Approximately 61,560 new cases of renal cell carcinoma (RCC) were estimated to be diagnosed in the USA in 2015, with 14,080 cancer-related deaths attributed to cancers of the kidneys and the renal pelvis. More than one-half of these patients were diagnosed incidentally on cross-sectional imaging performed for non-related conditions. Increased incidental detection of small renal masses as well as advances in surgical techniques have led to development of nephron-sparing procedures for treatment in order to preserve renal function. Over the past decade, the options for the treatment of RCC have evolved to include radical nephrectomy as well as partial nephrectomy, laparoscopic nephrectomy and, in selected cases, percutaneous radiofrequency ablation (RFA), microwave ablation (MWA), and cryotherapy. Each therapy has unique clinical applications and benefits. This article illustrates various treatment modalities used in the therapy of RCC, with special emphasis on percutaneous ablative techniques.
RCC accounts for 85% of all renal tumors and is slightly more common in men than in women (1.6:1.0). Symptomatic RCC usually presents with a triad of flank pain, hematuria, and a palpable abdominal mass. Hematuria, either gross or microscopic, in any patient usually warrants evaluation by a computed tomographic (CT) scan. Other non-specific symptoms include weight loss, anemia, or fatigue. However, almost one-half of patients are asymptomatic at diagnosis and have incidentally detected tumors on cross-sectional imaging. Certain genetic syndromes such as von Hippel–Lindau (VHL) disease increase the incidence of RCC (accounting for approximately 2% of cases of RCC). Other risk factors include smoking, hypertension, obesity, and end-stage renal disease resulting in dialysis.
Clear-cell RCC is the most common histological subtype and is associated with VHL syndrome and end-stage renal disease (Table 22.1). Other inherited forms include familial clear-cell RCC. Papillary RCC, when sporadic, has a prominent male preponderance and is associated with almost 90% 5-year survival rates prior to metastatic spread. Papillary RCC has a lesser incidence of metastases than clear-cell but, when metastatic, is harder to treat. Papillary RCC is also seen in end-stage renal disease and in several familial syndromes. Other less common cell types include chromophobe RCC and collecting-duct RCC.
Diverse types of cancer genomics data are being collected widely and rapidly with the aim to systemically examine the origin and dynamics of different diseases. An important premise is that by integrating different types of genomics data, such as DNA copy number and RNA expression data, we will gain more knowledge about the underlying biological process. For example, high versus low correlation between a copy number aberration (CNA) for a gene marker and its abnormal RNA expression would indicate different disease mechanisms and therefore require different treatment strategies.
We propose a Bayesian model-based framework for the integration of different types of genomics data. We employ a mixture model (Parmigiani et al., 2002) for the observed expression data that defines latent indicators representing the differential expression status of each gene. By operating on the latent indicators, we effectively alleviate the high noise level in the original observed expression data. We integrate diverse types of genomics data through a regression of the latent variables across different data types. The regression model is naturally in agreement with the biological knowledge and allows for the easy incorporation of other covariates.
By definition, integration models must be able to borrow information from multiple genomic platforms, measured on the same patients and genes. For illustration purposes, we consider two of the most widely discussed genomic platforms: array comparative genomic hybridization (arrayCGH or aCGH), which measures DNA copy numbers, and expression microarrays, which measure RNA expression.
Recent advances in next-generation sequencing have hugely impacted biological research through high-throughput platforms that generate megabases of sequence data per day. These technologies improve both speed and cost and have found applications in genotyping, protein-DNA interactions (Barski et al., 2007; Mikkelsen et al., 2007), transcriptome analysis (Friedländer et al., 2008; Hafner et al., 2008; Vera et al., 2008), and de novo genome assembly (Chaisson and Pevzner, 2008). In this chapter, we focus on the Illumina/Solexa sequencing platform. However, data from other technologies have similar characteristics, and we expect models similar to the one presented here to remain useful also for these technologies.
Solexa sequencing (www.illumina.com) produces millions of polymerase chain reaction (PCR) amplified and labeled sequences of short reads. For each short read, the measurements of their fluorescent intensities are stored in an I × 4 matrix, where I is the length of the read (e.g., I = 36). Such amatrix corresponds to a colony. The positions i = 1, …, I in the short read are sequenced in cycles by a biochemical procedure called sequencing-by-synthesis. As a result, each row of the colony matrix contains measurements from a cycle in the experiment in which the sequence of a single base is synthesized. At each cycle, all four nucleotides (A, C, G, and T) labeled with four different fluorescent dyes are probed, thus producing a quadruple vector of fluorescent intensity scores.
The care of patients with malignant tumors has changed substantially in recent years. New chemotherapeutic agents have led to substantial prolongation of survival in patients with liver metastases. Advances in surgery and anesthesia have enabled the resection of tumors with much lower morbidity and mortality. Diagnostic imaging techniques have facilitated earlier detection and more detailed follow-up of patients with liver tumors. However, the most exciting advances have been in the field of interventional radiology. Percutaneous ethanol injection, which has been used most effectively and extensively in the Far East, demonstrated that it is possible to completely destroy small hepatocellular carcinomas, obviating the need for surgical removal. This paved the way for the development of other local methods of treatment based on heating or freezing malignant tumors.
This book describes the state of the art in one of the most exciting fields in modern medicine. The authors are all world authorities in their field. The volume focuses on interventional radiological techniques but also provides a summary of the pathology of liver tumors, as well as an account of modern medical and surgical methods of treatment.
We are still in the early stages of local tumor treatment. The early results are very promising, and it is very likely that, in time, traditional surgical techniques will be increasingly supplemented by image-guided methods. Coupled with advances in structural and functional imaging, these advances offer the hope that a substantial proportion of patients with hepatic malignancy can be treated effectively.
Approximately 38,890 new cases of renal cell carcinoma (RCC) were estimated to be diagnosed in the United States in 2006, with 12,840 cancer-related deaths attributed to cancers of the kidneys and the renal pelvis (1). More than one-half of these patients were diagnosed incidentally on cross-sectional imaging performed for non-related conditions (2). Increased incidental detection of small renal masses as well as advances in surgical techniques have led to development of nephron-sparing procedures for treatment in order to preserve renal function. Over the past decade, the options for the treatment of RCC have evolved to include radical nephrectomy as well as partial nephrectomy, laparoscopic nephrectomy and, in selected cases, percutaneous radiofrequency ablation (RFA) and cryotherapy. Each therapy has unique clinical applications and benefits. This article illustrates various treatment modalities used in the therapy of RCC with special emphasis on percutaneous ablative techniques.
RCC accounts for 85% of all renal tumors and is slightly more common in men than in women (1.6 to 1.0) (2). Symptomatic RCC usually presents with a triad of flank pain, hematuria and a palpable abdominal mass. Hematuria, either gross or microscopic, in any patient usually warrants evaluation by a computed tomographic (CT) scan. Other nonspecific symptoms include weight loss, anemia or fatigue. However, almost one-half the patients are asymptomatic at diagnosis and have incidentally detected tumors on cross-sectional imaging. Certain genetic syndromes such as von Hipple-Lindau (VHL) disease increase the incidence of RCC (accounting for approximately 2% of cases of RCC).
In the past, focal renal biopsy had a limited role in the management of renal masses. Potential complications and an overestimated risk of seeding the biopsy tract dissuaded operators from biopsy, and when performed definitive results were uncommon. Hence, urologists presumed that solid renal lesions over 3 cm and complex cysts were predominantly renal cell carcinomas (RCC) and rarely performed biopsy before surgical procedures.
Attitudes have changed to renal biopsy for a number of reasons, firstly, histological techniques have become more reliable. The morphology, immunocytochemical, and genetic profiles of RCC and its subtypes have been better described. Immunohistochemistry and special stains and genetic test are available to help differentiate tumor subtypes. Oncocytoma, oncocytic cancers, RCC and fat poor angiomyolipomas (AML) can now be differentiated histologically. There has also been a downward-stage migration of renal tumors at diagnosis and a substantial fraction of contemporary solid renal masses are benign. In one study, 12.8% of solid renal masses were found to be benign. When stratified by size, the proportion of benign masses was 25% for masses smaller than 3 cm, 30% for masses smaller than 2 cm, and 44% for masses smaller than 1 cm. Furthermore, small solid benign renal masses cannot be reliably distinguished from malignant masses by means of imaging findings alone.
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