-The better the differentiation of the cell, the more completely it retains the functional capabilities of its normal counterparts.

-The more rapidly growing and anaplastic a tumor, the less likely it is to have specialized functional activity.

-When dysplastic changes are marked and involve the entire thickness of the epithelium, the lesion is referred to as carcinoma in situ, a preinvasive stage of cancer.

-The rate of growth of malignant tumors correlates with their level of differentiation.

-Most cancers take years to develop; very few, if any, develop suddenly (days to months).

-Rapidly growing malignant tumors often contain central areas of ischemic necrosis because the tumor blood supply, derived from the host, fails to keep pace with the oxygen needs of the expanding mass of cells.

-Some benign neoplasms have a fibrous capsule surrounding them but not all do. This capsule involves the stroma when present.

-Next to the development of metastases, local invasiveness is the most reliable feature that distinguishes malignant from benign tumors.

-Approximately 30% of new patients with solid tumors present with clinically evident metastases. Another 20% have occult metastases at the time of diagnosis.

-In general, the more anaplastic and the larger the primary neoplasm, the more likely is metastatic spread

-Cancers grow by progressive infiltration, invasion, destruction, and penetration of the surrounding tissue

1. Seeding

-Neoplasms invade a natural body cavity

-Characteristic of cancers of the ovary, which often cover the peritoneal surfaces

-Can glaze all peritoneal surfaces yet not invade the underlying parenchyma

2. Lymphatic spread

-more typical of carcinomas

-may traverse all of the lymph nodes ultimately to reach the vascular compartment via the thoracic duct

-the necrotic products of the neoplasm and tumor antigens often evoke reactive changes in the nodes, such as enlargement and hyperplasia of the follicles (lymphadenitis) and proliferation of macrophages in the subcapsular sinuses (sinus histiocytosis)

3. Hematogenous spread

-more typical of sarcomas

-most feared consequence of a cancer

-arteries are penetrated less readily than veins

-liver and lungs are the most frequent secondary sites of hematogenous dissemination.

-Renal cell carcinoma often invades the renal vein up to the inferior vena cava reaching the right side of the heart

-prostatic carcinoma preferentially spreads to bone

-bronchogenic carcinomas involve the adrenals and brain

-neuroblastomas spread to the liver and bones

-skeletal muscles are rarely the site of secondary deposits

• Top 3 cancers for men: Prostate (30%), Lung and bronchus (14%), and Colon and rectum (11%)

• Top 3 cancers for women: Breast (31%), Lung and bronchus and colon and rectum (each 12%)

• Top 3 cancer deaths for men: Lung and Bronchus (31%), Prostate (11%), and Colon and rectum (10%)

• Top 3 cancer deaths for women: Lung and Bronchus (25%), Breast (15%), and Colon and rectum (11%)

Age: The frequency of cancer increases with age. Most cancer mortality occurs between the ages 55 and 75 years; the rate declines, along with the population base, after age 75. The rising incidence with age may be attributed to the accumulation of somatic mutations associated with the emergence of malignant neoplasms. The decline in immune competence that accompanies aging also is a factor.

Cancer causes slightly more than 10% of all deaths among children younger than 15 years. The major lethal cancers in children are leukemia, tumors of the CNS, lymphomas, soft tissue sarcomas, and bone sarcomas.

Occupation: Different occupations cause one to be exposed to various harmful agents. See question 5 and table 6-3 for a complete list.

Environment: Environmental factors are the predominant determinant of the most common sporadic cancers. There is no paucity of environmental carcinogens. They lurk in the environment, workplace, food, and personal practices. They can be anything from sunlight, diet, cigarette smoking, alcohol consumption, number of sex partners, etc. Some examples of environmental/geographic cancers: Death rates from breast cancer are about fourfold higher in America compared with Japan. The death rate for stomach carcinoma in men and women is about seven times higher in Japan than in the United States.

Heredity: Heredity forms of cancer can be divided into 3 categories which include the following: Inherited Cancer Syndromes (autosomal dominant), Familial cancers, and Autosomal Recessive Syndromes of Defective DNA Repair.

• Examples of Inherited Cancer Syndromes: Familial retinoblastoma, familial adenomatous polyposis, multiple endocrine neoplasia, neurofibromatosis types 1 and 2, von Hippel-Lindau syndrome

• Examples of Familial Cancers: Breast cancer, ovarian cancer, colon cancers

• Examples of Autosomal Recessive Syndromes of Defective DNA repair: Xeroderma pigmentosom, ataxia telangiectasia, bloom syndrome, and fanconi anemia.

Hereditary forms of cancer can be divided into 3 categories:

1. Inherited Cancer Syndromes (Autosomal Dominant)

-Occurs when inheritance of a single mutant gene greatly increases the risk of a person developing a tumor. The best example of this is childhood retinoblastoma (40% are familial).

-Carriers of this gene also have an increased risk of developing a secondary cancer, usually osteogenic sarcoma. A cancer suppressor gene has been implicated in the pathogenesis of this type.

-There may be multiple benign tumors in the affected tissue; sometimes, there are abnormalities in non-targeted tissue (café-au-lait spots (available at Lucy’s) in neurofibratosis)

2. Familial Cancers:

-Features that characterize this type include early onset age, tumors arising in 2 or more close relatives of the index case, and sometimes multiple or bilateral tumors.

-Not associated with specific marker phenotypes, e.g. familial colonic cancers do not arise in preexisting benign polyps.

-Transmission pattern isn’t clear, although certain familial cancers can linked to the inheritance of mutant genes (e.g. ovarian and breast cancer).

3. Autosomal Recessive Syndromes of Defective DNA Repair:

-One of the best studied examples is xeroderma pigmentosum, in which DNA repair is defective.

**In summary, no more than 5-10% of all human cancers fall into one of the 3 previous categories.

and are called “preneoplastic disorders”.

1. Persistent regenerative cell replication (e.g. squamous cell carcinoma in the margins of a chronic skin fistula or a long-unhealed skin wound; hepatocellular carcinoma in cirrhosis of the liver)

2. Hyperplastic and dysplastic proliferations (e.g. endometrial carcinoma in atypical endometrial hyperplasia; bronchogenic carcinoma in the dysplastic bronchial mucosa of habitual cigarette smokers)

3. Chronic atrophic gastritis (e.g. gastric carcinoma in pernicious anemia)

4. Chronic ulcerative colitis (e.g. an increased incidence of colorectal carcinoma in long-standing disease)

5. Leukoplakia of the oral cavity, vulva or penis (e.g. increased risk of sqaumous cell carcinoma)

6. Villous adenomas of the colon (e.g. high risk of transformation to colorectal carcinoma

**Are benign tumors cancerous? In general, NO. But it is better to say that each type of benign tumor is associated with a particular level of risk, from nonexistent to high. E.G. Adenomas of the colon can undergo malignant transformation 50% of the time, contrasted with the extremely rare malignant change of leiomyomas of the uterus.

1.Gastroesophageal Acid Reflux Disease (GERD, acid reflux ) is injury to the esophagus that develops from chronic exposure of the esophagus to acid coming up from the stomach (acid reflux).

2.In contrast, heartburn is the symptom of acid in the esophagus, characterized by a burning discomfort behind the breastbone (sternum).

3.Patients that have heartburn symptoms more than once a week are at risk of developing GERD (acid reflux).

4.A hiatal hernia is usually asymptomatic, but the presence of a hiatal hernia is a risk factor for development of GERD (acid reflux).

5.Trouble swallowing Dysphagia requires immediate medical attention Vomiting blood or partially digested blood (looks like coffee grounds) requires immediate medical attention as does digested blood in the stools.

6.Edema and basal hyperplasia (non-specific inflammatory changes) Lymphocytic inflammation (non-specific) Neutrophilic inflammation (usually either acid reflux or Helicobacter gastritis) Eosinophilic inflammation (usually due to acid reflux) Goblet cell intestinal metaplasia or Barretts esophagus.

7.Zollinger-Ellison syndrome can present with increased gastric acidity due to gastrin production.

8.Treatment Avoiding aggravating factors The rubric “lifestyle modifications” is the term physicians use when recommending non-pharmaceutical treatments for GERD.

9.Avoid eating for 2 hours before bedtime and elevate the head of the bed on 6 inch blocks.

10.Drug treatment A number of drugs are registered for the treatment of GERD, and they are amongst the most often prescribed forms of medication is most Western countries.

11.The upper part of the stomach is wrapped around the LES to strengthen the sphincter and prevent acid reflux and to repair a hiatal hernia.

• Whole HCG has both alpha and beta sub chains.
  
• The alpha chain is shared by LH, so that old tests for HCG could give a false positive by detecting the high levels of LH at the time of ovulation.
• The beta chain is unique to HCG.
  
• Output of HCG doubles every 1.5 days in the early weeks and every three days at about eight weeks.
  
• Ectopic pregnancy tends to produce less and the rate of increase is diminished.
  
• By the time normal pregnancy is producing > 6,000 iu./l., an intrauterine pregnancy can be seen on abdominal scan in almost all cases.
  
• (Transvaginal scanning is much more sensitive in detecting intrauterine pregnancy, and will almost always show a pregnancy with HCG levels > 1,000 iu./l.)
  
• Hence levels above these with no scan sighting of an intrauterine pregnancy suggest it is elsewhere.
  
• The same applies to a low rate of increase in HCG levels.
  
• A very low level of HCG after the early weeks is most probably due to a failed pregnancy (assuming the dates are correct) or ectopic pregnancy.
  
• HCG production peaks at about 12 - 14 weeks.
  
• Twin pregnancy and hydatidiform moles produce high levels, which may be the explanation for their association with hyperemesis.