ABSTRACT
A recent interpretation of the Stark Law limits cancer practices from delivering drugs to their patients by mail or courier-a perverse interpretation of a law meant to curb physician self-referrals and one that has led to patient harm.
Subject(s)
Neoplasms , Humans , Neoplasms/drug therapy , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/adverse effects , Health Services Accessibility/standardsABSTRACT
PURPOSE: Oral mucositis (OM) remains a common, debilitating toxicity of radiation therapy (RT) for head and neck cancer. The goal of this phase IIb, multi-institutional, randomized, double-blind trial was to compare the efficacy and safety of GC4419, a superoxide dismutase mimetic, with placebo to reduce the duration, incidence, and severity of severe OM (SOM). PATIENTS AND METHODS: A total of 223 patients (from 44 institutions) with locally advanced oral cavity or oropharynx cancer planned to be treated with definitive or postoperative intensity-modulated RT (IMRT; 60 to 72 Gy [≥ 50 Gy to two or more oral sites]) plus cisplatin (weekly or every 3 weeks) were randomly assigned to receive 30 mg (n = 73) or 90 mg (n = 76) of GC4419 or to receive placebo (n = 74) by 60-minute intravenous administration before each IMRT fraction. WHO grade of OM was assessed biweekly during IMRT and then weekly for up to 8 weeks after IMRT. The primary endpoint was duration of SOM tested for each active dose level versus placebo (intent-to-treat population, two-sided α of .05). The National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03, was used for adverse event grading. RESULTS: Baseline patient and tumor characteristics as well as treatment delivery were balanced. With 90 mg GC4419 versus placebo, SOM duration was significantly reduced (P = .024; median, 1.5 v 19 days). SOM incidence (43% v 65%; P = .009) and severity (grade 4 incidence, 16% v 30%; P = .045) also were improved. Intermediate improvements were seen with the 30-mg dose. Safety was comparable across arms, with no significant GC4419-specific toxicity nor increase of known toxicities of IMRT plus cisplatin. The 2-year follow-up for tumor outcomes is ongoing. CONCLUSION: GC4419 at a dose of 90 mg produced a significant, clinically meaningful reduction of SOM duration, incidence, and severity with acceptable safety. A phase III trial (ROMAN; ClinicalTrials.gov identifier: NCT03689712) has begun.
Subject(s)
Antineoplastic Agents/administration & dosage , Chemoradiotherapy, Adjuvant/adverse effects , Chemoradiotherapy/adverse effects , Cisplatin/administration & dosage , Mouth Neoplasms/drug therapy , Organometallic Compounds/therapeutic use , Oropharyngeal Neoplasms/drug therapy , Radiation Injuries/prevention & control , Radiation-Protective Agents/therapeutic use , Radiotherapy, Intensity-Modulated/adverse effects , Stomatitis/prevention & control , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Cisplatin/adverse effects , Double-Blind Method , Female , Humans , Incidence , Male , Middle Aged , Mouth Neoplasms/epidemiology , Mouth Neoplasms/pathology , Ontario , Oropharyngeal Neoplasms/epidemiology , Oropharyngeal Neoplasms/pathology , Radiation Injuries/diagnosis , Radiation Injuries/epidemiology , Radiation-Protective Agents/adverse effects , Risk Factors , Severity of Illness Index , Stomatitis/diagnosis , Stomatitis/epidemiology , Time Factors , Treatment Outcome , United StatesABSTRACT
OBJECTIVES: Marketing of the Natural American Spirit (NAS) cigarettes implies reduced risk of toxic exposures. We aimed to provide a comprehensive chemical characterization of these cigarettes. METHODS: We analyzed 13 varieties of NAS for a range of tobacco- and combustion-derived constituents. Cigarettes were smoked by 2 standard regimens and analyzed using our routine analytical procedures. We also analyzed tobacco filler and physical cigarette characteristics. RESULTS: Under intense smoking conditions, nicotine in smoke of NAS cigarettes averaged 3.3(±0.7) mg/cigarette, compared to 2.4(±0.4) in other brands. The levels of carcinogenic nitrosamines NNN and NNK varied extensively across NAS varieties, their sum ranging from 71 to 443 ng/cigarette. Levels of volatile toxicants were generally similar to, or higher than those found in other commercial US cigarettes. CONCLUSIONS: High nicotine content suggests that NAS cigarettes may be more addictive than many other brands. Similarly low TSNA levels were measured in some NAS varieties, independent of whether or not they were labeled as organic. Levels of other toxicants were similar to other brands. Consumer education and additional regulatory measures are needed to address the misperceptions that NAS cigarettes are safer than other commercial cigarette brands.
ABSTRACT
Effective communication is a requirement in the teamwork necessary for improved coordination to deliver patient-centered, value-based cancer care. Communication is particularly important when care providers are geographically distributed or work across organizations. We review organizational and teams research on communication to highlight psychological safety as a key determinant of high-quality communication within teams. We first present the concept of psychological safety, findings about its communication effects for teamwork, and factors that affect it. We focus on five factors applicable to cancer care delivery: familiarity, clinical hierarchy-related status differences, geographic dispersion, boundary spanning, and leader behavior. To illustrate how these factors facilitate or hinder psychologically safe communication and teamwork in cancer care, we review the case of a patient as she experiences the treatment-planning process for early-stage breast cancer in a community setting. Our analysis is summarized in a key principle: Teamwork in cancer care requires high-quality communication, which depends on psychological safety for all team members, clinicians and patients alike. We conclude with a discussion of the implications of psychological safety in clinical care and suggestions for future research.
Subject(s)
Breast Neoplasms/psychology , Communication , Patient Care Team/organization & administration , Adult , Breast Neoplasms/therapy , Female , Humans , PerceptionABSTRACT
Chromosomal instability (CIN) is a hallmark of cancer that contributes to tumour heterogeneity and other malignant properties. Aberrant centromere and kinetochore function causes CIN through chromosome missegregation, leading to aneuploidy, rearrangements and micronucleus formation. Here we develop a Centromere and kinetochore gene Expression Score (CES) signature that quantifies the centromere and kinetochore gene misexpression in cancers. High CES values correlate with increased levels of genomic instability and several specific adverse tumour properties, and prognosticate poor patient survival for breast and lung cancers, especially early-stage tumours. They also signify high levels of genomic instability that sensitize cancer cells to additional genotoxicity. Thus, the CES signature forecasts patient response to adjuvant chemotherapy or radiotherapy. Our results demonstrate the prognostic and predictive power of the CES, suggest a role for centromere misregulation in cancer progression, and support the idea that tumours with extremely high CIN are less tolerant to specific genotoxic therapies.
Subject(s)
Breast Neoplasms/genetics , Centromere/genetics , Chromosomal Instability/genetics , Gene Expression Regulation, Neoplastic , Lung Neoplasms/genetics , Breast/pathology , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Breast Neoplasms/therapy , Centromere/metabolism , Chemotherapy, Adjuvant/methods , Datasets as Topic , Female , Gene Expression Profiling/methods , Humans , Kaplan-Meier Estimate , Lung/pathology , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Neoplasm Staging , Prognosis , Radiotherapy, Adjuvant/methods , Tissue Array Analysis/methods , Treatment OutcomeABSTRACT
Proliferating trichilemmal cyst (PTC), a rare benign tumor, is a fascinating follicular neoplasm. It occurs on head and neck region of elderly women and its histologic hallmark is trichilemmal keratinization. A 70-year-old female presented to skin outpatient department with complaints of a slowly growing mass on scalp for the past 2 years. On examination, the lesion was firm, mobile, painless, and measured 6 × 5 × 3 cm and was not fixed to the underlying bone. Laboratory investigations were unremarkable. Excisional biopsy was done. Histopathology revealed well-demarcated tumor with variably sized lobules of squamous epithelium undergoing an abrupt change into eosinophilic amorphous keratin without granular cell layer (trichilemmal keratinization). PTC should be differentiated from trichilemmal cyst as it has potential for malignant transformation. Thus, complete excision is recommended for all benign proliferating variants owing to their potential for locally aggressive behavior and malignant transformation.
ABSTRACT
Arsenic and nicotine exposure has been a major health concern globally. Individually both these toxicants increase the risk to various diseases including cancers. However, limited information exists on the co-exposure. In this study, we evaluate the effects of their individual and combined exposure and if co-exposure to these toxicants might have a synergism or antagonism. Male rats were exposed to a very low dose of arsenic (25 ppm in drinking water) or nicotine (0.25 mg/kg, sub-cutaneously) for a period of 5 months and post exposure various biochemical variables indicative of oxidative stress and apoptosis evaluated. Almost all glutathione linked enzymes showed marked alteration in individual as well as co-exposure treated groups. While serum creatinine and apoptosis indicator, lactate dehydrogenase (LDH) were significantly increased in both treatments, an additive effect was noted in co-exposure group. A similar trend was also seen in brain and liver but not in kidneys. Gene expression studies showed marked reduction in catalase, Cu-Zn SOD, GST, there was a significant up regulation in Bax, caspase 3 in various tissues along with urinary 8-OHdG levels, indicative of DNA damage and apoptosis. Interestingly, a decrease in liver arsenic concentration was noted in co-exposed group compared to arsenic alone exposed group. In conclusion, the present study suggests that arsenic and nicotine exhibited significant toxicity during individual exposure whereas co-exposure to these toxins showed variable conditions (indicative of both synergism and antagonism) in male rats.
ABSTRACT
Stereotactic body radiotherapy (SBRT) and stereotactic radiosurgery (SRS) are advanced radiotherapy delivery techniques that allow for the delivery of high-dose per fraction radiation. Advances in imaging technology and intensity modulation have allowed SRS and SBRT to be used for the treatment of tumors in close proximity to the spinal cord and cauda equina, in particular spinal metastases. While the initial treatment of spinal metastases is often conventional palliative radiotherapy, treatment failure is not uncommon, and conventional re-irradiation may not be feasible due to spinal cord tolerance. SBRT and SRS have emerged as important techniques for the treatment of spinal metastases in the proximity of previously irradiated spinal cord. Here we review the current data on the use of SBRT and SRS spinal re-irradiation, and future directions for these important treatment modalities.
Subject(s)
Radiosurgery/methods , Salvage Therapy/methods , Spinal Neoplasms/surgery , Animals , Humans , Palliative Care/methods , Spinal Neoplasms/pathology , Spinal Neoplasms/secondaryABSTRACT
Giant cell fibroblastoma (GCF) is a rare soft tissue tumour that occurs almost exclusively in children younger than 10 years of age and is mostly located in the superficial soft tissues of the back and thighs. We present a rare case of GCF with encephalocele in a 1.5-year-old boy who presented with a swelling in the occipital area of the scalp since birth. CT scan suggested encephalocele without any suspicion of a mass lesion. On histopathology, an ill-defined proliferation of fibroblasts in a heavily collagenised and focally myxoid stroma was seen containing numerous multinucleated cells having a floret-like appearance along with mature glial tissue bordering a cystic space. Immunohistochemically, the stromal cells were positive for both, vimentin (diffuse) and CD34 (focal) thereby confirming the histological diagnosis of GCF. This case highlights the unusual coexistence of GCF with congenital defects and its histogenetic resemblance to dermatofibrosarcoma protuberans.
Subject(s)
Dermatofibrosarcoma/pathology , Encephalocele/pathology , Head and Neck Neoplasms/pathology , Skin Neoplasms/pathology , Dermatofibrosarcoma/complications , Encephalocele/complications , Head and Neck Neoplasms/complications , Humans , Infant , Male , Skin Neoplasms/complicationsABSTRACT
Cholesterol granuloma of the breast is an unusual non-neoplastic condition which frequently resembles malignancy clinically as well as radiologically. We herein report a case of a 28-year-old woman who presented with a lump in the upper outer quadrant of right breast. Physical examination and ultrasonography strongly suggested a carcinomatous lesion, but histopathological examination confirmed the diagnosis to be cholestrol granulomas. This article highlights the perplexing clinical presentation of cholesterol granulomas and affirms the role of histopathological examination in diagnosing these lesions correctly.
Subject(s)
Breast Diseases/diagnosis , Breast Neoplasms/diagnosis , Cholesterol , Granuloma, Foreign-Body/diagnosis , Adult , Diagnosis, Differential , Female , HumansABSTRACT
Cluster DNA damage refers to two or more lesions in a single turn of the DNA helix. Such clustering may occur with bulky DNA lesions, which may be responsible for their sequence-dependent repair and mutational outcomes. Here we prepared three 16-mer cluster duplexes in which two fluoroacetylaminofluorene adducts (dG-FAAF) are separated by zero, one, and two nucleotides in the Escherichia coli NarI mutational hot spot (5'-CTCTCG1G2CG3CCATCAC-3'): 5'-CG1*G2*CG3CC-3', 5'-CG1G2*CG3*CC-3', and 5'-CG1*G2CG3*CC-3' (G* = dG-FAAF), respectively. We conducted spectroscopic, thermodynamic, and molecular dynamics studies of these di-FAAF duplexes, and the results were compared with those of the corresponding mono-FAAF adducts in the same NarI sequence [Jain, V., et al. (2012) Nucleic Acids Res. 40, 3939-3951]. Our nucleotide excision repair results showed the diadducts were more reparable than the corresponding monoadducts. Moreover, we observed dramatic flanking base sequence effects on their repair efficiency in the following order: NarI-G2G3 > NarI-G1G3 > NarI-G1G2. The nuclear magnetic resonance, circular dichroism, ultraviolet melting, and molecular dynamics simulation results revealed that in contrast to the monoadducts, diadducts produced a synergistic effect on duplex destabilization. In addition, dG-FAAF at G2G3 and G1G3 destacks the neighboring bases, with greater destabilization occurring with the former. Overall, the results indicate the importance of base stacking and related thermal and thermodynamic destabilization in the repair of bulky cluster arylamine DNA adducts.
Subject(s)
2-Acetylaminofluorene/chemistry , DNA Adducts/metabolism , Deoxyribonucleases, Type II Site-Specific/metabolism , Endodeoxyribonucleases/metabolism , Escherichia coli Proteins/metabolism , Escherichia coli/metabolism , Base Pairing , Base Sequence , Cluster Analysis , DNA Adducts/chemistry , DNA Repair , Deoxyribonucleases, Type II Site-Specific/chemistry , Deoxyribonucleases, Type II Site-Specific/genetics , Molecular Dynamics Simulation , Mutation , Oligodeoxyribonucleotides/chemical synthesis , Oligodeoxyribonucleotides/chemistry , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , ThermodynamicsABSTRACT
Ash-leaf spots, a diagnostic manifestation of tuberous sclerosis complex, are sometimes difficult to differentiate from other hypopigmented lesions. Vitiligo, naevus anaemicus and naevus depigmentosus are important clinical differentials for ash-leaf spots. Among these naevus depigmentosus poses maximum difficulty because of clinical as well as histological similarities. Here we describe a 6-month-old child with multiple segmental hypopigmented macules over the face. In isolation lesions appeared to be those of naevus depigmentosus. However, the presence of other manifestations of tuberous sclerosis favoured the diagnosis of ash-leaf spots. Important similarities and differences between the two have also been discussed.
Subject(s)
Nevus/diagnosis , Diagnosis, Differential , Humans , Infant , Male , Nevus/pathologyABSTRACT
We present a case of a 15-year-old girl with a pulsatile, rapidly enlarging mass at the root of the nose suspected to be malignant. Excisional biopsy showed worrisome histological features; however, a final diagnosis of cellular schwannoma was reached excluding the possibility of malignant peripheral nerve sheath tumour by histological and immunohistochemical attributes. Cellular schwannoma, a pseudosarcomatous entity, is a rare benign neoplasm that may cause bone erosion and may be mistaken for a malignancy, clinically and histologically. Diagnosis of cellular schwannoma is essential to prevent mismanagement as it never metastasises and responds to local excision as opposed to aggressive treatment required by a malignant neoplasm.
Subject(s)
Nerve Sheath Neoplasms/diagnosis , Neurilemmoma/diagnosis , Nose Neoplasms/diagnosis , Peripheral Nervous System Neoplasms/diagnosis , Adolescent , Diagnosis, Differential , Female , Humans , Nerve Sheath Neoplasms/pathology , Neurilemmoma/pathology , Nose Neoplasms/pathology , Peripheral Nervous System Neoplasms/pathologyABSTRACT
We present a case of a salivary gland tumour in a 25-year-old woman with lymphadenopathy and a clinical suspicion of lymphoma. The patient had a history of rapidly enlarging mass near angle of jaw which was resected and sent for histopathological examination. A final diagnosis of acinic cell tumour with dedifferentiation was made by histomorphological and immunohistochemical studies. Acinic cell tumour can mimic any salivary neoplasm phenotypically because of its varied architectural patterns of presentation with varied cell types, hence called the harlequin of salivary gland. Acinic cell tumour with dedifferentiation is a rare aggressive variant and requires adjuvant radiotherapy for better prognosis, hence the need for accurate diagnosis and communication to the surgeon.
Subject(s)
Carcinoma, Acinar Cell/diagnosis , Salivary Gland Neoplasms/diagnosis , Adult , Carcinoma, Acinar Cell/radiotherapy , Carcinoma, Acinar Cell/surgery , Combined Modality Therapy , Diagnosis, Differential , Female , Humans , Salivary Gland Neoplasms/radiotherapy , Salivary Gland Neoplasms/surgery , Treatment OutcomeABSTRACT
Actinomycosis is a rare, torpid, suppurative and chronic granulomatous infection caused by a Gram-positive organism that was initially thought to be a fungus. These organisms normally live as commensals in the human oral cavity, respiratory and digestive tracts, but become invasive when they gain access to the subcutaneous tissue through a musosal lesion, the triggering events being dental caries, dental manipulation and maxillofacial trauma. It is often misdiagnosed as it can mimic numerous infectious and non-infectious diseases. We describe an interesting case of cervical actinomycosis that was misdiagnosed as sebaceous cyst and precisely identified after histopathological examination of the tissue.
Subject(s)
Actinomyces/isolation & purification , Actinomycosis, Cervicofacial/diagnosis , Epidermal Cyst/diagnosis , Actinomycosis, Cervicofacial/microbiology , Biopsy , Diagnosis, Differential , Diagnostic Errors , Female , Humans , Young AdultABSTRACT
Primary bone lymphoma (PBL) is an uncommon clinical entity and a rare presentation of non-Hodgkin's lymphoma. PBL accounts for less than 5% of malignant bone tumors, 4-5% of extra nodal lymphoma and less than 1% of all non-Hodgkin's lymphoma. Diffuse large-B-cell lymphoma (DLBCL) accounts for the majority of cases of PBL. The incidence of PBL is so rare that many of its aspects remain unknown. A number of studies have been reported from western countries but only a few reports are available from Asia. Out of 20,000 bone lesions received in our department over 5 years, only 5 cases were primary bone lymphoma; all of which were DLBCL. We report our experience on PBLs with main emphasis on two unusual presentations of this rare tumor.
ABSTRACT
We present a case of a 60-year-old woman with multiple right axillary swellings. Patient had a history of lump with pigmentation over back for which she was operated upon. There was also a nodule over resected scar on back. A final diagnosis of malignant melanoma (recurrent and metastatic to axillary lymph nodes) was rendered with the help of fine-needle aspiration cytology (FNAC). Malignant melanomas are the most lethal of cancers of the skin and are notorious for the great variability of cytological presentation. We discuss the role of FNAC in early diagnosis and prognostication of recurrent and metastatic disease.
Subject(s)
Lymphatic Metastasis/pathology , Melanoma/pathology , Neoplasm Recurrence, Local/pathology , Skin Neoplasms/pathology , Biopsy, Fine-Needle , Diagnosis, Differential , Early Diagnosis , Female , Humans , Lymph Nodes/pathology , Melanins/metabolism , Middle Aged , Prognosis , Skin/pathologyABSTRACT
Sweet's syndrome is a neutrophilic inflammatory dermatosis presenting with sudden onset tender red to purple papules and nodules, fever and neutrophilia. Gastrointestinal and urinary tract infections, pregnancy, inflammatory bowel disease, drugs and malignancy are some of the known aetiological factors. Paraneoplastic Sweet's syndrome accounts for 15-20% cases and thus forms an important subset. At times its onset helps in suspecting an underlying malignancy, thus making timely intervention possible. In the present case report Sweet's syndrome was the presenting feature of gall bladder adenocarcinoma; an association that has been rarely reported before.
Subject(s)
Adenocarcinoma/complications , Gallbladder Neoplasms/complications , Paraneoplastic Syndromes/etiology , Sweet Syndrome/etiology , Abdominal Pain/etiology , Adenocarcinoma/diagnosis , Adenocarcinoma/surgery , Anti-Inflammatory Agents/therapeutic use , Cholecystectomy , Female , Gallbladder Neoplasms/diagnosis , Gallbladder Neoplasms/surgery , Humans , Middle Aged , Paraneoplastic Syndromes/drug therapy , Paraneoplastic Syndromes/pathology , Prednisolone/therapeutic use , Sweet Syndrome/drug therapy , Sweet Syndrome/pathologyABSTRACT
Nicotine affects a variety of cellular process ranging from induction of gene expression to secretion of hormones and modulation of enzymatic activities. The objective of the present study was to study the dose dependent toxicity of nicotine on the oxidative stress in young, adult and old rats which were administered 0.75, 3 and 6 mg kg(-1) nicotine as nicotine hydrogen tartarate intraperitoneally for a period of seven days. No changes were observed in blood catalase (CAT) activity and level of blood reactive oxygen species (ROS) in any of the age group at the lowest dose of nicotine. However, at the highest dose (6 mg kg(-1) nicotine) ROS level increased significantly from 1.17 to 1.41 microM ml(-1) in young rats and from 1.13 to 1.40 microM ml(-1) in old rats. However, no change was observed in blood ROS levels of adult rats. Administration of 3 mg kg(-1) nicotine resulted in an increase in level of reduced glutathione (GSH) in rats of all the age groups. The young animals were the most sensitive as a dose of 6 mg kg(-1) resulted in decline in the levels of reduced GSH to 0.89 mg ml(-1) as compared to normal control (1.03 mg ml(-1)). The antioxidant enzymes SOD and CAT were sensitive to a dose of 6 mg kg(-1) as it resulted in decline of the enzymatic activity in all age group animals. Also, administration of nicotine at a lower dose of 3 mg kg(-1) inhibited SOD activity from 1.48 to 1.20 units min(-1) mg(-1) protein in old rats. Catalase activity showed a similar trend at a dose of 3 mg kg(-1). Administration of nicotine also increased the blood lipid peroxidation levels at all three doses in young and old rats dose dependently. Nicotine exposure also increased ROS in brain at the doses of 3 and 6 mg kg(-1) in all the three age groups. Brain GSH decreased significantly at high dose of nicotine (6 mg kg(-1) b.wt.) in adult rats (4.27 mg g(-1)) and old rats (3.68 mg g(-1)) but in young rats level increased to 4.40 mg g(-1) at the lower dose (0.75 mg kg nicotine). Brain lipid peroxidation increased at all three doses of nicotine in young as well as old rats as compared to their respective normal control. The SOD activity increased significantly in young (2.88 units min(-1) mg(-1) protein) and old rats (1.81 units min(-1) mg(-1) protein) as compared to their respective normal at a dose of 6 mg kg(-1). Interestingly, the SOD activity decreased in adult rats (2.18 units min(-1) mg(-1) protein) as compared to its normal control. Catalase activity decreased at the dose of 3 mg kg(-1) and 6 mg kg(-1) nicotine in young and old rats but no effect was observed in adult rats at any of the doses. Acetylcholine esterase (AchE) activity decreased in a dose dependent manner in adult and old rats. Overall, the results of the study indicate that young and old rats are more sensitive to nicotine induced oxidative stress as compared to the adult ones.