Risk Factors of Postoperative Pancreatic Fistula in Curative Gastric Cancer Surgery

Gastric cancer is one of the leading causes of cancer death worldwide, especially in Eastern Asia.1 Despite the recent advances in chemotherapy and radiotherapy, surgical resection is still important for the treatment of gastric cancer.2 Subtotal or total gastrectomy with radical lymph node dissection has been considered as standard surgical treatment for gastric cancer.2, 3 Radical lymphadenectomy is performed for gastric cancer in many Asian countries and in some specialized centers in the Western countries.4 Recently, laparoscopic gastrectomy has been popular in early gastric cancer treatment and its indication is being tried to be extended to advanced gastric cancer.5, 6

Radical gastric surgery with lymphadenectomy can guarantee a better survival in gastric cancer. However it may also cause complications.7 Postoperative pancreatic fistula (POPF) is a serious complication after radical gastrectomy with lymphadenectomy. However, there are few reports about POPF after curative gastrectomy for gastric cancer, especially about comparison between laparoscopic and open gastrectomy.8-10 The purpose of this study is to evaluate the actual incidence and risk factors of POPF in both laparoscopic and open gastrectomy for gastric cancer during short concentrated two years in the experienced high volume center.

Nine hundred patients who underwent curative radical gastrectomy with lymph node dissection for gastric cancer between January 2009 and December 2010 were included in this retrospective study (laparoscopic gastrectomy in 594 patients, open gastrectomy in 306 patients). This retrospective study was approved by Seoul National University Bundang Hospital Institutional Review Board (B-1309-218-104). Preoperative staging was evaluated by using a gastric endoscopic ultrasonography and an abdomino-pelvic computed tomography (CT) scan. Open or laparoscopic gastrectomy was performed by experienced surgeons using standardized procedures.11

For each patient, preoperative, operative, and postoperative characteristics were evaluated. Postoperative complications were defined according to previous report.12 The POPF is defined by the International Study Group on Pancreatic Fistula.13 POPF is diagnosed when the drain amylase is three times higher than upper normal limit of serum amylase on the postoperative third day. However, the clinical diagnosis is also important. POPF is also diagnosed when there are the clinical findings such as sign of infection, re-admission, sepsis, reoperation and fluid collection on CT. 'Grade A' means temporary fistula with no incidence of infection, hospital readmission, septicemia, reoperation, and others and does not affect the duration of hospital stay. 'Grade B' indicates continuous fistula with clinical evidences of infection. In addition, patient may be readmitted to hospital. 'Grade C' may involve the incidence of infection, readmission, and reoperation. Antibiotics or inotropics may be used for the treatment of septicemia. Moreover, external drainage may be involved by performing percutaneous drainage insertion. In this study, grade B and C were defined as POPF. Patients were divided into two groups according to existence of POPF: POPF group and non-POPF group. The clinicopathologic characteristics and surgical outcomes were compared between the two groups.

Morbidity and mortality rates after gastric cancer surgery were reported as around 20% and 1%, respectively.7, 14, 15 Laparoscopic gastrectomy is considered to have less morbidity rate than open surgery.14 The majority of complications can be resolved with conservative management. However, some major complications need active interventions including reoperation. Pancreatic fistula is one of the significant complications which may affect clinical courses and lead to mortality. Many previous studies investigated the causes of POPF in total gastrectomy or laparoscopic gastrectomy.8-10, 16-20 However, this study aimed to identify the overall incidence and risk factors of POPF after various curative surgeries for gastric cancer patients.

The incidence of POPF has been reported as 1.7% to 22.1%.8-10, 16, 17 It depended on the type of surgery and stage. In open total gastrectomy, POPF rates ranged 13.0% to 22.1%.9, 16, 19 In early gastric cancer patients who underwent laparoscopic gastrectomy, incidence of POPF was 1.7% to 7%.8, 17 Our study, consistent with previous reports, showed that overall POPF rate was 3.3% (30 out of 900 patients), 1.1% in early gastric cancer patients, 1.51% in laparoscopic gastrectomy, 6.86% in open gastrectomy, and 13.8% in total gastrectomy.

A few studies have reported risk factors of POPF. Nobuoka et al.16 analyzed the causes of POPF on 740 gastric cancer patients who underwent total gastrectomy and reported that BMI and total gastrectomy with pancreatosplectomy are the influencing factors. Katai et al.20 showed that pancreas-related abscess was more likely to occur in older, obese patients undergoing node dissection along the distal splenic artery. Tanaka et al.18 identified visceral fat area and splenectomy were significant predictors of pancreatic fistula after total gastrectomy in gastric cancer. Jiang et al.8 examined 798 early gastric cancer patients who received laparoscopic surgery, and suggested male and high BMI are the causing factors of POPF. The present study showed that total gastrectomy, distal pancreatectomy and open gastrectomy were the independent risk factors for POPF, but neither male gender nor BMI. The possible mechanism of POPF can be conjectured. Total gastrectomy with radical suprapancreatic lymph node dissection can cause pancreatic injury and subsequent pancreatic fistula. So, POPF rates were reported higher in total gastrectomy than in distal gastrectomy. Combined resection such as distal pancreatectomy or splenectomy can be a risk factor for POPF in total gastrectomy as previously reported.16, 18

Contrast to total gastrectomy, laparoscopic distal gastrectomy for early gastric cancer had different risk factors because combined resection or lymph node dissection around distal splenic artery and splenic hilum is not necessary.8 In laparoscopic gastrectomy for early gastric cancer, excessive retraction of pancreas by an assistant or inappropriate use of ultrasonic coagulating shears might injure pancreas. Obama et al.10 reported that the rate of POPF was higher in laparoscopic gastrectomy than in open gastrectomy for early gastric cancer (7% vs. 2%). However, our study showed that POPF occurred less frequently in laparoscopic gastrectomy than open gastrectomy (1.51% in laparoscopic gastrectomy vs. 6.86% in open gastrectomy, P<0.001). Advanced gastric cancers were included in our study, which is different from the previous study.10 Higher rate of POPF in open gastrectomy may result from that open gastrectomy was performed more frequently in advanced gastric cancers which needed combined resection. However, because multivariate analysis showed that laparoscopic or open gastrectomy was the independent influencing factor for POPF, this result suggests that laparoscopic gastrectomy might be a good procedure to reduce POPF in gastric cancer. To clarify POPF rate is lower in laparoscopic gastrectomy than open gastrectomy, stage or procedure matched analysis was done. Although statistical significance was not seen in stage I, II, III, distal or proximal gastrectomy, and total gastrectomy with combined resection due to small number of POPF cases, laparoscopic gastrectomy had a consistent tendency of lower POPF rates than open gastrectomy. The reason why laparoscopic gastrectomy can reduce POPF rate is possibly that surgeon can perform fine lymph node dissection around splenic artery and pancreas because of wide and magnified operative field under laparoscopic view. By contrast to laparoscopic surgery, one should perform lymph node dissection at deep seated area such as distal splenic artery and splenic hilum through small window in open surgery and might do blunt dissection and injure pancreas capsule or parenchyma.

In summary, POPF is one of the major complications that can occur after radical gastrectomy. In spite of that, the actual incidence and risk factors of POPF in gastrectomy for gastric cancer is not well known. This study aimed to identify the overall incidence and risk factors of POPF after various curative surgeries for gastric cancer patients in high volume center. Laparoscopic gastrectomy had an advantage over open gastrectomy in terms of lower POPF rate. Total gastrectomy and combined resection such as distal pancreatectomy should be performed carefully to minimize POPF in gastric cancer surgery.