Articles 1 – 20 of 343
Original Research
Open Access
Epidemiological Determinants of Advanced Prostate Cancer in Elderly Men in the United States
Jinani Jayasekera1, Eberechukwu Onukwugha2, Christopher Cadham1, Sarah Tom3, Donna Harrington4, Michael Naslund5
First Published June 26, 2019.https://doi.org/10.1177/1179554919855116
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In this study, we examined the effects of individual-level and area-level characteristics on advanced prostate cancer diagnosis among Medicare eligible older men (ages 70+ years). We analyzed patients from the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2000-2007) linked to US Census and County Business Patterns data. Cluster-adjusted logistic regression models were used to quantify the effects of individual preventive health behavior, clinical and demographic characteristics, area-level health services supply, and socioeconomic characteristics on stage at diagnosis. The fully adjusted model was used to estimate county-specific effects and predicted probabilities of advanced prostate cancer. In the adjusted analyses, low intensity of annual prostate-specific antigen (PSA) testing and other preventive health behavior, high comorbidity, African American race, and lower county socioeconomic and health services supply characteristics were statistically significantly associated with a higher likelihood of distant prostate cancer diagnosis. The fully adjusted predicted proportions of advanced prostate cancer diagnosis across 158 counties ranged from 3% to 15% (mean: 6%, SD: 7%). County-level socioeconomic and health services supply characteristics, individual-level preventive health behavior, demographic and clinical characteristics are determinants of advanced stage prostate cancer diagnosis among older Medicare beneficiaries; other health care-related factors such as family history, lifestyle choices, and health-seeking behavior should also be considered as explanatory factors.
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Original Research
Open Access
Improvement of Chemotherapy Solutions Production Procedure in a Hospital Central Chemotherapy Preparation Unit: A Systematic Risk Assessment to Prevent Avoidable Harm in Cancer Patients
Klio Bourika1, Angelos Koutras2, Haralambos Kalofonos2, Anna Vicha3, Ekaterini Tsiata4, Evangelia Papadimitriou1, Konstantinos Avgoustakis5, Zoi Panagi4
First Published June 10, 2019.https://doi.org/10.1177/1179554919852933
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Objective:
This study was designed to reevaluate and improve the quality and safety of the chemotherapy preparation in a Central Chemotherapy Preparation Unit of a Public Hospital.
Methods:
A failure modes, effects, and criticality analysis (FMECA) was conducted by a multidisciplinary team. All potential failure modes at each stage of the chemotherapy preparation were recorded, and the associated risks were scored for their severity, occurrence, and detectability with a risk priority number (RPN). Corrective actions were suggested, and new RPNs were estimated for the modified process.
Results:
Failure modes, effects, and criticality analysis and priority matrix construction, revealed that the partial compliance of Unit’s premises with international standards (RPNstage: 307), the human errors throughout the compounding (RPNstage: 223)—labeling (RPNstage: 216)—prescribing (RPNstage: 198) steps, and the violation of working protocols by employees (RPNstage: 215), were the most important risks for which either urgent or immediate corrective actions had to be taken. Modifying the procedure through the proposed corrective actions is expected to lead to a significant (71.3%) risk containment, with a total RPNpreparation process reduction from 2102 to 604.
Conclusions:
Failure modes, effects, and criticality analysis and priority matrix development identified and prioritized effectively the risks associated with chemotherapy preparation allowing for the improvement of health services to cancer patients.
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Original Research
Open Access
Tumor Size and Overall Survival in Patients With Platinum-Resistant Ovarian Cancer Treated With Chemotherapy and Bevacizumab
Alexandre Sostelly, François Mercier
First Published May 28, 2019.https://doi.org/10.1177/1179554919852071
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Introduction:
Ovarian cancer is now recognized as a constellation of distinct subtypes of neoplasia involving the ovary and related structures. As a consequence of this heterogeneity, the analysis of covariates influencing the overall survival is crucial in this disease segment. In this work, an overall survival model incorporating tumor kinetics metrics in patients with platinum-resistant ovarian cancer was developed from the randomized, open label, phase 3 AURELIA trial.
Methods:
Tumor size data from 361 patients randomly allocated to the bevacizumab + chemotherapy or chemotherapy study arm were collected at baseline and every 8 to 9 weeks until disease progression. Patients continued to be followed for survival after treatment discontinuation. A landmarked Cox proportional hazard survival model was developed to characterize the overall survival distribution.
Results:
Two sets of factors were found to be influential on survival time: those describing the type and severity of disease (Eastern Cooperative Oncology Group [ECOG], Féderation Internationale de Gynécologie et d’Obstétrique [FIGO] stages, presence of ascites) and those summarizing the key features of the tumor kinetic model (tumor shrinkage at week 8 and tumor size at treatment onset). The treatment group was not required in the final model as the drug effect was accounted for in the tumor kinetics model.
Conclusions:
This work has identified both ascites and tumor kinetics metrics as being the 2 most influential factors to explain variability in overall survival in patients with platinum-resistant ovarian cancer.
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Original Research
Open Access
Expression of Bone Morphogenetic Protein-7 Significantly Correlates With Non-small Cell Lung Cancer Progression and Prognosis: A Retrospective Cohort Study
Masaya Aoki, Tadashi Umehara, Go Kamimura, Nobuhiro Imamura, Shoichiro Morizono, Yuto Nonaka, Takuya Tokunaga, Aya Harada Takeda, Koki Maeda, Yui Watanabe, Toshiyuki Nagata, Tsunayuki Otsuka, Naoya Yokomakura, Kota Kariatsumari, Masakazu Yanagi, Masami Sato
First Published May 28, 2019.https://doi.org/10.1177/1179554919852087
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Background:
Bone morphogenetic protein-7 (BMP-7) is a signaling molecule belonging to the transforming growth factor-β superfamily. Recent studies have demonstrated that BMP-7 is expressed in various human cancers and plays an important role in the progression of their cancers. The purpose of this study was to investigate the clinicopathologic and prognostic impact of BMP-7 expression in clinical samples of non-small cell lung cancer.
Methods:
This study enrolled 160 patients with non-small cell lung cancer who underwent complete resection. Expression of BMP-7 in cancer tissue was evaluated by immunohistochemistry. Correlations between expression of BMP-7 and clinicopathologic factors and prognosis were analyzed.
Results:
In non-small cell lung cancer, BMP-7 expression was identified not only in cell membranes but also in the cytoplasm of cancer cells. Expression of BMP-7 correlated with p-T (P = .047), N factor (P = .013), and p-stage (P = .046). Overall survival rate was significantly lower in the BMP-7-positive group than in the BMP-7-negative group (P = .004). Multivariate analysis indicated that BMP-7 expression was one of the independent prognosis factors of overall survival (P = .021). Furthermore, among patients with postoperative recurrence (n = 58), the BMP-7-positive group (n = 29) had a significantly poorer prognosis than the BMP-7-negative group (n = 29) (P = .012).
Conclusions:
Expression of BMP-7 in non-small cell lung cancer was correlated with clinicopathologic factors and poorer prognosis. BMP-7 expression may be a useful predictor of aggressive activity of tumor behavior and postoperative outcome of patients with non-small cell lung cancer.
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Review
Open Access
Follicular Dendritic Cell Sarcoma or Not? A Series of 5 Diagnostically Challenging Cases
Nicolas Lopez-Hisijos, Reeba Omman, Stefan Pambuccian, Kamran Mirza
First Published May 23, 2019.https://doi.org/10.1177/1179554919844531
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Imperfect or unusual presentation, morphology, or immunophenotype can make the diagnosis of follicular dendritic cell sarcoma (FDCS) very challenging. To illustrate this, we present 5 unique cases from the archives of our tertiary care academic medical center that presented a diagnostic challenge wherein FDCS was the top differential diagnostic possibility. The workup of these cases, including multiple expert consultations, highlights the importance of avoiding specific pitfalls in the diagnosis of FDCS.
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Original Research
Open Access
Major Stressful Life Events and Risk of Developing Lung Cancer: A Case-Control Study
Syed H Jafri1, Faisal Ali1, Arash Mollaeian1, Syed Mojiz Hasan12, Rahat Hussain3, Bindu Akkanti3, Jessica Williams1, Mahran Shoukier4, Hazem el-Osta15
First Published May 1, 2019.https://doi.org/10.1177/1179554919835798
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Background:
Lung cancer is the leading cause of cancer-related mortality and is strongly linked with smoking. We sought to determine whether major stressful life events (e.g. divorce) are also a risk factor for developing lung cancers.
Methods:
We performed a matched case-control study. Cases (CA) were lung cancer patients diagnosed within the previous 12 months. Controls (CO) were patients without a prior history of malignancy. Data on major stressful life events were collected using the modified Holmes-Rahe stress scale. The primary endpoint was the odds of having a major stressful life event between CA and CO. A sample of 360 patients (CA = 120, CO = 240) was needed to achieve 80% power to detect an odds ratio (OR) of 2.00 versus the alternative of equal odds using χ2 = 0.05.
Results:
Between May 2015 and December 2016, we enrolled 301 patients (CA = 102, CO = 199), matched for median age (CA = 64.4 years, CO = 63.9 years), sex (CA-Male = 48%, CO-Male = 49.2%), and smoking status (ever smoker, CA = 84%, CO = 85%). There was no difference in lifetime stressful life event rate between CA and CO (95% vs 93.9%; P = .68). However, CA were significantly more likely to have had a stressful event within the preceding 5 years than CO (CA = 77.4% vs CO = 65.8%; P = .03, OR = 1.78). β-blocker use was significantly higher among CO (CA = 29.4%, CO = 49.7%; P = .0007, OR = 0.42), suggesting a protective effect.
Conclusion:
Patients with lung cancer are significantly more likely to have had a major stressful life event within the preceding 5 years. In addition, use of β-blockers may be protective against lung cancer.
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Original Research
Open Access
Investigation of Complications Following Port Insertion in a Cancer Patient Population: A Retrospective Analysis
William Paul Skelton, IV1, Aaron J Franke1, Samantha Welniak1, Raphael C Bosse1, Fares Ayoub1, Martina Murphy2, Jason S Starr2
First Published April 24, 2019.https://doi.org/10.1177/1179554919844770
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Central venous access devices, specifically implantable ports, play an essential role in the care of oncology patients; however, complications are prevalent. This retrospective single-institutional review was performed to identify rates of complications from port placement and potential factors associated with these events. A retrospective analysis of 539 cancer patients who underwent port insertion between March 2016 and March 2017 at our institution was conducted. Data examining 18 potentially predictive factors were collected, and multivariate analysis was conducted using logistic regression and odds ratios (ORs) with standard errors to determine predictive factors. Out of 539 patients, 100 patients (19%) experienced 1 complication, and 12 patients (2%) experienced 2 or more complications. An overall lower rate of complications was seen in patients on therapeutic anticoagulation (OR: 0.17, P < .001) or on antiplatelet agents (OR: 0.47, P = .02). No patients on therapeutic anticoagulation developed venous thromboembolism (VTE; 0%). Right-sided port insertion was associated with decreased rates of infection (OR: 0.44, P = .04). Insertion as inpatient was associated with an increased risk for mechanical failure (OR: 4.60, P < .01). This analysis identified multiple predictive factors that can potentially put patients at a higher risk of experiencing complications following port insertion. Our data show lower rates of VTE for patients on anticoagulation or antiplatelet therapy. Further analysis is also necessary to determine why port insertion as an inpatient places patients at a higher risk of complications. This study highlights the risks associated with port placement and prompts the clinician to have an informed discussion with the patient weighing the risks and benefits.
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Case Report
Open Access
Myoepithelial Cell Carcinoma of the Oral Tongue: Case Report and Review of the Literature
Robert G Nicholas1, Josh A Hanson2, Duncan A Meiklejohn1
First Published April 2, 2019.https://doi.org/10.1177/1179554919838254
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Background:
Myoepithelial cell carcinoma is a rare malignant neoplasm of salivary gland origin that typically presents in the parotid gland and minor salivary glands. It has been described previously in head and neck sites such as buccal mucosa, alveolar ridge, and base of tongue.
Methods:
A 55-year-old man presented with 30 years of right-sided tongue pain and 10 years of gradually worsening ulceration. Physical examination demonstrated a 2.5 cm ulcerative lesion of the anterior right oral tongue. An initial biopsy was consistent with moderately to poorly differentiated squamous cell carcinoma. Imaging included a positron emission tomography (PET)/computed tomography (CT) scan that demonstrated the right tongue lesion as well as hypermetabolic right level II adenopathy. The patient underwent surgical excision of the right tongue, upper aerodigestive tract endoscopy, and a bilateral supraomohyoid neck dissection. The tongue defect was closed primarily.
Results:
Final pathology of the surgical specimen demonstrated myoepithelial cell carcinoma. All of the margins were free of tumor and no cervical lymph nodes showed metastasis. Immunohistochemistry demonstrated myoepithelial differentiation. The tumor did not show EWSR1 gene rearrangement on genetic testing, suggesting salivary gland origin. Multidisciplinary tumor board evaluation recommended no adjuvant therapy. The patient recovered well after surgery and nearly a year later is without evidence of recurrent or residual disease.
Conclusions:
We present the first reported case of myoepithelial cell carcinoma with primary origin in the oral tongue and review the available literature on this unusual tumor. We discuss the clinical, pathological, and immunohistochemical features and treatment of myoepithelial cell carcinoma.
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Review
Open Access
The Current Landscape of Treatment in Non-Metastatic Castration-Resistant Prostate Cancer
Joelle El-Amm1, Jeanny B Aragon-Ching2
First Published March 7, 2019.https://doi.org/10.1177/1179554919833927
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Non-metastatic castration-resistant prostate cancer (nmCRPC) is a heterogeneous disease with variable potential in developing into overt metastases. It is an area of increased unmet need in advanced prostate cancer and for which there had been no great treatments until recent US Food and Drug Administration (FDA) approval of 2 novel anti-androgens apalutamide and enzalutamide, which were both approved given benefit in metastasis-free survival. Early data on the use of darolutamide, another novel anti-androgen, are also explored. This review discusses the pivotal trials that led to the approval of apalutamide and enzalutamide in the nmCRPC setting and discusses the key promises and challenges with the use of these agents.
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Original Research
Open Access
PAK1 Expression in Pancreatic Cancer: Clinicopathological Characteristics and Prognostic Significance
Nikolaos Symeonidis12, Maria Lambropoulou3, Efstathios Pavlidis1, Constantinos Anagnostopoulos4, Alexandra Tsaroucha5, Athanasia Kotini6, Christina Nikolaidou3, Anastasia Kiziridou7, Constantinos Simopoulos5
First Published February 18, 2019.https://doi.org/10.1177/1179554919831990
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Background:
Improvement of the management of pancreatic cancer requires a better understanding of the genetic and molecular changes responsible for the development of the disease. The family of p21-activated kinases (PAKs) and especially PAK1 appears to mediate many cellular processes that contribute to the development and progression of pancreatic cancer, but the clinical relevance of PAK1 expression with the disease still remains unclear. Aim of the study was to assess the clinical value and the potential prognostic significance of PAK1 in pancreatic adenocarcinoma.
Methods:
We investigated the relationship between the PAK1 expression and the clinical and histopathologic characteristics of pancreatic cancer patients and the potential significance of PAK1 on survival. We examined tissue samples from 51 patients operated for pancreatic cancer. PAK1 expression was investigated with immunohistochemistry and correlated to clinicopathological parameters.
Results:
PAK1 was detected in all tumor samples and high expression was found in most patients. High PAK1 expression was also associated with younger age and well-differentiated tumors, but no association was found between PAK1 expression and Tumor-Node-Metastasis stage as well as deceased or alive status on follow-up. Moderate to high PAK1 expression favored higher 6-month and 1-year survival and low PAK1 expression 2-year survival but without statistical significance.
Conclusions
Our results indicate that PAK1 could potentially be used as a prognostic marker in pancreatic cancer. Further studies could clarify whether utilization of PAK1 in therapeutic protocols for the treatment of pancreatic cancer will render them more effective.
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Access to Palliative Care for Cancer Patients Living in a Northern and Rural Environment in Ontario, Canada: The Effects of Geographic Region and Rurality on End-of-Life Care in a Population-Based Decedent Cancer Cohort
Michael SC Conlon1234, Joseph M Caswell12, Stacey A Santi1, Barbara Ballantyne567, Margaret L Meigs1, Andrew Knight45678, Craig C Earle9, Mark Hartman68
First Published February 14, 2019.https://doi.org/10.1177/1179554919829500
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Background:
Access to palliative care has been associated with improving quality of life and reducing the use of potentially aggressive end-of-life care. However, many challenges and barriers exist in providing palliative care to residents in northern and rural settings in Ontario, Canada.
Aim:
The purpose of this study was to examine access to palliative care and associations with the use of end-of-life care in a decedent cohort of northern and southern, rural and urban, residents.
Design:
Using linked administrative databases, residents were classified into geographic and rural categories. Regression methods were used to define use and associations of palliative and end-of-life care and death in acute care hospital.
Setting/Participants:
A decedent cancer cohort of Ontario residents (2007-2012).
Results:
Northern rural residents were less likely to receive palliative care (adjusted odds ratio [OR] = 0.90, 95% confidence interval [CI]: 0.83-0.97). Those not receiving palliative care were more likely to receive potentially aggressive end-of-life care and die in an acute care hospital (adjusted OR = 1.20, 95% CI: 1.02-1.41).
Conclusions:
Palliative care was significantly associated with reduced use of aggressive end-of-life care; however, disparities exist in rural locations, especially those in the north. Higher usage of emergency department (ED) and hospital resources at end of life in rural locations also reflects differing roles of rural community hospitals compared with urban hospitals. Improving access to palliative care in rural and northern locations is an important care issue and may reduce use of potentially aggressive end-of-life care.
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Case Report
Open Access
A Surgical Case of Inflammatory Myofibroblastic Tumor of the Liver: Potentially Characteristic Gross Features
Jiro Watanabe1, Sohsuke Yamada12, Yasuyuki Sasaguri13, Xin Guo2, Nozomu Kurose2, Kouji Kitada4, Masaru Inagaki4, Hiromi Iwagaki4
First Published February 12, 2019.https://doi.org/10.1177/1179554919829498
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We herein reported a very rare surgical case of inflammatory myofibroblastic tumor (IMT) of the liver, showing potentially unique and specific gross findings on its cut surface: our IMT demonstrated a relatively well-demarcated and partly infiltrative and likely extrahepatic (ie serosal) but not intrahepatic mass, appearing firm and hemorrhagic, and yellow-whitish in color. The patient, who was a woman in her early 70s with 2-year follow-up for lung cryptococcosis and traffic accident, incidentally presented with unenhanced and low-density, heterogeneous mass on abdominal dynamic CT in the peripheral right lobe of the liver. We could conclusively diagnose the current lesion as the hepatic IMT after thorough analyses including a wide panel of immunohistochemical antibodies. Despite that, all clinicians and pathologists should be aware that the potentially characteristic, extrahepatic gross feature of IMT of the liver might also be one of the powerful supplementary tools for reaching its correct diagnosis. One of our aims in the presented case report is to emphasize that the hepatic IMT should be considered clinicopathologically in the differential diagnosis of mass lesions on the liver.
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Original Research
Open Access
Efficacy of Regorafenib in Metastatic Colorectal Cancer: A Multi-institutional Retrospective Study
Ali Aljubran1, Mahmoud A Elshenawy12, Magdy Kandil3, Muhammed N Zahir1, Ahmed Shaheen4, Ahmed Gad15, Omar Alshaer6, Ahmed Alzahrani1, Abdelmonem Eldali7, Shouki Bazarbashi1
First Published January 30, 2019.https://doi.org/10.1177/1179554918825447
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Background:
Regorafenib is a multi-kinase inhibitor approved for treatment of refractory advanced colorectal cancer. It was found in the clinical trials to have a modest benefit and significant toxicity. Our aim was to assess the outcome in our local clinic practice.
Patients and methods:
Records of patients with confirmed colorectal cancer treated with regorafenib were reviewed. Clinical, pathological, and molecular data were collected. Efficacy and factors of possible prognostic significance were analyzed.
Results:
A total of 78 patients with metastatic colorectal cancer were treated with regorafenib from February 2014 to February 2016 in 4 different institutions (median age: 50.5 years; male: 40 [51.3%]; KRAS mutant: 41 [52%]; right colonic primary: 18 [23%]). A total of 52 patients (66.7%) had Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1, whereas in 25 patients (32.1%) it was >1. In total, 58 patients (74%) had dose reduction. No patient achieved objective response, 15 patients (19%) achieved stable disease, and 56 patients (72%) had progressive disease. With a median follow-up of 6.5 months, the median progression-free survival was 2.8 months (95% confidence interval [CI], 2.5-3.3) and overall survival was 8.0 months (95% CI, 6.2-9.7). Only performance status of ⩽1 had a statistically significant impact on progression-free survival and overall survival in both univariate and multivariate analyses.
Conclusions:
Regorafenib in our clinical practice has equal efficacy to reported data from pivotal registration trials. Our data suggest that performance status is the most important prognostic factor in patients treated with regorafenib, suggesting a careful selection of patients.
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Tumor Treating Fields for Glioblastoma Treatment: Patient Satisfaction and Compliance With the Second-Generation Optune® System
Adrian Kinzel1, Michael Ambrogi2, Michael Varshaver2, Eilon D Kirson3
First Published January 29, 2019.https://doi.org/10.1177/1179554918825449
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Background:
Tumor treating fields (TTFields) are a non-invasive antimitotic therapy that delivers alternating electric fields via the Optune® system. The Phase III EF-14 trial in newly diagnosed glioblastoma multiforme (GBM) showed significantly improved progression-free, overall and long-term survival when Optune was used together with maintenance temozolomide (TMZ) compared with TMZ alone. Compliance (average monthly use) was associated with better clinical outcome. The first-generation Optune system weighed approximately 6 pounds (~2.7 kg). The second-generation redesigned Optune system weighs 2.7 pounds (~1.2 kg). We tested and compared GBM patient experience with the second-generation system versus the first-generation system.
Methods:
Ten newly diagnosed and recurrent GBM patients in Germany (median age: 52.9 years [31-79]) were prospectively monitored over the first month of transitioning from the first-generation to the second-generation Optune system. Questionnaires using a numerical analog scale assessed feedback at baseline (first generation) and after 1 month of second-generation use.
Results:
After transitioning to the second-generation system, compliance improved by more than 10% in four patients, was maintained in five patients and decreased by more than 10% in one patient. Following transition, eight out of nine patients reported a reduction in the triggering of malfunction alarms. Self-reported patient feedback showed improved handling and portability (weight, mobility) of the second- versus the first-generation Optune system.
Conclusions:
This patient user survey suggests that patient satisfaction with the second-generation Optune system is improved versus the first-generation system. Improved features of the new system help patients achieve and maintain a higher rate of treatment compliance.
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Hepatotoxicities Induced by Neoadjuvant Chemotherapy in Colorectal Cancer Liver Metastases: Distinguishing the True From the False
Marie Desjardin1, Benjamin Bonhomme2, Brigitte Le Bail3, Serge Evrard1, Véronique Brouste4, Gregoire Desolneux1, Marianne Fonck1, Yves Bécouarn1, Dominique Béchade1
First Published January 22, 2019.https://doi.org/10.1177/1179554918825450
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Abstract
Background:
Pre-operative chemotherapy for colorectal liver metastasis (CRLM) is thought to be the cause of hepatotoxicity of non-tumoural parenchyma. Studies on hepatotoxicity are contradictory. We investigated the impact of a single-line pre-operative chemotherapy on non-tumoural liver analysed by an expert hepatico-pancreatico-biliary pathologist, and the consequences on surgical outcomes.
Patients and methods:
Patients operated for CRLM, after a pure first-line pre-operative chemotherapy, were retrospectively included. Two comparative histopathological analyses were performed for vascular toxicity and steatohepatitis.
Results:
Between 2003 and 2015, 147 patients were included. Chemotherapy was based on oxaliplatin (40.1%), irinotecan (55.8%), or both (4.1%). The expert pathologist described 38.8% of vascular lesions including dilation, nodular regeneration, and peliosis. In multivariate analysis, vascular lesions correlated to male sex (P = .01), pre-operative platelets <150 g/L (P = .04), and aspartate aminotransferase to platelet ratio index (APRI) score >0.36 (P = .02). Steatohepatitis was observed in 15 patients (10.2%), more frequently after irinotecan (14.8% vs 3.4%, P = .01; odds ratio [OR] = 7.3; 95% confidence interval [CI] = [1.5-34.7]), and for patients with body mass index (BMI) >25 kg/m2 (P = .004; OR = 10.0; 95% CI = [2.1-47.5]). A total of 29 patients (19.7%) developed major complications with 2 risk factors: portal vein obstruction (PVO) and septic surgery. Reproducibility assessment of steatohepatitis and dilated lesions by 2 pathologists showed moderate agreement (Kappa score 0.53 and 0.54, respectively).
Conclusions:
There is a probable association between non-alcoholic steatohepatitis (NASH) and irinotecan. Oxaliplatin seems to lead to higher vascular lesions. Except in the presence of pre-existent comorbidities, liver toxicities should not restrain the use of pre-operative chemotherapy prior to parenchymal-sparing surgery.
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Programmed Death-ligand 1 Expression With Clone 22C3 in Non-small Cell Lung Cancer: A Single Institution Experience
Maiko Takeda1, Takahiko Kasai1, Maiko Naito2, Akihiro Tamiya2, Yoshihiko Taniguchi2, Nobuhiko Saijo2, Yoko Naoki2, Kyoichi Okishio3, Shigeki Shimizu4, Kensuke Kojima5, Akihiro Nagoya5, Tetsuki Sakamoto5, Tomoki Utsumi5, Hyung-Eun Yoon5, Akihide Matsumura5, Shinji Atagi3
First Published January 9, 2019.https://doi.org/10.1177/1179554918821314
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Background:
In recent years, the anti-programmed cell death 1 (PD-1) drug pembrolizumab (Keytruda) was approved for treatment of unresectable advanced non-small cell lung cancer (NSCLC) as first- or second-line therapy depending on the clone 22C3-programmed death-ligand 1 (PD-L1) immunohistochemical expression score by the companion diagnostic assay. We herein evaluated 22C3-PD-L1 expression of NSCLC in a single institution experience and compared it with clinicopathologic features.
Materials and methods:
We assessed 22C3-PD-L1 expressions of 411 patients with NSCLC from our institution, including in past specimens. Programmed death-ligand 1 immunohistochemistry (IHC) testing was performed using the PD-L1 clone 22C3 pharmDx kit (Agilent Technologies/Dako, Carpinteria, CA, USA). Patients were separated into 3 groups with <1% (no expression), 1% to 49% (low expression), or ⩾50% (high expression) positive tumor cells.
Results:
In all, 137 patients (33%) did not express PD-L1, 155 (38%) showed low expression, and 119 (29%) demonstrated high expression. Archival samples showed lower PD-L1 expression than that of recent samples, and the ratios of no expression case significantly increased by using paraffin blocks embedded particularly in more than 4 years ago. Programmed death-ligand 1 positivity was significantly associated with male sex, smoking, higher tumor grade, squamous cell carcinoma in histologic type, wild-type EGFR, and ALK rearrangement positive.
Conclusions:
The rate of 22C3-PD-L1 expression of NSCLC detected in this study was similar to the frequencies of the previous reports, although the ratio of expression case decreased when using old paraffin blocks.
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The Nephroprotective Effect of Mannitol in Head and Neck Cancer Patients Receiving Cisplatin Therapy
Erik Hägerström1, Lotte Lindberg2, Jens Bentzen3, Kasper Brødbæk4, Bo Zerahn2, Bent Kristensen2
First Published January 7, 2019.https://doi.org/10.1177/1179554918821320
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Introduction:
Cisplatin is used as treatment for several different malignancies and a well-known complication is irreversible kidney damage. To protect the kidneys, this treatment is often combined with mannitol infusion to promote osmotic diuresis. Earlier studies investigating the nephroprotective effect of mannitol have shown conflicting results.
Objective:
To investigate changes in kidney function in head and neck cancer patients treated with cisplatin with and without additional mannitol infusion.
Methods:
A single center, retrospective cohort study of patients with squamous cell carcinoma of the head and neck receiving radiotherapy with cisplatin. Patient data were collected from November 2013 to December 2014.
Results:
After exclusion, a total of 78 patients were considered evaluable. They were equally distributed between a mannitol and a non-mannitol group and anthropomorphometrically similar. 51Cr-EDTA clearance declined in the mannitol group from 99.7 (19.9) to 96.4 (20.8) mL/min and in the non-mannitol group from 102.2 (17.8) to 92.3 (23.1) mL/min.
Conclusions:
There was a significantly smaller decrease in 51Cr-EDTA clearance in the mannitol group indicating a nephroprotective effect of mannitol.
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Correlation Between the Sites of Onset of Basal Cell Carcinoma and the Embryonic Fusion Planes in the Auricle
Giovanni Nicoletti123, Marco Mario Tresoldi13, Alberto Malovini4, Sebastien Prigent1, Manuela Agozzino5, Angela Faga236
First Published December 7, 2018.https://doi.org/10.1177/1179554918817328
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Abstract
Objectives:
This study aims at the identification of the distribution of basal cell carcinomas (BCCs) in the auricle in correlation with the currently most credited sites of the embryonic fusion planes of the auricle.
Methods:
An overall number of 69 patients with 72 BCCs of the auricle were enrolled in the study over a period of 14 years, from June 2003 to October 2017. All the cases underwent medical preoperative digital photography and the specific location of each BCC was coded on an original full-size anatomical diagram of the auricle derived from the reports by Streeter, Wood-Jones, Park, Porter, and Minoux showing the currently most credited sites of the embryonic fusion planes arbitrarily featured as two 5-mm-wide ribbon-like areas: (1) the hyoid-mandibular fusion plane (HM-FP) running from the upper margin of the tragus toward the concha and then deflecting toward the lower margin of the tragus and (2) the free ear fold-hyoid fusion plane (FEFH-FP) running from the cranial-most portion of the helix to the mid-portion of the ascending helix. The latter fusion planes were comprehensively termed embryological fusion planes (EFP) while all of the remaining surface of the auricle was comprehensively termed non-fusion area (NFA). The surfaces of all of the latter areas were calculated using the ImageJ software.
Results:
According to our data, the greatest number of BCCs was observed within the currently most credited sites of the embryonic fusion planes of the auricle. The latter sites displayed a 12-fold increased tumor incidence in comparison with the remaining surface of the ear.
Conclusions:
A correspondence between the sites of onset of BCCs and the sites of merging and/or fusion of embryonal processes was demonstrated in the auricle. Therefore, the latter sites might be considered as high-risk areas for the development of a BCC. Such an evidence provides further support to the hypothesis of an embryological pathogenesis of BCC.
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Case Report
Open Access
A Rare Primary Tumor of the Thyroid Gland: A New Case of Leiomyoma and Literature Review
Yanling Zhang12, Heng Tang2, Huaiyuan Hu2, Xiang Yong2
First Published November 26, 2018.https://doi.org/10.1177/1179554918813535
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Primary leiomyomas of the thyroid are very rare. We here report a case of a 53-year-old woman with a painless mass at the right thyroid, revealed by physical examination. The patient underwent a lobectomy. Frozen sections showed a spindle cell tumor of the thyroid gland. The nuclei of some of the tumor cells were obviously enlarged and deeply stained. Pseudocapsule invasion was observed in small foci. Samples showed neither mitosis nor necrosis and the nature of the tumor was difficult to determine. Paraffin sections showed a well-circumscribed nodular composed of intersecting fascicles of spindled to slightly epithelioid cells with eosinophilic cytoplasm and blunt-ended, cigar-shaped nuclei. We observed no significant nuclear atypia, mitotsis, or necrosis. Immunohistochemical staining showed the tumor cells to be positive for α-smooth muscle actin and h-caldesmon but negative for TG, TTF1, PAX8, S-100, CT, CK, and CD34. The ki-67 index was very low (<1%). Primary thyroid leiomyoma is rare and difficult to diagnose using frozen sections. Diagnosis requires immunohistochemical staining. Leiomyoma may be mistaken for other thyroid tumors also characterized by spindle cells.
Original Research
Open Access
Epidemiological Determinants of Advanced Prostate Cancer in Elderly Men in the United States
Jinani Jayasekera1, Eberechukwu Onukwugha2, Christopher Cadham1, Sarah Tom3, Donna Harrington4, Michael Naslund5
First Published June 26, 2019.https://doi.org/10.1177/1179554919855116
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Abstract
In this study, we examined the effects of individual-level and area-level characteristics on advanced prostate cancer diagnosis among Medicare eligible older men (ages 70+ years). We analyzed patients from the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2000-2007) linked to US Census and County Business Patterns data. Cluster-adjusted logistic regression models were used to quantify the effects of individual preventive health behavior, clinical and demographic characteristics, area-level health services supply, and socioeconomic characteristics on stage at diagnosis. The fully adjusted model was used to estimate county-specific effects and predicted probabilities of advanced prostate cancer. In the adjusted analyses, low intensity of annual prostate-specific antigen (PSA) testing and other preventive health behavior, high comorbidity, African American race, and lower county socioeconomic and health services supply characteristics were statistically significantly associated with a higher likelihood of distant prostate cancer diagnosis. The fully adjusted predicted proportions of advanced prostate cancer diagnosis across 158 counties ranged from 3% to 15% (mean: 6%, SD: 7%). County-level socioeconomic and health services supply characteristics, individual-level preventive health behavior, demographic and clinical characteristics are determinants of advanced stage prostate cancer diagnosis among older Medicare beneficiaries; other health care-related factors such as family history, lifestyle choices, and health-seeking behavior should also be considered as explanatory factors.
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Open Access
Improvement of Chemotherapy Solutions Production Procedure in a Hospital Central Chemotherapy Preparation Unit: A Systematic Risk Assessment to Prevent Avoidable Harm in Cancer Patients
Klio Bourika1, Angelos Koutras2, Haralambos Kalofonos2, Anna Vicha3, Ekaterini Tsiata4, Evangelia Papadimitriou1, Konstantinos Avgoustakis5, Zoi Panagi4
First Published June 10, 2019.https://doi.org/10.1177/1179554919852933
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Abstract
Objective:
This study was designed to reevaluate and improve the quality and safety of the chemotherapy preparation in a Central Chemotherapy Preparation Unit of a Public Hospital.
Methods:
A failure modes, effects, and criticality analysis (FMECA) was conducted by a multidisciplinary team. All potential failure modes at each stage of the chemotherapy preparation were recorded, and the associated risks were scored for their severity, occurrence, and detectability with a risk priority number (RPN). Corrective actions were suggested, and new RPNs were estimated for the modified process.
Results:
Failure modes, effects, and criticality analysis and priority matrix construction, revealed that the partial compliance of Unit’s premises with international standards (RPNstage: 307), the human errors throughout the compounding (RPNstage: 223)—labeling (RPNstage: 216)—prescribing (RPNstage: 198) steps, and the violation of working protocols by employees (RPNstage: 215), were the most important risks for which either urgent or immediate corrective actions had to be taken. Modifying the procedure through the proposed corrective actions is expected to lead to a significant (71.3%) risk containment, with a total RPNpreparation process reduction from 2102 to 604.
Conclusions:
Failure modes, effects, and criticality analysis and priority matrix development identified and prioritized effectively the risks associated with chemotherapy preparation allowing for the improvement of health services to cancer patients.
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Tumor Size and Overall Survival in Patients With Platinum-Resistant Ovarian Cancer Treated With Chemotherapy and Bevacizumab
Alexandre Sostelly, François Mercier
First Published May 28, 2019.https://doi.org/10.1177/1179554919852071
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Introduction:
Ovarian cancer is now recognized as a constellation of distinct subtypes of neoplasia involving the ovary and related structures. As a consequence of this heterogeneity, the analysis of covariates influencing the overall survival is crucial in this disease segment. In this work, an overall survival model incorporating tumor kinetics metrics in patients with platinum-resistant ovarian cancer was developed from the randomized, open label, phase 3 AURELIA trial.
Methods:
Tumor size data from 361 patients randomly allocated to the bevacizumab + chemotherapy or chemotherapy study arm were collected at baseline and every 8 to 9 weeks until disease progression. Patients continued to be followed for survival after treatment discontinuation. A landmarked Cox proportional hazard survival model was developed to characterize the overall survival distribution.
Results:
Two sets of factors were found to be influential on survival time: those describing the type and severity of disease (Eastern Cooperative Oncology Group [ECOG], Féderation Internationale de Gynécologie et d’Obstétrique [FIGO] stages, presence of ascites) and those summarizing the key features of the tumor kinetic model (tumor shrinkage at week 8 and tumor size at treatment onset). The treatment group was not required in the final model as the drug effect was accounted for in the tumor kinetics model.
Conclusions:
This work has identified both ascites and tumor kinetics metrics as being the 2 most influential factors to explain variability in overall survival in patients with platinum-resistant ovarian cancer.
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Expression of Bone Morphogenetic Protein-7 Significantly Correlates With Non-small Cell Lung Cancer Progression and Prognosis: A Retrospective Cohort Study
Masaya Aoki, Tadashi Umehara, Go Kamimura, Nobuhiro Imamura, Shoichiro Morizono, Yuto Nonaka, Takuya Tokunaga, Aya Harada Takeda, Koki Maeda, Yui Watanabe, Toshiyuki Nagata, Tsunayuki Otsuka, Naoya Yokomakura, Kota Kariatsumari, Masakazu Yanagi, Masami Sato
First Published May 28, 2019.https://doi.org/10.1177/1179554919852087
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Background:
Bone morphogenetic protein-7 (BMP-7) is a signaling molecule belonging to the transforming growth factor-β superfamily. Recent studies have demonstrated that BMP-7 is expressed in various human cancers and plays an important role in the progression of their cancers. The purpose of this study was to investigate the clinicopathologic and prognostic impact of BMP-7 expression in clinical samples of non-small cell lung cancer.
Methods:
This study enrolled 160 patients with non-small cell lung cancer who underwent complete resection. Expression of BMP-7 in cancer tissue was evaluated by immunohistochemistry. Correlations between expression of BMP-7 and clinicopathologic factors and prognosis were analyzed.
Results:
In non-small cell lung cancer, BMP-7 expression was identified not only in cell membranes but also in the cytoplasm of cancer cells. Expression of BMP-7 correlated with p-T (P = .047), N factor (P = .013), and p-stage (P = .046). Overall survival rate was significantly lower in the BMP-7-positive group than in the BMP-7-negative group (P = .004). Multivariate analysis indicated that BMP-7 expression was one of the independent prognosis factors of overall survival (P = .021). Furthermore, among patients with postoperative recurrence (n = 58), the BMP-7-positive group (n = 29) had a significantly poorer prognosis than the BMP-7-negative group (n = 29) (P = .012).
Conclusions:
Expression of BMP-7 in non-small cell lung cancer was correlated with clinicopathologic factors and poorer prognosis. BMP-7 expression may be a useful predictor of aggressive activity of tumor behavior and postoperative outcome of patients with non-small cell lung cancer.
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Review
Open Access
Follicular Dendritic Cell Sarcoma or Not? A Series of 5 Diagnostically Challenging Cases
Nicolas Lopez-Hisijos, Reeba Omman, Stefan Pambuccian, Kamran Mirza
First Published May 23, 2019.https://doi.org/10.1177/1179554919844531
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Abstract
Imperfect or unusual presentation, morphology, or immunophenotype can make the diagnosis of follicular dendritic cell sarcoma (FDCS) very challenging. To illustrate this, we present 5 unique cases from the archives of our tertiary care academic medical center that presented a diagnostic challenge wherein FDCS was the top differential diagnostic possibility. The workup of these cases, including multiple expert consultations, highlights the importance of avoiding specific pitfalls in the diagnosis of FDCS.
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Major Stressful Life Events and Risk of Developing Lung Cancer: A Case-Control Study
Syed H Jafri1, Faisal Ali1, Arash Mollaeian1, Syed Mojiz Hasan12, Rahat Hussain3, Bindu Akkanti3, Jessica Williams1, Mahran Shoukier4, Hazem el-Osta15
First Published May 1, 2019.https://doi.org/10.1177/1179554919835798
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Abstract
Background:
Lung cancer is the leading cause of cancer-related mortality and is strongly linked with smoking. We sought to determine whether major stressful life events (e.g. divorce) are also a risk factor for developing lung cancers.
Methods:
We performed a matched case-control study. Cases (CA) were lung cancer patients diagnosed within the previous 12 months. Controls (CO) were patients without a prior history of malignancy. Data on major stressful life events were collected using the modified Holmes-Rahe stress scale. The primary endpoint was the odds of having a major stressful life event between CA and CO. A sample of 360 patients (CA = 120, CO = 240) was needed to achieve 80% power to detect an odds ratio (OR) of 2.00 versus the alternative of equal odds using χ2 = 0.05.
Results:
Between May 2015 and December 2016, we enrolled 301 patients (CA = 102, CO = 199), matched for median age (CA = 64.4 years, CO = 63.9 years), sex (CA-Male = 48%, CO-Male = 49.2%), and smoking status (ever smoker, CA = 84%, CO = 85%). There was no difference in lifetime stressful life event rate between CA and CO (95% vs 93.9%; P = .68). However, CA were significantly more likely to have had a stressful event within the preceding 5 years than CO (CA = 77.4% vs CO = 65.8%; P = .03, OR = 1.78). β-blocker use was significantly higher among CO (CA = 29.4%, CO = 49.7%; P = .0007, OR = 0.42), suggesting a protective effect.
Conclusion:
Patients with lung cancer are significantly more likely to have had a major stressful life event within the preceding 5 years. In addition, use of β-blockers may be protective against lung cancer.
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Open Access
Investigation of Complications Following Port Insertion in a Cancer Patient Population: A Retrospective Analysis
William Paul Skelton, IV1, Aaron J Franke1, Samantha Welniak1, Raphael C Bosse1, Fares Ayoub1, Martina Murphy2, Jason S Starr2
First Published April 24, 2019.https://doi.org/10.1177/1179554919844770
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Abstract
Central venous access devices, specifically implantable ports, play an essential role in the care of oncology patients; however, complications are prevalent. This retrospective single-institutional review was performed to identify rates of complications from port placement and potential factors associated with these events. A retrospective analysis of 539 cancer patients who underwent port insertion between March 2016 and March 2017 at our institution was conducted. Data examining 18 potentially predictive factors were collected, and multivariate analysis was conducted using logistic regression and odds ratios (ORs) with standard errors to determine predictive factors. Out of 539 patients, 100 patients (19%) experienced 1 complication, and 12 patients (2%) experienced 2 or more complications. An overall lower rate of complications was seen in patients on therapeutic anticoagulation (OR: 0.17, P < .001) or on antiplatelet agents (OR: 0.47, P = .02). No patients on therapeutic anticoagulation developed venous thromboembolism (VTE; 0%). Right-sided port insertion was associated with decreased rates of infection (OR: 0.44, P = .04). Insertion as inpatient was associated with an increased risk for mechanical failure (OR: 4.60, P < .01). This analysis identified multiple predictive factors that can potentially put patients at a higher risk of experiencing complications following port insertion. Our data show lower rates of VTE for patients on anticoagulation or antiplatelet therapy. Further analysis is also necessary to determine why port insertion as an inpatient places patients at a higher risk of complications. This study highlights the risks associated with port placement and prompts the clinician to have an informed discussion with the patient weighing the risks and benefits.
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Case Report
Open Access
Myoepithelial Cell Carcinoma of the Oral Tongue: Case Report and Review of the Literature
Robert G Nicholas1, Josh A Hanson2, Duncan A Meiklejohn1
First Published April 2, 2019.https://doi.org/10.1177/1179554919838254
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Abstract
Background:
Myoepithelial cell carcinoma is a rare malignant neoplasm of salivary gland origin that typically presents in the parotid gland and minor salivary glands. It has been described previously in head and neck sites such as buccal mucosa, alveolar ridge, and base of tongue.
Methods:
A 55-year-old man presented with 30 years of right-sided tongue pain and 10 years of gradually worsening ulceration. Physical examination demonstrated a 2.5 cm ulcerative lesion of the anterior right oral tongue. An initial biopsy was consistent with moderately to poorly differentiated squamous cell carcinoma. Imaging included a positron emission tomography (PET)/computed tomography (CT) scan that demonstrated the right tongue lesion as well as hypermetabolic right level II adenopathy. The patient underwent surgical excision of the right tongue, upper aerodigestive tract endoscopy, and a bilateral supraomohyoid neck dissection. The tongue defect was closed primarily.
Results:
Final pathology of the surgical specimen demonstrated myoepithelial cell carcinoma. All of the margins were free of tumor and no cervical lymph nodes showed metastasis. Immunohistochemistry demonstrated myoepithelial differentiation. The tumor did not show EWSR1 gene rearrangement on genetic testing, suggesting salivary gland origin. Multidisciplinary tumor board evaluation recommended no adjuvant therapy. The patient recovered well after surgery and nearly a year later is without evidence of recurrent or residual disease.
Conclusions:
We present the first reported case of myoepithelial cell carcinoma with primary origin in the oral tongue and review the available literature on this unusual tumor. We discuss the clinical, pathological, and immunohistochemical features and treatment of myoepithelial cell carcinoma.
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Review
Open Access
The Current Landscape of Treatment in Non-Metastatic Castration-Resistant Prostate Cancer
Joelle El-Amm1, Jeanny B Aragon-Ching2
First Published March 7, 2019.https://doi.org/10.1177/1179554919833927
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Abstract
Non-metastatic castration-resistant prostate cancer (nmCRPC) is a heterogeneous disease with variable potential in developing into overt metastases. It is an area of increased unmet need in advanced prostate cancer and for which there had been no great treatments until recent US Food and Drug Administration (FDA) approval of 2 novel anti-androgens apalutamide and enzalutamide, which were both approved given benefit in metastasis-free survival. Early data on the use of darolutamide, another novel anti-androgen, are also explored. This review discusses the pivotal trials that led to the approval of apalutamide and enzalutamide in the nmCRPC setting and discusses the key promises and challenges with the use of these agents.
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PAK1 Expression in Pancreatic Cancer: Clinicopathological Characteristics and Prognostic Significance
Nikolaos Symeonidis12, Maria Lambropoulou3, Efstathios Pavlidis1, Constantinos Anagnostopoulos4, Alexandra Tsaroucha5, Athanasia Kotini6, Christina Nikolaidou3, Anastasia Kiziridou7, Constantinos Simopoulos5
First Published February 18, 2019.https://doi.org/10.1177/1179554919831990
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Abstract
Background:
Improvement of the management of pancreatic cancer requires a better understanding of the genetic and molecular changes responsible for the development of the disease. The family of p21-activated kinases (PAKs) and especially PAK1 appears to mediate many cellular processes that contribute to the development and progression of pancreatic cancer, but the clinical relevance of PAK1 expression with the disease still remains unclear. Aim of the study was to assess the clinical value and the potential prognostic significance of PAK1 in pancreatic adenocarcinoma.
Methods:
We investigated the relationship between the PAK1 expression and the clinical and histopathologic characteristics of pancreatic cancer patients and the potential significance of PAK1 on survival. We examined tissue samples from 51 patients operated for pancreatic cancer. PAK1 expression was investigated with immunohistochemistry and correlated to clinicopathological parameters.
Results:
PAK1 was detected in all tumor samples and high expression was found in most patients. High PAK1 expression was also associated with younger age and well-differentiated tumors, but no association was found between PAK1 expression and Tumor-Node-Metastasis stage as well as deceased or alive status on follow-up. Moderate to high PAK1 expression favored higher 6-month and 1-year survival and low PAK1 expression 2-year survival but without statistical significance.
Conclusions
Our results indicate that PAK1 could potentially be used as a prognostic marker in pancreatic cancer. Further studies could clarify whether utilization of PAK1 in therapeutic protocols for the treatment of pancreatic cancer will render them more effective.
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Access to Palliative Care for Cancer Patients Living in a Northern and Rural Environment in Ontario, Canada: The Effects of Geographic Region and Rurality on End-of-Life Care in a Population-Based Decedent Cancer Cohort
Michael SC Conlon1234, Joseph M Caswell12, Stacey A Santi1, Barbara Ballantyne567, Margaret L Meigs1, Andrew Knight45678, Craig C Earle9, Mark Hartman68
First Published February 14, 2019.https://doi.org/10.1177/1179554919829500
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Abstract
Background:
Access to palliative care has been associated with improving quality of life and reducing the use of potentially aggressive end-of-life care. However, many challenges and barriers exist in providing palliative care to residents in northern and rural settings in Ontario, Canada.
Aim:
The purpose of this study was to examine access to palliative care and associations with the use of end-of-life care in a decedent cohort of northern and southern, rural and urban, residents.
Design:
Using linked administrative databases, residents were classified into geographic and rural categories. Regression methods were used to define use and associations of palliative and end-of-life care and death in acute care hospital.
Setting/Participants:
A decedent cancer cohort of Ontario residents (2007-2012).
Results:
Northern rural residents were less likely to receive palliative care (adjusted odds ratio [OR] = 0.90, 95% confidence interval [CI]: 0.83-0.97). Those not receiving palliative care were more likely to receive potentially aggressive end-of-life care and die in an acute care hospital (adjusted OR = 1.20, 95% CI: 1.02-1.41).
Conclusions:
Palliative care was significantly associated with reduced use of aggressive end-of-life care; however, disparities exist in rural locations, especially those in the north. Higher usage of emergency department (ED) and hospital resources at end of life in rural locations also reflects differing roles of rural community hospitals compared with urban hospitals. Improving access to palliative care in rural and northern locations is an important care issue and may reduce use of potentially aggressive end-of-life care.
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Case Report
Open Access
A Surgical Case of Inflammatory Myofibroblastic Tumor of the Liver: Potentially Characteristic Gross Features
Jiro Watanabe1, Sohsuke Yamada12, Yasuyuki Sasaguri13, Xin Guo2, Nozomu Kurose2, Kouji Kitada4, Masaru Inagaki4, Hiromi Iwagaki4
First Published February 12, 2019.https://doi.org/10.1177/1179554919829498
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Abstract
We herein reported a very rare surgical case of inflammatory myofibroblastic tumor (IMT) of the liver, showing potentially unique and specific gross findings on its cut surface: our IMT demonstrated a relatively well-demarcated and partly infiltrative and likely extrahepatic (ie serosal) but not intrahepatic mass, appearing firm and hemorrhagic, and yellow-whitish in color. The patient, who was a woman in her early 70s with 2-year follow-up for lung cryptococcosis and traffic accident, incidentally presented with unenhanced and low-density, heterogeneous mass on abdominal dynamic CT in the peripheral right lobe of the liver. We could conclusively diagnose the current lesion as the hepatic IMT after thorough analyses including a wide panel of immunohistochemical antibodies. Despite that, all clinicians and pathologists should be aware that the potentially characteristic, extrahepatic gross feature of IMT of the liver might also be one of the powerful supplementary tools for reaching its correct diagnosis. One of our aims in the presented case report is to emphasize that the hepatic IMT should be considered clinicopathologically in the differential diagnosis of mass lesions on the liver.
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Open Access
Efficacy of Regorafenib in Metastatic Colorectal Cancer: A Multi-institutional Retrospective Study
Ali Aljubran1, Mahmoud A Elshenawy12, Magdy Kandil3, Muhammed N Zahir1, Ahmed Shaheen4, Ahmed Gad15, Omar Alshaer6, Ahmed Alzahrani1, Abdelmonem Eldali7, Shouki Bazarbashi1
First Published January 30, 2019.https://doi.org/10.1177/1179554918825447
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Abstract
Background:
Regorafenib is a multi-kinase inhibitor approved for treatment of refractory advanced colorectal cancer. It was found in the clinical trials to have a modest benefit and significant toxicity. Our aim was to assess the outcome in our local clinic practice.
Patients and methods:
Records of patients with confirmed colorectal cancer treated with regorafenib were reviewed. Clinical, pathological, and molecular data were collected. Efficacy and factors of possible prognostic significance were analyzed.
Results:
A total of 78 patients with metastatic colorectal cancer were treated with regorafenib from February 2014 to February 2016 in 4 different institutions (median age: 50.5 years; male: 40 [51.3%]; KRAS mutant: 41 [52%]; right colonic primary: 18 [23%]). A total of 52 patients (66.7%) had Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1, whereas in 25 patients (32.1%) it was >1. In total, 58 patients (74%) had dose reduction. No patient achieved objective response, 15 patients (19%) achieved stable disease, and 56 patients (72%) had progressive disease. With a median follow-up of 6.5 months, the median progression-free survival was 2.8 months (95% confidence interval [CI], 2.5-3.3) and overall survival was 8.0 months (95% CI, 6.2-9.7). Only performance status of ⩽1 had a statistically significant impact on progression-free survival and overall survival in both univariate and multivariate analyses.
Conclusions:
Regorafenib in our clinical practice has equal efficacy to reported data from pivotal registration trials. Our data suggest that performance status is the most important prognostic factor in patients treated with regorafenib, suggesting a careful selection of patients.
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Tumor Treating Fields for Glioblastoma Treatment: Patient Satisfaction and Compliance With the Second-Generation Optune® System
Adrian Kinzel1, Michael Ambrogi2, Michael Varshaver2, Eilon D Kirson3
First Published January 29, 2019.https://doi.org/10.1177/1179554918825449
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Abstract
Background:
Tumor treating fields (TTFields) are a non-invasive antimitotic therapy that delivers alternating electric fields via the Optune® system. The Phase III EF-14 trial in newly diagnosed glioblastoma multiforme (GBM) showed significantly improved progression-free, overall and long-term survival when Optune was used together with maintenance temozolomide (TMZ) compared with TMZ alone. Compliance (average monthly use) was associated with better clinical outcome. The first-generation Optune system weighed approximately 6 pounds (~2.7 kg). The second-generation redesigned Optune system weighs 2.7 pounds (~1.2 kg). We tested and compared GBM patient experience with the second-generation system versus the first-generation system.
Methods:
Ten newly diagnosed and recurrent GBM patients in Germany (median age: 52.9 years [31-79]) were prospectively monitored over the first month of transitioning from the first-generation to the second-generation Optune system. Questionnaires using a numerical analog scale assessed feedback at baseline (first generation) and after 1 month of second-generation use.
Results:
After transitioning to the second-generation system, compliance improved by more than 10% in four patients, was maintained in five patients and decreased by more than 10% in one patient. Following transition, eight out of nine patients reported a reduction in the triggering of malfunction alarms. Self-reported patient feedback showed improved handling and portability (weight, mobility) of the second- versus the first-generation Optune system.
Conclusions:
This patient user survey suggests that patient satisfaction with the second-generation Optune system is improved versus the first-generation system. Improved features of the new system help patients achieve and maintain a higher rate of treatment compliance.
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Hepatotoxicities Induced by Neoadjuvant Chemotherapy in Colorectal Cancer Liver Metastases: Distinguishing the True From the False
Marie Desjardin1, Benjamin Bonhomme2, Brigitte Le Bail3, Serge Evrard1, Véronique Brouste4, Gregoire Desolneux1, Marianne Fonck1, Yves Bécouarn1, Dominique Béchade1
First Published January 22, 2019.https://doi.org/10.1177/1179554918825450
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Abstract
Background:
Pre-operative chemotherapy for colorectal liver metastasis (CRLM) is thought to be the cause of hepatotoxicity of non-tumoural parenchyma. Studies on hepatotoxicity are contradictory. We investigated the impact of a single-line pre-operative chemotherapy on non-tumoural liver analysed by an expert hepatico-pancreatico-biliary pathologist, and the consequences on surgical outcomes.
Patients and methods:
Patients operated for CRLM, after a pure first-line pre-operative chemotherapy, were retrospectively included. Two comparative histopathological analyses were performed for vascular toxicity and steatohepatitis.
Results:
Between 2003 and 2015, 147 patients were included. Chemotherapy was based on oxaliplatin (40.1%), irinotecan (55.8%), or both (4.1%). The expert pathologist described 38.8% of vascular lesions including dilation, nodular regeneration, and peliosis. In multivariate analysis, vascular lesions correlated to male sex (P = .01), pre-operative platelets <150 g/L (P = .04), and aspartate aminotransferase to platelet ratio index (APRI) score >0.36 (P = .02). Steatohepatitis was observed in 15 patients (10.2%), more frequently after irinotecan (14.8% vs 3.4%, P = .01; odds ratio [OR] = 7.3; 95% confidence interval [CI] = [1.5-34.7]), and for patients with body mass index (BMI) >25 kg/m2 (P = .004; OR = 10.0; 95% CI = [2.1-47.5]). A total of 29 patients (19.7%) developed major complications with 2 risk factors: portal vein obstruction (PVO) and septic surgery. Reproducibility assessment of steatohepatitis and dilated lesions by 2 pathologists showed moderate agreement (Kappa score 0.53 and 0.54, respectively).
Conclusions:
There is a probable association between non-alcoholic steatohepatitis (NASH) and irinotecan. Oxaliplatin seems to lead to higher vascular lesions. Except in the presence of pre-existent comorbidities, liver toxicities should not restrain the use of pre-operative chemotherapy prior to parenchymal-sparing surgery.
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Programmed Death-ligand 1 Expression With Clone 22C3 in Non-small Cell Lung Cancer: A Single Institution Experience
Maiko Takeda1, Takahiko Kasai1, Maiko Naito2, Akihiro Tamiya2, Yoshihiko Taniguchi2, Nobuhiko Saijo2, Yoko Naoki2, Kyoichi Okishio3, Shigeki Shimizu4, Kensuke Kojima5, Akihiro Nagoya5, Tetsuki Sakamoto5, Tomoki Utsumi5, Hyung-Eun Yoon5, Akihide Matsumura5, Shinji Atagi3
First Published January 9, 2019.https://doi.org/10.1177/1179554918821314
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Abstract
Background:
In recent years, the anti-programmed cell death 1 (PD-1) drug pembrolizumab (Keytruda) was approved for treatment of unresectable advanced non-small cell lung cancer (NSCLC) as first- or second-line therapy depending on the clone 22C3-programmed death-ligand 1 (PD-L1) immunohistochemical expression score by the companion diagnostic assay. We herein evaluated 22C3-PD-L1 expression of NSCLC in a single institution experience and compared it with clinicopathologic features.
Materials and methods:
We assessed 22C3-PD-L1 expressions of 411 patients with NSCLC from our institution, including in past specimens. Programmed death-ligand 1 immunohistochemistry (IHC) testing was performed using the PD-L1 clone 22C3 pharmDx kit (Agilent Technologies/Dako, Carpinteria, CA, USA). Patients were separated into 3 groups with <1% (no expression), 1% to 49% (low expression), or ⩾50% (high expression) positive tumor cells.
Results:
In all, 137 patients (33%) did not express PD-L1, 155 (38%) showed low expression, and 119 (29%) demonstrated high expression. Archival samples showed lower PD-L1 expression than that of recent samples, and the ratios of no expression case significantly increased by using paraffin blocks embedded particularly in more than 4 years ago. Programmed death-ligand 1 positivity was significantly associated with male sex, smoking, higher tumor grade, squamous cell carcinoma in histologic type, wild-type EGFR, and ALK rearrangement positive.
Conclusions:
The rate of 22C3-PD-L1 expression of NSCLC detected in this study was similar to the frequencies of the previous reports, although the ratio of expression case decreased when using old paraffin blocks.
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Original Research
Open Access
The Nephroprotective Effect of Mannitol in Head and Neck Cancer Patients Receiving Cisplatin Therapy
Erik Hägerström1, Lotte Lindberg2, Jens Bentzen3, Kasper Brødbæk4, Bo Zerahn2, Bent Kristensen2
First Published January 7, 2019.https://doi.org/10.1177/1179554918821320
Abstract
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Abstract
Introduction:
Cisplatin is used as treatment for several different malignancies and a well-known complication is irreversible kidney damage. To protect the kidneys, this treatment is often combined with mannitol infusion to promote osmotic diuresis. Earlier studies investigating the nephroprotective effect of mannitol have shown conflicting results.
Objective:
To investigate changes in kidney function in head and neck cancer patients treated with cisplatin with and without additional mannitol infusion.
Methods:
A single center, retrospective cohort study of patients with squamous cell carcinoma of the head and neck receiving radiotherapy with cisplatin. Patient data were collected from November 2013 to December 2014.
Results:
After exclusion, a total of 78 patients were considered evaluable. They were equally distributed between a mannitol and a non-mannitol group and anthropomorphometrically similar. 51Cr-EDTA clearance declined in the mannitol group from 99.7 (19.9) to 96.4 (20.8) mL/min and in the non-mannitol group from 102.2 (17.8) to 92.3 (23.1) mL/min.
Conclusions:
There was a significantly smaller decrease in 51Cr-EDTA clearance in the mannitol group indicating a nephroprotective effect of mannitol.
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Original Research
Open Access
Correlation Between the Sites of Onset of Basal Cell Carcinoma and the Embryonic Fusion Planes in the Auricle
Giovanni Nicoletti123, Marco Mario Tresoldi13, Alberto Malovini4, Sebastien Prigent1, Manuela Agozzino5, Angela Faga236
First Published December 7, 2018.https://doi.org/10.1177/1179554918817328
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Abstract
Objectives:
This study aims at the identification of the distribution of basal cell carcinomas (BCCs) in the auricle in correlation with the currently most credited sites of the embryonic fusion planes of the auricle.
Methods:
An overall number of 69 patients with 72 BCCs of the auricle were enrolled in the study over a period of 14 years, from June 2003 to October 2017. All the cases underwent medical preoperative digital photography and the specific location of each BCC was coded on an original full-size anatomical diagram of the auricle derived from the reports by Streeter, Wood-Jones, Park, Porter, and Minoux showing the currently most credited sites of the embryonic fusion planes arbitrarily featured as two 5-mm-wide ribbon-like areas: (1) the hyoid-mandibular fusion plane (HM-FP) running from the upper margin of the tragus toward the concha and then deflecting toward the lower margin of the tragus and (2) the free ear fold-hyoid fusion plane (FEFH-FP) running from the cranial-most portion of the helix to the mid-portion of the ascending helix. The latter fusion planes were comprehensively termed embryological fusion planes (EFP) while all of the remaining surface of the auricle was comprehensively termed non-fusion area (NFA). The surfaces of all of the latter areas were calculated using the ImageJ software.
Results:
According to our data, the greatest number of BCCs was observed within the currently most credited sites of the embryonic fusion planes of the auricle. The latter sites displayed a 12-fold increased tumor incidence in comparison with the remaining surface of the ear.
Conclusions:
A correspondence between the sites of onset of BCCs and the sites of merging and/or fusion of embryonal processes was demonstrated in the auricle. Therefore, the latter sites might be considered as high-risk areas for the development of a BCC. Such an evidence provides further support to the hypothesis of an embryological pathogenesis of BCC.
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Case Report
Open Access
A Rare Primary Tumor of the Thyroid Gland: A New Case of Leiomyoma and Literature Review
Yanling Zhang12, Heng Tang2, Huaiyuan Hu2, Xiang Yong2
First Published November 26, 2018.https://doi.org/10.1177/1179554918813535
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Abstract
Primary leiomyomas of the thyroid are very rare. We here report a case of a 53-year-old woman with a painless mass at the right thyroid, revealed by physical examination. The patient underwent a lobectomy. Frozen sections showed a spindle cell tumor of the thyroid gland. The nuclei of some of the tumor cells were obviously enlarged and deeply stained. Pseudocapsule invasion was observed in small foci. Samples showed neither mitosis nor necrosis and the nature of the tumor was difficult to determine. Paraffin sections showed a well-circumscribed nodular composed of intersecting fascicles of spindled to slightly epithelioid cells with eosinophilic cytoplasm and blunt-ended, cigar-shaped nuclei. We observed no significant nuclear atypia, mitotsis, or necrosis. Immunohistochemical staining showed the tumor cells to be positive for α-smooth muscle actin and h-caldesmon but negative for TG, TTF1, PAX8, S-100, CT, CK, and CD34. The ki-67 index was very low (<1%). Primary thyroid leiomyoma is rare and difficult to diagnose using frozen sections. Diagnosis requires immunohistochemical staining. Leiomyoma may be mistaken for other thyroid tumors also characterized by spindle cells.
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