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BMC Cancer May 2024Total pelvic exenteration (TPE), an en bloc resection is an ultraradical operation for malignancies, and refers to the removal of organs inside the pelvis, including... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Total pelvic exenteration (TPE), an en bloc resection is an ultraradical operation for malignancies, and refers to the removal of organs inside the pelvis, including female reproductive organs, lower urological organs and involved parts of the digestive system. The aim of this meta-analysis is to estimate the intra-operative mortality, in-hospital mortality, 30- and 90-day mortality rate and overall mortality rate (MR) following TPE in colorectal, gynecological, urological, and miscellaneous cancers.
METHODS
This is a systematic review and meta-analysis in which three international databases including Medline through PubMed, Scopus and Web of Science on November 2023 were searched. To screen and select relevant studies, retrieved articles were entered into Endnote software. The required information was extracted from the full text of the retrieved articles by the authors. Effect measures in this study was the intra-operative, in-hospital, and 90-day and overall MR following TPE. All analyzes are performed using Stata software version 16 (Stata Corp, College Station, TX).
RESULTS
In this systematic review, 1751 primary studies retrieved, of which 98 articles (5343 cases) entered into this systematic review. The overall mortality rate was 30.57% in colorectal cancers, 25.5% in gynecological cancers and 12.42% in Miscellaneous. The highest rate of mortality is related to the overall mortality rate of colorectal cancers. The MR in open surgeries was higher than in minimally invasive surgeries, and also in primary advanced cancers, it was higher than in recurrent cancers.
CONCLUSION
In conclusion, it can be said that performing TPE in a specialized surgical center with careful patient eligibility evaluation is a viable option for advanced malignancies of the pelvic organs.
Topics: Humans; Pelvic Exenteration; Female; Hospital Mortality; Neoplasms; Genital Neoplasms, Female; Male
PubMed: 38750417
DOI: 10.1186/s12885-024-12377-5 -
European Urology Oncology Oct 2020Optimal management of prostate cancer (PCa) patients with lymph node invasion at radical prostatectomy and pelvic lymph node dissection still remains unclear.
CONTEXT
Optimal management of prostate cancer (PCa) patients with lymph node invasion at radical prostatectomy and pelvic lymph node dissection still remains unclear.
OBJECTIVE
To assess the effectiveness of postoperative treatment strategies for pathologically node-positive PCa patients. The secondary aim was to identify the most relevant prognostic factors to guide the management of pN1 patients.
EVIDENCE ACQUISITION
A systematic review was performed in January 2020 using Medline, Embase, and other databases. A total of 5063 articles were screened, and 26 studies including 12 537 men were selected for data synthesis and included in the current review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations.
EVIDENCE SYNTHESIS
Ten-year biochemical recurrence (BCR)-free, clinical recurrence-free, cancer-specific (CSS), and overall (OS) survival rates ranged from 28% to 56%, 70% to 92%, 72% to 98%, and 60% to 87.6%, respectively. A total of seven, five, and six studies assessed the oncological outcomes of observation, adjuvant radiotherapy (aRT), or adjuvant androgen deprivation therapy (ADT), respectively. Initial observation followed by salvage therapies at the time of recurrence represents a safe option in selected patients with a low disease burden. The use of aRT with or without ADT might improve survival in men with locally advanced disease and a higher number of positive nodes. Risk stratification according to pathological Gleason score, number of positive nodes, pathological stage, and surgical margins status is the key to risk stratification and selection of the optimal postoperative therapy. Limitations of this systematic review are the retrospective design of the studies included and the lack of data on adverse events.
CONCLUSIONS
While the majority of men with pN1 disease would experience BCR after surgery, long-term disease-free survival has been reported in selected patients. Management options to improve oncological outcomes include observation versus adjuvant therapies such as aRT and/or ADT. Disease characteristics should be used to select the optimal postoperative management for pN1 PCa patients.
PATIENT SUMMARY
Finding node-positive prostate cancer after a radical prostatectomy often leads to high postoperative prostate-specific antigen levels and is overall a poor prognostic factor. However, this does not necessarily translate into poor survival for all men. Management can be tailored to the severity of disease and options include observation, androgen deprivation therapy, and/or radiotherapy.
Topics: Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Pelvis; Prostatectomy; Prostatic Neoplasms
PubMed: 32933887
DOI: 10.1016/j.euo.2020.08.005 -
International Urogynecology Journal Apr 2018Pelvic floor disorders (PFDs) negatively affect quality of life in the general population, and their prevalence in gynecologic cancer survivors has not been... (Review)
Review
INTRODUCTION AND HYPOTHESIS
Pelvic floor disorders (PFDs) negatively affect quality of life in the general population, and their prevalence in gynecologic cancer survivors has not been systematically described. This study aimed to determine the prevalence of PFDs in cancer survivors. We hypothesized that the prevalence of PFDs in the gynecologic cancer population would be higher than in the general female population.
METHODS
We searched PubMed (1809 to present), EMBASE (1974 to present), and the Cochrane Central Register of Controlled Trials (CENTRAL) through May 2017. The search combined subject headings, title, and abstract words for gynecologic cancer, PFDs, and prevalence. Any studies evaluating the prevalence of PFDs in gynecologic malignancies were included.
RESULTS
A total of 550 articles met the designated search criteria and 31 articles were included in this review. In cervical cancer survivors, before treatment the prevalences of stress urinary incontinence (SUI), urgency urinary incontinence (UUI) and fecal incontinence (FI) were 24-29%, 8-18% and 6%, respectively, and after treatment the prevalences of SUI, UUI, urinary retention, FI, fecal urge, dyspareunia and vaginal dryness were 4-76%, 4-59%, 0.4-39%, 2-34%, 3-49%, 12-58% and 15-47%, respectively. In uterine cancer survivors, before treatment the prevalences of SUI, UUI and FI were 29-36%, 15-25% and 3%, respectively, and after treatment the prevalences of urinary incontinence (UI) and dyspareunia were 2-44% and 7-39%, respectively. In vulvar cancer survivors, after treatment the prevalences of UI, SUI and FI were 4-32%, 6-20% and 1-20%, respectively. In ovarian cancer survivors, the prevalences of SUI, UUI, prolapse and sexual dysfunction were 32-42%, 15-39%, 17% and 62-75%, respectively.
CONCLUSIONS
PFDs are prevalent in gynecologic cancer survivors and this is an important area of clinical concern and future research.
Topics: Cancer Survivors; Female; Genital Neoplasms, Female; Humans; Pelvic Floor Disorders; Prevalence
PubMed: 28929201
DOI: 10.1007/s00192-017-3467-4 -
Gynecologic Oncology Nov 2020Imaging is essential in detecting lymph node metastases for radiotherapy treatment planning in locally advanced cervical cancer (LACC). There are not many data on the...
PURPOSE
Imaging is essential in detecting lymph node metastases for radiotherapy treatment planning in locally advanced cervical cancer (LACC). There are not many data on the performance of [F]FDG-PET(CT) in showing lymph node metastases in LACC. We pooled sensitivity and specificity of [F]FDG-PET(CT) for detecting pelvic and/or para-aortic lymph node metastases in patients with LACC. Also, the positive and negative posttest probabilities at high and low levels of prevalence were determined.
METHODS
MEDLINE and EMBASE searches were performed and quality characteristics assessed. Logit-sensitivity and logit-specificity estimates with corresponding standard errors were calculated. Summary estimates of sensitivity and specificity with corresponding 95% confidence intervals (CIs) were calculated by anti-logit transformation. Positive and negative likelihood ratios (LRs) were calculated from the mean logit-sensitivity and mean logit-specificity and the corresponding standard errors. The posttest probabilities were determined by Bayesian approach.
RESULTS
Twelve studies were included with a total of 778 patients aged 10-85 years. For pelvic nodes, summary estimates of sensitivity, specificity, LR+ and LR- were: 0.88 (95%CI: 0.40-0.99), 0.93 (95%CI: 0.85-0.97), 11.90 (95%CI: 5.32-26.62) and 0.13 (95%CI: 0.01-1.08). At the lowest prevalence of 0.15 the positive predictive value (PPV) and negative predictive value (NPV) were 0.68 and 0.98, at the highest prevalence of 0.65, 0.96 and 0.81. For the para-aortic nodes, the summary estimates of sensitivity, specificity LR+ and LR- were: 0.40 (95%CI: 0.18-0.66), 0.93 (95%CI: 0.91-0.95), 6.08 (95%CI: 2.90-12.78) and 0.64 (95%CI: 0.42-0.99), respectively. At the lowest prevalence of 0.17 the PPV and NPV were 0.55 and 0.88, at the highest prevalence of 0.50, 0.86 and 0.61.
CONCLUSION
The PPV and NPV of [F]FDG-PET(CT) showing lymph node metastases in patients with LACC improves with higher prevalence. Prevalence and predictive values should be taken into account when determining therapeutic strategies based on [F]FDG-PET(CT).
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Female; Fluorodeoxyglucose F18; Humans; Lymphatic Metastasis; Middle Aged; Positron Emission Tomography Computed Tomography; Predictive Value of Tests; Radiopharmaceuticals; Uterine Cervical Neoplasms; Young Adult
PubMed: 32921477
DOI: 10.1016/j.ygyno.2020.08.021 -
World Journal of Urology Feb 2012To provide systematic review of the literature on the long-standing complications of genitourinary schistosomiasis. (Review)
Review
OBJECTIVES
To provide systematic review of the literature on the long-standing complications of genitourinary schistosomiasis.
MATERIALS AND METHODS
The PubMed literature database was searched from inception to December 2010. The following keywords were used: schistosomiasis, bilharziasis, and genitourinary. Only English language publications were utilized.
RESULTS
Variable tissue reactions to bilharzial eggs with subsequent healing or progression and complications in the urinary tract mainly affect the urinary bladder and pelvic segments of the ureters. These lesions may assume an atrophic, proliferative, or neoplastic pattern. Although the pathology is usually extensive in the submucosal, all layers from the mucous membrane through deep to the perivesical or periureteral tissues may be involved. Main fixed bilharzial urologic sequelae include chronic bladder ulcers, leucoplakia, vesical granuloma, contracted bladder, bladder neck contracture, stricture ureters, and bladder carcinoma. These sequelae may lead to marked morphologic and functional changes of the urinary tract, and ultimately, mortality can follow from renal failure or bladder cancer.
CONCLUSIONS
Urinary schistosomiasis is a preventable disease through nationwide snail control and mass therapy with oral antibilharzial drugs. If not properly treated, long-standing urinary complications may result in serious sequelae that may lead to mortality from renal failure or bladder cancer.
Topics: Carcinoma, Squamous Cell; Genitalia, Male; Humans; Male; Nephrotic Syndrome; Schistosomiasis haematobia; Ureteral Obstruction; Urinary Bladder Neoplasms; Urinary Calculi; Urinary Tract
PubMed: 21909645
DOI: 10.1007/s00345-011-0751-7 -
Diseases of the Colon and Rectum Apr 2013Pelvic exenteration is a potentially curative treatment for locally advanced primary or recurrent rectal cancer. (Review)
Review
BACKGROUND
Pelvic exenteration is a potentially curative treatment for locally advanced primary or recurrent rectal cancer.
OBJECTIVE
This systematic review examines the current evidence regarding clinical and oncological outcomes in patients with locally advanced primary and recurrent rectal cancer who undergo pelvic exenteration.
DATA SOURCES
A literature search of PubMed, Medline, and the Cochrane library was undertaken, and studies published in the English language from January 2000 to August 2012 were identified.
STUDY SELECTION
Prospective and retrospective studies that report outcomes of pelvic exenteration for primary advanced and locally recurrent rectal cancer with or without subgroup evaluation were included for examination.
MAIN OUTCOME MEASURES
Oncological outcomes included 5-year survival, median survival, and local recurrence rates. Clinical outcomes included complication rates and perioperative mortality rates.
RESULTS
A total of 23 studies with 1049 patients were reviewed. The complication rates ranged from 37% to 100% (median, 57%) and the perioperative mortality rate ranged from 0% to 25% (median, 2.2%). The rate of local recurrence ranged from 4.8% to 61% (median, 22%). The median survival for primary advanced rectal cancers was 14 to 93 months (median, 35.5 months) and 8 to 38 months (median, 24 months) for locally recurrent rectal cancer.
LIMITATIONS
Our review was limited by the small sample sizes from single-institutional studies reporting outcomes over long periods of time with heterogeneity in both the disease and treatments reported.
CONCLUSIONS
Although the human costs and risks are significant, the potentially favorable survival outcomes make this acceptable in the absence of other effective treatment modalities that would otherwise result in debilitating symptoms that afflict patients who have advanced pelvic malignancy.
Topics: Humans; Neoplasm Recurrence, Local; Pelvic Exenteration; Postoperative Complications; Rectal Neoplasms
PubMed: 23478621
DOI: 10.1097/DCR.0b013e31827a7868 -
Archives of Gynecology and Obstetrics Sep 2019The aim of this study was to assess the diagnostic accuracy of preoperative F-FDG PET or PET/CT in detecting pelvic lymph node (PLN) and para-aortic lymph node (PALN)...
Diagnostic accuracy of preoperative F-FDG PET or PET/CT in detecting pelvic and para-aortic lymph node metastasis in patients with endometrial cancer: a systematic review and meta-analysis.
PURPOSE
The aim of this study was to assess the diagnostic accuracy of preoperative F-FDG PET or PET/CT in detecting pelvic lymph node (PLN) and para-aortic lymph node (PALN) metastasis in patients with endometrial cancer (EC) in systematic review and meta-analysis format.
METHODS
A comprehensive search was performed on PubMed, Cochrane Library, EMBASE, Web of science, SpringerLink and Science Direct for studies reporting the diagnostic value of preoperative F-FDG PET or PET/CT in detecting PLN and PALN metastasis had been published up to August 8, 2018. Studies were included if enough data could be extracted for calculation of diagnostic accuracy indices.
RESULTS
Nineteen studies (1431 patients in total) were included in the analysis. On a lymph node basis, the overall pooled sensitivity, specificity, AUC and overall diagnostic accuracy (Q* index) of F-FDG PET or PET/CT in detecting total lymph node metastasis were 0.68 (95% CI 0.63-0.73), 0.96 (95% CI 0.96-0.97), 0.82, and 0.75, respectively. The corresponding indices for detecting PLN metastasis were 0.61 (95% CI 0.52-0.69), 0.96 (95% CI 0.95-0.97), 0.79, and 0.73, respectively. And the corresponding value for detection of PALN were 0.70 (95% CI 0.58-0.79), 0.92 (95% CI 0.9-0.94), 0.84, and 0.77, respectively. Data based on patients also performed well.
CONCLUSIONS
F-FDG PET and PET/CT both have excellent diagnostic performance for detecting lymph node metastasis, including PLN and PALN metastasis, in patients with endometrial cancer preoperatively. Though the utility of this method is limited due to its moderate sensitivity, it can help surgeons make better-tailored surgical decision for its high specificity.
Topics: Abdomen; Endometrial Neoplasms; Female; Fluorodeoxyglucose F18; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Pelvis; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Sensitivity and Specificity
PubMed: 31165242
DOI: 10.1007/s00404-019-05207-8 -
European Journal of Surgical Oncology :... Aug 2016Pelvic exenteration is a radical operative treatment reserved for the management of a number of advanced primary and recurrent pelvic malignancies, including, rectal,... (Review)
Review
BACKGROUND
Pelvic exenteration is a radical operative treatment reserved for the management of a number of advanced primary and recurrent pelvic malignancies, including, rectal, gynaecological and urological. The advances in radiological staging, surgical techniques and greater use of chemotherapeutic agents haves translated clinically into improvements in the overall survival of this cohort of patients, irrespective of underlying disease pathology. Consequently, a greater proportion of the surviving population will present to healthcare professionals with a range of physical and psychological issues, therefore the profiling and understanding of the health-related quality of life (HrQoL) is integral to the long term management of this cohort of patients. The aim of this systematic review is to identify HrQoL themes from the current literature relevant to patients undergoing a pelvic exenteration.
METHODS
Literature searches were performed in three databases: MEDLINE (1975-November 2015), EMBASE and CINAHL. Each study was evaluated with regards to its design and statistical methodology. Data quality was reviewed in accordance with the Newcastle-Ottowa score and Critical Appraisal Skills Programme Checklist (CAPS) for quantitative and qualitative data accordingly. A narrative synthesis of all identified HrQoL issues was undertaken using the principles of content analysis.
RESULTS
A total of 24 studies were identified; 20 quantitative and 4 qualitative with 976 patients assessed in total. HrQoL was assessed as the main primary endpoint in 15 studies. The majority of studies were retrospective. Baseline data prior to the initiation of treatments were available in 6 studies alone. Nine themes were identified across the literature, which included body image, social impact, sexual function, treatment expectations, symptoms, communication, psychological impact, relationships and work and finance.
CONCLUSIONS
Pelvic exenteration has a wide ranging impact on patients HrQoL affecting a range of physical and psychological domains.
Topics: Activities of Daily Living; Employment; Female; Genital Neoplasms, Female; Health Status; Humans; Interpersonal Relations; Male; Mental Health; Pelvic Exenteration; Quality of Life; Rectal Neoplasms; Reproductive Health; Role; Social Participation; Urologic Neoplasms
PubMed: 26968226
DOI: 10.1016/j.ejso.2016.01.007 -
International Journal of Gynecological... Oct 2023A systematic pelvic and para-aortic lymphadenectomy remains the surgical standard management of early-stage epithelial ovarian cancer. Sentinel lymph node mapping is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A systematic pelvic and para-aortic lymphadenectomy remains the surgical standard management of early-stage epithelial ovarian cancer. Sentinel lymph node mapping is being investigated as an alternative procedure; however, data reporting sentinel lymph node performance are heterogeneous and limited.
OBJECTIVE
This study aimed to evaluate the detection rate and diagnostic accuracy of sentinel lymph node mapping in patients with early-stage ovarian cancer.
METHODS
A systematic search was conducted in Medline (through PubMed), Embase, Scopus, and the Cochrane Library. We included patients with clinical stage I-II ovarian cancer undergoing a sentinel lymph node biopsy and a pelvic and para-aortic lymphadenectomy as a reference standard. We conducted a meta-analysis for the detection rates and measures of diagnostic accuracy and assessed the risk of bias using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) with identifying number CRD42022351497.
RESULTS
After duplicate removal, we identified 540 studies, 18 were assessed for eligibility, and nine studies including 113 patients were analyzed. The pooled detection rates were 93.3% per patient (95% CI 77.8% to 100%; I=74.3%, p<0.0001), and the sentinel lymph node technique correctly identified 11 of 12 patients with lymph node metastases, with a negative predictive value per patient of 100% (95% CI 97.6% to 100%; I=0%). The combination of indocyanine green and Tc-albumin nanocolloid had the best detection rate (100% (95% CI 94% to 100%; I=0%)) when injected into the utero-ovarian and infundibulo-pelvic ligaments.
CONCLUSION
Sentinel lymph node biopsy in early-stage ovarian cancer showed a high detection rate and negative predictive value. The utero-ovarian and infundibulo-pelvic injection using the indocyanine green and technetium-99 combination could increase sentinel lymph node detection rates. However, given the limited quality of evidence and the small number of reports, results from ongoing trials are awaited before its implementation in routine clinical practice.
Topics: Humans; Female; Sentinel Lymph Node; Indocyanine Green; Coloring Agents; Sentinel Lymph Node Biopsy; Lymph Node Excision; Carcinoma, Ovarian Epithelial; Lymphadenopathy; Ovarian Neoplasms; Lymph Nodes
PubMed: 37487662
DOI: 10.1136/ijgc-2023-004572 -
The Cochrane Database of Systematic... Oct 2017This is an update of a previous Cochrane review published in Issue 1, 2010 and updated in Issue 9, 2015. The role of lymphadenectomy in surgical management of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of a previous Cochrane review published in Issue 1, 2010 and updated in Issue 9, 2015. The role of lymphadenectomy in surgical management of endometrial cancer remains controversial. Lymph node metastases can be found in approximately 10% of women who before surgery are thought to have cancer confined to the womb. Removal of all pelvic and para-aortic lymph nodes (lymphadenectomy) at initial surgery has been widely advocated, and pelvic and para-aortic lymphadenectomy remains part of the FIGO (International Federation of Gynaecology and Obstetrics) staging system for endometrial cancer. This recommendation is based on data from studies that suggested improvement in survival following pelvic and para-aortic lymphadenectomy. However, these studies were not randomised controlled trials (RCTs), and treatment of pelvic lymph nodes may not confer a direct therapeutic benefit, other than allocating women to poorer prognosis groups. Furthermore, the Cochrane review and meta-analysis of RCTs of routine adjuvant radiotherapy to treat possible lymph node metastases in women with early-stage endometrial cancer found no survival advantage. Surgical removal of pelvic and para-aortic lymph nodes has serious potential short-term and long-term sequelae. Therefore, it is important to investigate the clinical value of this treatment.
OBJECTIVES
To evaluate the effectiveness and safety of lymphadenectomy for the management of endometrial cancer.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase to June 2009 for the original review, updated the search to June 2015 for the last updated version and further extended the search to March 2017 for this version of the review. We also searched registers of clinical trials, abstracts of scientific meetings, and reference lists of included studies, and we contacted experts in the field.
SELECTION CRITERIA
RCTs and quasi-RCTs that compared lymphadenectomy versus no lymphadenectomy in adult women diagnosed with endometrial cancer.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed risk of bias. Hazard ratios (HRs) for overall and progression-free survival and risk ratios (RRs) comparing adverse events in women who received lymphadenectomy versus those with no lymphadenectomy were pooled in random-effects meta-analyses. We assessed the quality of the evidence using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach.
MAIN RESULTS
978 unique references were identified via the search strategy. All but 50 were excluded by title and abstract screening. Three RCTs met the inclusion criteria; for one small RCT, data were insufficient for inclusion in the meta-analysis. The two RCTs included in the analysis randomly assigned 1945 women, reported HRs for survival adjusted for prognostic factors and based on 1851 women and had an overall low risk of bias, as they satisfied four of the assessment criteria. The third study had an overall unclear risk of bias, as information provided was not adequate concerning random sequence generation, allocation concealment, blinding, or completeness of outcome reporting.Results of the meta-analysis remained unchanged from the previous versions of this review and indicated no differences in overall and recurrence-free survival between women who underwent lymphadenectomy and those who did not undergo lymphadenectomy (pooled hazard ratio (HR) 1.07, 95% confidence interval (CI) 0.81 to 1.43; HR 1.23, 95% CI 0.96 to 1.58 for overall and recurrence-free survival, respectively) (1851 participants, two studies; moderate-quality evidence).We found no difference in risk of direct surgical morbidity between women who underwent lymphadenectomy and those who did not undergo lymphadenectomy. However, women who underwent lymphadenectomy had a significantly higher risk of surgery-related systemic morbidity and lymphoedema/lymphocyst formation than those who did not undergo lymphadenectomy (RR 3.72, 95% CI 1.04 to 13.27; RR 8.39, 95% CI 4.06 to 17.33 for risk of surgery-related systemic morbidity and lymphoedema/lymphocyst formation, respectively) (1922 participants, two studies; high-quality evidence).
AUTHORS' CONCLUSIONS
This review found no evidence that lymphadenectomy decreases risk of death or disease recurrence compared with no lymphadenectomy in women with presumed stage I disease. Evidence on serious adverse events suggests that women who undergo lymphadenectomy are more likely to experience surgery-related systemic morbidity or lymphoedema/lymphocyst formation. Currently, no RCT evidence shows the impact of lymphadenectomy in women with higher-stage disease and in those at high risk of disease recurrence.
Topics: Adult; Disease-Free Survival; Endometrial Neoplasms; Female; Humans; Lymph Node Excision; Lymphatic Metastasis; Lymphedema; Lymphocele; Postoperative Complications; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 28968482
DOI: 10.1002/14651858.CD007585.pub4