Knowledge, perceptions, attitudes, and barriers pertaining to genetic literacy among surgeons: a scoping review.

BACKGROUND: The rapid evolution of genetic technologies and utilization of genetic information for clinical decision-making has necessitated increased surgeon participation in genetic counselling, testing, and appropriate referral of patients for genetic services, without formal training in genetics. We performed a scoping review to describe surgeons' knowledge, perceptions, attitudes, and barriers pertaining to genetic literacy in the management of patients who had confirmed cancer or who were potentially genetically at risk. METHODS: We conducted a scoping review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews checklist. We performed a comprehensive literature search, and 2 reviewers independently screened studies for inclusion. These studies included surgeons involved in the care of patients with confirmed gastrointestinal, breast, and endocrine and neuroendocrine cancers, or patients who were potentially genetically at risk for these cancers. RESULTS: We analyzed 17 studies, all of which used survey or interview-based formats. Many surgeons engaged in genetic counselling, testing, and referral, but reported low confidence and comfort in doing so. Knowledge assessments showed lower confidence in identifying genetic inheritance patterns and hereditary cancer syndromes, but awareness was higher among surgeons with greater clinical volume or subspecialty training in oncology. Surgeons felt responsible for facilitating these services and explicitly requested educational support in genetics. Barriers to genetic literacy were identified and catalogued at patient, surgeon, and system levels. CONCLUSION: Surgeons frequently engage in genetics-related tasks despite a lack of formal genetics training, and often report low knowledge, comfort, and confidence in providing such services. We have identified several barriers to genetic literacy that can be used to develop interventions to enhance genetic literacy among surgeons.

Delayed Versus Early Laparoscopic Appendectomy for Adult Patients With Acute Appendicitis: A Randomized Controlled Trial.

OBJECTIVE: To assess whether delaying appendectomy until the following morning is non-inferior to immediate surgery in those with acute appendicitis presenting at night. BACKGROUND: Despite a lack of supporting evidence, those with acute appendicitis who present at night frequently have surgery delayed until the after morning. METHODS: The delay trial is a noninferiority randomized controlled trial conducted between 2018 and 22 at 2 tertiary care hospitals in Canada. Adults with imaging confirmed acute appendicitis who presented at night (8:00 pm -4:00 am ). Delaying surgery until after 6:00 am was compared with immediate surgery. The primary outcome was 30-day postoperative complications. An a prior noninferiority margin of 15% was deemed clinically relevant. RESULTS: One hundred twenty-seven of the planned 140 patients were enrolled in the Delayed Versus Early Laparoscopic Appendectomy (DELAY) trial (59 in the delayed group and 68 in the immediate group). The two groups were similar at baseline. The mean time between the decision to operate and surgery was longer in the delayed group (11.0 vs 4.4 hours, P < 0.0001). The primary outcome occurred in 6/59 (10.2%) of those in the delayed group versus 15/67 (22.4%) of those in the immediate group ( P = 0.07). The difference between groups met the a priori noninferiority criteria of +15% (risk difference -12.2%, 95% CI: -24.4% to +0.4%, test of noninferiority P < 0.0001). CONCLUSIONS: The DELAY study is the first trial to assess delaying appendectomy in those with acute appendicitis. We demonstrate the noninferiority of delaying surgery until the after morning.

Predictors of Postoperative Liver Decompensation Events After Resection in Patients with Cirrhosis and Hepatocellular Carcinoma: A Population-Based Study.

BACKGROUND: Appropriate patient selection for liver resection in hepatocellular carcinoma (HCC) is critical to mitigation of major liver-related postoperative complications. Currently, no standard prognostic tool exists to predict the risk of postoperative liver decompensation events (POLDEs) after partial hepatectomy for patients with cirrhosis and HCC. This study aimed to identify independent preoperative predictors of POLDEs for future development of prognostic tools to improve surgical decision-making. METHODS: This population-based, retrospective cohort study investigated patients with cirrhosis and incident HCC between 2007 and 2017, identified using administrative health data from Ontario, Canada. The occurrence of a POLDE or death within 2 years after surgery was described. Multivariable Cox regression identified independent predictors of POLDE-free survival, as well as cause-specific hazards for POLDEs and death. RESULTS: Among 611 patients with cirrhosis and HCC who underwent liver resection, 160 (26.2%) experienced at least one POLDE, and 189 (30.9%) died within 2 years after surgery. Diabetes, cirrhosis etiology, major liver resection, and previous non-malignant decompensation were independent predictors of POLDE-free survival. Except for extent of resection, the same risk factors were associated with POLDEs in the cause-specific analysis. In contrast, only age and history of previous non-malignant decompensation were independent predictors of mortality. CONCLUSIONS: Among patients with cirrhosis undergoing resection for HCC, patient and disease-related factors are associated with POLDEs and POLDE-free survival. These factors can be used both to inform clinical practice and to advance the development of preoperative prognostic tools, which may lead to improved outcomes for this population.

Laparoscopic ischaemic conditioning of the gastric conduit prior to a hybrid mckeown oesophagectomy may not decrease the risk of anastomotic leak.

INTRODUCTION: Morbidity associated with anastomotic leak after oesophagectomy is significant. Techniques to reduce this risk include ischaemic conditioning of the gastric conduit prior to oesophagectomy. AIM: To quantify the rate of anastomotic leak after a hybrid minimally invasive McKeown oesophagectomy preceded by laparoscopic gastric devascularization (LGD). MATERIAL AND METHODS: We identified patients who had undergone neoadjuvant chemoradiotherapy followed by LGD and McKeown oesophagectomy and conducted a retrospective case series. The primary outcome was anastomotic leak, and secondary outcomes included common post-operative complications within 30 days. RESULTS: Eleven patients were identified. Seventy-three per cent were male, and 7 of 11 patients were age 70+ years. 91% of tumours were located in the lower oesophagus or gastroesophageal junction (GEJ), and 72% of the series had clinical stage of II-III. The median ischaemic conditioning time was 15 days. Eighteen per cent of patients developed an anastomotic leak, and all were managed non-operatively. One patient developed an anastomotic stricture. Three patients developed pneumonia. Three patients suffered wound infection at the site of the neck incision. One had respiratory failure requiring ventilator support. None required reoperation or readmission. There were no mortalities following either operation. CONCLUSIONS: Laparoscopic ischaemic conditioning via LGD prior to a hybrid McKeown oesophagectomy for malignancy was associated with a leak rate similar to previously published data for a McKeown oesophagectomy without prior LGD.

Appraisal of multivariable prognostic models for post-operative liver decompensation following partial hepatectomy: a systematic review.

BACKGROUND: Few reports have evaluated prognostic modelling studies of tools used for surgical decision-making. This systematic review aimed to describe and critically appraise studies that have developed or validated multivariable prognostic models for post-operative liver decompensation following partial hepatectomy. METHODS: This study was designed using the CHARMS checklist. Following a comprehensive literature search, two reviewers independently screened candidate references for inclusion and abstracted relevant study details. Qualitative assessment was performed using the PROBAST tool. RESULTS: We identified 36 prognostic modelling studies; 25 focused on development only, 3 developed and validated models, and 8 validated pre-existing models. None compared routine use of a prognostic model against standard clinical practice. Most studies used single-institution, retrospective cohort designs, conducted in Eastern populations. In total, 15 different outcome definitions for post-operative liver decompensation events were used. Statistical concerns surrounding model overfitting, performance assessment, and internal validation led to high risk of bias for all studies. CONCLUSIONS: Current prognostic models for post-operative liver decompensation following partial hepatectomy may not be valid for routine clinical use due to design and methodologic concerns. Landmark resources and reporting guidelines such as the TRIPOD statement may assist researchers, and additionally, model impact assessment studies represent opportunities for future research.

Evaluating bowel enterotomy closures in simulated deep body cavities using the reversing half-hitch alternating post and square knots: a randomized controlled trial.

Background: Square knots can be difficult to construct in deep body cavities. The reversing half-hitch alternating post (RHAP) surgical knot has noninferior tensile strength and performance characteristics in deep body cavities. We compared the enterotomy repairs of novice learners in simulated deep body cavities using RHAP versus square knots after proficiency-based training. Methods: Undergraduate students were randomized to RHAP (n = 10) or square knot (n = 10) groups and trained to defined proficiency. They then performed hand-sewn enterotomy repairs of cadaveric porcine small bowels on flat surfaces and in simulated deep body cavities. We recorded time to knot-tying proficiency and to enterotomy repair, and burst pressures for the repair. Results: Mean time-to-proficiency in knot tying was equivalent between the RHAP and square knot groups (23 [standard deviation (SD) 3] v. 21 [SD 2] min, p = 0.33). Mean time for enterotomy repair in deep cavities was shorter for the RHAP group (16 [SD 2] min v. 21 [SD 1] min, p = 0.02). Mean burst pressures for enterotomy repair were equivalent on flat surfaces (128 [SD 41] v. 101 [SD 36] mm Hg, p = 0.31), and were significantly higher for the RHAP group in simulated deep body cavities (32 [SD 13] v. 105 [SD 37] mm Hg, p = 0.05). Conclusion: The RHAP knots appear to have superior performance versus square knots when tied in a deep body cavity by novice learners. Future work should focus on demonstrating the clinical relevance and broad utility of the RHAP knot in abdominal surgery. Both knot types should be taught to novice learners.

Contexte: L'exécution de noeuds plats peut être difficile dans les cavités corporelles profondes. Les noeuds de type demi-clé inversée alternée (RHAP, pour reversing halfhitch alternating post) ont une résistance à la traction et un rendement semblables à ceux des noeuds plats dans ces cavités. Nous avons comparé l'efficacité des noeuds plats et des noeuds de type RHAP réalisés par de nouveaux apprenants dans des cavités profondes simulées, après leur avoir enseigné les compétences nécessaires. Méthodes: Les étudiants de premier cycle ont été aléatoirement répartis en 2 groupes, soit le groupe RHAP (n = 10) et le groupe noeud plat (n = 10), et ont reçu une formation pour développer des compétences prédéfinies. Ils ont ensuite suturé à la main un intestin grêle provenant d'un cadavre de porc, sur une surface plane et à l'intérieur d'une cavité profonde simulée. Nous avons mesuré le temps nécessaire à l'exécution du noeud et à la suture complète de l'incision, de même que la pression que pouvait subir cette suture sans se rompre. Résultats: Le temps moyen d'exécution du noeud était semblable entre les groupes RHAP et noeud plat (23 min [écart type (E.T.) 3 min] c. 21 min [E.T. 2 min]; p = 0,33). Le temps moyen nécessaire à la suture de l'incision dans la cavité profonde était plus court dans le groupe RHAP (16 min [E.T. 2 min] c. 21 min [E.T. 1 min]; p = 0,02). La pression moyenne que pouvait subir la suture sans se rompre était comparable pour les sutures effectuées sur une surface plane (128 mm Hg [E.T. 41 mm Hg] c. 101 mm Hg [E.T. 36 mm Hg]; p = 0,31), mais était significativement plus élevée dans le groupe RHAP pour les sutures faites dans la cavité profonde (32 mm Hg [E.T. 13 mm Hg] c. 105 mm Hg [E.T. 37 mm Hg], p = 0,05). Conclusion: Les noeuds de type RHAP semblent avoir un rendement supérieur à celui des noeuds plats lorsqu'ils sont réalisés dans une cavité profonde par de nouveaux apprenants. Des études ultérieures devraient se pencher sur la pertinence clinique et l'utilité générale de ces noeuds en chirurgie abdominale. Les 2 types de noeuds devraient être enseignés aux nouveaux apprenants.

Delayed vs. Early Appendectomy (DELAY) trial for adult patients with acute appendicitis: Study protocol for a randomized controlled trial.

INTRODUCTION: Early appendectomy in patients diagnosed with acute appendicitis is the current standard of treatment in North America. Timely intervention is suggested to avoid the complications associated with perforated appendicitis; however, safety of nighttime operating is a competing concern, with mixed results demonstrated thus far. OBJECTIVES: This multi-center prospective randomized controlled trial aims to assess whether delaying appendectomy until the following morning versus early appendectomy overnight affects the rate of surgical complications in adult patients diagnosed with acute appendicitis in the evening hours. METHODS: This is a randomized, controlled trial across two academic institutions with blinded outcome assessors. Patients presenting with imaging-confirmed appendicitis with an expected appendectomy between 8 pm and 4 am and within 6 h of decision to operate will be randomized to early appendectomy (with 6 h of randomization, control arm) or delayed to the following morning (after 6 am, intervention arm). Primary outcome will be 30 day postoperative complications, defined as a composite of: mortality, readmission to hospital, emergency department visit, percutaneous drain insertion, reoperation, prolonged hospital stay (>7 days), and postoperative complications. Secondary outcome measures are operative time, length of stay, time to emergency department visit and compliance to treatment. DISCUSSION: This is a feasible and pragmatic clinical trial, intended to provide evidence for challenging decision making for the most common surgical disease worldwide. Results of this study will aid surgeons and health care administrators on how to appropriately triage appendectomies for patients with acute appendicitis who present overnight.

Considerations for conducting systematic reviews: evaluating the performance of different methods for de-duplicating references.

BACKGROUND: Systematic reviews involve searching multiple bibliographic databases to identify eligible studies. As this type of evidence synthesis is increasingly pursued, the use of various electronic platforms can help researchers improve the efficiency and quality of their research. We examined the accuracy and efficiency of commonly used electronic methods for flagging and removing duplicate references during this process. METHODS: A heterogeneous sample of references was obtained by conducting a similar topical search in MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and PsycINFO databases. References were de-duplicated via manual abstraction to create a benchmark set. The default settings were then used in Ovid multifile search, EndNote desktop, Mendeley, Zotero, Covidence, and Rayyan to de-duplicate the sample of references independently. Using the benchmark set as reference, the number of false-negative and false-positive duplicate references for each method was identified, and accuracy, sensitivity, and specificity were determined. RESULTS: We found that the most accurate methods for identifying duplicate references were Ovid, Covidence, and Rayyan. Ovid and Covidence possessed the highest specificity for identifying duplicate references, while Rayyan demonstrated the highest sensitivity. CONCLUSION: This study reveals the strengths and weaknesses of commonly used de-duplication methods and provides strategies for improving their performance to avoid unintentionally removing eligible studies and introducing bias into systematic reviews. Along with availability, ease-of-use, functionality, and capability, these findings are important to consider when researchers are selecting database platforms and supporting software programs for conducting systematic reviews.

Systematic review support received and needed by researchers: a survey of libraries supporting Ontario medical schools.

Introduction: Finding efficient ways to meet the growing demand for library systematic review support is imperative for facilitating the production of high-quality research. The objectives of this study were threefold: 1) to ascertain the systematic review support provided by health sciences libraries at Ontario medical schools and their affiliated hospitals, 2) to determine the perceived educational needs by researchers at these institutions, and 3) to assess the potential usefulness of freely available, online educational modules for researchers that discuss all stages of the systematic review process. Methods: We conducted a cross-sectional survey in June and July of 2020. Data was analyzed and presented using median and interquartile range (IQR) for continuous measures, and in proportions for categorical measures. Results: 13 of 19 libraries invited provided usable data. Most libraries spent more time supporting systematic reviews via collaboration and participation than by providing educational support. The perceived needs of library users were contrary to the perceived gaps in researcher support provided by the library/institution. All libraries reported they would find freely available, online educational modules useful for training researchers. Discussion: The next steps for our inter-professional research team will be to develop freely available, online education modules that introduce researchers to all stages of the systematic review process. These modules cannot replace the value that direct support from librarians, biostatisticians or methodology experts can provide, however, they may offer a more efficient way for libraries to familiarize researchers and trainees with best practices and universally accepted reporting guidelines for performing a high-quality review.

Perioperative blood transfusion and resection of colorectal cancer liver metastases: outcomes in routine clinical practice.

BACKGROUND: Prior work has shown associations between blood transfusion (BT) and inferior outcomes during resection for colorectal cancer liver metastases (CRLM). Herein, we describe short and long-term outcomes relating to perioperative BT in routine clinical practice. METHODS: All CRLM resections in Ontario, Canada from 2002 to 2009 were identified using the Ontario Cancer Registry. Log-binomial regression and Cox regression were used to explore factors associated with receipt of BT and the association of BT with 5-year cancer specific (CSS) and overall survival (OS), respectively. RESULTS: The study included 1310 patients; 31% (403/1310) had perioperative BT. Transfused patients had longer median length of stay (9 vs. 7 days, p < 0.001), higher 90-day mortality (9% vs. 1%, p < 0.001), greater 90-day readmission (28% vs. 16%, p < 0.001), and inferior 5-year CSS (41% vs. 48%, p = <0.001) and OS (38% vs. 47%, p < 0.001). Transfusion was independently associated with inferior CSS (HR = 1.35, 95% CI: 1.11-1.63) and OS (HR = 1.30, 95% CI: 1.10-1.53), however, excluding 90-day postoperative deaths showed these associations were no longer significant. CONCLUSION: Perioperative BT is common in patients undergoing resection of CRLM. While transfusion is associated with greater morbidity, mortality, and inferior survival, after excluding early postoperative deaths, BT does not appear to be independently associated with CSS or OS.

Management of rectal cancer in Canada: an evidence-based comparison of clinical practice guidelines

Background: Rectal cancer requires a multidisciplinary and multimodality treatment approach. Clinical practice guidelines (CPGs) provide a framework for delivering consistent, evidence-based health care. We compared provincial/territorial CPGs across Canada to identify areas of variability and evaluate their quality. Methods: We retrieved CPGs from Canadian organizations responsible for cancer care oversight and evaluated their quality and developmental methodology using the AGREE-II instrument. Recommendations for diagnostic and staging investigations, treatment by stage, and post-treatment surveillance of stage I­III rectal cancers were abstracted and compared. Results: We identified 7 sets of CPGs for analysis, varying in content, presentation, quality, and year last updated. Differences were noted in locoregional staging: 4 recommended magnetic resonance imaging over endorectal ultrasonography, 2 recommended either modality, and 3 specified scenarios for one over the other. Recommendations also varied for use of staging computed tomography of the chest versus chest radiography and for surgical management and indications for transanal excision. Recommendations for neoadjuvant therapy in stage II/III disease also differed: 3 guidelines recommended long-course chemoradiation over short-course radiation therapy alone, while 3 others recommended short-course radiation in specific clinical scenarios. Adjuvant chemotherapy for stage II/III disease was uniformly recommended, with variable protocols. The use of proctosigmoidoscopy and interval/duration of endoscopic post-treatment surveillance varied among guidelines. Conclusion: Canadian CPGs vary in their recommendations for staging, treatment, and surveillance of rectal cancer. Some of these differences reflect areas with limited definitive evidence. Consistent guidelines with uniform implementation across provinces/territories may lead to more equitable care to patients.

Contexte: Le cancer rectal requiert une approche thérapeutique multidisciplinaire et multimodalité. Les guides de pratique clinique (GPC) procurent un cadre pour assurer la prestation de soins de santé constants reposant sur des données probantes. Nous avons comparé les GPC des provinces et des territoires canadiens pour identifier les secteurs où ils varient et pour en évaluer la qualité. Méthodes: Nous avons obtenu les GPC des organisations canadiennes responsables des soins oncologiques et nous avons évalué leur qualité et la méthodologie de leur élaboration au moyen de l'outil AGREE II (Appraisal of Guidelines for Research & Evaluation). Nous avons extrait et comparé les recommandations en ce qui concerne les épreuves diagnostiques et la stadification, les traitements en fonction du stade et la surveillance post-thérapeutique du cancer rectal de stade I à III. Résultats: Nous avons recensé 7 GPC aux fins de cette analyse; leur contenu, leur présentation, leur qualité et l'année de leur plus récente mise à jour variaient. Des différences ont été observées au plan de la stadification locorégionale : 4 recommandaient l'imagerie par résonnance magnétique plutôt que l'échographie endorectale, 2 recommandaient l'une ou l'autre et 3 précisaient des circonstances où utiliser l'une plutôt que l'autre. Les recommandations variaient aussi pour ce qui est de l'utilisation de la scintigraphie c. radiographie thoracique de stadification, de la prise en charge chirurgicale et des indications de l'excision transanale. Les recommandations variaient également en ce qui concerne le traitement néoadjuvant pour la maladie de stade II/III : 3 guides recommandaient un traitement par chimioradiothérapie à long terme plutôt qu'une brève radiothérapie seule, tandis que 3 autres recommandaient une radiothérapie brève dans certains cas particuliers. La chimiothérapie adjuvante pour la maladie de stade II/III était uniformément recommandée, mais les protocoles variaient. L'utilisation de la proctosigmoïdoscopie et l'intervalle/durée de la surveillance endoscopique post-thérapeutique variaient d'un guide à l'autre. Conclusion: Les GPC canadiens varient quant à leurs recommandations pour la stadification, le traitement et la surveillance du cancer rectal. Certaines de ces différences témoignent du manque de données probantes concluantes dans certains secteurs. L'uniformisation des guides et de leur application entre les provinces et les territoires pourrait faciliter une prestation plus équitable des soins aux patients.

Scapular Bronchogenic Cyst in a Girl Presenting as Recurrent Cellulitis: A Case Report and Review of the Literature.

Bronchogenic cysts are rare, congenital cysts originating from respiratory epithelium and typically found within the chest. Cutaneous bronchogenic cysts are exceedingly uncommon, with only 19 reported cases in the scapular region and almost exclusively occurring in male patients. Herein, we present the case of a female patient with recurrent cellulitis secondary to a bronchogenic cyst, which was diagnosed after surgical excision. We also provide a review of the literature to consolidate the current understanding of cutaneous scapular bronchogenic cysts. To our knowledge, this is the first such case reported from Canada.

Duplicate publication in radiology journals.

OBJECTIVE: The purpose of this study is to evaluate the rate of duplicate publication in radiology journals. The secondary objective is to evaluate the sensitivity of iThenticate. MATERIALS AND METHODS: From January 1993 to December 2013, Déjà Vu (a database of highly similar citations) and PubMed were used to search for similar citations in 53 radiology journals. Citations were screened independently by two reviewers and verified by a third using predefined criteria to determine true cases of duplicate publication. The overall rate of duplicate publication was calculated; analysis of rate by journal, impact factor, and publication year was performed. The sensitivity of iThenticate was evaluated by analyzing all identified duplicate publications. RESULTS: From 128,818 citations in the included journals, 1786 (Déjà Vu) and 104 (PubMed) were flagged as potential duplicates. Of these, 248 (226 from Déjà Vu and 22 from PubMed) were classified as true duplicate publications after application of our criteria. The overall rate was 1.92/1000 citations; it varied widely across journals from zero to over 10/1000 citations, showed no correlation with impact factor (R(2) = 0.06; p = 0.093), and no change over time (R(2) = 0.28; p = 0.515). iThenticate flagged 153 of 248 (61.9%) duplicates as "possible duplicates" (defined as overall percentage match > 30%) and identified the corresponding duplicate citation pair in 140 of 248 (56.7%) cases; in 98 of these, the duplicate citation pair was the highest percentage similarity match. CONCLUSION: Duplicate publications in radiology journals are uncommon. The rate varies widely between journals, but was not associated with journal impact factor and did not change over time. iThenticate shows promise for identification of duplicate publications; however, refinements may be necessary to maximize its effectiveness.

KISS1R induces invasiveness of estrogen receptor-negative human mammary epithelial and breast cancer cells.

Kisspeptins (KPs), peptide products of the KISS1 metastasis-suppressor gene, are endogenous ligands for a G protein-coupled receptor (KISS1R). KISS1 acts as a metastasis suppressor in numerous human cancers. However, recent studies have demonstrated that an increase in KISS1 and KISS1R expression in patient breast tumors correlates with higher tumor grade and metastatic potential. We have shown that KP-10 stimulates invasion of estrogen receptor α (ERα)-negative MDA-MB-231 breast cancer cells via transactivation of the epidermal growth factor receptor (EGFR). Here, we report that either KP-10 treatment of ERα-negative nonmalignant mammary epithelial MCF10A cells or expression of KISS1R in MCF10A cells induced a mesenchymal phenotype and stimulated invasiveness. Similarly, exogenous expression of KISS1R in ERα-negative SKBR3 breast cancer cells was sufficient to trigger invasion and induced extravasation in vivo. In contrast, KP-10 failed to transactivate EGFR or stimulate invasiveness in the ERα-positive MCF7 and T47D breast cancer cells. This suggested that ERα negatively regulates KISS1R-dependent breast cancer cell migration, invasion, and EGFR transactivation. In support of this, we found that these KP-10-induced effects were ablated upon exogenous expression of ERα in the MDA-MB-231 cells, by down-regulating KISS1R expression. Lastly, we have identified IQGAP1, an actin cytoskeletal binding protein as a novel binding partner of KISS1R, and have shown that KISS1R regulates EGFR transactivation in breast cancer cells in an IQGAP1-dependent manner. Overall, our data strongly suggest that the ERα status of mammary cells dictates whether KISS1R may be a novel clinical target for treating breast cancer metastasis.