The Role of Systematic Lymphadenectomy in Low-Grade Serous Ovarian Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the role of systematic lymphadenectomy in low-grade serous ovarian cancer (LGSOC) and determine its impact on clinical outcomes in overall survival (OS) and disease-free survival (DFS) terms. METHODS: A comprehensive, systematic computer literature search on PubMed was performed using the following Medical Subject Headings (MeSH) terms: "low grade serous ovarian cancer" AND/OR "lymphadenectomy" AND/OR "staging" AND/OR "ovarian cancer" AND/OR "cytoreduction". Separate searches were performed with MeSH terms on MEDLINE and EMBASE to extract all the relevant literature available. We included only patients with histologically confirmed LGSOC. RESULTS: Three studies were considered in the quantitative analysis. Systematic lymphadenectomy in LGSOC failed to provide a significant OS or PFS benefit in LGSOC when compared to no lymphadenectomy in the entire (all the stages) population (for OS: HR = 1.15, 95% CI [0.42, 3.18] I2 = 84% and for PFS: HR = 1.46, 95% CI [0.63, 3.41], I2 = 71%), nor did it in the subtype analysis regarding FIGO stages. For FIGO early-stage I-II LGSOC, the DFS data were pooled (HR = 1.48, 95% CI [0.58, 3.78], I2 = 75%). In patients with advanced-stage (FIGO II-IV), we also failed to prove survival benefit for lymphadenectomy in OS (HR = 1.74, 95% CI [0.87, 3.48], I2 = 11%) or DFS (HR = 1.48, 95% CI [0.58, 3.78], I2 = 75%) compared to no lymphadenectomy. CONCLUSION: More extensive prospective research is mandatory to understand the real impact of lymphadenectomy on survival in LGSOC. The existing literature does not provide strong evidence.

[Ecology: The blind spot in pathology research]. / Écologie : l'angle mort de la recherche en ACP.

INTRODUCTION: The 2015 Paris Agreement has been the first restrictive agreement in the fight against climate change. The newer generations of pathologists, who feel more anxiety due to environmental problems than their predecessors, are asked to publish research works while they are harder and harder to and in a context of demographical tensions. We wanted to measure the rise of ecology research in pathology since the Paris Agreement. MATERIAL & METHODS: Over a ten years study period (2013-2022), we have identified via PubMed the number of articles in which forty-three terms taken from the sustainable development vocabulary appeared in ten renowned international pathology journals, selected for their SJR index from ScimagoJr and their impact factor, plus the Annales de pathologie, and compared their means of incidence between the 2013-2015 (m1) and 2016-2022 (m2) periods. The same process has been applied for "artificial intelligence", "deep learning" and "digital pathology". RESULTS: A total of 1336 articles have been identified. Only "digital pathology" (fromm1=8,33 to m2=23,29; p=0,010) and "deep learning" (fromm1=0 to m2=10,14; p=0,034) saw their incidence rise significantly. A significant decrease has been observed with "biological" (fromm1=70,00 to m2=56,86; p=0,020). DISCUSSION-CONCLUSIONS: Pathology reacts to trends but research in ecology has remained in the blind spot since 2015. However there seems to be an awakening as editorials, articles and communications in congress have blossomed the last two years.

Anatomy, embryology, and imaging of situs ambiguous with polysplenia and left IVC.

The situs ambiguous or heterotaxy syndrome is a type of syndrome that involves multiple visceral abnormalities, vascular ones and associated with left isomerism. Malformation of gastroenterologic system includes polysplenia (segmented spleen or multiple splenules), agenesis (partial or complete) of the dorsal pancreas and anomalous of the inferior vena cava implantation. Here, we describe and show the anatomy of a patient with left side inferior vena cava, situs ambiguous (complete common mesentery), polysplenia, and short pancreas. We also discuss about the embryologic process and the implications of these anomalies during gynecologic, digestive, and liver surgeries.

TRANSLACOL project: Nodal human papillomavirus tumoral DNA detection by ddPCR for survival prediction in early cervical cancer patients without pelvic lymph node invasion.

INTRODUCTION: In early cervical cancer (EEC), 10 to 15% of patients without nodal metastasis (N-) will suffer from recurrences with further similar survival as N+ patients. However, no clinical, imaging or pathological risk-factor is today available to identify them. In the present study, we hypothesized that the N- histologically characterized patients who present a poor prognosis could be patients for whom metastasis are missed by classical procedure. Therefore, we propose to research HPV tumoral DNA (HPVtDNA) in pelvic Sentinel Lymph Nodes (SLN) biopsy using ultrasensitive droplet-based digital PCR (ddPCR) to detect eventual occult metastasis. MATERIALS AND METHODS: Sixty HPV16, HPV18 or HPV33 positive EEC N- patients with available SLN were included. In SLN, HPV16 E6, HPV18 E7 and HPV33 E6 gene were respectively detected using ultrasensitive ddPCR technology. Survival data were analysed using Kaplan-Meier-curves and log-rank-test to compare progression-free survival (PFS) and disease-specific survival (DSS) in two groups according to their HPVtDNA status in SLN. RESULTS: More than half (51.7%) of the patients finally showed HPVtDNA positivity in SLN initially diagnosed as negative by histology. Two patients with negative HPVtDNA SLN and 6 with positive HPVtDNA SLN group presented recurrence. Finally, all of the 4 deaths listed in our study occurred in the positive HPVtDNA SLN group. CONCLUSION: These observations hint that the use of ultrasensitive ddPCR to detect HPVtDNA in SLN could allow the identification of two subgroups of histologically N- patients that may have different prognosis and outcome. To our knowledge, our study is the first one to evaluate the detection of HPVtDNA in SLN in early cervical cancer using ddPCR highlighting its interest as a complementary tool for N- specific early cervical cancer diagnosis.

HPV Molecular Genotyping as a Differential Diagnosis Tool in Cervical Cancer Metastasis.

BACKGROUND: Differentiating metastatic cervical cancer from another primary tumor can be difficult in patients with a history of cervical cancer and a distant lesion. The use of routine HPV molecular detection and genotyping tests could help in these cases. The objective of this study was to identify if an easy-to-use HPV molecular genotyping assay would allow differentiating between HPV tumor metastasis and a new independent primary non-HPV-induced tumor. MATERIALS AND METHODS: Between 2010 and 2020, we identified patients with a primary cervical carcinoma who also had another secondary lesion. This identification included a clinical and histologic differential diagnosis of metastatic cervical cancer versus a new primary cancer or metastatic cancer from another site. We used a routine multiplex real-time PCR (rt-PCR) AnyplexTM II HPV28 (Seegene, Seoul, Republic of Korea) to detect the high-risk (HR)-HPV genome in the distant lesions in these patients. RESULTS: Eight cases of cervical cancer with a new secondary lesion were identified. In seven, HR-HPV DNA was detected in the biopsy of the distant lesion, which confirmed the diagnosis of cervical cancer metastasis. In the remaining case, no HPV was detected in the secondary lung biopsy, confirming the diagnosis of new primary lung cancer. CONCLUSION: Our results pave the way for HPV molecular genotyping use in cases of newly diagnosed distant lesions in patients with a history of HPV cervical neoplasia by using a routine diagnosis process to complete the clinical and histologic differential diagnosis when confronted with ambiguous situations.

Traditional Systemic Treatment Options in Advanced Low-Grade Serous Ovarian Cancer after Successful Cytoreduction: A Systematic Review and Meta-Analysis.

OBJECTIVE: We performed a systematic literature review and a subsequent meta-analysis to compare traditional treatment options, i.e., antihormonal and cytotoxic, in LGSOC. METHODS: We conducted a systematic literature review in MEDBASE and MEDLINE between September 2000 and June 2021 for women who received cytotoxic chemotherapy and/or antihormonal treatment after primary cytoreduction due to stage II-IV LGSOC and also at relapse. PFS and OS were calculated depending on the type of their adjuvant treatment. For each endpoint in the meta-analysis, pooled HR was calculated using the random effect model with the inverse variance weighted method. Only primary patients were included in the subsequent meta-analysis due to the small number of studies in the relapsed setting. RESULTS: Five eligible first-line studies were included. Systemic chemotherapy failed to provide a significant OS benefit when compared to no systemic treatment (pooled HR = 1.01, 95% CI [0.79, 1.29]) after successful cytoreduction. Moreover, systemic chemotherapy followed by antihormonal treatment also did not result to a significant PFS or OS benefit when compared to systemic chemotherapy alone (for PSF: pooled HR = 0.59, 95% CI [0.33, 1.04]; for OS: pooled HR = 0.83, 95% CI [0.50, 1.39]). There were insufficient data from studies in the recurrent setting to allow their inclusion in the meta-analysis. CONCLUSIONS: In this meta-analysis, we failed to identify a traditional cytotoxic or antihormonal systemic treatment option that was associated with a significant OS or PFS benefit when administered following successful cytoreduction for advanced LGSOC. Prospective randomized studies are urgently warranted to define optimal adjuvant options in this challenging disease.

Intracervical double-balloon catheter versus dinoprostone for cervical ripening in labor induction in pregnancies with a high risk of uterine hyperstimulation.

PURPOSE: There are numerous methods for cervical ripening although not all of them are indicated in women presenting a higher risk of uterine hyperstimulation. To compare the efficacy and security of the two methods for cervical ripening in the induction of labor in these pregnancies. METHODS: Retrospective analysis of two cohorts consisting of pregnant women who gave birth from 2016 to 2019 (112 inductions with dinoprostone and 112 with intracervical double- balloon). RESULTS: There are statistically significant differences in favor of dinoprostone in deliveries that occurred before 12 h since the start of the induction (28.6% vs 13.4%, p = 0.005) and a higher rate of cervical ripening (55.4% vs 33.9%; p = 0.001). There were no statistically significant differences in induction time, the percentage of women delivering within 24 h or beyond, nor in the type of delivery. Additionally, a decreased need of oxytocin (60.7% vs 42.9%; p = 0.001) and a lower dose when used has been observed in the dinoprostone group. However, Dinoprostone also has a higher rate of minor maternal complications as uterine hyperstimulation (18.8% vs 3.6%; p = 0.001) and altered cardiotocography (26.8% vs 4.5%; p = 0.001). No significant difference has been found between the two groups regarding severe complications. CONCLUSIONS: Dinoprostone presents a greater efficacy for cervical ripening and delivery in ≤ 12 h, with less need of oxytocin perfusion than inductions using an intracervical double-balloon. There is no significant difference in severe maternal complications between the two groups. In conclusion, Dinoprostone could be an effective and safe option for patients at risk of uterine hyperstimulation.

Complete pathological response to olaparib and bevacizumab in advanced cervical cancer following chemoradiation in a BRCA1 mutation carrier: a case report.

BACKGROUND: Homologous recombination deficiency is a marker of response to poly(ADP-ribose) polymerase inhibitors in different cancer types including ovary, prostate, and pancreatic cancer. To date, no report about poly(ADP-ribose) polymerase inhibitors has been published on cervical cancer. CASE PRESENTATION: Here we present the case of a patient with cervical cancer treated in this setting. A 49-year-old woman diagnosed with International Federation of Obstetricians and Gynecologists stage 2018 IIIC2 locally advanced undifferentiated cervical cancer received first-line chemoradiotherapy followed by carboplatin, paclitaxel, and bevacizumab with partial response. Because of a family history of cancers, the patient was tested and found positive for a pathogenic BRCA1 germline and somatic mutation, which motivated bevacizumab plus olaparib maintenance treatment. A simple hysterectomy was performed after 2 years stable disease; pathological report showed complete pathological response, and 12 months follow-up showed no recurrence. CONCLUSION: Poly(ADP-ribose) polymerase inhibitors could be an alternative maintenance treatment for patients with persistent advanced cervical cancer previously treated with platinum, especially when familial history of cancers is reported. Clinical trials using poly(ADP-ribose) polymerase inhibitors for advanced cervical cancer are warranted.

Endocervical microglandular hyperplasia: Colposcopic aspects, physiopathology and differential diagnosis.

Endocervical microglandular hyperplasia (MGH) is a reactive type of glandular lesion that may be confused with endocervical adenocarcinoma from the macroscopic and the colposcopic findings, as well as from a histological. Differential diagnosis is very important. Here, we report a case of a 21 years-old women with a challenging differential diagnosis in the colposcopy and a MGH as histological finding.

Use of fluorescence to guide surgical resection in vulvo-vaginal neoplasia: Two case reports.

We report hereby two cases of fluorescence-guided surgical resection with Indocyanine green in vulvo-vaginal neoplasia. The first case was a 86-year old patient who had a high-grade squamous intraepithelial lesion of the left small lip and on the vulvar fork. After a first incomplete surgery, a second fluorescence-guided vulvectomy was performed with ICG injected intravenously to determine intraoperatively surgical margins. At final pathologic examination, surgical margins were free of disease and postoperative course was uneventful. The second case was a 44-year old patient who had a clear cell carcinoma of the upper vagina. She underwent a fluorescence-guided colpo-hysterectomy with pelvic lymphadenectomy. ICG was injected one centimeter around the tumor and highlighted intraoperatively the limits of the vaginal resection. On the specimens, surgical margins were also negative. Peritumoral or intravenous injection of ICG are promising techniques for the intraoperative identification of surgical margins in gynecologic malignancies.

Does a pre-operative conization improve disease-free survival in early-stage cervical cancer?

PURPOSE: Ever since the recent findings showing the lack of benefit of minimally invasive surgery (MIS) versus open surgery in early-stage cervical cancer, gynecologists have tried to explain these results. The primary objective of our study was to assess the impact of pre-operative conization on disease-free survival (DFS) in early-stage cervical cancer. The secondary objective was to analyze the peri-operative morbidity associated with a pre-operative conization. METHODS: All patients undergoing a surgical management for early-stage squamous carcinoma or adenocarcinoma cervical cancer (IA1, IA2, IB1 and IB2 FIGO 2018) at a French university hospital from 2004 to 2018 were retrospectively included. We examined the association between conization and DFS using a Cox regression model. We also analyzed the morbidity associated with pre-operative conization. RESULTS: 48.4% (44/91) of the patients had a pre-operative conization (defined by a conization up to 90 days prior to surgery). 86.8% underwent MIS. There was a non-significant increase in the DFS with one patient presenting a recurrence in the conization group (2.3%) and six (12.8%) in the no conization group (log rank = 0.09). In univariate analysis, conization, definitive FIGO stage and pre-operative tumor size were associated with DFS (p < 0.2). Only pre-operative tumor size was significantly associated with DFS in multivariate analysis. There was a non-significant increase of adverse events in the conization group (43.2% in the conization group versus 23.4%, p = 0.06). CONCLUSION: Conization, through a reduction of tumor size, could improve DFS. Carefully selected patients could still benefit from minimally invasive surgery.

Subspecialty training in Europe: a report by the European Network of Young Gynaecological Oncologists.

BACKGROUND: ESGO (European Society of Gynaecological Oncology) and partners are continually improving the developmental opportunities for gynaecological oncology fellows. The objectives of this survey were to evaluate the progress in the infrastructure of the training systems in Europe over the past decade. We also evaluated training and assessment techniques, the perceived relevance of ENYGO (European Network of Young Gynaecological Oncologists) initiatives, and unmet needs of trainees. METHODOLOGY: National representatives of ENYGO from 39 countries were contacted with an electronic survey. A graduation in well/moderately/loosely-structured training systems was performed. Descriptive statistical analysis and frequency tables, as well as two-sided Fisher's exact test, were used. RESULTS: National representatives from 33 countries answered our survey questionnaire, yielding a response rate of 85%. A national fellowship is offered in 22 countries (66.7%). A logbook to document progress during training is mandatory in 24 (72.7%) countries. A logbook of experience is only utilized in a minority of nations (18%) for assessment purposes. In 42.4% of countries, objective assessments are recognized. Trainees in most countries (22 (66.7%)) requested additional training in advanced laparoscopic surgery. 13 (39.4%) countries have a loosely-structured training system, 11 (33.3%) a moderately-structured training system, and 9 (27.3%) a well-structured training system. CONCLUSION: Since the last publication in 2011, ENYGO was able to implement new activities, workshops, and online education to support training of gynaecological oncology fellows, which were all rated by the respondents as highly useful. This survey also reveals the limitations in establishing more accredited centers, centralized cancer care, and the lack of laparoscopic training.

[Sentinel lymph node biopsy in early-stage cervical cancer: current state of art]. / Place du ganglion sentinelle dans les cancers du col utérin débutants.

Lymph node status is the most important prognostic factor of survival in women with early stage cervical cancer. Sentinel lymph node (SLN) biopsy is an accurate method for the assessment of lymph nodal involvement in early-stages cervical cancer and has been increasingly used instead of systematic pelvic lymph node dissection (PLND). Less-radical lymph node dissection decreases the associated morbidity of PLND, especially the risk of lower-leg lymphoedema, which affects severely patient quality of life. SLN biopsy allows nodes ultrastaging and provides supplementary histological information by increasing the detection of tumor low-volume (isolated tumors cells and micrometastases). Moreover, SLN biopsy provides accurate anatomical information on pelvic lymphatic drainage pathway by identifying nodes outside of routine lymphadenectomy areas. Selection of a population at low-risk of nodal metastasis, a minimal training, and simple rules may ensure a low false negative rate. Several studies have shown that SLN mapping in these patients is feasible, with excellent detection rates and sensitivity. Combined detection with technetium-99 and blue dye has been widely used but recently, there has been increasing interest in the use of fluorescent dies such as indocyanine green (ICG) which would improve SLN detection. Although recent international guidelines recommend performing SLN biopsy in addition to PLND, SLN biopsy alone is not the gold-standard yet due to lack of prospective evidence, especially on long-term oncological safety. Some points remain controversial such as the low accuracy of intraoperative SLN status assessment by frozen section and the impact of micrometastasis on prognostic. The prospective randomized clinical trial SENTICOL III will answer to these problematics.