Over 28,000 gynecologic oncology patients were treated at our institution during the study time period, and 53 patients (0.19%) met the inclusion criteria for the study. The median patient age was 56 years (range 31-90 years) with a median BMI of 25.0 (range 16.2-44.6). Table 1 presents patient demographic characteristics. Patients who were diagnosed with rare gynecologic cancer diagnoses were classified as “other” and included one patient with pelvic spindle cell carcinoma and one patient with adenocarcinoma of the rectovaginal septum. Four patients were found to have synchronous primaries at the time of the initial staging surgery. Two patients had synchronous ovarian and endometrial cancer, one patient had concomitant cervical and endometrial cancer, and one patient was found to have synchronous endometrial and colon cancer.
After diagnosis of intestinal perforation, 47 (88.7%) of patients were treated with surgical intervention with 6 (11.3%) patients managed conservatively. The etiology for the perforation was unknown for 29 (54.7%) of patients, but 8 (15.1%) patients were found to have tumor invading bowel serosa. Seven (13.2%) patients were suspected to have colitis, appendicitis, or proctitis as the inciting factor for perforation, and 9 (17.0%) had iatrogenic perforations or perforations diagnosed within 2 weeks after staging surgery, colonoscopy, or intraperitoneal catheter placement.
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Twenty-three (43%) patients were receiving active chemotherapy at the time of intestinal perforation with 10 (19%) patients receiving taxane-based treatment (TC). One patient received bevacizumab and capecitabine two days prior to perforation, and a second patient had received combination carboplatin, paclitaxel, and bevacizumab approximately 4 weeks prior to perforation. Seventy-seven percent of cervical cancer and 63% of uterine cancer patients were not under active treatment compared to patients with ovarian/primary peritoneal and other cancers, 35% and 33%, respectively. Cervical and uterine cancer patients were combined into a single category due to small sample sizes. When patients were categorized either as ovarian/primary peritoneal/other cancers or cervical/uterine cancer, the association between disease site grouping and treatment status was statistically significant at p<0.01. No difference in age, BMI or race was found when comparing those receiving active treatment at the time of perforation to those not on active treatment.
Neither disease site nor history of prior abdominal or pelvic radiotherapy impacted survival from the time of perforation. Twenty-eight patients (52.8%) had a history of radiation therapy with perforations occurring as follows: 7 small bowel perforations with 1 documented perforation in the distal jejunum, 8 ileal perforations, 8 rectosigmoid perforations, 2 appendiceal perforations, and 3 perforations in unknown locations. Based on available records, it is difficult to determine the precise proportion of perforations which occurred in the irradiated fields. However, all 28 patients had a history of pelvic radiotherapy, and 25 of these perforations could have occurred within the standard pelvic fields.
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When examined in a univariate fashion, there was no statistically significant difference in survival from the time of perforation with respect to smoking history, history of bowel surgery or injury during the most recent abdominal surgery prior to perforation, or patients’ presentation with abdominal pain, nausea/vomiting, fever, abnormal bowel movements, potential perforation etiology, or site of bowel perforation. However, patients who were without evidence of disease or who were newly diagnosed with a gynecologic malignancy were found to have a median survival time of 24.7 and 28.1 months, respectively, compared to patients with stable or progressive disease with a median survival time of 3.67 months from the time of perforation (p=0.006). Patients who underwent surgery for treatment of their bowel perforation had a longer median survival time compared to patients who were treated conservatively, including observation (13.7 months compared to 0.50 months, p=0.007). Survival from the time of perforation differed when compared by BMI groups (p-0.013). Patients with a normal BMI (18.5-25.0 kg/m2) had the longest survival time of 68.0 months, compared to underweight (BMI <18.5 kg/m2) and overweight patients (BMI 25.1-30.0 kg/m2), 14.10, and 13.7 months. Patients who were obese (BMI >30.0) had the shortest survival time of 2.47 months.
Prognostic factors examined by Cox regression in a univariate fashion are listed in Table 2. BMI, disease status, WBC, bicarbonate level, APACHE II, and treatment of perforation were all significantly associated with risk of death. When these variables, along with cancer treatment at the time of intestinal perforation, were included in a multivariate regression, only APACHE II scores remained significantly associated with an increased risk of death (HR=1.20, 95%CI 1.12, 1.29). Patients who had APACHE II scores < 15 had a median survival of 28.13 months compared to a survival of 2.90 months in those with scores ≥15 (p<0.0001) (Figure 1).
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