Appendix cancer historical perspective

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Soroush Seifirad, M.D.[2]

Overview

Appendix cancer was first described in the published literature by Sir George Thos. Beatson, an English surgeon, in 1913. Development of surgical sciences revolutionized cancer care, appendix cancer was not an exception. Introduction of chemotherapy agents such as 5-fluorouracil (5-FU), irinotecan, oxaliplatin, vascular endothelial growth factor receptor inhibitors (bevacizumab), epidermal growth factor receptor inhibitors (cetuximab and panitumumab), aflibercept, regorafenib, inhibitor of angiogenic tyrosine kinases (including the VEGF receptors 1, 2,and 3), capecitabine as well as introduction of intraperitoneal chemotherapy including hyperthermic intraperitoneal chemotherapyadvanced appendix cancer treatment. Development of new Imagingmodalities such as CT scan, MRI as well as specific imaging modalities such as somatostatin scintigraphy also transfigured approaching to the patients with appendix cancer. Genetic studies introduced novel horizons in approaching patients with appendix cancer.

Historical Perspective

Discovery

• Appendix cancer was first described in the published literature by Sir George Thos. Beatson, an English surgeon, in 1913.

Landmark Events in the Development of Treatment Strategies

• Surgical sciences development

• First recorded appendectomy performed on December 6, 1735, at St. George's Hospital in London.
• First reported anesthesia (December 1846. Ether anesthesia, Paris, France), although traditionally Persian surgeons such as Razi prescribed wine to sedate their patients before painful procedures.
• First laparoscopic operation in humans performed by Swedish surgeon, Hans Christian Jacobaeus, on 1910 in Stockholm.

• Chemotherapy

• Introduction of 5-fluorouracil (5-FU) the first coorectal chemotherapy agent, 1957.
• Introduction of Octereotide analogs to control symptoms of carcinoid syndrome.
• Intraperitoneal chemotherapy including hyperthermic intraperitoneal chemotherapy plus/minus early postoperative intraperitoneal chemotherapy (EPIC) by Spratt et al. in the 1980s.
• Development of new chemotherapy agents (1990s) such as:

• Irinotecan (approved for medical use in the United States in 1996)
• Oxaliplatin (approved for medical use in the United States in 2002)
• Vascular endothelial growth factor receptor inhibitors (bevacizumab)
• Epidermal growth factor receptor inhibitors (cetuximab and panitumumab)
• Aflibercept
• Regorafenib: inhibitor of angiogenic tyrosine kinases (including the VEGF receptors 1,2, and 3)
• Capecitabine or 5-FU with or without a platinum drug

• Development of new Imaging modalities

• CT scan, MRI as well as specific imaging modalities such as somatostatin scintigraphy revolutionized approaching to the patients with appendix cancer

Future horizons

• Genetic studies revolutionized cancer treatment; appendix cancer is not an exception.
• Traditionally appandiceal cancers were approached the same as colorectal cancers. Recent genetic studies demonstrated that appendiceal tumors are clearly differ from colorectal cancers.
  • Presence of mutated TP53 and APC genes were significantly lower in appendiceal cancers compared to colorectal cancers.

• It has been shown that mutation profiles are associated with the patients’ prognosis.
  • Mutations in the TP53 significantly decrease life expectancy in patients with appendix cancer.
  • Regardless of tumor grade, Tp 53 mutations were associated with poorer outcomes.
  • Patients with GNAS mutations had a life expectancy of 10 years after diagnosis.
  • Appendiceal tumors with GNAS mutations rarely develop into high-grade tumors.

Famous Cases

The following are a few famous cases of appendix cancer:

• Celebrated actress, Audrey Hepburn was the most famous victims of appendix cancer, she passed away in 1993.

• Stuart Scott, ESPN sportscast anchor was diagnosed with appendix cancer in 2007 and died 8 years later in 2015.