The Impact of Obesity on Surgical Complications and Disease Recurrence in Endometrial Cancer: A Retrospective Study of 267 Patients

Background: Obesity is a well-known risk factor for many health problems including endometrial cancer. In addition, it may act as an obstacle to achieving optimal treatment of endometrial cancer and may be associated with disease recurrence. Aim: To explore the impact of obesity on the operative procedure, recurrence of disease and survival in patients with endometrial cancer. Methods: A retrospective study of 267 patients with endometrial carcinoma who underwent surgery at the Oncology CenterMansoura University from January 2011 to December 2017. Patients were divided according to their body mass index (BMI) into two groups, Group 1 with a BMI <30 and Group 2 with a BMI ≥30. Results: Group 1 included 46 patients and Group 2 included 221. The mean operative time was longer in Group 2 without statistically significant difference. Twenty-two (47.8%) patients in Group 1 and 71 (32.1%) in Group 2 underwent lymphadenectomy (p=0.062). The estimated blood loss was significantly higher in Group 2 (p<0.05). No statistically significant difference was found between the two groups regarding the intra or post-operative complications, despite the high incidence of complications in Group 2. The median disease-free survival (DFS) was 74 months in Group 1 vs. 66 months in Group 2. Obesity did not have a statistically significant impact on DFS among the studied cases (p=0.24). Conclusion: In the current study, obesity did not significantly impact the operative procedure, surgical complications or DFS in patient with endometrial cancer.


INTRODUCTION
Obesity is a well-known risk factor for many health problems including cardiovascular diseases, type 2 diabetes and a number of cancers 1 . One of the most common cancers associated with obesity is endometrial cancer 1 . Many research works had been conducted to study the relation between obesity and increased risk of endometrial cancer [2][3][4] .
In addition to the increased risk of endometrial cancer in obese patients, obesity may act as an obstacle to achieving optimal treatment in patients already diagnosed with endometrial cancer. Several studies have discussed the impact of obesity on the surgical outcome and the survival rate among this group of patients [5][6][7][8] .
While the gold standard management for endometrial cancer is surgery whether by laparoscopy or open technique 9, 10 , obese patients usually have a higher risk of intra and postoperative complications compared to patients with normal BMI 5 . Also, obese patients have problems considering the postoperative adjuvant treatment as a proportion of them may require postoperative adjuvant radiotherapy which is not easily applicable specially with morbid obesity 11 , as not all the radiotherapy machines can accommodate these weights specially in developing countries.
In this retrospective study, we investigated the impact of obesity among patients with endometrial cancer on the operative complications, postoperative outcomes, recurrence rate and survival.

METHODS
This retrospective study was approved by the Institution Review Board of the Faculty of Medicine -Mansoura university (approval # RP. 19.06.32).
The institutional registry at the Oncology Center-Mansoura University (OCMU) and the Clinical Oncology and Nuclear Medicine Department at Mansoura University hospitals were thoroughly revised for endometrial cancer patients treated in a 7-year period from January 2011 to December 2017. Patients were followed up till December 2018.
We included women aged 18-75 years with a pathologically proven endometrial cancer who underwent surgery. Exclusion criteria were no definite pathologic diagnosis, endometrial sarcoma, second malignancy or inadequate data documentation.
The preoperative assessment of patients included a detailed history (age, associated comorbidities, previous laparotomy or abdominal surgery), physical examination (including weight, height and body mass index [BMI]), preoperative abdominopelvic magnetic resonance imaging or computed tomography, examination under anesthesia, tumor characteristics (pathological type, grade and International Federation of Gynecology and Obstetrics [FIGO] stage) and routine biochemical examination.
Complete operative data and intraoperative and postoperative complications information were collected in addition to other treatment modalities including radiotherapy and chemotherapy.
Obesity was defined as a BMI of ≥30 and, accordingly, patients were divided into two groups. The BMI of Group 1 was <30 and that of Group 2 was ≥30.
Data were analyzed using IBM SPSS software package version 22.0. Qualitative data were described as number and percent. Quantitative data were described as median (range) if non-parametric or mean (standard deviation) if parametric after testing normality using Kolmogrov-Smirnov test. Chi-Square test was used for comparison of two or more groups and Fischer Exact test was used as a correction for Chi-Square test when more than 25% of cells have count less than 5 in 2*2 tables. The median duration of the follow up was calculated after the end of treatment. Survival data was calculated by Kaplan-Meier test and log rank test was used to test effect the of BMI on disease free survival (DFS). A p value <0.05 was considered significant.

RESULTS
Eighty-three patients were excluded from the study as they did not meet the inclusion criteria; 45 patients were not operated upon and the other 38 had endometrial sarcoma. Two hundred and sixty-seven patients were included in the study, 46 (17.2%) in Group 1 (BMI <30) and 221 (82.8%) patients in Group 2 (BMI ≥30).
The characteristics of patients with a comparison between the two groups are shown in Table 1. Only the prevalence of comorbidities differed significantly and was higher in Group 2. There was no significant difference between both groups regarding the pathological type, tumor grade, FIGO staging or previous laparotomy / laparoscopy. Fifteen (32.6%) patients in Group 1 and 66 (29.8%) in Group 2 did not receive adjuvant therapy (p=0.65). Table 2 illustrates the operative details and the prevalence of complications in the two groups. All the patients with endometrioid pathology FIGO stage more than IB and patients with FIGO stage IA G3 underwent hysterectomy, bilateral salpingoophrectomy and pelvic lymphadenectomy. All other patients with other pathology types (clear cell, serous, carcinosarcoma) were planned for hysterectomy, bilateral salpingoophrectomy and pelvic +/-para-aortic lymphadenectomy with omentectomy. The operative time was longer in Group 2, but with no statistically significant value. Overall, the prevalence of intraoperative and postoperative complications did not differ significantly between the 2 groups. Only one patient in Group 1 had an intraoperative complication in the form of injury of the external iliac vein which was repaired successfully. Seven patients in Group 2 experienced intraoperative complications; 3 patients had vascular injuries which were controlled, 2 patients had bladder tear that was repaired with leaving uretheral catheter in place for 10 days, one patient had ureteral injury that was repaired immediately with insertion of ureteric stent and the last one had an iatrogenic intestinal injury.
Two patients in Group 1 experienced post-operative wound infection. Regarding the post-operative complications in Group 2; 3 patients had deep venous thrombosis, 2 patients developed pulmonary embolism (managed successfully with anti-coagulants), 7 patients had postoperative lymphorrhea (managed conservatively in 5 patients while 2 patients required insertion of a tube drain), and 18 patients experienced postoperative wound infection. Only the estimated blood loss was significantly higher in Group 2.

DISCUSSION
Obesity is a well-known global problem that is contributing to many health problems. Egypt is a one of the most affected countries by obesity. In a report from previous study, it was found that around 19 million Egyptians representing about 35% of adults were obese. Also, more than 10 percent which represents about 3.6 million of children were considerably overweight 8 . In our study, we examined the impact of obesity on the operative complications and recurrence in patients with endometrial cancer in an Egyptian cancer care setting. Type I endometrial cancers were more common in obese patients in our study as reported by others [12][13][14] . As regard the operative procedures, obesity did not significantly impact the surgical procedures in both groups as regard the number of patients who underwent lymphadenectomy, the median number of harvested lymph nodes and the intraoperative complications. However, the obese group had significantly more blood loss than the non-obese group. The higher blood loss in obese patients was reported in several previous studies [15][16][17] . The operative time was reported to be significantly longer in obese patients in some studies 16,18 . Although the operative time was longer among obese patients in our study, this was not statistically significant as also reported by other retrospective studies 18,19 . Similar to our findings, Erkanli et al, Santoso et al and Rabischong et al reported that the intra and post-operative complication rates did not differ significantly between the obese and non-obese patients 7,16,19 .
Von Gruenign et al. stated that obesity is associated with higher mortality rates attributed to causes other than endometrial cancer and not the disease recurrence 20 . Also, Modesitt et al did not find significant association between progression free survival and BMI 21 . In another two studies, obesity did not affect the overall survival of endometrial cancer patients who underwent surgery 22,23 . Our finding that obesity did not affect DFS confirms the lack of association between obesity and survival reported by these studies.
This study has a number of limitations including that the study was retrospective, not all the patients were operated by the same surgeons, the number of patients with BMI <30 was relatively low in our locality and the relatively short period of follow up.

Conclusion
In our study, obesity did not have a significant impact on postoperative complications or DFS of endometrial cancer patients who underwent surgery. However, our study had a number of limitations necessitating future better-designed studies with longer follow up to consolidate the results.