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ORIGINAL ARTICLE
Year : 2020  |  Volume : 16  |  Issue : 7  |  Page : 1611-1616

Prognostic significance of postoperative complication after curative resection for patients with gastric cancer


Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China

Date of Submission16-Oct-2019
Date of Decision01-Jan-2020
Date of Acceptance03-Jul-2020
Date of Web Publication9-Feb-2021

Correspondence Address:
Gang Zhao
Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1630, Dongfang Road, Shanghai 200127
P.R. China
Hui Cao
Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1630, Dongfang Road, Shanghai 200127
P.R. China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_856_19

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 > Abstract 


Purposes: To investigate the impact of postoperative complication on long-term survival in gastric cancer patients after curative resection.
Methods: A total 663 gastric cancer patients undergoing potentially curative resection during January 2010 to November 2014 were studied. Complications were classified according to the Clavien-Dindo severity classification.
Results: Postoperative complications occurred in 138 of 663 cases (20.8%). Multivariate analysis identified >65 years old (P = 0.001), male (P = 0.035), and total gastrectomy (P = 0.037) as independent risk factors for postoperative complications. The 5-year overall survival rate was 48.7% in the no complication group, which was significantly better than that in the complication group (42.7%, P = 0.01). Further stratified analysis by cancer staging revealed that decline in 5-year overall survival due to postoperative complication existed among stage I (P = 0.032), II (P = 0.041), and III (P = 0.001) patients. Cox proportional hazards model showed that increasing pT (P = 0.013) and pN (P = 0.001) grade, advanced pTNM (P = 0.001) stage, total gastrectomy (P = 0.001), and postoperative complication (P = 0.006) were independent prognostic factors.
Conclusion: Postoperative complications have a significant negative impact on the long-term survival in gastric cancer patients even if the tumor is resected curatively.

Keywords: Clavien-Dindo severity classification, curative gastrectomy, gastric cancer, postoperative complication, prognosis


How to cite this article:
Yu F, Huang C, Cheng G, Xia X, Zhao G, Cao H. Prognostic significance of postoperative complication after curative resection for patients with gastric cancer. J Can Res Ther 2020;16:1611-6

How to cite this URL:
Yu F, Huang C, Cheng G, Xia X, Zhao G, Cao H. Prognostic significance of postoperative complication after curative resection for patients with gastric cancer. J Can Res Ther [serial online] 2020 [cited 2021 Mar 8];16:1611-6. Available from: https://www.cancerjournal.net/text.asp?2020/16/7/1611/308774




 > Introduction Top


Gastric cancer is one of the most frequent digestive system malignant tumors with the fourth most common cancerous diseases and ranked second among the deadliest cancers.[1] In the East Asia, most cases occur in China where gastric cancer is the third highest among malignant tumors in males and the fourth in females.[2] Clinically, >50% Chinese gastric cancer patients were usually admitted to the middle or even advanced stage at diagnosis and gastrectomy with D2 lymphadenectomy is therefore the standard treatment for them.[3] However, this surgery would also inevitablly bring simultaneous postoperative complications which worth drawing great attention.

Despite the best efforts of gastrointestinal surgeons and progress of surgical instruments, the incidence of postoperative complications was reported to range from 20% to 35%.[4],[5],[6] Complications do seriously affect the postoperative recovery such as increasing length of hospital stay, cost, and early mortality.[7] Moreover, complications cause some unfavorable influences on overall survival of patients with colorectal, esophageal, or breast cancer after resection.[8],[9],[10] The association between the prognosis and postoperative complications in gastric cancer has not been confirmed. Therefore, in this study, a large number of gastric cancer patients who received radical gastrectomy would be analyzed to investigate the effect of postoperative complications on long-term survival of these patients.


 > Materials and Methods Top


Study subjects

This study was a retrospective analysis of collected data from the Department of gastrointestinal surgery at Renji hospital in Shanghai. Patients receiving radical gastrectomy with D2 lymphadenectomy for primary gastric cancer from January 2010 to November 2014 were included. Besides, eligibility criteria were as follows: (a) gastric adenocarcinoma identified by endoscopic histopathological examination; (b) open radical gastrectomy with standardized D2 lymphadenectomy; (c) histologically confirmed R0 resection; (c) availability of complete follow-up data; (d) more than 15 lymph nodes retrieved; and (e) gastric cancer patients with stage II and III received at least three cycles of 5-Fu-based postoperative chemotherapy. The exclusion criteria were as follows: (a) there are clear distant metastasis in the operation; (b) palliative surgery were performed; and (c) patients who received neoadjuvant chemotherapy or stage II and III patients received less than three cycles of 5-Fu-based postoperative chemotherapy. Finally, a total 663 gastric patients were enrolled in the study according to inclusion criteria and exclusion criteria. The clinical and pathological characteristics including perioperative management course such as infection, bleeding, leak, and obstruction were collected from our medical database records. The data collection and analysis were approved and supervised by the Research Ethics Committee (2018-105) of Ren Ji hospital. It was also registered in the Chinese Clinical Trial Register (SN. ChiCTR-PIC-17012358). Informed consent was obtained from all individual participants included in the study.

Variables and definitions

Gastric cancer staging was performed according to the 7th ed.ition of the UICC TNM classification.[11] The Clavien-Dindo classification was adopted to group postoperative complications.[12],[13] Grade I included any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic, and radiological interventions. Allowed therapeutic regimens are drugs such as antiemetics, antipyretics, analgetics, diuretics, and electrolytes and physiotherapy. This grade also includes wound infections opened at the bedside. Patients were classified to grade II if antibiotics were administered; grade III means surgical intervention were indicated; patients would be regarded as grade IV if intensive care unit were required for patients; postoperative mortality was defined as a grade V complications. If multiple complications occurred in a single patients, the highest grade was used.[14] Furthermore, the definition of each complication was based on the literature.[15],[16],[17],[18],[19],[20] Infectious complications were defined as pneumonia,[16],[17] urinary tract infection,[21] anastomotic leak,[21] or any surgical site infection.[18] Otherwise intestinal ileus,[20] remnant gastric stasis,[21] postoperative bleeding[19] were regarded as noninfectious complications.

Follow-up

All patients were followed up by outpatient or phone calls with intervals of 6 months until December 2018 or death. Overall survival was defined as the interval between the date of surgery and the date of death or the end of follow-up. At each visit, the patient underwent physical examination by his attending surgeons and blood analysis (hematology and biochemistry) was required. Endoscopy and computed tomography were performed according to recommendation by Japanese Gastric Cancer Treatment Guidelines[22] or recurrent disease was suspected.

Statistical analyses

The Chi-squared or Fisher's exact test were used for discrete variables. Independent variables in the univariate analysis were all entered into the multivariate logistic regression model. The 5-year survival rates were calculated using the Kaplan–Meier method, and the log-rank test was used to compare the groups. Independent prognostic factors were identified using the Cox proportional hazards model. The SPSS 13.0 statistical software package was used for the analysis (SPSS Inc., Chicago, IL, USA). A P < 0.05 was considered statistically significant.


 > Results Top


The clinicopathological characteristics of all the patients are shown in [Table 1]. A total 663 patients who received R0 resection for gastric cancer were included in this study. The overall incidence of postoperative complication was 138/663 (20.8%). There were 6 patients with Grade I complications, 132 with Grade II, 5 with Grade III, 6 with Grade IV, and 2 with Grade V. There were no significant differences in BMI, ASA, pT category, pN category, pathological stage, during of operation, estimated blood loss, or intraoperative blood transfusion between complication and no complication group. Postoperative complications were closely associated with >65 years old, male, and total gastrectomy (P < 0.05). The multivariate analysis revealed that in our practice, >65 years old (odds ratio [OR] = 1.887, P = 0.001), male (OR = 1.574, P = 0.035), and total gastrectomy (OR = 1.516, P = 0.037) were found to be independent predictors of postoperative complications [Table 2].
Table 1: Univariate analyses for risk factors of postoperative complications

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Table 2: Multivariate analyss for risk factors of postoperative complications

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In the median follow-up period of 45 months, the 5-year overall survival rate was 48.7% in the no complication group which was significantly better than that in the complication group [42.7%, P = 0.05, [Figure 1]a and [Table 3]]. Besides, patients with ASA III, increasing pT and pN grade, advanced pTNM stage, intraoperative blood transfusion, and total gastrectomy also had a significantly worse long-term survival compared to those without above-mentioned variables [P < 0.05, [Table 3]]. [Table 4] shows the results of Cox proportional hazards model which was used to identify independent prognostic factors for worse overall survival. Only increasing pT and pN grade, advanced pTNM stage, total gastrectomy, and postoperative complication remained independently associated with worse overall survival. Further stratified analysis by cancer stage revealed that decrease in 5-year overall survival due to postoperative complication existed among stage I, II, and III patients [Figure 1]b,[Figure 1]c,[Figure 1]d, all P < 0.05].
Figure 1: Overall survival curves for all patients and various stages patients grouped by complication or not. (a) All patients (P = 0.01); (b) Stage I patients (P = 0.032); (c) Stage II patients (P = 0.041); (d) Stage III patients (P = 0.001)

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Table 3: Univariate analysis of the factors affecting 5-year overall survival in patients who underwent curative resection for gastric cancer

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Table 4: Multivariate analysis of the factors affecting 5-year overall survival in patients who underwent curative resection for gastric cancer

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 > Discussion Top


Postoperative complications have been considered as a risk factor of many malignant tumor such as breast cancer, pancreatic cancer and colorectal cancer.[10],[23],[24] However, as to gastric cancer, few studies focused on the relationship between postoperative complications and prognosis. In the present study, we adopted the modified Clavien-Dindo classification, which graded complications mainly according to the therapeutic consequences of complications, then to evaluate the occurrence and severity of postoperative complications. We found postoperative complications could pose a significant negative effect on long-term survival not only in all patients but also in I, II, and III stage patients, respectively. Comparing to previous study that using their own criteria to grade the severity of the complications and then analyzing its effects on prognosis,[25],[26],[27] our results were more comparable because of the unified complication criteria.[14]

It is unclear why postoperative complications deteriorate the long-term outcome of cancer patients. One possible explanation is the immune suppression.[28],[29] Specifically, immune cells, in particular natural killer cells and cytotoxic T lymphocytes, might be compromised when surgical trauma and tissue damage occurred. Another possible factor is inflammation cells. For example, neutrophils are the predominant circulating leukocytes and can be activated by infection are able to promote metastasis by neutrophil extracellular traps (NETs). Inhibiting NETs formation could reduce the risk of cancer recurrence.[30],[31] Besides, the inflammatory cells in tumor tissues induce tissue remodeling and angiogenesis.[32] The long-term follow-ups performed in randomized trials have shown that aspirin reduces the risk of colorectal cancer after a delay of several years, possibly via inhibition of COX-2, which is one of the major inflammatory cytokines.[33] Last but not the least, delayed adjuvant chemotherapy induced by postoperative complications might be correlated with poorer survival.[34],[35]

There are many limitations in this study. First, this is a retrospective and single center analysis and thus might be subject to several biases; The cases in our study is not large enough and our present results still require verification by a large number of prospective randomized clinical trials. Last, more detailed classification system of complications such as infectious severity, complication sites or therapeutic expenses have not done in our study due to the relatively insufficient samples.


 > Conclusion Top


The results we have demonstrated the possibility that the poor prognosis could be induced by postoperative complications after curative resection in patients with GC, suggesting surgeons are supposed to perform the surgery with meticulous care in order to decrease the complication rate for prognosis improvement. Further basic and clinical studies concerning the mechanisms and relationship between inflammatory mediators and poor prognosis are necessary to be elucidated.

Acknowledgment

Supported by Shanghai Sailing Program, No. 17YF1415700; Shanghai Municipal Commission of Health and Family Planning, No. 2017BR043; Shanghai Hospital Development Center, No. 16CR2022A; the National Natural Science Foundation of China, No. 81802313.

Financial support and sponsorship

National Natural Science Foundation of China 81802313.

Shanghai Hospital Development Center 16CR2022A.

Shanghai Municipal Commission of Health and Family Planning 2017BR043.

Shanghai Sailing Program 17YF1415700.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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