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Patients with myeloproliferative neoplasms (MPNs) face chronic symptom burden. Online symptom assessment studies allow for recruitment of large numbers of motivated patients, but patient self-selection can lead to sampling bias. This study evaluated how gender representativeness in MPN symptom surveys and trials impacted symptom score mean estimates, using data from 4825 survey respondents and 291 trial participants with MPNs. The survey data showed that men participated at a rate roughly 50% less than what would be expected based on prevalence, and women reported higher scores than men on average for six of 10 symptoms. Together, this led to potential over estimation in six of 10 symptom score means (ranging from 5.8% to 15.3% overestimated). The trial data showed less gender-based sampling bias compared to the survey data. Studies utilizing online symptom surveys should implement study design features to recruit more men, assess for gender participation imbalances, and provide weighted estimates where appropriate.

Purpose: Automated scalp cooling (ASC) is available to patients undergoing chemotherapy for breast cancer to decrease chemotherapy-induced alopecia. This study sought to elucidate patient and chemotherapy nursing perspectives on the ASC experience., Methods: This is a survey-based study of chemotherapy nursing staff and patients with breast cancer regarding perceived efficacy, side effects, administration, support, and overall opinions of ASC. Chemotherapy nurses across a large, multi-regional tertiary healthcare system completed a one-time survey regarding their experiences in administering ASC. Breast cancer patients who utilized ASC were surveyed along with a control group who underwent alopecia-inducing chemotherapy without ASC use for comparison., Results: The majority of nursing responses reported inadequate technical support, an increased burden of administering ASC compared to other clinical duties, and that they would not recommend ASC to a family member or friend. Patients who underwent ASC reported significantly less hair loss and were significantly less likely to shave their heads or wear a wig, but this did not translate into significant differences in body image or psychosocial wellbeing responses. Time investment was the most significant burden related to ASC., Conclusion: Patients using ASC reported significantly less hair loss compared to those not using ASC during alopecia-inducing breast cancer chemotherapy, but this did not translate to improved body image. The majority of chemotherapy nurses reported they lacked adequate support in administering ASC and would not recommend it. Enhanced nursing support may provide a means for improving the ASC experience for both nursing staff and patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This study investigates Enhanced Recovery After Surgery (ERAS®) protocols' impact on long-term opioid and sedative use following mastectomy with or without implant-based breast reconstruction (IBBR)., Summary Background Data: ERAS® protocols for patients undergoing mastectomy with or without IBBR are associated with decreased length of stay, increased rate of same-day discharge, decreased postoperative pain, and decreased postoperative opioid requirements. However, less is known about their effect on opioid and sedative use beyond 90 days after surgery., Methods: A retrospective review of all patients undergoing mastectomy with or without IBBR at a single institution between January 2013 and December 2019. Mastectomy ERAS® protocols were implemented in February 2017, creating two groups: pre-ERAS® and ERAS®. Baseline characteristics and prevalence of chronic opioid and sedative use were compared. Univariable and multivariable logistic regression predicted factors associated with increased odds of chronic opioid and sedative use., Results: 756 patients were evaluated: 405 pre-ERAS® and 351 ERAS®. Post-ERAS®, chronic opioid use decreased in opioid-naïve (40% vs. 30%, P=0.024) and opioid-tolerant patients (58% vs. 37%, P=0.002), with no increase in chronic sedative use. There were decreased odds of chronic opioid use for all ERAS® patients (OR=0.57, 95% CI: 0.42-0.76)), and of IBBR patients, those receiving subcutaneous implants (OR=0.31, 95% CI: 0.20-0.48). There was increased chronic opioid-use odds if undergoing bilateral surgery (OR=1.54, 95% CI: 1.14-2.08), two-stage reconstruction (OR=9.78, 95% CI: 5.94-16.09), and for patients with higher PACU pain scores (OR=1.09, 95% CI: 1.03-1.14) or >150 discharge OMEs (OR=2.63, 95% CI: 1.48-4.68)., Conclusion: ERAS® protocols for mastectomy patients with or without IBR are associated with decreases in chronic opioid use, without concomitant increases in chronic sedative use., Competing Interests: Disclosures/ Funding: The authors have no financial or other conflicts of interest pertaining to this research to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Chronic inflammation is integral to myeloproliferative neoplasm (MPN) pathogenesis. JAK inhibitors reduce cytokine levels, but not without significant side effects. Nutrition is a low-risk approach to reduce inflammation and ameliorate symptoms in MPN. We performed a randomized, parallel-arm study to determine the feasibility of an education-focused Mediterranean diet intervention among patients with MPN., Experimental Design: We randomly assigned patients with MPN to either a Mediterranean diet or standard U.S. Dietary Guidelines for Americans (USDA). Groups received equal but separate education with registered dietician counseling and written dietary resources. Patients were prospectively followed for feasibility, adherence, and symptom burden assessments. Biological samples were collected at four timepoints during the 15-week study to explore changes in inflammatory biomarkers and gut microbiome., Results: The Mediterranean diet was as easy to follow for patients with MPN as the standard USDA diet. Approximately 80% of the patients in the Mediterranean diet group achieved a Mediterranean Diet Adherence Score of ≥8 throughout the entire active intervention period, whereas less than 50% of the USDA group achieved a score of ≥8 at any timepoint. Improvement in symptom burden was observed in both diet groups. No significant changes were observed in inflammatory cytokines. The diversity and composition of the gut microbiome remained stable throughout the duration of the intervention., Conclusions: With dietician counseling and written education, patients with MPN can adhere to a Mediterranean eating pattern. Diet interventions may be further developed as a component of MPN care, and potentially incorporated into the management of other hematologic conditions., Significance: Diet is a central tenant of management of chronic conditions characterized by subclinical inflammation, such as cardiovascular disease, but has not entered the treatment algorithm for clonal hematologic disorders. Here, we establish that a Mediterranean diet intervention is feasible in the MPN patient population and can improve symptom burden. These findings warrant large dietary interventions in patients with hematologic disorders to test the impact of diet on clinical outcomes., (© 2024 The Authors; Published by the American Association for Cancer Research.)

Introduction: Inpatient hyperglycemia is an established independent risk factor among several patient cohorts for hospital readmission. This has not been studied after kidney transplantation. Nearly one-third of patients who have undergone a kidney transplant reportedly experience 30-day readmission., Methods: Data on first-time solitary kidney transplantations were retrieved between September 2015 and December 2018. Information was linked to the electronic health records to determine diagnosis of diabetes mellitus and extract glucometric and insulin therapy data. Univariate logistic regression analysis and the XGBoost algorithm were used to predict 30-day readmission. We report the average performance of the models on the testing set on bootstrapped partitions of the data to ensure statistical significance., Results: The cohort included 1036 patients who received kidney transplantation; 224 (22%) experienced 30-day readmission. The machine learning algorithm was able to predict 30-day readmission with an average area under the receiver operator curve (AUC) of 78% with (76.1%, 79.9%) 95% confidence interval (CI). We observed statistically significant differences in the presence of pretransplant diabetes, inpatient-hyperglycemia, inpatient-hypoglycemia, minimum and maximum glucose values among those with higher 30-day readmission rates. The XGBoost model identified the index admission length of stay, presence of hyper- and hypoglycemia, the recipient and donor body mass index (BMI) values, presence of delayed graft function, and African American race as the most predictive risk factors of 30-day readmission. Additionally, significant variations in the therapeutic management of blood glucose by providers were observed., Conclusions: Suboptimal glucose metrics during hospitalization after kidney transplantation are associated with an increased risk for 30-day hospital readmission. Optimizing hospital blood glucose management, a modifiable factor, after kidney transplantation may reduce the risk of 30-day readmission., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Myeloid neoplasms (myelodysplastic syndrome [MDS], myelofibrosis, and chronic myelomonocytic [CMML]) are aggressive hematological malignancies for which, despite recent approvals, novel therapies are needed to improve clinical outcomes. The hedgehog (HH) pathway is one of the main pathways for cancer stem cells survival and several HH inhibitors (HHi) are approved in clinical practice., Methods: Sonidegib (SON), an oral HHi, was tested in this phase 1/1b trial in combination with azacitidine (AZA, 75 mg/m 2 days ×7) in patients with newly diagnosed and relapsed/refractory (r/r) chronic MN or acute myeloid leukemia (AML)., Results: Sixty-two patients (28 [45%] newly diagnosed) were treated in this study, including 10 patients in the dose-finding component and 52 patients in phase 1b. SON 200 mg oral daily on days 1-28 each cycle was deemed the recommended dose for phase 1b. Out of 21 rrAML patients, two achieved response (one complete response/one morphologic leukemia-free state) with no responses seen in seven r/r MDS/CMML patients. In newly diagnosed AML/MDS, response was seen in six (three had complete remission, two had morphological leukemia-free status) of 27 patients. Median overall survival was 26.4 and 4.7 months for newly diagnosed MDS and AML, respectively. Safety was satisfactory with common (>20%) side effects including fatigue, constipation, nausea, cough, insomnia, and diarrhea. Only 7% of patients died in the study, and none of the deaths were deemed related to treatment., Conclusions: Our study shows that AZA + SON are a safe combination in a patient with MN. Similar to other hedgehog inhibitors, this combination yielded limited response rate in patients with myeloid neoplasms., (© 2023 American Cancer Society.)

There is limited research on the impact of revisional surgery after breast reconstruction on patient experience and postoperative quality of life (QoL)., Methods: Patients undergoing mastectomy with immediate implant-based or autologous free-flap breast reconstruction from 2008 to 2020 were reviewed. These patients were categorized by revisions (0-1, 2-3, and 4+) and surveyed on QoL metrics using BREAST-Q and Was It Worth It? (WIWI) questionnaires. BREAST-Q QoL, satisfaction, and WIWI metrics between revision groups were evaluated., Results: Among 252 patients, a total of 150 patients (60%) underwent zero to one revisions, 72 patients (28%) underwent two to three revisions, and 30 patients (12%) underwent four or more revisions. Median follow-up was 6 years (range, 1-11 years). BREAST-Q satisfaction among patients with four or more revisions was significantly lower ( P = 0.03), while core QoL domains (chest physical, psychosocial, and sexual well-being) did not significantly differ. Analysis of unplanned reoperations due to complications and breast satisfaction showed no significant difference in QoL scores between groups ( P = 0.08). Regarding WIWI QoL metrics, four or more revisions were associated with a higher rate of worse QoL ( P = 0.035) and worse overall experience ( P = 0.001). Most patients in all revision groups felt it was worthwhile to undergo breast reconstruction (86%), would choose breast reconstruction again (83%), and would recommend breast reconstruction to others (79%)., Conclusions: Overall, a majority of patients undergoing revisions after breast reconstruction still have a worthwhile experience. Although reoperations after breast reconstruction do not significantly impact long-term BREAST-Q QoL domains, patients undergoing four or more revisions have significantly lower breast satisfaction, worse QoL, and a postoperative experience worse than expected., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background: This study aimed to evaluate how enhanced recovery (ER) protocols and same-day discharge (SDD) influences patients' postoperative quality of life (QOL)., Methods: Patients who underwent mastectomy with implant-based breast reconstruction from 2008 to 2020 were identified in a prospective database. The study assessed QOL with BREAST-Q and Was It Worth It? (WIWI) questionnaires. Responses were compared between the ER and pre-ER groups and between the SDD and hospital stay (HS) groups using one-way analysis of variance (ANOVA) and chi-square tests., Results: The inclusion criteria were met by 568 patients, with a 43% response rate, and 217 patients were included for analysis. Chest physical well-being was lower for the ER cohort, but postoperative breast satisfaction was higher. Psychosocial status, sexual well-being, and satisfaction with information given did not differ significantly between the ER group and the pre-ER or SDD group. In the compared groups, QOL did not differ significantly., Conclusions: Enhanced recovery with SDD after mastectomy using implant-based reconstruction did not have an adverse impact on patient postoperative QOL., (© 2023. Society of Surgical Oncology.)

Minimal residual disease (MRD) assays allow response assessment in patients with multiple myeloma (MM), and negativity is associated with improved survival outcomes. The role of highly sensitive next generation sequencing (NGS) MRD in combination with functional imaging remains to be validated. We performed a retrospective analysis on MM patients who underwent frontline autologous stem cell transplant (ASCT). Patients were evaluated at day 100 post-ASCT with NGS-MRD and positron emission tomography (PET-CT). Patients with ≥ 2 MRD measurements were included in a secondary analysis for sequential measurements. 186 patients were included. At day 100, 45 (24.2%) patients achieved MRD negativity at a sensitivity threshold of 10 -6 . MRD negativity was the most predictive factor for longer time to next treatment (TTNT). Negativity rates did not differ according to MM subtype, R-ISS Stage nor cytogenetic risk. PET-CT and MRD had poor agreement, with high rates of PET-CT negativity in MRD-positive patients. Patients with sustained MRD negativity had longer TTNT, regardless of baseline risk characteristics. Our results show that the ability to measure deeper and sustainable responses distinguishes patients with better outcomes. Achieving MRD negativity was the strongest prognostic marker and could help guide therapy-related decisions and serve as a response marker for clinical trials., (© 2023. The Author(s).)

Aim: To determine overall survival (OS) and glycemic control in patients with cancer and diabetes., Materials & methods: Patients of our institution with breast, colon, lung, pancreas and prostate cancer were retrospectively reviewed. OS was compared between matched patients with and without diabetes, and changes in glucose value over time were assessed., Results: For 3934 patients each with and without diabetes, adjusted analysis showed no difference in OS according to diabetes status (hazard ratio: 1.07; 95% CI: 0.96-1.20). Mean glucose values decreased over time in patients with and without diabetes (p = 0.01)., Conclusion: In this large study of patients with five common cancers, the co-occurrence of diabetes did not affect OS. Cancer did not adversely affect glucose levels., (© 2023 Mayo Foundation for Medical Education & Research.)

Purpose/objectives: To assess adverse events (AEs) and disease-specific outcomes after proton therapy for isolated local-regional recurrence (LRR) of breast cancer after mastectomy without prior radiotherapy (RT)., Materials/methods: Patients were identified from a multi-institutional prospective registry and included if diagnosed with invasive breast cancer, initially underwent mastectomy without adjuvant RT, experienced an LRR, and subsequently underwent salvage treatment, including proton therapy. Follow-up and cancer outcomes were measured from the date of RT completion., Results: Nineteen patients were included. Seventeen patients were treated with proton therapy to the chest wall and comprehensive regional lymphatics (17/19, 90%). Maximum grade AE was grade 2 in 13 (69%) patients and grade 3 in 4 (21%) patients. All patients with grade 3 AE received > 60 GyE (p=0.04, Spearman correlation coefficient=0.5). At the last follow-up, 90% of patients were alive with no LRR or distant recurrence., Conclusions: For breast cancer patients with isolated LRR after initial mastectomy without adjuvant RT, proton therapy is well-tolerated in the salvage setting with excellent loco-regional control. All grade 3 AEs occurred in patients receiving > 60 GyE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Laughlin, Bhangoo, Niska, Thorpe, Girardo, Anderson, Kosiorek, McGee, Hartsell, Chang, Rossi, Tsai, Choi and Vargas.)

Background: Neoadjuvant endocrine therapy (NET) can help downstage certain breast cancers prior to surgical resection. This study measured the accuracy of conventional mammography (MMG), ultrasound (US), magnetic resonance imaging (MRI), and contrast-enhanced mammography (CEM) for assessing breast tumor size in response to NET., Patients and Methods: Patients who underwent surgery after NET from 2013 to 2021 were identified. The maximal dimension of residual tumor on imaging was compared with the maximal dimension on final pathology. Lin's concordance correlation coefficient (r c ) and Spearman's rank correlation coefficient (r) were used to assess agreement., Results: In total, 119 patients with invasive breast cancer underwent NET, posttreatment imaging, and surgery. Tumor size reported on posttreatment CEM correlated with size on final pathology to within 1 cm in n = 42 (58%) of patients, equivalent to the accuracy of MRI (n = 35, 58%). Size was accurately predicted by US in 54% and in 48% of MMG. Posttreatment imaging tumor size was moderately correlated with final tumor size on pathology CEM (r = 0.49; r c  = 0.38), MRI (r = 0.52; r c  = 0.45), and US (r = 0.41; r c  = 0.28). MMG was weakly correlated (r = 0.21; r c  = 0.16). Similar findings were shown in subgroup analysis; in those who received all four post-NET imaging, CEM and MRI again performed comparably, with r = 0.36 and 0.41, respectively, US (r = 0.43) and MMG (r = 0.28)., Conclusions: Compared with mammography and US, CEM and MRI had higher accuracy in estimating final tumor size for breast cancers treated with NET. Contrast-enhanced imaging is a helpful adjunct when response to preoperative therapy will impact clinical management., (© 2022. Society of Surgical Oncology.)

Background: Enhanced recovery after surgery (ERAS) protocols following mastectomy with or without implant-based breast reconstruction (IBBR) include ketorolac for multimodal perioperative analgesia. There are concerns that ketorolac could be associated with increased risk of postoperative hematoma formation., Methods: Retrospective review of patients undergoing mastectomy with or without IBBR between January 2013 and December 2019 at a single institution. Patients received 15 mg, 30 mg, or no ketorolac depending on ERAS protocol adherence, patient characteristics, and surgeon preference. Clinically significant hematoma was defined as requiring surgical intervention on day of surgery or postoperative day 1. Patients were compared by demographics, surgical characteristics, ketorolac dose, and hematoma prevalence. Univariable and multivariable logistic regression evaluated hematoma formation odds., Results: Eight hundred patients met inclusion criteria: 477 received ketorolac. Those who received ketorolac were younger, had lower ASA scores, were more likely to have bilateral procedures and undergo concomitant IBBR, had longer operative times, were less likely to take antiplatelet or anticoagulation medications, had higher PACU pain scores, and had higher incidence of hematomas requiring surgical intervention. Of the cohort, 4.4% had clinically significant hematomas. The 15 mg and 30 mg ketorolac groups had similar prevalence (6.0% vs 5.8%, p = 0.95). On univariable regression, there were increased odds of hematoma formation in patients who were younger, had bilateral procedures, had longer OR times, and who received ketorolac. On multivariable regression, none of the prior variables remained significant., Conclusion: After accounting for associations with longer operative times, concomitant IBBR, and bilateral procedures, ketorolac administration did not remain an independent risk factor for hematoma formation., (© 2022. Society of Surgical Oncology.)

Background: Radium (Ra)-223 is an established treatment option for patients with metastatic castrate-resistant prostate cancer (mCRPC) who have symptomatic bone metastases without soft tissue disease. Studies have indicated genetic aberrations that regulate DNA damage response (DDR) in prostate cancer can increase susceptibility to treatments such as poly ADP-ribose polymerase inhibitors and platinum-based therapies. This study aims to evaluate mCRPC response to Ra-223 stratified by tumor genomics., Methods: This is a retrospective study of mCRPC patients who received Ra-223 and genetic testing within the Mayo Clinic database (Arizona, Florida, and Minnesota) and Tulane Cancer Center. Patient demographics, genetic aberrations, treatment responses in terms of alkaline phosphatase (ALP) and prostate-specific antigen (PSA), and survival were assessed. Primary end points were ALP and PSA response. Secondary end points were progression-free survival (PFS) and overall survival (OS) from time of first radium treatment., Results: One hundred and twenty-seven mCRPC patients treated with Ra-223 had germline and/or somatic genetic sequencing. The median age at time of diagnosis and Ra-223 treatment was 61.0 and 68.6 years, respectively. Seventy-nine (62.2%) had Gleason score ≥ 8 at time of diagnosis. 50.4% received prior docetaxel, and 12.6% received prior cabazitaxel. Notable alterations include TP53 (51.7%), BRCA 1/2 (15.0%), PTEN (13.4%), ATM (11.7%), TMPRSS2-ERG (8.2%), RB deletion (3.4%), and CDK12 (1.9%). There was no significant difference in ALP or PSA response among the different genetic aberrations. Patients with a TMPRSS2-ERG mutation exhibited a trend toward lower OS 15.4 months (95% confidence interval [CI] 10.0-NR) versus 26.8 months (95% CI 20.9-35.1). Patients with an RB deletion had a lower PFS 6.0 months (95% CI 1.28-NR) versus 9.0 months (95% CI 7.3-11.1) and a lower OS 13.9 months (95% CI 5.2-NR) versus 26.5 months (95% CI 19.8-33.8)., Conclusions: Among mCRPC patients treated with Ra-223 at Mayo Clinic and Tulane Cancer Center, we did not find any clear negative predictors of biochemical response or survival to treatment. TMPRSS2-ERG and RB mutations were associated with a worse OS. Prospective studies and larger sample sizes are needed to determine the impact of genetic aberrations in response to Ra-223., (© 2022 Wiley Periodicals LLC.)

Background: The effect of postoperative sensation on quality-of-life (QoL) following nipple-sparing mastectomy (NSM) with implant-based reconstruction is not well described. We evaluated the impact of breast and nipple sensation on patient QoL by using BREAST-Q., Methods: Patients undergoing NSM with implant reconstruction from 2008 to 2020 were mailed a survey to characterize their postoperative breast and nipple sensation. BREAST-Q metrics were compared between totally numb patients and those with sensation., Results: A total of 349 patients were included. Overall, 131 (38%) responded; response rates regarding breast and nipple sensation were 36% (N = 124/349) and 34% (N = 117/349). Median time from surgery to survey completion was 6 years. The majority had bilateral procedures (101, 77%), including direct-to-implant (99, 76%) and tissue expander (32, 24%) reconstruction. Regarding breast sensation, the majority of patients reported their reconstructed breasts as totally numb (47, 38%) or much less sensation than before surgery (59, 48%). Regarding nipple sensation, the majority of patients reported their nipples were totally numb (67, 57%) or had much less sensation than before surgery (37, 32%). Total numbness of reconstructed breasts resulted in a significantly lower chest physical well-being (mean score: 73.5 vs. 81.2, respectively, P = 0.048). Total numbness of postoperative nipple(s) resulted in significantly lower chest physical (mean score: 74.8 vs. 85.2, respectively, P = 0.007), psychosocial (mean score 77.4 vs. 84.4, respectively, P = 0.041), and sexual well-being (mean score: 55.7 vs. 68.3, respectively, P = 0.002)., Conclusions: Long-term breast and nipple sensation are significantly diminished after NSM with implant reconstruction. Patients with preserved sensation experience better physical, psychosocial, and sexual well-being., Competing Interests: Declaration of competing interest None declared., (Copyright © 2022 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Altered tumor suppressor genes (TSG-alt) in prostate cancer are associated with worse outcomes. The prognostic value of TSG-alt in metastatic, hormone-sensitive prostate cancer (M1-HSPC) is unknown. We evaluated the effects of TSG-alt on outcomes in M1-HSPC and their prognostic impact by first-line treatment., Methods: We retrospectively identified patients with M1-HSPC at our institution treated with first-line androgen deprivation therapy plus docetaxel (ADT + D) or abiraterone acetate (ADT + A). TSG-alt was defined as any alteration in one or more TSG. The main outcomes were Kaplan-Meier-estimated progression-free survival (PFS) and overall survival, analyzed with the log-rank test. Clinical characteristics were compared with the χ 2 test and Kruskal-Wallis rank sum test. Cox regression was used for univariate and multivariable analyses., Results: We identified 97 patients with M1-HSPC: 48 (49%) with ADT + A and 49 (51%) with ADT + D. Of 96 patients with data available, 33 (34%) had 1 TSG-alt, 16 (17%) had 2 TSG-alt, and 2 (2%) had 3 TSG-alt. The most common alterations were in TP53 (36%) and PTEN (31%); 6% had RB1 alterations. Median PFS was 13.1 (95% CI, 10.3-26.0) months for patients with normal TSGs (TSG-normal) vs. 7.8 (95% CI, 5.8-10.5) months for TSG-alt (P = 0.005). Median PFS was lower for patients with TSG-alt vs TSG-normal for those with ADT + A (TSG-alt: 8.0 [95% CI, 5.8-13.8] months vs. TSG-normal: 23.2 [95% CI, 13.1-not estimated] months), but not with ADT + D (TSG-alt: 7.8 [95% CI, 5.7-12.9] months vs. TSG-normal: 9.5 [95% CI, 4.8-24.7] months). On multivariable analysis, only TSG-alt predicted worse PFS (hazard ratio, 2.37; 95% CI, 1.42-3.96; P < 0.001)., Conclusions: The presence of TSG-alt outperforms clinical criteria for predicting early progression during first-line treatment of M1-HSPC. ADT + A was less effective in patients with than without TSG-alt. Confirmation of these findings may establish the need for inclusion of molecular stratification in treatment algorithms., (© 2021. The Author(s).)

Background: FGFR2 genomic alterations are observed in 10-20% of cholangiocarcinoma (CCA). Although FGFR2 fusions are an important actionable target, FGFR2 protein expression has not been thoroughly characterized., Aims: To evaluate FGFR2 protein expression in cholangiocarcinoma harboring FGFR2 genomic alterations., Methods: FGFR2 protein expression was evaluated in 99 CCA cases with two different antibodies. FGFR2 genomic alterations were confirmed via next-generating sequencing (NGS) or FISH. Primary objective was to determine the specificity and sensitivity of FGFR2 immunohistochemistry staining for detecting FGFR2 genomic alterations. Secondary objectives included overall FGFR2 immunohistochemistry staining in CCA patients, and evaluation of whether FGFR2 expression correlates with clinical outcomes including overall survival (OS), progression-free survival (PFS), and time-to-tumor recurrence (TTR)., Results: Immunohistochemistry staining with two antibodies against FGFR2, FPR2-D, and clone 98706 showed high accuracy (78.7% and 91.9%) and specificity (82.9% and 97.7%), and moderate sensitivity (53.9% and 57.1%), respectively, when compared with the standard methods for detecting FGFR2 genomic alterations. In a median follow-up of 72 months, there were no statistically significant differences in OS, PFS, and TTR, for patients with positive or negative FGFR2 staining., Conclusion: FGFR2 protein expression by immunohistochemistry has high specificity and therefore could be used to imply the presence of FGFR2 genomic alterations in the context of a positive test. In the case of a negative test, NGS or FISH would be necessary to ascertain cases with FGFR2 genomic alterations., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Study Objective: To determine whether advancing a manipulator increased the distance of the ureter to the cervix and/or vagina., Design: Prospective., Setting: Academic institution., Patients: A total of 22 intact fresh-frozen female pelvises., Interventions: A total of 6 ureteral distances were measured per pelvis. Included were the following measurements on each side: (1) from the lateral cervical wall to the ureter at the intersection with the uterine artery; (2) from the lateral cervical wall to the parametrial ureter; and (3) from the vagina to the ureter at the intersection with the uterine artery. All measurements were obtained with and without advancement of a uterine manipulator., Measurements and Main Results: The average distance from the ureter to the cervix and vagina without advancing the manipulator was 2.8 and 3.1 cm, respectively, and the distance from the parametrial ureter to the cervix was 3.3 cm. When the manipulator was advanced, all ureteral distances increased by 0.8, 0.6, and 0.6 cm, respectively, in 12 of the 22 pelvises (55%). Advancing the manipulator did not increase at least 1 of the distances in 10 of the 22 pelvises (45%). The advancement of the manipulator lengthened the 2 shortest ureteral distances of 1 cm noted in 1 pelvis (4.5%) by 0.9 and 0.4 cm., Conclusion: The uterine manipulator increased the distance of the ureter to the cervix and vagina for all measurements in 55.5% of the pelvises. The greatest increase was 0.9 cm. The manipulator did not increase at least 1 of the distances in 10 of the 22 pelvises (45.4%)., (Copyright © 2022 AAGL. Published by Elsevier Inc. All rights reserved.)

Background: Limited data exist outlining reoperations after direct-to-implant (DTI), tissue expander (TE) and autologous free-flap breast reconstruction., Methods: Patients undergoing mastectomy with reconstruction from 2008 to 18 were reviewed. Patient factors, surgical techniques, planned, unplanned, and total reoperations were analyzed., Results: Among 544 total patients, the majority underwent DTI (294, 54%) or TE (176, 32%); 74 (14%) received autologous free-flaps. Majority of DTI patients (55%) underwent subsequent reoperations. Compared to autologous tissue, DTI had less patients undergo additional surgery (76% vs. 55%, P = 0.001). Incidence of total unplanned reoperations did not significantly differ between reconstructive groups. The rate of unplanned reoperations due to complications was lowest for DTI (39%) when compared to TE (48%) and autologous (55%, P = 0.015). Compared to TE, DTI carried a lower risk for ≥2 total reoperations (OR = 0.21, 95% CI 0.13-0.33, P < 0.001)., Conclusions: Seldom "one and done," additional surgery after DTI remains significant., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The goal of therapy for patients with essential thrombocythemia (ET) and polycythemia vera (PV) is to reduce thrombotic events by normalizing blood counts. Hydroxyurea (HU) and interferon-α (IFN-α) are the most frequently used cytoreductive options for patients with ET and PV at high risk for vascular complications. Myeloproliferative Disorders Research Consortium 112 was an investigator-initiated, phase 3 trial comparing HU to pegylated IFN-α (PEG) in treatment-naïve, high-risk patients with ET/PV. The primary endpoint was complete response (CR) rate at 12 months. A total of 168 patients were treated for a median of 81.0 weeks. CR for HU was 37% and 35% for PEG (P = .80) at 12 months. At 24 to 36 months, CR was 20% to 17% for HU and 29% to 33% for PEG. PEG led to a greater reduction in JAK2V617F at 24 months, but histopathologic responses were more frequent with HU. Thrombotic events and disease progression were infrequent in both arms, whereas grade 3/4 adverse events were more frequent with PEG (46% vs 28%). At 12 months of treatment, there was no significant difference in CR rates between HU and PEG. This study indicates that PEG and HU are both effective treatments for PV and ET. With longer treatment, PEG was more effective in normalizing blood counts and reducing driver mutation burden, whereas HU produced more histopathologic responses. Despite these differences, both agents did not differ in limiting thrombotic events and disease progression in high-risk patients with ET/PV. This trial was registered at www.clinicaltrials.gov as #NCT01259856., (© 2022 by The American Society of Hematology.)

Background: The relationship between tumor-infiltrating lymphocytes (TILs) and regression in melanoma is unknown. This report describes a large multicenter study assessing the association between TILs and regression., Methods: The Sentinel Lymph Node Working Group database was queried from 1993 to 2018 for cases with TILs and regression data. Clinicopathologic factors were correlated with regression and TIL status, sentinel lymph node (SLN) status, and overall survival (OS)., Results: The study enrolled 2450 patients. In 1811 cases, TILs (73.9%) were present, with regression present in 328 of these 1811 (18.1%) cases and in 49 (7.7%) of 639 cases without TILs. The presence of TILs was significantly associated with regression (p < 0.0001) as well as a negative SLN (p < 0.05). However, when TILs were stratified by regression status, only absence or presence of both TILs and regression were significantly associated with SLN metastases (p = 0.038). Although the presence of TILs was associated with OS (p < 0.05), regression status by itself was not (p = 0.2058 and 0.252, respectively). Furthermore, when TILs were stratified by regression status, only the presence of TILs with or without regression was significantly associated with improved OS (p = 0.0081 and 0.0137, respectively) versus the absence of both TILs and regression, with regression status not significantly affecting OS for patients with or without TILs (p = 0.2314 and 0.65, respectively)., Conclusions: Regression is highly correlated with TILs, but only TILs are significantly associated with SLN metastasis and OS in melanoma patients, whereas regression is not. The impact of regression on outcomes ultimately appears dependent upon the absence or presence of TILs., (© 2022. Society of Surgical Oncology.)

Background: The significance of tumor-infiltrating lymphocytes (TILs) in melanoma is debated. This article presents a multicenter, retrospective study assessing the predictive and prognostic value of TILs., Methods: The Sentinel Lymph Node Working Group database was queried from 1993 to 2018 for cases with known TIL data. TILs were categorized as absent or present, which included nonbrisk (NB), brisk (B), and present but unspecified TIL levels. Clinicopathologic factors were correlated with TILs, sentinel lymph node (SLN) status, and melanoma-specific survival (MSS)., Results: Overall, 3203 patients were included. The median thickness was 1.5 mm, and 469 cases had SLN metastases. TILs were present in 2458 cases (76.7%), with NB, B, and unspecified TILs seen in 1691 (68.8%), 691 (28.1%), and 76 (3.1%), respectively. Multivariable analysis showed that the presence of TILs significantly predicted a negative SLN biopsy (P < .05). The median follow-up was 25.2 months. MSS was significantly better for cases with TILs than cases without TILs (P < .001). According to multivariable analysis, age, gender, thickness, mitotic rate, ulceration, lymphovascular invasion, and SLN status were significantly prognostic of MSS (all P values < .05). Although TILs were not prognostic of MSS, when multiple imputation was used and the SLN status was excluded, the presence of TILs was significantly prognostic of improved MSS (hazard ratio, 0.78; 95% confidence interval, 0.64-0.95; P = .0154)., Conclusions: TILs are a favorable marker because their presence significantly predicts a negative SLN, and the absence of TILs may be a prognostic marker of worse survival in patients with a positive SLN but not a negative SLN. TILs may also serve as a prognostic marker of survival when the SLN status is not considered., (© 2022 American Cancer Society.)

Background and Objectives: The prognostic significance of regression in predicting melanoma recurrences is unknown. We present a large multicenter study correlating regression with recurrence., Methods: The Sentinel Lymph Node Working Group database was queried from 1993 to 2018 for cases with regression data. Clinicopathologic factors were correlated with overall and first-site of recurrence and with recurrence-free survival (RFS)., Results: There were 4790 patients and the median follow-up was 39.6 months. Regression and recurrences were seen in 1081 (22.6%) and 773 (16.1%) cases, respectively. First-site locoregional and distant recurrences were seen in 412 (8.6%) and 352 (7.3%) patients, respectively. Regression was seen in 15.8% and 24.7% of all cases with and without recurrences (p < 0.0001), respectively, while regression was seen in 14.3% and 17.9% of first-site locoregional and distant recurrent cases, respectively, compared with 23.3% and 22.9% of patients with regression and without first-site locoregional and distant recurrences, respectively (p = 0.29). On multivariable analysis, after controlling for age, gender, thickness, ulceration, lymphovascular invasion, and sentinel lymph node status, regression significantly predicted improved RFS (p = 0.004) and fewer first-site regional recurrences (p = 0.017)., Conclusion: Our data suggest that regression is a favorable prognostic marker in melanoma and predicts significantly better RFS and decreased first-site regional recurrences., (© 2021 Wiley Periodicals LLC.)

Background: Neoadjuvant therapy aims to preoperatively downstage breast cancer patients. We evaluated nodal upstaging in clinically node-negative (cN0) patients receiving neoadjuvant chemotherapy (NAC) and neoadjuvant endocrine therapy (NET)., Methods: cN0 patients undergoing neoadjuvant therapy from 2009 to 2018 were reviewed. Univariate and multivariate analyses evaluated rates of nodal upstaging., Results: A total of 228 cN0 patients with a mean age of 55 years underwent neoadjuvant therapy for Stage I-III invasive carcinoma. Subtypes included ER+/HER2- = 93 (40%), HER2+ = 61 (27%), and triple negative (TNBC) = 74 (33%). Among ER+/HER2- patients, 65 (70%) underwent NET. Overall, 49 patients (21%) were upstaged due to occult nodal disease. Factors associated with higher rates of occult nodal disease included advanced stage on initial presentation (P = .008), larger presenting tumor size (P = .009), low/intermediate tumor grade (P = .025), and ER+/HER2- subtype (P < .001); incidence of occult nodal disease by subtype included: ER+/HER2- = 37%, HER2+ = 15%, TNBC = 8%. Patients experiencing a breast pCR had a significantly lower rate of nodal upstaging compared to those with residual tumor (4% vs. 96%, P < .001). On multivariate analysis, ER+/HER- patients exhibited higher risk of occult nodal disease when compared to patients with HER2+ (odds ratio [OR] = 3.4, 95% CI, 1.2-9.8, P = .003) and TNBC (OR = 5.7, 95% CI, 1.7-19.6, P = .003). Comparing NAC vs. NET in ER+/HER2- patients showed no difference in rates of occult nodal disease (39% vs. 35%, P = .13)., Conclusions: ER+/HER2- subtype carries higher risk for occult nodal disease after neoadjuvant therapy; NAC versus NET in these patients does not affect nodal upstaging., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Patients with essential thrombocythaemia or polycythaemia vera have several symptoms that can worsen their quality of life. We aimed to assess how symptom burden changes over time with cytoreductive therapy., Methods: We performed a post-hoc analysis of data from MPN-RC 111-a single-arm, open-label, phase 2, multicentre trial at 17 hospitals and cancer centres in Italy and the USA, evaluating the clinical-haematological response to pegylated interferon alfa-2a in patients who were resistant or intolerant to hydroxyurea (NCT01259817)-and MPN-RC 112-a randomised, open-label, phase 3, multicentre trial at 25 hospitals and cancer centres in France, Germany, Israel, Italy, the UK, and the USA, comparing the clinical-haematological response to pegylated interferon alfa-2a versus hydroxyurea in therapy-naive patients with either high-risk essential thrombocythaemia or polycythaemia vera (NCT01258856). Patients completed the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) and the European Organisation for the Research and Treatment of Cancer Core Quality of Life Questionnaire through 12 months after initiation of treatment as secondary endpoints. In this post-hoc analysis, we examined the association of symptom burden with the clinical-haematological response at 12 months and the effect of baseline symptom burden (ie, high burden [total symptom score ≥20] vs low burden [total symptom score <20]) on subsequent changes in symptoms, estimated via mixed models. A clinically significant improvement in symptom burden was defined as 50% or greater improvement in the MPN-SAF total symptom score from baseline to 12 months in patients with a total symptom score greater than zero at baseline., Findings: 135 patients were enrolled in MPN-RC 111 between Feb 15, 2012, and Dec 23, 2015, and 168 were enrolled in MPN-RC 112 between Sept 24, 2011, and June 30, 2016. For this analysis, we included data from 114 patients from MPN-RC 111 (64 [56%] with essential thrombocythaemia and 50 [44%] with polycythaemia vera; 56 [49%] were female, and 100 [91%] of 110 were white) and 166 patients from MPN-RC 112 (79 [48%] with essential thrombocythaemia and 87 [52%] with polycythaemia vera; 68 [41%] were female, and 145 [93%] of 156 were white). At 12 months, a clinically significant improvement in symptom burden was reported by 12 (32%) of 38 complete responders and seven (20%) of 35 partial responders treated with pegylated interferon alfa-2a in MPN-RC 111; five (19%) of 27 complete responders and six (18%) of 34 partial responders treated with pegylated interferon alfa-2a in MPN-112; and eight (27%) of 30 complete responders and six (22%) of 27 partial responders treated with hydroxyurea in MPN-112. More complete and partial responders reported a clinically significant improvement than did non-responders (44 [22%] of 191 complete and partial responders vs four [5%] of 76 non-responders; Fisher's exact p=0·0003). Symptom burden improved between 3 and 12 months in patients with high baseline symptom burden, both those treated with pegylated interferon alfa-2a (mean total symptom score change -10·2, 95% CI -13·2 to -7·2) and those treated with hydroxyurea (-6·8, -11·2 to -2·4). However, symptom burden worsened between 3 and 12 months in patients with low baseline symptom burden (patients treated with pegylated interferon alfa-2a: mean total symptom score change 3·2, 95% CI 0·9 to 5·4; patients treated with hydroxyurea: 3·4, 0·6 to 6·2)., Interpretation: Results can inform treatment decisions, including treatment timing and goals in managing essential thrombocythaemia and polycythaemia vera, because measuring symptom burden from the patient perspective is crucial to understanding treatment efficacy and tolerability., Funding: US National Cancer Institute of the National Institutes of Health, and Roche Genentech., Competing Interests: Declaration of interests JM reports funding from PharmaEssentia and consulting fees from PharmaEssentia. RAM reports funding from Celgene, Incyte, AbbVie, Samus, Genotech, Promedior, CTI, and Constellation; and consulting fees from Novartis, Sierra Onc, LaJolla, Pharma, and Constellation. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background and Aims: Biliary tract cancers (BTCs) are uncommon, but highly lethal, gastrointestinal malignancies. Gemcitabine/cisplatin is a standard-of-care systemic therapy, but has a modest impact on survival and harbors toxicities, including myelosuppression, nephropathy, neuropathy, and ototoxicity. Whereas BTCs are characterized by aberrations activating the cyclinD1/cyclin-dependent kinase (CDK)4/6/CDK inhibitor 2a/retinoblastoma pathway, clinical use of CDK4/6 inhibitors as monotherapy is limited by lack of validated biomarkers, diffident preclinical efficacy, and development of acquired drug resistance. Emerging studies have explored therapeutic strategies to enhance the antitumor efficacy of CDK4/6 inhibitors by the combination with chemotherapy regimens, but their mechanism of action remains elusive., Approach and Results: Here, we report in vitro and in vivo synergy in BTC models, showing enhanced efficacy, reduced toxicity, and better survival with a combination comprising gemcitabine/cisplatin and CDK4/6 inhibitors. Furthermore, we demonstrated that abemaciclib monotherapy had only modest efficacy attributable to autophagy-induced resistance. Notably, triplet therapy was able to potentiate efficacy through elimination of the autophagic flux. Correspondingly, abemaciclib potentiated ribonucleotide reductase catalytic subunit M1 reduction, resulting in sensitization to gemcitabine., Conclusions: As such, these data provide robust preclinical mechanistic evidence of synergy between gemcitabine/cisplatin and CDK4/6 inhibitors and delineate a path forward for translation of these findings to preliminary clinical studies in advanced BTC patients., (© 2021 by the American Association for the Study of Liver Diseases.)

Diabetes insipidus (DI) is an uncommon perioperative complication that can occur secondary to medications or surgical manipulation and can cause significant hypovolemia and electrolyte abnormalities. We reviewed and evaluated the current literature and identified 29 cases of DI related to medications commonly used in anesthesia such as propofol, dexmedetomidine, sevoflurane, ketamine, and opioids. This review summarizes the case reports and frequency of DI with each medication and presents possible pathophysiology. Medication-induced DI should be included in the differential diagnosis when intraoperative polyuria is identified. Early identification, removal of the agent, and treatment of intraoperative DI are critical to minimize complications., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 International Anesthesia Research Society.)

Background: The prognostic significance of regression in melanoma is debated. We present a large multicenter study correlating regression with sentinel lymph node metastasis and melanoma-specific survival., Methods: The Sentinel Lymph Node Working Group database was reviewed from 1993 to 2018. Patients with known regression and sentinel lymph node status were included. Clinicopathologic factors were correlated with regression, sentinel lymph node status, and melanoma-specific survival., Results: There were 4,790 patients; median follow-up was 39.6 months. Regression was present in 1,081 (22.6%) cases, and 798 (16.7%) patients had sentinel lymph node metastases. On multivariable analysis, male sex, truncal tumors, and decreasing thickness were significantly associated with regression (P < .05), whereas head/neck or leg tumors had lower rates of regression (P < .05). Regression was significantly correlated with a decreased risk of sentinel lymph node disease on multivariable analysis (odds ratio 0.68, 95% confidence interval 0.54-0.85; P = .0008). Multivariable analysis also showed that increasing age, male sex, increasing thickness, ulceration, lymphovascular invasion, microsatellitosis, and sentinel lymph node metastasis were significantly (P < .05) associated with worse melanoma-specific survival, while regression was significantly associated with better melanoma-specific survival (hazard ratio 0.75, 95% confidence interval 0.57-0.99; P = .043)., Conclusion: This large study shows that regression is significantly associated with better outcomes in patients with melanoma and is correlated with a lower risk of sentinel lymph node metastasis and a better melanoma-specific survival., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Patients with myeloproliferative neoplasms (MPNs) suffer from chronic and progressive symptom burden. MPN trials capturing patient-reported symptoms routinely administer the MPN Symptom Assessment Form (SAF). The MPN-10 assesses 10 of the most clinically relevant symptoms, including fatigue and generates a Total Symptom Score (TSS). The original MPN-10 included a fatigue item from the Brief Fatigue Inventory (BFI). The myelofibrosis-specific symptom assessment tool called the MFSAF v4 utilizes a fatigue item developed to be consistent with other items within the SAF. This study sought to validate a modified version of the MPN-10 TSS using the SAF fatigue item for harmonization with MFSAF v4., Methods: Survey data from two cohorts of patients with essential thrombocythemia, polycythemia vera, or myelofibrosis assessing MPN characteristics and symptom burden were used., Results and Conclusion: BFI and SAF fatigue items were highly correlated in raw score (Pearson r = 0.88), comparable in their severity categorizations (89% agreement for severe versus non-severe) and respective contributions to the TSS (both Cronbach's alpha = 0.89). Reliability of SAF fatigue was acceptable and independently associated with known disease-related characteristics (splenomegaly, low quality-of-life, and distress). Fatigue in patients with MPNs is measured with high similarity using the SAF fatigue item within the MPN-10 in harmonization with the MFSAF v4., Competing Interests: RM received research funding from Celgene, Incyte, Abbvie, Samus, Genotech, Promedior, CTI, and Constellation Pharmaceuticals, as well as received consultancy fees from Novartis, Sierra Oncology, LA Jolla Pharmaceuticals, Pharma, and Constellation Pharmaceuticals. AD received consultancy fees from Constellation Pharmaceuticals, as well as royalties from licensing for commercial purposes of the MPN-SAF., (Copyright 2021, Langlais et al.)

Background: Same-day discharge after mastectomy is a recently described treatment approach. Limited data exist investigating whether same-day discharge can be successfully implemented in patients undergoing mastectomy with immediate implant-based breast reconstruction (IBR)., Methods: Patients having mastectomy with IBR from 2013 to 2019 were reviewed. Enhanced recovery with same-day discharge was implemented in 2017. Patient characteristics, oncologic treatments, surgical techniques, and 90-day postoperative complications and reoperations were analyzed comparing enhanced recovery patients with historical controls., Results: A total of 363 patients underwent nipple-sparing (214, 59%) or skin-sparing (149, 41%) mastectomy with 1-stage (270, 74%) or tissue expander (93, 26%) IBR. Enhanced recovery was used for 151 patients, with 79 of these patients (52%) discharged same-day. Overall, enhanced recovery patients experienced a significantly lower rate of 90-day complications (21% vs 41%, P < 0.001), including hematoma (3% vs 11%, P = 0.002), mastectomy flap necrosis (7% vs 15%, P = 0.02), seroma (1% vs 9%, P < 0.001), and wound breakdown (3% vs 9%, P = 0.05). Postoperative complication rates did not significantly differ among enhanced recovery patients discharged same day. Postoperative admissions significantly decreased after enhanced recovery implementation (100% to 48%, P < 0.001), and admitted enhanced recovery patients experienced a lower length of stay (1.2 vs 1.8, P < 0.001). Enhanced recovery patients experienced a lower incidence of ≥1 unplanned reoperation (22% vs 33%, P = 0.01); overall average unplanned and total reoperations did not significantly differ between groups., Conclusions: In conjunction with enhanced recovery practices, same-day discharge after mastectomy with IBR is a safe and feasible treatment approach., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Study conducted to determine frequency and timing of unplanned breast implant removal after mastectomy, reconstruction, and postmastectomy radiation (PMRT). From 2010-2017, 52 patients underwent mastectomy, reconstruction, and PMRT. With median follow-up of 3.1 years, 23 patients (44%) experienced implant removal. Implant removal occurred in 9 (17%) patients before starting PMRT and 14 (27%) patients after starting PMRT. Implant removal rates were similar for hypofractionated PMRT compared with standard fractionation and for proton compared with photon PMRT. Implant removal is common for women undergoing mastectomy and reconstruction followed by PMRT. The risk is clinically significant even before starting radiation., (© 2021 Wiley Periodicals LLC.)

Background: The purpose of this study is to evaluate how prior breast augmentation impacts rates of complications and risk for reoperation after mastectomy with concurrent breast reconstruction., Methods: Patients undergoing nipple-sparing, skin-sparing, or simple mastectomy with implant-based reconstruction from 2008 to 2018 were identified in a prospective database. Postoperative complications and reoperations were then analyzed comparing patients with prior augmentation to patients without history of previous breast surgery., Results: A total of 468 patients were identified with a median follow-up of 4 years. Of these, 72 had prior augmentation mammoplasty. These patients underwent nipple-sparing (52, 72%), skin-sparing (15, 21%), or simple (5, 7%) mastectomy with immediate direct-to-implant (46, 61%) or tissue expander (26, 35%) reconstruction. On univariate analysis, this cohort had a lower body mass index (23.3 vs 25.3, P = 0.003), a higher rate of nipple-sparing mastectomy (72% vs 54%, P = 0.01), and a higher prevalence of stage I disease (44% vs 33%, P = 0.04). Differences in age, comorbidities, reconstructive techniques, tumor size, and neoadjuvant/adjuvant therapies were not significant. Overall complication rate between patients with or without prior augmentation did not significantly differ (51% vs 50%, P = 0.83); no significant differences in rates of surgical site infection, hematoma, mastectomy skin flap/wound necrosis, nipple complications, implant loss, or capsular contracture were found. Analysis of reoperations between patients with and without prior augmentation revealed no significant differences in average number of subsequent planned, unplanned, or total reoperations. On multivariate analysis, prior breast augmentation was found to be associated with significantly increased risk for undergoing ≥1 unplanned reoperation (odds ratio, 2.28; 95% confidence interval, 1.28-4.05, P = 0.005)., Conclusions: Prior augmentation mammoplasty does not significantly affect rates of postoperative complications after mastectomy with concurrent reconstruction. Although prior augmentation does not affect number of subsequent reoperations on average, it does increase the risk of experiencing 1 or more unplanned reoperation after mastectomy with reconstruction., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Capsular contracture causes pain, poor cosmesis, and reoperations. This study analyzes its incidence and risk factors in a more modern treatment era., Methods: Patients undergoing mastectomy with implant reconstruction from 2010 to 18 were reviewed. Univariate and multivariate analysis evaluated rates and risk factors for capsular contracture., Results: Among 451 patients, the majority underwent nipple-sparing mastectomy (262, 58.1%) with one-stage reconstruction (283, 62.7%) utilizing subpectoral implants (353, 77.4%) and acellular dermal matrix (354, 78.5%). Overall capsular contracture incidence was 9.8%; the rate after post-mastectomy radiation therapy (PMRT) was 18.7%, and 7.5% for patients without PMRT. Significant factors included neoadjuvant chemotherapy (P = 0.006), hematoma (P = 0.047), and PMRT (P = 0.001). Multivariate analysis showed that PMRT increased risk of capsular contracture (OR = 3.12, 95% CI 1.55-6.26, P = 0.001), and adjuvant chemotherapy was protective (OR = 0.289, 95% CI 0.114-0.731, P = 0.01)., Conclusions: Incidence of capsular contracture is lower than previously reported. Advancing therapeutic techniques may reduce the risk of this complication., Competing Interests: Declaration of competing interest The authors have no financial or commercial conflicts of interest to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Refractory septic shock is associated with high morbidity and mortality. Hydroxocobalamin is used to treat postoperative vasoplegia; however, data supporting its use in the setting of refractory septic shock is limited and restricted to case reports. This study evaluates the effect of hydroxocobalamin on mean arterial pressure and vasopressor requirements in a series of patients with refractory septic shock., Design: Single-center, retrospective analysis., Setting: Urban, tertiary-care ICU., Patients: Adult ICU patients with refractory septic shock treated with hydroxocobalamin between August 2018 and January 2020., Interventions: Hydroxocobalamin 5 g IV infusion., Measurements and Main Results: Twenty-six patients were included for the analysis. Administration of hydroxocobalamin was associated with an increase in mean arterial pressure at 1, 6, and 24 hours postdose (+16.3, +14.3, and +16.3 mm Hg, respectively; p < 0.001). Increase in mean arterial pressure from baseline remained statistically significant when controlling for sex, age, and comorbid conditions. There was no change in the norepinephrine equivalents patients required 1 hour following hydroxocobalamin administration, but a statistically significant decrease in norepinephrine equivalent was observed at 6 and 24 hours postdose ( p < 0.001)., Conclusions: Hydroxocobalamin provides sustained hemodynamic benefit at 24 hours in patients with refractory septic shock., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Design features of phase I, II, and III clinical trials of pharmaceutical interventions in myelofibrosis (MF) are discussed. Model-assisted and model-based designs for phase I trials are useful for maximizing therapeutic benefit and include novel approaches to dose escalation. Trials in MF have shifted to accommodate new challenges following approval of JAK inhibitor therapies. Standardized response criteria exist; however, alternative measures of response when evaluating newer agents may be needed. Noninferiority and other adaptive designs can be used to incorporate design changes over time. Patient-reported outcomes, including quality-of-life and symptom assessment, should be included as outcome measures., Competing Interests: Conflicts of interest disclosure(s) Dr A.C. Dueck receives royalties from commercial licensing of the MPN-SAF. Data analysis and writing of this publication were supported by National Cancer Institute grants P01 CA108671 and P30 CA015083., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Thrombosis is the largest contributor to morbidity and mortality in patients with polycythemia vera (PV) and essential thrombocythemia (ET). Our understanding of the risk factors and pathophysiology of thrombosis in PV and ET patients is developing, including recent insights into the role of aberrant platelet-neutrophil interactions, JAK2 mutated endothelial cells and the pro-thrombotic inflammatory milieu. To date, few available therapies have demonstrated the ability to reduce the thrombotic burden in patients with these diseases. Although numerous therapeutic agents have been investigated in both PV and ET patients, few studies are designed to assess their impact on thrombotic events. In this review, we first describe the burden of thrombosis in patients with these myeloproliferative neoplasms (MPNs) and briefly explore their pathophysiologic mechanisms. We then critically assess and summarize the evidence behind currently available therapies with attention toward thrombotic endpoints. Finally, we describe a path forward for clinical research in MPNs that involves surrogate endpoint validation, biomarker development, and clinical trial design strategies in order to accurately assess reduction of thrombotic events when evaluating novel therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tremblay, Kosiorek, Dueck and Hoffman.)

Aim: We aimed to determine the impact of diabetes mellitus (DM) on survival of patients with neuroendocrine tumors (NETs) and of NETs on glycemic control., Patients & Methods: Patients with newly diagnosed NETs with/without DM were matched 1:1 by age, sex and diagnosis year (2005-2017), and survival compared (Kaplan-Meier and Cox proportional hazards). Mixed models compared hemoglobin A 1c (HbA 1c ) and glucose during the year after cancer diagnosis., Results: Three-year overall survival was 72% (95% CI: 60-86%) for DM patients versus 80% (95% CI: 70-92%) for non-DM patients (p = 0.82). Hazard ratio was 1.33 (95% CI: 0.56-3.16; p = 0.51); mean DM HbA 1c , 7.3%., Conclusion: DM did not adversely affect survival of patients with NET. NET and its treatment did not affect glycemic control., Competing Interests: Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript., (© 2021 Mayo Foundation for Medical Education and Research.)

Aim: To evaluate associations between survival and glycemic control in age-matched patients with endometrial or ovarian cancer, with/without diabetes mellitus (DM)., Patients & Methods: Patients with newly diagnosed ovarian or endometrial cancer with and without DM were compared., Results: The study included 84 patients with ovarian cancer (28, DM); 96 with endometrial cancer (48 with, 48 without DM). DM patients did not have worse overall or progression-free survival than non-DM patients. Glycemic control was not associated with either cancer., Conclusion: There was no association between DM and survival for patients with uterine or ovarian cancer. In addition, there was no association between uterine and ovarian cancer and glycemic control. Additional studies to confirm these observations in larger populations are required., Competing Interests: Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants, patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript., (© 2020 Mayo Foundation for Medical Education and Research.)

Myeloproliferative neoplasms (MPNs) are characterized by significant symptom burden. Integrative medicine (IM) offers unique symptom management strategies. This study describes IM interventions utilized by MPN patients and the association with symptom burden, quality of life, depression, and fatigue adjusted for lifestyle confounders. MPN patients were surveyed online for IM utilization, MPN symptom burden (MPN-Symptom Assessment Form Total Symptom Score), depression (Patient Health Questionnaire), fatigue (Brief Fatigue Inventory), and a single question on overall quality of life. Measures were compared by IM participation and adjusted for alcohol and tobacco use, BMI, diet, and MPN type using multiple linear and logistic regression. A total of 858 participants were included in the analysis. Aerobic activity (p =< 0.001) and strength training (p = 0.01) were associated with lower mean symptom burden while massage (p =< 0.001) and support groups (p =< 0.001) were associated with higher levels of symptom burden. Higher quality of life was reported in massage (p = 0.04) and support groups (p = 0.002) while lower quality of life was noted in aerobic activity (p =< 0.001) and strength training (p = 0.001). A lower depression screening score was noted in those participating in aerobic activity (p = 0.006), yoga (p = 0.03), and strength training (p = 0.02). Lower fatigue was noted in those participating in aerobic activity (p =< 0.001) and strength training (p = 0.03) while higher fatigue was noted in those participating in massage (p =< 0.001) and breathing techniques (p = 0.02). Data available on request from the authors. This international survey of MPN patients on IM usage, has shown that patients who participated in a form of IM had a pattern of decreased levels of symptom burden, fatigue, depression, and higher QoL, as adjusted for health lifestyle practices overall., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction The systemic therapies available to patients with metastatic prostate cancer (mPC) have improved dramatically over the past decade. Anecdotal experience suggests that the increased available lines of therapy have changed the profile of mPC to include a higher prevalence of visceral metastases. Materials and Methods A retrospective review of 472 patients with prostate cancer who died in 2009 and in 2016 was performed. Patients with metastatic disease who had imaging within six months of death were included. A total of 164 patients were eligible for analysis. Results Overall rates of visceral and distant metastases, including the lung, liver, adrenal, brain, renal, spleen, and thyroid, were higher in patients who died in 2016 as compared to those who died in 2009 (40.0% and 26.1%, respectively, p-value = 0.07). Forty-four percent of patients who died in 2016 used five or more lines of systemic treatments compared to 26.1% of patients in 2009. Conclusion The emergence of new systemic therapies for mPC is changing the natural history of the disease. Visceral metastases are being seen with increasing frequency than in the past. This observation is important for clinicians who are monitoring patients with prostate cancer to maintain a high suspicion for visceral disease., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2020, Nafissi et al.)

Background: Philadelphia chromosome negative myeloproliferative neoplasms (MPNs), including essential thrombocythemia, polycythemia vera, and myelofibrosis, have severe function-limiting symptom burden that is experienced by the majority of patients. Previous studies have suggested that depression may be present in over a quarter of MPN patients, but to date no studies have evaluated the relationship between depression and other variables such as symptoms., Methods: A 70-item internet based survey regarding fatigue and mood symptoms was developed by a multidisciplinary team of MPN investigators, patients and patient advocates including Patient Health Questionnaire and the Myeloproliferative Neoplasm Symptom Assessment Form was completed by over 1300 patients with MPN diagnosis., Results: There were 309 respondents (23%) with PHQ-2 scores ≥ 3. In this analysis, we found worse systemic symptom burden in individuals reporting depressive symptoms., Conclusion: This analysis suggests the importance of depression in contributing to as well as confounding symptomatology in MPN patients, and suggests that this critical variable should also be addressed by clinicians and researchers alike when comprehensively assessing symptom burden etiologies., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Myeloproliferative neoplasms (MPN) that have evolved into accelerated or blast phase disease (MPN-AP/BP) have poor outcomes with limited treatment options and therefore represent an urgent unmet need. We have previously demonstrated in a multicenter, phase 1 trial conducted through the Myeloproliferative Neoplasms Research Consortium that the combination of ruxolitinib and decitabine is safe and tolerable and is associated with a favorable overall survival (OS). In this phase 2 trial, 25 patients with MPN-AP/BP were treated at the recommended phase 2 dose of ruxolitinib 25 mg twice daily for the induction cycle followed by 10 mg twice daily for subsequent cycles in combination with decitabine 20 mg/m2 for 5 consecutive days in a 28-day cycle. Nineteen patients died during the study follow-up. The median OS for all patients on study was 9.5 months (95% confidence interval, 4.3-12.0). Overall response rate (complete remission + incomplete platelet recovery + partial remission) was 11/25 (44%) and response was not associated with improved survival. We conclude that the combination of decitabine and ruxolitinib was well tolerated, demonstrated favorable OS, and represents a therapeutic option for this high-risk patient population. This trial was registered at www.clinicaltrials.gov as #NCT02076191., (© 2020 by The American Society of Hematology.)

Aim: We examined the effect of diabetes on survival in patients with lymphoma and the effect of lymphoma on glycemic control., Patients & Methods: Patients with lymphoma with and without diabetes (2005-2016) were retrospectively identified and matched 1:1. Overall survival and progression-free survival were estimated by the Kaplan-Meier method. Hemoglobin A 1c (HbA 1c ) and glucose levels during the year after cancer diagnosis were compared by mixed models., Results: For patients with diabetes, mean HbA 1c during the year after lymphoma diagnosis was 6.7%. Estimated 5-year progression-free survival for patients with versus without diabetes was 63% (95% CI: 53-76%) versus 58% (95% CI: 46-71%) (p = 0.42)., Conclusion: Lymphoma and its treatment did not affect glycemic control. Diabetes did not decrease lymphoma-specific survival., Competing Interests: Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript., (© 2020 Mayo Foundation for Medical Education and Research.)

Aim: We examined the association between diabetes and survival in patients with acute and chronic myeloid leukemia and the association of leukemia with glycemic control., Patients & Methods: Patients with leukemia with and without diabetes (2007-2015) were retrospectively identified and matched 1:1 (n = 70 per group). Overall survival was estimated by the Kaplan-Meier method. Hemoglobin A 1c  and glucose levels the year after leukemia diagnosis were compared by mixed models., Results: Among 25 of 70 patients with diabetes, mean hemoglobin A 1c during the year after leukemia diagnosis was 6.8%. Kaplan-Meier-estimated 3-year survival was 46% for diabetes patients versus 45% for controls (p = 0.79)., Conclusion: No associations were found between leukemia, diabetes, survival and glycemic control., Competing Interests: Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript., (© 2020 Mayo Foundation for Medical Education and Research.)

Aim: To evaluate overall survival (OS), glycemic control in cancer patients with and without diabetes mellitus (DM)., Patients & Methods: Patients (2010-2015) with newly diagnosed prostate, breast, lung, colorectal and pancreatic cancers were identified in institutional cancer registry. Data linked to National Death Index for vital status. 5-year OS estimated; glucose and hemoglobin A 1c assessed during year postdiagnosis., Results: We identified 1404 patients (non-DM, n = 936; DM, n = 468). DM cohort had 168 deaths (36%); non-DM, 267 (29%). 5-year OS estimated at 58% (95% CI: 53-64%) for DM and 67% (95% CI: 64-71%) for controls; for matched pairs, hazard ratio: 1.35 (95% CI: 1.02-1.79). Cancer did not harm glycemic control., Conclusion: OS among cancer patients with DM was lower than without DM., Competing Interests: Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript., (© 2020 Mayo Foundation for Medical Education and Research.)

Background: Enhanced recovery after surgery (ERAS ® ) principles have been beneficial in major abdominal surgery. ERAS ® was instituted in our breast surgery practice in 2017. The goal of this study was to evaluate the feasibility of outpatient mastectomies before and after ERAS ® ., Methods: A retrospective review of all mastectomies between 1/2013 and 6/2018 was performed. Patients receiving autologous flap reconstruction were excluded. The institution-specific ERAS ® pathway began on February 1, 2017. Patient characteristics, operative intervention, and postoperative outcomes were compared between pre-ERAS ® and post-ERAS ® groups and between outpatient and inpatient subgroups. Continuous and categorical variables were compared using Wilcoxon rank-sum and Chi-square analyses., Results: A total of 487 patients were analyzed. Three hundred and forty-seven (71%) were prior to ERAS ® and 140 after (29%). The two groups were not significantly different in background characteristics. Same-day discharge occurred in 58.6% of post-ERAS ® patients versus 7.2% of pre-ERAS ® patients (p < 0.001). Liposomal bupivacaine block was used for pain control more in the post-ERAS ® group, 62.1% versus 6.1% (p < 0.001). Reconstruction type differed with 45.7% of the post-ERAS ® group undergoing direct-to-implant reconstruction versus 34.3% of pre-ERAS ® patients (p < 0.001) and with higher rates of submuscular implant and tissue expander placement in the pre-ERAS ® versus post-ERAS ® group (p < 0.001). Complications rates were lower in the post-ERAS ® group versus pre-ERAS ® group, 32.9% versus 52.4% (p < 0.001). The outpatient subgroup had higher rates of liposomal bupivacaine administration 74.4% versus 44.8% (p < 0.001). Baseline characteristics and complication rates did not differ between outpatient and admitted subgroups., Conclusion: ERAS ® principles can be applied to breast cancer patients and allow for outpatient mastectomies with no increase in postoperative morbidity.