(In the figure, red wording indicates the central role of DNA damage and defects in DNA repair in progression to cancer.) When DNA repair is deficient DNA damage remains in cells at a higher than usual level (5th level) and cause increased frequencies of mutation and/or epimutation (6th level). Mutation rates increase substantially in cells defective in DNA mismatch repair or in homologous recombinational repair (HRR). Chromosomal rearrangements and aneuploidy also increase in HRR defective cells.Higher levels of DNA damage cause increased mutation (right side of figure) and increased epimutation. During repair of DNA double strand breaks, or repair of other DNA damage, incompletely cleared repair sites can cause epigenetic gene silencing.Deficient expression of DNA repair proteins due to an inherited mutation can increase cancer risks. Individuals with an inherited impairment in any of 34 DNA repair genes (see article DNA repair-deficiency disorder) have increased cancer risk, with some defects ensuring a 100% lifetime chance of cancer (e.g. p53 mutations). Germ line DNA repair mutations are noted on the figures left side. However, such germline mutations (which cause highly penetrant cancer syndromes) are the cause of only about 1 percent of cancers.In sporadic cancers, deficiencies in DNA repair are occasionally caused by a mutation in a DNA repair gene but are much more frequently caused by epigenetic alterations that reduce or silence expression of DNA repair genes. This is indicated in the figure at the 3rd level.
The vascular atraumatic forceps (DeBakey)were widely used for grasping vascular tissue and causing minimal damage to the vessels. This invention led to the development of the Dacron aortic graft for the repair of aortic aneurysms. Around the mid 1900s, Alfred Washington Adson, a pioneer in neuroscience at Mayo Clinic, invented Adson forceps that allows the lifting and removal of neural tissue. Hemostat/clamp
Hemostats are forceps that aim to obliterate the lumen of vessels and to obtain adherence to the crushed surfaces and vascular hemostasis. Originally, this notion of crushing did not exist and arterial catch forceps simply clamped vessels temporarily prior to ligature or cautery. In 1867, Eugene Koeberle, who accidentally found arterial forceps with a catch closure came away spontaneously without the need for ligature, and invented “pince hémostatique,” which have pin and hole catches. In 1882, the Kocher clamp was created by Emil Theodor Kocher, who significantly contributed to thyroidectomies (removal of all or a part of the thyroid gland) and decompressive craniotomy. This invention decreases the risk of contamination while cutting dense tissue. Later, Dr. William Henry Welch and William Stewart Halsted contributed to the invention of clamps and Halsted-Mosquito Hemostats, which were used to clamp small blood vessels.