Background and Aims: The complication rate after surgery for gastric cancer varies according to the particular definition of morbidity, so it’s necessary to report them using a standardized method, the Clavien-Dindo system. The purpose of this study was to prospectively analyze all post-gastrectomy complications in patients with gastric adenocarcinoma according to the severity grade using Clavien-Dindo system, in order to identify risk factors for postoperative complications and their prognostic significance on survival. Methods: This study is based on data from 90 consecutive patients who underwent gastrectomy for gastric neoplasia between January 2010 and February 2014 at the same unit. 15 patients were excluded (benign tumors, GISTs, missing data). Complications were categorized according to the Clavien-Dindo classification (uncomplicated patients vs patients classified ≥Grade I). The following risk factors were studied: age, BMI, sex, operation method, extent of resection, duration of surgery, transfusions, TNM staging, and lymph node ratio. Multivariate logistic regression was used to evaluate the association between risk factors and presence of complications. To assess the effect on overall survival, after selection of covariates using backward elimination, the Cox proportional hazard model was applied. Results: Among these patients, 49 (65.3%) developed complications, stratified as follows: Grade I, 6 (8%); Grade II, 24 (32%); Grade III, 6 (8%); Grade IV, 13 (17.3%). The laparoscopic technique (OR = 0.050; 95% CI = 0.005 - 0.550, p = 0.0143) and no transfusions (OR = 0.219; 95% CI = 0.058 - 0.827, p = 0.0251) were found to reduce the incidence of postoperative complications in the multivariate analysis. With regard to the survival analysis, lymph node ratio, malnutrition, extended resection and presence of complications were significant predictors of reduced survival in the multivariate analysis. Conclusions: Some variables can predict the risk of postoperative complications, the occurrence of which is a predictor of reduced probability of survival. In this respect it’s essential to reduce complications.
Gastric cancer is the fourth most common malignancy and the second most common cause of cancer-related death worldwide [
Surgery still remains the main method for successful treatment of gastric cancer and the incidence of post- operative complications can be regarded as an index showing the outcomes of surgical performance [
Accurate grading of complications is essential to analyze surgical outcomes, but methods for classification of complications are not uniform. The Clavien-Dindo system, proposed in 2004 [
Many studies have shown that, in gastric cancer, the presence/absence of complications is an important factor that could influence the prognosis of patients following curative gastrectomy [
In gastric surgery the most commonly reported complications were intra-abdominal abscesses, wound infection, necrosis or dehiscence, diffuse peritonitis, sepsis, malnutrition, fluid and electrolyte disturbances, acute cholecystitis, pancreatitis, abdominal bleeding and pneumonia [
The reason why post-operative complications affect prognosis remains open to speculation; many studies [
The aims of this study were: firstly, to analyze post-gastrectomy complications for gastric adenocarcinoma by prospectively collecting complication data according to the Clavien-Dindo system in order to investigate risk factors for post-operative complications; secondly, to assess the impact of postoperative complications on long- term survival.
The present study was limited to the last years of our series because it seemed mandatory to evaluate data prospectively collected on account of the peculiar accuracy of Clavien-Dindo classification.
A total of 90 consecutive patients with gastric neoplasia underwent surgery between January 2010 and February 2014 in our surgical unit, that is a secondary-care unit located in a high-risk gastric cancer area. Eligibility criteria for inclusion in this study were as follows: 1) gastric adenocarcinoma identified by histopathological examination; 2) availability of information regarding postoperative complications and mortality. As a result, 75 patients were eligible, whereas 15 patients were excluded: 2 GISTs, 1 lymphoma, 6 benign tumors, 6 missing data. Patients were asked about their informed consent and approval by the ethic committee was requested. For each patient we analyzed the following parameters: age, sex, BMI, operation method, extent of resection, duration of surgery, pre- and intra-operative transfusions, TNM staging, lymph node ratio. 5 patients were lost to follow-up, so they were excluded from the survival analysis. 70 patients were followed up for a minimum of 6 months after gastric resection.
The Clavien-Dindo classification was used to grade post-operative complications: complications were defined as “any deviation from an uneventful post-operative course” within the hospital stay and we considered as complicated patients those with complication grade ≥ I (
Grades | Definition |
---|---|
Grade I | Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic and radiological interventions. |
Allowed therapeutic regimens are: drugs as antiemetics, antipyretics, analgetics, diuretics and electrolytes and physiotherapy. This grade also includes wound infections opened at the bedside. | |
Grade II | Requiring pharmacological treatment with drugs other than such allowed for Grade I complications. |
Blood transfusions and total parenteral nutrition are also included. | |
Grade III | Requiring surgical, endoscopic or radiological intervention. |
IIIa | Intervention not under general anesthesia. |
IIIb | Intervention under general anesthesia. |
Grade IV | Life-threatening complication (including CNS complications)‡ requiring IC/ICU-management. |
Iva | Single organ dysfunction (including dialysis). |
IVb | Multi organ dysfunction. |
Grade V | Death of a patient. |
Suffix “d” | If the patient suffers from a complication at the time of discharge, the suffix “d” (for “disability”) is added to the respective grade of complication. This label indicates the need for a follow-up to fully evaluate the complication. |
‡Brain hemorrhage, ischemic stroke, subarrachnoidal bleeding, but excluding transient ischemic attacks (TIA); IC: Intermediate care; ICU: Intensive care unit.
All statistical analyses were performed by SAS Version 9.3. Spearman’s rank correlation coefficient was used to identify relation between quantitative parameters and chi-square index for qualitative variables. To evaluate the association between qualitative and quantitative parameters the simple linear regression was applied.
Multivariate logistic regression was used to evaluate the association between risk factors and presence of complications. Stepwise approach for variable selection was used. To evaluate discriminant capability of the risk factors included in the model, area under ROC curve was used.
To evaluate the association between qualitative and quantitative variables and complications chi-square test was used. Survival analysis was performed by Kaplan-Meier curves with log-rank test. To assess the effect on overall survival, after selection of covariates using backward elimination, the Cox proportional hazard model was applied. p < 0.05 indicated significant differences.
Clinicopathological characteristics of the 75 patients are summarized in
Of the 75 patients who underwent gastrectomy, 49 (65.3%) developed complications. The numbers of Clavien- Dindo Grade I, II, III, IV and V complications were 6 (8%), 24 (32%), 6 (8%), 13 (17.3%) and 0 (0%), respectively (
After assessing the absence of correlation between the above-mentioned parameters, using a multivariate logistic
Parameter | Patients | |||||
---|---|---|---|---|---|---|
N | % | |||||
Preoperative parameters | Age | Adults | (<70) | 26 | 34.7% | |
Elderlies | (≥70) | 49 | 65.3% | |||
Sex | Males | 43 | 57.3% | |||
Females | 32 | 42.7% | ||||
BMI | Underweight | (<18.5) | 4 | 5.3% | ||
Normal weight | (18.5 - 25) | 36 | 48.0% | |||
Overweight/obese | (≥25) | 35 | 46.7% | |||
Transfusions | No | 45 | 60.0% | |||
Intraoperative parameters | Yes | 30 | 40.0% | |||
Extent of resection | Total gastrectomy | 22 | 29.3% | |||
Subtotal gastrectomy | 37 | 49.3% | ||||
Extended resection | 16 | 21.3% | ||||
Surgical approach | Open | 48 | 64.0% | |||
VL | 11 | 14.7% | ||||
VL converted | 16 | 21.3% | ||||
Intent | Curative | 62 | 82.7% | |||
Palliative | 13 | 17.3% | ||||
Histological parameters | T | ≤T2 | 14 | 18.7% | ||
≥T3 | 61 | 81.3% | ||||
Lymphoadenectomy | <25 | 29 | 38.7% | |||
≥25 | 46 | 61.3% | ||||
N | 0 | 19 | 25.3% | |||
1 | 10 | 13.3% | ||||
2 | 20 | 26.7% | ||||
3 | 26 | 34.7% | ||||
Lymph node ratio (NR) | 0% | 19 | 25.3% | |||
0% - 20% | 23 | 30.7% | ||||
≥20% | 33 | 44.0% | ||||
Stadium | IA + IB | 11 | 14.7% | |||
IIA + IIB + IIIA | 34 | 45.3% | ||||
IIIB + IIIC + IV | 30 | 40.0% |
Operation approach | Mean | Dev. std. | Median | Minimum | Maximum |
---|---|---|---|---|---|
Open | 227.81 | 62.21 | 217.50 | 150.00 | 425.00 |
VL | 329.09 | 45.65 | 345.00 | 240.00 | 390.00 |
VL converted | 280.62 | 69.08 | 280.00 | 160.00 | 450.00 |
Operation approach | Mean | Dev. std. | Median | Minimum | Maximum |
---|---|---|---|---|---|
Open | 12.56 | 5.32 | 10.00 | 8.00 | 32.00 |
VL | 9.90 | 3.20 | 9.00 | 7.00 | 19.00 |
VL converted | 11.68 | 3.60 | 10.00 | 8.00 | 19.00 |
regression model, significant factors were: the laparoscopic technique (OR = 0.050; 95% CI = 0.005 - 0.550, p = 0.0143) and no transfusions (OR = 0.219; 95% CI = 0.058 - 0.827, p = 0.0251), which were found to reduce post-operative complications (
Afterwards, the influence of post-operative complications and other risk factors on survival was evaluated. As far as perioperative transfusions are concerned, the differences between survival curves do not attain statistical significance (p = 0.3775) (
- Post-operative complications: patients complicated ≥Grade I have a poorer prognosis than not complicated (HR = 7.39; 95% CI = 1.64 - 33.21, p = 0.0091);
- BMI: underweight patients have a worse prognosis than overweight/obese (HR = 8.402; 95% CI = 1.08 - 64.90, p = 0.0413);
Analysis of maximum likelihood estimates | |||||||
---|---|---|---|---|---|---|---|
Parameter | Estimate | Standard error | Wald χ2 | p | Odds ratio | 95% CI | |
Transfusions | NO | −1.5172 | 0.6772 | 5.0201 | 0.0251 | 0.219 | 0.058 - 0.827 |
Surgical approach | VL | −2.9941 | 1.2224 | 5.9996 | 0.0143 | 0.05 | 0.005 - 0.550 |
VL converted | −0.9878 | 0.7337 | 1.8126 | 0.1782 | 0.372 | 0.088 - 1.569 |
- Extent of resection: patients undergoing subtotal gastrectomy show a better prognosis than those undergoing total gastrectomy (HR = 0.308; 95% CI = 0.098 - 0.966, p = 0.0434);
- Lymph node ratio: patients with NR ≥ 0.2 show a survival probability lower than those with NR = 0 (HR = 14.380; 95% CI = 1.716 - 120.534, p = 0.0140), whereas there is no difference between NR = 0 and NR between 0 and 0.2 (HR = 2.179; 95% CI = 0.201 - 23.607, p = 0.5218).
Analysis of maximum likelihood estimates | |||||||
---|---|---|---|---|---|---|---|
Parameter | Parameter estimate | Standard error | χ2 | p | Hazard ratio | 95% CI | |
Complications | 1.99954 | 0.76711 | 6.7944 | 0.0091 | 7.386 | 1.642 - 33.219 | |
Trasfusions | No | 1.01648 | 0.63223 | 2.5849 | 0.1079 | 2.763 | 0.8 - 9.54 |
BMI | Normal weight | 0.9845 | 0.59492 | 2.7386 | 0.098 | 2.676 | 0.834 - 8.588 |
Underweight | 2.12851 | 1.04308 | 4.164 | 0.0413 | 8.402 | 1.088 - 64.904 | |
Extent of resection | Extended | −0.3498 | 0.60408 | 0.3353 | 0.5625 | 0.705 | 0.216 - 2.304 |
Subtotal | −1.17814 | 0.5833 | 4.0796 | 0.0434 | 0.308 | 0.098 - 0.966 | |
Lymph node ratio | >0, <0.2 | 0.77875 | 1.21566 | 0.4104 | 0.5218 | 2.179 | 0.201 - 23.607 |
≥0.2 | 2.66581 | 1.08474 | 6.0395 | 0.014 | 14.38 | 1.716 - 120.534 |
Our patients are representative of a western gastric cancer series whereas most studies on this item evaluate eastern people. Western patients suffer from greater heart, lung and metabolic comorbidities and have a higher BMI than eastern people [
If we compare our findings with the results of the Clavien-Dindo study which included 6336 patients, the lower percentage of complications in this latter study is evident. However, some of the differences may be due to the inclusion in their group of patients who underwent minor surgical procedures [
Quing-Guo Li et al. [
Results similar to ours were obtained in Ju-Hee Lee et al. study [
In our study, age is not a significant risk factor for complications, conversely other studies [
The relationship between obesity and complications is still controversial: most studies report an increasing risk in obese patients, because of technical complexity due to poorer surgical exposure, blood oozing from soft tissue, dissection planes hindered by adipose tissue, difficulty with anastomoses, and so forth [
Moreover, in our clinical records, obese patients were only 5, all of whom belonged to class I obesity (BMI ≥ 30 and <35). This is the reason why no technical difficulties were due to the excess of adipose tissue in our series. On the contrary, all our patients with BMI < 18.5 (underweight) developed postoperative complications. In our records they are represented by only 4 patients (5.4%). However, similar results were reported by other studies in larger series [
As previously reported, overweight/obese patients may even have a better prognosis [
Previous studies focused the attention between intraoperative bleeding loss (IBL) and complications [
The surgical technique seems to have a statistically significant effect: patients undergoing open surgery have a greater risk to develop complications than those undergoing laparoscopy. This finding agrees with other studies [
Technique | Complications in 3 levels | ||
---|---|---|---|
≥III˚ | N.C | ||
Open | 15 | 22 | 11 |
20.00 | 29.33 | 14.67 | |
31.25 | 45.83 | 22.92 | |
78.95 | 73.33 | 42.31 | |
VL | 1 | 2 | 8 |
1.33 | 2.67 | 10.67 | |
9.09 | 18.18 | 72.73 | |
5.26 | 6.67 | 30.77 | |
VL converted | 3 | 6 | 7 |
4.00 | 8.00 | 9.33 | |
18.75 | 37.50 | 43.75 | |
15.79 | 20.00 | 26.92 |
As far as long-term results are concerned, no deaths were observed in the laparoscopic group, although differences in overall survival between the laparoscopic and laparotomic group were not attained.
Recently, robot-assisted gastrectomy has been introduced for gastric cancer treatment and its advantages/ disadvantages in comparison with the other techniques are under investigation. K.M. Kim et al. [
In our study the duration of hospitalization proceeds at the same pace of the incidence of postoperative complications, but it cannot be considered as a risk factor for complications since it can be evaluated only a posteriori. However, it must be questioned whether complications influence the hospital stay or patients who have longer hospital stay have more probability to develop complications.
In this respect, possible benefits due to fast track surgery, must be underlined. In our study, stage of the disease and nodal status (i.e. NR) did not appear to be correlated with the incidence of complications. However, they are obviously related to the survival rate: NR was shown as an independent prognostic factor.
Our finding of a relationship between postoperative complications and reduction of survival probability is in agreement with previous papers [
The incidence of postoperative complications varies according to the different classifications. Recently, the Clavien-Dindo system, which is characterized by objectivity and reproducibility, has been proposed for and applied to most surgical specialties. For this reason it makes possible comparisons between different series. The present results, as previously reported in an interim analysis [
Significant risk factor for postoperative complications are represented by surgical approach and pre/intra- operative transfusions. Laparoscopic approach appears to be capable of reducing post-operative complications and of increasing overall survival. Moreover, patients who didn’t receive transfusions in the perioperative period showed lower incidence of complications.
The effect of complications on long term survival seems also worth of notice. According to several studies the inflammatory response determined by complications, as well as by transfusions, cause immunosuppression, which, in turn, could promote neoplastic cell proliferation and metastatic potentiality.
In view of these findings, two strategies may be consequently adopted. First of all it seems useful to promote laparoscopic approach (that, in turn, reduces intraoperative blood loss and postoperative complications) and anyway to discourage perioperative transfusions in oncologic patients. In this respect, when needed, alternative methods must be used in order to improve hemoglobin levels in the preoperative period. Secondly, because of the relevant impact of postoperative complications on prognosis, an adequate perioperative care is mandatory in order to prevent complications due to possible comorbidities.