- Email: [email protected]
Surgery for stage IV gastric cancer
The American Journal of Surgery 187 (2004) 543–546
Scientific paper
Surgery for stage IV gastric cancer Heriberto Medina-Franco, M.D.*, Alan Contreras-Saldı´var, M.D., Antonio Ramos-De La Medina, M.D., Pedro Palacios-Sanchez, M.D., Rube´n Corte´s-Gonza´lez, M.D., Javier Alvarez-Tostado Ugarte, M.D. Salvador Zubiran National Institute of Medical Sciences and Nutrition, Vasco de Quiroga 15, Tlalpan, Mexico City 14000, Mexico. Manuscript received November 18, 2002; revised manuscript June 13, 2003 Presented as a poster at the 55th Annual Cancer Symposium, Denver, Colorado, March 14 –17, 2002
Abstract Background: Surgical treatment for stage IV gastric cancer is controversial. Methods: We analyzed the surgical experience with advanced gastric carcinoma in a tertiary referral center in Mexico City from 1995 through 2000. We analyzed surgical morbidity, mortality, and factors associated with prognosis. Survival was analyzed with the Kaplan-Meier method, and the curves were compared with the log-rank test. Significance was assigned at P ⬍0.05. Results: Seventy-six cases were identified. Mean patient age was 56 ⫾ 14.5 years. Thirty-nine patients (51.3%) were women. Patients were grouped according to surgical procedure: group 1 underwent resection (40 patients), group 2 underwent bypass procedures (10 patients), and group 3 underwent either celiotomy and biopsy alone or jejunostomy placement (26 patients). Twenty patients (26%) developed operative complications, but most were minor. There was no difference in morbidity between surgical groups and no difference according to patient’s age. Operative mortality was 2.6%. Good palliation of symptoms was significantly more common in group 1 patients (82%) than in group 2 patients (60%) (P ⫽ 0.0001). Median survival was 8 months (95% confidence interval 4 to 12) for the entire cohort and 13, 5, and 3 months for groups 1, 2, and 3, respectively (P ⫽ 0.00001 for group 1 vs groups 2 and 3). Conclusions: Surgical resection for stage IV gastric cancer can be done with low operative mortality and acceptable morbidity rates, and it provides patients with good symptomatic relief. Advanced patient age is not a contraindication for surgical treatment. © 2004 Excerpta Medica, Inc. All rights reserved. Keywords: Gastric cancer; Metastatic; Palliation; Stage IV; Surgery
The incidence of gastric cancer has decreased during the last 3 decades in the western hemisphere; however, it is still one of the major causes of death caused by malignant disease in many countries. In Mexico, like in other Latin American countries, this neoplasm is the most common malignant gastrointestinal disease, and most patients have advanced disease at presentation [1,2]. Surgery provides the only possibility of cure in patients with gastric cancer. In the Western hemisphere, a potential curative resection is undertaken in ⬍40% to 60% of patients [3,4] compared with 75% to 80% of patients in Japan [5]. Palliative surgery traditionally has been offered to patients who do not undergo curative surgery.
The benefit of palliative surgery for stomach carcinoma is controversial [5–7]. There are questions about the survival advantage of the resection, quality of life of this group of patients, and the morbidity and mortality rates of surgery under these circumstances [8]. With the advent of laparoscopy, some investigators have suggested avoiding surgical exploration in patients with stage IV gastric carcinoma [9]. The purpose of this study was to review the recent experience of one tertiary referral institution in Mexico City with surgical treatment of patients having American Joint Committee on Cancer (AJCC) (TNM) stage IV gastric carcinoma. Methods
* Corresponding author. Tel.: ⫹52-5-55737333/2140; fax: ⫹52-555739321 E-mail address: [email protected]
From January 1, 1995 trough December 31, 2000, 201 patients with gastric adenocarcinoma were entered into the
0002-9610/04/$ – see front matter © 2004 Excerpta Medica, Inc. All rights reserved. doi:10.1016/j.amjsurg.2003.12.045
544
H. Medina-Franco et al. / The American Journal of Surgery 187 (2004) 543–546
Tumor Registry of the National Institute of Nutrition Hospital in Mexico City. Of these, 118 were classified as having AJCC stage IV cancer (58.7%) according to the most recent review of the AJCC staging system [10]. Patients with visceral metastases according to preoperative staging studies (computed axial tomography scan) as well as those not considered fit for surgery for medical reasons (poor performance status or severe comorbidities) did not undergo surgical exploration. We identified 76 patients with stage IV gastric cancer who underwent any type of surgical procedure at our institution. Surgeons chose the type of surgical procedure and any additional treatment based on individual patient need. Gastric bypass was performed only in patients with gastric outlet obstruction. We retrospectively reviewed the clinical, demographic, and pathologic characteristics of this subgroup of patients. Because the study was done using chart review, we were not required to obtain Institutional Review Board approval according to the regulations of our institution. We analyzed surgical morbidity, mortality, and factors associated with surgical outcome. Symptoms were carefully recorded as was the ability of the surgical procedure to alleviate them. Good palliation of gastrointestinal bleeding was considered when the patient did not receive a blood transfusion from the time of perioperative period until death. Palliation of gastric outlet obstruction and dysphagia was defined as the ability to eat by mouth until the patient’s death or until the last follow-up examination. Date of last follow-up was October 30, 2001. Survival was calculated from the time of surgical treatment and was analyzed using the Kaplan-Meier method, and the curves were compared with the log-rank test. Categorical variables were compared with the chi-square test and continuous variables with Fisher’s Exact test. Significance was assigned at P ⬍0.05.
Results Seventy-six patients were identified from surgical records. Mean patient age was 56 ⫾ 14 years. Thirteen patients (17.1%) were ⱕ40 years old, and 18 (23.7%) were ⱖ70 years old. Thirty-nine patients (51.3%) were women and 37 (48.7%) were men. Presenting symptoms included abdominal pain (79% of patients), weight loss (defined as ⬎10% weight loss in the previous 6 months; 74%), gastrointestinal bleeding (chronic anemia with hemoglobin ⬍10 g/dL; 46%), gastric outlet obstruction (45%), and dysphagia (22%). Only 10 patients (13.2%) were considered truly asymptomatic. The most common histologic type was poorly differentiated signet cell adenocarcinoma (80.3%). Thirteen patients (17.1%) had moderately differentiated adenocarcinoma, and only one had a well-differentiated tumor. One patient was not classified. The locations of the tumors were as follows: antrum in 20 patients (26.3%), corpus and fundus in 46
Table 1 Type of surgical procedures in patients with stage IV gastric adenocarcinoma Surgical procedure
No. (%) (n ⫽ 76)
Total gastrectomy Partial gastrectomy Gastrojejunostomy Celiotomy and biopsy Jejunostomy placement Gastrostomy placement
24 (31.6) 16 (21.1) 10 (13.2) 16 (21.1) 9 (11.8) 1 (1.3)
(60.5%), and the entire stomach in 10 (13.2%). In 89% of patients, the reason for stage IV gastric cancer classification was the presence of peritoneal implants with ascites. None of these patients underwent radical surgery. All resected patients had lymph node metastases, and 11% were classified as stage IV because ⬎15 nodes with metastases were involved. The types of surgical procedures are listed in Table 1. Patients were grouped according to type of surgical procedure: group 1 underwent resection (40 patients), group 2 underwent bypass procedures (10 patients), and group 3 underwent either celiotomy and biopsy alone or gastrointestinal tube placement (26 patients). All total gastrectomies were reconstructed with a Roux-en-Y gastric bypass and partial gastrectomies with using the Billroth II technique. No patient had any additional organ removed. Twenty patients (26%) presented operative complications, but most were minor. Surgical morbidity is listed in Table 2. The only factor associated with morbidity was albumin ⬍3.0 g/dL (66% vs 18%, P ⫽ 0.04). There was no difference in morbidity between surgical groups and no difference according to patient’s age. Only two patients died in the 30-day period after surgery, yielding a surgical mortality rate of 2.6% for the entire cohort. One patient underwent total gastrectomy and died on postoperative day 11 from leaking anastomosis and abdominal sepsis; the second patient underwent celiotomy only and died from pneumonia on postoperative day 22. According to surgical procedure,
Table 2 Surgical complications Complication
No. (%)* (n ⫽ 76)
Anastomotic leak Wound infection Intestinal obstruction Abdominal abscess Septicemia Pneumonia Renal failure Pancreatic fistula
5 (10.0†*) 5 (6.6) 3 (3.9) 2 (2.6) 2 (2.6) 1 (1.3) 1 (1.3) 1 (1.3)
* Two patients presented with ⬎1 surgical complication. † Percentage based on patients who had an anastomosis (n ⫽ 50).
H. Medina-Franco et al. / The American Journal of Surgery 187 (2004) 543–546
545
Table 3 Symptomatic palliation according to surgical procedure No. patients (%) symptom (n ⫽ 76)
Surgical group: No. patients
Good palliation (%)
Bleeding: 35 patients (46)
1:29 2:NA 3:6 1:10
24/29 (83) NA NA 8/10 (80)
2:NA 3:17 1:13
NA NA 11/13 (85)
2:10 3:11
6/10 (60) (P ⬎ 0.01) NA
Dysphagia: 17 patients (22)
Gastric outlet obstruction: 34 patients (45)
Group 1: resection; group 2: gastric bypass; group 3: celiotomy and biopsy. NA ⫽ Not applicable.
total gastrectomy represented 4.2% and celiotomy 6.25% of surgical mortality. Other procedures were not associated with fatal outcome. Excluding 10 asymptomatic patients, effective palliation was obtained in 67% of patients with gastrointestinal bleeding, in 50% of patients with gastric outlet obstruction, and in 47% of patients with dysphagia. These numbers included the entire cohort of surgical patients. Palliation of symptoms according to surgical procedure is listed in Table 3. Good palliation of symptoms was significantly more common in group 1 patients (82%) than in group 2 patients (60%; P ⫽ 0.0001). Taking into account only patients with gastric outlet obstruction, good palliation was obtained in 85% of patients with resection versus 60% of patients with gastric bypass (P ⫽ 0.0001; Table 3). Forty patients (52.6%) received systemic chemotherapy. Regarding palliation of symptoms and again excluding asymptomatic patients, good palliation of symptoms was obtained in 78.8% of patients who received chemotherapy versus 54.5% of those who did not receive it (P ⫽ 0.04). The effect of chemotherapy on palliation of symptoms was obscured because more patients in the resection group received chemotherapy (67.5%) than did patients in groups 2 and 3 (36.1%; P ⫽ 0.001). With a median follow-up of 9 months, median survival rate for the entire cohort of patients was 8 months (95% confidence interval 4 to 12). At the time of last follow-up, 53% of patients had died from their disease. There was a significant difference in survival between patients who underwent resection (median survival 13 months) compared with those who underwent bypass (median survival 5 months), celiotomy, or tube placement (median survival 3 months) (P ⫽ 0.001). The Kaplan-Meier curves for these groups are depicted in Fig. 1. There was no difference in survival rates according to other factors including the use or not of systemic chemotherapy.
Fig. 1. Effect of surgical resection on survival (P ⫽ 0.001).
Comments Currently, the majority of patients with gastric carcinoma have their disease diagnosed when the disease is advanced beyond the hope of surgical cure. The current report confirms that 58.7% of our patients had stage IV disease. However, the benefit of surgery for stage IV disease is controversial. Although distal subtotal gastrectomy is performed commonly for carcinoma of the gastric antrum or body nonresectable for cure, total gastrectomy generally is not regarded as an acceptable palliative procedure. This opinion is related to concerns about increased operative mortality and morbidity rates, reports of short survival, and poor quality of life in surviving patients [8]. The main questions are related: Should resection should be done whenever feasible, and will resection provide meaningful palliation? Previous studies have mixed different tumor stages when analyzing palliative procedures. In the series of Monson et al. [11], looking at the benefit of palliative total gastrectomy for advanced gastric cancer, only 33% of patients had stage IV disease. In the study from the Birmingham Cancer Registry [4] regarding palliative surgery for gastric cancer, 79% had stage IV disease, but only 6% of this population underwent palliative resection. In the current series, all patients had histologically proven stage IV gastric adenocarcinoma according to the most recent AJCC pathologic staging system [10]. The laparotomy rate in this series was 64.4% for the entire group of patients with stage IV disease, and the resection rate was 52.6% in this group. Different from some groups in Japan [12], we precluded laparotomy in those patients with visceral metastases as shown by preoperative imaging studies, but the laparotomy and resection rates in the present series compared favorably with those in other population-based studies [4,13]. In the study from the American College of Surgeons, the surgical mortality rate in patients with stage IV gastric cancer was 31%, which makes it difficult to justify any type of surgical procedure in this population with very poor
546
H. Medina-Franco et al. / The American Journal of Surgery 187 (2004) 543–546
prognoses [13]. Other old [6,14] and new [5,15,16] published series have all shown longer survival and lower perioperative mortality rates in patients undergoing resection compared with all other forms of palliative treatment, with the best results being obtained with partial gastrectomy. The series by ReMine [6] provided detailed accounts of palliative treatment in 196 patients. Significantly longer survival was shown in those undergoing resection compared with all other treatments including bypass procedures. This difference is less obvious if only patients with preoperative obstructive symptoms are compared. Overall, quality of life—assessed by the relief of preoperative symptoms—was also better after resection than after gastroenterostomy. Similar results were reported in a comparison of palliative resection and gastroenterostomy in 379 patients [14]. Both survival and quality of life were better in the resection group. This was most obvious in those with locally advanced rather than metastatic disease. Hanazaki et al. [5] compared 84 patients who underwent palliative gastrectomy with 100 patients who underwent nonresectable surgery. They found that palliative gastrectomy, compared with nonresectable surgery, improved prognosis even in patients with peritoneal dissemination and/or distant lymph node metastasis; however, they did not find any benefit in patients with synchronous liver metastasis. In the present series, survival was significantly better in patients who underwent resection compared with those who underwent bypass procedures or celiotomy alone. Actually, there was no difference in survival between these last two groups. What is most important, however, is to obtain good palliation of symptoms in this population with very poor prognoses. Our results agree with those of other series [5,6,14 –16] regarding resection providing much better palliation of symptoms than gastroenterostomy given that results with bypass procedures have been very poor. The results of the present series cannot rule out or support the palliative role of systemic chemotherapy. The results were obscured by the fact that most patients in the resection group received treatment compared with those who did not. Cytotoxic therapy did not seem to improve survival in this group of patients, even when taking into account the fact that more patients in the resection group received such therapy. The only factor associated with prolonged survival was the ability to perform a resective procedure. Because of the very low surgical mortality rate in this series (2.6%), we did not find any factor associated with this adverse outcome. However, regarding surgical morbidity, the only factor associated with this result was a low serum albumin level. Advanced age was not associated with adverse surgical outcome, which is similar to the results ob-
tained by Bittner et al. [17]. This investigator reported surgical mortality and morbidity rates of 3% and 33.7%, respectively, for elderly patients. In summary, surgical resection in patients with stage IV gastric carcinoma can be done with low surgical mortality and low morbidity rates. Resective procedures may confer some survival advantage in this group of patients, but most important, they provide patients with good palliation of symptoms compared with results obtained from bypass procedures or systemic chemotherapy. Advanced age, itself, should not be considered a contraindication for surgery.
References [1] Young AY, Hayek M, Howe G. Epidemiology of gastric cancer. Semin Oncol 1996;23:281–91. [2] Medina-Franco H, Heslin MJ, Cortes-Gonzalez R. Clinicopathological characteristics of gastric carcinoma in young and elderly patients: a comparative study. Ann Surg Oncol 2000;7:515–9. [3] Craven JL, Cushieri A. Treatment of gastric cancer. Clin Oncol 1984;3:309 –12. [4] Hallissey MT, Allum WH, Roginski C, et al. Palliative surgery for gastric cancer. Cancer 1988;62:440 – 4. [5] Hanazaki K, Sodeyama H, Mochizuki Y, et al. Palliative gastrectomy for advanced gastric cancer. Hepatogastroenterology 2001;48:285–9. [6] ReMine WH. Palliative operations for incurable gastric cancer. World J Surg 1979;3:721– 4. [7] Bozzeti F, Bonfanti G, Audisio RA, et al. Prognosis of patients after palliative surgical procedures for carcinoma of the stomach. Surg Gynecol Obstet 1980;164:151–5. [8] Boddie AW, McMurtrey MJ, Giacco GG, et al. Palliative gastrectomy and esophagogastrectomy. A reevaluation. Cancer 1983;51:1195– 1200. [9] Conlon KC. Staging laparoscopy for gastric cancer. Ann Ital Chir 2001;72:33–7. [10] American Cancer Society, American Joint Committee on Cancer. AJCC Cancer Staging Manual. 5th ed. Lippincott-Raven, 1997. [11] Monson JRT, Donohue JH, McIlrath DC, et al. Total gastrectomy for advanced cancer. A worthwhile palliative procedure. Cancer 1991; 68:1863– 8. [12] Koga S, Kawaguchi H, Kishimoto H, et al. Therapeutic significance of non curative gastrectomy for gastric cancer with liver metastasis. Am J Surg 1990;140:356 –9. [13] Wanebo HJ, Kennedy BJ, Chmiel J, et al. Cancer of the stomach. A patient care study by the American College of Surgeons. Ann Surg 1993;218:583–92. [14] Lawrence W, McNeer G. The effectiveness of surgery for palliation of incurable gastric cancer. Cancer 1958;11:28 –32. [15] Doglietto GB, Pacelli F, Caprino P, et al. Surgery: independent prognostic factor in curable and far advanced gastric cancer. World J Surg 2000;24:459 – 63. [16] Meijer S, DeBakker OJ, Hoitsma HF. Palliative resection in gastric cancer. J Surg Oncol 1983;23:77– 80. [17] Bittner R, Butters M, Ulrich M, et al. Total gastrectomy. Updated operative mortality and long-term survival with particular reference to patients older than 70 years of age. Ann Surg 1996;224:37– 42.
Scientific paper
Surgery for stage IV gastric cancer Heriberto Medina-Franco, M.D.*, Alan Contreras-Saldı´var, M.D., Antonio Ramos-De La Medina, M.D., Pedro Palacios-Sanchez, M.D., Rube´n Corte´s-Gonza´lez, M.D., Javier Alvarez-Tostado Ugarte, M.D. Salvador Zubiran National Institute of Medical Sciences and Nutrition, Vasco de Quiroga 15, Tlalpan, Mexico City 14000, Mexico. Manuscript received November 18, 2002; revised manuscript June 13, 2003 Presented as a poster at the 55th Annual Cancer Symposium, Denver, Colorado, March 14 –17, 2002
Abstract Background: Surgical treatment for stage IV gastric cancer is controversial. Methods: We analyzed the surgical experience with advanced gastric carcinoma in a tertiary referral center in Mexico City from 1995 through 2000. We analyzed surgical morbidity, mortality, and factors associated with prognosis. Survival was analyzed with the Kaplan-Meier method, and the curves were compared with the log-rank test. Significance was assigned at P ⬍0.05. Results: Seventy-six cases were identified. Mean patient age was 56 ⫾ 14.5 years. Thirty-nine patients (51.3%) were women. Patients were grouped according to surgical procedure: group 1 underwent resection (40 patients), group 2 underwent bypass procedures (10 patients), and group 3 underwent either celiotomy and biopsy alone or jejunostomy placement (26 patients). Twenty patients (26%) developed operative complications, but most were minor. There was no difference in morbidity between surgical groups and no difference according to patient’s age. Operative mortality was 2.6%. Good palliation of symptoms was significantly more common in group 1 patients (82%) than in group 2 patients (60%) (P ⫽ 0.0001). Median survival was 8 months (95% confidence interval 4 to 12) for the entire cohort and 13, 5, and 3 months for groups 1, 2, and 3, respectively (P ⫽ 0.00001 for group 1 vs groups 2 and 3). Conclusions: Surgical resection for stage IV gastric cancer can be done with low operative mortality and acceptable morbidity rates, and it provides patients with good symptomatic relief. Advanced patient age is not a contraindication for surgical treatment. © 2004 Excerpta Medica, Inc. All rights reserved. Keywords: Gastric cancer; Metastatic; Palliation; Stage IV; Surgery
The incidence of gastric cancer has decreased during the last 3 decades in the western hemisphere; however, it is still one of the major causes of death caused by malignant disease in many countries. In Mexico, like in other Latin American countries, this neoplasm is the most common malignant gastrointestinal disease, and most patients have advanced disease at presentation [1,2]. Surgery provides the only possibility of cure in patients with gastric cancer. In the Western hemisphere, a potential curative resection is undertaken in ⬍40% to 60% of patients [3,4] compared with 75% to 80% of patients in Japan [5]. Palliative surgery traditionally has been offered to patients who do not undergo curative surgery.
The benefit of palliative surgery for stomach carcinoma is controversial [5–7]. There are questions about the survival advantage of the resection, quality of life of this group of patients, and the morbidity and mortality rates of surgery under these circumstances [8]. With the advent of laparoscopy, some investigators have suggested avoiding surgical exploration in patients with stage IV gastric carcinoma [9]. The purpose of this study was to review the recent experience of one tertiary referral institution in Mexico City with surgical treatment of patients having American Joint Committee on Cancer (AJCC) (TNM) stage IV gastric carcinoma. Methods
* Corresponding author. Tel.: ⫹52-5-55737333/2140; fax: ⫹52-555739321 E-mail address: [email protected]
From January 1, 1995 trough December 31, 2000, 201 patients with gastric adenocarcinoma were entered into the
0002-9610/04/$ – see front matter © 2004 Excerpta Medica, Inc. All rights reserved. doi:10.1016/j.amjsurg.2003.12.045
544
H. Medina-Franco et al. / The American Journal of Surgery 187 (2004) 543–546
Tumor Registry of the National Institute of Nutrition Hospital in Mexico City. Of these, 118 were classified as having AJCC stage IV cancer (58.7%) according to the most recent review of the AJCC staging system [10]. Patients with visceral metastases according to preoperative staging studies (computed axial tomography scan) as well as those not considered fit for surgery for medical reasons (poor performance status or severe comorbidities) did not undergo surgical exploration. We identified 76 patients with stage IV gastric cancer who underwent any type of surgical procedure at our institution. Surgeons chose the type of surgical procedure and any additional treatment based on individual patient need. Gastric bypass was performed only in patients with gastric outlet obstruction. We retrospectively reviewed the clinical, demographic, and pathologic characteristics of this subgroup of patients. Because the study was done using chart review, we were not required to obtain Institutional Review Board approval according to the regulations of our institution. We analyzed surgical morbidity, mortality, and factors associated with surgical outcome. Symptoms were carefully recorded as was the ability of the surgical procedure to alleviate them. Good palliation of gastrointestinal bleeding was considered when the patient did not receive a blood transfusion from the time of perioperative period until death. Palliation of gastric outlet obstruction and dysphagia was defined as the ability to eat by mouth until the patient’s death or until the last follow-up examination. Date of last follow-up was October 30, 2001. Survival was calculated from the time of surgical treatment and was analyzed using the Kaplan-Meier method, and the curves were compared with the log-rank test. Categorical variables were compared with the chi-square test and continuous variables with Fisher’s Exact test. Significance was assigned at P ⬍0.05.
Results Seventy-six patients were identified from surgical records. Mean patient age was 56 ⫾ 14 years. Thirteen patients (17.1%) were ⱕ40 years old, and 18 (23.7%) were ⱖ70 years old. Thirty-nine patients (51.3%) were women and 37 (48.7%) were men. Presenting symptoms included abdominal pain (79% of patients), weight loss (defined as ⬎10% weight loss in the previous 6 months; 74%), gastrointestinal bleeding (chronic anemia with hemoglobin ⬍10 g/dL; 46%), gastric outlet obstruction (45%), and dysphagia (22%). Only 10 patients (13.2%) were considered truly asymptomatic. The most common histologic type was poorly differentiated signet cell adenocarcinoma (80.3%). Thirteen patients (17.1%) had moderately differentiated adenocarcinoma, and only one had a well-differentiated tumor. One patient was not classified. The locations of the tumors were as follows: antrum in 20 patients (26.3%), corpus and fundus in 46
Table 1 Type of surgical procedures in patients with stage IV gastric adenocarcinoma Surgical procedure
No. (%) (n ⫽ 76)
Total gastrectomy Partial gastrectomy Gastrojejunostomy Celiotomy and biopsy Jejunostomy placement Gastrostomy placement
24 (31.6) 16 (21.1) 10 (13.2) 16 (21.1) 9 (11.8) 1 (1.3)
(60.5%), and the entire stomach in 10 (13.2%). In 89% of patients, the reason for stage IV gastric cancer classification was the presence of peritoneal implants with ascites. None of these patients underwent radical surgery. All resected patients had lymph node metastases, and 11% were classified as stage IV because ⬎15 nodes with metastases were involved. The types of surgical procedures are listed in Table 1. Patients were grouped according to type of surgical procedure: group 1 underwent resection (40 patients), group 2 underwent bypass procedures (10 patients), and group 3 underwent either celiotomy and biopsy alone or gastrointestinal tube placement (26 patients). All total gastrectomies were reconstructed with a Roux-en-Y gastric bypass and partial gastrectomies with using the Billroth II technique. No patient had any additional organ removed. Twenty patients (26%) presented operative complications, but most were minor. Surgical morbidity is listed in Table 2. The only factor associated with morbidity was albumin ⬍3.0 g/dL (66% vs 18%, P ⫽ 0.04). There was no difference in morbidity between surgical groups and no difference according to patient’s age. Only two patients died in the 30-day period after surgery, yielding a surgical mortality rate of 2.6% for the entire cohort. One patient underwent total gastrectomy and died on postoperative day 11 from leaking anastomosis and abdominal sepsis; the second patient underwent celiotomy only and died from pneumonia on postoperative day 22. According to surgical procedure,
Table 2 Surgical complications Complication
No. (%)* (n ⫽ 76)
Anastomotic leak Wound infection Intestinal obstruction Abdominal abscess Septicemia Pneumonia Renal failure Pancreatic fistula
5 (10.0†*) 5 (6.6) 3 (3.9) 2 (2.6) 2 (2.6) 1 (1.3) 1 (1.3) 1 (1.3)
* Two patients presented with ⬎1 surgical complication. † Percentage based on patients who had an anastomosis (n ⫽ 50).
H. Medina-Franco et al. / The American Journal of Surgery 187 (2004) 543–546
545
Table 3 Symptomatic palliation according to surgical procedure No. patients (%) symptom (n ⫽ 76)
Surgical group: No. patients
Good palliation (%)
Bleeding: 35 patients (46)
1:29 2:NA 3:6 1:10
24/29 (83) NA NA 8/10 (80)
2:NA 3:17 1:13
NA NA 11/13 (85)
2:10 3:11
6/10 (60) (P ⬎ 0.01) NA
Dysphagia: 17 patients (22)
Gastric outlet obstruction: 34 patients (45)
Group 1: resection; group 2: gastric bypass; group 3: celiotomy and biopsy. NA ⫽ Not applicable.
total gastrectomy represented 4.2% and celiotomy 6.25% of surgical mortality. Other procedures were not associated with fatal outcome. Excluding 10 asymptomatic patients, effective palliation was obtained in 67% of patients with gastrointestinal bleeding, in 50% of patients with gastric outlet obstruction, and in 47% of patients with dysphagia. These numbers included the entire cohort of surgical patients. Palliation of symptoms according to surgical procedure is listed in Table 3. Good palliation of symptoms was significantly more common in group 1 patients (82%) than in group 2 patients (60%; P ⫽ 0.0001). Taking into account only patients with gastric outlet obstruction, good palliation was obtained in 85% of patients with resection versus 60% of patients with gastric bypass (P ⫽ 0.0001; Table 3). Forty patients (52.6%) received systemic chemotherapy. Regarding palliation of symptoms and again excluding asymptomatic patients, good palliation of symptoms was obtained in 78.8% of patients who received chemotherapy versus 54.5% of those who did not receive it (P ⫽ 0.04). The effect of chemotherapy on palliation of symptoms was obscured because more patients in the resection group received chemotherapy (67.5%) than did patients in groups 2 and 3 (36.1%; P ⫽ 0.001). With a median follow-up of 9 months, median survival rate for the entire cohort of patients was 8 months (95% confidence interval 4 to 12). At the time of last follow-up, 53% of patients had died from their disease. There was a significant difference in survival between patients who underwent resection (median survival 13 months) compared with those who underwent bypass (median survival 5 months), celiotomy, or tube placement (median survival 3 months) (P ⫽ 0.001). The Kaplan-Meier curves for these groups are depicted in Fig. 1. There was no difference in survival rates according to other factors including the use or not of systemic chemotherapy.
Fig. 1. Effect of surgical resection on survival (P ⫽ 0.001).
Comments Currently, the majority of patients with gastric carcinoma have their disease diagnosed when the disease is advanced beyond the hope of surgical cure. The current report confirms that 58.7% of our patients had stage IV disease. However, the benefit of surgery for stage IV disease is controversial. Although distal subtotal gastrectomy is performed commonly for carcinoma of the gastric antrum or body nonresectable for cure, total gastrectomy generally is not regarded as an acceptable palliative procedure. This opinion is related to concerns about increased operative mortality and morbidity rates, reports of short survival, and poor quality of life in surviving patients [8]. The main questions are related: Should resection should be done whenever feasible, and will resection provide meaningful palliation? Previous studies have mixed different tumor stages when analyzing palliative procedures. In the series of Monson et al. [11], looking at the benefit of palliative total gastrectomy for advanced gastric cancer, only 33% of patients had stage IV disease. In the study from the Birmingham Cancer Registry [4] regarding palliative surgery for gastric cancer, 79% had stage IV disease, but only 6% of this population underwent palliative resection. In the current series, all patients had histologically proven stage IV gastric adenocarcinoma according to the most recent AJCC pathologic staging system [10]. The laparotomy rate in this series was 64.4% for the entire group of patients with stage IV disease, and the resection rate was 52.6% in this group. Different from some groups in Japan [12], we precluded laparotomy in those patients with visceral metastases as shown by preoperative imaging studies, but the laparotomy and resection rates in the present series compared favorably with those in other population-based studies [4,13]. In the study from the American College of Surgeons, the surgical mortality rate in patients with stage IV gastric cancer was 31%, which makes it difficult to justify any type of surgical procedure in this population with very poor
546
H. Medina-Franco et al. / The American Journal of Surgery 187 (2004) 543–546
prognoses [13]. Other old [6,14] and new [5,15,16] published series have all shown longer survival and lower perioperative mortality rates in patients undergoing resection compared with all other forms of palliative treatment, with the best results being obtained with partial gastrectomy. The series by ReMine [6] provided detailed accounts of palliative treatment in 196 patients. Significantly longer survival was shown in those undergoing resection compared with all other treatments including bypass procedures. This difference is less obvious if only patients with preoperative obstructive symptoms are compared. Overall, quality of life—assessed by the relief of preoperative symptoms—was also better after resection than after gastroenterostomy. Similar results were reported in a comparison of palliative resection and gastroenterostomy in 379 patients [14]. Both survival and quality of life were better in the resection group. This was most obvious in those with locally advanced rather than metastatic disease. Hanazaki et al. [5] compared 84 patients who underwent palliative gastrectomy with 100 patients who underwent nonresectable surgery. They found that palliative gastrectomy, compared with nonresectable surgery, improved prognosis even in patients with peritoneal dissemination and/or distant lymph node metastasis; however, they did not find any benefit in patients with synchronous liver metastasis. In the present series, survival was significantly better in patients who underwent resection compared with those who underwent bypass procedures or celiotomy alone. Actually, there was no difference in survival between these last two groups. What is most important, however, is to obtain good palliation of symptoms in this population with very poor prognoses. Our results agree with those of other series [5,6,14 –16] regarding resection providing much better palliation of symptoms than gastroenterostomy given that results with bypass procedures have been very poor. The results of the present series cannot rule out or support the palliative role of systemic chemotherapy. The results were obscured by the fact that most patients in the resection group received treatment compared with those who did not. Cytotoxic therapy did not seem to improve survival in this group of patients, even when taking into account the fact that more patients in the resection group received such therapy. The only factor associated with prolonged survival was the ability to perform a resective procedure. Because of the very low surgical mortality rate in this series (2.6%), we did not find any factor associated with this adverse outcome. However, regarding surgical morbidity, the only factor associated with this result was a low serum albumin level. Advanced age was not associated with adverse surgical outcome, which is similar to the results ob-
tained by Bittner et al. [17]. This investigator reported surgical mortality and morbidity rates of 3% and 33.7%, respectively, for elderly patients. In summary, surgical resection in patients with stage IV gastric carcinoma can be done with low surgical mortality and low morbidity rates. Resective procedures may confer some survival advantage in this group of patients, but most important, they provide patients with good palliation of symptoms compared with results obtained from bypass procedures or systemic chemotherapy. Advanced age, itself, should not be considered a contraindication for surgery.
References [1] Young AY, Hayek M, Howe G. Epidemiology of gastric cancer. Semin Oncol 1996;23:281–91. [2] Medina-Franco H, Heslin MJ, Cortes-Gonzalez R. Clinicopathological characteristics of gastric carcinoma in young and elderly patients: a comparative study. Ann Surg Oncol 2000;7:515–9. [3] Craven JL, Cushieri A. Treatment of gastric cancer. Clin Oncol 1984;3:309 –12. [4] Hallissey MT, Allum WH, Roginski C, et al. Palliative surgery for gastric cancer. Cancer 1988;62:440 – 4. [5] Hanazaki K, Sodeyama H, Mochizuki Y, et al. Palliative gastrectomy for advanced gastric cancer. Hepatogastroenterology 2001;48:285–9. [6] ReMine WH. Palliative operations for incurable gastric cancer. World J Surg 1979;3:721– 4. [7] Bozzeti F, Bonfanti G, Audisio RA, et al. Prognosis of patients after palliative surgical procedures for carcinoma of the stomach. Surg Gynecol Obstet 1980;164:151–5. [8] Boddie AW, McMurtrey MJ, Giacco GG, et al. Palliative gastrectomy and esophagogastrectomy. A reevaluation. Cancer 1983;51:1195– 1200. [9] Conlon KC. Staging laparoscopy for gastric cancer. Ann Ital Chir 2001;72:33–7. [10] American Cancer Society, American Joint Committee on Cancer. AJCC Cancer Staging Manual. 5th ed. Lippincott-Raven, 1997. [11] Monson JRT, Donohue JH, McIlrath DC, et al. Total gastrectomy for advanced cancer. A worthwhile palliative procedure. Cancer 1991; 68:1863– 8. [12] Koga S, Kawaguchi H, Kishimoto H, et al. Therapeutic significance of non curative gastrectomy for gastric cancer with liver metastasis. Am J Surg 1990;140:356 –9. [13] Wanebo HJ, Kennedy BJ, Chmiel J, et al. Cancer of the stomach. A patient care study by the American College of Surgeons. Ann Surg 1993;218:583–92. [14] Lawrence W, McNeer G. The effectiveness of surgery for palliation of incurable gastric cancer. Cancer 1958;11:28 –32. [15] Doglietto GB, Pacelli F, Caprino P, et al. Surgery: independent prognostic factor in curable and far advanced gastric cancer. World J Surg 2000;24:459 – 63. [16] Meijer S, DeBakker OJ, Hoitsma HF. Palliative resection in gastric cancer. J Surg Oncol 1983;23:77– 80. [17] Bittner R, Butters M, Ulrich M, et al. Total gastrectomy. Updated operative mortality and long-term survival with particular reference to patients older than 70 years of age. Ann Surg 1996;224:37– 42.