwhile, 20 of 125 (16.0%) gastric TNM stage II cancers were upstaged to esophageal TNM stage III cancers. The 5-year survival rates of gastric TNM stage II and esophageal TNM stage III in this study were 84.6% and 51.4%, respectively. The investigators argued that the new guidelines did not adequately distinguish GEJ tumors, because upstaging did not correlate with clinical outcomes.


Surgical Staging


Two-thirds of patients with gastric cancer in the United States present with advanced disease, and the majority show no significant findings on physical examination. The development of specific physical signs usually indicates metastatic disease.


For years, laparotomy was the standard surgical procedure for staging. On gross inspection, the decision between a resection with curative intent versus a nontherapeutic or noncurative procedure was made based on nodal disease, extension into adjacent organs, or distant metastasis. Preoperative CT scans and MRI have not been able to detect noncurative disease in all patients. As technology has progressed, new staging modalities have emerged, including staging laparoscopy, endoscopic and intraoperative ultrasound, and peritoneal washings for cytology. With advances made in neoadjuvant chemotherapy, minimally invasive staging methods have become more important for optimal management.


Staging laparoscopy was compared with preoperative staging CT scan by Burke and colleagues. Between 1990 and 1995, 103 patients with newly diagnosed gastric adenocarcinoma and no evidence of intra-abdominal metastatic disease on CT scan underwent staging laparoscopy. Sixty contemporary patients who underwent staging laparotomy were selected from the same prospective database as a control. Frozen sections were taken of suspicious lesions to evaluate for metastasis: 32 (31.1%) had biopsy-proved metastatic disease and 71 had no laparoscopic evidence of metastasis, of whom 6 (8.5%) had metastases on laparotomy (n = 3) or in distant lymph nodes after resection (n = 3). In this study, staging laparoscopy had a sensitivity of 94% and a specificity of 100%. Patients with metastatic disease confirmed during laparoscopy avoided the unnecessary morbidity of laparotomy. Karanicolas and colleagues reviewed the Surveillance, Epidemiology and End Results cancer database to analyze frequency of staging laparoscopy in the general population. Patients over 65 years of age diagnosed with gastric adenocarcinoma between 1998 and 2005 who underwent a surgical procedure related to gastric cancer were identified. Of 6388 patients, 506 (8%) underwent staging laparoscopy, of whom 306 (60%) underwent therapeutic intervention, 49 (10%) proceeded to laparotomy but no therapeutic procedure, and 151 (30%) underwent only laparoscopy. Use of staging laparoscopy increased over time (5.5% in 1998 to 11.1% in 2005, P <.01), and patients tended to be young and white, living in the Northeast, and with proximal cancers, and they had fewer comorbidities than those who did not undergo staging laparoscopy. Although increasing in use, staging laparoscopy seems to remain underutilized in its potential benefit of avoiding unnecessary laparotomy.


To evaluate endoscopic ultrasound (EUS) compared with staging laparoscopy, Power and colleagues prospectively reviewed patients being evaluated for neoadjuvant chemotherapy. Between 2003 and 2005, 94 patients without evidence of metastatic disease on staging CT scan or MRI were analyzed. Those with T1–2 and N0 lesions on EUS were considered low risk for M1 disease (n = 26), and those with T3–4 or N+ were considered high risk (n = 68). Those deemed high risk by EUS most often had tumors at the GE junction or gastric cardia. Staging laparoscopy detected M1 disease in 18 (19%) patients, of whom 17 had been high risk by EUS; the other patient was low risk by EUS but had linitis plastica, which some investigators consider high risk in and of itself. In this study, EUS was 89% sensitive (95% CI, 67%–99%) and 100% specific (95% CI, 95%–100%) in predicting M1 disease when followed by staging laparoscopy. This compared favorably with staging laparoscopy alone, with sensitivity 95% (74%–100%) and specificity 100% (95%–100%). The investigators suggest that in centers with sufficient experience, high-risk lesions on EUS may be a deciding factor in who requires a staging laparoscopy to limit unnecessary or low-yield procedures. Often-present esophageal strictures, however, may limit the application of EUS.


EUS cannot assess the presence of liver or retroperitoneal metastasis. Smith and colleagues prospectively evaluated the benefit of laparoscopic ultrasound (LUS) when added to staging laparoscopy for esophageal and gastric cancers. After standard noninvasive staging work-up, patients with potentially resectable disease underwent complete staging laparoscopy followed by LUS. Of 93 patients, 18 (19.4%) were considered unresectable on staging laparoscopy. Of the remaining 75 patients, 9 (12.0%) were determined unresectable on LUS—4 with esophageal cancer had celiac and para-aortic lymph node disease and 5 with gastric cancer had liver metastases, liver or pancreatic invasion, or celiac and para-aortic lymph node disease. Staging laparoscopy and LUS had a combined 29.0% reduction in unnecessary laparotomy. The investigators concluded that LUS provides a small added benefit to staging laparoscopy in preventing low-yield laparotomy. Hulscher and colleagues narrowed their evaluation of LUS to adenocarcinoma of the gastric cardia with distal esophageal involvement. Between 1995 and 1999, 48 patients with potentially resectable disease on preoperative imaging underwent staging laparoscopy with LUS. Laparoscopy detected distant metastases in 7 (14.6%) and LUS detected distant metastases in an additional 4 (8.3%) patients, resulting in a combined 23% reduction in unnecessary laparotomy.


Bentrem and colleagues evaluated peritoneal cytology as a predictor of poor outcomes before attempted gastric cancer resection. Between 1993 and 2002, 371 patients underwent staging laparoscopy with peritoneal lavage cytology performed before undergoing R0 resection; 24 (6.5%) had positive cytology, which was associated with T stage (10% of T3–4 vs 2% of T1–2; P = .02) and overall stage (11% of stage III, 7% of stage II, 2% of stage I; P = .002). On multivariate analysis, poorer overall survival was associated with positive cytology (relative risk 2.7, P <.001), distal tumor location, and preoperative T stage and N stage. The investigators suggest that peritoneal lavage cytology should be considered in assessing a patient’s prognosis after attempted curative resection. Mezhir and colleagues re-evaluated outcomes of gastric cancer patients with positive cytology, because the TNM 7th edition considers positive peritoneal lavage equivalent to M1 disease. Patients who had undergone staging laparoscopy with positive peritoneal lavage between 1993 and 2009 were included whereas those with ascites or who had undergone chemotherapy were excluded. Of the 291 patients included, 198 (68%) had gross peritoneal disease or visceral metastases seen on staging laparoscopy. In the remaining 93 patients, only positive peritoneal cytology indicated M1 disease. Median overall survival was 1 year, with 80% mortality at that time. Patients with gross metastatic disease had poor disease-specific survival, and those with positive cytology fared only slightly better. Peritoneal cytology, particularly for patients without evidence of gross metastasis, should be factored into the decision of whether to proceed with resection.




Extent of gastric resection


Distal Disease


For years, there was debate over subtotal gastrectomy (SG) versus total gastrectomy (TG) as the optimal procedure for gastric antrum malignancies. Gouzi and colleagues published the first randomized study comparing SG and TG for distal lesions in 1989. From 1980 to 1985, 169 patients of any age with a potentially curable distal gastric malignancy underwent either SG or TG, without routine splenectomy. SG and TG were similar in terms of perioperative morbidity (34% vs 33%) and mortality (3.2% vs 1.6%). Overall 5-year survival was 48%, similar to contemporary Western retrospective studies. Nodal involvement and serosal invasion were associated with survival, whereas extent of resection was not. Although the trial suffered from a small study population, the investigators concluded that SG was a viable treatment option for distal gastric cancer.


Bozzetti and colleagues conducted a larger randomized controlled trial to compare SG and TG. Patients with distal cancers underwent staging laparotomy to confirm that the location of the primary lesion was at least 6 cm away from the gastric cardia and that there was no N3 disease or unresectable disease. From 1982 to 1993, 624 patients were included, 320 in the SG group and 306 in the TG group. All underwent D2 dissection, splenectomy was optional, and 6-cm margins were obtained when possible. Although perioperative mortality was similar between SG and TG (1.3% vs 2.3%, P = .27), morbidity was greater in the TG group (15.5% vs 10.3%, P = .05), which was attributed to complications associated with splenectomy. Mean length of stay was improved in the SG group (13.8 days vs 15.4 days, P <.001). Bozzetti and colleagues subsequently published 5-year survival data as well as descriptive data. Results of permanent sections revealed R1 resection in 15 (4.7%) patients in the SG group versus 6 (2%) patients in the TG group. Only 10 patients overall received adjuvant chemotherapy. Patients with larger tumors, higher tumor grade, and nodal involvement fared worse. Five-year survival rates between SG and TG were similar (65.3% vs 62.4%; hazard ratio [HR] 95% CI not significant).


Because the aforementioned studies did not include data on number of lymph nodes dissected and because the range of tumor grade was variable, de Manzoni and colleagues conducted a prospective multicenter trial comparing SG with TG in patients with a T3 lesion of the gastric antrum. During 1996, 117 patients who underwent potentially curative surgery with D2 dissection were analyzed; 77 (65.8%) underwent SG whereas 40 underwent TG without splenectomy. Overall perioperative morbidity (14.5%) and mortality (2.6%) were not associated with extent of resection. The median number of lymph nodes dissected was 30. Median survival was improved in the SG group (38 months vs 23 months, P = .011) as was 5-year survival (36% vs 22%). On multivariate analysis, only nodal disease was independently associated with survival. The study was limited in that it was not randomized, and surgeon preference had an effect in that elderly patients were more likely to undergo SG instead of TG. It seemed, however, that even in distal lesions involving the serosa, performing SG instead of TG had no adverse effect on survival.


One of the primary arguments in favor of SG over TG when possible was the effect on quality of life. Davies and colleagues evaluated 47 consecutive patients who had presented with gastric cancer and underwent potential R0 resection. TG was performed for lesions of the proximal and middle thirds of the stomach (n = 26), and SG was performed for those of the distal third (n = 21). D2 dissection was performed, and the spleen and pancreas were preserved when possible. No patient received adjuvant chemotherapy. Quality of life was assessed preoperatively and at 1, 3, 6, and 12 months postoperatively using 5 validated questionnaires. The interviewer was blinded to the procedure the patient had received. Of the 5 assessment tools used, only the Rotterdam symptom checklist and the Troidl index achieved a statistically significant difference between the SG and TG groups through 12 months postoperatively. Each one indicated improved quality of life in the SG group over the TG group.


Based on approximately equivalent long-term survival rates, generally higher operative morbidity and mortality of patients undergoing TG, and improved quality of life for patients undergoing SG, for distal gastric cancer the procedure of choice is SG, provided that adequate proximal margins of 5 cm to 6 cm are able to be obtained.


Proximal Disease


The adequacy of proximal gastrectomy (PG) versus TG for tumors of the proximal one-third of the stomach has been the subject of various studies. Harrison and colleagues published one of the first studies to evaluate the long-term outcomes of each procedure. Between 1985 and 1995, 98 patients underwent surgery other than esophagogastrectomy for proximal tumors; 65 (66%) patients underwent PG and 33 underwent TG, all via an abdominal approach. Tumor differentiation and stage were similar between the groups, but tumor size was larger in the TG group (7 cm vs 4 cm, P = .02) and more lymph nodes were harvested. Proximal margins were similar between the groups, but distal margins were improved in the TG group (6.5 ± 1.2 cm vs 3.9 ± 0.5 cm, P <.05). Overall 5-year survival was similar (41% in TG vs 43% in PG). Kim and colleagues retrospectively reviewed patients who underwent either PG or TG for proximal gastric cancer. PG was performed only when the cancer was limited to the proximal one-third. Between 1992 and 2000, 43 patients underwent PG and 104 underwent TG. Thoracotomy was performed in 3 PG (7.0%) and 7 TG (6.7%), splenectomy and distal pancreatectomy in 18 PG (41.8%) and 15 TG (14.4%), and splenectomy alone in 8 PG (18.6%) and 13 TG (12.5%). The groups were fairly well matched for tumor characteristics, including size and differentiation, although all T4 lesions were resected via TG. The majority of the PG group underwent D1 dissection, whereas the majority of the TG group underwent at least D2 dissection. The PG group experienced higher perioperative morbidity (48.8% vs 14.4%, P <.001), most commonly anastomotic strictures, and higher rate of recurrence (39.5% vs 4.8%, P <.001). Overall 5-year survival was similar (48.6% in TG vs 46.0% in PG, P = .972). This remained true for stage I or stage II disease; however, for stage III disease, 5-year survival after TG was significantly improved (38.4% vs 17.1%, P = .035). Therefore, given higher rates of concomitant organ resection and perioperative morbidity as well as more challenging D2 dissection, PG could only be recommended for early gastric cancer with adequate margins and limited nodal involvement.


Regarding management specifically of proximal early gastric cancer, An and colleagues compared PG with TG. From 2000 to 2005, 423 patients underwent PG (n = 89 [21.0%]) or TG (n = 334 [79.0%]) for stage I or stage II proximal gastric adenocarcinoma. The TG group had larger tumors (4.0 cm vs 2.5 cm, P <.001) and more mean lymph nodes harvested (39.1 vs 22.4, P <.001). PG was associated with higher morbidity (61.8% vs 12.6%, P <.001), most often anastomotic stenosis and esophageal reflux, and these were successfully treated with balloon dilatation. Five-year survival was similar between the 2 groups (99.2% in PG vs 98.5% in TG, P = .57), as were long-term body weight and nutritional markers. The investigators could not recommend PG over TG for proximal early gastric cancer based on the frequency of postoperative complications.


Resection of Adjacent Organs


Although direct tumor involvement of the spleen or distal pancreas warrants resection to achieve potential R0 resection and remove pathologic lymph nodes, routine splenectomy and distal pancreatectomy as part of a D2 dissection adds early morbidity without a proven long-term survival benefit. The most common complications cited are postoperative infection and pancreatic fistula. Yu and colleagues made one of the clearest arguments against routine splenectomy. Between 1995 and 1999, patients undergoing TG for proximal gastric adenocarcinoma were randomized to undergo splenic resection versus preservation. Those with pancreas or spleen invasion, gastrosplenic ligament involvement, or hilar or splenic artery lymph node disease were excluded. Of 207 patients who met criteria, 104 (50.2%) underwent splenectomy. The resection and preservation groups had similar perioperative morbidity (15.4% vs 8.7%, P = .142) and mortality (1.9% vs 1.0%), median length of stay (11 days in each group), median number of harvested lymph nodes (40 in each group), and overall 5-year survival (54.8% vs 48.8%, P = .503). With no survival benefit or improved lymph node yield, routine splenectomy could not be recommended.


To evaluate extension of gastric cancer resection to adjacent organs, Shchepotin and colleagues retrospectively reviewed 353 patients who underwent multiorgan resection of T4 gastric cancers between 1974 and 1994. Resection of adjacent organs was based on gross appearance; permanent section revealed that 39 (11%) had desmoplastic reactions instead of direct tumor invasion. Patients with tumors localized to the distal one-third or the cardia underwent SG (n = 237, 67.1%) and the remainder underwent TG (n = 116, 32.9%). N1 or N2 lymph node involvement was present in 137 (38.8%) patients. Transverse colectomy was performed in 159 (45.0%) patients, combined splenectomy and distal pancreatectomy in 150 (42.5%), left hepatic lobectomy in 101 (28.5%), and proximal pancreatectomy in 37 (10.5%). Overall, 254 (71.9%) had 1 extra organ removed, 73 (20.7%) had 2 removed, and 26 (7.4%) had 3 or more resected. Perioperative morbidity was 31.2% (most commonly intra-abdominal abscess) and mortality was 13.6%. Overall 5-year survival was 25%, 37% among node-negative patients versus 15% among node-positive patients. Number or type of organ resected did not affect survival.


Martin and colleagues retrospectively reviewed adjacent organ resection among R0 resections from 1985 to 2000. Of 1133 patients who underwent PG, SG, or TG, 865 underwent gastrectomy alone whereas 268 underwent gastrectomy with additional organ resection. Additional organ resection was more common with proximal cancers, and more often TG was performed. The most common additional organs resected were spleen (45.9%), spleen and pancreas (14.2%), spleen and colon (6.7%), colon (6.0%), pancreas (4.5%), and other (22.8%). Additional organ resection was associated with more-invasive cancers and increased nodal involvement. Postoperative mortality was similar even with additional organ resections (3.7% vs 3.6%). Five-year survival for the additional organ resection group was 32%, similar to contemporary studies; on multivariate analysis, T stage and N stage were independently associated with survival, whereas number or type of additional organs resected was not. Risk of recurrence was, however, higher in the additional resection group (52% vs 42%, P = .003). With appropriate identification of T3 or T4 tumors, the investigators recommended additional organ resection due to its potential benefit and low additional morbidity and mortality.


Several subsequent series have supported the role of extended organ resection for patients who have potentially curable disease ( Table 2 ). Kobayashi and colleagues retrospectively reviewed patients presenting between 1993 and 2000, 82 of whom had invasion into adjacent organs. Extended resections included distal pancreatectomy and splenectomy (n = 36), transverse colectomy (n = 35), and other (n = 34). Some patients underwent noncurative resections due to peritoneal dissemination or liver or distant lymph node involvement. The most common postoperative complication was pancreatic fistula. Kunisaki and colleagues retrospectively reviewed 117 patients with T4 gastric adenocarcinoma undergoing surgery from 1994 to 1999. Thirty-eight (32.5%) were attempted curative resections, whereas the remainder were noncurative in intent due to peritoneal dissemination, liver or para-aortic involvement, positive margins, distant metastasis, or unresectable bulky lymph node disease. The most commonly involved organs were pancreas (52.1%), transverse colon (37.6%), and liver (8.5%). Fifteen (12.8%) patients underwent multiple additional organ resections. The most common postoperative complication was pancreatic fistula. Carboni and colleagues performed a similar retrospective review, identifying 65 patients with advanced gastric adenocarcinoma undergoing surgery between 1979 and 2004. Extended resections included spleen (n = 31), pancreas (n = 28), colon (n = 16), and other (n = 24). Desmoplastic reaction instead of tumor invasion was confirmed in 13 (20%) patients. Medical complications produced half of the operative morbidity and an additional 7 perioperative deaths. Other small series have been published but do not report 5-year mortality, limiting comparison.



Table 2

Multiple organ resections in treatment of invasive gastric cancer












































Author Patients Tumor Grade 30-Day Mortality 30-Day Morbidity R0 Resection 5-Year Survival R0 5-Year Survival Recurrence Rate
Kobayashi et al, 2004 82 T3, T4 1.2% 28% 50 (61.0%) 31.1% 36.9% ( P = .004) NR
Kunisaki et al, 2006 117 T4 4.3% 22.2% 38 (32.5%) 16.0% 32.2% ( P <.0001) 50%
Carboni et al, 2005 65 T3, T4 1.5% 27.7% 40 (61.5%) 21.8% 30.6% ( P = .001) NR

Abbreviation: NR, not reported.


Resection of Gastroesophageal Junction Tumors


Although it is generally accepted that Siewert type I tumors are best treated by esophagectomy, the optimal surgical management of proximal gastric tumors, grades II and III, has been debated. Ito and colleagues retrospectively reviewed the charts of all patients with Siewert type II or III lesions presenting between 1991 and 2001; 82 patients were included for analysis, 59 (72.0%) had Siewert type II lesions and 23 (28.0%) had type III lesions. Operative management consisted of 27 (33%) total esophagectomy (mostly transthoracic), 24 (29%) extended gastrectomy with thoracotomy, and 31 (38%) extended gastrectomy without thoracotomy. More patients with type II cancer had received neoadjuvant chemotherapy than those with type III cancer. Overall perioperative mortality was 2.4% and morbidity was 20%. Morbidity among the esophagectomy group was higher (33% vs 11%, P = .014), and thoracotomy had no significant effect on morbidity in the extended gastrectomy group (13% with vs 10% without, P = .74). There was no significant difference in tumor grade, T stage, or N stage between esophagectomy and gastrectomy groups. Overall mean number of lymph nodes resected was suboptimal (median 6), but 65% were determined to have an R0 resection. Those who underwent extended gastrectomy had positive margins more frequently (38% vs 7%, P = .04), and this was associated with T3 and T4 lesions. Margin information was used to determine that the optimal proximal gross margin length was 6 cm and the distal margin length 4 cm. Five-year mortality was similar among the 3 groups (esophagectomy 30%, extended gastrectomy with thoracotomy 23%, extended gastrectomy without thoracotomy 34%; P = .16). On multivariate analysis, positive margins, increased patient age, and nodal disease were independently associated with poorer survival. The investigators recommended whichever surgical approach would best achieve adequate gross margins and improved lymph node harvesting.


Laparoscopic Gastric Resection


In recent years, surgeons have been performing laparoscopic-assisted or robotic-assisted gastric cancer resections, but laparoscopic extended lymph node dissection is technically challenging and requires experience. To assess the adequacy of totally laparoscopic SG, Huscher and colleagues conducted a randomized prospective trial comparing laparoscopic and open approaches. Between 1992 and 1996, 59 patients with distal gastric cancer underwent either open or laparoscopic SG with D1 or D2 dissection and Roux-en-Y or Billroth II reconstructions. No patient from the laparoscopic group was reported to have port site metastasis on follow-up. The laparoscopic group had less operative blood loss (229 mL vs 391 mL, P <.001), shorter length of stay (10.3 days vs 14.5 days, P <.001), and quicker return to diet (5.1 days vs 7.4 days, P <.001). Differences in perioperative morbidity (26.7% vs 27.6%) and mortality (3.3% vs 6.7%) and overall 5-year survival (58.9% vs 55.7%) were not statistically significant. Lee and colleagues demonstrated similar benefits by prospectively analyzing 34 patients with distal lesions less than 5 cm and without significant serosal involvement who had undergone potentially curative laparoscopic gastrectomy between 1998 and 2005, matching them to 34 patients who had undergone open surgery for similar pathology. No patients were converted from laparoscopic to open. Mean operative time (283 minutes vs 195 minutes, P <.001) was longer in the laparoscopic group, whereas estimated blood loss (74 mL vs 190 mL, P <.001), return of bowel function (2.9 days vs 4.9 days, P <.01), and length of stay (8.5 days vs 12.1 days, P <.001) were all improved in the laparoscopic approach compared with open surgery. Perioperative morbidity and survival during follow-up were similar.


To compare laparoscopic with open SG and TG, Moisan and colleagues prospectively analyzed 31 patients who had undergone laparoscopic SG or TG for adenocarcinoma between 2005 and 2010. The 31 patients were case-matched by randomly selecting patients from the open surgery group with similar T stage, extent of gastrectomy, age, and gender. All included patients who lived longer than 30 days postoperatively, achieved R0 resection, had at least D1 dissection, did not undergo splenectomy or pancreatectomy, and did not have neoadjuvant chemotherapy. Patients were fairly evenly distributed by stage (I–III) and tumor location (upper vs middle vs lower third); 22 patients in each group underwent TG and 9 underwent SG. As before, the laparoscopic group experienced longer mean operative time (250 minutes vs 210 minutes, P = .007), less mean estimated blood loss (100 mL vs 300 mL, P <.001), faster return to diet (4 days vs 7 days, P <.001), and shorter length of stay (7 days vs 10.5 days, P = .001). Perioperative morbidity was identical (12.9%) and the difference in median number of retrieved nodes was nonsignificant (35 vs 39). Overall 3-year survival was not significantly different (82.3% vs 86.9%, P = .557).


The laparoscopic approach specifically for proximal gastric tumors was retrospectively reviewed by Ahn and colleagues. Between 2003 and 2009, 131 patients underwent either laparoscopic PG (LAPG) or laparoscopic TG (LATG). Fifty patients underwent LAPG and 81 underwent LATG; a common reason to perform LATG instead was a tumor size too large to provide a remnant of sufficient capacity to allow return of postoperative gastric function. Patient demographics between the groups were similar. LAPG patients experienced shorter operative time and less blood loss as well as lower rate of splenectomy (0 vs 6). All LAPG and most LATG patients (86.4%) underwent D1 dissection. The LAPG group had similar staging compared with the LATG group but smaller tumors (2.8 ± 1.3 cm vs 4.0 ± 2.7 cm, P = .002), shorter proximal margins (3.5 ± 2.3 cm vs 4.4 ± 2.3 cm, P = .038) and distal margins (4.0 ± 1.6 cm vs 14.3 ± 4.2 cm, P <.001), and fewer mean harvested lymph nodes (33.1 vs 47.4, P <.001). Return to diet, return of bowel function, hospital length of stay, and early morbidity were similar. Late morbidity among the LAPG group, however, was higher (44.0% vs 22.2%, P = .005), most commonly reflux symptoms or anastomotic stenosis. This joins a growing body of data that demonstrates similar long-term outcomes between open and laparoscopic approaches for the resection of gastric tumors.


Role of Endoscopic Resection


Two endoscopic treatment modalities are in wide use today in Eastern centers and selectively used in Western centers: endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Originally, Japanese guidelines indicated EMR for less than 2 cm, well-differentiated, nonulcerated gastric cancer lesions confined to the mucosa before they invaded the submucosa and subsequently the lymphatic system. Later, guidelines were expanded to include differentiated, nonulcerated mucosal cancer greater than 2 cm; differentiated, ulcerated mucosal cancer up to 3 cm; and undifferentiated, nonulcerated, mucosal cancer up to 2 cm. After excision of the lesion using these techniques, histologic staging is used to determine adequacy of the excision and need for subsequent surgery.


These endoscopic techniques must be carefully applied, however. Ishikawa and colleagues retrospectively reviewed the histology specimens of resections with D2 dissections for early gastric adenocarcinoma from 1980 to 2004. Of 278 specimens, 156 were mucosal and 122 were submucosal lesions. Ulceration was present in 41 (26.3%) of mucosal cancers, of which 6 (14.6%) also had lymph node metastasis, all only to the N1 tier. Ulceration was present in 21 (18.3%) of submucosal cancers, of which 10 (47.6%) had lymph node involvement. Of the 101 nonulcerated submucosal cancers, however, 18 (17.8%) had nodal disease. Overall, 3 cases that would have met extended criteria for EMR or ESD were found to have lymph node metastasis, which has been shown the major prognostic factor in early gastric cancer. The investigators suggest that the safest use of EMR/ESD is for nonulcerated mucosal lesions of any size and ulcerated mucosal lesions less than 2 cm in diameter.

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Sep 6, 2017 | Posted by in GASTROENTEROLOGY | Comments Off on Surgical Considerations in the Treatment of Gastric Cancer

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