Abstract
Objective
To identify risk factors associated with and evaluate the impact of anastomotic leakage on oncological outcomes in patients with advanced-stage (Fédération Internationale de Gynécologie et d’Obstétrique [International Federation of Gynaecology and Obstetrics], FIGO grade III–IV) high-grade serous ovarian cancer who underwent rectosigmoid resection with primary anastomosis during cytoreductive surgery.
Materials and methods
The data of 102 patients treated between September 2015 and October 2024 at two tertiary gynaecologic oncology centres were retrospectively analyzed. Demographic, clinical, intraoperative, and postoperative parameters were reviewed. Anastomotic leakage was diagnosed on the basis of clinical, radiological, or intraoperative findings. Progression-free survival (PFS) and overall survival (OS) were analysed using the Kaplan–Meier method.
Results
Rectosigmoid anastomotic leakage occurred in 9 (8.8%) patients—all of whom were surgically managed—and was not attributed to mortality. Patients with greater intraoperative blood loss, a greater number of transfused red blood cell units and lower serum albumin levels on postoperative day 1 demonstrated a significantly increased risk of anastomotic leakage. Although anastomotic leakage significantly delayed the initiation of adjuvant chemotherapy (median 39.5 days vs. 18 days), no statistically significant difference in PFS or OS was identified under the prespecified endpoint definition (time zero at completion of adjuvant chemotherapy).
Conclusion
Rectosigmoid resection with primary anastomosis can be safely performed in patients with advanced high-grade serous ovarian cancer as part of cytoreductive surgery. Intraoperative haemorrhage, the need for perioperative transfusion, and early postoperative hypoalbuminaemia are key predictors of anastomotic leakage. Anastomotic leakage was associated with delayed initiation of adjuvant chemotherapy; however, no statistically significant difference in PFS or OS was detected under the prespecified endpoint definition. However, these survival findings should be interpreted as exploratory in light of potential guarantee-time bias and unmeasured temporal changes in systemic therapy.
Supplementary Information
The online version contains supplementary material available at 10.1186/s13048-026-02003-2.
Keywords: Ovarian cancer, Rectosigmoid anastomosis, Anastomotic leakage, Survival
Introduction
Among gynaecologic malignancies, ovarian cancer is the leading cause of mortality [1]. Ovarian cancers are a heterogeneous group of neoplasms with multiple histologic subtypes that subtypes differ in terms of pathophysiology, treatment approach, response to adjuvant chemotherapy, and overall patient survival outcomes. Approximately 70–80% of all ovarian cancers are classified as high-grade serous ovarian carcinomas (HGSOCs).
Nearly 75% of patients with ovarian cancer present at an advanced stage; at the time of diagnosis, the disease is often found to have spread to peritoneal surfaces, the pouch of Douglas, rectum, and colon. The most important factor influencing survival in patients with ovarian cancer is the presence of residual tumour following surgery [2]. Therefore, the main objective of surgery is to achieve complete tumour resection with no macroscopic residual disease. To this end, additional procedures such as peritonectomy, upper abdominal surgery, small and large bowel resections, and rectosigmoid resection may be performed. Previous studies have reported that rectosigmoid resection is necessary in approximately 20–60% of patients who undergo cytoreductive surgery for advanced ovarian cancer [3, 4].
In addition to perioperative morbidity, the extent of pelvic bowel disease may also have oncologic implications in patients with advanced ovarian cancer. In a cohort that underwent optimal cytoreductive surgery, Douglas peritonectomy and rectosigmoid resection yielded comparable survival outcomes, underscoring the need to achieve complete macroscopic resection for obtaining a favourable outcome; notably, mesocolic nodal status was not associated with disease-free or overall survival [5]. More recently, mesenteric lymph node (MLN) involvement has been reported to be common among patients undergoing rectosigmoid resection and to increase with greater bowel wall infiltration, while MLN positivity has been linked to a higher rate of isolated aortic/celiac trunk nodal recurrence [6]. These observations suggest that documenting the characteristics of bowel infiltration and mesenteric/mesocolic nodal disease may be important when interpreting oncologic outcomes in patients requiring rectosigmoid resection [6].
Although the addition of rectosigmoid resection to cytoreductive surgery helps achieve optimal tumour debulking and improves survival, it has also been associated with increased postoperative morbidity [7–9]. Anastomotic leakage is among the most serious complications following rectosigmoid resection, as it can lead to reoperation, infection, peritonitis, abscess or fistula formation, prolonged hospitalization, delayed adjuvant chemotherapy, increased recurrence rates, increased postoperative mortality, and decreased overall survival [10, 11]. Anastomotic leakage after rectosigmoid resection in ovarian cancer cytoreduction has been evaluated in several studies; however, there is substantial heterogeneity across studies with respect to histologic composition, disease burden, surgical complexity, definitions of leakage, and postoperative pathways, which complicates cross-study comparisons and interpretations.
The primary endpoint of the present study was to identify the factors associated with anastomotic leakage in patients with advanced-stage HGSOC who underwent rectosigmoid resection. The secondary endpoint was to evaluate the effects of anastomotic leakage on oncologic outcomes.
Materials and methods
Between September 2015 and October 2024, patients with advanced-stage (Fédération Internationale de Gynécologie et d’Obstétrique [International Federation of Gynaecology and Obstetrics], FIGO 2014 stage III and IV) HGSOC who underwent rectosigmoid resection with primary anastomosis at two tertiary referral centres were included in the study. Patients with other concomitant tumours, who underwent secondary cytoreductive surgery for recurrent disease, and with other histopathologic subtypes—including low-grade serous carcinoma—were excluded. Demographic and clinical characteristics, as well as preoperative, intraoperative, and postoperative variables and laboratory data, were obtained from the patient electronic medical records and files. Candidate predictors of anastomotic leakage were prespecified and grouped according to their temporal relationship with the operation as preoperative, intraoperative, and early postoperative variables. Preoperative variables included demographics and baseline clinical status (e.g., age, comorbidity, American Society of Anesthesiologists (ASA) class), disease-related factors (e.g., FIGO stage and extent of disease), baseline laboratory parameters (including serum albumin), and preoperative preparatory measures (e.g., bowel preparation). Intraoperative variables included surgical complexity (e.g., extent of bowel resection and additional upper abdominal procedures), operative time, estimated blood loss, the need for intraoperative transfusion, and intraoperative adverse events. Early postoperative variables included immediate postoperative laboratory values (including postoperative albumin), early postoperative transfusion, and early postoperative complications occurring prior to the outcome of interest. For continuous variables, cut-offs for estimated blood loss, transfusion exposure, and serum albumin levels were derived using a cohort-based approach to ensure adequate group sizes and stable model estimation while maintaining clinical interpretability. These thresholds were therefore treated as exploratory rather than as externally validated clinical limits. Accordingly, the results are reported using cautious language and interpreted as risk stratification signals within this dataset. The study was approved by the institutional ethics committee (Approval No: 1–24-343). All procedures were performed in accordance with the ethical standards of the institutional research committee and with the 1964 Declaration of Helsinki and its later amendments.
Patients with systemic diseases such as cardiovascular disorders, diabetes mellitus, chronic pulmonary disease, renal failure, or immune system dysfunction were defined as having comorbidities. Surgical procedures were classified as “complex” or “noncomplex.” Total hysterectomy, bilateral salpingo-oophorectomy, retroperitoneal lymphadenectomy, total omentectomy, appendectomy, pelvic peritonectomy, rectosigmoid resection, and primary anastomosis were defined as noncomplex surgical procedures. Advanced surgical procedures, including small and large bowel resection, splenectomy, hepatic metastasectomy, diaphragmatic peritoneal stripping, and distal pancreatectomy, were categorized as complex surgeries. If at least one of these advanced procedures was performed, the patient was classified as belonging to the “complex surgery” group.
Maximal (complete) cytoreduction was defined as no visible residual disease at the end of surgery. Optimal cytoreduction was defined as a maximum residual tumour diameter ≤ 1 cm, and suboptimal cytoreduction was defined as a maximum residual tumour diameter > 1 cm. All surgical procedures, including advanced techniques, were performed by the same gynaecologic oncology surgical team to ensure uniformity. All patients underwent preoperative mechanical bowel preparation with a low-residue diet and combined oral bowel preparation and rectal enema. All patients received perioperative antibiotic prophylaxis: cefazolin 2 g IV in the absence of β-lactam allergy and metronidazole 500 mg IV plus gentamicin 5 mg/kg IV in patients otherwise.
Following resection, an end-to-end anastomosis was created using a circular stapler, and a drain was routinely placed adjacent to the anastomotic site. All patients received postoperative antibiotics, and the timing of drain removal was left to the discretion of the senior surgeon. Additional anastomosis was defined as any bowel anastomosis constructed in addition to the rectosigmoid anastomosis, e.g., created as a result of additional bowel resections outside the rectosigmoid segment. A diverting ileostomy was created at the discretion of the senior surgeon in patients considered at relatively high risk for leakage. In such patients, leakage was evaluated using the same composite criteria (clinical suspicion, CT findings). Given that diversion may attenuate overt feculent output, a low threshold for CT imaging was applied in the presence of postoperative sepsis, persistent ileus, localized abdominal/pelvic signs, or unexplained inflammatory deterioration. Anastomotic leakage was ascertained using a composite approach based on clinical findings, cross-sectional imaging, and surgical confirmation when re-exploration was performed. Clinical suspicion was triggered by one or more of the following: fever or sepsis of unclear source, abdominal pain/peritonitis, and persistent ileus or pelvic abscess. When leakage was suspected, contrast-enhanced computed tomography (CT) (with additional oral/rectal contrast) was used to identify extraluminal contrast extravasation, peri-anastomotic gas/fluid collections, and abscesses adjacent to the anastomosis. In patients who underwent reoperation, the diagnosis and leak site were confirmed intraoperatively.
To distinguish rectosigmoid anastomotic leakage from leakage involving other bowel anastomoses, each event was site adjudicated on the basis of imaging and/or intraoperative findings. Events were classified as rectosigmoid leakage when the rectosigmoid anastomosis was involved; leakage occurring exclusively at nonrectosigmoid anastomoses (e.g., ileoileal, ileocolic, or colocolic) was classified as other anastomotic leakage.
Survival analysis
Progression-free survival (PFS) was defined as the interval from the completion date of first-line adjuvant chemotherapy to the first radiological or clinical evidence of disease progression or the last follow-up for patients without recurrence. Overall survival (OS) was defined as the interval from the completion date of first-line adjuvant chemotherapy to death from any cause or the last follow-up. This time zero definition was prespecified to standardize the onset of risk after delivery of frontline systemic therapy and to minimize heterogeneity attributable to perioperative recovery time. However, using the time zero method inherently requires patients to remain alive (and progression free) upon chemotherapy completion until that date; because postoperative complications such as anastomotic leakage can delay initiation and therefore completion of adjuvant chemotherapy, this approach may introduce immortal time (guarantee-time) bias, potentially attenuating between-group differences. Accordingly, survival comparisons are presented as exploratory, hypothesis-generating analyses rather than definitive causal estimates. Because diverting loop ileostomy was not randomly assigned and reflected intraoperative risk stratification, any comparison involving ileostomy status is vulnerable to selection bias (confounding by indication). Ileostomy is therefore reported descriptively, and its relationship with leakage is not interpreted to be causal. In the presence of few events (including the absence of leakage among diverted patients in our cohort), modelling ileostomy as a predictor may be unstable and should be approached with caution. All patients received platinum–taxane chemotherapy (carboplatin plus paclitaxel) as a first-line treatment. The use of bevacizumab and PARP inhibitors varied over the study period, but inconsistent data precluded modelling these treatments as time-varying covariates in survival analyses. Patients who received neoadjuvant chemotherapy (NACT) were excluded from survival analyses because their treatment pathway introduces a fundamentally different time structure relative to that of primary debulking surgery, limiting comparability and potentially confounding associations between postoperative complications (including anastomotic healing) and oncologic outcomes.
Patients were systematically evaluated at three-month intervals during the first two years, every six months from years two to five, and annually thereafter. At each visit, a gynaecologic examination, serum CA-125 measurement, and abdominal ultrasonography were routinely performed. When clinically indicated, additional imaging methods, such as computed tomography, positron emission tomography or magnetic resonance imaging, were utilized.
Statistical analysis
Statistical analyses were performed using SPSS version 22.0 (Statistical Package for the Social Sciences for Windows, Version 22.0, IBM Corp., Armonk, NY, USA, 2013). The distribution of continuous variables was assessed using the Kolmogorov–Smirnov test. Categorical variables were analysed using the Pearson chi-square (χ²) test or Fisher’s exact test, as appropriate, and are expressed as frequencies and percentages. The Mann–Whitney U test was used to compare nonnormally distributed continuous variables between groups. PFS and OS were estimated using the Kaplan–Meier method, and survival curves were compared using the log-rank test. A p value of < 0.05 was considered to indicate statistical significance.
Results
A total of 102 patients were included in the study. The median patient age was 56 years (range, 24–79), and 76.4% had FIGO stage III disease. During the preoperative period, 59.8% of the patients had at least one systemic comorbidity, and 17.6% were smokers. A total of 14.7% of patients had received neoadjuvant chemotherapy. A total of 85% of the patients had an ASA score of 1–2 (Table 1).
Table 1.
The features of the entire cohort
| Preoperative parameters | ||
|---|---|---|
| n | % | |
| Presence of co-morbidity | 61 | 59.8 |
| Smoking | 18 | 17.6 |
| Preoperative chemotherapy except for neoadjuvant chemotherapy | 3 | 2.9 |
| Neoadjuvant chemotherapy | 15 | 14.7 |
| Preoperative given erythrocyte suspension | 5 | 4.9 |
| Preoperative given fresh frozen plasma | 0 | 0 |
| Mean ± SD | Median (range) | |
| Age (year) | 55 ± 11.38 | 56 (24–79) |
| Body mass index (kg/m2) | 28.1 ± 5.31 | 28.2 (17.1–41.4) |
| ASA score | 2.3 ± 0.61 | 2 (1–3) |
| The time interval from previous operation to main operation (month) | 138.1 ± 151.10 | 120 (1–480) |
| Preoperative given erythrocyte suspension (unit) | 1.6 ± 0.55 | 2 (1–2) |
| The time when the erythrocyte suspension was performed preoperatively (day) | 1.3 ± 1.17 | 1.5 (0–3) |
| Hemoglobin level (g/dl) | 12 ± 1.39 | 12 (8.8–15.4) |
| Leukocyte count (/µL) | 7306.1 ± 2031.11 | 6925 (3400 − 12.940) |
| Neutrophil count (/µL) | 5058.3 ± 1917.14 | 5075 (1170 − 11.040) |
| Platelet count (103/mm3) | 350.441 ± 138.155 | 342.000 (110.000–931.000.000.000) |
| Albumin level (g/dl) | 3.8 ± 0.62 | 3.9 (1.8–5.1) |
| Intraoperative parameters | ||
|---|---|---|
| n | % | |
| Ascites | 64 | 62.7 |
| Intraoperative given erythrocyte suspension (unit) | 83 | 81.4 |
| Nasogastric tube | 83 | 81.4 |
| Abdominal drain | 102 | 100 |
| Mean ± SD | Median (range) | |
| The duration of operation (minute) | 385 ± 103.03 | 360 (180–660) |
| Ascites volume (ml) | 2874.2 ± 2602.32 | 2000 (100 − 10.000) |
| Bleeding volume (ml) | 1552.7 ± 1114.04 | 1300 (125–7000) |
| Given crystalloid fluid quantity (ml) | 6305.4 ± 2275.86 | 6000 (2000-13.000.000) |
| Given colloid fluid quantity (ml) | 1135.9 ± 567.53 | 1000 (100–2800) |
| Intraoperative given erythrocyte suspension (unit) | 2.45 ± 1.39 | 2 (1–8) |
| Intraoperative given fresh frozen plasma (unit) | 2.5 ± 1.14 | 2 (1–5) |
| Intraoperative given total fluid (ml) | 7964.8 ± 2904.53 | 7500 (2000 − 16.200) |
| Postoperative parameters | ||
| n | % | |
| Postoperative given erythrocyte suspension | 42 | 41.2 |
| Postoperative given fresh frozen plasma | 17 | 16.7 |
| Postoperative given albumin | 95 | 93.1 |
| Postoperative given antibiotic | 102 | 100 |
| Mean ± SD | Median (range) | |
| Postoperative given erythrocyte suspension (unit) | 1.93 ± 0.75 | 2 (1–4) |
| Postoperative given fresh frozen plasma (unit) | 2 ± 0.71 | 2 (1–4) |
| The time when the erythrocyte suspension was performed postoperatively (day) | 3.4 ± 4.91 | 2 (1–21) |
| Albumin (postoperative 1 st day) (g/dl) | 2.3 ± 0.60 | 2.4 (1–3.6.6) |
| Removed of nasogastric tube after operation (day) | 1.9 ± 1.23 | 2 (1–7) |
| Removed of abdominal drain after operation (day) | 9 ± 4.02 | 8 (3–28) |
| Oral intake after operation (day) | 4.3 ± 1.52 | 4 (2–11) |
ASA American Society of Anesthesia
Intraoperative parameters, including operative time, estimated blood loss, and the amount of intravenous fluids administered, were evaluated. The mean operative time was 385 ± 103 min, the mean estimated blood loss was 1553 ± 1114 mL, and the mean total amount of fluids administered intraoperatively, including crystalloids and colloids, was 7965 ± 2905 mL (Table 1).
During the postoperative period, 41.2% of patients received red blood cell transfusions, 16.7% received fresh frozen plasma, and 93.1% received albumin replacement. The median time to nasogastric tube removal was 2 days (range, 1–7), the median time to initiation of oral intake was 4 days (range, 2–11), and the median time to the removal of drains placed at the site of anastomosis was 8 days (range, 3–28) (Table 1).
The majority of patients underwent abdominal hysterectomy and bilateral salpingo-oophorectomy with systematic pelvic and para-aortic lymph node dissection. All patients underwent rectosigmoid resection and primary anastomosis as part of cytoreductive surgery. Omentectomy was performed in all patients, whereas diaphragmatic stripping was performed in 67.6%, pelvic peritonectomy in 42.2%, splenectomy in 35.3%, and hepatic metastasectomy in 14.7%. Additionally, distal pancreatectomy was performed in 3.9% of the patients, and cholecystectomy was performed in 8.8%. Complex surgery was performed in 75.5% of the patients. In addition to rectosigmoid resection, additional colon segment resection was performed in 13.7% of patients, and small bowel resection was performed in 4.9%; as a result, 12 (11.8%) patients underwent additional anastomoses, defined as any bowel anastomosis constructed outside of the rectosigmoid junction. At the senior surgeon’s discretion, protective ileostomy was performed in 8 (7.8%) patients considered at high risk for anastomotic leakage. Maximal cytoreduction was achieved in 94.1% of patients, and optimal cytoreduction was achieved in 5.9% (Table 2).
Table 2.
Operation procedures
| Procedure | n | % | |
|---|---|---|---|
| Hysterectomy | 99 | 97.1 | |
| Oophorectomy | 99 | 97.1 | |
| Pelvic lymphadenectomy | 101 | 99 | |
| Paraaortic lymphadenectomy | 101 | 99 | |
| Omentectomy | 102 | 100 | |
| Pelvic peritonectomy | 43 | 42.2 | |
| Diaphragm stripping | 69 | 67.6 | |
| Splenectomy | 36 | 35.3 | |
| Hepatic metastasectomy | 15 | 14.7 | |
| Distal pancreatectomy | 4 | 3.9 | |
| Cholesistectomy | 9 | 8.8 | |
| Appendectomy | 66 | 64.7 | |
| Small bowel resection | 5 | 4.9 | |
| Ileostomy | 8 | 7.8 | |
| Colonic resection except for rectosigmoid resection | 14 | 13.7 | |
| Another anastomosis except for rectosigmoid anastomosis* | 12 | 11.8 | |
| Complex surgery | 77 | 75.5 | |
| Surgical outcome | Optimal cytoreduction (residue tumor <1 cm) | 6 | 5.9 |
| Maximal cytoreduction (no residue tumor) | 96 | 94.1 | |
* Any bowel anastomosis constructed other than the rectosigmoid anastomosis (e.g., ileoileal, ileocolic, or colocolic), performed due to additional bowel resection
Rectosigmoid anastomotic leakage occurred in 9 (8.8%) patients, while leakage involving other bowel anastomoses (ileocolic, ileoileal, or colocolic) was detected in 4 (3.9%) patients. Rectosigmoid anastomotic leakage developed at a median of 8 days (range, 4–17) postoperatively. All rectosigmoid anastomotic leaks were managed surgically, and no mortality was attributable to the complication.
Preoperative factors, including age; body mass index; the presence of comorbidities; smoking status; the use of neoadjuvant chemotherapy; the ASA score; and preoperative haemoglobin, leukocyte, neutrophil, platelet, and albumin levels, were not significantly associated with anastomotic leakage (Table 3).
Table 3.
Relation between preoperative factors and rectosigmoid anastomotic leakage
| Preoperative factors | Rectosigmoid anastomotic leakage | P value | ||||
|---|---|---|---|---|---|---|
| Yes | No | |||||
| n | % | n | % | |||
| Age (year) 1 | ≤ 56 | 4 | 7.7 | 48 | 92.3 | 0.681 |
| > 56 | 5 | 10 | 45 | 90 | ||
| Age (year) 2 | < 65 | 7 | 8.9 | 72 | 91.1 | 0.980 |
| ≥ 65 | 2 | 8.7 | 21 | 91.3 | ||
| Body mass index (kg/m2) 1 | ≤ 28.2 | 5 | 9.6 | 47 | 90.4 | 0.774 |
| > 28.2 | 4 | 8 | 46 | 92 | ||
| Smoking | Absent | 9 | 10.7 | 75 | 89.3 | 0.146 |
| Present | 0 | 0 | 18 | 100 | ||
| Co-morbidity | Absent | 4 | 9.8 | 37 | 90.2 | 0.785 |
| Present | 5 | 8.2 | 56 | 91.8 | ||
| Neoadjuvant chemotherapy | Not received | 8 | 9.2 | 79 | 90.8 | 0.750 |
| Received | 1 | 6.7 | 14 | 93.3 | ||
| ASA score | 1&2 | 4 | 6 | 63 | 94 | 0.160 |
| 3&4 | 5 | 14.3 | 30 | 85.7 | ||
| Preoperative transfusion of erythrocyte suspension | No | 8 | 8.2 | 89 | 91.8 | 0.366 |
| Yes | 1 | 20 | 4 | 80 | ||
| Hemoglobin level (g/dl) 3 | ≤ 12 | 3 | 5.9 | 48 | 94.1 | 0.295 |
| > 12 | 6 | 11.8 | 45 | 88.2 | ||
| Leukocyte count (/µL) 3 | ≤ 10.000 | 7 | 7.7 | 84 | 92.3 | 0.247 |
| > 10.000 | 2 | 18.2 | 9 | 81.8 | ||
| Neutrophil count (/µL) 3 | ≤ 8000 | 8 | 8.3 | 88 | 91.7 | 0.485 |
| > 8000 | 1 | 16.7 | 5 | 83.3 | ||
| Platelet count (/mm3) 3 | ≤ 400.000 | 6 | 8.2 | 67 | 91.8 | 0.733 |
| > 400.000 | 3 | 10.3 | 26 | 89.7 | ||
| Albumin level (g/dl) 3, 4 | ≤ 3.5 | 0 | 0 | 17 | 100 | 0.266 |
| > 3.5 | 4 | 6.9 | 54 | 93.1 | ||
ASA American Society of Anesthesia
1Median value
2 Geriatric age
3Reference value; upper of normal limit our institution
4 n = 75 (Twenty-seven patients excluded, because of they didn’t have preoperative albumin level report)
During the intraoperative period, the amount of blood loss and the number of transfused red blood cell units were found to be significant determinants of anastomotic leakage. However, the duration of surgery; the presence of ascites; the need for resection of the small bowel; the need for the resection of colon segments other than the rectosigmoid segment; the need for complex surgery; and the amounts of intraoperatively administered crystalloids, colloids, or fresh frozen plasma were not significantly correlated with the risk of leakage. Anastomotic leakage was observed in 14.9% of patients with intraoperative blood loss exceeding 1300 mL but in only 3.6% of those with less blood loss (p = 0.046). Among patients who received more than two units of red blood cells, leakage was detected in 23.1%, whereas it occurred in 3.3% of those transfused with fewer units (p = 0.004) (Table 4).
Table 4.
Relation between intraoperative factors and rectosigmoid anastomotic leakage
| Intraoperative factors | Rectosigmoid anastomotic leakage | P value | ||||
|---|---|---|---|---|---|---|
| Yes | No | |||||
| n | % | n | % | |||
| The duration of the operation (minutes) 1 | ≤360 | 2 | 4.8 | 40 | 95.2 | 0.226 |
| >360 | 7 | 11.7 | 53 | 88.3 | ||
| Ascites | No | 6 | 15.8 | 32 | 84.2 | 0.056 |
| Yes | 3 | 4.7 | 61 | 95.3 | ||
| Colon resection except rectosigmoid resection | Not performed | 9 | 10.2 | 79 | 89.8 | 0.210 |
| Performed | 0 | 0 | 14 | 100 | ||
| Small bowel resection | Not performed | 9 | 9.3 | 88 | 90.7 | 0.476 |
| Performed | 0 | 0 | 5 | 100 | ||
| Ileostomy | Not performed | 9 | 9.6 | 85 | 90.4 | 0.359 |
| Performed | 0 | 0 | 8 | 100 | ||
| Appendectomy | Not performed | 2 | 5.6 | 34 | 94.4 | 0.390 |
| Performed | 7 | 10.6 | 59 | 89.4 | ||
| Surgery type | Non-complex | 0 | 0 | 25 | 100 | 0.073 |
| Complex | 9 | 11.7 | 68 | 88.3 | ||
| Cytoreduction | Optimal (residue tumor <1cm) | 0 | 0 | 6 | 100 | 0.432 |
| Maximal (no residue tumor) | 9 | 9.4 | 87 | 90.6 | ||
| Amount of the bleeding (ml) 1 | ≤1300 | 2 | 3.6 | 53 | 96.4 | 0.046 |
| >1300 | 7 | 14.9 | 40 | 85.1 | ||
| Amount of the applied total fluid (ml) 1 | ≤7500 | 3 | 5.7 | 50 | 94.3 | 0.241 |
| >7500 | 6 | 12.2 | 43 | 87.8 | ||
| Amount of the applied crystalloid fluid (ml) 1 | ≤6000 | 3 | 5.7 | 50 | 94.3 | 0.241 |
| >6000 | 6 | 12.2 | 43 | 87.8 | ||
| Amount of the applied colloid fluid (ml)1 | ≤1000 | 5 | 7.7 | 60 | 92.3 | 0.593 |
| >1000 | 4 | 10.8 | 33 | 89.2 | ||
| Intraoperative transfusion of erythrocyte suspension | No | 1 | 5.3 | 18 | 94.7 | 0.544 |
| Yes | 8 | 9.6 | 75 | 90.4 | ||
| Amount of the erythrocyte suspension (unite) 1 | ≤2 | 2 | 3.5 | 55 | 96.5 | 0.004 |
| >2 | 6 | 23.1 | 20 | 76.9 | ||
| Intraoperative transfusion of fresh frozen plasma | No | 4 | 8.5 | 43 | 91.5 | 0.918 |
| Yes | 5 | 9.1 | 50 | 90.9 | ||
| Amount of the fresh frozen plasma (unite) 1 | ≤2 | 2 | 5.4 | 35 | 94.6 | 0.173 |
| >2 | 3 | 16.7 | 15 | 83.3 | ||
1Median value
In the early postoperative period, the serum albumin level was a significant predictor of anastomotic leakage. Among patients with a postoperative day 1 albumin level ≤ 2.4 g/dL, 17% developed rectosigmoid anastomotic leakage, whereas no leakage occurred in patients with an albumin level > 2.4 g/dL (p = 0.004). No significant association was observed between anastomotic leakage and postoperative red blood cell or plasma transfusion, duration of nasogastric tube placement beyond 2 days, or timing of oral intake initiation (Table 5).
Table 5.
Relation between postoperative factors and rectosigmoid anastomotic leakage
| Postoperative factors | Rectosigmoid anastomotic leakage | P value | ||||
|---|---|---|---|---|---|---|
| Yes | No | |||||
| n | % | n | % | |||
| Postoperative transfusion of erythrocyte suspension 1 | No | 7 | 11.7 | 53 | 88.3 | 0.226 |
| Yes | 2 | 4.8 | 40 | 95.2 | ||
| Amount of the erythrocyte suspension (unite) 1 | ≤ 2 | 2 | 5.3 | 36 | 94.7 | 0.638 |
| > 2 | 0 | 0 | 4 | 100 | ||
| The time of the applying the erythrocyte suspension (days) 1 | ≤ 2 | 2 | 6.3 | 30 | 93.8 | 0.418 |
| > 2 | 0 | 0 | 10 | 100 | ||
| Postoperative transfusion of fresh frozen plasma | No | 8 | 9.4 | 77 | 90.6 | 0.640 |
| Yes | 1 | 5.9 | 16 | 94.1 | ||
| Albumin transfusion | No | 2 | 28.6 | 5 | 71.4 | 0.056 |
| Yes | 7 | 7.4 | 88 | 92.6 | ||
| Albumin level, postoperative 1 st day (g/dl) 1, 2 | ≤ 2.4 | 9 | 17 | 44 | 83 | 0.004 |
| > 2.4 | 0 | 0 | 44 | 100 | ||
| Removed of nasogastric tube after operation (day) 1, 3 | ≤ 2 | 4 | 6.5 | 58 | 93.5 | 0.091 |
| > 2 | 4 | 19 | 17 | 81 | ||
| Oral intake (day) 1 | ≤ 4 | 3 | 7.5 | 37 | 92.5 | 0.705 |
| > 4 | 6 | 9.7 | 56 | 90.3 | ||
1 Median value
2 n = 97 (Five patients excluded, because of they didn’t have postoperative 1 st day albumin level report)
3 n = 83 (The day of the removed of nasogastric tube after operation in 19 patients didn’t known)
The median interval to initiation of adjuvant chemotherapy was 19 days (range, 8–102) for the overall cohort. In cases where anastomotic leakage occurred, the initiation of adjuvant chemotherapy was significantly delayed, with a median of 39.5 days, compared with 18 days in patients without leakage (p < 0.001). All patients received carboplatin–paclitaxel treatment.
Survival analysis
After 15 patients who received neoadjuvant chemotherapy were excluded, survival analysis was performed for the remaining 87 patients. The median follow-up duration was 20 months (range, 1–117). During this period, recurrence occurred in 43.7% of the patients. The 3-year PFS and 5-year PFS rates were 32% and 23%, respectively. The 3-year OS and 5-year OS rates were approximately 72% and 43%, respectively. Oncologic outcomes were similar between patients who developed rectosigmoid leakage and those who did not. The 3-year PFS rate was 43% in patients with anastomotic leakage and 32% in patients without anastomotic leakage (p = 0.567) (Fig. 1), while the respective 3-year OS rates were 71% and 73% (p = 0.184) (Fig. 2).
Fig. 1.
Kaplan–Meier curve for progression-free survival according to the presence of rectosigmoid anastomotic leakage (p = 0.567)
Fig. 2.
Overall survival according to the presence of rectosigmoid anastomotic leakage (p = 0.184)
Discussion
In this study, we evaluated outcomes in patients with advanced-stage HGSOC who underwent rectosigmoid resection during cytoreductive surgery. The incidence of anastomotic leakage was 8.8%, occurring at a median of 8 days (range, 4–17) after the operation. Anastomotic leakage was statistically associated with intraoperative blood loss, the number of transfused red blood cell units, and postoperative day 1 albumin levels. However, age, ASA score, multiple bowel resections, multiorgan resection, operation duration, and comorbidities were not related to the occurrence of leakage. In our cohort, anastomotic leakage was associated with a clinically meaningful delay in the initiation of adjuvant chemotherapy; nevertheless, no statistically significant difference in PFS or OS was observed under the prespecified endpoint definition (time zero at completion of adjuvant chemotherapy). Importantly, the decision to use the time zero, method to standardize follow-up after the completion of frontline systemic therapy may have led to immortal time (guarantee-time) bias because patients must remain alive and progression-free until chemotherapy completion, and leakage-related delays could differentially lengthen this “guaranteed” period. Therefore, survival comparisons should be interpreted as exploratory and not as definitive evidence of the absence of effect [12, 13].
Previous studies in colorectal cancer cohorts have reported that the incidence of anastomotic leakage varies between 2% and 19%, depending on the surgical team’s experience [14, 15]. During cytoreductive surgery for advanced ovarian cancer, the reported incidence of bowel anastomotic leakage ranges from 3% to 14% [16–18]. In a study by Kim et al.. including 770 patients with primary ovarian cancer, the incidence of anastomotic leakage following rectosigmoid resection was 4.2% [17]. In a meta-analysis of 84 studies of patients who underwent surgery for rectal cancer, Paun et al.. reported a leakage rate of 11% [19]. Hablase et al.. compared women who underwent surgery for ovarian and colorectal cancers and reported no significant difference in leakage rates between groups (4.7% in the ovarian cancer cohort versus 1.9% in the colorectal cancer cohort (p = 0.082)) [20].
In the present study, intraoperative blood loss and the need for blood transfusion were significantly associated with the risk of anastomotic leakage. As the amount of blood loss and the number of transfused red blood cell units increased, so did the risk of leakage. Park et al.. reported that intraoperative blood loss was a significant predictor of anastomotic leakage in patients who underwent rectal cancer surgery [21]. Similarly, a case–control study from the Swedish Rectal Cancer Registry revealed that severe intraoperative bleeding was significantly associated with an increased risk of colorectal anastomotic leakage [22]. Other studies by Telem et al.. have demonstrated that when intraoperative blood loss exceeds 200 mL among patients undergoing colorectal surgery, the risk of leakage increases significantly [23, 24].
In our study, anastomotic leakage occurred in 17% of patients whose postoperative day 1 albumin level was less than 2.4 g/dL, whereas no leakage was observed in those with higher levels. Shimura et al.. reported early postoperative hypoalbuminaemia as an independent risk factor for anastomotic leakage in 196 colorectal cancer patients [25]. Similarly, Hu et al.. reported that a decrease of 27.2% or more in serum albumin levels after the operation compared with those before the operation significantly increased the risk of leakage in female patients who underwent sphincter-preserving rectal surgery [26].
Prophylactic ileostomy was performed in only 7.8% of our cohort, and no anastomotic leakage occurred in these patients. However, the role of protective stoma formation remains controversial. Vargiu et al.. reported that a restrictive policy towards diverting stoma creation in patients undergoing rectosigmoid resection did not affect leakage rates but was associated with more severe complications, longer hospitalization, and delayed chemotherapy [27].
Gallotta et al.. reported similar survival outcomes after Douglas peritonectomy versus rectosigmoid resection in optimally cytoreduced patients, emphasizing that complete macroscopic resection is the dominant determinant of a favourable prognosis rather than the specific pelvic procedure performed [5]. Mesenteric dissemination may represent an additional determinant of disease behaviour and recurrence patterns in advanced ovarian cancer patients. In patients who underwent rectosigmoid resection, MLN metastases were frequent and the number of metastases increased with increasing depth of bowel wall invasion and were associated with an increased risk of isolated aortic/celiac trunk nodal relapse [6]. Taken together, these data suggest that in addition to postoperative complications such as anastomotic leakage, the pattern and depth of bowel involvement and mesenteric/mesocolic nodal disease could modify oncologic trajectories and may partially explain heterogeneity across studies [6].
In addition, systemic therapy for advanced ovarian cancer has evolved substantially over the study period, with increasing incorporation of bevacizumab and PARP inhibitor maintenance in select patients, both of which can influence progression dynamics and survival [28, 29]. In the present retrospective dataset, bevacizumab and maintenance strategies were not consistently captured, precluding adjustment for these potential confounders; this limitation may contribute to heterogeneity across studies and should be considered in the interpretation of survival endpoints.
Wright and Seagle reported that delays in initiating chemotherapy beyond six weeks were associated with poor survival, whereas Tewari reported that delays exceeding 36 days adversely affected overall survival [30–32]. In our cohort, maximal cytoreduction was achieved in approximately 94.1% of patients. Although anastomotic leakage significantly delayed the initiation of adjuvant chemotherapy, no statistically significant difference in PFS or OS was detected under the prespecified endpoint definition (time zero at completion of adjuvant chemotherapy). These survival findings should be interpreted as exploratory, given the methodological considerations related to the chosen time zero and the available follow-up and event distribution in our cohort (median follow-up 20 months; recurrence in 43.7%). Similarly, Trillsch et al.. reported no statistically significant association between anastomotic leakage and PFS/OS in an exploratory analysis of radical multivisceral surgery for advanced ovarian cancer [33]. Other studies have likewise reported no statistically significant differences in long-term oncologic outcomes; however, heterogeneity in cohort composition and endpoint definitions across studies warrants cautious interpretation [18, 34, 35].
The strengths of this study include the use of a standardized surgical technique for all anastomoses, ensuring homogeneity, and the high rate (94%) of maximal cytoreduction across the cohort. Furthermore, the inclusion of a single histologic subtype allowed for a clearer evaluation of the relationship between leakage and oncologic outcomes. This study is limited by its retrospective design. In addition, the distance between the colorectal anastomosis and the anal verge was not consistently documented. Detailed pelvic bowel disease variables, including rectosigmoid invasion depth and mesenteric/mesocolic nodal involvement, were not consistently documented, which limited meaningful subgroup analyses. In addition, the use of bevacizumab and maintenance strategies evolved over the study period and may have influenced PFS/OS; however, these data were inconsistently captured in this retrospective dataset, precluding adjustment in survival models.
Conclusion
Rectosigmoid resection with primary anastomosis is a safe surgical procedure for achieving optimal cytoreduction in patients with advanced ovarian cancer. Anastomotic leakage occurs in approximately one in ten patients who undergo this procedure for advanced HGSOC. Intraoperative blood loss and early postoperative hypoalbuminaemia are key determinants of leakage. Although anastomotic leakage delayed the initiation of adjuvant chemotherapy, no statistically significant difference in PFS or OS was detected under the prespecified endpoint definition (from completion of adjuvant chemotherapy). Given the potential for guarantee-time bias and the inability to fully account for temporal changes in systemic therapy (including bevacizumab/PARP maintenance), these survival findings should be considered exploratory and hypothesis generating.
Supplementary Information
Authors’ contributions
Arife Ebru Taşcı: Conceptualization, study design, data acquisition, data analysis and interpretation, manuscript drafting, and overall supervision.Fatih Kılıç: Data curation, statistical analysis, and critical revision of the manuscript.Mehmet Ünsal: Methodology, validation, and data interpretation.Okan Aytekin: Data collection, investigation, and resources.Yeşim Özkaya Uçar: Data analysis, writing—review and editing.Gülşah Tiryaki Güner: Data collection and project administration.Burak Ersak: Software support, data visualization, and statistical validation.Ayşe Buran: Clinical data acquisition and literature review.İbrahim Ethem Canbulut: Data collection and manuscript preparation.Caner Çakır: Data collection and investigation.Sevgi Koç: Clinical support and resources.Nurettin Boran: Supervision, critical revision, and approval of the final version.Özlem Moraloğlu Tekin: Conceptualization, supervision, and project administration.Yaprak Üstün: Methodological oversight, review, and final approval of the manuscript.Ahmet Taner Turan: Senior supervision, conceptual guidance, and final approval of the submitted version.All authors have read and approved the final version of the manuscript and agree to be accountable for all aspects of the work, ensuring that any questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Data availability
The datasets generated and/or analysed during the current study are available from the corresponding author upon reasonable request.
Declarations
Ethics approval and consent to participate
This study was approved by Ankara Bilkent City Hospital No. 1 Medical Research Scientific and Ethics Committee (Approval No: 1-24-343; Date: 03 July 2024). Given that this was a retrospective file review, the requirement for informed consent was waived by the same committee.
Given that this study was a retrospective file review, informed consent was waived by Ankara Bilkent City Hospital No. 1 Medical Research Scientific and Ethics Committee (Approval No: 1-24-343, Date: 03 July 2024).
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Supplementary Materials
Data Availability Statement
The datasets generated and/or analysed during the current study are available from the corresponding author upon reasonable request.