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1.
Gynecol Oncol ; 182: 148-155, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38266401

RESUMO

OBJECTIVE: The prognostic significance of positive peritoneal cytology in endometrial cancer has long been debated. In 2009, the Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) removed cytology as a staging criterion from the endometrial cancer staging system. However, there is still evidence that positive peritoneal cytology may decrease survival among patients with endometrial cancer. The aim of this study was to determine the prognostic significance of positive peritoneal cytology among the different molecular subgroups. METHODS: This study included patients with endometrial cancer who underwent primary surgical treatment between 2004 and 2015 at the Bern University Hospital, Switzerland, with molecular classification of the primary tumor and peritoneal cytology performed. RESULTS: A total, 250 patients with endometrial cancer were enrolled. Peritoneal cytology was assessed in 206 patients, of whom 24% were positive: 25% of the POLEmut, 16% of the MMRd, 41% of the p53abn, and 24% of the NSMP cases. The mean follow-up was 128.7 months. Presence of positive peritoneal cytology was associated with significantly decreased mean recurrence-free and overall survival in patients with p53abn (p = .003 and p = .001) and NSMP (p = .020 and p = .049) endometrial cancer. In multivariable Cox regression analysis, positive peritoneal cytology remained an independent predictor of recurrence (p = .033) and death (p = .008) in p53abn endometrial cancer patients. CONCLUSION: Positive peritoneal cytology is associated with worse oncologic outcomes in NSMP and p53abn endometrial cancer and remains an independent predictor of recurrence and death in patients with p53abn endometrial cancer.


Assuntos
Neoplasias do Endométrio , Feminino , Humanos , Neoplasias do Endométrio/patologia , Prognóstico , Peritônio/patologia , Suíça , Estudos Retrospectivos , Estadiamento de Neoplasias
2.
Int J Gynecol Cancer ; 33(10): 1595-1601, 2023 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-37567597

RESUMO

OBJECTIVE: To investigate whether a change in the Fagotti score (ΔFagotti) following neoadjuvant chemotherapy is predictive of resection to no residual disease (R0) and survival in women diagnosed with ovarian cancer. METHODS: Women treated with neoadjuvant chemotherapy for newly diagnosed ovarian cancer between January 2012 and June 2021 at the Bern University Hospital were included in this retrospective cohort study. Fagotti scores before and after neoadjuvant chemotherapy treatment were assessed for a potential association with resection status at interval debulking surgery defined as no residual disease (R0), macroscopic residual disease with a diameter of 0.1-1 cm (R1) or >1 cm (R2), and survival. RESULTS: During the study period, 130 patients received neoadjuvant chemotherapy, mainly in response to advanced ovarian cancer International Federation of Gynecology and Obstetrics (FIGO) stages IIIC (68.5%) or IV (20.8%). 91 patients (70%) experienced a relapse and 81 (62%) died due to their disease. Median overall survival was 40 months (95% CI 30.6 to 49.4). Fagotti scores dropped from a mean of 7.8 (95% CI 7.14 to 8.42) at diagnosis to 3.9 (95% CI 3.34 to 4.46, p<0.001) after neoadjuvant therapy. This decrease was associated with resection status during interval debulking surgery (mean ΔFagotti -4.9 in R0, -2.2 in R1, -0.6 in R2, p<0.001). Women whose Fagotti score declined more than 2 points after neoadjuvant chemotherapy (n=51/88, 58%) survived significantly longer (median overall survival of 42 vs 32 months, p=0.048). CONCLUSION: Fagotti scores and ΔFagotti scores are associated with complete cytoreduction at interval debulking surgery and longer overall survival in women treated with neoadjuvant chemotherapy for ovarian cancer. These markers are valuable for individualized patient treatment planning and should always be performed after neoadjuvant therapy.


Assuntos
Terapia Neoadjuvante , Neoplasias Ovarianas , Humanos , Feminino , Estudos Retrospectivos , Estadiamento de Neoplasias , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/patologia , Carcinoma Epitelial do Ovário/cirurgia , Procedimentos Cirúrgicos de Citorredução , Quimioterapia Adjuvante
3.
Int J Gynecol Cancer ; 33(11): 1702-1707, 2023 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-37666529

RESUMO

OBJECTIVE: Lymphovascular space invasion (LVSI) is a known prognostic factor for oncological outcome in endometrial cancer patients. However, little is known about the prognostic value of LVSI among the different molecular subgroups. The aim of this study was to determine the prognostic dependence of LVSI from the molecular signature. METHODS: This study included endometrial cancer patients who underwent primary surgical treatment between February 2004 and February 2016 at the Karolinska University Hospital, Sweden and the Bern University Hospital, Switzerland (KImBer cohort). All cases had complete molecular analysis performed on the primary tumor according to the WHO Classification of Tumors, 5th edition. LVSI was reviewed by reference pathologists for all pathology slides. RESULTS: A total of 589 endometrial cancer patients were included in this study, consisting of 40 POLEmut (polymerase epsilon ultramutated), 198 MMRd (mismatch repair deficient), 83 p53abn (p53 abnormal), and 268 NSMP (non-specific molecular profile) cases. Altogether, 17% of tumors showed LVSI: 25% of the POLEmut, 19% of the MMRd, 30% of the p53abn, and 10% of the NSMP cases. There was a significant correlation of LVSI with lymph node metastasis in the entire study cohort (p<0.001), remaining significant in the MMRd (p=0.020), p53abn (p<0.001), and NSMP (p<0.001) subgroups. Mean follow-up was 89 months (95% CI 86 to 93). The presence of LVSI significantly decreased recurrence-free survival among patients with MMRd, p53abn, and NSMP endometrial cancer, and overall survival in patients with p53abn and NSMP tumors. In patients with NSMP endometrial cancer, evidence of substantial LVSI remained a significant independent predictor of recurrence in multivariable Cox regression analysis including tumor stage and grade (HR 7.5, 95% CI 2.2 to 25.5, p=o.001). CONCLUSION: The presence of LVSI was associated with recurrence in each subgroup of patients with MMRd, p53abn, and NSMP endometrial cancer, and LVSI remained an independent predictor of recurrence in NSMP endometrial cancer patients.


Assuntos
Neoplasias do Endométrio , Feminino , Humanos , Prognóstico , Neoplasias do Endométrio/patologia , Metástase Linfática , Suécia , Estudos Retrospectivos
4.
Ann Surg Oncol ; 29(13): 8320-8333, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36057902

RESUMO

BACKGROUND: Minimally invasive surgery is the standard approach in early-stage endometrial cancer according to evidence showing no compromise in oncological outcomes, but lower morbidity compared with open surgery. However, there are limited data available on the oncological safety of the use of intrauterine manipulators in endometrial cancer. PATIENTS AND METHODS: This prospective multicenter study included patients with endometrial cancer undergoing laparoscopic staging surgery with the use of an intrauterine manipulator. We obtained three different sets of peritoneal washings: at the beginning of the surgical procedure, after the insertion of the intrauterine manipulator, and after the closure of the vaginal vault. The rate of positive peritoneal cytology conversion and its association with oncological outcomes was assessed. RESULTS: A total of 124 patients were included. Peritoneal cytology was negative in 98 (group 1) and positive in 26 (group 2) patients. In group 2, 16 patients presented with positive cytology at the beginning of the surgery (group 2a) and 10 patients had positive cytology conversion during the procedure (group 2b). Recurrence rate was significantly different among the study groups, amounting to 9.2%, 25.0%, and 60.0% for groups 1, 2a, and 2b, respectively (p < 0.001). Group 1 showed the best recurrence-free and overall survival, followed by group 2a, while patients in group 2b had the worst oncological outcomes (p = 0.002 and p = 0.053, respectively). Peritoneal cytology was an independent predictor of recurrence and death on multivariable analysis. CONCLUSION: A total of 8.1% of patients with endometrial cancer undergoing minimally invasive surgery with intrauterine manipulation showed positive peritoneal cytology conversion associated with significantly worse oncological outcome.


Assuntos
Neoplasias do Endométrio , Laparoscopia , Feminino , Humanos , Estudos Prospectivos , Neoplasias do Endométrio/patologia , Peritônio/patologia , Procedimentos Cirúrgicos Minimamente Invasivos , Laparoscopia/métodos , Estadiamento de Neoplasias , Estudos Retrospectivos
5.
Gynecol Oncol ; 162(2): 394-400, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34127276

RESUMO

INTRODUCTION: In 2021, a joint ESGO/ESTRO/ESP committee updated their evidence-based guidelines for endometrial cancer, recommending a new risk grouping incorporating both clinicopathologic and molecular parameters. We applied the new risk grouping and compared the results to those of the prior 2016 clinicopathologic system. MATERIALS AND METHODS: We classified molecularly a cohort of 604 women diagnosed with endometrial cancer using immunohistochemistry for TP53 and MMR proteins on a tissue microarray, as well as Sanger sequencing for POLE mutations. These results, combined with clinicopathologic data, allowed the patients to be risk grouped using both the new 2021 molecular/clinicopathologic parameters and the prior 2016 clinicopathologic system. RESULTS: The application of the 2021 molecular markers shows Kaplan-Meier curves with a significant difference between the groups for all survival. Molecular classification under the 2021 guidelines revealed a total of 39 patients (39/594, 7%) with a change in risk group in relation to the 2016 classification system: the shift was alone due to either P53abn or POLEmut molecular marker. In order to ensure correct 2021 molecular risk classification, not all patients with endometrial cancer need a molecular diagnostic: 433 (72.9%) cases would need to be analyzed by TP53 IHC, only 46 (7.7%) by MMR IHC and 286 (48.1%) POLE sequencing reactions. CONCLUSION: Application of the 2021 molecular risk groups is feasible and shows significant differences in survival. IHC for TP53 and MMR and applying POLE sequencing is only needed in selected cases and leads to shifting risk groups both upward and downward for a sizeable number of patients. It is possible to significantly reduce the number of analyses required to implement the classification if resources are limited.


Assuntos
Biomarcadores Tumorais/genética , Reparo de Erro de Pareamento de DNA , Neoplasias do Endométrio/mortalidade , Recidiva Local de Neoplasia/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , DNA Polimerase II/genética , Intervalo Livre de Doença , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/terapia , Medicina Baseada em Evidências/normas , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Oncologia/normas , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/prevenção & controle , Proteínas de Ligação a Poli-ADP-Ribose/genética , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Medição de Risco/métodos , Medição de Risco/normas , Fatores de Risco , Proteína Supressora de Tumor p53/genética
6.
Acta Obstet Gynecol Scand ; 99(5): 591-597, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31943126

RESUMO

INTRODUCTION: Endometriosis is a common health problem, affecting 10% of women of reproductive age. Laparoscopic surgery is proven to relieve pain and to improve fertility in women with endometriosis. However, identifying peritoneal endometriosis lesions may be difficult due to their polymorphic aspects. Endometriosis lesions harbor a high degree of neovascularization. The visualization of tissue perfusion by the additional use of near infrared fluorescence imaging with indocyanine green (ICG) may improve the detection of endometriosis lesions. MATERIAL AND METHODS: In a single-center, prospective, single-arm pilot study, patients undergoing laparoscopic surgery for suspected endometriosis and/or infertility were recruited. All patients first had white light imaging with systematical documentation of all suspicious areas. ICG was then administered intravenously at .3 mg/kg bodyweight and the near infrared imaging was activated and an identical documentation of suspected lesions was performed again. After removal, the specimen were sent to pathology. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov NCT03850158. RESULTS: In total, 173 suspected lesions were identified and excised, of which 150 had histologically proven endometriosis. Of the total number, 166 suspected lesions were detected using white-light and 32 with ICG. Among the 32 suspected lesions found with ICG, 22 were confirmed to be endometriosis. Seven additional lesions were identified with ICG alone, of which only one was histologically proven endometriosis. Positive predictive values were 89.8%, 68.8% and 86.7% for white-light laparoscopy alone, near-infrared (NIR)-ICG visualization alone, and the combination of white-light and NIR-ICG, respectively. ICG exposure time, previous abdominal surgery and rARSM stage showed a statistically significant impact on the ICG detection rate. In seven patients, ICG was used for the resection of deep infiltrating nodules from the rectum. In these cases, NIR fluorescence imaging with ICG was useful to define the borders between an endometriotic nodule and healthy tissue. CONCLUSIONS: The diagnostic value of NIR-ICG imaging in identifying endometriosis appears to be minimal. ICG exposure time over 20 minutes, no previous abdominal surgery and low rASRM stages have a significant positive effect on the ICG detection rate. NIR fluorescence imaging with ICG was helpful in the resection of deep infiltrating nodules in providing a better visualization of endometriosis.


Assuntos
Corantes/administração & dosagem , Endometriose/diagnóstico por imagem , Endometriose/patologia , Verde de Indocianina/administração & dosagem , Adulto , Endometriose/cirurgia , Feminino , Humanos , Laparoscopia/métodos , Pessoa de Meia-Idade , Imagem Óptica/métodos , Projetos Piloto , Estudos Prospectivos , Espectroscopia de Luz Próxima ao Infravermelho
7.
Ther Umsch ; 77(4): 164-170, 2020.
Artigo em Alemão | MEDLINE | ID: mdl-32772692

RESUMO

Management of Pelvic Inflammatory Disease Abstract. Pelvic inflammatory disease (PID) is a common medical problem, but the diagnosis of PID can be challenging because the clinical manifestations may mimic those of other pelvic and abdominal processes. As PID might cause late complications such as infertility or chronic pelvic pain, it is of prime importance that the diagnosis of PID is made promptly to assure the early onset of an adequate antibiotic therapy. Where uncomplicated PID usually has a favorable course, complicated forms with tubo-ovarian abscess generally require surgical exploration.


Assuntos
Doença Inflamatória Pélvica/diagnóstico , Doença Inflamatória Pélvica/tratamento farmacológico , Doença Inflamatória Pélvica/terapia , Antibacterianos/uso terapêutico , Feminino , Humanos , Dor Pélvica/diagnóstico
11.
J Minim Invasive Gynecol ; 24(7): 1079-1080, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28400220

RESUMO

STUDY OBJECTIVE: To show a new technique of using single-incision laparoscopic surgery (SILS) equipment in vaginal surgery to create a "pneumovagina." DESIGN: Explanatory video demonstrating the technique and intraoperative findings. SETTING: University hospital. PATIENT: The 68-year-old patient was referred with a vaginal mesh erosion that resulted in abscess formation at the vaginal apex. The patient was symptomatic with an increasingly foul-smelling vaginal discharge for about 1 year. She had a laparoscopic sacrocolpopexy in a remote hospital 22 months before the current operation and had a total abdominal hysterectomy 15 years ago. The, patient's history was uneventful without dyspareunia, incontinence or voiding difficulties, and she was otherwise content with the sacrocolpopexy result. The local institutional review board granted exemption for this publication. INTERVENTION: Frequently, pelvic organ prolapse can only be effectively treated if the surgical procedure comprises support of the central compartment. Laparoscopic sacrocolpopexy shows superior outcomes for this indication, with success rates of up to 96%. However, a rare side effect of laparoscopic sacrocolpopexy is mesh erosion, occurring in up to 2.4% [1]. These erosions are usually treated laparoscopically [2]. In this video we show an alternative route for excision of a symptomatic exposed mesh by using a transvaginal approach: The SILS trocar is used vaginally for abscess irrigation and mesh excision with minimally invasive instruments. MEASUREMENTS AND MAIN RESULTS: For treatment of the abscess and removal of the exposed mesh, the SILS trocar was placed vaginally, and laparoscopic instruments were used. The abscess was incised, cleansed and irrigated, debrided, and the mesh excised. Because no mesh material was exposed after excision, the vagina was not closed to avoid creating a cavity with the risk of promoting reabscess formation, and secondary wound healing was anticipated. Laparoscopy was used to confirm that no intra-abdominal lesion coexisted or occurred. There were no signs of further infection of the residual mesh beyond the area exposed in the vagina. The patient's only symptom was foul-smelling discharge, but no back pain or signs of systemic inflammation were found. Knowing that foreign body (mesh) infection usually needs to be treated by complete mesh removal, we did not have any clues of distant mesh infection and counseled the patient that if reinfection occurred a second surgery might be necessary. Nevertheless, we treated this patient with abscess drainage and removal of large parts of the mesh. Thus, the operation was not extended to a complete mesh excision to prevent major surgery and the risk of recurrent prolapse. Particularly, the area of the mesh excision was inspected with the rendezvous technique (light source vaginally, laparoscopic pelvic view with laparoscopic light source switched off) to identify the area of mesh excision from the intra-abdominal area. Sigmoid and rectum were distant to this area, suggesting that no bowel lesion occurred. No complications occurred in the postoperative course. In the follow-up visit 6 months postoperatively the patient was asymptomatic, and the vaginal examination was uneventful with no recurrent erosion. Although improved oversight and richness of detail achieved by the vaginal SILS method is helpful in patients like our case with a suspended vaginal vault, its costs need to be balanced against conventional vaginal approaches (e.g., use of a Lonestar retractor). CONCLUSION: The SILS trocar and laparoscope used (SILS Port; Covidien, New Haven, CT) vaginally provide a magnificent and detailed view to allow for exact preparation by means of microinvasive instruments in vaginal surgery, even more in patients with a suspended vaginal vault where access to the apex can be tricky. The "pneumovagina" created by CO2 insufflation further helps to expose the vaginal apex. The rendezvous technique can additionally be used to identify intra-abominal lesions.


Assuntos
Laparoscopia/métodos , Telas Cirúrgicas/efeitos adversos , Vagina/cirurgia , Falha de Equipamento , Feminino , Humanos , Pessoa de Meia-Idade
12.
Ann Surg Oncol ; 23(7): 2206-11, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26790667

RESUMO

BACKGROUND: In endometrial cancer (EMCA), indocyanine green (ICG) sentinel lymph node (SLN) mapping has been reported, mainly in conjunction with robotic surgery. OBJECTIVE: We aimed to evaluate detection rates, sensitivity, and false negative (FN) rate of laparoscopic ICG SLN mapping in EMCA, and to evaluate differences in surgical outcomes between patients subjected to SLN biopsy only versus lymphadenectomy. METHODS: A retrospective analysis of EMCA patients undergoing ICG SLN mapping ± pelvic (PLND) and/or para-aortic lymphadenectomy (PALND) was performed. Detection rates were calculated for the entire cohort. Sensitivity and FN rates were calculated for patients undergoing lymphadenectomy after SLN mapping, and surgical outcome was compared among patients undergoing SLN mapping only versus lymphadenectomy. RESULTS: Of 75 patients, 33 underwent SLN mapping and 42 underwent SLN mapping followed by PLND/PALND. Overall and bilateral detection rates were 96 % (72/75) and 88 % (66/75), respectively, and the median number of removed SLNs, pelvic non-SLNs (NSLN) and para-aortic NSLNs was 3, 27, and 19, respectively. With a FN rate of 8.3 %, only one patient had bilateral FN SLNs and a metastatic para-aortal NSLN. Estimated blood loss (EBL) and operative (OR) time were significantly lower in patients undergoing SLN mapping only. No differences in complication rates between patients undergoing SLN mapping only and patients undergoing lymphadenectomy were recorded. CONCLUSIONS: Laparoscopic ICG SLN mapping has excellent overall and bilateral detection rates and a low FN rate. Compared with lymphadenectomy, SLN biopsy is associated with significantly lower EBL and shorter OR time.


Assuntos
Adenocarcinoma de Células Claras/patologia , Carcinossarcoma/patologia , Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/patologia , Verde de Indocianina , Laparoscopia/métodos , Linfonodo Sentinela/patologia , Adenocarcinoma de Células Claras/diagnóstico por imagem , Adenocarcinoma de Células Claras/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinossarcoma/diagnóstico por imagem , Carcinossarcoma/cirurgia , Corantes , Cistadenocarcinoma Seroso/diagnóstico por imagem , Cistadenocarcinoma Seroso/cirurgia , Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/cirurgia , Feminino , Seguimentos , Humanos , Excisão de Linfonodo , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Estudos Retrospectivos , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo Sentinela
14.
Cancers (Basel) ; 16(3)2024 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-38339422

RESUMO

Lynch syndrome is an inherited tumor syndrome caused by a pathogenic germline variant in DNA mismatch repair genes. As the leading cause of hereditary endometrial cancer, international guidelines recommend universal screening in women with endometrial cancer. However, testing for Lynch syndrome is not yet well established in clinical practice. The aim of this study was to evaluate adherence to our Lynch syndrome screening algorithm. A retrospective, single-center cohort study was conducted of all endometrial cancer patients undergoing surgical treatment at the Bern University Hospital, Switzerland, between 2017 and 2022. Adherence to immunohistochemical analysis of mismatch repair status, and, if indicated, to MLH1 promoter hypermethylation and to genetic counseling and testing was assessed. Of all 331 endometrial cancer patients, 102 (30.8%) were mismatch repair-deficient and 3 (0.9%) patients were diagnosed with Lynch syndrome. Overall screening adherence was 78.2%, with a notable improvement over the six years from 61.4% to 90.6%. A major reason for non-adherence was lack of provider recommendation for testing, with advanced patient age as a potential patient risk factor. Simplification of the algorithm through standardized reflex screening was recommended to provide optimal medical care for those affected and to allow for cascading testing of at-risk relatives.

15.
Cancers (Basel) ; 16(1)2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38201495

RESUMO

BACKGROUND: SLN mapping has emerged as a standard of care in endometrial cancer due to its high sensitivity and significant reduction in morbidity. Although lymphovascular space invasion (LVSI) is a known risk factor for lymph node metastasis and recurrence, evidence on the reliability of SLN mapping in LVSI-positive patients is scarce. The aim of this study was to determine the impact of LVSI on the diagnostic performance of SLN mapping. METHODS: This retrospective cohort study included patients with endometrial cancer who underwent primary surgical treatment at the Bern University Hospital, Switzerland, between 2012 and 2022. RESULTS: LVSI was present in 22% of patients and was significantly associated with lymph node metastasis (p < 0.001) and recurrence (p < 0.001). In node-negative patients with only SLN mapping performed, LVSI was an independent predictor of recurrence during multivariable Cox regression analysis (p = 0.036). The negative predictive value of SLN mapping was 91.5% and was significantly lower in tumors with LVSI (75.0%) compared to LVSI-negative tumors (95.6%, p = 0.004). CONCLUSION: The presence of LVSI was significantly associated with worse oncological outcomes. LVSI was an independent predictor of recurrence in node-negative patients with only SLN mapping performed. Furthermore, the negative predictive value of SLN mapping was significantly lower in LVSI-positive tumors.

16.
Front Med (Lausanne) ; 10: 1110529, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37035329

RESUMO

Introduction: Over the years, the molecular classification of endometrial carcinoma has evolved significantly. Both POLEmut and MMRdef cases share tumor biological similarities like high tumor mutational burden and induce strong lymphatic reactions. While therefore use case scenarios for pretesting with tumor-infiltrating lymphocytes to replace molecular analysis did not show promising results, such testing may be warranted in cases where an inverse prediction, such as that of POLEwt, is being considered. For that reason we used a spatial digital pathology method to quantitatively examine CD3+ and CD8+ immune infiltrates in comparison to conventional histopathological parameters, prognostics and as potential pretest before molecular analysis. Methods: We applied a four-color multiplex immunofluorescence assay for pan-cytokeratin, CD3, CD8, and DAPI on 252 endometrial carcinomas as testing and compared it to further 213 cases as validation cohort from a similar multiplexing assay. We quantitatively assessed immune infiltrates in microscopic distances within the carcinoma, in a close distance of 50 microns, and in more distant areas. Results: Regarding prognostics, high CD3+ and CD8+ densities in intra-tumoral and close subregions pointed toward a favorable outcome. However, TCGA subtyping outperforms prognostication of CD3 and CD8 based parameters. Different CD3+ and CD8+ densities were significantly associated with the TCGA subgroups, but not consistently for histopathological parameter. In the testing cohort, intra-tumoral densities of less than 50 intra-tumoral CD8+ cells/mm2 were the most suitable parameter to assume a POLEwt, irrespective of an MMRdef, NSMP or p53abn background. An application to the validation cohort corroborates these findings with an overall sensitivity of 95.5%. Discussion: Molecular confirmation of POLEmut cases remains the gold standard. Even if CD3+ and CD8+ cell densities appeared less prognostic than TCGA, low intra-tumoral CD8+ values predict a POLE wild-type at substantial percentage rates, but not vice versa. This inverse correlation might be useful to increase pretest probabilities in consecutive POLE testing. Molecular subtyping is currently not conducted in one-third of cases deemed low-risk based on conventional clinical and histopathological parameters. However, this percentage could potentially be increased to two-thirds by excluding sequencing of predicted POLE wild-type cases, which could be determined through precise quantification of intra-tumoral CD8+ cells.

17.
Cancers (Basel) ; 15(7)2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-37046712

RESUMO

The aim of this study was to assess the impact of low-volume metastasis (LVM) on disease-free survival (DFS) in women with apparent early-stage endometrial cancer (EC) who underwent sentinel lymph node (SLN) mapping. Patients with pre-operative early-stage EC were retrospectively collected from an international collaboration including 13 referring institutions. A total of 1428 patients were included in this analysis. One hundred and eighty-six patients (13%) had lymph node involvement. Fifty-nine percent of positive SLN exhibited micrometastases, 26.9% micrometastases, and 14% isolated tumor cells. Seventeen patients with positive lymph nodes did not receive any adjuvant therapy. At a median follow-up of 33.3 months, the disease had recurred in 114 women (8%). Patients with micrometastases in the lymph nodes had a worse prognosis of disease-free survival compared to patients with negative nodes or LVM. The rate of recurrence was significantly higher for women with micrometastases than those with low-volume metastases (HR = 2.61; p = 0.01). The administration of adjuvant treatment in patients with LVM, without uterine risk factors, remains a matter of debate and requires further evaluation.

18.
J Clin Med ; 11(5)2022 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-35268248

RESUMO

Higher cesarean section rates and better ultrasound diagnostics have led to a more frequent diagnosis of isthmocele, a cesarean scar defect. Sometimes, endometriosis is found in the isthmocele, but simultaneous extrauterine endometriosis and endometriosis in the isthmocele have not yet been reported. Additionally, the surgical technique to repair the isthmocele is the subject of ongoing controversy. The aim of this study is to analyze a possible correlation between uterine scar (isthmocele) endometriosis and extrauterine endometriosis and to investigate the outcome of laparoscopic isthmocele resection in the rendezvous technique. In this single-center retrospective study, we included 83 women of reproductive age with symptomatic isthmocele undergoing laparoscopic isthmocele repair in rendezvous technique from 2004 to 2020 at the University of Bern. We collected data on patient and surgical characteristics as well as on postoperative outcomes (symptoms, further pregnancy, and pregnancy outcomes) retrospectively. We analyzed and compared these data for patients with and without endometriosis. Endometriosis was diagnosed during surgery in 22 out of 83 operated patients (26.5%). Diagnosis of isthmocele endometriosis (n = 9, 11%) was significantly higher in patients with extrauterine endometriosis (n = 6, p = 0.004). While the duration of surgery was significantly longer for patients with endometriosis (p = 0.006), the groups did not differ with regard to blood loss or complications. In addition, both groups showed similar indications for isthmocele repair (infertility, abnormal uterine bleeding, or dysmenorrhea). Surgery significantly improved abnormal uterine bleeding (χ2 p < 0.001), dysmenorrhea (χ2, p = 0.03), and infertility (χ2, p < 0.001). Regardless of the presence of endometriosis, 25 of 40 (63%) infertile patients became pregnant after surgery. In one out of eight pregnancies, however, we observed scar complications during pregnancy such as uterine scar pregnancy (n = 3), uterine scar dehiscence (n = 3), and placenta previa (n = 1). Endometriosis is a non-negligible intraoperative finding in patients with symptomatic isthmocele. The laparoscopic approach in the rendezvous technique is safe and effective. Therefore, this method should be recommended, especially in women with secondary infertility, and preoperatively simultaneous endometriosis resection should be discussed with the patient. In follow-up, postoperative pregnancies have to be monitored with care.

19.
Virchows Arch ; 481(3): 421-432, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35854139

RESUMO

Sentinel lymph nodes are widely accepted in the treatment of endometrial carcinoma. Whereas surgical aspects are well studied, the pathological work-up in terms of grossing, frozen section, and the so-called ultra-staging is still a matter of debate. This results in conflicting national or center-based recommendations. In a series of consecutive 833 sentinel lymph nodes from 206 patients in endometrial carcinomas, we compared three different grossing techniques and the use of frozen section in terms of anatomy, detection rates, and survival. In total, 42 macro-metastases, 6 micro-metastases, and 25 nodes with isolated tumor cells were found. Lymph nodes affected at least with micro-metastasis were about 0.5cm enlarged. Detection rates in lamellation technique increased with a step of 5.9% to 8.3% in comparison to bi-valved or complete embedding. The lamellation technique presented with a slight beneficial prognosis in pN0 subgroup (OS, p=0.05), which besides size effects might be attributed to trimming loss. In frozen section, this effect was less pronounced than expected (OS, p=0.56). Ultra-staging only revealed additional micro-metastases and isolated tumor cells. Exclusively, macro-metastases showed poor survival (p<0.001). In multivariate analysis, T-stage, subtype, and lympho-vascular invasion status outperformed this staging parameter significantly. Grossing of sentinel lymph nodes is the most essential step with evidence to prefer lamellation in 2 mm steps. Step sectioning should consider widely spaced protocols to exclude macro-metastases. Frozen sections might add value to the intra-operative assessment of endometrial carcinoma in selected cases. The excellent biological behavior of cases with isolated tumor cells might question the routine application of pan-cytokeratin as ultra-staging method.


Assuntos
Carcinoma , Neoplasias do Endométrio , Linfonodo Sentinela , Carcinoma/patologia , Neoplasias do Endométrio/patologia , Feminino , Secções Congeladas , Humanos , Queratinas , Excisão de Linfonodo , Metástase Linfática , Estadiamento de Neoplasias , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela
20.
J Clin Med ; 10(20)2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34682850

RESUMO

(1) Background: The aim of this study was to evaluate the impact of endometriosis on postoperative pain following laparoscopic hysterectomy; (2) Methods: A total of 214 women who underwent a laparoscopic hysterectomy between January 2013 and October 2017 were divided into four subgroups as follows: (1) endometriosis with chronic pain before the surgery (n = 57); (2) pain-free endometriosis (n = 50); (3) pain before the surgery without endometriosis (n = 40); (4) absence of both preoperative pain and endometriosis (n = 67). Postoperative pain was compared by using Visual Analog Scale (VAS) scores and by tracking the use of painkillers during the day of surgery and the first two postoperative days; (3) Results: Women with chronic pain before the surgery reported higher VAS scores during the first postoperative days, while the use of analgesics was similar across the groups. There was no difference in the postoperative pain when comparing endometriosis patients to non-endometriosis patients; (4) Conclusions: Women with chronic pelvic pain demonstrated increased postoperative pain after laparoscopic hysterectomy, which was independent of the presence or severity of endometriosis. The increased VAS scores did not, however, translate into equally greater use of painkillers, possibly due to the standardised protocols of analgesia in the immediate postoperative period. These findings support the need for careful postsurgical pain management in patients with pain identified as an indication for hysterectomy, independent of the extent of the surgery or underlying diagnosis.

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