Superparamagnetic iron oxide (SPIO) for sentinel lymph node detection in vulvar cancer.

OBJECTIVES: Sentinel lymph node (SLN) detection with superparamagnetic iron oxide (SPIO) nanoparticles has been widely studied and standardized for breast and prostate cancer, but there is scarce evidence concerning its use in vulvar cancer. The objective of this study was to compare SLN detection using a SPIO tracer injected at the time of the surgery detected by a magnetometer, with the standard procedure of using a technetium 99 radioisotope (Tc99) detected by a gamma probe, in patients with vulvar cancer. METHODS: The SPIO vulvar cancer study was a single-center prospective interventional non-inferiority study of SPIO compared to Tc99, conducted between 2016 and 2021 in patients who met the GROINSS-V study inclusion criteria for selective sentinel lymph node dissection in vulvar cancer. RESULTS: We included 18 patients and a total of 41 SLNs. The level of agreement between tracers was 92.7% (80.6%-97.4%), corresponding to 38 out of 41 SLNs, which confirms the non-inferiority of SPIO compared to Tc99. The SLN detection rate per groin was 96.3 (81.7%-99.3) using Tc99 and 100% (87.5%-100%) using SPIO. Both tracers had a detection rate of 100% for positive lymph nodes. CONCLUSIONS: The use of SPIO as a tracer for detecting SLNs in patients with vulvar cancer has shown to be non-inferior to that of the standard radiotracer, with the advantages of not requiring nuclear medicine and being able to inject it at the time of surgery after induction of anesthesia.

Aortic sentinel node detection in endometrial cancer: 6 year prospective study.

OBJECTIVE: The aim of this study was to describe our final results using dual cervical and fundal indocyanine green injection for the detection of sentinel lymph nodes (SLNs) in endometrial cancer along parametrial and infundibular drainage pathways. METHODS: We conducted a prospective observational study between 26 June 2014 and 31 December 2020 enrolling 332 patients that underwent laparoscopic surgery for endometrial cancer at our hospital. In all cases, we performed SLN biopsy with dual cervical and fundal indocyanine green injection identifying pelvic and aortic SLNs. All SLNs were processed with an ultrastaging technique. A total of 172 patients also underwent total pelvic and para-aortic lymphadenectomy. RESULTS: The detection rates were as follows: 94.0% overall for SLNs; 91.3% overall for pelvic SLNs; 70.5% for bilateral SLNs; 68.1% for para-aortic SLNs, and 3.0% for isolated paraaortic SLNs. We found lymph node involvement in 56 (16.9%) cases, macrometastasis in 22, micrometastasis in 12 and isolated tumor cells in 22. Fourteen patients had isolated aortic nodal involvement, representing 25% of the positive cases. There was one false negative (SLN biopsy negative but lymphadenectomy positive). Applying the SLN algorithm, the sensitivity of the dual injection technique for SLN detection was 98.3% (95% CI 91-99.7), specificity 100% (95% CI 98.5-100), negative predictive value 99.6% (95% CI 97.8-99.9), and positive predictive value 100% (95% CI 93.8-100). Overall survival at 60 months was 91.35%, with no differences between patients with negative nodes, isolated tumor cells and treated nodal micrometastasis. CONCLUSIONS: Dual sentinel node injection is a feasible technique that achieves adequate detection rates. Additionally, this technique allows a high rate of aortic detection, identifying a non-negligible percentage of isolated aortic metastases. Aortic metastases in endometrial cancer account for as many as a quarter of the positive cases and should be considered, especially in high-risk patients.

Transperitoneal vs extraperitoneal approach for aortic sentinel node detection in endometrial cancer.

BACKGROUND: Although the sentinel lymph node technique in endometrial cancer is currently replacing pelvic and aortic lymphadenectomy for the evaluation of lymph node status in endometrial cancer, its performance is not yet standardized. OBJECTIVE: This study aimed to describe the detection rates and locations of aortic sentinel lymph node detection after dual cervical and fundal indocyanine green injection in patients with endometrial cancer, using the transperitoneal and extraperitoneal approaches. STUDY DESIGN: Between June 26, 2014 and December 31, 2019, 278 patients underwent laparoscopic surgery for endometrial cancer at our institution. In all cases, we performed sentinel lymph node biopsy with dual cervical and fundal indocyanine green injection, and back-up lymphadenectomy in high-risk cases. A post hoc analysis was performed to evaluate differences between the transperitoneal and extraperitoneal approach to aortic sentinel lymph nodes. RESULTS: The detection rates were as follows: overall detection rate: 93.2% (259/278); pelvic detection rate: 90.3% (251/278); bilateral pelvic detection rate: 68.0% (189/278); aortic detection rate: 66.9% (186/278); and isolated aortic detection rate: 2.88% (8/278). Transperitoneal and extraperitoneal aortic detection rates were similar (65.0% and 69.6%, respectively), with no significant differences (P=.441). Isolated aortic metastases were similar in both groups (2% vs 4.7%, respectively; P=.185). The laterality of aortic sentinel lymph node detection was influenced by the surgical approach (P=.002), but not its location above or below the inferior mesenteric artery (P=.166 and P=.556, respectively). CONCLUSION: The detection rates at the aortic level were similar between the transperitoneal and extraperitoneal approaches, with no impact on subsequent pelvic detection. The transperitoneal approach detected more laterocaval, precaval, and interaortocaval nodes, whereas the extraperitoneal approach detected more preaortic and left lateroaortic nodes.

Maximizing sentinel node detection in endometrial cancer with dual cervical and transcervical fundal indocyanine green injection: 5-year single-center prospective study.

OBJECTIVE: The aim of this study was to describe our latest results using dual cervical and fundal indocyanine green injection for detection of sentinel lymph node (SLN) in endometrial cancer. METHODS: A prospective observational study was conducted between 26 June 2014 and 31 December 2019 with 278 patients that underwent laparoscopic surgery for endometrial cancer at our institution. In all cases, we performed SLN biopsy with dual cervical and fundal indocyanine green injection. All SLNs were processed with an ultrastaging technique. A total of 128 patients also underwent total pelvic and paraaortic lymphadenectomy. RESULTS: The detection rates were as follows: 93.5 % (260/278) overall for SLNs; 90.7 % (252/278) overall for pelvic SLNs; 68.0 % (189/278) for bilateral SLNs; 66.9 % (186/278) for paraaortic SLNs, and 2.9 % (8/278) for isolated paraaortic SLNs. We found macroscopic lymph node metastasis in 26 patients (10.0 %) and microdisease in lymph nodes in another 48 patients, raising the overall rate of lymph node involvement to 16.2 %. There was one false negative (negative SLN biopsy but positive lymphadenectomy). Applying the SLN algorithm, the sensitivity of detection was 97.9 % (95 % CI 89.1-99.6), specificity 100 % (95 % CI 98.2-100), negative predictive value 99.5 % (95 % CI 97.4-99.9), and positive predictive value 100 % (95 % CI 92.4-100). CONCLUSIONS: Dual sentinel node injection is a feasible technique that achieves adequate detection rates. Additionally, this technique allows a high rate of aortic detection, identifying a non-negligible percentage of isolated aortic metastases. Aortic metastases in endometrial cancer are possible and we should not give up actively looking for them.

Impact of restaging lymphadenectomy after sentinel node biopsy on endometrial cancer.

INTRODUCTION: Approximately 10 % of patients with an intra-operative diagnosis of low-risk endometrial cancer (EC) will be upstaged after a definitive histological evaluation of hysterectomy and bilateral adnexectomy samples. This study aimed to explore the results associated with the performance of pelvic and para-aortic lymphadenectomy for restaging after upstaging/upgrading these patients, and to compare those who underwent sentinel lymph node biopsy (SNB) in the first procedure with those who did not. MATERIALS AND METHODS: This retrospective cohort study included 27 patients diagnosed with low-risk EC (based on the criteria of the European Society of Medical Oncology/European Society of Gynecological Oncology/European Society for Radiotherapy and Oncology), who underwent surgical laparoscopic restaging due to upstaging based on the final histological result at Hospital Universitario Donostia from April 2013 to September 2018. Surgical and oncological results were compared between patients who underwent hysterectomy and double adnexectomy without any additional procedures (SNB-; n = 17) and patients who also underwent pelvic&aortic sentinel node biopsysen (SNB+; n = 10). The main outcome evaluated in the study was intra-operative complications. Secondary outcomes were mean operative time, length of hospital stay, number of nodes obtained, progression-free survival (PFS) and overall survival (OS). RESULTS: The median duration of restaging surgery was 240 [interquartile range (IQR) 180-300) min in the SNB(-) group and 300 (IQR 247.5-330) min in the SNB(+) group; this difference was significant (one-sided Student's t-test, p = 0.0295). With regard to intra-operative complications, there were 17.65 % and 40 % in the SNB(-) and SNB(+) groups, respectively, all of which were vascular; this difference was not significant. There were no significant difference in the length of hospital stay, number of pelvic nodes obtained, PFS or OS between the groups. CONCLUSION: Women with EC who require lymph node restaging due to upstaging, and have previously undergone SNB, experience more surgical complications and a longer operative time. The authors advise against performing second restaging surgery in these patients.

Maximizing Sentinel Lymph Node Detection: Aortic Sentinel Lymph Node Detection in Endometrial Cancer.

STUDY OBJECTIVE: To determine the importance of a dual (cervical and fundal) indocyanine green (ICG) injection and thorough dissection for the detection of sentinel lymph nodes (SLNs). DESIGN: Description and step-by-step demonstration of the surgical procedure using video (Canadian Task Force classification III). SETTING: Hospital Universitario Donostia, San Sebastián, Spain. PATIENTS: A 60-year-old woman with a diagnosis of IAG1 endometrial adenocarcinoma (EC). INTERVENTIONS: The patient received a cervical and transcervical fundal ICG injection for para-aortic and pelvic SLN detection in the setting of a research protocol, followed by a total hysterectomy and bilateral salpingo-oophorectomy with a frozen section of the uterus as a standard approach [1]. Institutional Review Board approval was obtained for the research protocol of this study. MEASUREMENTS AND MAIN RESULTS: Dual ICG injection [2] adds the benefit of a cervical injection (that best evaluates the pelvic region [3]) to the fundal injection, with better spread to the lumboaortic pathway [4] so as not to lose the aortic drainage and aortic SLN, whose relevance is still discussed due to its low incidence of metastasis [5]. This search does not add to the associated morbidity but is associated with increased operative time. For pelvic SLN dissection, patience and good training are key; the surgeon must always be on the lookout for uncommon pathways if no SLN is detected in the classical areas. The final histological classification was upgraded to a grade IIIC2 (ie, micrometastasis in the aortic and pelvic-right pararectal space) EC, 3 cm G1 with no lymphovascular invasion. CONCLUSION: Dual ICG injection allows comprehensive mapping not only of pelvic SLNs, but also of para-aortic SLNs, in EC, maximizing the identification of all possible affected areas. Nonetheless, the relevance of its added benefit requires further evaluation.

Sentinel Node Biopsy in Endometrial Cancer With Dual Cervical and Fundal Indocyanine Green Injection.

PURPOSE: The aim of this study was describe a novel sentinel lymph node (SLN) tracer injection procedure featuring dual cervical and fundal indocyanine green (ICG) injection for endometrial cancer and results of SLN biopsy. METHODS: Between June 26, 2014 and October 31, 2016, 111 patients underwent laparoscopic surgery for endometrial cancer at our institution. In all cases, we performed SLN biopsy with dual cervical and fundal ICG injection. All SLNs were processed with an ultrastaging technique. A total of 69 patients also underwent total pelvic and paraaortic lymphadenectomy. RESULTS: The detection rates were as follows: 92.79% (103/111) overall for SLNs; 89.19% (99/111) overall for pelvic SLNs; 61.26% (68/111) for bilateral SLNs; 59.46% (66/111) for paraaortic SLNs, and 4% (4/111) for isolated paraaortic SLNs. We found macroscopic lymph node metastasis in 11 patients (9.9%) and microdisease in lymph nodes in another 10 patients, raising the overall rate of lymph node involvement to 18.92%. There was 1 false-negative (negative SLN biopsy but positive aortic lymphadenectomy) and another positive case in 1 undetected SLN. The sensitivity of detection was 94.44%, specificity 100%, negative predictive value 97.83%, and negative likelihood ratio 0.06 for intermediate and high-risk endometrial cancer groups. CONCLUSIONS: The SLN biopsy with both cervical and fundal ICG injection offers good overall detection rates and improved mapping of the aortic area. The SLN ultrastaging increases the number of nodes considered positive.

Desprescripción de tratamientos de larga duración con bisfosfonatos para la osteoporosis en atención primaria en el País Vasco / Deprescribing long-term treatments with bisphosphonates for osteoporosis in primary care in the Basque Country (Spain)

Objetivo: Evaluar el impacto de una intervención multifactorial para promover la desprescripción de tratamientos con bisfosfonatos de duración superior a 5 años (BF5a) en la Comarca Gipuzkoa y compararlo con la intervención estándar en el resto de las organizaciones de servicios (OS) de Osakidetza. Métodos: Estudio de evaluación del impacto de dos intervenciones con medida de resultados antes y después, con un seguimiento de 8 meses. Se incluyeron todos los pacientes de Osakidetza que en julio de 2013 tenían un tratamiento activo con BF5a (prescripción electrónica). La intervención estándar (9 OS) consistió en el envío de un documento de consenso sobre desprescripción de BF5a y en facilitar los identificadores de pacientes con BF5a para su revisión por el médico de atención primaria. La intervención multifactorial (Comarca Gipuzkoa) incluyó, además, un consenso local con los especialistas de referencia y sesiones de formación en los centros de salud. Resultados: Se incluyeron 18.725 pacientes, el 94,7% mujeres. Con la intervención estándar, los porcentajes de desprescripción oscilaron entre el 26,4% (C. Bilbao) y el 49,4% (C. Araba), siendo del 37,2% en su conjunto. Con la intervención multifactorial la desprescripción fue del 44,6%, un 7,4% superior a la estándar (p <0,0001; intervalo de confianza del 95% [IC95%]: 5,4-9,4). Los desplazamientos a otros tratamientos fueron menos frecuentes con la intervención multifactorial, con una diferencia del 3,7% (p <0.0001; IC95%: −2,2 a −5,2). Conclusiones: Las intervenciones estándar y multifactorial son muy efectivas para disminuir los tratamientos innecesarios con bisfosfonatos. La intervención multifactorial es más efectiva que la estándar, aunque más compleja de llevar a cabo (AU)

Objective: To evaluate the impact of a multifactorial intervention to promote bisphosphonate deprescription after over 5 years of use (BF5y) in a health care organisation (HCO) in Gipuzkoa (Spain) and to compare it with the standard intervention in other HCOs in the Basque Health Service-Osakidetza. Methods: An 8-month follow-up study (results from before and after) to assess the impact of two interventions. All patients from Osakidetza receiving BF5y treatment (electronic prescription) in July 2013 were included. The standard intervention (9 HCOs) consisted of mailing a consensus statement on BF5y deprescribing and facilitating patient identifiers with BF5y prescription for review by the primary care physician. The multifactorial intervention (Gipuzkoa) also included a local consensus with leading specialists and training sessions in health centres. Results: 18,725 patients were included; 94.7% were women. Standard intervention deprescribing rates ranged from 26.4% (Bilbao) to 49.4% (Araba), being 37.2% overall. The multifactorial intervention deprescribing rate was 44.6%, 7.4% (p <0.0001; 95% confidence interval [95%CI]: 5.4-9.4) higher than standard intervention. Changes to other treatments were less common with the multifactorial intervention, with a difference of 3.7% (p <0.0001; 95%CI: −2.2 to −5.2). Conclusions: Standard and multifactorial interventions are very effective in reducing unnecessary treatments with bisphosphonates. The multifactorial intervention is more effective than the standard one, although more complex to implement (AU)

[Deprescribing long-term treatments with bisphosphonates for osteoporosis in primary care in the Basque Country (Spain)]. / Desprescripción de tratamientos de larga duración con bisfosfonatos para la osteoporosis en atención primaria en el País Vasco.

OBJECTIVE: To evaluate the impact of a multifactorial intervention to promote bisphosphonate deprescription after over 5 years of use (BF5y) in a health care organisation (HCO) in Gipuzkoa (Spain) and to compare it with the standard intervention in other HCOs in the Basque Health Service-Osakidetza. METHODS: An 8-month follow-up study (results from before and after) to assess the impact of two interventions. All patients from Osakidetza receiving BF5y treatment (electronic prescription) in July 2013 were included. The standard intervention (9 HCOs) consisted of mailing a consensus statement on BF5y deprescribing and facilitating patient identifiers with BF5y prescription for review by the primary care physician. The multifactorial intervention (Gipuzkoa) also included a local consensus with leading specialists and training sessions in health centres. RESULTS: 18,725 patients were included; 94.7% were women. Standard intervention deprescribing rates ranged from 26.4% (Bilbao) to 49.4% (Araba), being 37.2% overall. The multifactorial intervention deprescribing rate was 44.6%, 7.4% (p <0.0001; 95% confidence interval [95%CI]: 5.4-9.4) higher than standard intervention. Changes to other treatments were less common with the multifactorial intervention, with a difference of 3.7% (p <0.0001; 95%CI: -2.2 to -5.2). CONCLUSIONS: Standard and multifactorial interventions are very effective in reducing unnecessary treatments with bisphosphonates. The multifactorial intervention is more effective than the standard one, although more complex to implement.

Robotic retroperitoneal paraaortic lymphadenectomy at Donostia University Hospital.

The purpose of this study was to describe our robotic retroperitoneal para-aortic lymphadenectomy technique and its associated outcomes as well as the advantages and disadvantages. We prospectively collected data on all retroperitoneal aortocaval lymphadenectomy procedures performed at Donostia University Hospital from December 2011 to April 2013 using the da Vinci S robotic system (Intuitive Surgical, Sunnyvale,CA). A total of 13 of these procedures were performed. The mean patient age was 60.3 years (SD, 10.18). Most patients were obese with a mean body mass index of 31.95 kg/m(2) (SD, 5), and 9 had endometrial cancer. Five individuals were restaged: 4 because of lymphovascular space invasion and 1 because of lymphovascular space invasion with G3 histology. There were 2 cases of Fédération Internationale de Gynécologie et d'Obstétrique stage IB endometrial cancer: 1 of papillary serous histology and 1 of G3. Two patients had advanced cervical cancer, and 2 had early-stage ovarian cancer. The median para-aortic lymph node yield was 12 (range, 4-21). In 3 patients, it was necessary to convert the procedure to transperitoneal access because of technical difficulties; 1 of these required laparotomy. The mean surgical time was 323 minutes (SD, 58) although this included additional complex procedures. Robotic para-aortic retroperitoneal lymphadenectomy is feasible and offers the advantages of retroperitoneal access.