POSTOPERATIVE COMPLICATIONS ASSOCIATED WITH PELVIC EXENTERATION IN WOMEN WITH GYNECOLOGICAL CANCER: AN INTEGRATIVE REVIEW*

Objective: to identify the main complications arising from the pelvic exenteration surgery in gynecological cancer and the in-hospital death outcome after the surgical procedure. Method: an integrative literature review considering 23 articles published from 2012 to 2020 in the LILACS and IBECS databases. The descriptors used were the following: genital cancer, gynecological cancer, pelvic exenteration, exenteration, postoperative complications, surgical complications and death , combined by means of the AND or OR Boolean connectors. Results: surgical applicability was verified for cervical, uterine, ovarian, vaginal and vulvar cancer; age was associated with comorbidities (diabetes and hypertension); total pelvic exenteration was predominant; and there were high mean surgical and hospitalization times due to infections. Contributions to the area: this research enables improvements in the health care provided in the PE pre-, peri-and post-operative periods, as it elucidates the main problems resulting from this surgery, their stratifications and management options. DESCRIPTORS: Neoplasms in the Female Genitals


INTRODUCTION
The therapeutic measures to approach gynecological cancer can vary and be combined in several ways according to staging of the disease and to the patient's clinical condition 1 .Pelvic Exenteration (PE) was described by Brunschwig in 1948 as a palliative procedure for the symptoms caused by locally advanced gynecological tumors.With the advancement in surgical techniques, PE evolved from a palliative to a curative procedure 2 .
Exenterations require extensive reconstruction and surgical recovery with significant morbidity and mortality associated with them, requiring careful selection of the patient to balance the cure or symptom palliation objectives [2][3] .They also require that the patient remains in the Intensive Care Unit immediately after the surgery, in addition to rigorous monitoring.Mortality is between 1% and 16% and its causes include sepsis, thromboembolism, kidney disease and cardiopulmonary failure.Infections (19%-86%), anastomotic leaks (8%-36%), fistulas (8%-36%) and intestinal and urethral obstructions (5%-10%) are some of the most frequent morbidities [2][3][4] .
Evaluating the postoperative complications associated with PE in gynecological cancer is indispensable for professionals caring for patients with this disease, in addition to favoring practice grounded on validated instruments.The method used by Clavien-Dindo to classify post-surgical complications was formulated in 2004 and has been used in studies to assess complications in patients subjected to several types of surgery 5 .
The objective of this study was to identify the main complications arising from the PE surgery in gynecological cancer and in-hospital death after the surgical procedure as outcome.
This is an Integrative Literature Review (ILR) that gathers, assesses and synthesizes the results of research studies on a specific theme.Development of the study included the following stages: identification of the topic and selection of the research question; definition of the inclusion and exclusion criteria; and identification, categorization, analysis, interpretation and presentation of the results 6 .
The research guiding question (In women with gynecological cancer, how do PE surgeries influence the occurrence of post-surgical complications resulting in death during hospitalization?) was defined using the PICOT (Population, Intervention, Control, Outcome and Time) mnemonics, which ensured better traceability of the publications.
The study search was conducted from January to March 2020 in the following databases: National Library of Medicine National Institutes of Health (PubMed), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) and Índice Bibliográfico Español en Ciencias de la Salud (IBECS).The Descriptors in Health Sciences (Descritores em Ciências da Saúde, DeCS) and from the MeSH database were the following: genital cancer, gynecological cancer, pelvic exenteration, exenteration, postoperative complications, surgical complications and death, combined by means of the AND or OR Boolean connectors.
The inclusion criteria adopted corresponded to primary studies published in full in English, Spanish and Portuguese; published between 2012 and 2020; addressing PE performance with curative or palliative purposes, exclusively for diagnoses of oncogynecological malignancies; and which assessed post-surgical complications and postsurgical in-hospital deaths.

METHOD
Postoperative complications associated with pelvic exenteration in women with gynecological cancer: an integrative review Silva IA da, Carneiro IC do RS, Santana ME de, Ferreira IP.
The exclusion criteria corresponded to secondary productions and case studies, in addition to papers addressing PE performance only targeting at exposure to surgical techniques.Consequently, 23 novel research studies were selected for the review, meeting the inclusion criteria.Source: Silva IA; Carneiro ICRS; Santana ME; Ferreira IP. 2020 (7) .
The assumptions established in national research studies were considered during data extraction and when evaluating the level of evidence of the productions 6,8 .The articles were identified by title, year, country, database, level of evidence, objectives and main results.
The Results and Discussion sections are presented in a descriptive way, grouped into semantic categories originated from saturation of the following information: clinical characterization; characterization of the surgical procedure; characterization of the postsurgical complications; and in-hospital death after PE as outcome.

RESULTS
The studies selected are presented in Chart 1.
The search showed nonexistence of publications in Brazilian journals, although two research studies (9%) were produced at the national level; six (26%) were published in the International Journal of Gynecological Cancer and five (22%) in Gynecologic Oncology (Chart 1).
Regarding the research designs, 23 (100%) were retrospective studies, with only two (9%) cohort studies among them.In relation to the time to conduct the studies, four (17%) required nine years to be concluded; another four (17%) lasted three years; three (13%) required 11 years; two (9%) studies considered a 17-year time frame; and another two (9%) covered 13 years.
In relation to the sample, the highest number was 282 women 8 and the smallest sample had 10 participants 9 .The total sum of participants was 1,552, with a mean of 67.47 in each research study.The effect of body mass index on surgical outcomes and survival following pelvic exenteration. assess the viability and efficacy of Minimally-Invasive PE (MIPE) in a series of multiinstitutional Italian cases of women with gynecological cancer and a literature review.

DISCUSSION
The studies were categorized into four areas, emphasizing the main findings to synthesize them, directing the results to knowledge about the profile of the major complications resulting from pelvic exenteration surgeries in gynecological cancer to promote practice grounded on scientific knowledge.

Clinical characterization
The publications have variables in common such as age, characteristics of the tumors, classification of the type of surgical procedure used, and complications arising from the PE surgeries.The mean age was 56±10 years old, although it should not be considered individually as a determinant for selection.However, aging is associated with comorbidities, which can contraindicate the surgery when they are not controlled 11 .
Silva IA da, Carneiro IC do RS, Santana ME de, Ferreira IP.
In a study conducted with 161 women, although age was a determinant in the incidence of comorbidities such as diabetes mellitus and systemic arterial hypertension, this factor does not imply higher frequencies of postoperative complications in aged women 11 .
In relation to the characteristics of the tumors in 1,545 participants, the most frequently diagnosed cancer was cervical with 963 (62%), followed by uterine with 179 (12%), ovarian with 141 (9%) vaginal with 139 (9%) and vulvar with 105 (7%).The histopathological types were evaluated in 744 women, with prevalence of the squamous cell carcinoma type in 358 (48%).
Various types of onco-gynecological conditions can be treated by means of exenteration surgeries, depending on the disease staging evidenced, the patient's clinical condition, and previous consent to undergo the surgery 8,12,21 .
PE can be appropriate for patients with advanced or recurrent primary tumors that cannot be treated with radiotherapy.Complete resection with no evidence of residual disease has been associated with better results with a five-year survival rate of 74% against 21% when complete resectability is not possible 2,18 .
The occurrence of vulvar cancer (105 [7%]) was quite limited when compared to the cervical and uterine cancer diagnoses, being more frequent in aged patients.The outcome for an exenterative course of action arises from the absence of routine outpatient gynecological monitoring.Regarding the women from the young age group, they predominantly present cervical cancer diagnoses 11 .
In cervical cancer cases, PE has been used for centrally recurrent carcinoma and for adenocarcinoma, with well-documented cure potential and survival rates varying from 16% to 60%.It is directly correlated to complete tumor resection, evidencing that resectability is established as a key aspect of preoperative planning 2 .
Most of the recurrent uterine tumors spread beyond the pelvis, making PE an appropriate intervention for only a selected group of patients with recurrent uterine malignancies 2,[9][10]19 . Womn with ovarian cancer are susceptible to the dissemination of malignant cells inside the abdomen, and are seldom candidates for PE [1][2]20 .
A retrospective study analyzed 35 cases of patients with ovarian cancer that were subjected to modified posterior PE with a curative purpose.The survival analysis in relation to residual disease confirmed an optimistic prognosis in patients with optimal resection, with a mean disease-free survival period of 33.6 months in R0 patients, 19.6 months in R1 patients, and 14.3 months in R2 patients.There were post-surgical complications in 83% of the patients, with early complications as the most frequent (65.7%).More severe complications (Grades III and IV) were evidenced in 37.7% of the patients.There were no cases of surgery-associated mortality 23 .
The PE indications are recurrent in cases of necrosis secondary to the radiotherapy treatment, including hemorrhages due to tumor invasion and fistulas 12,22,[29][30][31] Characterization of the surgical procedure The profile of the surgical procedures was well characterized, with six surgical techniques standing out: Total PE (TPE), Posterior PE (PPE), Anterior PE (APE), Anterior PE with Total Vaginectomy (APETV), Modified Posterior PE (MPPE), and Laterally Extended Endopelvic Resection (LEER).
It is worth noting the prevalence of TPE, which was performed in 877 (57%) patients, with a mean of 38 procedures per study 9 ; followed by APE, performed in 346 (22%) women, with a mean of 15 procedures per study; and by PPE, performed in 198 (13%) patients, with a mean of nine procedures per study.
Performing urinary and/or intestinal diversions is crucial to preserve survival of patients with gynecological cancer.In all 23 studies, 411 (51%) corresponded to the incontinent type, ileal conduit subtype, with high incidence of containment pouches for urinary diversion, by means of the Indiana, Miami and Mainz techniques, with 71 (9%).Intestinal diversions were observed in 419 citations, by means of the Hartman Colostomy techniques and with a frequency of 235 (56%), followed by colorectal anastomosis with 129 (31%).Twenty (87%) publications addressed surgical time as a useful parameter to analyze the patients, and 18 (78%) addressed hospitalization time after performing PE due to gynecological tumors.The mean time required to perform the surgical procedure was 485 minutes, ranging from a minimum of 269 23 to a maximum of 648 12 .Extended surgical times are associated with the surgical technical abilities of the professionals involved and with local neoplastic involvement 12 .
The mean hospitalization time was 24 days 24 , with a maximum of 65 days 25 , justified by the postoperative complications related to paralytic ileus and intestinal anastomosis leaks, observed in three patients.
The most incident complications observed after performing PE surgeries secondary to gynecological cancer were infections, with abdominal and pelvic abscesses standing out.The urinary complications can be related to events such as problems performing the urinary diversion and occurrence of renal failure.The intestinal complications were mainly related to the creation of diversions, although some problems related to anastomosis patency were also notified.
Suture dehiscence was reported 176 times (10%), which may explain the high number of surgical reapproaches.The fistulas (7%) were the result of the illness process itself and of the involvement of multiple pelvic organs, as well as to the complication secondary to the surgery.It was possible to observe respiratory, cardiac and blood-related complications in participants who stayed many days in the hospital environment.Rehospitalization (postsurgical complication) was found in 34 (2%) cases.

In-hospital death after PE as outcome
A total of 27 deaths were detected in this research series 8 , a factor that can be analyzed considering the large sample of patients (n=282) and their collective pathological profile: advanced or recurrent cervical cancer and already subjected to 212 previous surgeries.
Post-surgical morbidities are determinants in the outcome of in-hospital death.The authors verify this fact when detecting high occurrence of post-surgical infections (n=20), fistulas (n=42), anastomosis leak (n=21) and thrombosis (n=10) in their sample 8 .The outcomes other than in-hospital death (n=13) were recorded in four different productions reporting 379 post-surgical complications, with infections standing out (n=109) 4,10,22,29 .
Consequently, an integrated multiprofessional team is of fundamental importance for success of the procedure, contributing to reducing adverse events and deaths.
The PE technique represents a challenge for care management by the multiprofessional team due to the complexity of the pathologies eligible for the surgical act.Therefore, this review achieved the objectives outlined when highlighting the main complications arising from the procedure and the outcome of premature death in the hospital environment.It was evident that infectious complications are still the most incident ones despite the pharmacotherapeutic advances, a fact that can be explained by radicality of the procedure.The need to conduct new studies to discuss mortality after PE is noted, considering its association with the total number of post-surgical complications evidenced.
Observation and management of post-PE complications should be priorities for the care team, with the objective of rapidly reversing the harmful effects.For this, the use of classification tools should be a common practice in the hospital environment, always applied and rethought considering the institutional particularities and those of the assisted clientele, aiming at their better dissemination and feasibility in the professional scope.
The study brings about a number of contributions for Nursing, in the sense of improving the health care provided in the PE pre-, peri-and post-operative periods.

Figure 1 -
Figure 1 -Flowchart corresponding to selection of the articles for the Integrative Literature Review.
protocol: LE: Level of Evidence; Part.(n): Number of participants studied in each publication; Age (x): Mean age of the research subjects; Diagnoses (n): Number of diagnoses surveyed in each research study; PE (n): Number of exenteration procedures performed per publication; TPE: Total PE; APE: Anterior PE; PPE: Posterior PE; Surgery time (min) (x): Mean time to perform the surgeries, computed in minutes; Hosp.time (d) (x): Mean hospitalization time, computed in days; Assessment of the complications (n): Discrimination of the methods to assess the complications; Most frequent complications (n): Most frequent complications in each publication, with their respective number of occurrences in the subjects; Death (n): Number of deaths recorded after performing the PE surgeries, still during hospitalization; (---): Data not measured; LEER: Laterally Extended Endopelvic Resection.
Silva IA da, Carneiro IC do RS, Santana ME de, Ferreira IP.Silva IA da, Carneiro IC do RS, Santana ME de, Ferreira IP.