Diseases of of the the Esophagus Esophagus (2015) (2016) ••, 29,••–•• 229–235 Diseases DOI: 10.1111/dote.12327 10.1111/dote.12327 DOI:
Original article
Impact of body mass index on postoperative complications and long-term survival in patients with esophageal squamous cell cancer K. Kamachi, S. Ozawa, T. Hayashi, A. Kazuno, E. Ito, H. Makuuchi Department of Gastroenterological Surgery, Tokai University School of Medicine, Kanagawa, Japan
SUMMARY. Undernutrition and cachexia have been suggested to be risk factors for postoperative complications and survival in cancer patients. The aim of this study was to investigate whether body mass index (BMI) is related to the short-term and long-term outcomes in patients who undergo an esophagectomy for the resection of esophageal squamous cell cancer (ESCC). Three hundred forty patients who underwent an esophagectomy for the resection of ESCC between 2003 and 2008 were retrospectively reviewed. The patients were divided into two groups: an L-BMI group characterized by a BMI < 18.5 kg/m2 and an N-BMI group characterized by a BMI ≥ 18.5 kg/m2. Clinical and pathological outcome were compared between groups. The study included 40 patients in the L-BMI group and 300 patients in the N-BMI group. A clinicopathological assessment showed that nodal involvement was seen more frequently in the L-BMI group (P = 0.016). Pulmonary complications seemed to occur more frequently in the L-BMI group (P = 0.006). The 5-year overall survival rate was higher in the N-BMI group (63.6%) than in the L-BMI group (32.3%) (P < 0.001). The 5-year disease-free survival rate was also higher in the N-BMI group (58.0%) than in the L-BMI group (33.6%) (P = 0.001). In multivariate analysis, the BMI (hazard ratio, 2.154; 95% CI, 1.349–3.440, P = 0.001) was found to be an independent prognostic factor for overall survival. Our data suggested that a lower BMI not only increased pulmonary complications but also impaired overall and disease-free survival after an esophagectomy for the resection of ESCC. KEY WORDS: body mass index, cachexia, esophageal cancer.
INTRODUCTION States of cancer-related undernutrition such as malnutrition and weight loss are pathological conditions that are often seen in cancer-bearing patients, and they are also important prognostic factors.1,2 Moreover, weight loss has been reported to increase postoperative complications in a variety of cancers and to worsen the prognosis.3 Upper gastrointestinal cancers, in particular, including esophageal cancer, are often accompanied by malnutrition and weight loss.4 A decrease in dietary intake due to such symptoms as dysphagia and an association between systemic inflammation and metabolic disorders called cancerous cachexia have been considered as causes.5,6 Address correspondence to: Prof Soji Ozawam, MD, PhD, FACS, Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimosoya, Isehara, Kanagawa 259-1143, Japan. Email: [email protected] Financial support: No Grant support for the research. Conflict of interest: The authors declare that they have no conflict of interest. C 2015 International Society for Diseases of the Esophagus V ©
Obesity usually increases postoperative complications.7 Abundant adipose tissue makes surgery more difficult, and as a result, operation times become longer and blood loss increases.8 Moreover, many obese patients have coronary disease or impaired glucose tolerance as preexisting diseases, and they are factors that increase postoperative complications.9 For that reason, there have already been many reports on high preoperative body mass indexes (BMIs) and postoperative complications.10 However, there have been few studies on the opposite of obesity, i.e. low body weight and postoperative complications in esophageal cancer patients. There have already been many reports11–13 on BMI and the outcome of postoperative esophageal cancer patients, and the results in those reports have often been that BMI has no impact on the prognosis. However, the debate has centered on patients with Barrett’s esophagus and esophageal adenocarcinoma (EAC), which are associated with gastrointestinal reflux disease (GERD) in Western European countries, where overweight (BMI ≥ 25 kg/m2) and obese 229 1
230 Diseasesofof Esophagus 2 Diseases thethe Esophagus
(BMI ≥ 30 kg/m2) are common, and the impact of preoperative undernutrition on the prognosis of esophageal cancer patients who have undergone esophagectomy is not clearly understood.12 In the present study, we retrospectively analyzed the effect of preoperative low BMI on the short-term outcome and long-term prognosis of esophageal squamous cell cancer (ESCC) patients who had undergone esophagectomy.
MATERIALS AND METHODS Patients and nutritional parameters The subjects were the 340 consecutive patients with squamous cell cancer of the intrathoracic esophagus (the upper, middle and lower thoracic portion) who had undergone esophagectomy in the Department of Surgery of Tokai University, School of Medicine between January 2003 and December 2008. Their body height and body weight were measured during the initial examination, and their BMI was calculated according to the World Health Organization criteria. The patients were sorted on the basis of their BMI into a normal or obese BMI (N-BMI; BMI ≥ 18.5 kg/ m2) group and a low-BMI (L-BMI; BMI < 18.5 kg/ m2) group. Two preoperative nutritional parameters were analyzed, that is, the percentage of ideal body weight (%IBW) and the prognostic nutritional index (PNI): %IBW = body weight (kg)/actual body weight (kg) × 100, PNI = 10 × albumin (g/dL) + 0.005 × total lymphocyte count (/mm3). Patients underwent an operation within 3 weeks after the initial assessment. Enteral or parenteral nutritional support was provided, as necessary, to ensure that the patients did not lose weight prior to the operation. We conducted the study by reviewing their charts and analyzing and comparing retrospectively accumulated data in regard to patient factors, tumor factors, postoperative complications, recurrence rates, and cumulative survival rates. We excluded (i) patients who had received chemotherapy, radiotherapy, or chemoradiotherapy preoperatively, (ii) cT4 patients (diagnosed by esophagography and computed tomography), (iii) patients whose pathological findings showed that the lesion was not ESCC, and (iv) patients whose preoperative BMI was unknown. Surgery Subtotal resection of the thoracic esophagus plus regional lymph node dissection was performed through right thoracotomy in every patient. The tumor and adjacent lymph nodes were resected en bloc. The mediastinal lymph nodes (paraesophageal lymph nodes, tracheal lymph nodes, tracheobronchial lymph nodes, supradiaphragmatic
lymph nodes, posterior mediastinal lymph nodes), perigastric lymph nodes (paracardial lymph nodes, lesser curvature lymph nodes, lymph nodes along the left gastric artery, lymph nodes along the common hepatic artery, lymph nodes along the splenic artery, lymph nodes around the celiac artery), and cervical lymph nodes (cervical paraesophageal lymph nodes, deep cervical lymph nodes, supraclavicular lymph nodes) were considered regional lymph nodes, and three-field dissection was performed in every case. Node-positive patients received adjuvant chemotherapy with CDDP and 5-FU. Pathological staging of the surgical specimens was performed according to the Union Internationale Contre le Cancer tumor node metastasis classification, 7th edition.14 Definition of complications All complications that occurred during the period between the end of the operation and discharge from the hospital were extracted from the charts. Complications were described based on the Clavien-Dindo classification, and patients with a grade of more than II according to the Clavien-Dindo classification were counted. Pulmonary complications were defined as pneumonia, atelectasis, and acute respiratory distress syndrome that required mechanical respiratory support, reintubation, tracheotomy, or surgical drainage 48 hours or more postoperatively. Anastomotic leakage defined to be treated at the bedside or under fluoroscopic guidance. Wound infection was defined as an incision infection in which microorganisms were detected in drainage fluid, and the patient did not manifest a systemic inflammatory response syndrome (SIRS). Sepsis was defined as a bacterial infection accompanied by SIRS. Anastomotic stenosis was defined as a lesion in a patient who complained of symptoms of a stenosis and in whom endoscopic or surgical treatment was performed. Rebleeding was defined as bleeding that required endoscopic, surgical, or interventional radiology hemostasis when conservative treatment by blood transfusion alone was impossible. Reoperation was defined as patients who required surgical treatments under general anesthesia, and the reoperation rate was calculated as follows: the number of patients who underwent reoperation was divided by the total number of patients who underwent the initial operation. The 90-day mortality rate was calculated by dividing the number of patients who died within 90 days after the initial operation by the total number of patients who underwent the initial operation. Statistical analysis All of the statistical analyses were performed by using the SPSS Statistical Software Package, version SPSS C 2015 International Society for Diseases of the Esophagus V ©
BMI BMIand andesophageal esophagealcancer canceroutcome outcome 231 3
Table 1 Clinicopathological characteristics BMI < 18.5 kg/m2 n = 40 (%)
BMI ≥ 18.5 kg/m2 n = 300 (%) Age Median (range) Gender (M:F) Male Female ASA score 1 2 3 Tumor location Upper Middle Lower Tumor depth T1 T2 T3 T4 Nodal involvement N0 N1 N2 N3 Stage I II III IV Histological grade Well Moderately Poorly Radicality of surgery R0 R1 R2 Comorbidities Diabetes Hypertension Hepatitis Renal disease COPD Cardiac diseases %IBW, median (range) PNI, median (range) Adjuvant therapy
63.6 (41–81)
62.8 (51–83)
273 (91) 27 (9)
33 (82.5) 7 (17.5)
111 (37) 132 (44) 57 (19)
10 (25) 21 (52.5) 9 (22.5)
31 (10.3) 176 (58.7) 93 (31)
1 (2.5) 22 (55) 17 (42.5)
147 (49) 36 (12) 109 (36.3) 8 (2.7)
12 (30) 8 (20) 19 (47.5) 1 (2.5)
126 (42) 87 (29) 56 (18.7) 31 (10.3)
9 (22.5) 10 (25) 12 (30) 9 (22.5)
104 (34.7) 72 (24) 97 (32.3) 27 (9)
8 (20) 8 (20) 18 (45) 6 (15)
73 (24.3) 165 (55) 62 (20.7)
12 (30) 22 (55) 6 (15)
292 (97.3) 7 (2.4) 1 (0.3)
40 (100) 0 (0) 0 (0)
P-value – 0.092 0.330
0.148
0.130
0.016
0.137
0.600
0.579
18 (6) 39 (13) 10 (3.3) 6 (2) 4 (13.3) 13 (43.3) 101.1 (84.2–154.1) 52.7 (35–68.5) 109 (36.3)
4 (10) 3 (7.5) 0 (0) 4 (10) 1 (2.5) 3 (7.5) 80.2 (67.6–84.1) 49.7 (40.1–52.8) 12 (30)
0.309 0.445 0.614 0.021 0.467 0.416
Original article
Impact of body mass index on postoperative complications and long-term survival in patients with esophageal squamous cell cancer K. Kamachi, S. Ozawa, T. Hayashi, A. Kazuno, E. Ito, H. Makuuchi Department of Gastroenterological Surgery, Tokai University School of Medicine, Kanagawa, Japan
SUMMARY. Undernutrition and cachexia have been suggested to be risk factors for postoperative complications and survival in cancer patients. The aim of this study was to investigate whether body mass index (BMI) is related to the short-term and long-term outcomes in patients who undergo an esophagectomy for the resection of esophageal squamous cell cancer (ESCC). Three hundred forty patients who underwent an esophagectomy for the resection of ESCC between 2003 and 2008 were retrospectively reviewed. The patients were divided into two groups: an L-BMI group characterized by a BMI < 18.5 kg/m2 and an N-BMI group characterized by a BMI ≥ 18.5 kg/m2. Clinical and pathological outcome were compared between groups. The study included 40 patients in the L-BMI group and 300 patients in the N-BMI group. A clinicopathological assessment showed that nodal involvement was seen more frequently in the L-BMI group (P = 0.016). Pulmonary complications seemed to occur more frequently in the L-BMI group (P = 0.006). The 5-year overall survival rate was higher in the N-BMI group (63.6%) than in the L-BMI group (32.3%) (P < 0.001). The 5-year disease-free survival rate was also higher in the N-BMI group (58.0%) than in the L-BMI group (33.6%) (P = 0.001). In multivariate analysis, the BMI (hazard ratio, 2.154; 95% CI, 1.349–3.440, P = 0.001) was found to be an independent prognostic factor for overall survival. Our data suggested that a lower BMI not only increased pulmonary complications but also impaired overall and disease-free survival after an esophagectomy for the resection of ESCC. KEY WORDS: body mass index, cachexia, esophageal cancer.
INTRODUCTION States of cancer-related undernutrition such as malnutrition and weight loss are pathological conditions that are often seen in cancer-bearing patients, and they are also important prognostic factors.1,2 Moreover, weight loss has been reported to increase postoperative complications in a variety of cancers and to worsen the prognosis.3 Upper gastrointestinal cancers, in particular, including esophageal cancer, are often accompanied by malnutrition and weight loss.4 A decrease in dietary intake due to such symptoms as dysphagia and an association between systemic inflammation and metabolic disorders called cancerous cachexia have been considered as causes.5,6 Address correspondence to: Prof Soji Ozawam, MD, PhD, FACS, Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimosoya, Isehara, Kanagawa 259-1143, Japan. Email: [email protected] Financial support: No Grant support for the research. Conflict of interest: The authors declare that they have no conflict of interest. C 2015 International Society for Diseases of the Esophagus V ©
Obesity usually increases postoperative complications.7 Abundant adipose tissue makes surgery more difficult, and as a result, operation times become longer and blood loss increases.8 Moreover, many obese patients have coronary disease or impaired glucose tolerance as preexisting diseases, and they are factors that increase postoperative complications.9 For that reason, there have already been many reports on high preoperative body mass indexes (BMIs) and postoperative complications.10 However, there have been few studies on the opposite of obesity, i.e. low body weight and postoperative complications in esophageal cancer patients. There have already been many reports11–13 on BMI and the outcome of postoperative esophageal cancer patients, and the results in those reports have often been that BMI has no impact on the prognosis. However, the debate has centered on patients with Barrett’s esophagus and esophageal adenocarcinoma (EAC), which are associated with gastrointestinal reflux disease (GERD) in Western European countries, where overweight (BMI ≥ 25 kg/m2) and obese 229 1
230 Diseasesofof Esophagus 2 Diseases thethe Esophagus
(BMI ≥ 30 kg/m2) are common, and the impact of preoperative undernutrition on the prognosis of esophageal cancer patients who have undergone esophagectomy is not clearly understood.12 In the present study, we retrospectively analyzed the effect of preoperative low BMI on the short-term outcome and long-term prognosis of esophageal squamous cell cancer (ESCC) patients who had undergone esophagectomy.
MATERIALS AND METHODS Patients and nutritional parameters The subjects were the 340 consecutive patients with squamous cell cancer of the intrathoracic esophagus (the upper, middle and lower thoracic portion) who had undergone esophagectomy in the Department of Surgery of Tokai University, School of Medicine between January 2003 and December 2008. Their body height and body weight were measured during the initial examination, and their BMI was calculated according to the World Health Organization criteria. The patients were sorted on the basis of their BMI into a normal or obese BMI (N-BMI; BMI ≥ 18.5 kg/ m2) group and a low-BMI (L-BMI; BMI < 18.5 kg/ m2) group. Two preoperative nutritional parameters were analyzed, that is, the percentage of ideal body weight (%IBW) and the prognostic nutritional index (PNI): %IBW = body weight (kg)/actual body weight (kg) × 100, PNI = 10 × albumin (g/dL) + 0.005 × total lymphocyte count (/mm3). Patients underwent an operation within 3 weeks after the initial assessment. Enteral or parenteral nutritional support was provided, as necessary, to ensure that the patients did not lose weight prior to the operation. We conducted the study by reviewing their charts and analyzing and comparing retrospectively accumulated data in regard to patient factors, tumor factors, postoperative complications, recurrence rates, and cumulative survival rates. We excluded (i) patients who had received chemotherapy, radiotherapy, or chemoradiotherapy preoperatively, (ii) cT4 patients (diagnosed by esophagography and computed tomography), (iii) patients whose pathological findings showed that the lesion was not ESCC, and (iv) patients whose preoperative BMI was unknown. Surgery Subtotal resection of the thoracic esophagus plus regional lymph node dissection was performed through right thoracotomy in every patient. The tumor and adjacent lymph nodes were resected en bloc. The mediastinal lymph nodes (paraesophageal lymph nodes, tracheal lymph nodes, tracheobronchial lymph nodes, supradiaphragmatic
lymph nodes, posterior mediastinal lymph nodes), perigastric lymph nodes (paracardial lymph nodes, lesser curvature lymph nodes, lymph nodes along the left gastric artery, lymph nodes along the common hepatic artery, lymph nodes along the splenic artery, lymph nodes around the celiac artery), and cervical lymph nodes (cervical paraesophageal lymph nodes, deep cervical lymph nodes, supraclavicular lymph nodes) were considered regional lymph nodes, and three-field dissection was performed in every case. Node-positive patients received adjuvant chemotherapy with CDDP and 5-FU. Pathological staging of the surgical specimens was performed according to the Union Internationale Contre le Cancer tumor node metastasis classification, 7th edition.14 Definition of complications All complications that occurred during the period between the end of the operation and discharge from the hospital were extracted from the charts. Complications were described based on the Clavien-Dindo classification, and patients with a grade of more than II according to the Clavien-Dindo classification were counted. Pulmonary complications were defined as pneumonia, atelectasis, and acute respiratory distress syndrome that required mechanical respiratory support, reintubation, tracheotomy, or surgical drainage 48 hours or more postoperatively. Anastomotic leakage defined to be treated at the bedside or under fluoroscopic guidance. Wound infection was defined as an incision infection in which microorganisms were detected in drainage fluid, and the patient did not manifest a systemic inflammatory response syndrome (SIRS). Sepsis was defined as a bacterial infection accompanied by SIRS. Anastomotic stenosis was defined as a lesion in a patient who complained of symptoms of a stenosis and in whom endoscopic or surgical treatment was performed. Rebleeding was defined as bleeding that required endoscopic, surgical, or interventional radiology hemostasis when conservative treatment by blood transfusion alone was impossible. Reoperation was defined as patients who required surgical treatments under general anesthesia, and the reoperation rate was calculated as follows: the number of patients who underwent reoperation was divided by the total number of patients who underwent the initial operation. The 90-day mortality rate was calculated by dividing the number of patients who died within 90 days after the initial operation by the total number of patients who underwent the initial operation. Statistical analysis All of the statistical analyses were performed by using the SPSS Statistical Software Package, version SPSS C 2015 International Society for Diseases of the Esophagus V ©
BMI BMIand andesophageal esophagealcancer canceroutcome outcome 231 3
Table 1 Clinicopathological characteristics BMI < 18.5 kg/m2 n = 40 (%)
BMI ≥ 18.5 kg/m2 n = 300 (%) Age Median (range) Gender (M:F) Male Female ASA score 1 2 3 Tumor location Upper Middle Lower Tumor depth T1 T2 T3 T4 Nodal involvement N0 N1 N2 N3 Stage I II III IV Histological grade Well Moderately Poorly Radicality of surgery R0 R1 R2 Comorbidities Diabetes Hypertension Hepatitis Renal disease COPD Cardiac diseases %IBW, median (range) PNI, median (range) Adjuvant therapy
63.6 (41–81)
62.8 (51–83)
273 (91) 27 (9)
33 (82.5) 7 (17.5)
111 (37) 132 (44) 57 (19)
10 (25) 21 (52.5) 9 (22.5)
31 (10.3) 176 (58.7) 93 (31)
1 (2.5) 22 (55) 17 (42.5)
147 (49) 36 (12) 109 (36.3) 8 (2.7)
12 (30) 8 (20) 19 (47.5) 1 (2.5)
126 (42) 87 (29) 56 (18.7) 31 (10.3)
9 (22.5) 10 (25) 12 (30) 9 (22.5)
104 (34.7) 72 (24) 97 (32.3) 27 (9)
8 (20) 8 (20) 18 (45) 6 (15)
73 (24.3) 165 (55) 62 (20.7)
12 (30) 22 (55) 6 (15)
292 (97.3) 7 (2.4) 1 (0.3)
40 (100) 0 (0) 0 (0)
P-value – 0.092 0.330
0.148
0.130
0.016
0.137
0.600
0.579
18 (6) 39 (13) 10 (3.3) 6 (2) 4 (13.3) 13 (43.3) 101.1 (84.2–154.1) 52.7 (35–68.5) 109 (36.3)
4 (10) 3 (7.5) 0 (0) 4 (10) 1 (2.5) 3 (7.5) 80.2 (67.6–84.1) 49.7 (40.1–52.8) 12 (30)
0.309 0.445 0.614 0.021 0.467 0.416
