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Introduction to Cancer
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The multiple genetic changes that result in cancer may take many years to accumulate. During this time, the biological behavior of the premalignant cells slowly changes from the properties of normal cells to cancer-like properties. Premalignant tissue can have a distinctive appearance under the microscope, and among the distinguishing traits are an increased number of dividing cells, variation in nuclear size and shape, variation in cell size and shape, loss of specialized cell features, and loss of normal tissue organization. Dysplasia is an example of an abnormal type of excessive cell proliferation characterized by a loss of normal tissue arrangement and cell structure in premalignant cells. These early neoplastic changes are distinct from hyperplasia, a reversible increase in cell division caused by an external stimulus, such as a hormonal imbalance or chronic irritation. The most severe cases of dysplasia are referred to as carcinoma in situ, meaning an uncontrolled growth of cells that remains in the original location and has not progressed to invading other tissues. Nevertheless, a carcinoma in situ may develop into an invasive malignancy and is usually removed surgically, if possible. The various mechanisms of cellular DNA damage are described below.
Bladder cancer
Published in Anju Sahdev, Sarah J. Vinnicombe, Husband & Reznek's Imaging in Oncology, 2020
The majority of urothelial carcinomas arise on the lateral bladder walls (approximately 47%) or in the region of the trigone (approximately 20%). At the time of presentation, approximately one-third of patients with urothelial bladder tumours have multifocal disease, and indeed the whole of the bladder epithelium may be abnormal, showing areas of squamous metaplasia and CIS. The presence of carcinoma in situ is associated with an increased incidence of recurrence and an increased risk of development of invasive disease (8,9). Unlike other premalignant ‘in situ’ conditions, CIS of the bladder is recognized as a high-grade malignancy by definition because of its high rates of progression and recurrence. While malignant bladder cancer appears to be on the decline, rates of CIS are increasing in males in the UK (10). Urothelial cancers may be associated with synchronous or metachronous development of tumours elsewhere in the urinary tract, including the renal pelvis and ureter.
Cancer of the Cervix Uteri
Published in Jennifer L. Kelsey, Nancy G. Hildreth, Breast and Gynecologic Cancer Epidemiology, 2019
Jennifer L. Kelsey, Nancy G. Hildreth
Good evidence exists that invasive cervical cancer is usually preceded by carcinoma in situ, which is in turn frequently preceded by cervical dysplasia. However, what has been called cervical dysplasia actually consists of a variety of lesions and the term “dysplasia” is used differently by various pathologists. These reservations notwithstanding, what has been called cervical dysplasia most often occurs in the 20- to 29-year age group, carcinoma in situ in the 30- to 39-year group, and invasive cervical cancer after the age of 40.4 Carcinoma in situ is frequently found at the margins of invasive cancers,5 and in situ lesions are sometimes found in previous biopsies of patients who develop invasive cancer.6 Furthermore, women with dysplasia are at high risk for carcinoma in situ, while women with carcinoma in situ are at high risk for invasive cervical cancer. Stern and Neely,7 for instance, found from a follow-up study in a clinic population that about 85% of the women developing carcinoma in situ or invasive carcinoma had been in the 1% of the population previously classified as having dysplasia.
Signaling new therapeutic opportunities: cytokines in prostate cancer
Published in Expert Opinion on Biological Therapy, 2022
Elias Chandran, Luke Meininger, Fatima Karzai, Ravi A Madan
The very short half-life of IL-15 of 40 min, coupled with its requirement for trans-presentation by IL-15Rα, limits therapeutic use in its free form. To overcome this, an IL-15 superagonist receptor α fusion complex (IL-15RαFc), N-803 (previously known as ALT-803), was designed by (1) altering the IL-15 molecule with a N72D mutation, (2) complexing it with the extracellular IL-15 receptor alpha (IL-15Rα) sushi domain, and (3) fusing it to the IgG1 Fc domain. This significantly prolongs the half-life to 25 h and increases its biological activity 25-fold [45,69]. N-803 has been evaluated in several clinical trials with promising results. In a phase I trial, monotherapy with subcutaneous N-803 demonstrated a good safety profile, with the commonest grade 1–2 AEs including injection site reactions (82%), hypertension (65%), gastrointestinal symptoms (65%), hypotension (59%), and chills (47%), but no incidences of severe cytokine release syndrome or capillary leak syndrome [66]. The QUILT 3.032 phase II/III trial evaluated intravesical N-803 with BCG in 160 patients with BCG-unresponsive non-muscle invasive bladder cancer. In the carcinoma in situ (cis) cohort, 59 out of 83 patients (71%) attained a complete response, maintained for a median duration of 24.1 months. In the papillary cohort, disease-free survival was 53% at 18 months. Remarkably, 90% of the patients avoided cystectomy at 2 years of follow-up [70]. N-803 has FDA breakthrough designation since 2019 [71], and full approval has been sought based on these data [72].
Combining Clinical Parameters and Immunohistochemical Markers Might Strengthen Prediction of Recurrence of Non-Muscle Invasive Bladder Cancer
Published in Journal of Investigative Surgery, 2022
Bladder cancer is a frequent cancer of both men and women with an estimated 429.000 new case and 165.000 new deaths per annum world-wide. Despite the scientific and technological improvements, bladder cancer has a high rate of recurrence varies between 50% and 90%. It has been suggested that several factors such as old age, smoking, multiplicity, hydronephrosis, tumor grade, presence of carcinoma in situ, tumor size larger than 3 cm is associated with high risk of progression [1]. To date varies nomograms such as EORTC [2] and CUETO [3] have been suggested to predict recurrence and progress in non-muscle invasive bladder cancer (NMIBC) [1]. Although these nomograms give us an opinion on risk of tumor progression and recurrence, they don’t represent a comprehensive picture of tumor aggressiveness. With the developments in microarray and next-generation sequencing technology, several studies have been conducted to determine the molecular markers capable of predicting NMIBC behavior [4–6]. In this context, some researchers have been suggested to combine molecular biomarkers with clinicopathological parameters to improve risk stratification of NMIBC [7]. Similar to those efforts combining immunohistochemical analysis of Ki67, P53 and CK20 with widely utilized clinicopathologic parameters might be not only useful but cost-effective [8]. The utility of immunohistochemistry to assess bladder cancers’ biologic behavior is not well-determined. However, promising results have been reported related to utility CK5/6, CD44, CK20 and p53 expression [9].
Penile Sparing Techniques For Penile Cancer
Published in Postgraduate Medicine, 2020
Due to the rarity of the malignancy, there are no randomized prospective clinical trials comparing different PST to each other or to the gold standard treatments of partial and total penectomy. The selection of PST depends on the location of the tumor, tumor grade, and stage (based on biopsy, exam, and possibly imaging), provider experience, and the patient’s wishes/priorities (Table 2). For carcinoma in situ (Tis), circumcision, cryotherapy, excision, or topical chemotherapy can be utilized as a primary or combination therapy, with the majority of lesions managed successfully with surgical intervention [47]. Laser ablation, circumcision, glansectomy, glans resurfacing, and Mohs micrographic surgery can all be utilized for the management of small, localized penile cancer. Tumors involving only the foreskin may simply be managed by circumcision, but involvement of the glans may require glans resurfacing, or glansectomy depending on its extent. Superficial tumors involving the mid or proximal shaft may be amenable to wide local excision with the addition of a split-thickness skin graft for larger tumors [3,4,48,49].