A selective anatomically based lymph node sampling can replace a side specific pelvic lymphadenectomy in endometrial cancer with failed sentinel node mapping.

AIM: To evaluate the locations of metastatic pelvic sentinel nodes (SLN) and the proportion of SLNs outside and within defined typical anatomical positions along the upper paracervical lymphatic pathway (UPP). PATIENTS AND METHODS: Consecutive women with endometrial cancer (EC) of all risk groups underwent pelvic SLN-detection using cervically injected indocyanine green (ICG). A strict anatomically based algorithm and definitions of SLNs was adhered to. The positions of ICG-defined SLNs were intraoperatively depicted on an anatomical chart. All SLNs were examined using ultrastaging and immunohistochemistry. The proximal third of the obturator fossa and the interiliac area were defined as typical positions. The parauterine lymphovascular tissue (PULT) was separately removed. The proportions of metastatic SLNs, overall and isolated, typically, and atypically positioned were analyzed per woman. RESULTS: A median of two (range 1-12) SLN metastases along the UPP including the PULT were found in 162 women. 41 of 162 women (25.3 %) had isolated metastases in the obturator fossa harboring 49.1 % of all SLN metastases. Three women (1,9 %) had isolated PULT metastases. SLN metastases outside typical positions were identified in 28/162 women (17.3 %); isolated metastases were seen in seven women (4.3 %), so 95.7 % of pelvic node positive women had at least one metastatic SLN located at a typical position. CONCLUSION: A selective removal of lymph nodes at typical proximal obturator and interiliac positions and the PULT can replace a full side specific pelvic LND when SLN mapping is unsuccessful. The obturator fossa is the predominant location for metastatic disease.

Similar distribution of pelvic sentinel lymph nodes and nodal metastases in cervical and endometrial cancer. A prospective study based on lymphatic anatomy.

OBJECTIVE: Comparing the anatomical distribution of metastatic and non-metastatic pelvic sentinel lymph nodes (SLN) in cervical and endometrial cancer. METHODS: Detailed SLN mapping results were prospectively retrieved in cervical (n = 145) or high-risk endometrial cancer (n = 201) patients undergoing a robotic staging procedure. Cervically injected Indocyanine Green (ICG), allowing for reinjection in case of inadequate mapping, was used as tracer. An anatomically based definition of SLNs was adhered to evaluating the upper (UPP) and lower (LPP) paracervical lymphatic pathways. The positions of SLNs were intraoperatively depicted on an anatomical chart. A completory pelvic lymphadenectomy was performed. Mapping rates and anatomical distribution of SLNs and the location of pelvic nodal metastases were compared between groups. RESULTS: The bilateral mapping rate was 97.9% and 95.0% for cervical and endometrial cancer respectively (p = .16). The proportion of typically positioned (interiliac and proximal obturator fossa) SLNs along the UPP was similar between groups (78.1% vs 82.1%, p = .09), and the rate of metastatic SLNs in the obturator fossa was 54.1% and 48.6% respectively (p = .45). All pelvic node positive women (cervical cancer n = 19, endometrial cancer n = 37) had at least one metastatic SLN. Anatomically typical positions could not be defined along the LPP. CONCLUSION: The anatomical location of SLNs and SLN metastases are similar in cervical and endometrial cancer suggesting that sensitivity results for an SLN concept in endometrial cancer and cervical cancer can be accumulated.

Resection of the upper paracervical lymphovascular tissue should be an integral part of a pelvic sentinel lymph node algorithm in early stage cervical cancer.

OBJECTIVE: To investigate the prevalence of lymph nodes and lymph node metastases (LNMs) in the upper paracervical lymphovascular tissue (UPLT) in early stage cervical cancer. METHODS: In this prospective study consecutive women with stage IA1-IB1 cervical cancer underwent a pelvic lymphadenectomy including identification of sentinel nodes (SLNs) as part of a nodal staging procedure in conjunction with a robotic radical hysterectomy (RRH) or robotic radical trachelectomy (RRT). Indocyanine green (ICG) was used as tracer. The UPLT was separately removed and defined as "SLN-parametrium" and, as all SLN tissue, subjected to ultrastaging and immunohistochemistry. Primary endpoint was prevalence of lymph nodes and metastatic lymph nodes in the UPLT. Secondary endpoints were complications associated with removal of the UPLT. RESULTS: One hundred and forty-five women were analysed. Nineteen (13.1%) had pelvic LNMs, all identified by at least one metastatic SLN. In 76 women (52.4%) at least one UPLT lymph node was identified. Metastatic UPLT lymph nodes were identified in six women of which in three women (2.1% of all women and 15.8% of node positive women) without lateral pelvic LNMs. Thirteen women had lateral pelvic SLN LNMs with either no (n = 5) or benign (n = 8) UPLT lymph nodes. No intraoperative complications occurred due to the removal of the UPLT. CONCLUSION: Removal of the UPLT should be an integral part of the SLN concept in early stage cervical cancer.

Pelvic sentinel lymph node biopsy in endometrial cancer-a simplified algorithm based on histology and lymphatic anatomy.

OBJECTIVE: To achieve the full potential of sentinel lymph node (SLN) detection in endometrial cancer, both presumed low- and high-risk groups should be included. Perioperative resource use and complications should be minimized. Knowledge on distribution and common anatomical sites for metastatic SLNs may contribute to optimizing the concept while maintaining sensitivity. Proceeding from previous studies, simplified algorithms based on histology and lymphatic anatomy are proposed. METHODS: Data on mapping rates and locations of pelvic SLNs (metastatic and non-metastatic) from two previous prospective SLN studies in women with endometrial cancer were retrieved. Cervically injected indocyanine green was used as a tracer and an ipsilateral re-injection was performed in case of non-display of the upper and/or lower paracervical pathways. A systematic surgical algorithm was followed with clearly defined SLNs depicted on an anatomical chart. In high-risk endometrial cancer patients, removal of SLNs was followed by a pelvic and para-aortic lymphadenectomy. RESULTS: 423 study records were analyzed. The bilateral mapping rates of the upper and lower paracervical pathways were 88.9% and 39.7%, respectively. 72% of all SLNs were typically positioned along the upper paracervical pathway (interiliac and/or proximal obturator fossa) and 71 of 75 (94.6%) of pelvic node positive women had at least one metastatic SLN at either of these positions. Women with grade 1-2 endometroid cancers (n=275) had no isolated metastases along the lower paracervical pathway compared with two women with high-risk histologies (n=148). CONCLUSION: SLNs along the upper paracervical pathway should be identified in all endometrial cancer histological subtypes; removal of nodes at defined typical positions along the upper paracervical pathway may replace a site-specific lymphadenectomy in case of non-mapping despite tracer re-injection. Detection of SLNs along the lower paracervical pathway can be restricted to high-risk histologies and a full pre-sacral lymphadenectomy should be performed in case of non-display.

Combining Indocyanine Green and Tc99-nanocolloid does not increase the detection rate of sentinel lymph nodes in early stage cervical cancer compared to Indocyanine Green alone.

OBJECTIVE: To investigate whether combining two independent tracers increases the SLN-detection rate in cervical cancer. METHODS: Consecutive women with early stage cervical cancer planned for a robotic radical hysterectomy or a robotic radical trachelectomy with sentinel lymph node (SLN) detection were included. After cervical injections of Indocyanine green (ICG) and Tc99-nanocolloid (Tc99), near-infrared fluorescence imaging and a gamma probe were used to identify SLNs in the upper and lower paracervical pathways (UPP/LPP). A strict surgical algorithm was adhered to and the SLNs were defined as SLN-ICG, SLN-ICG+Tc99 or SLN-Tc99. In FIGO-stage ≥IA2 cancers a full pelvic lymph node dissection (PLND) was performed after detection of SLNs. The primary endpoint was the SLN detection rate per tracer and combination of tracers. Secondary endpoints were sensitivity and mapping rates of the SLN algorithm per tracer and combination of tracers. RESULTS: In the sixty-five analyzed women, the bilateral mapping rate was 98.5% for ICG and 60% for Tc99 (p < 0.01). Combining the tracers did not increase the bilateral detection rate. In three women (5%) Tc99 identified ICG-negative non-metastatic SLNs without impact on the bilateral detection rate. Eight women (12%) had lymph node metastases (LNMs), all had at least one metastatic SLN. Seven (35%) of the 20 metastatic SLNs were detected by ICG only and 12 (60%) were ICG and Tc99 positive. CONCLUSION: SLN detection rate was significantly higher using ICG compared with Tc99. ICG identified all patients with LNMs. Combining ICG and Tc99 did not improve the bilateral detection rate of SLNs.

Pelvic Sentinel lymph node detection in High-Risk Endometrial Cancer (SHREC-trial)-the final step towards a paradigm shift in surgical staging.

STUDY AIMS: To prospectively assess the diagnostic accuracy of a pelvic sentinel lymph node (SLN) algorithm in high-risk endometrial cancer (HREC). PATIENTS AND METHODS: Consecutive women with presumed FIGO stage I-II HREC underwent robotic surgery at two academic centres by five accredited surgeons. An anatomically based algorithm was adhered to, following cervical injection of indocyanine green (ICG), with reinjection of tracer in case of non-display of predefined lymphatic pathways. After removal of SLNs, a pelvic and infrarenal para-aortic lymphadenectomy was performed. Primary end-point was sensitivity of the SLN-ICG algorithm. Secondary end-points were sensitivity of the overall SLN algorithm (including macroscopically suspect nodes as SLNs), SLN mapping rates and morbidity of the SLN procedure. RESULTS: Two hundred fifty-seven women were analysed; 54 had pelvic lymph node metastases (LNMs), and 52 of those were correctly identified by the SLN-ICG algorithm. In two women (one with false-negative ICG-SLNs and one non-mapped woman), the pelvic LNMs were identified by the overall SLN algorithm. The SLN-ICG algorithm had a sensitivity of 98% (95% confidence interval [CI] 89-100) and a negative predictive value of 99.5% (95% CI 97-100). The sensitivity of the overall SLN algorithm was 100% (95% CI 92-100) and the negative predictive value was 100% (95% CI 98-100). The bilateral mapping rate was 95%. Two women (1%) had isolated para-aortic metastases. No adverse events occurred during the SLN procedure. CONCLUSION: With a complete sensitivity to detect pelvic LNMs, the described pelvic SLN algorithm can, in the hands of experienced surgeons, exclude overall nodal involvement in 99% and thereby safely replace a full lymphadenectomy in HREC.

Sentinel lymph node biopsy in endometrial cancer-Feasibility, safety and lymphatic complications.

OBJECTIVE: To compare the rate of lymphatic complications in women with endometrial cancer undergoing sentinel lymph node biopsy versus a full pelvic and infrarenal paraaortic lymphadenectomy, and to examine the overall feasibility and safety of the former. METHODS: A prospective study of 188 patients with endometrial cancer planned for robotic surgery. Indocyanine green was used to identify the sentinel lymph nodes. In low-risk patients the lymphadenectomy was restricted to removal of sentinel lymph nodes whereas in high-risk patients also a full lymphadenectomy was performed. The impact of the extent of the lymphadenectomy on the rate of complications was evaluated. RESULTS: The bilateral detection rate of sentinel lymph nodes was 96% after cervical tracer injection. No intraoperative complication was associated with the sentinel lymph node biopsy per se. Compared with hysterectomy alone, the additional average operative time for removal of sentinel lymph nodes was 33min whereas 91min were saved compared with a full pelvic and paraaortic lymphadenectomy. Sentinel lymph node biopsy alone resulted in a lower incidence of leg lymphedema than infrarenal paraaortic and pelvic lymphadenectomy (1.3% vs 18.1%, p=0.0003). CONCLUSION: The high feasibility, the absence of intraoperative complications and the low risk of lymphatic complications supports implementing detection of sentinel lymph nodes in low-risk endometrial cancer patients. Given that available preliminary data on sensitivity and false negative rates in high-risk patients are confirmed in further studies, we also believe that the reduction in lymphatic complications and operative time strongly motivates the sentinel lymph node concept in high-risk endometrial cancer.

Description of a reproducible anatomically based surgical algorithm for detection of pelvic sentinel lymph nodes in endometrial cancer.

OBJECTIVE: To describe and evaluate a reproducible, anatomically based surgical algorithm, including reinjection of tracer to enhance technical success rate, for detection of pelvic sentinel lymph nodes (SLNs) in endometrial cancer (EC). METHODS: A prospective study of 102 consecutive women with high risk EC scheduled for robotic surgery was conducted. Following cervical injection of a fluorescent dye, an algorithm for trans- and retroperitoneal identification of tracer display in the lower and upper paracervical pathways was strictly adhered to. To enhance the technical success rate, this included ipsilateral reinjection of tracer in case of non-display of any lymphatic pathway. The lymphatic pathways were kept intact by opening the avascular planes. To minimize disturbance from leaking dye, removal of SLNs was first performed along the lower paracervical (presacral) pathways followed by the more caudal upper paracervical pathways. In each pathway, the juxtauterine node with an afferent lymph vessel was defined as an SLN. After removal of SLNs, a complete pelvic and, unless contraindicated, infrarenal paraaortic lymph node dissection was performed. RESULTS: The bilateral detection rate including tracer reinjection was 96%. All 24 (23.5%) node positive patients had at least one metastatic SLN. Presacral lymph node metastases were discovered in 33.3% of the node positive patients. One patient (4.2%) had an isolated presacral lymph node metastasis. CONCLUSIONS: The described cranial-to-caudal anatomically based surgical SLN algorithm, including a presacral dissection and reinjection of tracer, results in a high SLN detection rate and identified all patients with lymph node metastases.

A study on uterine lymphatic anatomy for standardization of pelvic sentinel lymph node detection in endometrial cancer.

OBJECTIVE: To describe the anatomy of uterine lymphatic drainage following cervical or fundal tracer injection to enable standardization of a pelvic sentinel lymph node (SLN) concept in endometrial cancer (EC). METHODS: A prospective consecutive study of women with EC was conducted. A fluorescent dye (Indocyanine green) was injected into the cervix (n=60) or the uterine fundus (n=30). A systematic trans- and retroperitoneal mapping of uterine lymphatic drainage was performed. Positions of the pelvic SLNs, defined by afferent lymph vessels, and lymph node metastases were compared. RESULTS: Two consistent lymphatic pathways with pelvic SLNs were identified irrespective of injection site; an upper paracervical pathway (UPP) with draining medial external and/or obturator lymph nodes and a lower paracervical pathway (LPP) with draining internal iliac and/or presacral lymph nodes. Bilateral display of at least one pelvic pathway following cervical and fundal injection occurred in 98% and 80% respectively (p=0.005). Bilateral display of both pelvic pathways occurred in 30% and 20% respectively (p=0.6) as the LPP was less often displayed. Nearly one third of the 19% node positive patients had metastases along the LPP. No false negative SLNs were identified. CONCLUSIONS: Based on uterine lymphatic anatomy a bilateral detection of at least one SLN in both the UPP and LPP should be aimed for. Absence of display of the LPP may warrant a full presacral lymphadenectomy. Although pelvic pathways and positions of SLNs are independent of the tracer injection site, cervical injection is preferable due to a higher technical success rate.

The effect of increased experience on complications in robotic hysterectomy for malignant and benign gynecological disease.

The study objective was to assess the effect of increased experience on complications in robotic hysterectomy for malignant and benign gynecological disease. This is a retrospective cohort study. It is a Canadian Task Force classification II-2 study conducted at the University Hospital, Sweden. The patients were 949 women planned for robotic hysterectomy for malignant (75 %) and benign (25 %) gynecological disease between October 2005 and December 2013. They were continuously evaluated for the rate of intraoperative and postoperative complications up to 1-year post-surgery, the latter according to Clavien-Dindo classification following the introduction of robotic surgery with special awareness of complications possibly related to robot-specific risk factors, the description of refinement of practice and assessment of the effect of these measures. The rate of intraoperative complications, the overall rate of complications and the rate of ≥grade 3 complications decreased from the first to the last time period (4.8 vs 2.6 %, p = 0.037, 34 vs 19 %, p = 0.003 and 13.5 vs 3.2 %, p = 0.0003, respectively). The rate of intraoperative complications and the rate of postoperative complications possibly related to robot-specific risk factors was reduced from the first to the last time period (3.8 vs 0.6 %, p = 0.028 and 7.7 vs 1.5 %, p = 0.003, respectively). In patients undergoing robotic hysterectomy for malignant and benign gynecological disease intraoperative and postoperative complications and complications possibly related to the robotic approach diminish with training, experience and refinement of practice.

Robotic infrarenal paraaortic and pelvic nodal staging for endometrial cancer: feasibility and lymphatic complications.

INTRODUCTION: This study was designed to evaluate the feasibility and lymphatic complications of robotic pelvic and infrarenal paraaortic lymphadenectomy in endometrial cancer patients. MATERIAL AND METHODS: All patients diagnosed with high risk endometrial cancer during the study period were identified (n = 212). Clinical prospective data, with reassessment of lymphatic complications, was analysed for all cases (n = 140) planned for a complete robotic nodal staging. The outcome measures were: success rate of infrarenal paraaortic lymphadenectomy, the rate of lymphatic complications and factors associated with nodal yield. RESULTS: Of the 212 women, an open or restricted robotic procedure was performed in 57 women (27%) and no operation in 15 (7%), the latter due to disseminated disease or comorbidity. In 140 women (66%) in whom staging was intended, the lymphadenectomy included the infrarenal area in 70%, was restricted to the inframesenteric area in 21% and aborted or incomplete in 9%. The median number of paraaortic nodes was 10 (range 2-39). An unsuccessful staging was associated with high BMI and the surgeon's inexperience. At 1 year, three patients (2%) had developed a grade two lower limb lymphedema. Eleven women (8%) demonstrated pelvic lymphocysts; seven (64%) resolved spontaneously. Only one paraaortic lymphocyst was found; this required drainage. No cases of chylous ascites occurred. CONCLUSIONS: An infrarenal robotic paraaortic lymphadenectomy is feasible in 70% of high risk endometrial cancer cases when intended (88% in non-obese patients operated by experienced surgeons), but is restricted in obese patients and by surgeon's inexperience.

Robot-assisted laparoscopic hysterectomy in obese and morbidly obese women: surgical technique and comparison with open surgery.

OBJECTIVE: Comparison of surgical results on obese patients undergoing hysterectomy by robot-assisted laparoscopy or laparotomy. SETTING: University hospital. METHODS: All women (n=114) with a BMI ≥30 kg/m(2) who underwent a simple hysterectomy as the main surgical procedure between November 2005 and November 2009 were identified. Robot-assisted procedures (n=50) were separated into an early (learning phase) and a late (consolidated phase) group; open hysterectomy was considered an established method. Relevant data was retrieved from prospective protocols (robot) or from computerized patient charts (laparotomy) until 12 months after surgery. Complications leading to prolonged hospital stay, readmission/reoperation, intravenous antibiotic treatment or blood transfusion were considered significant. The surgical technique used for morbidly obese patients is described. RESULTS: Women in the late robot group (n=25) had shorter inpatient time (1.6 compared to 3.8 days, p<0.0001), less bleeding (100 compared to 300 mL, p<0.0001) and fewer complications (2/25 compared to 23/64, p=0.006) than women with open surgery (n=64) but a longer operating time (136 compared to 110 minutes, p=0.0004). For women with a BMI ≥35 kg/m(2) , surgical time in the late robot group and the laparotomy group was equal (136 compared to 128 minutes, p=0.31). CONCLUSIONS: Robot-assisted laparoscopic hysterectomy in a consolidated phase in obese women is associated with shorter hospital stay, less bleeding and fewer complications compared to laparotomy but, apart from women with BMI ≥35, a longer operative time.

All for one but not one for all: how multiple number representations are recruited in one numerical task.

Number processing recruits a complex network of multiple numerical representations. Usually the components of this network are examined in a between-task approach with the disadvantage of relying upon different instructions, tasks, and inhomogeneous stimulus sets across different studies. A within-task approach may avoid these disadvantages and access involved numerical representations more specifically. In the present study we employed a within-task approach to investigate numerical representations activated in the number bisection task (NBT) using parametric rapid event-related fMRI. Participants were to judge whether the central number of a triplet was also its arithmetic mean (e.g. 23_26_29) or not (e.g. 23_25_29). Activation in the left inferior parietal cortex was associated with the deployment of arithmetic fact knowledge, while activation of the intraparietal cortex indicated more intense magnitude processing, instrumental aspects of calculation and integration of the base-10 structure of two-digit numbers. These results replicate evidence from the literature. Furthermore, activation in the dorsolateral and ventrolateral prefrontal cortex revealed mechanisms of feature monitoring and inhibition as well as allocation of cognitive resources recruited to solve a specific triplet. We conclude that the network of numerical representations should rather be studied in a within-task approach than in varying between-task approaches.

On the impact of different number representations in the number bisection task.

The number bisection task--in which the numerical middle of two other numbers has to be determined (e.g., 6 is the numerical middle of 4 and 8)--has recently been used in neuropsychological case studies in addition to the number comparison task to assess quantitative capabilities in number processing. While factors determining difficulty in normal participants have often been systematically investigated in the number comparison task, this has not yet been done in the number bisection task. Based on a pilot study by van Herten (1999), we extracted four factors that we hypothesized to modulate difficulty in a verification version of the number bisection task in normal participants: Multiplicativity (whether or not the three numbers are part of a multiplication table), range (distance between the smallest and the largest number) for bisectable number triplets as well as distance of the middle number to the numerical middle, and bisection possibility for non-bisectable triplets. In the current study, we obtained large effects for all four factors on RT and accuracy data and some interesting interactions in normal participants. In a regression analysis, we additionally observed inhibitory effects of decade crossing and of ten inclusion (whether or not one of the three numbers was a decade number). We discuss the impact of these results for the use of the number bisection task as an assessment tool in neuropsychology. Finally, we examine the consequences of these results for models of number processing.