Short-term surgical complications after radical hysterectomy - a nationwide cohort study

Introduction: Centralization has, among other aspects, been argued to have an impact on quality of care in terms of surgical morbidity. Next, monitoring quality of care is essential in identifying areas of improvement. This nationwide cohort study was conducted to determine the rate of short-term surgical complications and to evaluate its possible predictors in women with early-stage cervical cancer. Material and methods: Women diagnosed with early-stage cervical cancer, 2009 FIGO stages IB1 and IIA1, between 2015 and 2017 who underwent radical hysterectomy with pelvic lymphadenectomy in 1 of the 9 specialized medical centers in the Netherlands, were identified from the Netherlands Cancer Registry. Women were excluded if primary treatment consisted of hysterectomy without parametrial dissection or radical trachelectomy. Women in whom radical hysterectomy was aborted during the procedure, were also excluded. Occurrence of intraoperative and postoperative complications and type of complications, developing within 30 days after surgery, were prospectively registered. Multivariable logistic regression analysis was used to identify predictors of surgical complications. Results: A total of 472 women were selected, of whom 166 (35%) developed surgical complications within 30 days after radical hysterectomy. The most frequent complications were urinary retention with catheterization in 73 women (15%) and excessive perioperative blood loss >1000 mL in 50 women (11%). Open surgery (odds ratio [OR] 3.42; 95% CI 1.73-6.76), chronic pulmonary disease (OR 3.14; 95% CI 1.45-6.79), vascular disease (OR 1.90; 95% CI 1.07-3.38), and medical center (OR 2.83; 95% CI 1.18-6.77) emerged as independent predictors of the occurrence of complications. Body mass index (OR 0.94; 95% CI 0.89-1.00) was found as a negative predictor of urinary retention. Open surgery (OR 36.65; 95% CI 7.10-189.12) and body mass index (OR 1.15; 95% CI 1.08-1.22) were found to be independent predictors of excessive perioperative blood loss. Conclusions: Short-term surgical complications developed in 35% of the women after radical hysterectomy for early-stage cervical cancer in the Netherlands, a nation with centralized surgical care. Comorbidities predict surgical complications, and open surgery is associated with excessive perioperative blood loss

Is less more in the surgical treatment of early-stage cervical cancer?

PURPOSE OF REVIEW: This article discusses recent developments towards less radical surgical treatment for early-stage cervical cancer. RECENT FINDINGS: Surgery is the standard treatment for early-stage cervical cancer. In the last decades, new treatment strategies have been developed aiming to reduce morbidity, without hampering oncological safety. We provide an update of the latest knowledge on safety and morbidity following less radical surgical procedures in early-stage cervical cancer. In cervical cancer with a tumour size of 2 cm or less, radical surgery (simple hysterectomy or fertility-sparing conisation) may be a well tolerated option. For patients with larger lesions (>2 cm) and wishing to preserve fertility, administration of neoadjuvant chemotherapy followed by less extensive surgery appears to be a feasible and well tolerated alternative to abdominal trachelectomy. With regard to lymph node assessment, increasing evidence shows the feasibility of the sentinel lymph node procedure instead of full pelvic lymphadenectomy. Prospective trials reporting on oncological safety are awaited.It is important to exercise caution when new surgical strategies are introduced. Despite promising retrospective data, prospective randomized studies may present unexpected results, for instance, minimally invasive radical hysterectomy showed inferior results compared to laparotomy. SUMMARY: There is a shift towards less radical treatment for early-stage cervical cancer. This review explores whether and when less is really more

Fertility-sparing surgery in gynecologic cancer: A systematic review

Fertility-sparing surgery (FSS) is increasingly being offered to women with a gynecological malignancy who wish to preserve fertility. In this systematic review, we evaluate the best evidence currently available on oncological and reproductive outcome after FSS for early stage cervical cancer, epithelial ovarian cancer, and endometrial cancer. An extensive literature search was conducted using the electronic databases Medline (OVID), Embase, and Cochrane Library to identify eligible studies published up to December 2020. In total, 153 studies were included with 7544, 3944, and 1229 patients who underwent FSS for cervical, ovarian, and endometrial cancer, respectively. We assessed the different FSS techniques that are available to preserve fertility, i.e., omitting removal of the uterine body and preserving at least one ovary. Overall, recurrence rates after FSS are reassuring and therefore, these conservative procedures seem oncologically safe in the current selection of patients with low-stage and low-grade disease. However, generalized conclusions should be made with caution due to the methodology of available studies, i.e., mostly retrospective cohort studies with a heterogeneous patient population, inducing selection bias. Moreover, about half of patients do not pursue pregnancy despite FSS and the reasons for these decisions have not yet been well studied. International collaboration will facilitate the collection of solid evidence on FSS and the related decision-making process to optimize patient selection and counseling

FIGO 2018 stage IB2 (2-4 cm) Cervical cancer treated with Neo-adjuvant chemotherapy followed by fertility Sparing Surgery (CONTESSA); Neo-Adjuvant Chemotherapy and Conservative Surgery in Cervical Cancer to Preserve Fertility (NEOCON-F). A PMHC, DGOG, GCIG/CCRN and multicenter study

BACKGROUND: There are limited data regarding the optimal management of pre-menopausal women with cervical lesions measuring 2-4 cm who desire to preserve fertility. PRIMARY OBJECTIVES: To evaluate the feasibility of preserving fertility. STUDY HYPOTHESIS: Neo-adjuvant chemotherapy will be effective in reducing the size of the tumor and will enable fertility-sparing surgery without compromising oncologic outcome. TRIAL DESIGN: Pre-menopausal women diagnosed with stage International Federation of Gynecology and Obstetrics (FIGO) IB2, 2-4 cm cervical cancer who wish to preserve fertility will receive three cycles of platinum/paclitaxel chemotherapy. Patients with complete/partial response will undergo fertility-sparing surgery. Patients will be followed for 3 years to monitor outcome. Patients with suboptimal response (residual lesion ≥2 cm) will receive definitive radical hysterectomy and/or chemoradiation. MAJOR ELIGIBILITY CRITERIA: Patients must have histologically confirmed invasive cervical cancer, 2-4 cm lesion, by clinical examination and magnetic resonance imaging (MRI), negative node, and pre-menopausal (≤40 years old). Following three cycles of neo-adjuvant chemotherapy, patients must achieve a complete/partial response (residual lesion <2 cm). Exclusion criteria include high-risk histology, tumor extension to uterine corpus/isthmus (as per MRI), and suboptimal response/progression following neo-adjuvant chemotherapy. PRIMARY ENDPOINTS: Assess the rate of functional uterus defined as successful fertility-sparing surgery and no adjuvant therapy. SAMPLE SIZE: A total of 90 evaluable patients will be needed to complete the study. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Expected complete accrual in 2022 with presentation of results by 2025. TRIAL REGISTRATION NUMBER: Pending ethics submission.status: publishe

Noninvasive, in vivo assessment of the cervical microcirculation using incident dark field imaging

Aim: This study evaluates the feasibility of handheld vital microscopy for noninvasive, objective assessment of the microcirculation of the human uterine cervix. We qualitatively and quantitatively describe the microcirculation in healthy subjects in order to provide a basis for its application in cervical pathology. Methods: Incident dark field imaging was used to image the microcirculation in four quadrants of the uterine ectocervix in ten healthy participants. If the squamocolumnar junction was visible, measurements were repeated on the endocervical columnar epithelium as well. Image acquisition time was recorded and participants scored the experienced level of discomfort. Angioarchitecture was classified according to Weber's classification. Quantitative parameters included capillary density (CD), total and perfused vessel density (TVD, PVD), proportion of perfused vessels (PPV) and microvascular flow index (MFI). Results: Image acquisition was easy, fast and well tolerated. Angioarchitecture was characterized by two distinctive and organized patterns; capillary loops underneath the squamous epithelium of the ectocervix and vascular networks underneath the columnar epithelium. In the image sequences containing capillary loops, mean CD was 33.2 cpll/mm2 (95% CI 28.2–38.2 cpll/mm2). In the image sequences with vascular networks, mean TVD was 12.5 mm/mm2 (95% CI 11.2–13.77 mm/mm2), mean PVD was 12.2 (95% CI 11.0–13.5 mm/mm2), MFI was 3 and PPV was 100%. Conclusions: Incident dark field imaging allows for noninvasive, real time visualization and objective evaluation and quantification of the microcirculation of the uterine cervix. The organized vascular patterns and optimal perfusion observed in healthy subjects allow for comparison with cervical pathology, for example in patients with cervical dysplasia or cervical cancer

The origin of tumor DNA in urine of urogenital cancer patients: Local shedding and transrenal excretion

In urogenital cancers, urine as a liquid biopsy for non-invasive cancer detection holds great promise for future clinical application. Their anatomical position allows for the local shedding of tumor DNA, but recent data indicate that tumor DNA in urine might also result from transrenal excretion. This study aims to assess the origin of tumor-associated DNA in the urine of 5 bladder and 25 cervical cancer patients. Besides natural voided urine, paired urine samples were collected in which contact with the local tumor was circumvented to bypass local shedding. The latter concerned nephrostomy urine in bladder cancer patients, and catheter urine in cervical cancer patients. Methylation levels of GHSR, SST, and ZIC1 were determined using paired bladder tumor tissues and cervical scrapes as a reference. Urinary methylation levels were compared to natural voided urine of matched controls. To support methylation results, mutation analysis was performed in urine and tissue samples of bladder cancer patients. Increased methylation levels were not only found in natural voided urine from bladder and cervical cancer patients, but also in the corresponding nephrostomy and catheter urine. DNA mutations detected in bladder tumor tissues were also detectable in all paired natural voided urine as well as in a subset of nephrostomy urine. These results provide the first evidence that the suitability of urine as a liquid biopsy for urogenital cancers relies both on the local shedding of tumor cells and cell fragments, as well as the transrenal excretion of tumor DNA into the urine

Non-invasive detection of endometrial cancer by DNA methylation analysis in urine

BACKGROUND: The incidence of endometrial cancer is rising, and current diagnostics often require invasive biopsy procedures. Urine may offer an alternative sample type, which is easily accessible and allows repetitive self-sampling at home. Here, we set out to investigate the feasibility of endometrial cancer detection in urine using DNA methylation analysis. RESULTS: Urine samples of endometrial cancer patients (n = 42) and healthy controls (n = 46) were separated into three fractions (full void urine, urine sediment, and urine supernatant) and tested for three DNA methylation markers (GHSR, SST, ZIC1). Strong to very strong correlations (r = 0.77-0.92) were found amongst the different urine fractions. All DNA methylation markers showed increased methylation levels in patients as compared to controls, in all urine fractions. The highest diagnostic potential for endometrial cancer detection in urine was found in full void urine, with area under the receiver operating characteristic curve values ranging from 0.86 to 0.95. CONCLUSIONS: This feasibility study demonstrates, for the first time, that DNA methylation analysis in urine could provide a non-invasive alternative for the detection of endometrial cancer. Further investigation is warranted to validate its clinical usefulness. Potential applications of this diagnostic approach include the screening of asymptomatic women, triaging women with postmenopausal bleeding symptoms, and monitoring women with increased endometrial cancer risk

Cervical cancer detection by DNA methylation analysis in urine

Abstract Urine samples provide a potential alternative to physician-taken or self-collected cervical samples for cervical screening. Screening by primary hrHPV testing requires additional risk assessment (so-called triage) of hrHPV-positive women. Molecular markers, such as DNA methylation, have proven most valuable for triage when applied to cervical specimens. This study was set out to compare hrHPV and DNA methylation results in paired urine and cervical scrapes, and to evaluate the feasibility of DNA methylation analysis in urine to detect cervical cancer. Urine samples (n = 41; native and sediment) and paired cervical scrapes (n = 38) from cervical cancer patients, and urine from 44 female controls, were tested for hrHPV and 6 methylation markers. Results on native urine and sediment were highly comparable. A strong agreement was found between hrHPV testing on urine and scrapes (kappa = 0.79). Also, methylation levels in urine were moderately to strongly correlated to those detected in scrapes (r = 0.508–0.717). All markers were significantly increased in urine from cervical cancer patients compared to controls and showed a good discriminatory power for cervical cancer (AUC = 0.744–0.887). Our results show a good agreement of urine-based molecular analysis with reference cervical samples, and suggest that urine-based DNA methylation testing may provide a promising strategy for cervical cancer detection