Medicolegal, infrastructural, and financial aspects in gynecologic cancer surgery and their implications in decision making processes: Quo Vadis?

Surgical decision making is complex and involves a combination of analytic, intuitive, and cognitive processes. Medicolegal, infrastructural, and financial factors may influence these processes depending on the context and setting, but to what extent can they influence surgical decision making in gynecologic oncology? This scoping review evaluates existing literature related to medicolegal, infrastructural, and financial aspects of gynecologic cancer surgery and their implications in surgical decision making. Our objective was to summarize the findings and limitations of published research, identify gaps in the literature, and make recommendations for future research to inform policy.

The global burden of cervical cancer requiring surgery: database estimates.

BACKGROUND: Scaling up surgical services for cervical cancer in low and middle income countries requires quantification of the need for those services. The aim of this study was to estimate the global burden of cervical cancer for which access to surgery is required. METHODS: This was a retrospective analysis of publicly available data. Cervical cancer incidence was extracted for each country from the World Health Organization, International Agency for Research, Global Cancer Observatory. The proportion of cases requiring surgery was extrapolated from the United States Surveillance, Epidemiology and End-Result database. The need for cervical cancer surgery was tested against development indicators. RESULTS: Data were available for 175 countries, representing 2.9 billion females aged 15 and over. There were approximately 566,911 women diagnosed with cervical cancer (95% CI 565,462-568,360). An estimated 56.9% of these women (322,686) would require surgery for diagnosis, treatment or palliation (95% CI 321,955 - 323,417). Cervical cancers for which surgery is required represent less than 1% of cancers in high income countries, and nearly 10% of cancers in low income countries. CONCLUSIONS: At least 300,000 cervical cancer cases worldwide require access to surgical services annually. Gathering data on available cervical cancer surgery services in LMIC are a critical next step.

Interventions to increase follow-up of abnormal cervical cancer screening results: A systematic literature review and meta-analysis.

INTRODUCTION: Ensuring timely follow-up of abnormal screening results is essential for eliminating cervical cancer. OBJECTIVE: The purpose of the study was to review single and multicomponent interventions designed to improve follow-up of women with abnormal cervical cancer screening results. We report on effectiveness across studies, and describe what aspects of these interventions might be more impactful. METHODS: Publications were searched between January 2000 and December 2022. The search included observational, quasi-experimental (pre-post studies) and randomized controlled studies describing at least one intervention to increase follow-up of women with abnormal cervical cancer screening results. Outcomes of studies included completion of any follow-up (i.e., attending a follow-up appointment), timely diagnosis (i.e., colposcopy results within 90 days of screening) and time to diagnostic resolution (i.e., days between screening and final diagnosis). We assessed risk of bias for observational and quasi-experimental studies using the Newcastle-Ottawa Scale (NOS) tool and the Cochrane collaboration tool for randomized studies. We conducted a meta-analysis using studies where data were provided to estimate a summary average effect of the interventions on follow-up of patients and to identify characteristics of studies associated with an increased effectiveness of interventions. We extracted the comparison and intervention proportions of women with follow-up before and after the intervention (control and intervention) and plotted the odds ratios (ORs) of completing follow-up along with the 95% confidence intervals (CIs) using forest plots for the interventions vs. controls when data were available. FINDINGS: From 7,457 identified studies, 28 met the inclusion criteria. Eleven (39%) of the included studies had used a randomized design. Most studies (63%) assessed completion of any follow-up visit as the primary outcome, whereas others measured time to definite diagnosis (15%) or diagnostic resolution (22%). Navigation was used as a type of intervention in 63% of the included studies. Most interventions utilized behavioral approaches to improve outcomes. The overall estimate of the OR for completion of follow-up for all interventions was 1.81 (1.36-2.42). The highest impact was for programs using more than one approach (multicomponent interventions) to improve outcomes with OR = 3.01 (2.03-4.46), compared with studies with single intervention approaches with OR = 1.56 (1.14-2.14). No statistical risks were noted from publication bias or small-study effects in the studies reviewed. CONCLUSION: Our findings revealed large heterogeneity in how follow-up of abnormal cervical cancer screening results was defined. Our results suggest that multicomponent interventions were more effective than single component interventions and should be used to improve follow-up after abnormal cervical cancer screening results. Navigation appears to be an important tool for improving follow-up. We also provide recommendations for future studies and implications for policy in terms of better defining outcomes for these interventions.

Mapping of Radiation Oncology and Gynecologic Oncology Services Available to Treat the Growing Burden of Cervical Cancer in Africa.

PURPOSE: To meet the demand for cervical cancer care in Africa, access to surgical and radiation therapy services needs to be understood. We thus mapped the availability of gynecologic and radiation therapy equipment and staffing for treating cervical cancer. METHODS AND MATERIALS: We collected data on gynecologic and radiation oncology staffing, equipment, and infrastructure capacities across Africa. Data was obtained from February to July 2021 through collaboration with international partners using Research Electronic Data Capture. Cancer incidence was taken from the International Agency for Research on Cancer's GLOBOCAN 2020 database. Treatment capacity, including the numbers of radiation oncologists, radiation therapists, physicists, gynecologic oncologists, and hospitals performing gynecologic surgeries, was calculated per 1000 cervical cancer cases. Adequate capacity was defined as 2 radiation oncologists and 2 gynecologic oncologists per 1000 cervical cancer cases. RESULTS: Forty-three of 54 African countries (79.6%) responded, and data were not reported for 11 countries (20.4%). Respondents from 31 countries (57.4%) reported access to specialist gynecologic oncology services, but staffing was adequate in only 11 countries (20.4%). Six countries (11%) reported that generalist obstetrician-gynecologists perform radical hysterectomies. Radiation oncologist access was available in 39 countries (72.2%), but staffing was adequate in only 16 countries (29.6%). Six countries (11%) had adequate staffing for both gynecologic and radiation oncology; 7 countries (13%) had no radiation or gynecologic oncologists. Access to external beam radiation therapy was available in 31 countries (57.4%), and access to brachytherapy was available in 25 countries (46.3%). The number of countries with training programs in gynecologic oncology, radiation oncology, medical physics, and radiation therapy were 14 (26%), 16 (30%), 11 (20%), and 17 (31%), respectively. CONCLUSIONS: We identified areas needing comprehensive cervical cancer care infrastructure, human resources, and training programs. There are major gaps in access to radiation oncologists and trained gynecologic oncologists in Africa.

Vaginal vault smear cytology in detection of recurrence after hysterectomy for early cervical cancer.

OBJECTIVE: To determine the role of vaginal vault cytology as a surveillance tool for the detection of recurrence in patients with early stage cervical cancer treated with hysterectomy without adjuvant therapy. METHODS: A retrospective cohort study was conducted of all women with cervical cancer treated with a hysterectomy from January 2000 to July 2016 at the Royal Brisbane & Women's Hospital, Australia. Women included were diagnosed with the equivalent of International Federation of Gynecology and Obstetrics (FIGO) 2018 stage 1A1 to 1B3 squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma, received either simple or radical hysterectomy with or without pelvic lymph node dissection, and did not receive adjuvant therapy. Age, stage, histology, surgical procedure, and details of individual surveillance regimens including examination findings and indications and results for all vault cytology tests performed in the first 5 years following surgical management were collected. RESULTS: A total of 155 women met the inclusion criteria. Most cases were FIGO 2018 stage 1B1 (61.9%) and squamous cell carcinoma (64.5%). Included women underwent a median of 80 months of surveillance (range 25-200, IQR 64-108). In the first 5 years of surveillance, there were a total of 1001 vault cytology smears performed, with a median of 6 smears (IQR 5-9) per woman. A total of 19 smears were abnormal (1.9%). Of the cohort of 155 women, 19 (12.3%) had an abnormality detected; 1 (0.65%) had a high-grade intraepithelial abnormality and 2 (1.3%) had recurrences detected on cytology; however, a lesion was also seen and biopsied in all three women. A total of 16 of 1001 smears (1.6%) had low-grade abnormalities detected, all of which resolved with clinical observation only. All were alive and well at last review. There were in total 6 (3.9%) recurrences, 2 (33%) of which had abnormal cytology as above, and all of which had a lesion to biopsy and/or abnormal medical imaging. CONCLUSIONS: The routine use of vaginal vault cytology in surveillance following hysterectomy for early stage cervical cancer did not appear to alter the detection of recurrent malignancy.

Accuracy of Smartphone Images of the Cervix After Acetic Acid Application for Diagnosing Cervical Intraepithelial Neoplasia Grade 2 or Greater in Women With Positive Cervical Screening: A Systematic Review and Meta-Analysis.

PURPOSE: Smartphones are used in cervical screening for visual inspection after acetic acid or Lugol's iodine (VIA/VILI) application to capture and share images to improve the sensitivity and interobserver variability of VIA/VILI. We undertook a systematic review and meta-analysis assessing the diagnostic accuracy of smartphone images of the cervix at the time of VIA/VILI (termed S-VIA) in the detection of precancerous lesions in women undergoing cervical screening. METHODS: This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies from January 1, 2010, to June 30, 2020, were assessed. MEDLINE/PubMed, Embase, CINAHL, Cochrane, and LILACS were searched. Cohort and cross-sectional studies were considered. S-VIA was compared with the reference standard of histopathology. We excluded studies where additional technology was added to the smartphone including artificial intelligence, enhanced visual assessment, and other algorithms to automatically diagnose precancerous lesions. The primary outcome was the accuracy of S-VIA for the diagnosis of cervical intraepithelial neoplasia grade 2 or greater (CIN 2+). Data were extracted, and we plotted the sensitivity, specificity, negative predictive value, and positive predictive value of S-VIA using forest plots. This study was prospectively registered with The International Prospective Register of Systematic Reviews:CRD42020204024. RESULTS: Six thousand three studies were screened, 71 full texts assessed, and eight studies met criteria for inclusion, with six included in the final meta-analysis. The sensitivity of S-VIA for the diagnosis of CIN 2+ was 74.56% (95% CI, 70.16 to 78.95; I2 61.30%), specificity was 61.75% (95% CI, 56.35 to 67.15; I2 95.00%), negative predictive value was 93.71% (95% CI, 92.81 to 94.61; I2 0%), and positive predictive value was 26.97% (95% CI, 24.13 to 29.81; I2 61.3%). CONCLUSION: Our results suggest that S-VIA has accuracy in the detection of CIN 2+ and may provide additional support to health care providers delivering care in low-resource settings.

Preventing Cervical Cancer Globally: Are We Making Progress?

An unacceptable number of women continue to die from cervical cancer around the world each year. Despite established primary and secondary prevention measures, and a natural history of disease which provides a long latent phase in which to intervene, there are still more than 500,000 women diagnosed with cervical cancer globally each year, and 300,000 related deaths. Approximately 90% of these cervical cancer cases and deaths occur in low- and middle-income countries (LMIC). The World Health Organization (WHO) recently launched a Global Strategy to Accelerate the Elimination of Cervical Cancer that outlines 3 key steps: (i) vaccination against human papillomavirus (HPV); (ii) cervical screening; and (iii) treatment of precancerous lesions and management of invasive cancer. Successful implementation of all 3 steps could reduce more than 40% of new cervical cancer cases and 5 million related deaths by 2050. However, this initiative requires high level commitment to HPV immunization programs, innovative approaches to screening, and strengthening of health systems to provide treatment for both precancerous lesions as well as invasive cervical cancer.

Cervical Cancer Prevention in Low- and Middle-Income Countries.

Cervical cancer is one of the commonest cancers afflicting women in low and middle income countries, however, both primary prevention with human papillomavirus vaccination, and secondary prevention with screening programs and treatment of preinvasive disease are possible. A coordinated approach to eliminating cervical cancer, as has been called for by the World Health Organization, requires a complex series of steps at all levels of a health system. This article outlines the current state of cervical cancer prevention in low and middle income countries, the innovations being employed to improve outcomes, and consideration of the next steps needed as we move towards global elimination.

Pretreatment With Mifepristone Compared With Misoprostol Alone for Delivery After Fetal Death Between 14 and 28 Weeks of Gestation: A Randomized Controlled Trial.

OBJECTIVE: To assess the efficacy of pretreatment with mifepristone before misoprostol, compared with misoprostol alone, for termination of pregnancy after a fetal death in the second trimester. METHODS: This prospective, double blind, placebo-controlled trial randomized women requiring a termination of pregnancy after fetal death between 14 and 28 weeks of gestation to placebo or 200 mg mifepristone orally 24-48 hours before the termination of pregnancy with misoprostol (400 micrograms every 6 hours vaginally for women at 24 weeks of gestation or less, and 200 micrograms every 4 hours vaginally for women at 24 weeks of gestation or more). Based on a median labor with misoprostol alone in the second trimester of 13 hours, a sample size of 116 women per group was planned to compare the primary outcome of time from administration of misoprostol to delivery. The trial was ceased after 66 women were enrolled secondary to prolonged time to achieve recruitment. RESULTS: From April 2013 to November 2016, 66 women were randomized (34 to placebo and 32 to mifepristone). There were no differences in the characteristics between the two groups. The median time for the primary outcome of administration of misoprostol to delivery in the placebo group was 10.5 hours, compared with 6.8 hours in the treatment group (hazard ratio 2.41 95% CI 1.39-4.17, P=.002). Women in the placebo group required more doses of misoprostol (3.4 vs 2.1, P=.002) and more misoprostol overall (1,181.8 micrograms, vs 767.7 micrograms, P=.003). There was no difference in maternal complications between the two groups. Women in the mifepristone group reported improved perception of the procedure. CONCLUSION: The sequential use of mifepristone and misoprostol for the termination of pregnancy after fetal deaths between 14 and 28 weeks of gestation reduces the time to delivery, compared with the use of misoprostol alone, with no worsening of maternal complications. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12612000884808.

Assessment of current follow-up for complete molar pregnancies: A single centre review.

BACKGROUND: Current guidelines recommend that resolution of a complete molar pregnancy (CMP) can only be confirmed once a negative ß-human chorionic gonadotropin (ß-hCG) has been maintained for six months following uterine surgical evacuation. However, multiple studies have found that the risk of developing gestational trophoblastic neoplasia (GTN) once a negative ß-hCG had been obtained is negligible, which suggests that a shorter follow-up may be reasonable. AIM: To determine the trend in ß-hCG following diagnosis of a CMP and the incidence of GTN, in a single unit. MATERIALS AND METHODS: All patients presenting to the tertiary hospital, Royal Prince Alfred Hospital Early Pregnancy Assessment Service (RPAH EPAS), with a histopathological diagnosis of a CMP between 2010 and 2017 were included. Data collected included age, parity, ß-hCG at diagnosis, subsequent ß-hCG levels, incidence of GTN and treatment required. RESULTS: Sixty-seven patients were diagnosed with CMP between January 2010 and July 2017 through RPAH EPAS. The mean age of women diagnosed with a CMP was 33 years. None of the 40 patients who spontaneously achieved a negative ß-hCG and completed their six months follow-up had a subsequent rise in ß-hCG. The median number of days from surgical evacuation to normalisation of ß-hCG was 55.5 days. Sixteen out of 67 patients who had a CMP required further management for persistent GTN. None of these patients achieved a negative ß-hCG prior to further management. CONCLUSIONS: Consideration could be made to decreasing the period of ß-hCG monitoring for women who achieve a spontaneous negative ß-hCG following surgical evacuation of a CMP.

Improving Diagnostic Classification of Stillbirths and Neonatal Deaths Using ICD-PM (International Classification of Diseases for Perinatal Mortality) Codes: Validation Study.

BACKGROUND: Stillbirths and neonatal deaths have long been imperfectly classified and recorded worldwide. In Hong Kong, the current code system is deficient (>90% cases with unknown causes) in providing the diagnoses of perinatal mortality cases. OBJECTIVE: The objective of this study was to apply the International Classification of Diseases for Perinatal Mortality (ICD-PM) system to existing perinatal death data. Further, the aim was to assess whether there was any change in the classifications of perinatal deaths compared with the existing classification system and identify any areas in which future interventions can be made. METHODS: We applied the ICD-PM (with International Statistical Classification of Diseases and Related Health Problems, 10th Revision) code system to existing perinatal death data in Kwong Wah Hospital, Hong Kong, to improve diagnostic classification. The study included stillbirths (after 24 weeks gestation) and neonatal deaths (from birth to 28 days). The retrospective data (5 years) from May 1, 2012, to April 30, 2017, were recoded by the principal investigator (HML) applying the ICD-PM, then validated by an overseas expert (EA) after she reviewed the detailed case summaries. The prospective application of ICD-PM from May 1, 2017, to April 30, 2019, was performed during the monthly multidisciplinary perinatal meetings and then also validated by EA for agreement. RESULTS: We analyzed the data of 34,920 deliveries, and 119 cases were included for analysis (92 stillbirths and 27 neonatal deaths). The overall agreement with EA of our codes using the ICD-PM was 93.2% (111/119); 92% (78/85) for the 5 years of retrospective codes and 97% (33/34) for the 2 years of prospective codes (P=.44). After the application of the ICD-PM, the overall proportion of unknown causes of perinatal mortality dropped from 34.5% (41/119) to 10.1% (12/119) of cases (P<.001). CONCLUSIONS: Using the ICD-PM would lead to a better classification of perinatal deaths, reduce the proportion of unknown diagnoses, and clearly link the maternal conditions with these perinatal deaths.

A systematic review and meta-analysis of sarcopenia as a prognostic factor in gynecological malignancy.

INTRODUCTION: Sarcopenia is a condition described as the progressive generalized loss of muscle mass and strength. While sarcopenia has been linked with poorer outcomes following a variety of malignancies, its relationship with all gynecological cancer clinical outcomes has, to date, not been evaluated. This review interrogates the concept of sarcopenia as a prognostic tool for oncological outcomes and adverse effects of treatments in all primary gynecological malignancies. METHODS: This systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines, searching PubMed, Embase, and CINAHL without date or language restriction for studies reporting on sarcopenia and gynecological malignancies. Random effects meta-analysis models were used to determine the effects of sarcopenia on progression-free survival, overall survival, and treatment-related adverse events. RESULTS: Data were analyzed from 13 studies, including 2446 patients (range 60-323) with ovarian cancer (n=1381), endometrial cancer (n=354), or cervical cancer (n=481). Sarcopenia was associated with lower progression-free survival (HR 1.69, 95% CI 1.03 to 2.76), overall survival (HR 1.33, 95% CI 1.08 to 1.64), and no increase in adverse events (HR 1.28, 95% CI 0.69 to 2.40). The risk of bias of the studies was mostly rated unclear, and Begg's and Egger's test revealed a potential publication bias for progression-free survival and overall survval, although the HRs remained significant when adjusting for it. CONCLUSION: Sarcopenia is associated with worse progression-free survival and overall survival in gynecological oncology malignancies. Further research is warranted to validate these findings in larger and prospective samples using standardized methodology and to examine if an intervention could reverse its effect in gynecological oncology trials.

A before and after study of the impact on obstetric and perinatal outcomes following the introduction of an educational package of fetal heart rate monitoring education coupled with umbilical artery lactate sampling in a low resource setting labor ward in South Africa.

INTRODUCTION: Rates of cesarean section (CS) are increasing and abnormal fetal heart rate tracing and concern about consequent acidosis remain one of the most common indications for primary CS. Umbilical artery (UA) lactate sampling provides clinicians with point of care feedback on CTG interpretation and intrapartum care and may result in altered future practice. MATERIALS AND METHODS: From 3rd March - 12th November 2014 we undertook a before and after study in Pretoria, South Africa, to determine the impact of introducing a clinical package of fetal heart rate monitoring education and prompt feedback with UA cord lactate sampling, using a hand-held meter, on maternal and perinatal outcomes. RESULTS: Nine hundred thirty-six consecutive samples were analyzed (pre n = 374 and post n = 562). There was no difference in mean lactate (4.6 mmol/L [95%CI 4.4-4.8] compared with 4.9 mmol/L [95%CI 4.7-5.1], p = 0.089). Suspected fetal compromise was reduced in the post-intervention period: 30·2% vs 22·1%, aOR 0·71, 95% CI 0·52-0·96, p = 0·027. Cesarean section rates were significantly reduced in the univariate analysis: pre- 40·3% vs post-intervention 31·6% (p = 0·007). This reduction remained significant when adjusted for previous cesarean section, primiparity, maternal HIV infection and preterm birth (aOR 0·72, 95%CI 0·54-0·98, p = 0·035). Neonatal outcomes did not differ between the two groups. CONCLUSION: The introduction of a clinical practice package of fetal heart rate monitoring education combined with routine UA cord lactate sampling has the potential to reduce the cesarean section rate without increasing adverse neonatal outcomes in a low-resource setting.

Morbidity after surgical management of cervical cancer in low and middle income countries: A systematic review and meta-analysis.

OBJECTIVE: To investigate morbidity for patients after the primary surgical management of cervical cancer in low and middle-income countries (LMIC). METHODS: The Pubmed, Cochrane, the Cochrane Central Register of Controlled Trials, Embase, LILACS and CINAHL were searched for published studies from 1st Jan 2000 to 30th June 2017 reporting outcomes of surgical management of cervical cancer in LMIC. Random-effects meta-analytical models were used to calculate pooled estimates of surgical complications including blood transfusions, ureteric, bladder, bowel, vascular and nerve injury, fistulae and thromboembolic events. Secondary outcomes included five-year progression free (PFS) and overall survival (OS). FINDINGS: Data were available for 46 studies, including 10,847 patients from 11 middle income countries. Pooled estimates were: blood transfusion 29% (95%CI 0.19-0.41, P = 0.00, I2 = 97.81), nerve injury 1% (95%CI 0.00-0.03, I2 77.80, P = 0.00), bowel injury, 0.5% (95%CI 0.01-0.01, I2 = 0.00, P = 0.77), bladder injury 1% (95%CI 0.01-0.02, P = 0.10, I2 = 32.2), ureteric injury 1% (95%CI 0.01-0.01, I2 0.00, P = 0.64), vascular injury 2% (95% CI 0.01-0.03, I2 60.22, P = 0.00), fistula 2% (95%CI 0.01-0.03, I2 = 77.32, P = 0.00,), pulmonary embolism 0.4% (95%CI 0.00-0.01, I2 26.69, P = 0.25), and infection 8% (95%CI 0.04-0.12, I2 95.72, P = 0.00). 5-year PFS was 83% for laparotomy, 84% for laparoscopy and OS was 85% for laparotomy cases and 80% for laparoscopy. CONCLUSION: This is the first systematic review and meta-analysis of surgical morbidity in cervical cancer in LMIC, which highlights the limitations of the current data and provides a benchmark for future health services research and policy implementation.

Applying the international classification of diseases to perinatal mortality data, South Africa.

OBJECTIVE: To examine the feasibility of applying the International Classification of Diseases-perinatal mortality (ICD-PM) coding to an existing data set in the classification of perinatal deaths. METHODS: One author, a researcher with a non-clinical public health background, applied the ICD-PM coding system to South Africa's national perinatal mortality audit system, the Perinatal Problem Identification Program. The database for this study included all perinatal deaths (n = 26 810), defined as either stillbirths (of birth weight > 1000 g and after 28 weeks of gestation) or early neonatal deaths (age 0-7 days), that occurred between 1 October 2013 and 31 December 2016. A clinical obstetrician verified the coding. FINDINGS: The South African classification system does not include the timing of death; however, under the ICD-PM system, deaths could be classified as antepartum (n = 15 619; 58.2%), intrapartum (n = 3725; 14.0%) or neonatal (n = 7466; 27.8%). Further, the South African classification system linked a maternal condition to only 40.3% (10 802/26 810) of all perinatal deaths; this proportion increased to 68.9% (18 467/26 810) under the ICD-PM system. CONCLUSION: The main benefit of using the clinically relevant and user-friendly ICD-PM system was an enhanced understanding of the data, in terms of both timing of death and maternal conditions. We have also demonstrated that it is feasible to convert an existing perinatal mortality classification system to one which is globally comparable and can inform policy-makers internationally.