Wednesday 29 May 2019

Targeted therapy

There are «some of the differences within cancer cells that enable them to thrive. Targeted therapy refers to treatment with drugs that have been developed to “target” these differences within the cell. Unlike chemotherapy, targeted therapy drugs alter the inner workings of the cell focusing on the part of the cancer cell that makes it different from the normal (...). Because they leave the healthy cells alone the side effects of targeted therapies are different from standard chemotherapy treatments. Targeted therapy works by one of the following: arresting the development of new blood vessels that feed the cancer cell, triggering the immune system to attack the cancer cell, changing proteins within the cancer cell, blocking or turning off signals telling the cancer cell to grow or divide, or carrying toxins directly to the cancer cell [1].»
It is «a type of treatment that uses drugs or other substances to identify and attack specific types of cancer cells with less harm to normal cells. Some targeted therapies block the action of certain enzymes, proteins, or other molecules involved in the growth and spread of cancer cells. Other types of targeted therapies help the immune system kill cancer cells or deliver toxic substances directly to cancer cells and kill them. Targeted therapy may have fewer side effects than other types of cancer treatment. Most targeted therapies are either small molecule drugs or monoclonal antibodies [2].»
«Targeted cancer therapies are drugs or other substances that block the growth and spread of cancer by interfering with specific molecules ("molecular targets") that are involved in the growth, progression, and spread of cancer. (...). Many different targeted therapies have been approved for use in cancer treatment. These therapies include hormone therapies, signal transduction inhibitors, gene expression modulators, apoptosis inducers, angiogenesis inhibitors, immunotherapies, and toxin delivery molecules.
  • Hormone therapies slow or stop the growth of hormone-sensitive tumors, which require certain hormones to grow. Hormone therapies act by preventing the body from producing the hormones or by interfering with the action of the hormones. Hormone therapies have been approved for both breast cancer and prostate cancer. 
  • Signal transduction inhibitors block the activities of molecules that participate in signal transduction, the process by which a cell responds to signals from its environment. During this process, once a cell has received a specific signal, the signal is relayed within the cell through a series of biochemical reactions that ultimately produce the appropriate response(s). In some cancers, the malignant cells are stimulated to divide continuously without being prompted to do so by external growth factors. Signal transduction inhibitors interfere with this inappropriate signaling. 
  • Gene expression modulators modify the function of proteins that play a role in controlling gene expression. 
  • Apoptosis inducers cause cancer cells to undergo a process of controlled cell death called apoptosis. Apoptosis is one method the body uses to get rid of unneeded or abnormal cells, but cancer cells have strategies to avoid apoptosis. Apoptosis inducers can get around these strategies to cause the death of cancer cells. 
  • Angiogenesis inhibitors block the growth of new blood vessels to tumors (a process called tumor angiogenesis). A blood supply is necessary for tumors to grow beyond a certain size because blood provides the oxygen and nutrients that tumors need for continued growth. Treatments that interfere with angiogenesis may block tumor growth. Some targeted therapies that inhibit angiogenesis interfere with the action of vascular endothelial growth factor (VEGF), a substance that stimulates new blood vessel formation. Other angiogenesis inhibitors target other molecules that stimulate new blood vessel growth. 
  • Immunotherapies trigger the immune system to destroy cancer cells. Some immunotherapies are monoclonal antibodies that recognize specific molecules on the surface of cancer cells. Binding of the monoclonal antibody to the target molecule results in the immune destruction of cells that express that target molecule. Other monoclonal antibodies bind to certain immune cells to help these cells better kill cancer cells.
  • Monoclonal antibodies that deliver toxic molecules can cause the death of cancer cells specifically. Once the antibody has bound to its target cell, the toxic molecule that is linked to the antibody — such as a radioactive substance or a poisonous chemical — is taken up by the cell, ultimately killing that cell. The toxin will not affect cells that lack the target for the antibody — i.e., the vast majority of cells in the body.
Cancer vaccines and gene therapy are sometimes considered targeted therapies because they interfere with the growth of specific cancer cells [3].»
Bibliographic references: 
[1] Cancer-champions.com. (n.d.). Chemotherapy, Immunotherapy, Targeted Therapy. What's the difference? | Cancer-Champions health-care consulting. [online] Available at: https://cancer-champions.com/chemotherapy-immunotherapy-targeted-therapy-whats-the-difference/ [Accessed 29 May 2019].
[2] National Cancer Institute. (n.d.). NCI Dictionary of Cancer Terms. [online] Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/targeted-therapy [Accessed 29 May 2019].
[3] National Cancer Institute. (n.d.). Targeted Cancer Therapies. [online] Available at: https://www.cancer.gov/about-cancer/treatment/types/targeted-therapies/targeted-therapies-fact-sheet [Accessed 29 May 2019].

Immunotherapy

It uses «the body’s immune system to fight cancer cells by stimulating the immune system. (...). Immunotherapy may be used by itself or with other types of treatment. The main types of immunotherapy being used to treat cancer include: monoclonal antibodies, immune checkpoint inhibitors, and cancer vaccines [1].»
It is «a type of therapy that uses substances to stimulate or suppress the immune system to help the body fight cancer, infection, and other diseases. Some types of immunotherapy only target certain cells of the immune system. Others affect the immune system in a general way. Types of immunotherapy include cytokines, vaccines, bacillus Calmette-Guerin (BCG), and some monoclonal antibodies [2].»

It is a type of targeted therapy.
Bibliographic references: 
[1] Cancer-champions.com. (n.d.). Chemotherapy, Immunotherapy, Targeted Therapy. What's the difference? | Cancer-Champions health-care consulting. [online] Available at: https://cancer-champions.com/chemotherapy-immunotherapy-targeted-therapy-whats-the-difference/ [Accessed 29 May 2019]. 
[2] National Cancer Institute. (n.d.). NCI Dictionary of Cancer Terms. [online] Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/immunotherapy [Accessed 29 May 2019].

Tuesday 28 May 2019

AJCC

American Joint Committee on Cancer

Regional lymph nodes in rectal cancer

Regional lymph nodes are located along the providing vessels of the rectum. The AJCC confines locoregional lymph node involvement to the following lymph nodes:
  • sigmoid mesenteric;
  • inferior mesenteric;
  • superior rectal/hemorrhoidal;
  • middle rectal/hemorrhoidal;
  • inferior rectal/hemorrhoidal or mesorectal;
  • perirectal;
  • sacral promontory (Gerota's);
  • lateral sacral;
  • presacral;
  • internal iliac.
Source: [1].

Lymph nodes outside of these areas are considered metastatic disease (M1) (for example, suspicious inguinal lymph nodes if the distal anal sphincter complex is involved) [1].


Coronal and axial drawings show the nodal stations relevant to anal and rectal cancers. Regional nodal stations are shown for anal cancers (blue-green) and rectal cancers (orange). Nodal stations considered metastatic for both anal and rectal cancer are shaded dark gray. Red and blue circles in the axial drawing are external and internal iliac arteries and veins.
Source: [2].

«Pelvic lymph nodes outside of the mesorectum — internal iliac, external iliac, obturator, and common iliac — are termed lateral pelvic lymph nodes (LPLNs). Rectal cancer with involved LPLNs is managed differently in the United States (US) compared to several countries in Asia. In the US, the AJCC defines only the internal iliac lymph nodes as regional, whereas external and common iliac lymph nodes are considered sites of metastatic disease. On the other hand, in Japan, all LPLNs are considered regional and patients are treated with curative intent [3-4]».

Differences in the understanding and management of LPLNs between the East and the West:
LLN = lateral lymph node; nCRT = neoadjuvant chemoradiotherapy; RT = radiotehrapy.
Source: [5]

Bibliographic references:
[1] van Loenhout R, Zijta F, Lahaye M, Beets-Tan R, Smithuis R. The Radiology Assistant: Rectal Cancer - MR staging 2.0 [Internet]. Radiologyassistant.nl. 2015 [cited 2019 May 28]. Available from: http://www.radiologyassistant.nl/en/p56195b237699d/rectal-cancer-mr-staging-20.html#in565b4b37b539c.
[2] Matalon SA, et al. Anorectal Cancer: Critical Anatomic and Staging Distinctions That Affect Use of Radiation Therapy. Radiographics. 2015 Nov-Dec;35(7):2090-107. Available at: https://doi.org/10.1148/rg.2015150037.
[3] Akiyoshi T, et al. Results of a Japanese nationwide multi-institutional study on lateral pelvic lymph node metastasis in low rectal cancer: is it regional or distant disease? Ann Surg. 2012 Jun;255(6):1129-34. Available at: https://doi.org/10.1097/SLA.0b013e3182565d9d.
[4] Yahya JB, et al. Does a fine line exist between regional and metastatic pelvic lymph nodes in rectal cancer-striking discordance between national guidelines and treatment recommendations by US radiation oncologists. J Gastrointest Oncol. 2018 Jun;9(3):441-447. Available at: https://doi.org/10.21037/jgo.2018.02.05.
[5] Radjindrin A, Shanmugam V. Does Lateral Pelvic Lymph node matters in rectal cancer. Glob Surg. 2018;4(4):1-3. Available at: https://doi.org/10.15761/GOS.1000196.

Sunday 26 May 2019

Anorectal anatomy

«Note the anal crypts and glands; 90 percent of anorectal fistulas originate in a cryptoglandular abscess. Also note the relationship of the crypts and glands to the internal and external sphincters.»

«The anal canal is 2.5 to 3.5 cm long and begins superiorly where the rectal ampulla is narrowed by the puborectalis sling (the levator ani muscle, which is palpable as the anorectal ring). It ends at the intersphincteric groove. Externally, the anal canal is surrounded by the internal and external anal sphincter muscles.
The superior half of the anal canal contains a series of longitudinal ridges called the anal columns (of Morgagni), which extend from the anorectal junction superiorly to the anal valves inferiorly. The anal valves form an irregular line called the dentate (or pectinate) line (colored purple in the diagram), which is an important anatomical landmark. The portions of the anal canal superior and inferior to it have different origins of arterial supply, nerve innervation, venous/lymphatic drainage, and epithelial lining.
The anal canal is internally lined with mucous membrane above the dentate line and anoderm below it. The upper portion of the anoderm (anal verge) consists of smooth, hairless skin; the lower portion of the anoderm (perianal skin) contains pigmented skin containing hair follicles and glands.»

Rectal division

Division of the upper, middle, and lower rectum [1]:
Image adapted from Surgical Anatomy of the Colon, Rectum, and Anus [Internet]. Abdominal Key. 2017 [cited 2019 May 29]. Available from: https://abdominalkey.com/surgical-anatomy-of-the-colon-rectum-and-anus/.

Measurement of rectal cancer with respect to the reference level and method:
Source: Schmoll HJ, Van Cutsem E, Stein A, Valentini V, Glimelius B, Haustermans K, et al. ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making. Ann Oncol2012;23(10):2479–516. Available at: https://doi.org/10.1093/annonc/mds236.

«The rectum extends from the anorectal junction to the sigmoid. The rectosigmoid junction is arbitrarily defined as 15 cm above the anorectal angle. A tumor more than 15 cm above the anorectal angle is regarded and treated as a sigmoid tumor. Rectal cancer can be divided into:
- Low rectal cancer: distal border is 0-5 cm from the anorectal angle;
- Mid rectal cancer: distal border is 5-10 cm from the anorectal angle;
- High rectal cancer: distal border is 10-15 cm from the anorectal angle.»
Source: The Radiology Assistant: Rectal Cancer - MR staging 2.0 [Internet]. Radiologyassistant.nl. 2015 [cited 2019 May 26]. Available from: http://www.radiologyassistant.nl/en/p56195b237699d/rectal-cancer-mr-staging-20.html.


Bibliographic references: