Cell Biochem Biophys DOI 10.1007/s12013-015-0546-3

ORIGINAL PAPER

Radical Gastrectomy Combined with Modified Gastric Bypass Surgery for Gastric Cancer Patients with Type 2 Diabetes Tao Liu • Guang-wei Xie • Qing-zhong Tian Jin Li



Ó Springer Science+Business Media New York 2015

Abstract The aim of the study is to explore the effectiveness of radical gastrectomy with modified gastric bypass surgery in treating gastric cancer patients with type 2 diabetes mellitus (T2DM). A total of 93 patients with gastric cancer and T2DM were treated in our hospital and enrolled in this study. Patients in group A (n = 30) had a body mass index (BMI) of [28 kg/m2. Radical total gastrectomy and modified esophagojejunal Roux-en-y anastomosis were performed on 13 patients, and radical distal subtotal gastrectomy and gastric remnant jejunal Roux-en-y anastomosis were performed on 17 patients. The data from groups B, C, and D were derived from 63 patients with gastric cancer and diabetes who were admitted to our hospital from January 2005 to July 2012. All patients underwent radical gastrectomy (including 21 cases of gastric cancer surgery with Billroth I anastomosis, 25 cases of radical gastrectomy with Roux-en-Y anastomosis and BMI [28 kg/m2, and 17 cases with BMI\28 kg/m2). The BMI, fasting blood glucose (FBG), meal after the 2-hour glucose (2 h PBG), C-peptide (C-P), and glycosylated hemoglobin (HbAIC) data were collected before and 6 and 12 months after surgery. In groups A and D, BMI, FBG, 2 h PBG, C-P, and HbAIC at the 6th and 12th post-operative months were significantly lower than those before the surgery. In group B, BMI, FBG, 2 h PBG, C-P, and HbAIC at the 6th

T. Liu  G. Xie  Q. Tian  J. Li (&) Department of Surgical Oncology, Xuzhou Hospital Affiliated to Southeast University (Xuzhou Central Hospital), Xuzhou 221009, Jiangsu, China e-mail: [email protected]

and 12th post-operative months did not decrease significantly, when compared with the pre-operative levels. In group C, BMI, FBG, 2 h PBG, C-P, and HbAIC at the 6th and 12th post-operative months decreased but showed no statistical significance. However, in comparison, groups A C showed significant differences after the surgeries. Radical gastrectomy combined with modified gastric bypass surgery is effective in treating patients with gastric cancer with type 2 diabetes, although this requires further investigation. Keywords Radical gastrectomy  Gastric cancer  Type 2 diabetes mellitus  Roux-en-y anastomosis

Background Currently, there are about 150 million patients with diabetes worldwide, including 40 million in China. The number is increasing by 1.2 million per year [7]. Obesity and type 2 diabetes mellitus (T2DM) are common among patients with gastric cancer, and since the Asian population has a lower cutoff value compared with their European counterparts, it is necessary to identify a surgical procedure that is suitable for such patients. To this end, we have modified the traditional gastric bypass surgery (with the lengths of the two ‘‘Y’’ loops of 15 and 50 cm, respectively) and applied this to patients with gastric cancer complicated by obesity and T2DM who were admitted to our hospital from January 2005 to July 2012. During the surgery, radical gastrectomy was conducted, followed by digestive tract reconstruction using the Roux-en-y anastomosis, which increased the lengths of the two ‘‘Y’’ loops to 100 cm. The outcomes were satisfactory. The relevant data are reported below.

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Cell Biochem Biophys

Subjects and Methods

Radical Distal Subtotal Gastrectomy and Roux-en-y Gastrojejunostomy

General Data In this study, patients (46 men and 50 women, aged 38–77 years, mean: 59 years) were diagnosed with gastric cancer. Before the surgery, 96 of them had T2DM. The inclusion criteria were as follows: (a) a history of diabetes for more than 1 year; (b) fasting plasma glucose (FPG) I [ 7.0 mmol/L or 2 h postprandial glucose (2 h PBG) C 11.1 mmol/L, or random blood glucose C11.1 mmol/L (WHO diagnostic criteria); (c) without serious complications of diabetes; and (d) pre-operative glucose control was good with oral hypoglycemic drugs. A pre-operative exam and preparation were performed to exclude those who could not tolerate surgery due to contraindications. Patients in group A had a body mass index (BMI) of[28 kg/m2. Radical total gastrectomy and modified esophagojejunal Roux-en-y anastomosis were performed in 13 patients, and radical distal subtotal gastrectomy and gastric remnant jejunal Roux-en-y anastomosis were performed in 17 patients. Insulin was adjusted for glucose control based on glucose monitoring for up to 1 week after surgery. After discharge, hypoglycemic agents or insulin injections were administered according to the original prescriptions and doses. The BMI, FBG, 2-hour postprandial glucose (2 h PBG), C-peptide (C-P), and glycosylated hemoglobin were monitored during follow-up at 6 and 12 months after surgery. The data from groups B, C, and D from the 63 patients with gastric cancer and diabetes admitted from January 2005 to July 2012 were investigated. All patients underwent radical gastrectomy (including 21 cases of gastric cancer surgery with Billroth I anastomosis, 25 cases of radical gastrectomy with Rou-en-Y anastomosis and BMI [28 kg/m2, and 17 cases with BMI \28 kg/m2). The BMI, FBG, 2 h PBG, C-P, and glycosylated hemoglobin (HbAIC) were measured before surgery and 6 and 12 months after surgery. Surgical Methods Radical Total Gastrectomy and Modified Esophagojejunal Roux-en-y Anastomosis After general anesthesia, radical total gastrectomy was performed. The digestive tract reconstruction was performed as follows: After the duodenal stump was sutured, the jejunum was cut off at 100 cm distal to the Treitz’s ligament. An end-to-end anastomosis was connected between the distal jejunum and the esophageal stump with a mechanical stapler, and another anastomosis was created between the proximal jejunum and the side of the distal jejunal output loop at around 100 cm distal to the first anastomosis.

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After routine abdominal exploration, radical distal subtotal gastrectomy was performed using the same method. The digestive tract reconstruction was done as follows: After the duodenal stump was sutured, the jejunum was cut off at 100 cm distal to the Treitz’s ligament. An end-to-end anastomosis was connected between the distal jejunum and the gastric stump with a mechanical stapler, and another anastomosis was created between the proximal jejunum and the side of the distal jejunal output loop at around 100 cm distal to the first anastomosis. Statistical Methods All data were analyzed using the SPSS 11.0 software. The measurement data were expressed as mean ± standard deviation (x ± SD) and analyzed using t test.

Results The comparisons of the changes of FBG, 2 h PBG, BMI, C-P, and HbAIC at 6 and 12 months after the surgery are summarized as follows. Comparison of the Changes of FBG at 6 and 12 Months After the Surgery in Different Groups Compared with the pre-operative levels, the FBG significantly decreased at 6 and 12 months after surgery in groups A and D (P \ 0.01), but not in group B. In group C, the decrease of FBG was not statistically significant (P [ 0.05) at the 6th post-operative month, but was statistically significant at the 12th post-operative month (P \ 0.05) (Table 1; Fig. 1). Comparison of the Changes of 2 h PBG at 6 and 12 Months After Surgery Among Different Groups Compared with the pre-operative level, the decrease of 2 h PBG was extremely significant (P \ 0.01) at 6 and 12 months after the surgery in groups A and D but not statistically significant in group B; in group C, the decrease of 2 h PBG was significant at 6 and 12 months after the surgery (Table 2; Fig. 2). Comparison of the Changes of BMI at 6 and 12 Months After Surgery Among Different Groups Compared with the pre-operative level, the decrease of BMI was significant (P \ 0.05) at 6 and 12 months after

Cell Biochem Biophys Table 1 Comparison of the changes of fasting blood glucose at 6 and 12 months after surgery among different groups (x ± S) Before operation

6 months after operation

12 months after operation

Group A

9.6400 ± 1.6500

6.5700 ± 1.2800**

5.9300 ± 1.3200**

Group B

10.3200 ± 1.7800

9.1500 ± 1.2600

9.0200 ± 1.6100

Group C

9.8100 ± 1.6200

8.1500 ± 1.3100

7.5100 ± 1.2700*

Group D

11.3100 ± 1.7700

8.2100 ± 1.4500**

6.9300 ± 1.3200**

* P \ 0.05, **P \ 0.01, compared with the pre-operative levels

Fig. 1 Comparison of the changes of fasting blood glucose at 6 and 12 months after surgery among different groups. *P \ 0.05, **P \ 0.01, compared with the pre-operative levels. NS not significant

Fig. 2 Changes of fasting blood glucose at 6 and 12 months after surgery among different groups. *P \ 0.05, **P \ 0.01, compared with the pre-operative levels. NS not significant

Table 2 Comparison of the changes of 2 h PBG at 6 and 12 months after surgery among different groups (x ± S) Before operation

6 months after operation

12 months after operation

Group A

17.230 ± 1.510

8.510 ± 0.920**

8.350 ± 0.940**

Group B

18.160 ± 1.910

17.130 ± 1.450

16.910 ± 1.410

Group C

19.530 ± 2.100

14.310 ± 1.420*

13.860 ± 1.680*

Group D

18.780 ± 1.570

10.710 ± 1.280**

9.470 ± 1.050**

* P \ 0.05, **P \ 0.01, compared with the pre-operative levels

the surgery in groups A and C, but not statistically significant in groups B and D (Table 3; Fig. 3).

Changes of HbAIC at 6 and 12 Months After Surgery Among Different Groups Compared with the pre-operative level, the decrease of 2 h PBG was extremely significant (P \ 0.01) at 6 and 12 months after the surgery in groups A and D, but not

statistically significant in groups B and C. (Table 4; Fig. 4). Changes of C-P at 6 and 12 Months After Surgery Among Different Groups Compared with the pre-operative level, the decrease of C-P was extremely significant (P \ 0.01) at 6 and 12 months after the surgery in groups A, C, and D, but not statistically significant in group B (Table 5; Fig. 5).

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Cell Biochem Biophys Table 3 Comparison of the changes of BMI at 6 and 12 months after surgery among different groups (x ± S) Before operation

6 months after operation

12 months after operation

Group A

30.500 ± 2.760

26.810 ± 2.180*

26.26 ± 2.590*

Group B

28.300 ± 2.130

27.910 ± 2.630

27.91 ± 2.630

Group C

31.450 ± 2.910

27.160 ± 2.180*

27.260 ± 2.710*

Group D

27.010 ± 2.140

26.820 ± 1.980

26.930 ± 2.560

* P \ 0.05, compared with the pre-operative levels

Fig. 3 Changes of BMI at 6 and 12 months after surgery among different groups. *P \ 0.05, **P \ 0.01, compared with the pre-operative levels. NS not significant

Discussion The surgical approaches for treatment of gastric cancer and the scope of lymph node dissection have now been well established. Billroth I, Billroth II, and Roux-en-Y are the main digestive tract reconstruction procedures. These procedures have advantages and disadvantages, and the surgeons will make their decisions based on clinical outcomes and personal preferences. Treatment of T2DM with gastric bypass surgery with an 83–95 % success rate has attracted the attention of scientists and has been widely carried out in the United States and Europe. It has become the only possible way to cure

Table 4 Changes of HbAIC at 6 and 12 months after surgery among different groups (x ± S)

** P \ 0.01, compared with the pre-operative levels

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diabetes. Since its introduction into China in 2004, it has witnessed rapidly growing and extensive application due to the high cure rate for T2DM [2, 8, 10] and achieved significant clinical efficacy [2]. Gastric bypass surgery and Roux-en-Y procedures for gastric cancer share many things in common. The main differences are that while most of the stomach is removed in gastric cancer resection, the involved part is instead bypassed in gastric bypass surgery, resulting in different lengths of the two ‘‘Y’’-shaped intestinal loops during reconstruction. The lengths of the two ‘‘Y’’ loops are exactly the main mechanism of gastric bypass treatment of diabetes, and studies have confirmed that gastric bypass is not the fundamental link of the treatment. Hence, we applied gastric bypass surgery in the treatment for gastric cancer with obesity and T2DM. A new study suggests that, for Chinese populations, the BMI cutoff values for overweight and obesity should be 24 and 28, respectively [6]. We used the criterion of BMI [28 kg/m2 to identify obese patients. During surgery, traditional radical gastrectomy was performed first, followed by gastrointestinal reconstruction using the Roux-en-Y procedure. Due to the lengths of the reconstructed ‘‘Y’’-shaped loop and that of the loop in the gastric bypass surgery, we achieved significant therapeutic effect. Post-operative blood glucose returned to normal in all patients. The technical improvements in this study do not affect the surgery for gastric cancer, as they do not increase the number of gastrointestinal anastomosis, extend the operation time, or increase the incidence of post-operative complications. Instead, the surgery significantly relieves the symptoms for diabetic patients and improves their quality of life. Therefore, it is expected to become a new treatment method for gastric cancer with obesity and T2DM. Our study also found that the traditional Roux-enY bypass surgery had a good hypoglycemic effect for non-

Before operation

6 months after operation

12 months after operation

Group A

9.500 ± 1.010

5.400 ± 0.570**

4.60 ± 0.370**

Group B

9.100 ± 1.120

8.800 ± 0.7300

9.2100 ± 1.230

Group C

8.900 ± 0.890

7.130 ± 0.8100

7.770 ± 0.5100

Group D

9.6000 ± 1.040

5.800 ± 0.470**

4.780 ± 0.330**

Cell Biochem Biophys

Fig. 4 Changes of HbAIC at 6 and 12 months after surgery among different groups. *P \ 0.05, **P \ 0.01, compared with the preoperative levels. NS not significant

obese diabetic patients, since the glycated hemoglobin and C-peptide decreased significantly. This is also consistent with domestic and foreign studies [3, 9]. The traditional Roux-en-Y reconstruction has a hypoglycemic effect for obese type 2 diabetic patients, but is not significant. In contrast, when the two Y-shaped loops are prolonged to 100 cm where the duodenum and jejunum are completely bypassed, the glucose and related testing parameters are significantly improved. We believe that this is related to the factors inhibiting the secretion of insulin, which are released by part of the jejunum that is not fully bypassed during the traditional approach. Therefore, we suggest the use of Roux-en-Y anastomosis whenever applicable for gastric cancer patients with non-obese T2DM, while, for obese patients, the addition of two Y loops of 100 cm can be used for effective blood sugar control during treatment of gastric cancer. Foreign studies and large-scale metaTable 5 Changes of C-P at 6 and 12 months after surgery among different groups (x ± S) Before operation

6 months after operation

12 months after operation

Group A

4.520 ± 0.750

7.970 ± 1.210**

8.12 ± 1.290**

Group B

4.310 ± 0.6300

4.580 ± 0.720

4.470 ± 0.620

Group C

3.980 ± 0.3900

7.050 ± 1.030**

7.110 ± 1.130**

Group D

4.230 ± 0.4300

6.930 ± 0.940**

7.2100 ± 1.110**

** P \ 0.01, compared with the pre-operative levels

Fig. 5 Changes of C-P at 6 and 12 months after surgery among different groups. *P \ 0.05, **P \ 0.01, compared with the preoperative levels. NS not significant

analyses have shown a significantly higher incidence of diabetes in cancer patients compared with the general population [1, 4, 5]. Meanwhile, research has shown that patients with gastric cancer and diabetes have significantly decreased median survival and three-year survival compared with uncomplicated gastric cancer patients [1]. Therefore, whether our effective control of post-operative glucose contributes to prolonging patients’ survival requires further research.

References 1. Bayram, A., Eksi, F., & Mehli, M. (2008). Prevalence of hepatitis E-virus antibodies in patients with chronic hepatitis band chronic hepatitis C. Gastroenterology, 134, 95–101. 2. Chen, M. Q., Wang, Y., Li, Z. J., et al. (2009). Value of gastric bypass in treating type 2 diabetes mellitus. Chinese Journal of Clinicians, 3(12), 2055–2058. 3. Kim, J. W., Cheong, J. H., Hyung, W. J., et al. (2012). Outcome after gastrectomy in gastric cancer patients with type 2 diabetes. World Journal of Gastroenterology, 18(1), 49–54. 4. Larsson, S. C., Mantzoros, C. S., & Wolk, A. (2007). Diabetes mellitus and risk of breast cancer: A meta analysis. International Journal of Cancer, 121, 856–868. 5. Lu, Y., Fang, Y., Wang, Q. Q., et al. (2010). A retrospectiveanalysis of the correlation between diabetes mellitus and cancer. Chinese Journal of Endocrinology and Metabolism, 26(3), 183–187. 6. Ashwell, M., Gunn, P., & Gibson, S. (2012). Waist-to-height ratio is a better screening tool than waist circumference and BMI for adult cardio metabolic risk factors: Systematic review and metaanalysis. Obesity Reviews, 13(3), 275–286.

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Cell Biochem Biophys 7. Shaw, J. E., Sieree, R. A., & Zimmet, P. Z. (2010). Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Research and Clinical Practice, 87(1), 4–14. 8. Sun, Q. L., Wang, Y., Zhang, X. G., et al. (2009). Establishment of a new gastric bypass animal-model with GK rats. Chinese Journal of Gastrointestinal Surgery, 12(6), 562–564.

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9. Sun, Q. L., ZhaoL, Li Y. M., et al. (2011). Surgical treatment of 10 patients with gastric cancer and type 2 diabetes mellitus. Chinese Journal of Clinicians, 5(4), 1197–1198. 10. Zhang, X. G., Yang, X. J., Xu, H., et al. (2005). Experiences in treating type 2 diabetes mellitus using gastric bypass. Chinese Journal of General Surgery, 20(9), 599.

Radical Gastrectomy Combined with Modified Gastric Bypass Surgery for Gastric Cancer Patients with Type 2 Diabetes.

The aim of the study is to explore the effectiveness of radical gastrectomy with modified gastric bypass surgery in treating gastric cancer patients w...
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