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ObjectiveWhile human papillomavirus (HPV) has been shown to play a significant role in cervical cancer carcinogenesis (HPV associated cases), a considerable percentage of cervical cancers occur independently of HPV status (HPV independent).MethodsIn this retrospective study of 254 locally advanced cervical cancer patients treated with chemoradiotherapy and radical surgery, HPV genotypes were determined using the Anyplex II HPV28 kit that uses multiplex, real time polymerase chain reaction technology. The primary endpoints of this study were to evaluate the complete response to chemoradiotherapy (pathologic complete response), the presence of microscopic (<3 mm, pathologic micro partial response, group 1) and macroscopic (>3 mm, pathologic macro partial response, group 2) residual carcinoma in the cervix, and the persistence of metastatic lymph nodes (group 3) in HPV independent cervical cancers. Secondary endpoints were evaluation of disease-free survival and overall survival.ResultsOf 254 patients studied, 21 cases (8.3%) of cervical cancer were determined to be HPV independent. The percentage of pathologic complete response was found to be higher in the HPV associated group compared with the HPV independent group (pConclusionsThis study showed that HPV status at diagnosis could be a relevant factor for clinical outcomes in locally advanced cervical cancer patients.

Background Exclusive chemoradiation (E-CT/RT) represents the standard of treatment for locally advanced cervical cancer (LACC). Chemoradiation (CT/RT) followed by radical surgery (RS) may play a role for patients with a suboptimal response to CT/RT or in low-income countries with limited access to radiotherapy. Histologic assessment of residual tumor after CT/RT and RS allows accurate definition of prognostic categories. Methods Data on patients with FIGO stages 1B2 to 4A cervical cancer managed by CT/RT and RS from June 1996 to March 2020 were retrospectively analyzed. Pathologic response on the cervix was defined as complete (pCR), microscopic (persistent tumor foci ≤ 3 mm) (pmicroR), or macroscopic (persistent tumor foci > 3 mm) (pmacroR). Lymph node (LN) residual tumor was classified as absent or present. Results The 701 patients in this study underwent CT/RT and RS. Of the 701 patients, 293 (41.8%) had pCR, 188 (26.8%) had pmicroR, and 220 (31.4%) had pMacroR. Residual tumor was found in the pelvic lymph nodes of 66 (9.4%) patients and the aortic lymph nodes of 29 (4.1%) patients. The 5-year DFS and OS were respectively 86.6% and 92.5% in the pCR cases, 80.3% and 89.1% in the pmicroR cases, and 56.2% and 68.8% in the pmacroR cases. Among the patients with lymph node residual tumor, the 5-year DFS and OS were respectively 16.7% and 40% in the pCR cases, 35.4% and 53.3% in the pmicroR cases, and 31.7% and 31.1% in the pmacroR cases. Cervical residual tumor,, positive pelvic LNs, and positive aortic LNs were associated with worse DFS and OS in both the uni- and multivariate analyses. Conclusions Persistence of pathologic residual tumor on the cervix and LNs after CT/RT are reliable predictors of survival for LACC patients undergoing CT/RT and adjuvant surgery.

ObjectivesTo report on a consensus survey of experts on a recently proposed simplified nomenclature of surgical anatomy of the female pelvis for radical hysterectomy. The aim was to standardize surgical reports in clinical practice and understanding of the techniques in future surgical literature.MethodsThe anatomical definitions were included in 12 original images taken at the time of cadaver dissections. Denomination of the corresponding anatomical structures was based on the nomenclature recently proposed by the same team. A three step modified Delphi method was used to establish consensus. After a first round of online survey, the legends of the images were amended to respond to the comments of the experts. Second and third rounds were performed. Consensus was defined as a yes vote to each question regarding the images provided, and 75% was defined as the cut-off for agreement. Comments justifying the no votes were taken into account to amend the set of images and legends.ResultsA group of 32 international experts from all continents was convened. Consensus exceeded 90% for all five images documenting the surgical spaces. Consensus ranged between 81.3% and 96.9% for the six images documenting the ligamentous structures surrounding the cervix. Finally, consensus was lowest (75%) for the most recently defined denomination of the broad ligament (lymphovascular parauterine tissue or upper lymphatic pathway).ConclusionSimplified anatomic nomenclature is a robust tool to describe the surgical spaces of the female pelvis. The simplified definition of ligamentous structures reached a high level of consensus, even if the terms paracervix (instead of lateral parametrium), uterosacral ligament (replaced by rectovaginal ligament), vesicovaginal ligament, and lymphovascular parauterine tissue remain matters of debate.

Herein, we report a case of low-grade endometrial endometrioid carcinoma recurred on the vaginal stump, which showed a complete histotype shift toward a gastrointestinal-type carcinoma after chemotherapy. The recurrent tumor increased in volume during chemotherapy. Postchemotherapy histologic examination showed a pure mucinous signet-ring cell pattern with positivity for cytokeratin 20 and CDX2, focal SATB2 expression and negativity for cytokeratin 7 and estrogen and progesterone receptors. Such features led to consider a diagnosis of metastasis from a primary carcinoma of the gastrointestinal tract. The accurate exclusion of any primary lesions of gastrointestinal and of other sites allowed identifying the tumor as the recurrent endometrial carcinoma. Our case highlights that chemotherapy may induce a histotype shift from endometrioid carcinoma to gastrointestinal-type carcinoma; such occurrence might be a mechanism of resistance and might provide new insights on the sensitiveness of different histotypes to systemic therapies. Considering the possibility of a shift from endometrioid to gastrointestinal-type carcinoma may be useful for a correct diagnosis and an appropriate patient management.

The primary aim of the present study was to assess the incidence of ovarian metastasis/recurrence and the survival of patients undergoing radical hysterectomy with ovarian conservation (CONSERV) versus oophorectomy (OOPHOR). Secondary aim was to assess the incidence and the characteristics of menopausal symptoms in both groups.Retrospective, multi-center, observational cohort study including patients50 years with clinical FIGO 2009 stage IA1-IB1/IIA1 cervical carcinoma, treated by primary surgical treatment between 02/2007 and 07/2019. One-to-one case-control matching was used to adjust the baseline prognostic characteristics in survival analysis.419 patients were included. 264 in the OOPHOR (63.0%) and 155 (37.0%) in the CONSERV group. Ovarian transposition was performed in 28/155 (18.1%) patients. 1/264 (0.4%) patient had ovarian metastasis from endocervical adenocarcinoma. After propensity-matching, 310 patients were included in the survival analysis (155 per group). 5-year disease-free survival of patients undergoing CONSERV versus OOPHOR was 90.6% versus 82.2%, respectively (p = 0.028); 5-year overall survival was 94.3% versus 90.8%, respectively (p = 0.157). Two patients (1.3%) developed recurrence on the conserved ovary. CONSERV represented an independent protective factor of recurrence (HR:0.361, 95%CI 0.169-0.769; p = 0.008). 28 (20.6%) in the CONSERV group versus 116 (60.4%) in the OOPHOR group complained of menopausal symptoms during follow up (p 0.001). HRT was prescribed to 12.0% of patients (median HRT time was 20 months).CONSERV was associated with reduced risk of recurrence and menopausal symptoms in early-stage cervical cancer. As the risk of ovarian metastasis and ovarian recurrence is relatively low, CONSERV in pre-menopausal women has to be considered.

Ultrasound is a fast, accessible, reliable, and radiation-free imaging modality routinely used to assess the soft tissues around the shoulder. It enables to identify a wide range of pathological conditions. Furthermore, most ultrasound-guided musculoskeletal interventional procedures around the shoulder produce better results in terms of accuracy and clinical efficacy than those performed in a blinded fashion. Indeed, intra-articular and peri-articular interventional procedures can be easily performed under continuous ultrasound monitoring to ensure the correct position of the needle and to deliver the medication to a specific target. Several technical approaches and medications can be used to treat different causes of painful shoulder. Intra-articular injections are applied to treat acromioclavicular osteoarthritis as well as glenohumeral joint osteoarthritis and adhesive capsulitis. Subacromialsubdeltoid bursitis, either presenting as a primary inflammatory condition or secondary to rotator cuff disorders, can be easily approached using ultrasound guidance to aspirate synovial effusion and to inject medications. Ultrasound-guided percutaneous irrigation is a well-established technique increasingly applied to treat patients with rotator cuff calcific tendinopathy. Also, degenerative rotator cuff tendinopathy can be conservatively treated by image-guided interventions, specifically with needling under ultrasound guidance that can be associated with injections of platelet-rich plasma. Lastly, periarticular peripheral nerve block can be quickly and safely performed under ultrasound guidance, particularly in conditions involving the suprascapular nerve in the setting of pre-operative analgesia or pain treatment in glenohumeral osteoarthritis and adhesive capsulitis. In this article, the most common ultrasound-guided procedures around the shoulder have been reviewed to discuss indications and techniques.

Corded and hyalinized endometrioid carcinoma (CHEC) typically shows low-grade features and "no specific molecular profile" (NSMP). This study aimed to perform a clinicopathological and molecular characterization of endometrial CHEC with high-grade features. Immunohistochemistry for cytokeratin AE1/AE3, e-cadherin, β-catenin, estrogen receptor, progesterone receptor, p53, p16, and mismatch repair proteins was performed. A next-generation sequencing kit was used to assess POLE, POLD1, APC, MLH1, MSH2, MSH6, PMS2, MUTYH, EPCAM, and CTNNB1. Molecular groups, i.e., POLE-mutant, mismatch repair deficient (MMRd), p53-abnormal, and NSMP, were assigned according to the TCGA classifier. Six high-grade endometrial CHECs were identified. The mean age was 57.5 years; 5/6 cases were uterine-confined. Five cases showed a diffusely and markedly atypical corded component and a MMRd or p53-abnormal signature; additional features included single-cell keratinization, necrosis, osteoid or myxoid/chondro-myxoid matrix, foci of anaplasia, and nuclear β-catenin expression. The remaining case showed a low mitotic count and a NSMP phenotype, with focal bizarre cells in an otherwise classical CH endometrioid carcinoma. All cases showed variably reduced expression of epithelial markers and hormone receptors in the corded component. No mutations were found in any of the analyzed genes. In conclusion, high-grade CHECs are a heterogeneous subset of biphasic endometrial carcinoma which show similarities and differences with classical CHEC and carcinosarcoma. These cases often show MMRd or p53-abnormal signatures.

Background: The aim of the present study was to assess the prognostic value of tumour-free distance (TFD), defined as the minimum distance of uninvolved stroma between the tumour and peri-cervical stromal ring, in early-stage cervical cancer. Methods: Patients with pathologic FIGO 2009 stage IA1–IIA2 cervical cancer, treated by primary radical surgical treatment between 01/2000 and 11/2019, were retrospectively included. Adjuvant treatment was administered according to the presence of previously established pathologic risk factors. TFD was measured histologically on the hysterectomy specimen. Pre-operative TFD measured at MRI-scan from a cohort of patients was reviewed and compared with pathology TFD. Results: 395 patients were included in the study. 93 (23.5%) patients had TFD ≤ 3.0 mm and 302 (76.5%) had TFD > 3.0 mm. TFD ≤ 3.0 mm together with lymph vascular space involvement represented the strongest predictor for lymph node metastasis at multivariate analysis. TFD ≤ 3.0 mm was associated with worse 5-year disease-free survival (DFS) and overall survival (OS), compared with TFD > 3.0 mm (p = 0.022 and p = 0.008, respectively). DFS difference was more evident in the subgroup of patients with low-risk factors who did not receive adjuvant treatment (p = 0.002). Cohen’s kappa demonstrated an agreement between TFD measured at pre-operative MRI-scan and histology of 0.654. Conclusions: Pathologic TFD ≤ 3.0 mm represents a poor prognostic factor significantly associated with lymph node metastasis and it may be considered a novel marker to select candidates for adjuvant treatment. The possibility to obtain this parameter by radiological imaging makes it a potential easy-measurable pre-operative marker to predict the presence of high-risk pathologic factors in early-stage cervical cancer.

Cervical carcinoma is a common gynecological malignancy that remains a challenge for oncologic gynecologists around the world [...]

The aim of this study was to investigate the prevalence of peritoneal human papillomavirus (HPV) infection in different clinical cervical cancer (CC) settings, and its association with potential clinical and/or histological factors. This is a single-center, prospective, observational study. Consecutive patients with newly diagnosed or recurrent/persistent CC, between March 2019 and April 2020, were included. A group of patients undergoing surgery for benign gynecological conditions was included as control group. All patients underwent HPV-DNA test in the cervix and in the peritoneal cavity simultaneously at time of surgery. Two-hundred seventy-two patients had cervical and peritoneal HPV test analyzed. Cervical and peritoneal HPV positivity (PHP) was found in 235 (88.0%) and 78 (28.7%) patients, respectively; the prevalence of PHP was 17.7% in early stage, 28.8% in locally advanced cervical cancer (LACC) and 46.6% in the metastatic/persistent/recurrent setting (P = .001). No control patient was found to have peritoneal HPV infection. Higher frequency of PHP was documented in patients with larger tumor size (P = .003), presence of cervical HPV 16/18 genotypes (P

To systematically review the current literature concerning the role of superb microvascular imaging (SMI), a novel Doppler technique that enables detection of fine vessels and slow blood flow, in the evaluation of musculoskeletal disorders. An online search of the literature was conducted for the period 2013 to April 2019 and included original articles written in English language. A data analysis was performed at the end of the literature search. Eight original articles with prospective design and one with retrospective design were included in this review: 4 studies focused on rheumatoid arthritis, 2 on rheumatoid and other arthritides, 1 on lateral epicondylosis and 2 on carpal tunnel syndrome. Sample size ranged from 26 to 83 patients. Despite some methodological differences, all studies compared the performance of SMI with that of a conventional Doppler technique such as power and color Doppler and found an improvement in vascularity detection with SMI. The main variations were in sample size, evaluated parameters and vascularity interpretation methods. Inter-observer agreement for SMI ranged from moderate to excellent. SMI is a promising tool for the diagnosis and treatment planning of different musculoskeletal disorders. Future investigations should include larger samples of patients with long-term follow-up.

Paget disease is a rare neoplasm of the skin that mainly involves the vulvar region. Vulvar Paget's disease (VPD) can spread beyond the apparent edges of the lesion resulting in a high risk of involved surgical margins. Our aim is to verify the efficacy of a preoperative vulvo-vaginal intensive clock mapping in the prediction of the invasiveness and the extension of VPD.All consecutive patients with primary VPD referred to our institution from July 2005 to December 2018 were subjected to a preoperative intensive biopsy mapping (clock mapping) of the vulvo-vaginal area: inside and outside the vulvar skin visible lesion, according to o'clock positions, and in the vagina. Patients with positive biopsies "only inside" or "also beyond" the visible lesion were included, respectively, in Group A and B. Surgical excision was drawn passing by the points with negative histology. Pathological findings of mapping biopsies were compared with those from radical surgery.A total of 28 women were enrolled. After clock mapping definitive histology: 17 (60.7%) and 11 (39.3%) patients were included in Group A and B. Definitive histology showed non-invasive, micro-invasive and invasive VPD, respectively, in 13 (46.4%), 11 (39.3%) and 4 (14.3%) patients, with 4 patients further upstaged. Overall, negative margins were found in 14 (50%) patients: 9 (32.1%) from Group A and 5 (17.9%) from Group B. In 23 cases (82.1%), clock mapping identified free surgical margins along the vulvo-perineal skin excision front.Preoperative clock mapping emerged as potentially useful workup tool to predict invasiveness and extension of VPD, to tailor surgical excision.

Herein, we present a morphological, immunohistochemical, and molecular analysis of three cases of endometrial giant cell carcinoma (EGCC) with a literature review. Patient age was 55 to 76 years. The tumors were limited to the uterus and showed dyshesive, bizarre giant cells with numerous atypical mitoses. Minor components were low-grade endometrioid, spindled/myxoid (case nos. 1 and 2), serous (case no. 3), and undifferentiated (all cases). The giant cells were e-cadherin-, cytokeratins/EMA + (focal/multifocal), hormone receptors + (focal/multifocal), vimentin + , p16 + (diffuse), CD68-, α-FP-, β-HCG-, muscle markers-, CD10-, and ERG-. Case no. 3 was p53-abnormal. All cases were mismatch repair-proficient and microsatellite-stable. No POLE mutations were detected. Based on our and previous reports, EGCC is often accompanied by a conventional carcinomatous component (mostly endometrioid) and shows partial loss epithelial markers and negativity for specific differentiation markers. EGCC shows evident similarities to both undifferentiated/dedifferentiated carcinoma and carcinosarcoma and should be managed similarly. Unlike the latter two, EGCC might preferentially derive from “no-specific-molecular-profile” carcinomas.

Preservation of ovarian function is important for the physical and psychosexual well-being of young patients with cancer. Patients with pelvic malignancies such as cervical or rectal cancer planned for radiotherapy may benefit from ovarian transposition with the aim of moving the ovaries outside the radiation field.1 Different surgical techniques have been reported previously.2,3 With the present video, we aim to standardize the surgical technique of laparoscopic ovarian transposition in ten steps. We present the case of a 30-year-old nulliparous woman diagnosed with grade 3 squamous cell cervical carcinoma having a largest tumor diameter of 41 mm on magnetic resonance imaging (MRI) scan. The tumor was staged as FIGO 2018 stage IIIC1r with a common iliac lymphadenopathy reported on both MRI and positron emission tomography (PET)/computed tomography (CT) scan. The multidisciplinary team recommended exclusive chemoradiation extended to paraaortic area. The patient underwent laparoscopic bilateral salpingectomy and bilateral ovarian transposition with extraperitonealization of the infundibulopelvic ligament. The procedure was divided into the following ten steps: division of uteroovarian ligament, incision of lateral pelvic peritoneum, identification of ureter, incision of medial pelvic peritoneum, skeletonization of the infundibulopelvic ligament, retroperitoneal tunnel in paracolic gutter, creating the window (as high as possible), mobilization of the ovary without torsion, intraperitonealization of the ovary, and fix ovary with clips (Fig. 1). Surgical time was 30 min, with minimal estimated blood loss. No intra- or postoperative complication was recorded. The patient started radiotherapy 14 days after the procedure. In conclusion, we showed that laparoscopic ovarian transposition in cervical cancer before radiotherapy can be standardized in ten steps with encouraging perioperative results, making it an easily reproducible procedure. Ovarian function is reported to be preserved in 62–65% of cases undergoing ovarian transposition and radiation therapy.4,5

Occult parametrial involvement in apparent early-stage cervical cancer might be overlooked with standard pathologic assessment. The primary endpoint of the present study was to assess the rate of positive parametrial lymph nodes and of microscopic continuous or discontinuous parametrial involvement. This is a retrospective, single-center, observational study including patients with FIGO 2018 stage IA1–IIA1 and IIIC1p in whom bilateral sentinel lymph node (SLN) detection and ultrastaging of SLN were performed according to institutional protocol, with surgery as primary treatment performed between May 2017 and February 2021, as well as type B2/C1/C2 (Querleu–Morrow) radical hysterectomy and usual histology (squamous cell, adenocarcinoma and adenosquamous carcinoma). Thirty-one patients were included in the study period. Six (18.7%) patients had metastatic lymph nodes, of whom four had only SLN metastasis (two cases of ITC, one case of micrometastasis and one case of macrometastasis). We found a macroscopic deposit of cancer cells in the parametrial lymph node of one patient (3.1%). There was a positive statistical correlation between the incidence of parametrial lymph node involvement and the metastatic pelvic lymph nodes (p = 0.038). When performed per patient, the sensitivity, negative predictive value and accuracy of parametrial lymph node involvement in predicting pelvic lymph node metastasis were 16.7%, 83.3% and 83.9%, respectively. Ultrastaging of parametrial tissue did not identify any occult continuous or discontinuous parametrial metastasis. In conclusion, the incidence of lymph node parametrial involvement in a retrospective series of early-stage cervical cancer was 3.1% of all included patients. Lymph node involvement of the parametrium was associated with lymph node metastasis. The sensitivity of parametrial lymph node involvement to predict pelvic lymph node metastasis was low. The lack of parametrial involvement revealed by parametrial ultrastaging could be related to the number of patients with tumors with a pathologic diameter < 2 cm (54.8%). Further prospective studies are needed to analyze the role of parametrial ultrastaging in early-stage cervical cancer and to assess whether it can be considered the “sentinel” of the sentinel lymph node.

This study investigated perioperative and mid-term clinical outcomes after laparoscopic sacrocolpopexy (LSCP) with light titanium-coated polypropylene (TCP) mesh in a large group of patients affected by International Continence Society stage II–IV pelvic organ prolapse (POP). This multicenter retrospective study included 217 patients treated with LSCP using TCP mesh. We aimed to (1) analyze the intra- and postoperative complication rates according to the ICS/IUGA Complication Classification Code guidelines, (2) evaluate the anatomical results and (3) assess postoperative patient satisfaction with the Patient Global Impression Improvement questionnaire. Nonparametric Wilcoxon signed-rank tests, χ2 test and Fisher’s exact test were used where appropriate. The intraoperative complications were two (0.9%) cases of hemorrhage, two (0.9%) cases of incidental cystotomy and four (1.8%) cases of incidental colpotomy. During the postoperative follow-up, we recorded mesh exposure in 3 (1.4%) out of 217 patients. These 3 patients were from a group of 22 women who underwent vaginal opening during surgery, while in the remaining 195 patients without incidental colpotomy, no mesh exposure was observed (13.6% vs. 0.0%, p

Liu and colleagues performed a retrospective study to validate a computed tomography (CT) scan-based radiomic model to detect lymph node metastasis in cervical cancer. The proposed model incorporating the arterial and venous phase CT-scan features represented a non-invasive method exhibiting high sensitivity in the prediction of lymph node metastasis. It is well established that lymph node metastasis is one of the most significant prognostic factors in cervical cancer. For this reason, management of cervical cancer is strictly related to lymph node status, with international guidelines recommending definitive chemo-radiation in case of metastatic lymph node. More and more evidence supports the use of sentinel lymph node in early-stage cervical cancer but its frozen section analysis may result in false negative results; in locally-advanced stages staging para-aortic lymphadenectomy is proposed by many Authors to tailor chemoradiotherapy treatment, with potential intra-and post-operative related complications. The use of a validated radiomic model able to predict lymph node metastases in radiologically normal lymph nodes may represent an essential tool to possibly spare lympadenectomy related morbidity.