A new centrality of the nodes in the network is proposed called alternate centrality, which can isolate effective drug targets in the complex signalling network. Alternate centrality metric defined ...over the network substructure (four nodes – motifs). The nodes involving in alternative activation in the motifs gain in metric values. Targeting high alternative centrality nodes hypothesised to be destructive free to the network due to their alternative activation mechanism. Overlapping and crosstalk among the gene products in the conserved network of MAPK pathways selected for the study. In silico knock-out of high alternate centrality nodes causing rewiring in the network is investigated using MCF-7 breast cancer cell line-based data. Degree of top alternate centrality nodes lies between the degree of bridging and pagerank nodes. Node deletion of high alternate centrality on the centralities such as eccentricity, closeness, betweenness, stress, centroid and radiality causes low perturbation. The authors identified the following alternate centrality nodes ERK1, ERK2, MEKK2, MKK5, MKK4, MLK3, MLK2, MLK1, MEKK4, MEKK1, TAK1, P38alpha, ZAK, DLK, LZK, MLTKa/b and P38beta as efficient drug targets for breast cancer. Alternate centrality identifies effective drug targets and is free from intertwined biological processes and lethality.
Quantum networks comprised of entangled end nodes serve stronger than the classical correlation for unparalleled quantum internet applications. However, practical quantum networking is affected by ...noise, which at its worst, causes end nodes to be described by pre-existing classical data. In such untrusted networks, determining quantum network fidelity and genuine multi-node entanglement becomes crucial. Here, we show that determining quantum network fidelity and genuine N-node entanglement in an untrusted star network requires only N + 1 measurement settings. This method establishes a semi-trusted framework, allowing some nodes to relax their assumptions. Our network determination method is enabled by detecting genuine N-node Einstein-Podolsky-Rosen steerability. Experimentally, using spontaneous parametric down-conversion entanglement sources, we demonstrate the determinations of genuine 3-photon and 4-photon quantum networks and the false positives of the widely used entanglement witness, the fidelity criterion of 1/2. Our results provide a scalable method for the determination of multipartite entanglement in realistic quantum networks.
Background
Technetium‐99 (99mTc) lymphoscintigraphy with blue dye injection is an accepted method for sentinel lymph node (SLN) mapping, but blue dye has known adverse effects, and injection of 99mTc ...may increase time under anesthesia for pediatric patients. Indocyanine green (ICG) may serve as an adjunct to assist with visibility and identification of SLNs. We hypothesized that sensitivity of ICG was similar to blue dye in SLN biopsies.
Methods
Thirty patients (36 procedures with 96 total specimens) underwent preoperative intradermal injection of 99mTc, followed by intradermal injection of isosulfan blue and ICG. Test characteristics of blue dye, ICG, and 99mTc included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).
Results
ICG had a sensitivity of 87% and PPV of 83% for detection of 99mTc‐hot lymph nodes; blue dye had a sensitivity of 44% and PPV of 97%. For detection of pathologically confirmed lymph nodes, ICG had a sensitivity of 84% and a positive predictive value (PPV) of 91%. 99mTc had a sensitivity of 82% and a PPV of 94%. ICG had no significant difference in odds of being positive in pathology‐confirmed lymph nodes compared to 99mTc (odds ratio OR, 0.818; 95% confidence interval CI, 0.3–2.172; p = .823) and had higher odds than isosulfan blue (OR, 0.025, 95% CI, 0.001–0.148; p < .001).
Conclusion
This study established the efficacy of ICG as an adjunct to SLNB in the pediatric and young adult population. ICG was safe, more efficacious than blue dye, and may obviate the need for lymphoscintigraphy in selected patients resulting in reduced time under anesthesia.
This trial in the pediatric and young adult oncology population studied patients undergoing sentinel lymph node biopsy with the use of gold‐standard technetium‐99, isosulfan blue, and indocyanine green. Indocyanine green was found to be safe, more efficacious than blue dye, and noninferior to technetium‐99, potentially obviating the need for nuclear scanning in select patient populations, resulting in reduced time under anesthesia.
It is unclear if sentinel node (SLN) mapping can replace pelvic- (PLD) and paraaortic lymphadenectomy (PALD) for high-risk endometrial cancer (EC). A diagnostically safe surgical algorithm, taking ...failed mapping cases into account, is not defined. We aimed to investigate the diagnostic accuracy of SLN mapping algorithms in women with exclusively high-risk EC.
We undertook a prospective national diagnostic cohort study of SLN mapping in women with high-risk EC from March 2017 to January 2023. The power calculation was based on the negative predictive value (NPV). Women underwent SLN mapping, PLD and PALD besides removal of suspicious and any FDG/PET–positive lymph nodes. Accuracy analyses were performed for five algorithms.
170/216 included women underwent SLN mapping, PLD and PALD and were included in accuracy analyses. 42/170 (24.7%) had nodal metastasis. The algorithm SLN and PLD in case of failed mapping, demonstrated a sensitivity of 86% (95% CI 74–100) and an NPV of 96% (95% CI 91–100). The sensitivity increased to 93% (95% CI 83–100) and the NPV to 98% (95% CI 94–100) if PLD was combined with removal of any PET-positive lymph nodes. Equivalent results were obtained if PLD and PALD were performed in non-mapping cases; sensitivity 93% (95% CI 83–100) and NPV 98% (95% CI 95–100).
SLN-mapping is a safe staging procedure in women with high-risk EC if strictly adhering to a surgical algorithm including removal of any PET-positive lymph nodes independent of location and PLD or PLD and PALD in case of failed mapping.
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•The diagnostic safety of SLN mapping for high-risk endometrial cancer is conditioned.•A safe algorithm includes the removal of any suspicious and PET-positive lymph nodes.•If failed SLN mapping, uni- or bilateral PLD should be performed.•If PET/CT is unavailable, PLD and PALD are recommended in case of failed mapping.•All accuracy analysis based on women who underwent both PLD and PALD as the reference standard.
Abstract Background Prostate cancer (PCa) patients with lymph node recurrence after radical prostatectomy (RP) are usually managed with androgen-deprivation therapy. Despite the absence of ...prospective randomized studies, salvage lymph node dissection (LND) has been proposed as an alternative treatment option. Objective To examine long-term outcomes of salvage LND in patients with nodal recurrent PCa documented by 11C-choline positron emission tomography/computed tomography (PET/CT) scan. Design, setting, and participants Overall, 59 patients affected by biochemical recurrence (BCR) with 11C-choline PET/CT scan with pathologic activity treated between 2002 and 2008 were included. Intervention Pelvic and/or retroperitoneal salvage LND. Outcome measurements and statistical analyses Biochemical response (BR) was defined as prostate-specific antigen (PSA) <0.2 ng/ml at 40 d after surgery. BCR for those who achieved BR was defined as a PSA >0.2 ng/ml. Clinical recurrence (CR) was defined as a positive PET/CT scan after salvage LND in the presence of a rising PSA. Kaplan-Meier curves assessed time to BCR, CR, and cancer-specific mortality (CSM). Cox regression analyses were fitted to assess predictors of CR. Results and limitations Median follow-up after salvage LND was 81.1 mo. Overall, 35 patients (59.3%) achieved BR. The 8-yr BCR-free survival rate in patients with complete BR was 23%. Overall, the 8-yr CR- and CSM-free survival rates were 38% and 81%, respectively. In multivariable analyses evaluating preoperative variables, PSA at salvage LND represented the only predictor of CR ( p = 0.03). When postoperative variables were considered, BR and the presence of retroperitoneal lymph node metastases were significantly associated with the risk of CR (all p ≤ 0.04). Our study is limited by the lack of a control group. Conclusions Salvage LND may represent a therapeutic option for patients with BCR after RP and nodal pathologic uptake at 11C-choline PET/CT scan. Although most patients progressed to BCR after salvage LND, roughly 40% of them experienced CR-free survival. Patient summary Salvage lymph node dissection may represent a therapeutic option for selected patients with nodal recurrence after radical prostatectomy. Roughly 40% of men did not show any further clinical recurrence at long-term follow-up after surgery.
Objectives
This study aimed to determine whether post-neoadjuvant therapy (NAT) axillary ultrasound (AUS) could reduce the false-negative rate (FNR) of sentinel lymph node biopsy (SLNB). We also ...performed subgroup analyses to identify the appropriate patient for SLNB.
Methods
A total of 220 patients with cytologically proven axillary node-positive breast cancer who underwent both SLNB and axillary lymph node dissection (ALND) after NAT were included. We calculated the FNR of SLNB. In the case of post-NAT AUS results available, AUS was classified as negative or positive. Then the FNR of post-NAT AUS combined with SLNB was evaluated. Subgroup analyses based on the number of sentinel lymph nodes removed, molecular subtypes, and the clinical N stage were also performed.
Results
The overall axillary lymph node pathological complete response rate was 45.5% (100/220). The FNR of SLNB alone was 15.8% (95%CI: 9.2 to 22.5%). Post-NAT AUS results were available for 181 patients. When combined negative post-NAT AUS results and SLNB, the FNR was reduced to 7.5% (95%CI: 2.4 to 12.7%). Subgroup analyses of the FNR for SLNB alone and negative post-NAT AUS combined with SLNB were shown as follows: in cases patients with less than three sentinel lymph nodes (SLNs) and at least three SLNs removed, the FNR was decreased from 24.5 to 13.2%, and 9.0 to 5.0%, respectively. The FNR was decreased from 20.8 to 10.5% in HR+/HER2+subgroup, 21.4 to 16.7% in HR−/HER2+subgroup, 15.9 to 7.0% in HR+/HER2− subgroup, and 0% in HR−/HER2− subgroup, respectively. For cN1 patients, the FNR was decreased from 18.1 to 12.1% while 17.1 to 3.6% for cN2 patients and 0% for cN3 patients.
Conclusion
Using negative post-NAT AUS may help to decrease the FNR and improve patient selection for SLNB.
The SENTIREC-endo study aims to investigate risks and benefits of a national protocolled adoption of sentinel lymph node (SLN) mapping in women with early-stage low-grade endometrial cancer (EC) with ...low- (LR) and intermediate-risk (IR) of lymph node metastases.
We performed a national multicenter prospective study of SLN-mapping in women with LR and IR EC from March 2017–February 2022. Postoperative complications were classified according to Clavien-Dindo. Lymphedema was assessed as a change score and as incidence of swelling and heaviness evaluated by validated patient-reported outcome measures at baseline and three months postoperatively.
627 women were included in the analyses; 458 with LR- and 169 with IR EC. The SLN detection rate was 94.3% (591/627). The overall incidence of lymph node metastases was 9.3% (58/627); 4.4% (20/458) in the LR- and 22.5% (38/169) in the IR group. Ultrastaging identified 62% (36/58) of metastases. The incidence of postoperative complications was 8% (50/627) but only 0.3% (2/627) experienced an intraoperative complication associated with the SLN procedure. The lymphedema change score was below the threshold for clinical importance 4.5/100 CI: (2.9–6.0), and the incidence of swelling and heaviness was low; 5.2% and 5.8%, respectively.
SLN mapping in women with LR and IR EC carries a very low risk of early lymphedema and peri- and postoperative complications. The national change in clinical practice contributed to a more correct treatment allocation for both risk groups and thus supports further international implementation of the SLN technique in early stage, low grade EC.
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•The SENTIREC-endo study undertook a national protocolled adoption of SLN mapping in women with low grade endometrial cancer.•The change in clinical practice contributed to a more correct treatment allocation independent of myometrial invasion.•SLN mapping carries a very low risk of perioperative complications in women with early-stage low grade endometrial cancer.•The risk of early lymphedema after SLN mapping is low, with an incidence of swelling in one or both legs of 5.2%.•The national adoption of SLN mapping for early-stage endometrial cancer prompted significant benefits and negligible harm.
The use of sentinel lymph node biopsy (SLNB) following neoadjuvant chemotherapy (NAC) in patients presenting with clinically positive lymph nodes remains controversial.
A computer-aided search of the ...literature regarding SLNB in clinically node-positive breast cancer treated with NAC was carried out to identify the false negative rate (FNR), sentinel lymph node identification rate (IR), and axillary pathological complete response (pCR).
Nineteen articles were used in the analysis yielding 3,398 patients. The pooled estimate of the FNR was 13% and that of the IR was 91%. The adjusted pCR rate was 47%. A trend toward significance was observed with only clinical stage N1 (cN1) disease whereby clinical stage N1 was associated with an increased pCR rate when compared to N2 or N3 disease (P = .06).
SLNB after NAC in biopsy-proven node-positive patients results in reasonably acceptable FNR and IR, making it a valid alternative management strategy to axillary dissection. More refined patient selection and optimal techniques can improve the FNR and IR in this patient population.
•The pooled estimate of false negative rate was 13%.•The pooled estimate of identification rate was 91%.•The adjusted pathological complete response rate was 47%.•There was a trend toward significance with only cN1 disease.•SLNB post NAC in node-positive patients is a valid alternative strategy to ALND.
Abstract Context There is controversy regarding the therapeutic role of pelvic lymph node dissection (PLND) in patients undergoing radical prostatectomy for prostate cancer (PCa). Objective To ...systematically review the relevant literature assessing the relative benefits and harms of PLND for oncological and non-oncological outcomes in patients undergoing radical prostatectomy for PCa. Evidence acquisition MEDLINE, MEDLINE In-Process, Embase, and the Cochrane Central Register of Controlled Trials were searched up to December 2015. Comparative studies evaluating no PLND, limited, standard, and (super)-extended PLND that reported oncological and non-oncological outcomes were included. Risk-of-bias and confounding assessments were performed. A narrative synthesis was undertaken. Evidence synthesis Overall, 66 studies recruiting a total of 275,269 patients were included (44 full-text articles and 22 conference abstracts). Oncological outcomes were addressed by 29 studies, one of which was a randomized clinical trial (RCT). Non-oncological outcomes were addressed by 43 studies, three of which were RCTs. There were high risks of bias and confounding in most studies. Conflicting results emerged when comparing biochemical and clinical recurrence, while no significant differences were observed among groups for survival. Conversely, the majority of studies showed that the more extensive the PLND, the greater the adverse outcomes in terms of operating time, blood loss, length of stay, and postoperative complications. No significant differences were observed in terms of urinary continence and erectile function recovery. Conclusions Although representing the most accurate staging procedure, PLND and its extension are associated with worse intraoperative and perioperative outcomes, whereas a direct therapeutic effect is still not evident from the current literature. The current poor quality of evidence indicates the need for robust and adequately powered clinical trials. Patient summary Based on a comprehensive review of the literature, this article summarizes the benefits and harms of removing lymph nodes during surgery to remove the prostate because of PCa. Although the quality of the data from the studies was poor, the review suggests that lymph node removal may not have any direct benefit on cancer outcomes and may instead result in more complications. Nevertheless, the procedure remains justified because it enables accurate assessment of cancer spread.
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