Conization Specimens Research Articles

Reduced cervical sampling of hysterectomy specimens with negative margins on conization: An opportunity to improve resource utilization.

The current recommendation for hysterectomy specimens performed for cervical cancer following conization is that the entire cervix be submitted for histologic examination. Given the high cost of medical procedures and concerns regarding difficulties with laboratory staffing, we sought to evaluate the potential for selective histologic examination in this setting. Post-conization hysterectomy cases were reviewed for the presence of residual disease in relation to the findings of the prior conization, with consideration of margin status. Residual disease was then assessed for clinical significance. The number of submitted blocks was recorded and the associated costs were estimated. Among 32 cases with invasive carcinoma, only cases with margins positive for invasive carcinoma on the conization specimen had residual invasion in the hysterectomy (n = 7), and there were no upgrades due to subtle microscopic disease; 1 case had a change in pathologic stage from pT1b1 to pT2b due to parametrial involvement in the setting of a grossly apparent lesion. Among 20 cases performed following a diagnosis of dysplasia, none were upgraded to invasive carcinoma. Based on protocol-based submission of the entire cervix, 16 blocks of cervix were submitted on average (range, 4-41). We estimate that representative sections from each cervical quadrant would save approximately 2 work hours for laboratory staff per case and up to 6 hours for larger cases, reducing costs for the laboratory accordingly. Selective cervical sampling in the setting of negative margins on conization provides an opportunity for improved resource utilization without compromising patient care; as this is a small study, confirmation of these findings in a larger number of cases may be warranted. Additional studies are necessary to determine what other contexts in surgical pathology could benefit from a similar reductive approach.

Comedo-like growth pattern in invasive early-stage cervical cancer: A new feature related to parametrial involvement

IntroductionThe standard surgical treatment for early-stage cervical cancer includes hysterectomy and bilateral oophorectomy along the removal of parametrial tissue to achieve surgical radicality. However, in recent years, the role of simple hysterectomy for cervical cancer with favorable prognostic characteristics has been re-evaluated. One of the challenges in early-stage cervical cancer is identifying predictive factors for neoplastic parametrial infiltration and lymph node metastases that cannot be detected during the preoperative assessment. We hypothesized that histological tumor growth patterns may be associated with these features and could thus be useful for the management of apparent early-stage cervical cancer. MethodWe identified 3 different histological patterns: the comedo-like, the infiltrative, and the expansive. We analyzed a series of clinic-pathological characteristics to determine the association of eachpatternwith aggressive features. Furthermore, we estimated odd ratios (ORs) in univariate and multivariate analyses for parametrial infiltration and lymph node metastasis. ResultsWe found that comedo-like pattern is associated to advanced FIGO stages, larger tumor size, lymphovascular space invasion, deeper invasion depth, parametrium involvement, and lymph node metastases. By univariate analysis, comedo-like pattern was statistically associated with both parametrial involvement (OR: 19.3, CI 5.47–68.6, p-value = < 0.001) and lymph node metastases (OR: 4.98, CI 1.71–14.5, p-value = 0.003). By multivariate analysis, the association between comedo-like pattern and parametrial involvement was confirmed (OR: 8.76, CI 2.34–32.75, p-value = 0.01). ConclusionThe specific growth pattern of cervical cancer, assessed in a conization specimen before hysterectomy, can be useful to tailor surgical radicality.

Follow-up of women with cervical adenocarcinoma in situ treated by conization: A single centre clinical experience

ObjectiveHysterectomy has been the historical gold standard final step in the treatment algorithm of adenocarcinoma in situ (AIS) recommended by most North American colposcopy guidelines. AIS disproportionately affects young childbearing age women, therefore a fertility sparing treatment option is desirable. Our study examines the impact of conservative treatment of AIS with conization followed by serial surveillance. MethodsA retrospective chart review was completed of patients treated for AIS from 2006 to 2020. Charts were identified by pathologic diagnosis of AIS on cervical and uterine specimens. Charts were excluded if AIS was not treated with conization, if AIS was not confirmed on initial conization specimen, or if invasive disease was found at initial conization. Results121 patient charts were analyzed. Median age of patients at first conization and hysterectomy was 34.8 and 40.9, respectively. First conization was by Cold Knife Cone in 58% of patients, and by Loop Electrosurgical Excisional Procedure in 42% of patients. Median follow-up period in our study was 609 days. 5% of patients had recurrence, with only one patient who recurred as cancer. One case of recurrence had a positive initial conization margin. Median time to recurrence was 700 days. 47% of patients underwent eventual hysterectomy. Residual AIS was found in 23% of hysterectomy specimens. Adenocarcinoma was diagnosed on hysterectomy specimen in four patients. ConclusionOur study demonstrates the oncologic safety of treating AIS with conization and serial surveillance. Routine hysterectomy completed as a part of the AIS treatment algorithm, as in current clinical guidelines, is unnecessary.

Reevaluation of negative cervical conizations: Frequency, diagnostic errors, risk factors and management

ObjectiveCervical conization is an effective treatment for precancerous lesions. However, in cases where no high-grade lesion is identified in the surgical specimen, managing these patients may be challenging due to the absence of established follow-up protocols for negative conizations. This study aimed to assess the negative conization rates at our institution by histopathological review, identify diagnostic errors, possible risk and recurrence factors and propose follow-up strategies for this group of patients. MethodsA retrospective study from January-2010 to December-2020 analyzed patients with negative conization including all surgical techniques and procedure indications. Biopsy and cervical conizations slides were reviewed and patients who kept a negative result underwent deeper levels sectioning of the paraffin blocks with immunohistochemical stains application: p16, Ki-67 and geminin. Data were compared with a control group composed by 29 women with CIN3. ResultsOut of 1022 conizations, 186 were negative (18.1%), with 151 cases selected for the study after excluding 35 patients. Following pathology review, 4 patients were excluded due to false-positive cervical biopsy results, 16 for false-negative conization results and 9 for hidden dysplasia identified after deeper sectioning. The remaining 122 patients were considered truly negative cones (11.9%) and exhibited IHC staining with p16 positive in 20.4% of cases, low Ki-67 expression, and low geminin score in most cases. Specimens with CIN 1 had higher prevalence of p16 staining, Ki-67 expression and geminin score when compared to absence of neoplasia, nevertheless geminin had no statistical difference. Older age, higher parity and IHC pattern with negative p16, low Ki-67 and geminin expressions were identified as risk factors for negative cones (p<0.05). Only 10 patients recurred for high-grade lesions, with no statistically significant risk factors identified. ConclusionsThe negative conization rate was 11.9%, with diagnostic errors identified across pre-surgical biopsy, cone specimen, and deeper levels. Risk factors included older age, higher parity, low expression of p16, Ki-67 and geminin (p<0.05). Recurrence represented 8.1% of the negative cones, without identification of statistically significant risk factors. Pathological review with deeper level sections and 2-year follow-up are recommended for patients with negative conizations.

Residual cervical H-SIL after cervical conization with positive margins. Is there any associated risk factor?

Introduction: Cervical cancer is the second leading cause of death from gynecological cancer. In Argentina, it is estimated that nearly 4,500 new cases are diagnosed each year and 1,800 women die from this disease. The human papillomavirus (HPV) is a necessary but not a major cause to develop this type of cancer and it is responsible for producing both low-grade (L-SIL) and high-grade (H-SIL) squamous intraepithelial lesions (SIL) depending on the viral serotype in addition to other factors specific to the infected patient. Cervical intraepithelial neoplasia (CIN) is treated by local ablation or excision techniques with lower morbidity. The choice of treatment depends on the degree and extent of the disease, as well as the patient age, risk factors and immunity to generate spontaneous regression or persistence/recurrence. Objective: To identify clinical or pathological factors in patients who presented residual lesion (H-SIL) in the surgical specimens of both re-conization and hysterectomy (HT). Materials and methods: A retrospective, observational study was carried out at Sanatorio Güemes, Buenos Aires, Argentina. All patients that underwent cervical conization with an electric scalpel and had positive margins in the surgical specimen between January 2017 and May 2022 inclusive were analyzed. Data was obtained from 43 patients who had positive cervical conization specimen margins at our institution in the time period described above. Two patients who only had the exocervical margin involved and also 11 patients who did not meet the inclusion criteria were excluded. Among patients (30), all were reoperated (16 underwent re-conization, while in 14 patients it was decided to have a total hysterectomy). Among all the patients who underwent a new surgical procedure, residual disease was found in 10 patients (33.3%), while 20 patients (66.6%) had no residual lesion. Results: The highest percentage of patients (66.6%) did not present residual lesions in the posterior resection specimens. The parameter exhibiting the most substantial influence in our analysis was the proportion of lesion extension, exerting a significant effect on the persistence/recurrence of the disease in subsequent surgical samples (Relative Risk [RR] 7.87, 95% Confidence Interval [CI] 1.13-54.66, p &lt; 0.01). Conclusion: This information brings us even closer to the new reports of bibliographical data: although the presence of the compromised endocervical margin is valuable for estimating the risk of disease persistence/recurrence, it is not sufficient. Therefore, there is a lack of information about the importance of other factors to predict this situation.

Cervical lymphoepithelioma-like carcinoma with deficient mismatch repair and loss of SMARCA4/BRG1: a case report and five related cases

BackgroundWe encountered a cervical lymphoepithelial carcinoma (LEC) possessing a predominantly solid architecture with deficient mismatch repair (dMMR) and loss of expression of the SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodeling complex subunit. This is the first case report of LEC with dMMR and loss of SWI/SNF complex subunit.Case presentationA 34-year-old woman presented at our hospital with menstrual irregularities and abnormal vaginal bleeding. Magnetic resonance imaging revealed an exophytic mass in the posterior uterine cervix. Biopsy specimens confirmed squamous cell carcinoma with a 2018 International Federation of Gynecology and Obstetrics (FIGO) uterine cervical cancer stage of IB2. In a subsequent conization specimen, the tumor appeared exophytic. Microscopically, the tumor cells formed a predominant solid architecture. Abundant lymphocytic infiltration was observed. The pathological diagnosis indicated human papillomavirus (HPV)-associated squamous cell carcinoma with LEC pattern and pT1b2. Immunohistochemically, high programmed death-ligand 1 (PD-L1) expression, dMMR, and loss of the switch/sucrose non-fermentable family-related, matrix-associated, actin-dependent regulator of chromatin subfamily member 4 (SMARCA4)/BRG1, an SWI/SNF complex subunit, were observed. The patient underwent a radical hysterectomy and is alive without disease one year and five months later. Our analysis of five additional LEC cases revealed a consistent association with high-risk HPV and elevated PD-L1 expression. In addition to the present case, another patient exhibited dMMR. The SWI/SNF complex was retained except in the present case. The prognosis was favorable in all cases.ConclusionsThis unique case of LEC with dMMR suggests a distinct clinical entity with potential immunotherapy implications. Analysis of the other five LEC cases revealed that LEC was immune hot, and immune checkpoint inhibitors may be effective. The two dMMR cases showed loss of MLH1 and PMS2 expressions, and prominently high tumor PD-L1 expression. In those cases, dMMR might have contributed to the morphological characteristics of LEC.

A confirmatory trial of modified radical hysterectomy for patients with FIGO stage IB1 cervical cancer with tumor diameter preoperatively estimated at 2 cm or less: Japan Clinical Oncology Group study, JCOG1101.

5532 Background: The standard surgery for Stage IB1 uterine cervical cancer is radical hysterectomy (RH, Piver class III hysterectomy). However, RH is highly invasive, and there is a need to establish less invasive techniques. We conducted a single-arm confirmatory trial (JCOG1101) to evaluate the efficacy and safety of modified radical hysterectomy (MRH) in patients with tumor diameter ≤ 2 cm Stage IB1 cervical cancer (jRCT: jRCTs031180167). Methods: From January 2013 to August 2017, 240 patients were enrolled from 40 institutions in Japan. Eligibility criteria included: (1) FIGO 2008 Stage IB1 cervical cancer; (2) histologically proven squamous cell carcinoma, adenocarcinoma (mucinous or endometrioid) or adenosquamous carcinoma; (3) tumor diameter ≤ 2 cm (measured by MRI or conization specimen); and (4) neither distant LN metastasis nor distant metastasis in CT. In case that the cancer could be microinvasive, conization was required to exclude Stage IA cases. The protocol surgery involved cutting the anterior layer of the vesicouterine ligament of the uterus and dissecting regional lymph nodes. Only laparotomy was permitted: laparoscopy and robotic surgery were not allowed. Postoperative irradiation was administered in cases where pelvic LN or parametrial invasion was positive, depth in the cervical wall invasion was ≥ 2/3, or surgical margin was &lt; 1 cm by pathological findings. The primary endpoint was 5-year overall survival (OS). We set the expected 5-year OS of MRH at 95.8% (5-year OS of RH in JCOG0806A, retrospective observational study) and the threshold 5-year OS at 90.8%. Results: Among 225 eligible patients, 193 (85.8%) were pT1b1 (UICC 7th), and 184 (81.8%) had pathological maximal tumor diameter ≤ 2 cm. Parametrial involvement, lymph node metastasis, ≥ 2/3 stromal invasion and &lt; 1 cm surgical margin were observed in 3 (1.3%), 16 (7.1%), 30 (13.3%) and 11 (4.9%) patients, respectively. Thirty-nine patients (17.3%) underwent adjuvant (chemo)radiation. Median follow-up was 77.7 months. Five patients (2.2%) died, and 5-year OS was 98.2% (90% CI: 96.0-99.2, &gt; 90.8%). Thirteen patients (5.8%) relapsed (8 local recurrence and 5 distant recurrence), and 5-year relapse-free survival was 94.7% (95% CI: 90.8-96.9%). Self-urination was observed in all patients, and residual urine disappearance up to 56 days after urethral catheter removal was observed in 213 patients (94.7%). Median time to disappearance of residual urine after urethral catheter removal was 1 day. There was no treatment-related death. Grade 3/4 non-hematological adverse events were observed in 17 patients (7.6%), including 8 infection and 4 hemorrhage. Conclusions: In this study, MRH was as effective as RH and less invasive. MRH can be considered a standard surgery for tumor diameter ≤ 2 cm Stage IB1 uterine cervical cancer. Clinical trial information: UMIN000009726 , jRCTs031180167 .

Distribution of cervical intraepithelial neoplasia is closely associated with HPV status and uterine position.

Although cervical intraepithelial neoplasia (CIN) lesions are considered to be not randomly distributed across the cervix, but predominantly in the anterior wall, the clinicopathological etiology remains unknown. Herein, we aimed to elucidate the relationship between quantitatively measured area of CIN2/3 and cervical cancer associated factors by retrospective cohort study. We analyzed 235 consecutive therapeutic conization specimens dissected as a single intact section to determine CIN2/3 area and its correlation with both clinical risk factors including human papillomavirus (HPV) status (single or multiple infection) and uterine position defined by transvaginal ultrasound. Cervical wall was classified into three groups: anterior: (11, 12, 1, and 2 o'clock), posterior (5, 6, 7, and 8 o'clock) and lateral (3, 4, 9, and 10 o'clock). Multiple regression revealed that younger age and HPV16 status were significantly correlated with CIN2/3 area (p = 0.0224 and p = 0.0075, respectively). The Jonckheere-Terpstra test showed a significant trend: CIN2/3 area was highest in the single HPV16 group, followed by the multiple HPV16 group and the non-HPV16 group (p < 0.0001). CIN2/3 area in the anterior wall was statistically significantly larger than the posterior and lateral wall (p = 0.0059 and p = 0.0107, respectively). CIN2/3 area in the anterior wall was significantly greater with anteversion-anteflexion than retroversion-retroflexion (p = 0.0485), whereas CIN2/3 area in the posterior wall was significantly larger with retroversion-retroflexion than anteversion-anteflexion (p = 0.0394). In conclusion, the topographical distribution of CIN2/3 area is closely associated with patient age, high-risk HPV status, especially single HPV16 infection and uterine position.

A cervical screening initiative for elderly women in Denmark

To assess outcome of a one-time human papillomavirus (HPV)-screening in 2017 of Danish women aged 70+. Women born 1947 or before were personally invited to have a cell-sample collected by their general practitioner. Screening- and follow-up samples were analyzed in hospital laboratories in the five Danish regions and registered centrally. Follow-up procedures varied slightly across regions. Cervical intraepithelial neoplasia 2 (CIN2) was recommended treatment threshold. Data were retrieved from the Danish Quality Database for Cervical Cancer Screening. We calculated CIN2+ and CIN3+ detection rates per 1000 screened women, and number of biopsies and conizations per detected CIN2+ case. We tabulated annual number of incident cervical cancer cases in Denmark for the years 2009-2020. In total, 359 763 women were invited of whom 108 585 (30% of invited) were screened; 4479 (4.1% of screened, and 4.3% of screened 70-74 years) tested HPV-positive; of whom 2419 (54% of HPV-positive) were recommended follow-up with colposcopy, biopsy and cervical sampling, and 2060 with cell-sample follow-up. In total, 2888 women had histology; of whom 1237 cone specimen and 1651 biopsy only. Out of 1000 screened women 11 (95% confidence interval [CI]: 11-12) had conization. In total, 579 women had CIN2+; 209 CIN2, 314 CIN3, and 56 cancer. Out of 1000 screened women five (95% CI: 5-6) had CIN2+. Detection rate of CIN2+ was highest in regions where conization was used as part of first-line follow-up. In 2009-2016, number of incident cervical cancers in women aged 70+ in Denmark fluctuated around 64; in 2017 it reached 83 cases; and by 2021 the number had decreased to 50. The prevalence of high-risk HPV of 4.3% in women aged 70-74 is in agreement with data from Australia, and the detection of five CIN+2 cases per 1000 screened women is in agreement with data for 65-69 year old women in Norway. Data are thus starting to accumulate on primary HPV-screening of elderly women. The screening resulted in a prevalence peak in incident cervical cancers, and it will therefore take some years before the cancer preventive effect of the screening can be evaluated.

Failure mechanism during incremental sheet forming of a commercial purity aluminum alloy

Incremental sheet forming (ISF) is known for many advantages over conventional forming, such as part flexibility, low tooling cost and higher formability. Previously various studies have explored the failure mechanism experimentally and numerically. However, limited studies have been performed on the micro-mechanics of failure during ISF process. This study involves failure mechanism during incremental sheet forming of a commercial purity aluminum alloy (AA1050). During experiments, failure (fracture) was observed in truncated cone specimens by increasing the wall angle from 71° to 72°. The mechanism behind failure was explored with detailed microstructural characterization and finite element (FE) simulations. Various samples were taken from the successfully formed and failed cones for microstructural analysis. The electron backscatter diffraction (EBSD) based microtexture measurements associate this failure with more grain fragmentation and necking or localized deformation in the failed cone. Further, the X-ray diffraction (XRD) based residual stress measurements indicate high positive (tensile) hydrostatic stresses (∼157 MPa) on the outer surface of the failed (fractured) cones. Finite element analysis (FEA) with Gurson-Tvergaard-Needleman (GTN) damage model was used for fracture prediction. The FEA results also support the residual hydrostatic stress evolution in the cones, albeit at a slightly different wall angle. Based on microstructural and finite element analysis it is concluded that deformation becomes inhomogeneous when the failure occurs during ISF process.

Measurement and Analysis of Anatomical Structures Associated with the Implantation of Anterior Mental Foramen Based on CBCT

To evaluate the occurrence and morphological characteristics of related anatomical structures in the anterior mental foramen region and to verify the measurement consistency by cone beam CT (CBCT) and specimen measurement. Thirty-two mandibular specimens were selected to measure the relevant anatomical structures and to take CBCT images of the specimens for 3D reconstruction using NNT-Viewer. The studies included the occurrence and diameter of the mental foramen, accessory foramen, median lingual foramen, the distance from the lower margin of the foramen to the lower margin of the mandible, and the distance from the upper margin of the foramen to the crest of the alveolar ridge. Thirty-two specimens including a total of 59 central lingual foramens, with a 100% probability of occurrence. Four specimens were found to have an accessory mental foramen, of which 1 had bilateral accessory mental foramens. Compared with direct observation, there were differences in the number of central lingual foramens in 3 specimens. The mean distance between the upper mental foramen edge and the alveolus crest was 13.7 mm. There were statistically significant differences between the two methods in measuring the distance (mm) between the central lingual aperture and the alveolar crest (P<0.05). Except for the distance between the central lingual aperture and the alveolar crest (ICC=0.658), the ICC of the other study variables was above 0.85. The measurement results of the two methods showed a high degree of consistency. The measurement results of CBCT in this study showed a high degree of consistency with the measurement results from specimens, and the relevant anatomical structures of jaw bones could be analyzed using CBCT before the operation in the intermental foramen region.

Risk factors for pathological upgrading in perimenopausal women with cervical intraepithelial neoplasia grade 2/3 following conization.

Postmenopausal women have a high risk for pathological upgrading in conization specimens due to pathological changes of the cervix. This study aimed to investigate the risk factors for pathological upgrading in conization specimens in Chinese women with cervical intraepithelial neoplasia grade 2/3 (Cervical intraepithelial neoplasia 2/3) ≥ 50 years of age. From January 2015 to December 2019, 443 CIN2/3 patients ≥ 50 years of age were retrospectively included and divided into the upgrade group (n = 47) and the non-upgrade group (n = 396) according to the presence or absence of pathological upgrading in the conization specimens. Multivariate logistic regression model was performed to analyze risk factors associated with pathological upgrading. The upgrade group was more likely to have gravidity < 2 times, postmenopausal period ≥ 5 years, higher incidences of endocervical glandular involvement (EGI) and human papillomavirus (HPV) 16/18 infection, as well as a lower incidence of cervical contactive bleeding and fewer cases undergoing endocervical curettage (all P < .05) than the non-upgrade group. Multivariate model showed that factors associated with pathological upgrading were postmenopausal period ≥ 5 years (OR = 2.55), EGI (OR = 17.71), endocervical curettage (OR = 0.33), and HPV type 16/18 (OR = 3.41) (all P < .05). The receiver operating characteristic analysis showed an area under curve of 0.782 (P < .001). Pathological upgrading in conization specimens is not uncommon in Chinese CIN2/3 patients ≥ 50 years of age. For those with high-risk factors of pathological upgrading (postmenopausal period ≥ 5 years, EGI, and HPV 16/18 infection), the follow-up interval can be appropriately shortened, and active intervention could be considered.

Absence of high-grade cervical intraepithelial neoplasia in conization specimens from patients with colposcopic biopsy-confirmed high-grade cervical intraepithelial neoplasia: Retrospective study of 1695 cases.

Few studies have investigated the absence of high-grade cervical intraepithelial neoplasia (CIN) in excised specimens, and sample sizes of these studies were limited. This study retrospectively analyzed clinical characteristics of 1695 patients with CIN 2/3 to determine the incidence rate and relative factors of CIN 1 or less in conization specimens from patients with colposcopic biopsy-confirmed CIN 2/3. The study group comprised 430 cases of CIN 1 or less in conization specimens, and the control group comprised 1142 cases with high-grade CIN lesions in conization specimens. Univariate and multivariate logistic regression models were established to evaluate relative factors. The 1–9 years follow-up data were analyzed to determine the persistence/recurrence rate. Multivariate logistic regression showed that patients aged 18–24 years (OR (95% CI) = 2.224 (1.014, 4.877)); with a negative hrHPV test result (OR (95% CI) = 3.210 (1.627, 6.331)); a cytology test result of normal (OR (95% CI) = 5.184 (3.138, 8.563)), ASC-US (OR (95% CI) = 3.420 (2.102, 5.564)), LSIL (OR (95% CI) = 2.588 (1.475, 4.541)), or ASC-H (OR (95% CI) = 2.434 (1.306, 4.539)); an indication of CIN 2 on biopsy (OR (95% CI) = 2.290 (1.694, 3.096)), and no glandular involvement (OR (95% CI) = 1.616 (1.205, 2.169)) were more likely to have an absence of high-grade dysplasia in conization specimens. There was no difference in the persistence/recurrence rate between the two groups (x2 = 1.55, P = 0.46). An age of 18–24 years, a negative hrHPV test result, a non-HSIL cytology test result, an indication of CIN 2 on biopsy, and no glandular involvement were relative factors for an absence of high-grade dysplasia in conization specimens. For patients with relative factors, especially young women, informed follow-up should be considered.

Influence of shear stress state on dynamic fracture of a glass ceramic Macor

The effect of shear stress on the dynamic failure of ceramic materials is not sufficiently investigated in the published literature. With the use of a bespoke split Hopkinson pressure bar, this paper presents an effort to investigate the dynamic shear compressive response of Macor, a model ceramic material with zero porosity and light weight characteristics. A cone specimen and cylindrical specimens with varying inclined angles are used to introduce the shear stress to the Macor ceramic. The dynamic failure initiation and crack propagation are monitored by the high speed photography and Digital Image Correlation techniques. It is found that the equivalent stress of Macor at the initiation of failure decreases nonlinearly with the increase of shear stress. The high speed images show that the crack originates from the minimum cross-section of the cone specimen and the obtuse angle corner of the inclined cylindrical specimens. The cracks propagate parallel to the inclined plane instead of the axial loading direction. The fractographic analysis shows the compacted zone in the shear fracture surfaces of the cone specimen and the inclined cylindrical specimens. This indicates a significant role of shear loading in the dynamic failure process of Macor.

Influence of Mo on the dynamic recrystallization behavior of Al–Cu–Mg–Ag alloy

High-throughput double cone specimens were used to study the influence of Mo on the microstructure evolution of Al–Cu–Mg–Ag alloy under a wide range of strain along the axis. The microstructure evolution was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and electron backscatter diffraction (EBSD). Results demonstrated that Al6(Fe, Mn, Mo) dispersoids formed in the Al–Cu–Mg–Ag alloy with the addition of 0.2% Mo during double-step homogenization. Meanwhile, rod-like Al20Cu2Mn3 and disk-like Al6(Fe, Mn, Mo) dispersoids segregated to opposite distribution in interdendritic regions and dendrite cores, respectively, which obviously eliminated the dispersoid-free zones and intragranular sparse regions. With different effective strains along the axis, Al6(Fe, Mn, Mo) dispersoids obviously reduced the transformation from Low-angle grain boundaries to High-angle grain boundaries. The nucleation and growth of dynamic recrystallization grains were effectively inhibited by the coupling of Al20Cu2Mn3 and Al6(Fe, Mn, Mo) dispersoids due to the obstruction of dislocation movement.

Cervical conization before primary radical hysterectomy has a protective effect on disease recurrence in early cervical cancer: A two-center matched cohort study (174)

Objectives: Preoperative cervical conization, while reducing the cervical mass size, might decrease the chance of tumor spillage during surgery. This study aimed to ascertain whether cervical conization before primary radical hysterectomy (RH) has a protective effect in patients with early cervical cancer. Methods: We retrospectively identified node-negative, marginnegative, parametria-negative, 2009 FIGO stage IB1 cervical cancer patients who received primary Type C RH at two tertiary institutional hospitals between July 2006 and June 2020. Whether they received preoperative cervical conization or not, patients were divided into conization group (n=144) and control group (n=434). To adjust for confounders, we conducted a 1:1 propensity score matching for histology, surgical approach, lymphovascular space invasion, and cervical mass size (calculated by summing pathologic tumor size on conization and uterine specimens). Then, survival outcomes were compared between the matched groups. Results: Overall, the conization group had less cervical mass size and received minimally invasive surgery (MIS) more frequently (p=0.010) and adjuvant treatment less often (p=0.002) compared to the control group. Of 37 patients who received preoperative conization and had no residual tumor in the uterine specimen, only one (2.7%) recurred during 56.5 months of a median observation period. After matching, the conization group showed significantly better progression-free survival (PFS) than the control group (3-year: 94.2% vs 86.3%; p=0.012), whereas no significant difference in overall survival (OS) was found. Subgroup analysis in the open RH (n=91) revealed that PFS did not differ by preoperative conization (p=0.799). In contrast, in the MIS RH subgroup (n=197), preoperative conization was associated with significantly better PFS (p=0.005). Conclusions: Despite the retrospective design, our matched cohort study suggests that preoperative cervical conization might have a protective effect on disease recurrence in early cervical cancer, especially for those who are planning to undergo MIS RH. Further prospective studies are warranted. Objectives: Preoperative cervical conization, while reducing the cervical mass size, might decrease the chance of tumor spillage during surgery. This study aimed to ascertain whether cervical conization before primary radical hysterectomy (RH) has a protective effect in patients with early cervical cancer. Methods: We retrospectively identified node-negative, marginnegative, parametria-negative, 2009 FIGO stage IB1 cervical cancer patients who received primary Type C RH at two tertiary institutional hospitals between July 2006 and June 2020. Whether they received preoperative cervical conization or not, patients were divided into conization group (n=144) and control group (n=434). To adjust for confounders, we conducted a 1:1 propensity score matching for histology, surgical approach, lymphovascular space invasion, and cervical mass size (calculated by summing pathologic tumor size on conization and uterine specimens). Then, survival outcomes were compared between the matched groups. Results: Overall, the conization group had less cervical mass size and received minimally invasive surgery (MIS) more frequently (p=0.010) and adjuvant treatment less often (p=0.002) compared to the control group. Of 37 patients who received preoperative conization and had no residual tumor in the uterine specimen, only one (2.7%) recurred during 56.5 months of a median observation period. After matching, the conization group showed significantly better progression-free survival (PFS) than the control group (3-year: 94.2% vs 86.3%; p=0.012), whereas no significant difference in overall survival (OS) was found. Subgroup analysis in the open RH (n=91) revealed that PFS did not differ by preoperative conization (p=0.799). In contrast, in the MIS RH subgroup (n=197), preoperative conization was associated with significantly better PFS (p=0.005). Conclusions: Despite the retrospective design, our matched cohort study suggests that preoperative cervical conization might have a protective effect on disease recurrence in early cervical cancer, especially for those who are planning to undergo MIS RH. Further prospective studies are warranted.

Predictors of high-grade residual disease after repeat conization in patients with positive surgical margins.

No consensus exists on the subsequent management strategy of patients who exhibit positive surgical margin (PSM) after re-excision of high-grade cervical intraepithelial neoplasia (CIN). The aim of the study is to examine the predictors related to the persistence of high-grade CIN lesions after re-excision, where PSM was left behind. The present retrospective study included patients with PSM who underwent repeated conization due to residual high-grade CIN lesions between January 2005 and December 2019. The SPSS software v20.0 was used for data interpretation and statistical analysis. P values less than 0.05 were accepted as statistically significant. Repeat conization was performed in 91 patients, 43 (47.3%) presented with PSM with high-grade CIN, 6 (6.5%) presented with micro-invasive carcinoma, and 42 (46.2%) presented with clear surgical margin or CIN 1 at the surgical margin. At the time of conization, patients who presented with lesions > 5 mm in repeat cone specimens, exhibited a significantly higher rate of residual disease (p < 0.001). Besides, the involvement of the endocervical margin with high-grade CIN was the predictor of residual disease in repeat cone specimens (p = 0.006). In the cone specimen, the presence of lesion size greater than 5 mm and involvement of the endocervical margin were the predictors of high-grade residual disease after re-excision. Whether it is the first or second procedure, great care must be given to excise the lesion entirely at the time of the conization, preferably in one piece.

Fertility-sparing surgery for early-stage cervical cancer: A case series study on the efficacy and feasibility of cervical conization followed by pelvic lymphadenectomy.

To evaluate the oncologic and obstetric outcomes of cervical conization followed by pelvic lymphadenectomy, which is used as a fertility-sparing procedure, in reproductive-aged patients with early-stage cervical cancer. We performed a retrospective study of patients with stage IA1-IB1 cervical cancer who underwent cervical conization followed by pelvic lymphadenectomy from 2011 to 2020 at Kumamoto University Hospital. In total, eight patients underwent conization followed by pelvic lymphadenectomy. The median age of the patients was 33 (range: 28-36) years. Four (50.0%) patients were nulliparous. Seven (87.5%) patients were diagnosed with squamous cell carcinoma (87.5%) and one (12.5%) with adenocarcinoma. Five (62.5%), two (25.0%), and one (12.5%) presented with stage IA1, IA2, and IB1 disease, respectively. Five (62.5%) patients had lymphovascular space invasion (LVSI) based on the assessment of specimens obtained via conization. However, none had lymph node metastasis based on pelvic lymphadenectomy. Regarding long-term oncologic outcomes, recurrence was not observed at a median follow-up of 60 (range: 8-107) months. In addition, obstetric outcomes were consistently favorable in terms of achieving pregnancy, preterm delivery, and live birth. During the study period, two patients who actively attempted to conceive had four pregnancies, resulting in full-term deliveries, and one was on her first trimester of pregnancy. Cervical conization combined with pelvic lymphadenectomy represents a feasible conservative management for histologically well-selected patients with early-stage cervical cancer. Furthermore, an optimal histopathological evaluation of conization specimens will contribute to decision-making regarding the use of this fertility-sparing procedure.

Laser conization for cervical intraepithelial neoplasia: Effectiveness and obstetric outcomes

PurposeTo evaluate the effectiveness and obstetric outcomes after laser conization for cervical intraepithelial neoplasia. MethodsThis retrospective study included 757 patients who underwent laser conization between 2014 and 2020. Patients with a diagnosis of invasive lesions or adenocarcinoma in situ were excluded. Histological data from the conization specimen, pre and postoperative histological and virological data (Human PapillomaVirus (HPV) test) and obstetric outcomes were collected from the medical record. The primary endpoint was the negative surgical margin rates after laser conization. The secondary endpoint were the size of the operative specimen, the postoperative virological test results (3 to 6 months after surgery), factors associated with negative or positive margin and postoperative obstetric outcomes (prematurity). Patient characteristics and outcomes were compared using Student's t-test, χ² test, or Fisher exact test. Values of p ≤ 0.05 were considered significant. ResultsThis study included 757 patients. Negative surgical margins were obtained in 76.1% of the cases and were associated with more negative HPV tests at 6 months (64.9% vs. 52.5%, p = 0.006) and fewer repeat surgeries (0.2% vs. 2.2%, p = 0.013) than for patients with positive margins. Among the patients under 43 years at the time of conization, 71 achieved a pregnancy with a term >22 weeks, and of these 66 (93%) delivered at term (≥37 weeks). ConclusionLaser conization appears to be an effective technique for the management of cervical intraepithelial neoplasia both in terms of the quality of the resection margins and the obstetric prognosis.

Can Conization Specimens Predict Sentinel Lymph Node Status in Early-Stage Cervical Cancer? A SENTICOL Group Study.

Simple SummaryLymph node involvement is one of the major prognosis factors for early-stage cervical cancer. Improvement in preoperative identification of node-positive patients may lead to a more accurate triage to primary chemoradiation for these patients instead of radical surgery followed by adjuvant radiotherapy, given the increased morbidity of combined treatment. Several studies have well established risk factors for node involvement, but they are based on final pathologic examination of radical hysterectomy specimens and are usually extrapolated for preoperative risk assessment. Among these risk factors, tumor size, lymphovascular space invasion (LVSI) and depth of stromal invasion might be assessed in conization specimens. Our findings suggest that patients with depth of stromal invasion lower than 10 mm and no LVSI in conization specimens had lower risk of micro- and macrometastatic SLN. In this subpopulation, full node dissection may be questionable in case of SLN unilateral detection.Background: The prognosis of patients with cervical cancer is significantly worsened in case of lymph node involvement. The goal of this study was to determine whether pathologic features in conization specimens can predict the sentinel lymph node (SLN) status in early-stage cervical cancer. Methods: An ancillary analysis of two prospective multicentric database on SLN biopsy for cervical cancer (SENTICOL I and II) was carried out. Patients with IA to IB2 2018 FIGO stage, who underwent preoperative conization before SLN biopsy were included. Results: Between January 2005 and July 2012, 161 patients from 25 French centers fulfilled the inclusion criteria. Macrometastases, micrometastases and Isolated tumor cells (ITCs) were found in 4 (2.5%), 6 (3.7%) and 5 (3.1%) patients respectively. Compared to negative SLN patients, patients with micrometastatic and macrometastatic SLN were more likely to have lymphovascular space invasion (LVSI) (60% vs. 29.5%, p = 0.04) and deep stromal invasion (DSI) ≥ 10 mm (50% vs. 17.8%, p = 0.04). Among the 93 patients with DSI < 10 mm and absence of LVSI on conization specimens, three patients (3.2%) had ITCs and only one (1.1%) had micrometastases. Conclusions: Patients with DSI < 10 mm and no LVSI in conization specimens had lower risk of micro- and macrometastatic SLN. In this subpopulation, full node dissection may be questionable in case of SLN unilateral detection.