Early-stage Cervical Carcinoma Research Articles

Diagnostic cervical excision in patients with HPV positivity, cytological abnormalities- and preoperative cervical stenosis

AimThere is currently no protocol for classifying patients with HPV persistence and preoperative stenosis of the cervical canal. This has a significant impact on cytology results, colposcopy results and the possibility of obtaining reliable cervical histology outcomes. Our analysis clearly shows that colposcopy and cytology underestimate the histological results in patients with limited visibility due to the presence of a type 3 transformation zone (TZ). Our analysis revealed a significant discrepancy between the colposcopy and cytology results and the histological outcomes. Insufficient colposcopy led to the underdiagnosis of dysplastic lesions in patients with a type 3 TZ and cervical stenosis. In the case of repeated cytological abnormalities and inadequate colposcopy examination, it is crucial to perform a diagnostic conization to exclude high-grade dysplastic changes and cervical carcinoma.MethodsWe conducted a retrospective analysis of 1,021 conizations performed in tertiary care hospital in Wolfsburg, Germany between 2014 and 2020. Of these surgical procedures, 89 were diagnostic conizations. In our analysis, we defined diagnostic conization as a procedure performed when there is HPV persistence and repeated cytologic abnormalities in combination with a type 3 TZ, and when it is not possible to retrieve a relevant cervical histology sample.ResultsIn this period, 8.7% of all conizations were diagnostic excisions. We found histological abnormalities in 48 of 89 patients (53.9%). The histological examination of the excised cone revealed high-grade cervical intraepithelial neoplasia (CIN/HSIL) in 9 patients (10.1%) and CIN 2+ (HSIL) in 23 out of the 89 patients (25.8%). Two cases of early-stage cervical carcinoma (FIGO IA1 and FIGO IA2) were confirmed (2.3%).ConclusionPatients with cervical stenosis, high-risk HPV persistence and repeated cytological abnormalities are at high risk of undetected high-grade cervical dysplasia. Histologic confirmation must be ensured in this patient consultation and this can be achieved by performing diagnostic excisions.

The research progress on radiation resistance of cervical cancer.

Cervical carcinoma is the most prevalent gynecology malignant tumor and ranks as the fourth most common cancer worldwide, thus posing a significant threat to the lives and health of women. Advanced and early-stage cervical carcinoma patients with high-risk factors require adjuvant treatment following surgery, with radiotherapy being the primary approach. However, the tolerance of cervical cancer to radiotherapy has become a major obstacle in its treatment. Recent studies have demonstrated that radiation resistance in cervical cancer is closely associated with DNA damage repair pathways, the tumor microenvironment, tumor stem cells, hypoxia, cell cycle arrest, and epigenetic mechanisms, among other factors. The development of tumor radiation resistance involves complex interactions between multiple genes, pathways, and mechanisms, wherein each factor interacts through one or more signaling pathways. This paper provides an overview of research progress on an understanding of the mechanism underlying radiation resistance in cervical cancer.

Deep-learning-based radiomics of intratumoral and peritumoral MRI images to predict the pathological features of adjuvant radiotherapy in early-stage cervical squamous cell carcinoma

BackgroundSurgery combined with radiotherapy substantially escalates the likelihood of encountering complications in early-stage cervical squamous cell carcinoma(ESCSCC). We aimed to investigate the feasibility of Deep-learning-based radiomics of intratumoral and peritumoral MRI images to predict the pathological features of adjuvant radiotherapy in ESCSCC and minimize the occurrence of adverse events associated with the treatment.MethodsA dataset comprising MR images was obtained from 289 patients who underwent radical hysterectomy and pelvic lymph node dissection between January 2019 and April 2022. The dataset was randomly divided into two cohorts in a 4:1 ratio.The postoperative radiotherapy options were evaluated according to the Peter/Sedlis standard. We extracted clinical features, as well as intratumoral and peritumoral radiomic features, using the least absolute shrinkage and selection operator (LASSO) regression. We constructed the Clinical Signature (Clinic_Sig), Radiomics Signature (Rad_Sig) and the Deep Transformer Learning Signature (DTL_Sig). Additionally, we fused the Rad_Sig with the DTL_Sig to create the Deep Learning Radiomic Signature (DLR_Sig). We evaluated the prediction performance of the models using the Area Under the Curve (AUC), calibration curve, and Decision Curve Analysis (DCA).ResultsThe DLR_Sig showed a high level of accuracy and predictive capability, as demonstrated by the area under the curve (AUC) of 0.98(95% CI: 0.97–0.99) for the training cohort and 0.79(95% CI: 0.67–0.90) for the test cohort. In addition, the Hosmer-Lemeshow test, which provided p-values of 0.87 for the training cohort and 0.15 for the test cohort, respectively, indicated a good fit. DeLong test showed that the predictive effectiveness of DLR_Sig was significantly better than that of the Clinic_Sig(P < 0.05 both the training and test cohorts). The calibration plot of DLR_Sig indicated excellent consistency between the actual and predicted probabilities, while the DCA curve demonstrating greater clinical utility for predicting the pathological features for adjuvant radiotherapy.ConclusionDLR_Sig based on intratumoral and peritumoral MRI images has the potential to preoperatively predict the pathological features of adjuvant radiotherapy in early-stage cervical squamous cell carcinoma (ESCSCC).

Impact of pelvic radiation therapy in patients with early neuroendocrine cervical carcinoma and no residual disease in the radical hysterectomy specimen: a NeCTuR study

ObjectiveThe impact of adjuvant pelvic radiation therapy on the rate and location of recurrences was evaluated in patients with early-stage (IA1–IB2) neuroendocrine cervical carcinoma who underwent prior conization or polypectomy...

Effect of laparoscopic-assisted transvaginal hysterectomy on wound complications in patients with early stage cervical cancer: A meta-analysis.

Laparoscopic-assisted vaginal radical hysterectomy (LARVH) and abdominal radical hysterectomy (ARH) have been widely applied to treat cervical carcinoma. But LARVH and ARH have not been fully investigated in treating cervical carcinoma after injury associated with injury. This research is intended to provide an up-to-date basis for comparing LARVH with ARH in early stage cervical carcinoma. Comparison between LARVH and ARH in cervical carcinoma was carried out through a combination of related research. Eligible articles from databases such as PubMed and Embase were screened using an established search strategy. This report covered the results of LARVH versus ARH in cervical carcinoma. The average difference and the 95% confidence interval (CI) were used for the combination of consecutive variables. The combination of categorical variables was performed with the odds ratio (OR) 95% confidence interval. Through the identification of 1137 publications, eight of them were chosen to be analysed. Among them, 363 were treated with LARVH and 326 were treated with ARH. Eight trials showed that LARVH was associated with a reduced risk of postoperative wound infection than ARH (OR, 0.23; 95% CI, 0.1-0.55, p = 0.0009). Five trials showed that there was no difference in the risk of postoperative bleeding after surgery (OR, 1.17; 95% CI, 0.42-3.29, p = 0.76). We also did not differ significantly in the duration of the surgery (OR, 1.79; 95% CI, -6.58 to 10.15, p = 0.68). So, the two surgical methods differ significantly only in the risk of postoperative wound infection.

Survival after sentinel lymph node biopsy for early cervical cancers: a systematic review and meta-analysis

BackgroundSentinel lymph node biopsy represents an alternative to pelvic lymphadenectomy for lymph node staging of early-stage cervical carcinoma, but prospective evidence on long-term oncological safety of sentinel lymph node biopsy...

Sequencing-based transcriptome analysis reveals diversification of immune response- and angiogenesis-related expression patterns of early-stage cervical carcinoma as compared with high-grade CIN.

Molecular diversity of virus-associated cervical cancer remains a relatively underexplored issue, and interrelations of immunologic and angiogenic features during the establishment of a particular landscape of the cervical cancer microenvironment are not well-characterized, especially for its earliest clinical stages, although this may provide insight into the mechanisms behind the differences in tumor aggressiveness, treatment responsiveness and prognosis. In this research, we were aimed at identifying transcriptomic landscapes of early-stage cervical carcinoma that differ substantially in their immune-related characteristics, patterns of signaling pathways and composition of the microenvironment in comparison with immediate precursor (intraepithelial) lesions. We performed the Illumina platform-based RNA sequencing using a panel of fresh tissue samples that included human papillomavirus-positive cervical intraepithelial neoplastic lesions (CIN), invasive squamous carcinoma of the cervix of FIGO IA1-IIB stages, and morphologically normal epithelium. The derived transcriptomic profiles were bioinformatically analyzed and compared by patterns of signaling pathway activation, distribution of tumor-infiltrating cell populations, and genomic regions involved. According to hierarchical cluster analysis of the whole-transcriptome profiles, tissue samples were distributed between three groups, or gene expression patterns (the one comprising most pre-cancer cases and the other two encompassing mostly early-stage invasive cancer cases). Differentially expressed genes were retrieved in each intergroup pairwise comparison followed by Gene Ontology analysis. Gene set enrichment analysis of the two groups of tumor samples in comparison with the CIN group identified substantial differences in immunological and angiogenic properties between tumorous groups suggesting the development of different molecular phenotypes. Cell composition analysis confirmed the diverse changes in the abundancies of immune and non-immune populations and, accordingly, different impacts of the immune and stromal compartments on the tumor microenvironment in these two groups of tumors compared to CIN. Positional gene expression analysis demonstrated that the identified transcriptomic differences were linked to different chromosomal regions and co-localized with particular gene families implicated in immune regulation, inflammation, cell differentiation, and tumor invasion. Overall, detection of different transcriptomic patterns of invasive cervical carcinoma at its earliest stages supports the diverse impacts of immune response- and angiogenesis-related mechanisms on the onset of tumor invasion and progression. This may provide new options for broadening the applicability and increasing the efficiency of target anti-angiogenic and immune-based therapy of virus-associated cervical carcinoma.

Retrospective study of the efficacy and safety of docetaxel/carboplatin combination therapy as postoperative adjuvant chemotherapy for nonsquamous cell carcinoma of the cervix.

Optimal adjuvant chemotherapy for nonsquamous cervical carcinoma has not yet been established. This study investigated the efficacy and safety of docetaxel/carboplatin (DC) for early-stage nonsquamous cell cervical carcinoma after radical hysterectomy (RH). We evaluated 157 patients with stage IB-IIB nonsquamous cervical carcinoma with intermediate risk and high risk treated at our institution with DC after type IIor III RH from 2007 to 2021. Patients received docetaxel (60-70mg/m2) and carboplatin (area under the curve 5-6) every 3weeks for six cycles. The primary endpoint was 2year recurrence-free survival (RFS) and the secondary endpoint was adverse events (AEs). There were 106 intermediate-risk and 51 high-risk patients. The high-risk patients included 11 with positive parametrial involvement, 20 with pelvic lymph node metastases, and 20 with both parametrial involvement and pelvic lymph node metastases. The 2year RFS rates for intermediate-risk, high-risk, and positive pelvic lymph nodes were 94.8% (95% confidence interval [CI], 87.9-97.8), 80.1% (95% CI, 64.1-89.5), and 74.5% (95% CI, 55.4-86.4), respectively. Sixteen patients had recurrence, including local recurrence (n = 6), distant metastasis (n = 9), and local and distant metastasis (n = 1). Hematologic toxicity was the most frequent AE, especially leukopenia and neutropenia. Nausea and constipation were the most frequent nonhematologic toxicities. DC therapy at our institution showed good 2year RFS, and postoperative adjuvant therapy with DC therapy is suggested as a useful strategy for patients with nonsquamous cervical carcinoma.

Characteristics of immune-active and immune-silent phenotypes of early-stage cervical carcinoma as revealed by transcriptome sequencing

Molecular classification, immuneheterogeneity, and the existence of distinct immunophenotypes of virus-associated cervical cancer (CeCa) remain as-yet weakly explored issues, and this is particularly true of its earliest clinical stages and pre-invasive forms: cervical intraepithelial neoplastic (CIN) lesions. The goal of the study was to identify transcriptomic landscapes of invasive CeCa at its initial progression that differ substantially in their immune-related characteristics, patterns of signaling pathways and composition of the microenvironment. Transcriptome profiling was carried out using RNA-sequencing on Illumina platform. A panel of surgical-derived tissue samples comprised human papillomavirus-positive CIN grade 1-3, cancer of FIGO IA1-IIB stages, and morphologically normal epithelium. Transcriptomic profiles were analyzed with the use of bioinformatics tools, such as gene set enrichment (GAGE) for signaling pathways, xCell enrichment for cell composition identification, and PREDA positional analysis of genomic data. Hierarchical clustering revealed heterogeneity of transcriptomic profiles within the early-stage CeCa, namely, the existence of two clusters of tumor samples and three functional patterns of genes showing coordinately altered expression. Pathway enrichment analysis on genes differently expressed between the two clusters/groups of CeCa samples (‘A' and ‘B') and CIN (group ‘C') suggested that invasive tumor progression in groups ‘A' and ‘B' might rely on immunologically dissimilar mechanisms. xCell analysis confirmed heterogeneity of changes in the abundancies of cell populations when comparing CeCa sample groups and CIN, along with differences in immune and stromal scores. PREDA demonstrated that these transcriptomic differences could be linked to different chromosomal regions and co-localized with particular gene families and potentially the reported virus integration hotspots. Overall, the existence and detectability of different transcriptomic immune-based phenotypes of invasive CeCa at its initial stages of progression is shown, which may provide new options to broaden the knowledge and applicability of target and immune anti-cancer therapy.

Comparison between laparoscopic and abdominal radical hysterectomy for cervical adenosquamous carcinoma at stage IA2 to IIA2: A multicenter retrospective study.

We aimed to compare the 5-year oncological outcomes of laparoscopic/abdominal radical hysterectomy (LRH/ARH) in patients with cervical adenosquamous carcinoma at stage IA2 to IIA2 based on the 2009 or 2018 International Federation of Gynecology and Obstetrics (FIGO) staging criteria. Based on the clinical diagnosis and treatment of cervical cancer in China (Four C) database, Cox risk regression models were applied to analyze tumor prognosis treated with ARH/LRH in FIGO 2009 and 2018 IA2-IIA2 patients and stratified findings according to tumor diameter (≤4 and >4cm subgroups). And to avoid bias, propensity score matching (PSM) was also used for the cohort study. Based on FIGO 2009 staging criteria (n=474), there was no significant difference between the ARH and LRH groups in 5-year disease-free survival (DFS) or overall survival (OS). Lymph node metastasis was a risk factor for 5-year DFS in this stage. After PSM, lymphovascular space invasion (LVSI) was an independent risk factor for 5-year OS in the tumors ≤4cm subgroup. Based on FIGO2018 staging criteria (n=322), cervical interstitial infiltration depth was an independent risk factor for 5-year OS in the total population and the tumor diameter ≤4cm subgroup. Laparoscopic surgery was not a risk factor affecting the oncologic prognosis of adenosquamous carcinoma of the cervix based on either FIGO 2009 or 2018 staging of stage IA2-IIA2. In addition, LRH may be considered for patients with early-stage cervical adenosquamous carcinoma.

Isolated para-aortic nodal recurrence after treatment of early stage cervical carcinoma

ObjectiveSurgical evaluation of lymph node metastasis is paramount in the treatment of cervical cancer. We sought to explore the outcomes of patients with and without para-aortic lymphadenectomy undergoing curative-intent radical hysterectomy for stage IA-IIA cervical cancer. MethodsInstitutional data were retrospectively reviewed to identify women undergoing curative-intent radical hysterectomy with concurrent lymphadenectomy for stage IA-IIA cervical carcinoma from 2004 to 2021. Any carcinoma histology was allowed. Clinical risk stratification was performed according to GOG 92 and GOG 109 protocols. Disease outcomes, patterns of recurrence, and survival were analyzed with Chi square, t-test, Kaplan-Meier, and Cox proportional hazards multivariable statistics. Results300 patients were identified, 265 met inclusion criteria. Median follow up was 56 months. Pelvic lymphadenectomy (PLND) was performed in 71%, with the remainder undergoing combined para-aortic dissection (PPaLND). Baseline patient demographics and presence of clinical risk factors were well balanced between groups. PPaLND was more common in patients undergoing open surgery (OR 10.58, p <.0001), and tumors were larger in this group (2.96 vs 2.12 cm, p = .0002) and more likely non-squamous histology (OR 2.02, p = .017). Recurrence of disease was present in 13% of cases, with no difference between PLND and PPaLND regardless of histology. There were zero cases of isolated PaLN recurrence in either group. Neither progression free nor overall survival was different between groups. Prophylactic extended field radiation (EFRT) was not prescribed. ConclusionOmission of PaLN dissection, in the absence of suspicious nodes, did not decrease survival. There were no isolated PaLN recurrences after PLND alone.

Prognostic Value of Inflammatory and Nutritional Markers for Patients With Early-Stage Poorly-to Moderately-Differentiated Cervical Squamous Cell Carcinoma.

The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammatory index (SII), systemic inflammation response index (SIRI), and Onodera's prognostic nutritional index (OPNI) have been reported as prognostic markers for various cancers. We evaluated the prognostic value of the NLR, PLR, MLR, SII, SIRI, and OPNI for poorly-to moderately-differentiated cervical squamous cell carcinoma (CSCC). We retrospectively analyzed the cases of 109 patients with early-stage poorly-to moderately-differentiated CSCC who underwent radical surgery at our institution in 2014-2017. The optimal cutoff points for the NLR, PLR, MLR, SII, SIRI, and OPNI were determined by receiver operating characteristic curves. Overall survival was analyzed by the Kaplan-Meier method. We performed a multivariate analysis using the Cox proportional hazard regression model to determine the independent prognostic indicators for early-stage poorly-to moderately-differentiated CSCC. The appropriate cutoff points were: NLR, 1.72; PLR, 111.96; MLR, .24; SII, 566.23; SIRI, 1.38; and OPNI, 52.68. The OS of the patients with a high OPNI (P = .04), low SII (P = .03), or low SIRI (P = .01) was significantly better. The uni- and multivariate analyses identified only the OPNI as an independent prognostic marker for early-stage poorly-to moderately-differentiated CSCC (P = .04 and P = .02). The OPNI is an independent prognostic marker for early-stage poorly-to moderately-differentiated CSCC; the NLR, PLR, MLR, SII, and SIRI are not.

Prevalent distribution and survival outcome of HPV infection in patients with early-stage cervical cancer in Hangzhou, China

ObjectivesTo describe the prevalent distribution of human papilloma virus (HPV) infection in patients with early-stage cervical squamous cell carcinoma (CSCC). To provide data on high-risk HPV (HR-HPV) infection and other clinicopathological factors for their correlations with the survival of CSCC patients.MethodsA total of 1425 patients with FIGO stages IA to IIA CSCC who underwent radical surgery between September 2008 and December 2012 were enrolled in the study. The prevalent distribution of HPV infection with different patient characteristics and survivals were analyzed with or without propensity score matching (PSM).ResultsThe overall infection rate of HPV was 84.3%, including 13 carcinogenic HR-HPV genotypes and 8 low-risk HPV genotypes with infection rates of 82.6% and 5.8%, respectively. The distribution of HPV infection were proportional in patients with either different age groups or different FIGO stages. HPV16 was the dominant subtype with an infection rate of 65.1%, followed by the other top four subtypesHPV58 (8.7%), 18 (7.7%) and 52 (4.5%). χ2 analysis revealed that increased preoperative serum squamous cell carcinoma antigen levels and lymphovascular space invasion (LVSI) were statistically associated with HPV status. However, regression analyses indicated that only deep stromal invasion, LVSI and lymph node metastasis were independent prognostic factors on 5-year overall survival (OS), but not HR-HPV infection status even in the second exploratory analysis (P = 0.939) based on the PSM applied to reduce selection bias.ConclusionsThis study provided baseline data on the prevalence characteristics of HPV infections in patients with early-stage CSCC, and HR-HPV infection was not a prognosticator of 5-year OS, other than FIGO stage, LVSI and lymph node metastasis.

Evaluation of Surgical Approaches and Use of Adjuvant Radiotherapy with Respect to Oncologic Outcomes in the Management of Clinically Early-Stage Cervical Carcinoma

The standard of care for early-stage cervix cancer is radical hysterectomy with pelvic lymphadenectomy. Adjuvant radiotherapy (RT) or chemoradiotherapy may be administered to reduce the risk of recurrence in patients considered to be at elevated risk based on a combination of pathologic factors. We performed a retrospective review to determine oncologic outcomes in patients treated for early-stage cervix cancer and to determine if surgical approach impacted oncologic outcomes or the decision to use adjuvant therapy. In total, 174 women underwent radical hysterectomy and pelvic lymphadenectomy over the 15-year period. Most of these women (146) had open surgery and 28 had minimally invasive surgery (MIS). In total, 81 had adjuvant pelvic RT; 76 in the open surgery group (52%) and 5 in the MIS group (18%). Five-year PFS and OS, respectively, were 84% and 91%. Five-year PFS was significantly lower in patients who had MIS vs. open surgery, without a difference in 5-year OS, suggesting MIS should be avoided. Five-year PFS was the same with RT or with its omission, despite those treated with RT having higher risk disease. We have demonstrated excellent outcomes in patients with early-stage cervix cancer after primary surgery and selective use of RT, with few recurrences and excellent survival.

High expression of PYK2 is associated with poor prognosis and cancer progression in early-stage cervical carcinoma.

Proline-rich tyrosine kinase-2 (PYK2), also known as calcium dependent tyrosine kinase, regulates different signal transduction cascades that control cell proliferation, migration, and invasion. However, the role of PYK2 in cervical cancer remains to be elucidated. The current study retrospectively included 134 patients with cervical cancer from December 2007 to September 2014. PYK2 expression was detected in tissue microarray and cervical cancer cell lines. Statistical analysis was performed to evaluate its clinicopathological significance. Small interfering RNA (siRNA) was employed to suppress endogenous PYK2 expression in cervical cancer cells to observe the biological function. PYK2 expression was up-regulated in cervical cancer specimens compared with paired adjacent normal cervical tissue samples. Statistical analyses indicated that PYK2 expression might be an independent prognostic indicator for patients with early-stage cervical cancer. A nomogram model was constructed based on PYK2 expression and other clinicopathological risk factors, and it performed well in predicting patients survival. In cellular studies, down-regulation of PYK2 remarkably inhibited cellular proliferation, migration and invasion. PYK2 expression possessed the potential to serve as a novel prognostic marker in cervical cancer patients.

“Malignant” Liver Lesions in an Incidental But High-Risk Patient

Question: A 48-year-old woman who suffered an accidental slip underwent abdominal computed tomography, which revealed multiple hepatic lesions in the whole liver. The patient was asymptomatic and physical examinations were unremarkable. She had normal growth and her body mass index was 23.9. No viral or autoimmune hepatitis was detected. The patient had a history of early-stage cervical carcinoma treated by radical hysterectomy 7 years ago without postoperative adjuvant therapy. History of smoking or taking oral contraceptives was denied. Laboratory tests showed the following results: alanine aminotransferase level of 14 U/L, aspartate aminotransferase level of 30 U/L, alkaline phosphatase level of 49 U/L, and bilirubin level of 13.1 μmol/L. Tumor markers of alpha-fetoprotein and CA19-9 were within normal range. Her blood count, electrolyte, glucose level, renal function, and coagulation tests were normal as well. Subsequent contrast-enhanced magnetic resonance (MR) imaging showed liver steatosis with multiple liver lesions in the whole liver. The largest lesion was found to be 28∗20 mm in segment V. The lesions were slightly hyperintense on T2-weighted sequences, with strong arterial enhancement, which persisted into the portal venous phase (Figure A). What is the diagnosis of the disease? See the Gastroenterology website (www.gastrojournal.org) for more information on submitting to Gastro Curbside Consult. The MR imaging showed multiple solid hepatic lesions characterized by predominant hypervascularization. Malignancy of multifocal hepatocellular carcinoma was first suspected, which is often hyper-vascular and encapsulated. However, cirrhosis and elevated tumor markers were not presented in our patient. Because the patient had a known primary malignancy of cervical carcinoma before, suspected diagnosis of hyper-vascular liver metastases was also included. In addition, focal nodular hyperplasia and liver adenomatosis sharing similar imaging features in noncirrhotic liver of women were considered for the differential diagnosis as well. The case was discussed with a multidisciplinary team. It was agreed that distinguishing the previously mentioned diseases might be challenging with imaging criteria alone and liver biopsy was required. The histopathologic examination showed cord-like arrangement of benign hepatocytes, which first excluded hepatocellular carcinoma and metastatic hepatic cancer. Additionally, moderate steatosis and lobar inflammation were observed (Figure B). The presence of fat and lack of portal venules distinguished adenomatosis from focal nodular hyperplasia, which led to the final diagnosis of liver adenomatosis. Additionally, adenomatosis is also characterized by thin-walled sinusoids supplied by arteries within hepatocytes, resulting in hypervascularity on arterial-phase imaging. Liver adenomatosis (LA) is defined as presence of 10 or more adenomas in the liver, which was first described by Flejou et al in 1985.1Flejou J.F. Barge J. Menu Y. et al.Liver adenomatosis. An entity distinct from liver adenoma?.Gastroenterology. 1985; 89: 1132-1138Abstract Full Text PDF PubMed Scopus (247) Google Scholar The known risk factors for the development of LA include exogenous estrogen or androgens, obesity, and glycogen storage disorder (GSD). Patients with GSD commonly present with hypoglycemia, hepatomegaly, and growth retardation at 3–6 months of age. LA of these patients usually has presentation of less than 20 years and progress in size and number. For our patient, oral contraceptives or steroids were denied. Although genetic testing was not performed, no typical clinical symptoms of GSD were observed at an early age, which lowered the risk of underlying GSD. The diagnosis of LA is mainly based on contrast-enhanced magnetic MR, which is the same for hepatic adenoma. Liver biopsy is recommended for cases in which imaging is inconclusive and histologic confirmation is able to distinguish between the 4 subtypes of adenomas.2Barbier L. Nault J.C. Dujardin F. et al.Natural history of liver adenomatosis: a long-term observational study.J Hepatol. 2019; 71: 1184-1192Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar Based on imaging findings, LA can be further classified as massive or multifocal. The former has a higher risk of hemorrhage, whereas, for asymptomatic patients with multifocal type, the risk of malignant transformation is substantially higher.3Lammert C. Toal E. Mathur K. et al.Large hepatic adenomas and hepatic adenomatosis: a multicenter study of risk factors, interventions, and complications.Am J Gastroenterol. 2022; 117: 1089-1096Crossref PubMed Scopus (2) Google Scholar The patient in our case with multiple lesions raised the question of its management because liver resection is not possible. Considering the possibility that different subtypes of nodules may exist with high-risk malignant transformation, a 3-month imaging surveillance program with MR and tumor marker assessment were instituted in our case. After 2 years of follow-up, the patient lives a normal life without disease progress based on radiographical findings and blood tests.

76: Evaluation of Use of Adjuvant Radiotherapy and Surgical Approach with Respect to Oncologic Outcomes in the Management of Early-Stage Cervical Carcinoma

76: Evaluation of Use of Adjuvant Radiotherapy and Surgical Approach with Respect to Oncologic Outcomes in the Management of Early-Stage Cervical Carcinoma

The effect of adjuvant radiotherapy on oncological outcomes in patients with early-stage cervical carcinoma with only intermediate-risk factors: a propensity score matching analysis

We aimed to evaluate whether adjuvant radiotherapy had a survival benefit for patients with early-stage cervical carcinoma with intermediate-risk factors. This study included patients who underwent radical hysterectomy and lymphadenectomy according to Wertheim–Okabayashi for stage IB1-IIA2 cervical carcinoma. Each patient had at least one intermediate-risk factor including tumour diameter ≥4 cm, deep stromal invasion, and positive lymphovascular space invasion (LVSI). Patients with lymph node metastasis, parametrial invasion, and positive surgical margins according to the final paraffin section were excluded. In total, 183 patients were included. Seventy-three (39.9%) patients had one, 85 (46.4%) had two, and 25 (13.7%) had three intermediate risk factors. Sixty-seven (36.6%) patients received adjuvant radiotherapy. There was a statistically significant difference in terms of stage, LVSI, and endometrial/uterine invasion between the groups that did and did not receive adjuvant radiotherapy (p = .024, p = .018, and p = .001, respectively). These two groups were homogenised by performing propensity score matching (PSM) analysis. In the new matched cohort (n = 134), 5-year disease-free survival (DFS) was 89.5% in the group that received adjuvant radiotherapy and 82% in the group that did not (HR: 0.484, 95% CI: [0.171–1.369]; p = .171). Also, receiving adjuvant radiotherapy was not associated with an improvement in oncologic outcomes in patients with one, two, or more intermediate risk factors. In univariate analysis, none of the risk factors was associated with DFS. In conclusion, adjuvant radiotherapy had no favourable effect on survival outcomes in patients with early-stage cervical carcinoma with only intermediate risk factors. IMPACT STATEMENT What is already known on this subject? Radiotherapy after radical hysterectomy in cervical carcinoma is accepted as the standard of care when high-risk factors – positive surgical margins, lymph node metastasis, and parametrial involvement – are found in the surgical specimen. However, the necessity of adjuvant radiotherapy in patients with intermediate-risk factors – deep stromal invasion, positive LVSI, tumour diameter ≥4 cm – is controversial. What do the results of this study add? We compared patients who received adjuvant radiotherapy and those who did not. No significant difference was found between the two groups in terms of oncologic outcomes. There was no difference between the two groups in terms of pelvic and extrapelvic recurrence rates. The number of positive intermediate-risk factors did not affect survival. Moreover, age, tumour type, stage, number of removed lymph nodes, grade, bilateral salpingo-oophorectomy, and endometrial/uterine invasion were not associated with DFS among patients with stage IB–IIA cervical carcinoma with only intermediate-risk factors. What are the implications of these findings for clinical practice and/or further research? Debate remains over the prognostic factors and the adjuvant treatment options in patients with early-stage cervical carcinoma who possess intermediate-risk factors. Adjuvant radiotherapy can be ignored if initial adequate surgery has been performed in this patient group.

Predicting lymph node status based on deep learning on histopathological images from primary tumor of early-stage cervical squamous cell carcinoma (080)

Objectives: To develop a new digital biomarker based on the convolutional neural network (CNN) analysis of primary tumor tissue, hence predicting lymph nodes (LNs) status in patients with early-stage cervical squamous cell carcinoma (CSCC). Methods: A total of 406 CSCC patients who underwent radical surgery between 2006 and 2014 were randomly selected, with their LNs status and hematoxylin-eosin (HE) stained primary tumor slides reviewed and confirmed by pathologists. Regions of interest (ROIs) were delineated by our pathology team. Slides were randomly divided into training, validation, and testing sets. With all Images preprocessed into patches, a CNN was trained to classify patches as LNs positive or negative. The CNN was further tested on a third independent population of 106 patients from The Cancer Genome Atlas (TCGA) database. Results: The cases included in the training set, validation set, and test set were 286, 60, and 60, respectively. Our classifier achieved an AUC of 0.86 (95% CI: 0.82-0.89) in cross-validation of slide-level LN status, 0.81 (95% CI: 0.77-0.86) on the test set, and 0.75 (95% CI: 0.71-0.82) on TCGA test set. For patients with positive LN, the digital signatures demonstrated good discrimination between patients with only pelvic LNs positive and patients with both pelvic and para-aortic LNs positive. The best performance model achieved an AUC of 0.91 (95% CI: 0.86-0.95) in the validation cohort and 0.87 (95% CI: 0.81-0.92) in the test cohort. Objectives: To develop a new digital biomarker based on the convolutional neural network (CNN) analysis of primary tumor tissue, hence predicting lymph nodes (LNs) status in patients with early-stage cervical squamous cell carcinoma (CSCC). Methods: A total of 406 CSCC patients who underwent radical surgery between 2006 and 2014 were randomly selected, with their LNs status and hematoxylin-eosin (HE) stained primary tumor slides reviewed and confirmed by pathologists. Regions of interest (ROIs) were delineated by our pathology team. Slides were randomly divided into training, validation, and testing sets. With all Images preprocessed into patches, a CNN was trained to classify patches as LNs positive or negative. The CNN was further tested on a third independent population of 106 patients from The Cancer Genome Atlas (TCGA) database. Results: The cases included in the training set, validation set, and test set were 286, 60, and 60, respectively. Our classifier achieved an AUC of 0.86 (95% CI: 0.82-0.89) in cross-validation of slide-level LN status, 0.81 (95% CI: 0.77-0.86) on the test set, and 0.75 (95% CI: 0.71-0.82) on TCGA test set. For patients with positive LN, the digital signatures demonstrated good discrimination between patients with only pelvic LNs positive and patients with both pelvic and para-aortic LNs positive. The best performance model achieved an AUC of 0.91 (95% CI: 0.86-0.95) in the validation cohort and 0.87 (95% CI: 0.81-0.92) in the test cohort.

The MEMORY Study: MulticentEr study of Minimally invasive surgery versus Open Radical hYsterectomy in the management of early-stage cervical cancer: Survival outcomes

ObjectiveThe Laparoscopic Approach to Cervical Cancer (LACC) trial found that minimally invasive radical hysterectomy compared to open radical hysterectomy compromised oncologic outcomes and was associated with worse progression-free survival (PFS) and overall survival (OS) in early-stage cervical carcinoma. We sought to assess oncologic outcomes at multiple centers between minimally invasive (MIS) radical hysterectomy and OPEN radical hysterectomy. MethodsThis is a multi-institutional, retrospective cohort study of patients with 2009 FIGO stage IA1 (with lymphovascular space invasion) to IB1 cervical carcinoma from 1/2007–12/2016. Patients who underwent preoperative therapy were excluded. Squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinomas were included. Appropriate statistical tests were used. ResultsWe identified 1093 cases for analysis—715 MIS (558 robotic [78%]) and 378. OPEN procedures. The OPEN cohort had more patients with tumors >2 cm, residual disease in the hysterectomy specimen, and more likely to have had adjuvant therapy. Median follow-up for the MIS and OPEN cohorts were 38.5 months (range, 0.03–149.51) and 54.98 months (range, 0.03–145.20), respectively. Three-year PFS rates were 87.9% (95% CI: 84.9–90.4%) and 89% (95% CI: 84.9–92%), respectively (P = 0.6). On multivariate analysis, the adjusted HR for recurrence/death was 0.70 (95% CI: 0.47–1.03; P = 0.07). Three-year OS rates were 95.8% (95% CI: 93.6–97.2%) and 96.6% (95% CI: 93.8–98.2%), respectively (P = 0.8). On multivariate analysis, the adjusted HR for death was 0.81 (95% CI: 0.43–1.52; P = 0.5). ConclusionThis multi-institutional analysis showed that an MIS compared to OPEN radical hysterectomy for cervical cancer did not appear to compromise oncologic outcomes, with similar PFS and OS.