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Surgical risk assessment for gynecological oncologic patients

Objective: Preoperative surgical risk assessment is important in terms of postoperative morbidity and mortality. Therefore, it is necessary to evaluate the efficacy and safety of these surgeries via an ideal risk assessment model, and reduce risks via applying some findings (for instance, perioperative beta-blockers). There are some risk assessment systems, but these have generally not been verified for patients with gynecologic cancer. The aim of this study was to assess the risk of surgery for gynecological oncologic patients and suggest an easy risk assessment model and risk reduction by applying our findings. Materials and Methods: We retrospectively analyzed 258 gynecologic patients with cancer. Age, diagnosis, staging, performance scale, metoprolol use, heart, renal diabetes, Chronic Obstructive Pulmonary disease, diabetes, operation type and length, carcinoma antigen 125, ascites, albumin, surgical procedure, hospitalization length, and complications were recorded. Results: Of the 258 patients, 173 patients (67.1%) had no complications, 43 patients (16.7%) had one and 42 patients (16.3%) had two or more complications. The most common complication was the acid-base imbalance (14%), followed by urinary tract infection (9.7%). Parameters associated with complications were performance status, ascites, operating length, metoprolol use, and upper abdominal surgery. In our proposed scoring model with a total score range 0-23, cut-off value points for both the presence and rate of complications was found as >5. Conclusion: In gynecological patients with cancer, the addition of metoprolol use and upper abdominal surgery within preoperative risk assessment evaluation parameters are significantly effective in predicting the rate and severity of complications. Moreover, we have suggested a simple, practical, and convenient scoring model for this evaluation.


Introduction
In 2016, approximately 105.000 new cases of gynecologic malignancies were estimated in the United States of America (1) . Two-thirds of these cases will undergo surgery (2) . Usually, complete tumor resection is a goal, and these surgeries may be expanded as upper abdominal surgery such as diaphragmatic peritoneal resection, splenectomy, and segmental liver resection according to the patients' condition and diagnosis (3) . It is necessary to evaluate the efficacy and safety of these surgeries because of the association between extensive surgical procedures and postoperative morbidity and mortality (4) . Furthermore, the initiation of postoperative chemotherapy may lag due to these complications (4) . For example, extensive debulking ovarian cancer surgery to no gross residual tumor may be accompanied by major complications in about 50% of these patients, especially in older patients, the risks of mortality and morbidity are greater (5) . There are some risk assessment systems for surgical risk assessment; however, generally, the predictive value of these systems has not been verified for patients with gynecologic cancer (6,7) . Therefore, a risk scoring model study was performed to predict major complications in patients with ovarian cancer who underwent laparoscopic interventions before primary debulking surgery. In the validation population, observed risk and predicted risks were 16.7% and 17.8%, respectively. The major contribution of this study was to provide a preoperative tool to predict outcomes (5) . An ideal risk assessment model would be simple, reproducible, authentic and correct, objective, and accessible to all patients, and especially able to perform personalized assessments of patients according to the use of patientspecific characteristics (5,8) . Furthermore, ideally, it should be low-cost and feasible to perform at the bedside (8) . Thus, as physicians, our endeavor is to perform a simple and practical risk assessment to prevent complications and assure decreased peri-operative healthcare costs and postoperative morbidity and mortality. Notably, when compared with other elections, conservative treatment or neoadjuvant chemotherapy can be performed instead of upfront surgical treatment (5,9) . Several studies have shown that the use of perioperative beta-blockers (metoprolol was shown as more suitable), reduces mortality in both cardiologically high and low-risk operations (10)(11)(12)(13) . The aim of this study was to assess the risk of surgery for gynecological oncologic patients and to suggest an easy risk assessment model that was feasible to perform at the bedside, and reduce risk of postoperative complications by applying our data and findings.

Study design
We retrospectively analyzed 258 patients with gynecologic cancer who underwent surgery between 2008 and 2017, and whose complete data were available. In our center, Eastern Cooperative Oncology Group (ECOG) performance status (PS) score findings and presence of systemic diseases are routinely determined and noted in patient files during the hospitalization of the patients. Additionally, we measure electrolytes and draw blood gases for all patients before and after surgery; we analyzed these data.

Statistical Analysis
Statistical analyses were performed using the Medcalc Software (version 16.8). Forward regression analysis was used to identify the predictive scoring parameters. P values of 0.05 or less were regarded as statistically significant. We used multiple regression analysis to predict the number of complications, presence of complications, and length of hospital stay. We assessed the area under the curves (AUC) of the receiver operating characteristic (ROC) curve for predicting models of risk scoring. To assess the optimal cut-off point, Youden's index (sensitivity + specificity-1) was used.

Results
The mean age of the entire population was 58.8±10.9 years, where 77 patients (29.8%) were aged ≥65 years. The median total surgical time was 4 (range, 0.5-13) hours. The number of patients who underwent surgery for primary disease was 214 (82.9%) and for the recurrent disease it was 44 (17.1%). The majority of the patients were early stage (61.2%). In our study, 157 patients (60.9%), 85 patients (32.9%) and 16 patients (6.2%) underwent surgery for uterine cancer, ovarian cancer, and cervical cancer, respectively. We follow up the patients according to enhanced recovery after surgery protocols (20,21) (Table 4). We assessed the performance of the scoring system using the ROC curve for estimating the presence of complications ( Figure 1A). Finally, we evaluated the estimated count of complications (>1) using the ROC curve according to the scoring system ( Figure 1B). In our scoring model, the total score range was between 0-23.

Main findings
Our study demonstrates that preoperative metoprolol use decreases and upper abdominal surgery increases the risk and number of postoperative complications in gynecological cancers. Additionally, other parameters that showed an association with postoperative complications and significance in our scoring system were the stage of the disease, ECOG, ascites, major pelvic surgery, total surgical time, and diabetes.

Results of the study in the context of other observations
Similar to previous studies, the most common type of gynecologic cancer was uterine cancer, followed by ovarian and cervical cancer in this study (1) . In gynecologic cancers, prediction of postoperative complications is important because the incidence of these diseases is progressively increasing (2,4) . As a consequence, postoperative morbidity, mortality, and healthcare costs can be reduced through the prevention of postoperative complications. Previous studies have depicted that several parameters such as age, advanced stage, poor performance, ascites ≥1000, hypoalbuminemia, extended surgical time, and extensive surgery were associated with a higher risk of postoperative complications (4)(5)(6)(22)(23)(24)(25)(26)(27) . There are several studies about surgical risk assessment. Although some studies have been evaluated for gynecological cancers, (2) generally they are non-specific in terms of gynecologic cancers or validated only for ovarian cancer (25)(26)(27)(28)(29) . On the other hand, several studies have shown that peri-operative beta-blockers use (metoprolol being more suitable and beneficial) was associated with reduced mortality among patients with high and low cardiac risk (10)(11)(12)(13) . In our study, we evaluated the effect of metoprolol use on postoperative mortality and morbidity and it was significantly correlated with the prediction of complications (p<0.0001). Some studies investigated the role of extended surgery on postoperative mortality and morbidity. Patankar et al. (26) reported that extended cytoreductive procedures were the strongest risk factor for complications in ovarian cancers. Conversely, Phillips et al. (27) found that the number of surgical procedures was significantly correlated with an increased risk of major morbidity, and was a better predictor of major postoperative morbidity than the highrisk performance alone. Also, in the prediction of major complications, they found that ultra-radical surgery was less useful than any solitary gastrointestinal resection. They identified standard surgery as "total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, pelvic and/ or para-aortic lymphadenectomy, and bowel surgery outside the definition of 'ultra-radical' (localized colonic resection, non-multiple bowel resection)" and ultra-radical surgery as "diaphragmatic stripping, extensive peritoneal stripping, multiple resections of the bowel (excluding localized colonic resection), liver resection, partial gastrectomy, cholecystectomy, splenectomy" (27) . In this study, upper abdominal surgery was found as a risk factor for postoperative complications. Other parameters that showed significance in our scoring system were the stage, ECOG, ascites, major pelvic surgery, total surgical time, and diabetes. Preoperative albumin levels, CA-125 levels, COPD, and heart and renal disease were parameters that were assessed in prior studies (4,6,7) . These parameters have been found  to be correlated significantly with postoperative complications. According to a study designed by Ataseven et al. (23) preoperative hypoalbuminemia had been found as an independent predictive parameter for severe postoperative complications in epithelial ovarian cancer. Conversely, in our study, no significant correlation was found between hypoalbuminemia and postoperative complications in gynecologic cancers. CA-125 levels had no significant correlation with postoperative complications, which was probably influenced by our study design with the inclusion of all gynecologic cancers. Also, there were not many patients with COPD, renal disease, and heart disease in the study population, and thus these parameters were not found eligible for predicting complications. In our study, after estimating the risk assessment with ROC analysis, we found the AUC as 0.60 for the presence of complications and 0.70 for the number of complications, respectively. We have arranged a simple, practical and convenient model for preoperative risk assessment in patients with gynecological cancer.

Study Limitations
The main strength of this study is the recommendation of a simple, practical, and convenient scoring model for preoperative risk assessment in patients with gynecologic cancer, also the addition of metoprolol use and upper abdominal surgery to preoperative risk assessment parameters.
Our study covered all gynecologic cancers and this is the main limitation of this study, Thus, to develop more effective scoring systems, further studies with specific patients and diagnostic groups are needed.

Preclinical/clinical implications
In this research study we investigated if any preclinical/clinical implications would forebode postoperative complications. As a result, the evaluation and prediction of metoprolol use, upper abdominal surgery, stage of disease, ECOG, ascites, major pelvic surgery, total surgical time, and diabetes status were found as effective parameters; thus, preoperative improvement of these parameters could be beneficial in terms of reducing postoperative complications in gynecologic cancers.

Conclusion
Several studies have shown that the use of perioperative metoprolol reduces mortality and morbidity in patients with both high and low cardiac risk. We added metoprolol use and upper abdominal surgery into the parameters of the evaluation system and as a result, metoprolol use decreased and upper abdominal surgery increased the risk and number of complications in gynecological cancers; therefore, these two parameters can also be used for predicting risk in patients with gynecologic cancer. Moreover, we have suggested a simple, practical and convenient scoring model for preoperative risk assessment in patients with gynecologic cancer.