Unusual painful pelvic masses: Extramedullary hematopoiesis with extramedullary multiple myeloma.

The coexistence of extramedullary hematopoiesis and extramedullary multiple myeloma can occur and present as painful pelvic masses. In such a case, normal hematopoietic cells may outnumber clonal plasma cells, posing a diagnostic challenge.

Real-World Outcomes of Latinx Versus Non-Latinx Patients Treated With First-Line Immunotherapy for Metastatic Renal-Cell Carcinoma.

BACKGROUND: There are limited data regarding the impact of ethnicity among patients receiving immune checkpoint inhibitors. We evaluated real-world outcomes between Latinx and non-Latinx patients with metastatic renal-cell carcinoma (mRCC) treated with first-line nivolumab/ipilimumab within 2 different healthcare settings. METHODS: We performed a retrospective analysis of patients with mRCC who received nivolumab/ipilimumab within the Los Angeles County Department of Health Services (LAC-DHS), a safety-net healthcare system, and the City of Hope Comprehensive Cancer Center (COH), a tertiary oncology center, between January 1, 2015 and December 31, 2021. Progression-free survival (PFS) and overall survival (OS) were determined using the Kaplan-Meier method and covariates were adjusted using multivariate Cox proportional hazards regression. RESULTS: Of 94 patients, 40 patients (43%) were Latinx while the remainder were non-Latinx (44 pts [46%] White, 7 pts [7%] Asian, and 3 pts [3%] Other). Fifty (53%) and 44 (47%) patients received their care at COH and LAC-DHS, respectively. Most Latinx patients (95%) were treated at LAC-DHS, and most non-Latinx patients (89%) were treated at COH. Pooled analysis by ethnicity demonstrated significantly shorter PFS in Latinx versus non-Latinx patients (10.1 vs. 25.2 months, hazard ratios [HR] 3.61, 95% CI 1.96-6.66, P ≤ .01). Multivariate analysis revealed a HR of 3.41 (95% CI 1.31-8.84; P = .01). At a median follow-up of 11.0 months, the median OS was not reached in either arm at the time of data cutoff. CONCLUSION: Latinx patients with mRCC had a shorter PFS treated with frontline nivolumab/ipilimumab compared to their non-Latinx counterparts. No difference was observed in OS although these data were immature. Larger studies are needed to further interrogate the social and economic determinants of ethnicity on clinical outcomes in mRCC.

Applying Lean Kaizen to Improve Timely Computed Tomography Scan Appointments for Oncology Patients in a Safety Net Hospital.

PURPOSE: Timely radiographic studies are essential to oncology care. At our institution, a safety net hospital in a large metropolitan area, baseline assessment determined that the overwhelming majority of outpatient computed tomographic (CT) scans for oncology patients were overdue and not scheduled within 2 weeks of their first requested date. METHODS: We conducted a series of structured, interdisciplinary meetings including staff from radiology, oncology, scheduling, and administration to critically review the scheduling process utilizing Lean Kaizen quality improvement methods. A new workflow was developed in which clinic staff scheduled CT scans before clinic discharge. Three months after our initial meeting, the new workflow was launched. We set a target of decreasing the percentage of overdue scans to below 20%. RESULTS: At baseline, 87% (65 of 75) of CT scans awaiting scheduling were overdue. Data were gathered at 5 and 10 weeks after implementation of our workflow. The percentage of CT scans overdue for scheduling was 17% (9 of 53) at 5 weeks and 0.97% (1 of 103) at 10 weeks after implementation. Clinic visit durations were not affected. CONCLUSION: The Lean Kaizen QI model was successful in decreasing the rate of oncology patients overdue for CT scan scheduling with minimal effects on clinic visit durations. This study demonstrated the importance of interdepartmental collaboration and continuous monitoring for improvement. Given the success of this project, this workflow will be expanded to other outpatient clinics within our institution.

Determinants of Psychosocial Distress in Breast Cancer Patients at a Safety Net Hospital.

INTRODUCTION: Psychosocial distress screening of cancer patients is an American College of Surgeons Commission on Cancer mandate for accredited cancer programs. We evaluated psychosocial distress in breast cancer patients to characterize risk factors for high distress scores at a safety net hospital. MATERIALS AND METHODS: The psychosocial distress screening form includes a list of potential issues and a distress score scaled from 1 through 10. Psychosocial distress screening results were retrospectively analyzed, along with patient demographics and clinical data. Cochran-Mantel-Haenszel test was applied to identify predictors for high distress scores, which were defined as a score of 5 and greater. RESULTS: 775 distress screens were completed by 171 breast cancer patients. High distress scores were reported in 21.3%. Patients who had no evidence of disease at time of screening were less likely to report a high distress score compared to those who were newly diagnosed or in active treatment (odds ratio 0.51, 95% CI, 0.38-0.68, P< .0001). Patients with high distress scores were more likely to report concerns with insurance (29.1% vs. 7.6%, P< .0001), transportation (16.4% vs. 4.6%, P< .0001), housing (15.2% vs 2.1%, P< .0001), sadness/depression (63.6% vs. 14.1, P< .0001), and physical issues (89.1% vs. 52.8%, P< .0001). CONCLUSION: Status of cancer at time of screening, particularly newly diagnosed cancer and active treatment of cancer were associated with high distress scores in this patient group. While there should be an emphasis to ensure patients with these risk factors receive psychosocial distress screening, routine periodic screening for all patients should continue to be implemented to ensure quality cancer care.

Characterizing the relationships between tertiary and community cancer providers: Results from a survey of medical oncologists in Southern California.

BACKGROUND: Tertiary cancer centers offer clinical expertise and multi-modal approaches to treatment alongside the integration of research protocols. Nevertheless, most patients receive their cancer care at community practices. A better understanding of the relationships between tertiary and community practice environments may enhance collaborations and advance patient care. METHODS: A 31-item survey was distributed to community and tertiary oncologists in Southern California using REDCap. Survey questions assessed the following attributes: demographics and features of clinical practice, referral patterns, availability and knowledge of clinical trials and precision medicine, strategies for knowledge acquisition, and integration of community and tertiary practices. RESULTS: The survey was distributed to 98 oncologists, 85 (87%) of whom completed it. In total, 52 (61%) respondents were community practitioners and 33 (38%) were tertiary oncologists. A majority (56%) of community oncologists defined themselves as general oncologists, whereas almost all (97%) tertiary oncologists reported a subspecialty. Clinical trial availability was the most common reason for patient referrals to tertiary centers (73%). The most frequent barrier to tertiary referral was financial considerations (59%). Clinical trials were offered by 97% of tertiary practitioners compared to 67% of community oncologists (p = 0.001). Most oncologists (82%) reported only a minimal-to-moderate understanding of clinical trials available at regional tertiary centers. CONCLUSIONS: Community oncologists refer patients to tertiary centers primarily with the intent of clinical trial enrollment; however, significant gaps exist in their knowledge of trial availability. Our results identify the need for enhanced communication and collaboration between community and tertiary providers to expand patients' access to clinical trials.

Immune Thrombocytopenic Purpura (ITP) as an Uncommon Extraintestinal Complication of Crohn's Disease: Case Vignette and Systematic Literature Review.

While the association of immune thrombocytopenic purpura (ITP) and inflammatory bowel disease (IBD) has been described in a few case reports, management of ITP as an extraintestinal manifestation of Crohn's disease (CD) is less studied. There are approximately a dozen cases describing the management of patients dually diagnosed with CD/ITP. Previous reports postulated that the mechanism of ITP in CD was through the presence of circulating immune complexes in the serum and antigenic mimicry due to increased mucosal permeability in active colitis, versus increased mucosal production of TH1-type proinflammatory cytokines during CD flares, which may account for remission of ITP with surgery for CD. We present a case of a 27-year-old man who presented with medically refractory CD and ITP who responded to surgical management with colectomy and splenectomy, along with a systematic review of the literature. These cases suggest that colectomy should be considered in the treatment of medically refractory ITP among patients with concomitant CD.

Characteristics and Trends of Adult Acute Lymphoblastic Leukemia in a Large, Public Safety-Net Hospital.

BACKGROUND: Management of acute lymphoblastic leukemia (ALL) in a socioeconomically vulnerable population without ready access to a hematopoietic stem cell transplant (HCT) center and clinical trials is challenging. Data regarding the outcomes of such patients are sparse. PATIENTS AND METHODS: This retrospective analysis included 90 consecutive patients with ALL who presented to Harbor-UCLA between 2003 and 2018. The primary objective was overall survival (OS), whereas secondary objectives included leukemia-free survival, toxicities of therapy, and referral for HCT and incidence of successful HCT. RESULTS: Most patients were male (56.7%) and Hispanic (72.2%). The median age of diagnosis was 36 years (range, 18-63 years). The median OS was 26.8 months (95% confidence interval [CI], 17.4-59.0 months). In patients who achieved complete remission with therapy, the median leukemia-free survival was 16.4 months. Fifty percent of patients experienced at least 1 episode of bacteremia, and nearly 25% of patients developed an invasive fungal infection. Thirty-six percent (n = 32) of patients were referred for HCT. The referral rate increased over time, which led to improved OS in patients who underwent evaluation at a tertiary cancer center (hazard ratio, 0.44; 95% CI, 0.21-0.89; P = .02). Patients who underwent HCT had significantly better OS compared with those who did not (OS not reached vs. 21.9 months; hazard ratio, 0.16; 95% CI, 0.04-0.68; P = .01). CONCLUSION: Risk stratification and evidence-based treatment approaches are important for patients with ALL treated in a resource-limited setting. Most patients can be induced successfully and achieve complete remission with therapy. Partnership with a cancer center with early referral for HCT can facilitate curative HCT to be performed.

Brain Complete Response to Cabozantinib prior to Radiation Therapy in Metastatic Renal Cell Carcinoma.

Cabozantinib represents an established vascular endothelial growth factor- (VEGF-) tyrosine kinase inhibitor (TKI) in the treatment paradigm of metastatic renal cell carcinoma (mRCC). Its activity in mRCC patients with brain metastases (BMs) has been largely underreported in prospective clinical trials. We present the unique case of a heavily pretreated mRCC patient with BMs who achieved a brain complete response to cabozantinib prior to receiving radiation therapy. We end with a literature review and discussion of the biologic rationale and growing evidence supporting the intracranial activity of cabozantinib.

Advances in Translational Research and Clinical Care in Pancreatic Cancer: Where Are We Headed?

While significant advances have been made in the treatment of many different solid tumors, pancreatic cancer remains a glaring exception. Overall 5-year survival rates for pancreatic cancer remain in the single digits. While newer chemotherapy regimens such as FOLFIRINOX and nab-paclitaxel/gemcitabine have demonstrated modest improvement in survival benefit for metastatic disease and have improved the resectability rates of previously borderline or locally advanced tumors, clinically significant improvements from immunotherapy and targeted therapy remain to be demonstrated. Regardless, a wealth of basic science research in pancreatic cancer has been directed at understanding its aggressive biology and its resistance to therapy. We present a brief summary of key areas of laboratory research and its translation to clinical care.

Retraction: Effect of pre- and post-surgery treatment with risedronate on trabecular bone loss in ovariectomized rats.

The following articles have been retracted by the Editorial Board of Experimental Animals, because some parts of their contents were published elsewhere.

Prescription medication use and antinuclear antibodies in the United States, 1999-2004.

BACKGROUND: Clinical reports link specific medications with the development of antinuclear antibodies (ANA), but population-based evidence is limited. OBJECTIVE: The present study investigated associations between prescription medication use and ANA in a representative sample of the adult noninstitutionalized US population, first focusing on medications previously related to ANA and then considering all medications reported in the National Health and Nutrition Examination Survey (NHANES). METHODS: Based on NHANES data (1999-2004) for 3608 adults (ages ≥18 years), we estimated odds ratios (ORs) and 95% confidence intervals (CIs) to assess associations between recent medication use and ANA (overall and in sex and age subgroups), adjusted for potential confounders and the survey sampling design. RESULTS: We found no evidence that most medications previously associated with ANA in specific individuals were risk factors for ANA in the general population, although statistical power was limited for some medications. Overall, ANA were less prevalent in adults who recently used any prescription medications compared with those who did not (OR = 0.73; CI = 0.57,0.93), and likewise several classes of medications were inversely associated with ANA, including hormones (OR = 0.73; CI = 0.55,0.98), thiazide diuretics (OR = 0.43; CI = 0.24,0.79), sulfonylureas (OR = 0.41; CI = 0.19,0.89), and selective serotonin reuptake inhibitor antidepressants (OR = 0.65; CI = 0.42,0.98). Positive associations with ANA were seen for loop diuretics (OR = 1.72; CI = 1.03,2.88) in all adults, and for benzodiazepines (OR = 2.11; CI = 1.09,4.10) and bronchodilators (OR = 1.83; CI = 1.00,3.38) in older (ages ≥60) adults. Estrogens were positively associated with ANA in older women (OR = 1.80; CI = 1.00,3.23) but inversely associated with ANA in younger (ages 18-59) women (OR = 0.43; CI = 0.20,0.93). Regarding individual medications, ANA were positively associated with ciprofloxacin (OR = 4.23; CI = 1.21,14.8), furosemide (OR = 1.79; CI = 1.09,2.93), and omeprazole (OR = 2.05; CI = 1.03,4.10) in all adults, and with salmeterol (OR = 3.76; CI = 1.66,8.52), tolterodine (OR = 6.64; CI = 1.45,30.5), and triamterene (OR = 3.10; CI = 1.08,8.88) in older adults. Also, in younger adults, hydrochlorothiazide was inversely associated with ANA (OR = 0.44; CI = 0.20,0.98). CONCLUSIONS: Our findings in the general population do not confirm most clinically reported positive associations between specific medications and ANA in some individuals. However, novel positive ANA associations with other medications, as well as unexplained inverse associations with certain classes of medications and overall medication use, deserve further research to clarify the possible roles of medications as risk and protective factors in the development of autoantibodies and autoimmune disease.

Capecitabine-induced hypertriglyceridemia: a rare but clinically relevant treatment-related adverse event.

Capecitabine-induced hypertriglyceridemia (CIHT) represents an increasingly significant treatment-related adverse event from capecitabine given its potential for both acute complications (acute pancreatitis) and chronic metabolic complications (cardiovascular disease). The incidence of CIHT is relatively rare and the majority of cases thus far reported have been managed with lipid-lowering therapy and/or discontinuation of capecitabine followed by resumption of the drug upon normalization of triglyceride levels. We present among the first U.S. cases of CIHT to be reported in the published literature and highlight management approaches for this rare but clinically relevant adverse event. Further understanding of the mechanisms of CIHT and its long-term adverse effects as well as effective preventive strategies, interventions, and monitoring strategies are prudent given the widespread and often prolonged use of capecitabine-based chemotherapy in gastrointestinal and other cancers.

A new era of neoadjuvant treatment with Pertuzumab: Should the 10-lymph node guideline for axillary lymph node dissection in breast cancer be revised?

BACKGROUND: Pertuzumab has improved pathologic complete response rates when compared with other chemotherapeutics in the treatment of HER-2 positive breast cancer patients. AIMS: We sought to determine if axillary lymph node dissections (ALNDs) yielding at least the national standard of 10 lymph nodes is lower in patients who received neoadjuvant pertuzumab. METHODS AND RESULTS: A retrospective database identified patients who underwent ALND for breast cancer. We compared the axillary lymph node retrieval rates in those who received or did not receive neoadjuvant pertuzumab. Of 139 breast cancer patients who underwent ALND, fewer than 10 axillary lymph nodes were found in 41.7% of patients who received neoadjuvant pertuzumab (P < 0.01) and 18.6% of patients who received neoadjuvant therapy without pertuzumab (P = 0.01). CONCLUSION: Neoadjuvant chemotherapy was associated with a significantly lower rate of "adequate" ALNDs as defined by current guidelines. The patient subset that received neoadjuvant pertuzumab was more likely to have fewer than 10 axillary lymph nodes retrieved.

Hybrid Completion of Aortic Repair after Type A Aortic Dissection in a Patient with Marfan's Syndrome.

Medicine and engineering are in collaboration to assist in the tackling of daunting surgical techniques which are associated with high rates of morbidity and mortality, in exchange for minimally invasive approaches with lower procedural risk. Endovascular procedures in general have already reduced the risk of surgery by limiting the extent of open surgery and often replacing it with purely percutaneous or hybrid procedures. Here, we describe a patient who had complex staged surgery with open repair of a proximal portion of a type A aortic dissection followed by a staged endovascular reconstruction of the arch and descending aorta by means of a fenestrated stent-graft to secure the left subclavian artery and the posterior cerebral circulation.

Kirschner Wire and Bone Cement is a Viable Alternative to Reconstruction of Large Iliac Bone Defects After Strut Bone Graft Harvesting.

STUDY DESIGN: A retrospective study. OBJECTIVE: To assess the safety and efficacy of iliac crest defect reconstruction using Kirschner wire (K-wire)/polymethylmethacrylate (PMMA) versus traditional autologous rib graft reconstruction. SUMMARY OF BACKGROUND DATA: The iliac crest has been the preferred donor site for strut bone graft for various spinal fusion surgeries. METHODS: Seventy-three patients (44 males and 29 females; average age: 57.2 y) were divided into 2 groups: the rib group (35 patients) and the K-wire/PMMA group (38 patients). All operations involved anterior spinal interbody fusion. Patients were followed-up, on average, for 34.2 months using plain radiographs and both pain and cosmesis visual analog scales (VAS) to assess the clinical results after surgery. RESULTS: Almost all patients had pain VAS scores of ≤1 and grade 1 cosmesis VAS scores with no significant difference between the 2 groups in terms of either pain or cosmesis (P=1.00 and 0.505, respectively). In addition, few complications were noted in both groups. Radiographic complications in the rib group and the K-wire group numbered 4 (11%) and 2 (5%), respectively; however, did not significantly differ between the 2 groups (P=0.418). One case required intraoperative revision of the length of the K-wire and 1 case needed reoperation for iliac ring fracture and K-wire migration. An additional case required revision due to a bad fall. CONCLUSIONS: K-wire and bone cement reconstruction is an effective and safe alternative method for large iliac bone defect repair when autologous rib graft is not available.

Thoracic endovascular aortic repair (TEVAR) in proximal (type A) aortic dissection: Ready for a broader application?

OBJECTIVE: Thoracic endovascular aortic repair (TEVAR) has demonstrated encouraging results and is gaining increasing acceptance as a treatment option for aortic aneurysms and dissections. Yet, its role in managing proximal aortic pathologies is unknown-this is important because in proximal (Stanford type A) aortic dissections, 10% to 30% are not accepted for surgery and 30% to 50% are technically amenable for TEVAR. We describe our case series of type A aortic dissections treated by using TEVAR. METHODS: Between year 2009 and 2016, 12 patients with acute, subacute, or chronic type A aortic dissection with the proximal entry tear located between the coronaries and brachiocephalic artery were treated with TEVAR at 3 centers. Various stent-graft configurations were used to seal the proximal entry tear in the ascending aorta under rapid pacing. RESULTS: A total of 12 patients (9 male, 3 female), mean age 81 ± 7 years, EuroSCORE II 9.1 ± 4.5, underwent TEVAR for the treatment of type A aortic dissection. Procedural success was achieved in 11 of 12 patients (91.7%). There was 1 minor stroke and 1 intraprocedural death. No additional deaths were reported at 30 days. At 36 months, there were 4 further deaths (all from nonaortic causes). The mean survival of these 4 deceased was 23 months (range 15-36 months). Follow-up computed tomography demonstrated favorable aortic remodeling. CONCLUSIONS: TEVAR is feasible and reveals promising early results in selected patients with type A aortic dissection who are poor candidates for surgical repair. The current iteration of stent-graft technology, however, needs to be adapted to features specific to the ascending aorta.

Aortic dissection.

Aortic dissection is a life-threatening condition caused by a tear in the intimal layer of the aorta or bleeding within the aortic wall, resulting in the separation (dissection) of the layers of the aortic wall. Aortic dissection is most common in those 65-75 years of age, with an incidence of 35 cases per 100,000 people per year in this population. Other risk factors include hypertension, dyslipidaemia and genetic disorders that involve the connective tissue, such as Marfan syndrome. Swift diagnostic confirmation and adequate treatment are crucial in managing affected patients. Contemporary management is multidisciplinary and includes serial non-invasive imaging, biomarker testing and genetic risk profiling for aortopathy. The choice of approach for repairing or replacing the damaged region of the aorta depends on the severity and the location of the dissection and the risks of complication from surgery. Open surgical repair is most commonly used for dissections involving the ascending aorta and the aortic arch, whereas minimally invasive endovascular intervention is appropriate for descending aorta dissections that are complicated by rupture, malperfusion, ongoing pain, hypotension or imaging features of high risk. Recent advances in the understanding of the underlying pathophysiology of aortic dissection have led to more patients being considered at substantial risk of complications and, therefore, in need of endovascular intervention rather than only medical or surgical intervention.

PDGF-AA promotes osteogenic differentiation and migration of mesenchymal stem cell by down-regulating PDGFRα and derepressing BMP-Smad1/5/8 signaling.

Platelet-derived growth factors (PDGFs) play important roles in skeletal development and bone fracture healing, yet how PDGFs execute their functions remains incompletely understood. Here we show that PDGF-AA, but not -AB or -BB, could activate the BMP-Smad1/5/8 pathway in mesenchymal stem cells (MSCs), which requires BMPRIA as well as PDGFRα. PDGF-AA promotes MSC osteogenic differentiation through the BMP-Smad1/5/8-Runx2/Osx axis and MSC migration via the BMP-Smad1/5/8-Twist1/Atf4 axis. Mechanistic studies show that PDGF-AA activates BMP-Smad1/5/8 signaling by feedback down-regulating PDGFRα, which frees BMPRI and allows for BMPRI-BMPRII complex formation to activate smad1/5/8, using BMP molecules in the microenvironment. This study unravels a physical and functional interaction between PDGFRα and BMPRI, which plays an important role in MSC differentiation and migration, and establishes a link between PDGF-AA and BMPs pathways, two essential regulators of embryonic development and tissue homeostasis.