Citations

AbstractBackgroundOncologic outcomes of human papillomavirus (HPV)‐related oropharyngeal squamous cell carcinoma (SCC) requiring resection of major muscular or neurovascular tissue during neck dissection for invasive nodal disease remain uncertain.MethodsPatients with HPV‐related oropharyngeal SCC requiring resection of major muscular or neurovascular tissue during their neck dissections were retrospectively identified.ResultsSeventy‐two patients were included. Regional and distant recurrences occurred in 6% and 17% of patients. Advanced T classification, pathological node number of 5 or more, and omission of adjuvant therapy were associated with decreased disease‐free survival (DFS). The addition of adjuvant chemotherapy was not associated with improved survival.ConclusionPatients with invasive nodal disease from HPV‐related oropharyngeal SCC can be managed with up‐front surgery and adjuvant therapy, as indicated with good regional control. Although distant recurrence was the primary site of failure, adjuvant chemotherapy was not associated with improved outcomes. The T classification, node number, and adjuvant radiotherapy are independent prognostic factors in this patient population.

BACKGROUNDOutcomes have improved significantly in multiple myeloma (MM), but racial disparities in health care access and survival exist. A comprehensive analysis exploring MM care and racial disparities is warranted.METHODSPatients with MM from 1991 to 2010 in the Surveillance, Epidemiology, and End Results‐Medicare database were evaluated for racial trends in clinical myeloma‐defining events (MDEs), the receipt of treatment (drugs and stem cell transplantation; [SCT]), the cost of care, and overall survival (OS).RESULTSAmong 35,842 patients, the frequency of all MDEs at diagnosis increased over time; whereas, in recent years (2006‐2010), all MDEs with the exception of renal dialysis decreased. Blacks had highest rates for all MDEs except bone fractures, which were highest in whites. Over time, the proportion of patients who received any treatment, multiple agents, and SCT increased significantly, and the largest increase was observed in the receipt of immunomodulatory drugs and steroids. There was greater receipt of bortezomib and SCT among whites and blacks and higher receipt of immunomodulatory drugs among Hispanics and Asians (P < .001). Medicare claims were highest during first 6 months after MM diagnosis for blacks and at any time after MM diagnosis for Hispanics. Over time, Medicare claims increased most steadily for Hispanics (P < .001). Hypercalcemia, renal dysfunction, and bone fractures were associated with inferior OS. Blacks and Asians had superior OS compared with whites, but racial differences in OS became less pronounced during 2006 through 2010 (P = .182) compared with prior years (P < .01). Better OS was noted among patients who had higher median incomes.CONCLUSIONSThe current results indicate that there have been significant changes in the management of patients with MM over time and provide an in‐depth understanding of the factors that may help explain racial disparities. Cancer 2018;124:1710‐21. © 2018 American Cancer Society

AbstractBackgroundThis study presents oncologic outcomes after transoral robotic surgery (TORS) ± adjuvant therapy for oropharyngeal squamous cell carcinoma (SCC).MethodsThree hundred fourteen patients undergoing TORS ± adjuvant therapy for oropharyngeal SCC from May 1, 2007, to May 31, 2015, are analyzed.ResultsMedian follow‐up was 3.3 years (interquartile range [IQR] 1.8‐5.3 years; range 1 day to 9.3 years). Estimated locoregional recurrence‐free survival, distant metastasis‐free survival (DMFS), overall survival (OS), and cancer‐specific survival (CSS) rates (95% confidence interval [CI] number still at risk) at 5 years after surgery were 92% (88‐95; 92), 90% (86‐94; 92), 86% (82‐92; 98), and 94% (91‐97; 98), respectively. Negative margins were achieved in 98% of cases. The adult comorbidity evaluation (ACE)‐27 comorbidity index, human papillomavirus (HPV) status, pathologic N classification, and number of attempts to clear margins were associated with death due to cancer (P = .003, P = .002, P = .030, and P = .002, respectively).ConclusionThe need to take ≥2 margins to achieve resection portends an increased risk of locoregional recurrence and death due to disease in oropharyngeal SCC.

Acquired angioedema due to C1 inhibitor deficiency (C1INH-AAE) is a rare and potentially fatal syndrome of bradykinin-mediated angioedema characterized by episodes of angioedema without urticaria. It typically manifests with nonpitting edema of the skin and edema in the gastrointestinal (GI) tract mucosa or upper airway. Edema of the upper airway and tongue may lead to life-threatening asphyxiation. C1INH-AAE is typically under-diagnosed because of its rarity and its propensity to mimic more common abdominal conditions and allergic reactions. In this article, we present the case of a 62-year-old male with a history of recently diagnosed chronic lymphocytic leukemia (CLL) who presented to our hospital with recurrent abdominal pain, initially suspected to haveClostridium difficilecolitis and diverticulitis. He received a final diagnosis of acquired angioedema due to C1 esterase inhibitor deficiency due to concomitant symptoms of lip swelling, cutaneous nonpitting edema of his lower extremities, and complement level deficiencies. He received acute treatment with C1 esterase replacement and icatibant and was maintained on C1 esterase infusions. He also underwent chemotherapy for his underlying CLL and did not experience further recurrence of his angioedema.

AbstractBackgroundTransthoracic impedance measurements (TIM) is primarily used for minute ventilation rate adaptive sensors in pacemakers. With elevated impedance, the TIM electrical signal itself is oversensed, causing device malfunction.ObjectiveWe report an increased incidence of TIM oversensing.MethodRetrospective chart review. We review existing records of 18 patients who have demonstrated device malfunction with TIM oversensing.ResultsWe have found a 1.8% incidence of TIM‐related oversensing in our patient population of 959 patients with contemporary Boston Scientific (Marlborough, MA, USA) pacemakers and cardiac resynchronization therapy pacemakers. One patient experienced a syncopal episode.ConclusionOversensing with pacing inhibition is apparent with the potential of adverse effects to patients.

Intravenous infusion of oncolytic reovirus in patients leads to infection of brain tumors, infiltration by cytotoxic T cells, and up-regulation of PD-L1.

BACKGROUND: Thrombocytopenia is frequently encountered in critically ill patients, often resulting in prophylactic transfusion of platelets for the prevention of bleeding complications. However, the efficacy of this practice remains unclear. The objective of this study was to determine the relationship between prophylactic platelet transfusion and bleeding complications in critically ill patients. METHODS: This is a retrospective cohort study of adults admitted to surgical, medical, or combined medical-surgical intensive care units (ICUs) at a single academic institution between January 1, 2009, and December 31, 2013. Inclusion criteria included age ≥18 years and a platelet count measured during ICU admission. Propensity-matched analyses were used to evaluate associations between prophylactic platelet transfusions and the outcomes of interest with a primary outcome of red blood cell transfusion in the ensuing 24 hours and secondary outcomes of ICU and hospital-free days and changes in sequential organ failure assessment scores. RESULTS: A total of 40,693 patients were included in the investigation with 3227 (7.9%) receiving a platelet transfusion and 1065 (33.0%) for which platelet transfusion was prophylactic in nature. In propensity-matched analyses, 994 patients with prophylactic platelet transfusion were matched to those without a transfusion. Patients receiving prophylactic platelets had significantly higher red blood cell transfusion rates (odds ratio 7.5 [5.9–9.5]; P < .001), fewer ICU-free days (mean [standard deviation] 20.8 [9.1] vs 22.7 [8.3] days; P = .004), fewer hospital-free days (13.0 [9.7] vs 15.8 [9.4] days; P < .001), and less improvement in sequential organ failure assessment scores (mean decrease of 0.2 [3.6] vs 1.8 [3.3]; P < .001) in the subsequent 24 hours. These findings appeared robust, persisting in multiple predefined sensitivity analyses. CONCLUSIONS: Prophylactic administration of platelets in the critically ill was not associated with improved clinical outcomes, though residual confounding may exist. Further investigation of platelet transfusion strategies in this population is warranted.

AbstractThe Melatonin Osteoporosis Prevention Study (MOPS) demonstrated that nightly melatonin resulted in a time‐dependent decrease in equilibrium ratios of serum osteoclasts and osteoblasts in perimenopausal women. This study examines mechanisms related to the ratios of osteoblasts and osteoclasts using coculture models (transwell or layered) of human mesenchymal stem cell (MSC) and human peripheral blood monocytes (PBMCs). Human MSC/PBMC cocultures exposed to melatonin in osteogenic (OS+) medium for 21 days induced osteoblast differentiation and mineralization; however, only in layered cocultures did melatonin inhibit osteoclastogenesis. Melatonin effects were mediated through MT2 melatonin receptors, MEK1/2, and MEK5. In layered but not transwell cocultures, melatonin increased OPG:RANKL ratios by inhibiting RANKL, suggesting that contact with osteoclasts during osteoblastogenesis inhibits RANKL secretion. Melatonin modulated expression of ERK1/2, ERK5, β1 integrin, GLUT4, and IRβ that was dependent upon the type of coculture; however, in both cultures, melatonin increased RUNX2 and decreased PPARγ expression, indicating a role for metabolic processes that control osteogenic vs adipogenic cell fates of MSCs. Furthermore, melatonin also has osteoblast‐inducing effects on human adipose‐derived MSCs. In vivo, one‐year nightly melatonin (15 mg/L) given to neu female mice in their drinking water increased pErk1/2, pErk5, Runx2, and Opg and Rankl levels in bone consistent with melatonin's already reported bone‐enhancing effects. Finally, analysis of daily logs from the MOPS demonstrated a significant improvement in mood and perhaps sleep quality in women receiving melatonin vs placebo. The osteoblast‐inducing, bone‐enhancing effects of melatonin and improvement in quality of life suggest that melatonin is a safe and effective bone loss therapy.

AbstractWe conducted a surveillance epidemiology and end results (SEER)‐based analysis to describe the incidence and characteristics of second primary acute lymphoblastic leukemia (sALL) among adults (≥18 years) with a history of primary malignancies (1M). Standardized incidence ratios (SIRs) of sALL cases were calculated by site and 1M stage. We also evaluated the differences in 5‐year sALL survival by age, site, and extent of 1M, latency of sALL after 1M, and evidence of underlying racial/ethnic disparity. We identified 10,956 patients with de‐novo/primary acute lymphoblastic leukemia (1ALL) and 772 with sALL. Women (49.1% vs. 42.9%), white patients (72.0% vs. 59.5%), older patients (58.8% vs. 25.2%; age ≥65 years), and patients diagnosed between 2003 and 2012 (66.8% vs. 53.9%) had a higher proportion of sALL compared with 1ALL. There was a significantly inferior median 5‐year survival for sALL patients compared to 1ALL (6 vs. 15 months; HR 1.20, 95% CI 1.10–1.31, P < 0.001). The median latency period was 60.0 months; the most common 1M among sALL patients were breast (17.9%) and prostate (17.4%). Patients with any 1M were at increased risk of developing sALL (SIR 1.76, 95% CI 1.58–1.95, P < 0.001). Hematological‐1M sites had significantly higher SIRs (hematological‐SIR 7.35; solid‐SIR 1.33; P < 0.001). We observed a significant increase in sALL incidence after a 1M and a significantly worse 5‐year survival with different demographic characteristics from 1ALL. There is a need to define appropriate screening methods for patients surviving their primary cancer.

AimsThere is limited information regarding the clinicopathological and immunohistochemical characteristics of gastric pyloric gland adenomas (PGAs).Methods and resultsSixty‐seven cases of gastric PGA from 57 patients were analysed. PGAs occurred with similar frequency in men and women (47.4 and 52.6%, respectively), with a mean age of 66 years. Most presented in the gastric body/fundus (67.2%). Fifteen cases (22.4%) developed against a background of autoimmune gastritis (AIG), whereas normal mucosa was seen in 35.8%. Only 16.4% (11 cases) developed in patients with a genetic predisposition, most commonly familial adenomatous polyposis. Low‐grade lesions had a mean size of 1.5 cm, while PGAs with high‐grade dysplasia (HGD) or adenocarcinoma had a mean size of 3.5 cm (P < 0.001) and more commonly showed tubulovillous architecture (50.0 versus 25.6% in low‐grade dysplasia; P = 0.040). Most PGAs (61.2%) co‐expressed mucin (MUC)5AC and MUC6 (mixed type), which was associated significantly with HGD or adenocarcinoma (P = 0.013). AIG was also associated with HGD (P = 0.027), but genetic predisposition did not correlate with the grade of dysplasia (P = 0.793). The recurrence rate of PGA was similar for high‐ (11.8%) and low‐grade lesions (7.4%) (P = 0.624).ConclusionsThe risk of HGD increases with the size of PGA, tubulovillous architecture and the presence of AIG as well as mixed immunophenotype. As the overall local recurrence rate is less than 10%, PGAs may be treated conservatively, but they should be excised completely if possible, particularly if they are large or show high‐grade features.