Treating Cancer

50 Things About 50 Cancers

This ebook from medical practitioner and family doctor Dr. Parajuli gives you all of the signs and symptoms that you need to know in order to catch cancer in the very early stages and protect yourself from it. You don't have to worry about if you have cancer anymore, and better yet you don't have to spend thousands of dollars to make sure of that either! All it takes is a bit of knowledge and you are on your way! This book also teaches about other aspects of cancer patients, such as how to live with different kinds of cancer, how to prepare yourself mentally to accept this reality if it IS a reality for you, and how to deal with doctors and insurance companies. This book is easy to read and in PDF format, so you don't have to worry at all about reading it. Make it easy on yourself! Continue reading...

Do I Have Cancer Overview

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Molecular Cancer Epidemiology

Molecular and genetic epidemiology represent two separate branches of epidemiology whose boundaries are overlapping. While molecular epidemiology evaluates the association of variations in known genes with risk of cancer, genetic epidemiology aims to identify the unknown genes that influence risk of malignancies.3-14 Moreover, molecular epidemiology also uses molecular markers to link exposures to cancer.7-13 The two terms are very often used interchangeably and are referred to in the following as molecular cancer epidemiology. Molecular cancer epidemiology identifies risk factors for the different cancer types at the population level. These studies are usually carried out as either case-control, cohort cross-sectional, or ecological studies.14 Case-control studies investigate patients with a specific cancer in relation to a healthy group (which serves as the control) while the cohort study assesses distribution of exposures to certain risk factors in a subset of a population and...

Risk Factors and Cancer

Cancer is a multifactorial disease, in which both environmental and genetic factors play a role. Part of the environmental factors are conditions of life that result in exposures to carcinogens depending on where people live and work as well as changes that people make in the world. Cancer shows both geographic and temporal variability, and there are different patterns of cancer at different places and different times which depend both on lifestyle and habits as well as environmental hazards.15 Risk factors in cancer etiology comprise four classes of external agents in carcinogenesis (carcinogens) physical, chemical and biological agents, and diet.12'13'15 The increasing knowledge of the process of carcinogenesis induced by chemical agents provides a major basis for cancer control and has unraveled the association between smoking and lung cancer. About 30 of all cancer deaths in the USA are due to the use of tobacco, and this death toll is still increasing reflecting smoking habits...

Cancer Screening Diagnosis and Prevention

Molecular biomarkers may be used to identify early responses to DNA damage and to assess cancer risk.45-47 Unscheduled DNA synthesis, chromosome aberrations, sister chromatid exchanges, and the micronucleus tests are some examples of these tumor markers. These markers are also referred to as genetic markers and can be scored in advance of preneoplastic lesions that are usually detected by histological methods.45-47 Genetic markers can also be used to show that the vast majority of cancers originate from a single stem cell. In addition to the clonogenic nature of cancer, there are numerous epigenetic events that create an environment for abnormal cell division, such as chronic inflammation or persistent stimulation of the immune system. A number of chromosomal abnormalities are associated with predisposition to cancer.48,49,51 The molecular pathology of the chromosome rearrangement are well understood and have been shown to inactivate tumor suppressors like the Wilms' tumor gene52 and...

Cancer and somatic evolution

1.1 What is cancer The development and healthy life of a human being requires the cooperation of more than ten million cells for the good of the organism. This cooperation is maintained by signals and cellular checkpoints which determine whether cells divide, die, or differentiate. The phenomenon of cancer can be defined on various levels. On the most basic level, cancer represents the collapse of this cooperation. This results in the selfish, uncontrolled growth of cells within the body which eventually leads to the death of the organism. The first chapter will discuss several aspects of cancer biology. This forms the background for the mathematical models which are presented in this book. Of course, cancer biology is a very complicated topic and involves many components which are not mentioned here. A comprehensive review of cancer biology is given in standard textbooks, such as Kinzler and Yogelstein (1998) . It is commonly thought that cancer is a disease of the DNA. That is,...

Treatment Options for Major Cancers and Future Directions

According to the most recent statistics, one in three people will be diagnosed with cancer during their lifetime. Increased life expectancy (cancer can be considered a disease of advanced years), environmental factors (e.g., exposure to carcinogens), and social habits (e.g., diet and or smoking) have dramatically increased the risk of cancer in Western populations. Breast, lung, colorectal, and prostate are the four major types of cancer in adults, and they account for over half of all cases diagnosed. The treatments of these major cancers depend upon a variety of factors, but the most common ones involved surgery combined with radiation and or chemotherapy. These treatments are briefly discussed in this section. Table 1 shows representative examples of anticancer agents and their mechanism of action. Depending on the tumor size and the stage of the disease, treatment for breast cancer may involved surgery, radiation therapy, chemotherapy, hormone therapy, or a combination of two or...

Screening for Cervical Cancer Precursors to Prevent Invasive Disease

In many developed countries a decline in the incidence and mortality of cervical cancer has been observed in the past 30 years. The description of a cytological technique of cervical cancer detection by Papanicolaou in 1941 has given rise to the most successful early detection scheme worldwide. Population-based screening programs or opportunistic screening systems have been implemented in many affluent countries for decades. Due to lack of resources and infrastructure, however, these programs have not been implemented easily in other, less developed parts of the world. The problems encountered in screening for cervical cancer precursors with the aim to prevent invasive carcinoma depend on many different social and political issues, such as lack of patient knowledge, unwillingness of patients to participate in a screening program, or program quality. These issues should be addressed accordingly. In early cancer detection, different cytological classification schemes, and depending on...

FSee 708 Kinase Inhibitors for Cancer

Cyclophosphamide, doxorubicin, and vincristine sulfate (CAV) cyclophosphamide, doxorubicin, and etoposide (CAE) etoposide and cisplatin (EP) and cyclophosphamide, etoposide, and vincristine (CEV). Depending on the extent of the disease, non-small cell lung carcinoma can be removed by surgical resection or treated with radiation therapy in combination with chemotherapy (e.g., gemcitabine hydrochloride together with cisplatin and vinorelbine). In addition to the preceding treatment modalities, photodynamic therapy is use for the care of patients with inoperable lung cancer or with distant metastasis. Surgery is the treatment of choice for colorectal cancer and, depending on the stage of the disease, chemotherapy and radiation are used as adjuvant treatment.76 For example, a cocktail of different agents (fluorouracil, leucovorin, and irinotecan) is used for metastatic colorectal cancer. An important advance in the treatment of colorectal cancer has been reported recently with...

The Cell Cycle and Cancer

A unique feature of cancer cells is high, indefinite cellular proliferation that continues without regard for the surrounding environment and the regulatory mechanisms that exist in normal cells. In normal tissues, cell division occurs in the context of a series of sequential biological events known as the cell cycle, which is composed of four different phases (Figure 1). DNA replication occurs in the so-called S (synthesis) phase, and cell division occurs in the M (mitosis) phase. These two main activities are preceded by two gap phases G1 to prepare cells for DNA synthesis, and G2 to allow cells the opportunity to check the integrity of the newly synthesize DNA and to prepare cell division. Phase transitions are controlled by a series of serine threonine kinases called cyclin-dependent kinases (CDKs) and their regulatory subunits named cyclins. Misregulation the cell cycle is a general event in diseases of uncontrolled cell growth and some of the most common alterations of this...

Nasopharyngeal Cancer

Nasopharyngeal cancer is a highly radioresponsive tumor. This is especially true for the World Health Organization (WHO) class II and III (nonkeratinizing and undifferentiated squamous cell carcinoma). In the United States, however, 30 to 50 of patients will have WHO class I (keratinized squamous cell carcinoma), which is associated with alcohol and tobacco use and is much less radiosensitive.77 Advanced-stage disease is associated with poor 5-year survival rates, within a range of 10 to 40 when treatment is with radiotherapy alone. For this reason, adding chemotherapy to the treatment protocol has been investigated.

Preoperative radiotherapy for oesophageal cancer

When the MRC set up a new Oesophageal Cancer Working Party in 1990, this working party considered conducting a randomized trial of surgical resection with or without pre-operative radiotherapy. A small planning group was given the task of pursuing this idea, but, having consulted widely and conducted a literature search, were aware that a number of randomized trials had already investigated this question. The results of these trials appeared conflicting, however, and none of the trials was large enough to provide a reliable answer. The planning group therefore suggested that a meta-analysis would be more appropriate, and this was carried out by the MRC CTU meta-analysis group. The results 13 did not show a clear role for pre-operative radiotherapy, nor did they show sufficient promise to generate enthusiasm for a further trial.

Intraportal fluorouracil for colorectal cancer

In 1989, the UK Coordinating Committee on Cancer Research identified improving survival of colorectal cancer patients as a national priority, and set up a working group to develop trial proposals. This group conducted a systematic review 14 of published adjuvant chemotherapy trials, and also contacted other trials organisations to find out about ongoing trials and to obtain, where possible, unpublished data. This review identified portal vein infusion of fluorouracil given immediately post-operatively for one week as a highly promising treatment six trials had evaluated this treatment and together they suggested a striking, and highly statistically significant, reduction in the annual odds of death. However, the total number of patients included in the trials was only 1500 (only 300 of whom had died) and a high proportion of randomized patients were excluded from the published analyses which may have biased results in favour of chemotherapy (see Section 9.4.1). The data were therefore...

Box 42 Control arms in advanced ovarian cancer trials

In the late 1990s, several chemotherapy regimens were in use in the treatment of advanced ovarian cancer. In the US, both cisplatin (P) alone and cyclophosphamide + cisplatin (CP) combinations were standard, although evidence from a meta-analysis of trials comparing CP with CAP (cyclophosphamide, doxorubicin, cisplatin) showed a survival benefit to the 3-drug combination 1 . The US Gynaecological Oncology Group (GOG) used CP as the control arm in one trial evaluating a paclitaxel-based combination 2 and P as the control in another 3 . The former trial showed striking benefits to the paclitaxel arm, which were at odds with the results of the European ICON3 trial 4 . ICON3 compared a similar paclitaxel combination with a control group comprising either CAP or single agent carboplatin. This choice followed from the results of the ICON2 trial 5 , which demonstrated the clinical equivalence of adequately dosed carboplatin and CAP. ICON3 did not find a benefit to the paclitaxel combination,...

Plasminogen Activation and Cancer

Plasmin are inhibited by the action of specific inhibitors, plasminogen activator inhibitor (PAI-1) and a2-antiplasmin, respectively uPA is secreted as a proenzyme that is reciprocally activated by the action of plasmin. Activation of the cascade is locally confined by the high-affinity binding between uPA or pro-uPA and the cell surface receptor uPAR. Mice lacking uPA display defects in extravascular fibrin degradation while cooperation is observed in transgenic animals that coexpress uPA and uPAR.192 In a similar manner to MMPs, stromal cells appear to be the major sources of plasminogen activity in most tumors. The stromal cell type producing uPA depends on the origin of the tumor, myofibroblasts being responsible in breast and colon and macrophages in prostate cancer. Elevated levels of uPA and uPAR in the blood and tissue are associated with poor prognosis in many types of cancer, regardless of their respective sources.193,194 Manipulation of uPA levels by overexpression,...

Complexity of Cancer Genetic Counselling

Genetic counselling is a highly complex process due to both objective and subjective factors. The information provided in the context of cancer genetic counselling, including the concept of risk, is objectively complex. More subjectively, this information must be provided to an individual, mostly a woman, who is often emotionally affected by a family history of cancer and who will have to consider the pros and cons of the necessities of surveillance or preventive surgical options. In addition, the counsellee also has to act as a messenger to the members of the family, whose relationships might subsequently be modified by the information.

Qualityof Life Issues in Head and Neck Cancer Management

Quality of life and quality of death are opposite sides of the same coin and both are presumably optimized when the likelihood of locoregional cancer recurrence is minimized. Quality-of-Life Issues in Head and Neck Cancer Management As we go beyond the year 2000, health care professionals, regardless of their area of practice, will be required (like it or not) to participate in evolving areas of medical practice that have not been part of the traditional medicine of earlier decades outcomes assessment, patient quality-of-life (QOL) issues, statistical methods such as decision analysis and meta-analysis, and new areas of patient interest such as alternative medicine, to name a few.1 A voluminous literature already exists concerning QOL assessment in head and neck cancer (HNC) patients, but it is too embryonic to have fostered distinct controversies at this point. This chapter presents a brief overview of where we have been, where we are, and where we are going on issues related to QOL...

Evaluation of Therapy in Advanced Head and Neck Cancer

As we ponder which of the approaches to advocate for our patients, it is important to have clear in our mind what ultimately determines success. Survival has always been the gold standard by which a particular therapy has been judged. However, in these advanced cancers there is no clear-cut evidence that any one approach offers a better chance at survival. In fact, as stated by Weymuller in 1994,18 using the therapeutic end points of survival and loco-regional control, it is true that no multi-institutional study that has utilized surgery as a form of treatment has demonstrated a significant separation between The increased sophistication of the reconstructive techniques employed following radical ablative surgery has certainly leveled the playing field in comparing the radical and organ preservation approaches resulting in improvement of not only cosmesis but function as well (e.g., pharynx, esophagus, mandible, and skin defects of the head and neck).19 Some structures (e.g., tongue...

Communication in Cancer Genetic Counselling

The three main objectives of doctor-patient communication in medicine are the creation of a trustful interpersonal relationship, exchange of information, and treatment-related decisions (Ong et al. 1995). The primary objective of cancer genetic counselling is exchange of information. However, to obtain an adequate level of informed consent, to minimize distress, improve satisfaction, and promote appropriate preventive behaviour, other aspects must also be taken into account, especially an evaluation of the patient's understanding of the information provided and of the emotional reactions induced by this information.

Twenty First Century View of Tamoxifen as a Treatment for Breast Cancer

The impact of the clinical introduction of tamoxifen on healthcare can be assessed through the work of the Early Breast Cancer Trialists Collaborative Group (EBCTCG) that meets in Oxford, UK every 5 years. The international group has met since 1984 to evaluate the impact of therapies on the treatment of breast cancer. The method is to integrate the positive and negative findings of all the world's randomized prospective clinical trials to reach a consensus on the merits of a treatment approach. Reports on the value of long-term adjuvant tamoxifen therapy in the treatment of node-positive and node-negative estrogen receptor-positive breast cancer can be documented through the EBCTCG publications.138-140 Overall, the reports document the enhanced survival and disease-free survival conferred by tamoxifen. The recent report by the EBCTG141 analyzes the results from 145 000 women in 194 trials of chemotherapy or hormonal therapy begun before 1995. The treatment of estrogen...

Tamoxifen and Breast Cancer Prevention

Thirty years ago, tamoxifen was shown to prevent the induction and promotion of carcinogen-induced mammary cancer in rats.92,200 Similarly, tamoxifen was also shown to prevent the development of mammary cancer induced by ionizing radiation in rats. These laboratory observations, coupled with the emerging preliminary clinical observation that adjuvant tamoxifen could prevent contralateral breast cancer in women,201 provided a rationale for Powles to start a toxicology study at the Royal Marsden Hospital, London, UK to test whether tamoxifen would be acceptable to prevent breast cancer in high-risk women. This vanguard study opened for recruitment in 19 8 6202 and was to provide important toxicological and compliance data for subsequent trialists. In the decade following the Powles initiative, several studies were started to answer the question ''Does tamoxifen have worth in the prevention of breast cancer in select high-risk women '' Eventually four studies were available to evaluate...

Organization of Cancer Genetic Counselling in France

Various models of cancer genetic counselling, depending on national or regional expertise and resources, have been developed (Hopwood 2005). In France, for example, the various professionals working in the field of cancer genetics, forming the Genetics and cancer group, have proposed guidelines for cancer genetic counselling, based on a multidisciplinary organization in which the various healthcare professionals meet with the counselee at various times. The first meeting is a long consultation, for which the counselee is encouraged to attend with a certain amount of preparation (maximum of information about the family history of cancer). The counselee is invited to attend the visit with one or several members of the family. The coun-selee's family tree is constructed and a maximum of information is obtained about all cancers in the family then, the geneticist describes the objectives of genetic counselling, the existence of genes and their possible alteration, the concept of risk, the...

Breast Cancer Adjuvant Therapy

Tamoxifen is the first hormonal chemotherapy drug and is used to block estrogen receptors.2 This drug historically was used for tumors that are estrogen or progesterone receptor positive. Now, tamoxifen is used in women that are receptor positive or negative for prophylaxis against a new breast cancer. This is used after cytotoxic chemotherapy. Tamoxifen functions to put the cancer cells in G0 phase of cell division by blocking the estrogen receptor. Either used as prophylaxis against further Table 9.6. Chemotherapeutic agents used in breast cancer cancer or in receptor positive patients, no increased benefit has been seen with more than 5 years use. The side effect is an increased risk of uterine cancer secondary to the estrogen receptor blockade stimulation. Molecular chemotherapy is being developed and one drug has been FDA approved. Herceptin is a monoclonal antibody to HER-2-neu. HER-2-neu is an epidermal growth factor receptor that has overexpression in poor prognosis breast...

Of Familial Breast Cancer Genetic Consultations

Butow and Lobb (2004) conducted a major study, examining in detail the process and content of genetic counselling in initial consultations with women from high-risk breast cancer families. Over 158 consultations of women unaffected and affected with breast cancer, conducted in 10 familial breast cancer clinics throughout Australia, were audiotaped and transcribed. A detailed coding system was developed to cover all facts thought to be important to be elicited from or conveyed to the consultant, and all behaviours thought to facilitate active involvement and expression of emotional concerns. This analysis evidenced that the average genetic counselling session was 61 min comparable to that of European clinics (Hopwood et al. 2003a) , that patients spoke on average one-third of the session and consultants demonstrated consistently good practice in providing detailed information on essential aspects related to familial breast cancer. The authors noted that, although the woman's agenda was...

Satisfaction with Cancer Genetic Counselling

Assessing the satisfaction of 36 counselees with cancer genetic counselling in The Netherlands, Bleiker and coworkers (1997) found generally high levels of satisfaction with the different aspects assessed. The areas identified as needing further attention were related to the information regarding the possible impact of genetic counselling and testing on daily life, communication between the clinical geneticist and other healthcare workers, and psychosocial support during and after genetic counselling.

Colorectal Cancer CT Colonography Virtual Colonoscopy

CTC is used for the detection of polyps and colorectal cancer in symptomatic patients, patients with failed colonoscopy (pain, sharp bowel curvatures or bowel stenosis) and in screening. CT of the air- or carbon dioxide-distended colon is performed in supine and prone positions, as some bowel segments may be collapsed in one position. This dual positioning also assists movement of residual fluid and stool that may obscure the bowel surface. The use of oral iodine contrast media (e.g. Gastrografin) has facilitated identification of submerged lesions as well as tagging of residual stool. The use of intravenous contrast medium has no clear advantage for polyp detection and may even be counterproductive with the use of oral fluid tagging. In symptomatic populations CTC is an accurate technique with a detection sensitivity for colorectal cancer of 95.9 and a specificity of > 99 17 . For patients with polyps > 10 mm, sensitivity is 85-92.5 and specificity 95-97.4 , while for patients...

Raloxifene and Breast Cancer Prevention

The rationale for the use of SERMs, including raloxifene, as breast cancer preventives is based on a strategic hypothesis formulated when SERM action was first recognized in the late 1980s. The evidence to support the use of raloxifene in this paradigm stems from observations made in the laboratory91,96 and the clinic165 along with close monitoring of ongoing osteoporosis placebo-controlled trials. Previous studies have shown that raloxifene inhibits the growth of dimethylbenzanthracene-induced rat mammary carcinoma94 but it prevents mammary cancer by reducing the incidence of N-nitrosomethylurea-induced tumors91'92 if given after the carcinogen but before the appearance of palpable tumors. However, as would be anticipated with a drug that has a short biological half-life, raloxifene is not superior to tamoxifen at equivalent doses.91 Studies have shown that raloxifene, when administered orally, is rapidly absorbed from the gastrointestinal tract and undergoes extensive phase II...

Of Cancer Genetic Counselling

Studies indicate that cancer genetic consultants present generally good practice in terms of the information they provide however, they less frequently demonstrate attention or skills to deal with the subjective aspects of the genetic counselling, i.e. verifying the counselee's understanding of the information, assessing emotional reactions or attitudes of informed family members. There is a growing number of guidelines for communicating risk, suggesting the need to develop and evaluate innovative communication strategies (Bottorff et al. 1998 Hopwood 2005). Genetic counsellors should also be encouraged to explore idiosyncratic risk beliefs, personal theories of inheritance, and personal or social support that underpin coping. Integration of risk information may be enhanced when emotional issues are addressed. Geneticists or genetic counsellors are confronted with the challenging task of providing objective information which is adapted to the individual, taking into account the...

Carcinogenicity Mutagenicity Studies

The toxicity and carcinogenicity of sodium hypochlorite has been examined extensively. Both published and unpublished studies have repeatedly demonstrated this ingredient's safety, and failed to raise any significant questions regarding acute toxicity or carcinogenicity. A number of studies that examine sodium hypochlorite's carcinogenic and mutagenic potential have been investigated by both in vitro and in vivo methods. One of the most common worldwide uses of chlorine and chlorine containing compounds (including sodium hypochlorite) is as a disinfectant for drinking water. This use has led a number of investigators to examine the carcinogenicity of chlorinated water. Hasegawa et al. 30 examined the effects on rats of a 104-week administration of sodium hypochlorite in drinking water at levels of 0.05-0.2 . No significant increase in incidence of any tumors was observed, leading the investigators to conclude that sodium hypochlorite showed no carcinogenic potential. Kurokawa examined...

E Paclitaxel intravenously 175 mg m2 on days 1 and 8 of 21 day cycle reported in control arm of phase III breast cancer

Benchmark nucleoside antimetabolite 5-FU, its prodrug capecitabine, the nucleoside analog gemcitabine, which has supplanted 5-FU as the standard of care in pancreatic cancer, and the antifolate pemetrexed. Also for comparison, representative adverse events for paclitaxel, which acts by inhibiting microtubule formation, are included. The antimetabolite drugs act by inhibiting processes in rapidly dividing cells, in both tumors and normal tissue. Thus, the observed toxicities tend to be associated with tissues that undergo relatively frequent cell division, such as bone marrow, gastrointestinal tract, and hair. A significant number of patients in the trials discontinued treatment due to the adverse events, indicating another challenge in the clinical use of such drugs. An additional hurdle for all chemotherapies is adapting the preclinical dosing regimen to the clinic. Efficacy doses for oncology drugs are determined in rodents (usually mice), and maximum tolerated doses are determined...

National Cancer Institute NCI database

The National Cancer Institute (NCI) database93 is a collection of more than half a million structures, assembled by the NCI's Developmental Therapeutics Program (DTP) or its predecessors in the course of NCI's anticancer screening. Approximately half of this database (c. 250 000 structures) is freely publicly available, and is therefore called the 'Open NCI Database'. It contains connection tables for structures, data such as cancer or AIDS screening results, approximately 127 000 CAS Registry Numbers, and 3600 measured logP values. The more recent NIH PubChem140 project provides freely available information on structure and biological activities of about 5 million small molecules.

Rectal Cancer Diagnostic Workup

Total Mesorectal Excision

Adenocarcinoma is the most common rectal malignancy. The diagnosis is usually histologically established prior to imaging. Cross-sectional imaging is used to stage the tumor. The treatment of rectal cancer depends on the extent of disease and has changed substantially over the last decade. EUS and MRI are important in the management of these patients. T2-weighted sequences are pivotal in MRI of rectal cancer. These provide optimal contrast between the rectal wall and surrounding fat and organs. T1-weighted sequences after intravenous contrast medium administration do not provide much additional information. No bowel preparation is necessary. The importance of T-staging has decreased with the widespread use of total mesorectal excision (TME). In this procedure, the rectal cancer and the surrounding envelope of mesorectal fat bordered by the mesorectal fascia is removed en bloc. This operation has been shown to reduce significantly tumor recurrence rate. For this treatment, determining...

Dietary factors and the risk of cancer

At present, much is known about the role of food intake in the etiology of cardiovascular diseases. The relationship between the intake of saturated fatty acids and the occurrence of ischemic heart diseases, for example, is now generally recognized. However, the role of food components in the induction of various types of cancer is less clear, although it is beyond doubt that dietary factors do play an important role. The types of cancer frequently occurring differ from one country to another. In Japan, cancer of the stomach occurs more often than in the US or Europe, while the incidence of breast and colon cancer is higher in the US and Europe than in Japan. The fact that in Japanese people who migrated to the US, the incidence of stomach cancer decreased whereas the incidence of breast and colon cancer increased, suggests that lifestyle and environmental factors are important. As far as the role of dietary factors in the etiology of cancer is concerned, laypersons mostly think that...

Risk Factors for Breast Cancer

A history of breast cancer Exposure to ionizing radiation Familial Risk Factors for Breast Cancer More than 50 of women in family have breast cancer Breast cancer present in more than I generation Multiple occurrences of breast cancer (> 3) in close relatives History of bilateral breast cancer High rate of co-existing ovarian cancer B. Nulliparity and increased age at first pregnancy are associated with an increased risk for breast cancer. Nulliparity alone accounts for 16 of new cases of breast cancer each year. The relative risk for breast cancer increases with advancing age. C. Race is an independent risk factor. While white women are at an increased risk for breast cancer, African American women with breast cancer have higher fatality rates and a later stage at diagnosis. D. A family history of breast cancer, especially in first-degree relatives, increases the risk. E. A history of breast cancer increases a woman's risk for subsequent breast cancers. If the woman has no family...

Apoptosis and Nervous System Cancer

Although it is easy philosophically and useful intellectually to refer to drugs as apoptosis inducers and to cells as targets for apoptosis induction, it has become clear that what that means in particular is dependent both upon the drug and the cell of reference. For example, Table 4.1 lists the molecular species proposed to be involved in blocking glioma or neuroblas-toma cell apoptosis in response to natural and or pharmacologic stimuli. The differences between these tumors in the proximal pathway that leads downstream to apoptosis demonstrate the probability that selective phar-macologic induction of apoptosis must rely on delineation and targeting of pathways that may be unique to each tumor type. As such, even within a tumor, different cells have different, hard-wired propensities and respond to different signals to undergo apoptosis. This heterogeneity at all levels represents a challenge for the future in cancer therapy.

Cancer initiation onehit and twohit stochastic models

The question of the origins of cancer is among the most important in our understanding of the disease. There is no universal answer to this question, as different cancers are initiated by different mechanisms. There are however certain patterns that can be recognized. Among the most important ones is cancer initiation via the inactivation of a tumor suppressor gene. The concept has evolved during the last 30 years. A defining landmark was the discovery of the Rb gene. Retinoblastoma is a rare and deadly cancer of the eye that afflicts children. It comes in two versions. One affects newborn infants and is characterized by multiple tumors. The other hits children when they are older and is usually characterized by only a single tumor. In 1971, Alfred Knud-son proposed an explanation, which became known as the famous Knud-son's two-hit hypothesis Knudson (1971) . According to his theory, in the early-onset version of retinoblastoma, children inherit a defective gene from one parent....

The Uterus Malignant Conditions Cervical Cancer

Patients with cervical cancer are staged according to the classification of the International Federation of Gynecology and Obstetrics (FIGO) (Table 1). Unfortu nately, FIGO staging is based primarily on clinical exam (neither cross-sectional imaging, nor lymph node status is routine), and staging errors of 15-24 for patients with Stage IB disease and 45-58 for patients with Stages IIA and IIB disease have been reported 19, 20 . MRI is the best single modality for the pre-operative staging of cervical cancer it is cost minimizing and it can alter therapy 21-23 . In a retrospective study, Hricak et al. found that women with cervical cancer > 2 cm whose initial staging examination was MR required fewer tests and fewer procedures compared to the standard work-up 22 . MR imaging correlates for FIGO staging have been developed and are summarized in Table 1. Table 1. Cervical cancer FIGO staging with corresponding MR imaging findings1 tive as surgery for FIGO stage IB (2) disease 27 . That...

Eventfree survival eventfree interval and cancerspecific survival

It is possible to include patients who have died before documented progressive disease by defining an event as progression of disease or death, using the phrase progression-free survival time to describe this outcome measure. Alternatively, it is possible to define an event as progression of disease only, censoring those patients who have died before their disease has progressed, using the phrase progression-free interval to describe this outcome. Which of these is most appropriate depends on the situation. In cancers where only a relatively small proportion of deaths are due to causes other than the cancer (less than 20 per cent, say), then it is safest (and conservative) to focus on the outcome measure progression-free survival. The reason for this is that a proportion of patients who have apparently died before documented progressive disease have probably died from their disease, but their disease has progressed too quickly to allow a formal assessment to be made. Further, a small...

MRI of Prostate Cancer Introduction

Prostate cancer continues to be the leading cancer among American men, with 184,500 new cases annually 1 . It has been estimated that 39,200 men died of prostate cancer in the U.S.A. in 1998. This makes prostate cancer the second cause of cancer-related death in men 2, 3 . Furthermore, the probability of developing prostate cancer from birth to death is 20 3 . Treatment selection is dependent on patient age and health, cancer stage and grade, morbidity and mortality of treatment, as well as patient and physician preference. The mainstay for organ-confined disease is either radical surgery or curative radiotherapy 4, 5 . This is only considered an option in the absence of seminal vesicle infiltration (SVI), extension through the prostatic capsule (extracapsular extension, ECE) or metastatic disease. Therefore, the purpose of staging is the possible detection of extraprostatic disease. Clinical staging by digital rectal examination (DRE) and prostate specific antigen (PSA) remains as...

Carcinogenesis Is A Multistep Procedure

The carcinogenic process is a multistep procedure, in which cells acquire properties of the malignant phenotype in a step-by-step manner. This phenotype is characterized by increased resistance to toxic compounds, enhanced cell turnover, uncontrolled growth, and capability of invasion and metastasis.1 The stepwise development of such changes can be summarized sequentially into three phases initiation, promotion, and progression2 (Figure 23.1). The first phase, initiation, involves a mutagenic event leading to a permanent genetic alteration. During the second phase, promotion, the initiated cells are stimulated to proliferate by a promoter, forming clonal cell expansions referred to as preneoplastic foci, or nodules. In the final step of the carcinogenic process, progression, preneoplastic cells aquire genomic instability and unregulated growth, with time leading to the neoplastic phenotype. Additional spontaneous mutations in growth regulatory genes of the labile DNA in these cells...

Hepatitis Induces Oxidative Dna Damage Of Importance For Hepatocarcinogenesis

Thus, experimental data strongly indicate that increased oxidative stress is an important pathogenic mechanism in hepatitis-induced liver damage, and these results are supported by clinical data on humans with hepatitis B and C. In these patients, plasma levels of vitamin E were decreased as compared with that of healthy controls, indicating depletion of antioxidants secondary to the hepatitis infection.21,23 Likewise, in an assay using the plasma ratio of oxidized and reduced ubiquinone as a marker of oxidative stress,20 patients with hepatitis were found to have a significantly increased ratio as compared with healthy controls.22 In a prospective randomized double-blind crossover study, patients with chronic hepatitis C refractory to alpha-interferon therapy were treated with high doses of vitamin E, which significantly reduced the serum activities of aminotransferases, indicating a reduction of the liver damage.50 These findings indicate that enhanced free radical production may be...

Multiplestage Design In Cancer Trials

As was discussed in Section 6.6, in phase II cancer trials, it is undesirable to stop a study early when the treatment appears to be effective but desirable when the treatment seems to be ineffective. For this purpose, a multiple-stage design is often employed to determine whether an experimental treatment holds sufficient promise to warrant further testing (see, e.g., Fleming, 1982 Simon, 1989 Chang et al., 1987 Therneau et al., 1990). The concept of a multiple-stage design is to permit early stopping when a moderately long sequence of initial failures occurs. Chow et al. (2003b) provided tables for sample size calculation for two-stage designs such as minimax design, Simon's optimal two-stage design, and flexible two-stage design and three-stage designs such as optimal three-stage design and flexible design for single-arm phase II cancer trials.

The Problem Colon Cancer

Colon cancer is the second leading cause of cancer death in the United States, and it accounts for approxi mately 10 of all cancer deaths in both men and women combined 2, 3 . 150,000 new cases and 50,000 deaths result from colon cancer every year in the United States 2 . This translates into 137 deaths per day or six deaths per hour. This is unfortunate, since most cases of colon cancer are preventable if detected as precancerous adenomas. It is estimated that up to 80-90 of all cases of colon cancer develop from small adenomas that undergo mutations and slowly advance over time 4 . However, it should be noted that most adenomas do not progress to colon cancer, and the vast majority of diminutive lesions (< 5 mm) in the colon are non-adenomas 5, 6 . This has led to debate in the medical community about the size at which a colon lesion should be considered clinically important 7 . Most gastroenterologists feel that the small lesions are probably not important if routine screening is...

Cancer and Tumor Angiogenesis

VEGF receptors obviously play a critical role in cancer because of their active regulation of angiogenesis and vascular permeability (see above reviews). There is also some evidence that they may have a more direct role in some cancers by regulating the proliferation or survival of the tumor cells. For example, VEGFr1 Flt1 has been reported to have the potential to transform cells when appropriately activated (Maru et al., 1998). In endothelial cells over-expressing VEGFr1 Flt1, PlGF binding has been shown to stimulate cell proliferation (Landgren et al., 1998). The specific ligands for VEGFr1 Flt1 (PlGF and VEGFB VRF) also induce the secretion of urokinase plasminogen activator (uPA) from endothelial cells (Landgren, 1998 Olofsson et al., 1998). Activation of the uPA is considered to be important for the invasive growth and metastasis of tumor cells (Conese and Blasi, 1995 Schmitt et al., 1995). Thus, these observations suggest that aberrant expression and or activation of VEGF...

The Tramp Mouse as a Model for Prostate Cancer

Prostate cancer ranks as one of the most common cancers among men. Consistent with this, prostate cancer is also one of the most frequent causes of male cancer-related death. Adenocarcinoma represents the predominant histologic type of prostate cancer, typically arising from malignant transformation of lumenal epithelial cells within glands comprising the peripheral zone of the prostate. Somewhat unique to this cancer are a number of key features. Androgens play an essential role not only in normal prostate development but also the pathogenesis of prostate cancer. Related to this, most prostate tumors are androgen-sensitive i.e., demonstrate initial regression following androgen removal or blockade, and then subsequent progression due to proliferation of androgen-inde-pendent or androgen-suppressed tumor cells. Human prostate cancer encompasses a wide spectrum of histologic grades ranging from the putative precursor lesion, prostate intraepithelial neoplasia (PIN), to...

In Silico Prediction of Carcinogenicity

Cancer is a disorder in which the mechanisms that control proliferation of cells no longer function adequately. Cancer is considered to be an all-or-none effect (i.e., a tumor is or is not present). Because most cancers are considered irreversible life-threatening changes, chemical carcinogenesis (chemically induced cancer development) has hitherto been perceived by many to be different from other forms of chemical toxicity. Currently there are no good in vitro assays that can be used to identify carcinogens. Most testing needs to be carried out in vivo, with bioassays for carcinogenicity consisting of exposing adequate numbers of animals to the test substance for a significant proportion of their normal life span. Typically, this is performed using both male and female rats and male and female mice over a 2 year test period. This combination helps to distinguish species and or gender specificity for the chemical being tested. This test is expensive and time-consuming to conduct, and...

Box 114 Search strategy for Medline to locate RCTs of chemotherapy radiotherapy or surgery in lung cancer

(lung adj cancer ).ab,ti. cancer with lung.ab,ti. UKCCCR cancer trials register Managed by the MRC Clinical Trials Unit, the UKCCCR Register is a comprehensive, fully searchable database of UK randomized controlled trials in all types of cancer. http www.cancer.gov search clinical trials Produced by the National Cancer Institute (USA), the main site is comprehensive covering latest information about cancer treatment, screening, prevention, genetics and supportive care. It includes PDQ, a searchable database of ongoing and closed international clinical trials (Phase I-III), both government and industry sponsored. Australian national registry, ultimately intended to include all disease areas, but currently restricted to cancer. Includes unpublished and ongoing trials.

Results of Poor Communication in Cancer

Poor communication can result in faulty clinical data collection, worsened clinical and psychosocial outcomes, greater likelihood of litigation (Levinson et al. 1997) and confusion over prognosis (Hagerty et al. 2005). In addition, many patients feel that they have received insufficient information and have not been properly involved in decision making about their treatment and care (Davison et al. 1995 Degner et al. 1997). A recent study examined the relationships between decisional role (preferred and assumed) at time of surgical treatment (baseline), congruence between assumed role at baseline and preferred role 3 years later (follow-up), and quality of life in 205 women diagnosed with breast cancer (Hack et al. 2005). The authors reported that a statistically significant number of women had decisional role regret, with most preferring greater involvement in treatment planning than was offered. Women who indicated at baseline that they were actively involved in choosing their...

The Challenge of Cancer

Cancer is fast becoming the leading cause of death in developed countries, causing untold suffering and misery for both patients and their families. Real progress has been achieved in treating certain cancers through the use of novel surgical approaches and pharmaceuticals. While cancers are still typically treated according to their anatomical origin, as our understanding of the underlying genetic causes increases, tumors will be increasingly typed according to the molecular mechanisms driving growth. Allied to the progress in treatment options from drugs (or combinations of drugs) targeting these mechanisms, the future treatment of cancer is likely to change substantially, and offers the promise of major improvements in the treatment of the disease. However, at present, many tumor types remain almost untreatable while factors such as an aging population,1 environmental pollution,2 tobacco smoking,3 and poor diet4 continue to impact negatively on the occurrence of cancer.

Megacolon and Colon Cancer

Chagasic megaesophagus increases the incidence of esophageal cancer, with a prevalence ranging from 3.9 to 9 . However, there is no known relationship between Chagasic mega-colon and colon adenocarcinoma. Despite any formal precursor relationship, there are a few reports in the literature of adenocarcinoma of the colon in patients with chagasic megacolon, one of them found by autopsy. More than 95 of the patients with Chagasic megacolon complain of constipation, and the majority have a bowel movement less frequently than every 10 days (Table 25.3). Thus, constipation, as described by many authors, might be considered an important factor in the genesis of colorectal cancer, as it prolongs the contact of potential carcinogens in the stool with the colonic mucosa.40-42 Therefore, it would be expected that a higher incidence of colorectal cancer would occur in individuals with Chagasic megacolon. However, no such association exists. Colorectal cancer could be underestimated or...

Signal Transduction and Cancer

What Neoplasia Tree Model Flow Chart

Cancer is a complex family of diseases characterized by host of cells that have acquired a malignant phenotype, rendering them more genetically unstable and less responsive to external stimuli and their own environment. In a landmark paper, Hanahan and Weinberg have described six 'hallmarks of cancer' that collectively lead to malignant growth5 self-sufficiency in growth signals, insensitivity to antigrowth signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis, and tissue invasion metastasis. One common underlying mechanism that can operate in many of these areas is aberrant intracellular signal transduction, brought about by the increased genetic instability of the cell.6 There are numerous examples where upregulation, or constitutive activation, of key signaling pathways allows the cell to proliferate in the absence of extracellular mitogenic signals7'8 or where downregulation of a death-signaling pathway allows the cell to evade apoptosis.9 Many of...

Treatment of endometrial cancer

The treatment of endometrial cancer is usually surgical, such as total abdominal hysterectomy, bilateral salpingo-oophorectomy and evaluation for metastatic disease, which may include pelvic or para-aortic lymphadenectomy, peritoneal cytologic examination and peritoneal biopsies. The extent of the surgical procedure is based on the stage of disease, which can be determined only at the time of the operation. B. For most patients whose cancers have progressed beyond stage IB grade 2, postoperative radiation therapy is recommended. Because tumor response to cytotoxic chemotherapy has been poor, chemotherapy is used only for palliation. C. Endometrial hyperplasia with atypia should be treated with hysterectomy except in extraordinary cases. Progestin treatment is a possibility in women younger than 40 years of age who refuse hysterectomy or who wish to retain their childbearing potential, but an endometrial biopsy should be performed every three months. Treatment of atypical...

The Solt And Farber Animal Model Of Chemical Hepatocarcinogenesis

When studying the effects of xenobiotics and antioxidants during liver carcinogenesis, experimental models have been created. One of the most commonly employed models for this purpose is the Solt and Farber model of chemical hepatocarcinogenesis,57 in which the effects of carcinogens or anticancer drugs can be studied sequentially during initiation, promotion, and progression respectively (Figure 23.3).53 In this animal model on rat liver, commonly known as the resistant hepa-tocyte model,3 initiation is accomplished by diethylnitrosamine (DEN), a genotoxic compound that causes extensive DNA damage. To induce cell proliferation before DNA repair is complete, DEN is administered in a high, necrogenic dose, which leads to a burst of regenerative cell division and fixation of the DNA damage, or DEN is combined with partial hepatectomy. After this treatment,

Blood Transfusion in Medicine I Cancer

The transfusion supportive care of patients with cancer is responsible for a large proportion of blood transfused within developed countries such as the United States, Europe and Japan. From the perspective of blood transfusion, it is useful to group patients with cancer into three different categories. First, hematologic malignancies in adults, which although comprising only 10 of all cancers in this population, account for much of the blood product use, especially platelets. Second, adult non-hematological malignancies, which, are mostly treated with local forms of treatments, such as surgery or radiation therapy. Although, chemotherapy may be used, cytopenias resulting from chemotherapy which require transfusion support are uncommon, outside of the context of lung, breast or ovarian carcinomas. Third, pediatric malignancies. Approximately 50 of pediatric malignancies are hematological malignancies however, solid tumors which occur in children, such as neuroblastomas, are more...

Bladder Cancer Staging

Bladder Carcinoma Mri

Local tumor extension, the degree of lymph node and distant metastases, and histologic tumor type largely determine treatment and prognosis. Therefore, exact staging is imperative. To determine local tumor extension (T), presence of lymph node (N) and distant metastases (M), the International Union against Cancer proposed a uniform clinical staging method (Table 1). In this table, a correlation is also presented between the TNM-system and MRI-findings. Patients with superficial tumors, i.e., tumors without muscle invasion (stages Ta and T1) are treated with local endoscopic resection followed by adjuvant intravesical installations. Patients with a tumor invading the muscle layer of the bladder wall or with minimal perivesical extension (stages T2a to T3a) will be treated by radical cystectomy and lymphadenectomy. However, if the tumor is in a more advanced stage (stages T3b-T4b) or if there are nodal or distant metastases, the patient will have palliative chemo- or radiation therapy....

Effects Of Dietary Supplementation Of Ubiquinone On Carcinogenesis

The results showing reduced levels of ubiquinone in HCCs are thus in concordance with data from experimental animal models and on human cancers. Increased levels of ubiquinone in preneoplastic foci may contribute to their increased resistance to oxidative stress. However, the reasons as to why these cells decrease their levels of ubiquinone during malignant transformation remain unclear. In light of these findings, reports of ubiquinone levels in blood from cancer patients is pertinent. Folkers et al. reported decreased blood levels of coenzyme Q10 in patients with myeloma and breast cancer.77 In this study, the fractions of cancer patients with blood levels of coenzyme Q10 below 0.5 g ml (breast cancer) and 0.7 xg ml (myeloma patients) were significantly increased compared with ordinary people. However, 49 of the ordinary people had levels below 0.8 ag ml, indicating a wide range of values in all groups studied. Only myeloma patients had significantly reduced mean blood levels of...

Cellular origins of cancer

Chapter 3 presented an extensive stochastic analysis of a two-hit model. In particular we calculated the probability of creating a double-mutant as a function of time, depending on the population size and the relative fitness of the intermediate type. Chapter 4 made the first attempt to apply this model to real-life carcinogenesis, by taking account of specific features of sporadic and familial colorectal cancers. One important consideration which was not included in the analysis so far is the population structure. In Chapters 3 and 4, the population of cells was completely homogeneous with respect to the patterns of mitosis apoptosis. In other words, cells were only characterized by their fitness, which was a function of acquired mutations. In some cases, this is not enough to grasp the essential dynamics of the system. An example is the colonic epithelial tissue. There, when talking about the dynamics of cell division and mutations, we may have to take into account the fact that...

Cancer and immune responses

As pointed out in the previous chapter, the body is characterized by defense systems which can limit the growth and pathogenicity of selfish tumor cells once they have arisen by a series of mutations. The previous chapter explored how the limitation of blood supply can prevent cancers from growing beyond a very small size and from progressing. This is a mechanism which is supported very well by experimental and clinical data, and which is also studied from a therapeutic point of view. Another mechanism which can potentially counter the growth of cancer cells is the immune system. As will become apparent in this chapter, however, the role of the immune system in cancer is highly debated and uncertain. The immune system defends human beings from intruders such as pathogens which would otherwise kill them. It does so by specifically recognizing proteins derived from the pathogens (for example, viruses, bacteria, or parasites). Through complicated mechanisms which will be discussed...

Example of an IPD metaanalysis Postoperative radiotherapy in nonsmallcell lung cancer

Introduction Worldwide, over half a million new cases of lung cancer are diagnosed each year 58 and it is the leading cause of cancer deaths. Surgery is the treatment of choice for non-small-cell lung cancer (NSCLC), and around one fifth of tumours are suitable for potentially curative resection 59 . However, even for patients with apparently completely resected disease, survival rates are disappointing - around 40 per cent at two years. In an effort to improve both local control and survival, the use of adjuvant post-operative radiotherapy (PORT) has been explored. Despite the conduct of a number of randomized trials, which had recruited a total of over 2000 patients, the role of PORT in the treatment of NSCLC remained unclear. Owing to their small size, individual trials did not have sufficient statistical power to detect moderate survival differences and had shown inconclusive and conflicting results. An international systematic review and meta-analysis was therefore initiated by...

Post 131I Cancer Risks

The increased risk of thyroid cancer after thyroid irradiation in childhood has been recognized for nearly 50 years 70 . Thus, a major concern of 131I therapy relates to the risk of thyroid cancer. Detractors of 131I therapy point to the increased rates of thyroid cancer and thyroid nodules observed in young children exposed to radiation from nuclear fallout at Hiroshima or after the Chernobyl nuclear reactor explosion. The thyroid gland is unique in its developmental sensitivity to malignancy following radiation exposure. Individuals older than 20 years of age do not have an increased risk of thyroid cancer when exposed to low-level thyroid irradiation 71-73 . Yet, when individuals are less than 20 years of age at the time of low-level thyroid irradiation, the thyroid cancer risks increases the younger one is 71-73 . In addition to age, the radiation dose plays a major role in cancer risk 70-73 . The risk of thyroid cancer and thyroid nodules is highest with exposure to low or...

Gallbladder and Biliary Duct Biliary System Cancer

Gallbladder cancer and biliary duct cancer are relatively rare and account for fewer than 1 of all cancers. In 2005, over 3200 cases will be diagnosed and almost 2000 people will die of this cancer. Gallbladder cancer occurs five times more often in Native Americans than in whites and is more common in white females than in African American females. Most cancers of the gallbladder and biliary tract are inoperable at the time of diagnosis. If the cancer has been found incidentally at the time of a cholecystectomy, longer survival may be possible. More than 75 of gallbladder cancers are nonpapillary adenocarcinomas and approximately 6 are papillary adenocarcinomas a small number are squamous cell, adenosquamous cell, mucinous, or small cell carcinomas. Papillary cancers have a better prognosis and grow along the connective tissue and blood vessels they are not as likely to metastasize to the liver and lymph nodes. Adenocar-cinomas occur most frequently at the bifurcation in the common...

Primary Cancer Sites Based on Neck Node Location

The primary cancer sites based on neck node location are as follows When assessing cervical adenopathy, one should also note the size of the lymph nodes, mobility or possible fixation of these lymph nodes to the skull base, prevertebral muscles, or carotid artery. The neck is staged according to the American Joint Committee on Cancer Clinical Nodal Staging Guidelines (1988). The oral cavity and the oropharynx are next examined. The patient is requested to remove dentures if these are present. Particular attention is paid to the posterior floor of the mouth and the adjacent tongue and tonsillar fossae as tumors in these areas can be easily missed on a cursory examination. Palpation of the oral cavity and oropharynx should be included in the assessment as some tumors are often palpable before being readily visualized. The ears are evaluated for the possible presence of a middle ear effusion which may be an early finding in cancer of the nasopharynx. A recommendation for delaying an open...

Cancer Epidemiology

Each year cancer is newly diagnosed in about 10 million of people worldwide, and it causes 5 million deaths. Cancer is second to cardiovascular disease as a cause of death in developed countries, and overall causes 10 of all deaths in the world. In most developed countries, one person in three will develop cancer during their lifetime, and this will increase to one in two by the year 2010 provided that the age of the population will increase as predicted.1'2 Cancer comprises over 200 distinct entities differing in their genetic basis, etiology, clinical characteristics, patterns of progression, and final outcome. In broad terms cancer can be classified into carcinomas and sarcomas according to the fetal germ layer from which tumors arise. Carcinomas arise within tissues derived from the fetal ectoderm or endoderm and include most of the common cancers in adults. Sarcomas are seen more frequently in children and arise from tissues originating from the fetal mesoderm which generate...

Cancer

The use of chemotherapy to treat patients with incurable metastatic or recurrent HNSCC is well established. The median survival for these patients is approximately 6 months, and chemotherapy has had little impact on overall survival. The goal of this treatment is the palliation of cancer-related symptoms attributable to a reduction in tumor burden. Previously treated cancer responds much differently than naive tumors, and unresectable tumors may respond differently than resectable tumors. Over the past 20 years, there has been a gradual evolution in the treatments offered to patients with head and neck squamous cell cancer (HNSCC). Although 60 to 80 of patients with early-stage I and II HNSCC can be cured with surgery and or radiation therapy, the cure rate falls to 30 or less for patients with locally advanced stage III and IV disease. Local and regional relapse accounts for most of the failures observed in patients treated with surgery and radiation therapy. A few patients...

Cancers

This is the first of a number of chapters which investigates the relationship between carcinogenesis and genetic instability. Here, we will examine the most basic scenario the generation of the first malignant cell. Does the presence of genetic instability result in a faster generation of the first malignant cell The mathematics in this chapter are applications of the formalisms developed in Chapter 3. Here we present a simple example of how stochastic models developed for two-hit processes can be applied to biological reality. We will concentrate on cancers which are initiated via the inactivation of a tumor suppressor gene. That is, both the maternal and the paternal copy of the gene have to lose function. A particular example which will be discussed in this context is colorectal cancer. Colorectal cancer is a major cause of mortality in the Western world. Approximately 5 of the population develop the disease, and about 40 of those diagnosed with it die within 5 years. Considerable...

Breast Cancer

Incidence roughly 1 in 10 women will develop breast cancer in their lifetime. Risk factors for breast cancer 1. History of breast cancer (biggest risk factor) 3. Age (breast cancer is rare before age 30 the incidence increases with age). Greatest risk in women > 75 years old, Signs and symptoms that suggest a mass is breast cancer until proved otherwise fixation of breast mass to the chest wall or overlying skin, satellite nodules or ulcers on the skin, lymphedema peau d'orange, matted or fixed axillary lymph nodes, inflammatory skirt changes (red, hot skin with enlargement of the breast due to inflammatory cancer), prolonged unilateral scaling erosion of the nipple with or without discharge (may be Paget's disease of the nipple), microcalcifications on mammography, and any new breast mass in a postmenopausal woman. The conservative approach is to biopsy every palpable breast mass in women over 35 when in doubt, especially if they have any risk factors. If the board question does...

Prostate Cancer

Age (not seen in men < 40 years old incidence increases with age 60 of men > .80 have prostate cancer) Patients present late, because early prostate cancer is asymptomatic. Look, for symptoms suggestive of benign prostatic hypertrophy (hesitancy, dysuria, frequency) with hematuria and or elevated prostate-specific antigen (PSA) or acid phosphatase. Acid phosphatase is elevated only when the cancer has broken through the capsule for this reason, it was replaced with the more sensitive PSA as a screening tool. Look for prostate irregularities (nodule) on rectal exam. Patients also commonly present with back pain from vertebral metastases (osteoblastic). Local prostate cancer is treated with surgery (prostatectomy). Patients with metastases have several options for hormonal therapy orchiectomy, gonadotropin-releasing hormone agonist (leuprolide), androgen-receptor antagonist (flutamide), estrogen (diethyistilbestrol), and others (e.g., cyproterone). Chemotherapy does not work, and...

Colorectal Cancer

Patients may present with asymptomatic blood in stool (visible streaks of blood on stool or guaiac-positive), anemia with right-sided colon cancer, change in stool caliber (pencil stool) or frequency (alternating constipation and frequency) with left-sided colon cancer. As with any cancer, look for weight loss. 2. Occult blood in the stool of a patient > 40 years old should be considered colon cancer until proved otherwise. To rule out colon cancer, either do flexible sigmoidoscopy and a 3. Carcinoerabryonic antigen (CIA) is often, elevated with colon cancer, and a preoperative level is usually measured. After surgery to remove the tumor, CEA should return to normal levels. Periodic, monitoring of CEA postoperatively helps to detect recurrence before it is clinically apparent. CEA is not used as a screening tool for colon cancer it is used only to follow known cancer, 5. Colon cancer frequently metastasizes to the li ver if the metastasis is solitary, surgical resection is often...

Cervical Cancer

Papanicolaou smears decrease the incidence and mortality of cervical cancer. Give female patients a Pap smear if they are due, even if they present with an unrelated complaint. Follow up any dysplastic Pap smear with colposcopy-directed biopsies and endocervical curettage. If the Pap smear shows microinvasive cancer, proceed to conization. Frankly invasive cancer needs surgery and or radiation. Risk factors for cervical cancer 5. High parity (which protects against endometrial cancer) Important points 1. Invasive cervical cancer begins in the transformation zone and usually presents with vaginal bleeding or discharge (may be postcoital, intermenstrual spotting, or abnormal menstrual bleeding). 3. Maternal, exposure to diethylstilbestrol causes daughters to get clear cell cancer of the cervix or vagina. Postmenopausal bleeding is cancer until proved otherwise endometrial cancer is the most common cancer If) present in this fashion (fourth most common cancer in women). Get an...

Lung Cancer

Changes in the structure of some of the many types of cells that make up the lungs may begin almost immediately upon exposure to carcinogens (cancer-causing substances). Some of the thousands of chemicals contained in tobacco smoke both inhaled directly and released into the air through secondhand smoke are known respiratory carcinogens. Substances such as radon, asbestos, arsenic, uranium, and certain petroleum products also can cause lung cancer. malignant, however, it can invade and destroy surrounding tissue and may spread to other parts of the body through the bloodstream, causing new tumors (called metastases) to form in other tissues. And because all blood flows through the lungs, cancer that begins elsewhere in the body may spread to the lungs. A tumor in one of the bronchi can irritate the lining of the airway and cause a persistent cough, which may cause the tumor to bleed. As it grows, the tumor may block the airway, resulting in repeated bouts of pneumonia or other...

Photocarcinogenesis

There is a strong association between exposure to reactive oxygen species generating sunlight and human nonmelanoma skin cancer. The relation between UV induction and melanoma is less clear and still controversially discussed in the scientific community. However, recent epidemiological studies and results from animal studies30-36 support the concept that recreational UV-exposure and sunburns with subsequent influx of ROS- generating inflammatory cells into the skin may play an important role in the etiology of cutaneous malignant melanoma. In a recent paper, the long-term combined application of the photosensitizing agent 8-methoxypsoralen and UVA irradiation, widely used for the treatment of psoriasis and other dermatological diseases, resulted in an increased incidence in melanoma development.37 Most likely similar to nonmelanoma skin cancer, melanoma undergoes a multistage development towards the fully malignant phenotype. Operationally, this process can be subdivided into three...

Melanoma Skin Cancer

M elanoma skin cancer is a type of skin cancer that originates from the melanocytes, frequently a nevus or mole. Melanocytes are melanin-producing cells that are interspersed in the inner layer of the epidermis. Melanin is a dark brown pigment that protects the epidermis and the superficial vasculature of the dermis. Nevi or moles are small, circumscribed aggregates of melanocytes. It is thought that the ultraviolet radiation (from direct sunlight or tanning beds) damages the DNA of melanocytes, impairing the DNA control over how and when cells grow and divide. These skin lesions tend to be hereditary, begin to grow in childhood, and become more numerous in young adulthood. Skin cancer is the most common cancer in the United States, and melanoma accounts for 4 of all skin cancer cases. Although the lifetime melanoma risk for the overall population is only 1.4 , melanoma is responsible for 79 of skin cancer deaths. According to the American Cancer Society, approximately 59,580 new...

Childhood Cancer

The occurrence of cancer in children is approximately 2 in Western industrialized countries. Although the incidence of cancer in children is small, it is still the second leading cause of death in children and the primary cause of death from pediatric illness (Smith and Gloeckler Ries 2002). In The Netherlands approximately 370 children per year (Visser et al. 1992) are diagnosed with cancer. Diagnoses typical in childhood cancer are leukemias (29 ) of which acute lymphocytic leukemia (ALL) is the most common, namely 22 of all diagnoses brain and other central nervous system (CNS) tumors (22 ) and cancer of the lymph glands (Hodgkin and non-Hodg-kin lymphoma's, 13 ). Other malignancies are less common, such as soft tissue sarcoma (e.g., rhabdomyosarcoma 7 ), tumors of the kidney (Wilms' tumor or nephroblastoma, 6 ), neuroblastoma (6 ) or bone tumors (e.g., Ewing and osteosarcoma, 4 ). Besides treatment with chemotherapy, surgery, and radiotherapy, children with cancer are confronted...

Gastric Cancer

Flexible fiberoptic endoscopy is the gold standard of the diagnosis of gastric cancer. It can appear as a polypoid lesion, plaque like lesion or a shalow ulceer in the mucosa. Each time one of these is seen in the stomach a minimum of seven biopsies should be obtained for a greater than 98 diagnostic accuracy. Brushing can also be used in conjugation with biopsy for a diagnostic accuracy of almost 100 , or brushing can be used alone. Both of these should be done at the edge of an ulcer, not the crater base.1

Oral Cancer

Oral cancer is one of the most debilitating and disfiguring types of cancer. Tumors affecting the lip, mouth, tongue, and soft palate (the part of the throat at the back of the mouth) can interfere with swallowing and speech. If the cancer spreads to other parts of the body, it can cause disability and even death. But if oral cancer is detected and treated early, it has a very high cure rate. More important is the fact that oral cancer is highly preventable. Tobacco use is the number one cause of oral cancer. A smoker's risk of oral cancer is two to four times higher than that of nonsmokers. In fact, people who are most at risk of developing oral cancer are men over age 40 who smoke cigarettes, cigars, or a pipe, or who use smokeless tobacco (chewing tobacco or snuff). Smokeless tobacco is particularly dangerous because it contains 100 times the amount of cancer-causing compounds found in other forms of tobacco. This fact is especially disturbing because the use of smokeless tobacco...

Skin Cancer

Skin cancer is the most commonly occurring type of cancer in the United States. Experts estimate that 40 to 50 percent of Americans who live to age 65 will eventually develop some form of skin cancer. The risk is highest for people who have red or blond hair, light-colored eyes, and fair skin that freckles easily. The two most common forms of skin cancer are basal cell carcinoma, which accounts for more than 90 percent of all skin cancers, and squamous cell carcinoma. Basal cell carcinoma is a slow-growing cancer, found in the base of the outer layer of skin, that rarely spreads to other parts of the body. Squamous cell carcinoma, which affects cells in the surface of the skin, also spreads infrequently, although it does so much more often than basal cell carcinoma. A less common type of skin cancer, malignant melanoma, is the most serious form of skin cancer. It spreads quickly and can be fatal. The number of people with melanoma has more than doubled in the United States since about...

Testicular Cancer

Testicular cancer is a growth of abnormal cells within a testicle. Doctors do not know the exact cause of testicular cancer. It accounts for only 1 percent of all cancers in men. However, it is the most common cancer in men aged 15 to 34. Testicular cancer is about four times more common in white men than in African American men, with rates for Hispanic, Native American, and Asian men between those two groups. Thanks to dramatic advances in therapeutic drugs, along with better diagnostic tests, survival rates for the cancer have been boosted significantly. Today, testicular cancer is frequently curable, especially with early diagnosis and treatment. There are two different types of testicular cancer seminomatous and non-seminomatous. Seminomas, which account for about 40 percent of all testicular cancers, are made up of a single type of immature germ cell (probably arising from the cells that produce sperm). Seminomas are usually slower growing and usually are found before they spread...

Cervical Intraepithelial Neoplasia

Low-grade precursors of cervical cancer have been called low-grade squamous intraepithelial lesions (LSIL), low-grade cervical intraepithelial neoplasia (CIN I), and mild dysplasia. A. Management III. High-grade lesions. High-grade squamous intraepithelial lesions (HSIL) include CIN II or III, moderate and severe dysplasia, and carcinoma in situ. Forty-three percent of CIN II lesions regress if left untreated, while 22 percent progress to carcinoma in situ or invasive cancer. For CIN III, the spontaneous regression rate is 32 percent, and 14 percent progress to invasive cancer if untreated.

Fluorescence In Situ Hybridization

Much has been achieved during the last decade in the human genome analysis due to the development of nonradioactive methods of DNA in situ hybridization. General usefulness of FISH for physical mapping (1-2) was greatly enhanced by improved DNA resolution. Interphase cytogenetics has become an useful diagnostic tool in cancer cytogenetics (3-11). The high resolution of FISH analysis allows for a sensitive visualization of gene alterations. This has implications for the diagnosis of constitutional microdeletion syndromes (Fig. 1A), translocations in a variety of human diseases (12-18) as well as the identification of deletions of tumor suppressor genes and amplification of oncogenes in different types of human malignancies (19-25) (Fig. 1B). Fiber FISH technique allows to produce decondensed stretched interphase chromatin for orientation and ordering cosmids, PACs, BACs, and YACs while gener- From Methods in Molecular Medicine, vol. 50 Colorectal Cancer Methods and Protocols Edited by...

Benign Breast Disease

Rarely does breast pain represent cancer however a thorough breast exam and evaluation should be performed. Breast pain is characterized as cyclical or noncyclical with treatment as determined by the type of pain present. Cyclic pain is probably hormonal in nature, since it can be associated with elevated prolactin levels and relieved with menopause. Noncyclic mastalgia affects older women and the origin of the pain should be discriminated as chest wall or breast pain.

Risk Factors and Genetics

Breast cancer risk factors are related to prolonged exposure to estrogen. This is seen in women with early menarche and late menopause, older high estrogen dose oral contraceptives, and nulliparity. The highest risk involves a personal history of breast cancer or lobular carcinoma in situ. Family history in a premenopausal first degree relative is also an important risk factor. Familial breast cancer has been associated with certain genes. The two main genes are BRCA I and BRCA II.1 BRCA I is found on chromosome 17 and is also associated with an increased risk of colon, ovarian, and prostate cancer. BRCA I is thought to function as a tumor suppressor gene in DNA repair. BRCA II, located on chromosome 13, is associated with male breast cancer. BRCA II is also thought to function as a tumor suppressor gene. Both of the above genes are inherited in an autosomal dominant pattern with incomplete penetrance. Prophylactic bilateral mastectomy has been shown to decrease breast cancer in women...

Treatment of menopausal symptoms with estrogen

Data from the WHI and the HERS trials has determined that continuous estrogen-progestin therapy increases the risk of breast cancer, coronary heart disease, stroke, and venous thromboembolism over an average follow-up of 5.2 years. As a result, the primary indication for estrogen therapy is for control of menopausal symptoms, such as hot flashes. 2. Estrogen therapy remains the gold standard for relief of menopausal symptoms, and is a reasonable option for most postmenopausal women, with the exception of those with a history of breast cancer, CHD, a previous venous thromboembolic event or stroke, or those at high risk for these complications. Estrogen therapy should be used for shortest duration possible (eg, 6 months to 5 years). 4. Adding a progestin. Endometrial hyperplasia and cancer can occur with unopposed estrogen therapy therefore, a progestin should be added in women who have not had a hysterectomy. Medroxyprogesterone (Provera), 1.5 mg, is usually given every day of the...

Yann R Parc and Kevin C Hailing 1 Introduction

In 1993, three research groups described a novel type of genomic instability, which has been called microsatellite instability (MSI) or replication error (RER), in a subset of sporadic colorectal cancers and in most tumors from patients with HNPCC (2-4). Microsatellite instability is a change of any length (due to either insertion or deletion of repeating units) in a microsatellite within a tumor when compared to normal tissue. From Methods in Molecular Medicine, vol. 50 Colorectal Cancer Methods and Protocols Edited by S. M. Powell Humana Press Inc., Totowa, NJ MSI has been reported in a variety of other malignancies (15). However, among sporadic tumors, the MSI-H phenotype appears to be most common in cancers of the stomach, endometrium and upper urinary tract (16). Interestingly, these are also the same types of tumors that frequently occur in HNPCC patients (17). MSI analysis can be used to 1) identify tumors with defective MMR (i.e., the tumors with the MSI-H phenotype), 2) as a...

Kevin C Halling and Patrick C Roche 1 Introduction

Defective DNA mismatch repair (MMR) occurs in the majority of tumors from patients with hereditary non-polyposis colorectal cancer (HNPCC) and approx 15 of sporadic colorectal cancer (CRC) (1,2). In HNPCC-associated tumors, defective MMR is most often due to inactivating mutations of the DNA MMR genes hMLHl and hMSH2 (3,4). Defective MMR in sporadic CRC, on the other hand, is generally due to hypermethylation of the hMLHl promoter (5-7). As might be expected, inactivating mutations of hMSH2 and hMLHl lead to a loss of hMSH2 or hMLHl expression respectively and hypermethylation of the hMLHl promoter to a loss of hMLHl expression (5-8). One of the hallmarks of defective DNA MMR is a type of genetic instability known as microsatellite instability (MSI). Tumors with defective DNA MMR generally exhibit MSI at the majority of the loci examined (MSI-H phenotype) (8,9). From Methods in Molecular Medicine, vol. 50 Colorectal Cancer Methods and Protocols Edited by S. M. Powell Humana Press...

Transvaginal ultrasonography of women not on estrogen replacement therapy

Transvaginal ultrasonography (TVUS) has been used to select postmenopausal women with abnormal uterine bleeding not on estrogen-replacement therapy (ERT) who are at highest risk of having endometrial hyperplasia cancer. 2. Endometrial biopsy is required for histological diagnosis if the stripe is > 4 mm and in women with persistent bleeding. Persistent bleeding is worrisome even when the endometrial thickness is < 4 mm, particularly if there are other risk factors for endometrial cancer. E. Transvaginal ultrasonography in women on ERT. TVUS is not a useful screening tool for excluding endometrial hyperplasia cancer in women on estrogen-replacement therapy that is given with cyclic progesterone.

Women age 35 and older

Mammography is recommended as part of the evaluation of any woman age 35 or older who has a breast mass. Mammography misses 10 to 20 percent of clinically palpable breast cancers. 2. Solid masses with malignant or suspicious cytology should receive definitive therapy or biopsy. Masses that are not suspicious need careful follow-up. Breast lumps found to be benign on both FNAB and mammography have about 1 percent risk of being cancer.

Premalignant Conditions

Adenomatous polyps are associated with an increased incidence of malignant disease. Mucosal atypia is more common. Dysplasia and carcinoma in situ may develop over time. Larger polyps and numerous polyps are associated with a higher risk of developing malignant disease. Endoscopic removal is indicated and considered sufficient for pedunculated lesions if the polyp is completely removed and no invasive cancer is found on pathologic examination. Endoscopic surveillance is indicated in the patient who demonstrates adenomatous polyps. Approximately 50 of patients with familial adenomatous polyposis have gastric polyps.

William R Wrightson Background

Colon cancer is the second leading cause of cancer deaths in the United States. There is a 5 risk in the US of developing colorectal cancer. Advances in the understanding and diagnostic screening of this disease has made an impact on overall survivability of this type of cancer. As many as 10 of all colorectal cancers can be found by digital rectal exam with 3-6 of patients having a synchronous lesion in the colon. The majority of colorectal cancers remain sporadic, 10 genetic or familial.

Steven M Powell 1 Introduction

Over the past decade, the genes that underlie the development of many human diseases have been identified and the diseases causing mutations within these genes have been unveiled. Many genetic alterations responsible for a variety of human disorders have been characterized. These alterations range from simple Mendelian inherited syndromes to more complex traits such as cancers that involve multiple genetic and environmental factors. Identification and characterization of disease-causing mutations has practical as well as biological implications. As our understanding of these alterations advances, the potential for developing molecular genetic markers with clinical applications increases. This improved understanding also opens new avenues for advances in diagnostic testing, prognostication, and design of preventative strategies or therapeutic interventions. Indeed, direct genetic testing for an inherited colorectal cancer predisposition syndromes, Familial Adenomatous Polyposis (FAP)...

Tissue Homogenization and DNA Extraction

H54 (N and T), normal and tumor DNAs from a patient with ulcerative colitis-associated colorectal cancer 4854, G28, JG613, JG831, and IG15 (N and T), DNAs from patients with gastric cancer AC31and AC44 (N and T), DNAs from patients with sporadic colorectal adenocarcinoma AC41 (N and T), DNAs from a patient with HNPCC. Mutations were demonstrated using primer set R4, except for 4854 N,T (with a mutation demonstrated using primer set R5). An abnormally migrating band, located just above or below the wild-type band, is visible in each of the tumor (T) lanes. Fig. 3. Mutation of IGFIIR. H54 (N and T), normal and tumor DNAs from a patient with ulcerative colitis-associated colorectal cancer 4854, G28, JG613, JG831, and IG15 (N and T), DNAs from patients with gastric cancer AC31and AC44 (N and T), DNAs from patients with sporadic colorectal adenocarcinoma AC41 (N and T), DNAs from a patient with HNPCC. Mutations were demonstrated using primer set R4, except for...

Clinical evaluation

Human papillomavirus is the most important factor contributing to the development of cervical intraepithelial neoplasia and cervical cancer. Other epidemiologic risk factors associated with cervical intraepithelial neoplasia and cervical cancer include history of sexual intercourse at an early age, multiple sexual partners, sexually transmitted diseases (including chlamydia), and smoking. Additional risk factors include a male partner or partners who have had multiple sexual partners previous history of squamous dysplasias of the cervix, vagina, or vulva and immunosuppression.

Staging of Carcinoma of the Cervix Uteri FIGO Nomenclature

La1 Measured stromal invasion of not more than 3.0 mm in depth and extension of not more than 7.0 mm Ia2 Measured stromal invasion of more than 3.0 mm and not more than 5.0 mm with an extension of not more than 7.0 mm Ib Clinically visible lesions limited to the cervix uteri or preclinical cancers greater than Stage la Ib1 Clinically visible lesions not more than 4.0 cm Stage III The carcinoma has extended to the pelvic wall. On rectal examination, there is no cancer-free space between the tumor and the pelvic wall. The tumor involves the lower third of the vagina. All cases with hydronephrosis or nonfunctioning kidney are included, unless they are known to be due to other causes.

Iiifigo staging systems

Chest X-rays are indicated in all patients with cervical cancer, and imaging of the urinary tract (IVP, magnetic resonance or computed tomography urogram) should be carried out in all patients with more than microscopic cervical cancer. Suspected rectal or bladder involvement requires confirmation by biopsy. V. Surgical evaluation. Although cervical cancer is staged clinically, the results of surgical staging can be used for treatment planning. The staging procedure can be performed through a laparotomy (transperitoneal or extraperitoneal) or laparoscopically. Surgical staging allows for a complete pelvic and paraaortic lymphadenectomy. Nodal tissue obtained at the time of surgery can detect microscopic disease. Staging offers an opportunity to resect bulky metastatic lymph nodes and allows for individualization of the radiation field. In premenopausal women, oophoropexy can be done at the same time to protect the ovaries from radiation damage. VI. Treatment of microinvasive...

Serous and clear cell adenocarcinomas

These cancers are considered in a separate category from endometrioid adenocarcinomas. They have a worse prognosis overall. Patients with serious carcinomas have a poorer survival. The 3 year survival is 40 for stage I disease. B. Serous and clear cell carcinomas are staged like ovarian cancer. A total abdominal hysterectomy and bilateral salpingo-oophorectomy, lymph node biopsy, and omental biopsy omentectomy are completed. Washings from the pelvis, gutters and diaphragm are obtained, and the diaphragm is sampled and peritoneal biopsies completed.

Clinical manifestations

Most ovarian cancers are diagnosed between the ages of 40 and 65. Symptoms of early stage disease are often vague. Acute symptoms due to ovarian rupture or torsion are unusual. As a result, 75 to 85 percent of cases of ovarian cancer are advanced at the time of diagnosis. More advanced disease is typically associated with abdominal distention, nausea, anorexia, or early satiety due to the presence of ascites and omental or bowel metastases.

Physical examination

Palpation of an asymptomatic adnexal mass during a routine pelvic examination is the usual presentation for ovarian cancer. The presence of a solid, irregular, fixed pelvic mass on pelvic examination is highly suggestive of an ovarian malignancy. However, endometriomas and tubo-ovarian abscesses are benign tumors that may be fixed, while cystadenofibromas and tubo-ovarian abscesses are benign masses that feel irregular. The diagnosis of malignancy is almost certain if a fixed, irregular pelvic mass is associated with an upper abdominal mass or ascites.

Diagnostic evaluation

CA 125 The preoperative evaluation of a woman with suspected ovarian cancer should include measurement of the CA 125 concentration. The serum CA 125 (normal < 35 U mL) is elevated (> 65 U mL) in 80 percent of women with epithelial ovarian cancer. It is also increased in patients with other malignancies, including endometrial cancer and certain pancreatic cancers in endometriosis, uterine leiomyoma, and pelvic inflammatory disease and in approximately 1 percent of healthy women.

Screening Guidelines

Mammography alone is 75 sensitive, and, when combined with CBE, the screening sensitivity for detecting breast cancer increases to 88 . Screening guidelines from the US Preventive Services Task Force suggest mammography alone or with CBE every 1 to 2 years for women aged 50 to 69 years. Recent evidence suggests a benefit from annual mammography with or without CBE for women aged 40 to 49 years.

History and physical examination

In the woman with a suspicious breast mass, risk factors and a family history of breast cancers should be assessed. A personal history of radiation to the chest or breast, breast masses, biopsies, history of collagen vascular disease, and menstrual and gynecologic history are also important. C. Any evidence of skin changes, ulceration, peau d'orange (thickening of skin to resemble an orange skin), or lymphedema is suspicious for locally advanced cancer. D. Immediate mammography should be obtained. A white blood count, hematocrit, and erythrocyte sedimentation rate may be needed if cancer is found.

Lauri A Aaltonen and Egle Avizienyte 1 Introduction

While Peutz-Jeghers syndrome (PJS) has been acknowledged as a clinical entity for decades (1,2), the molecular background for the disease has been unraveled only very recently. PJS has two cardinal features First, many but not all patients display mucocutaneous melanin pigmentation that is most prominently seen around the mouth, but can also be present for example in the buccal mucosa, lips, palms, feet, and in the anal region. Second, the patients have a predisposition to hamartomatous intestinal polyps. These lesions can occur anywhere in the gastrointestinal tract, but are most commonly seen in the small intestine (3). Tumor predisposition is not limited to intestinal hamarto-mas. The patients have a relatively unfocused increased risk of cancer, which has been reported to be 10- to 18-fold of that of the general population. Especially the relative risk for breast and gynecologic cancers is high (4,5). Other sites possibly involved include at least small and large intestine, and...

Lauri A Aaltonen Stina Roth and Charis Eng 1 Introduction

Cowden syndrome is a rare dominantly inherited condition with predisposition to benign hamartomatous polyposis of the intestine, as well as malignant tumors of the breast and thyroid, and possibly some other cancer types. Other features include macrocephaly and dysplastic cerebellar gangliocytomatosis with ataxia, as well as predisposition to formation of trichilemmomas of the skin (1). The latter are tumors of the hair root sheath. It should be noted that, according to the present knowledge and unlike the other hamartomatous polyposis syndromes juvenile polyposis and Peutz-Jeghers syndrome, Cowden disease does not confer a clearly increased risk of colon cancer. Indeed, in the only population-based study, the risk of colon cancer was 3 (2). The disease is so poorly recognized that it is difficult to estimate whether some risk is present adenomatous polyps in Cowden disease have been described (3). Clinical data of at least two Cowden syndrome families is compatible with colon cancer...

Clinical Presentation

Cough is probably the most common presenting symptom in lung cancer and is related to endobronchial erosion and irritation. Centrally located lesions may result in a change in a chronic cough, hemoptysis, pneumonia. More peripheral tumors may present with chest pain and or cough related to chest wall and pleural involvement. Local extension of lung cancers results is varying presentations and syndromes. Invasion of the recurrent laryngeal nerve may result in hoarseness in up to 8 of cases. Dysphagia may be an indication of esophageal extension and is seen in 1-5 of presentations. Paraveterbral extention with involvement of the sympathetic nerve plexus results in Horner's syndrome (meiosis, ptosis, ipsilateral anhydrosis). Superior vena cava syndrome results from extrinsic compression of the superior vena cava. Patients present with jugular venous distention, edema of the face neck and arms. Paraneoplastic syndromes occur in 10 of patients with lung cancer. Paraneoplastic syndromes...

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

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