Author:

Riccardo A. Audisio

Much has been written about how our ancestors used to diagnose and treat cancers thousands of years ago (1,2); these stepping stones occurred in ancient Egypt, Greece, and Rome, since these were the boundaries of the world we used to know. Despite evidence that Hua Tuo, the most eminent surgeon in ancient China (Han Dynasty, 141-207 AD), performed abdominal operations anesthetizing patients, and controlled pain with herbs and acupuncture, we are unaware of significant steps in the removal of malignant growths in the Far East. Therefore, our discussion is limited to the evidence we retrieved from the “Classic Word” (2), where surgery used to be performed as an experimental attempt to resolve acute problems. But when anaesthesia became available in 1846, the work advanced so speedily that the next hundred years became known as “the century of the surgeon”.

It is well known how surgical advancements developed during wartime, when innovative procedures and new instruments were devised; this is redundantly evident from the Middle Ages, through Napoleonic times, to the conflict in Vietnam.

Cancer predates the existence of humans on Earth, as evidenced by paleontological discoveries of tumors in animals (3).

Cancer surgery, however, followed a different path from general surgery. The origins of cancer surgery can be traced back to ancient times, with the earliest recorded descriptions found in Egyptian papyri dating back to 2500 BC: the earliest recorded description of human cancer dates back to the Edwin Smith Papyrus, which is estimated to be from around 3000 BC. This ancient document illustrates a case of breast cancer. Additionally, the Ebers Papyrus, dating from 1500 BC, provides further documentation, describing various types of tumors affecting the skin, uterus, stomach, and rectum. These ancient Egyptian texts portray cancer as a serious and incurable affliction, often associated with what was perceived as "the curse of the gods." Such historical accounts offer valuable insights into the ancient understanding of cancer and its implications for those affected. These beliefs were accepted until Hippocrates, the renowned Greek physician, who provided detailed observations of tumors, distinguishing between non-ulcer and ulcer-forming growths, which he named "carcinos," Greek for crab, due to their crab-like appearance with finger-like projections.

Subsequently, Celsus, a 2nd-century Greek philosopher and physician, building upon Hippocrates' work, adopted the Latin term "cancer" to describe these abnormal growths. The Greek term "oncos" meaning swelling, was used to describe them; "oncology" derives from it, characterizing the effort to treat such tumors.

Claudius Galen (130-200 AD), a Greek physician who practiced medicine in Rome, built upon the concepts introduced by Hippocrates, advancing theories about the nature of cancer. Galen proposed that tumors resulting from thick black bile were incurable, while those originating from thin yellow bile might be curable.

Oribasius of Baghdad (325-403 AD) further affirmed Galen's assertions, confirming that tumors indeed formed as a result of the accumulation of black bile. These contributions by Galen and Oribasius provided foundational insights into the understanding of cancer during their time. So far, the management of the disease has been based on theoretical speculations, rather than on observational studies and clinical experimentation.

During the Middle Ages, religious beliefs played a significant role in shaping societal views and inhibiting the advancement of knowledge, including in the realm of medicine. Within this context, there emerged a belief that cancer was an infectious disease. This notion likely stemmed from a combination of limited scientific understanding and the prevailing religious and cultural narratives of the time. As a result, misconceptions about the nature and causes of cancer persisted, impeding progress in its understanding and treatment.

The Renaissance was a period marked by profound transformations in various aspects of human civilization. Among these were the discovery and exploration of new continents, which expanded the geographical and cultural horizons of the known world. The Renaissance also witnessed a shift in astronomical understanding, as the Copernican system replaced the Ptolemaic model, revolutionizing humanity's perception of the cosmos. Scientific curiosity and exploration were inflated as never before, going beyond the limits of what was acceptable to the establishment, as in the case of Galileo Galilei.

Furthermore, the Renaissance era saw significant changes in social and economic structures, including the decline of the feudal system and the rise of commerce, which contributed to the growth of cities and the emergence of a new urban culture. In addition, innovations such as paper printing revolutionized the dissemination of knowledge, making information more accessible and facilitating the exchange of ideas across regions and disciplines. These developments collectively laid the groundwork for the intellectual, artistic, and scientific achievements that characterized the Renaissance. During this period scientists began conducting autopsies, merging the study of the human body with investigations into diseases like cancer. This interdisciplinary approach led to significant breakthroughs.

In the 16th century, luminaries such as the anatomist Andreas Vesalius and his contemporaries played instrumental roles in advancing medical knowledge. Through meticulous dissections and observations, they were able to refute ancient theories, including the existence of black bile as a cause of diseases like cancer. Vesalius, in particular, revolutionized anatomical understanding with his detailed illustrations and descriptions of human anatomy, laying the groundwork for modern medicine. These efforts to dissect and comprehend the human body not only contributed to the discrediting of outdated medical beliefs but also paved the way for more accurate diagnoses and treatments of diseases, including cancer.

In the 18th century, the Italian pathologist Gianbattista Morgagni (1682-1771) founded scientific oncology by performing autopsies to identify the patient's disease and reporting that cancer was the result of an 'organ lesion'.

A new and modern approach to understanding cancer emerged, laying the foundation for cancer epidemiology. Notable figures such as John Hill (1714-1775), Bernardino Ramazzini (1633-1714), Percivall Pott (1714-1788), and Ludwig Rehn (1849-1930) made significant contributions in this field.

In 1761 John Hill made connections between the use of snuff and nasal polyps, highlighting early links between lifestyle factors and specific types of cancer. Bernardino Ramazzini associated breast cancer with reproductive factors, pioneering the investigation into hormonal influences on cancer development.

Percivall Pott observed that chimney sweepers frequently developed scrotal cancer later in life, attributing it to exposure to soot. His findings provided crucial insights into occupational hazards and their association with cancer.

In the late 19th century, Ludwig Rehn noted a correlation between exposure to aniline dye and bladder cancer among industrial workers. This observation underscored the importance of environmental factors in cancer etiology, further advancing our understanding of the disease.

These pioneering epidemiological studies laid the groundwork for contemporary approaches to cancer research and prevention, emphasizing the multifaceted nature of cancer causation and the importance of identifying risk factors for effective intervention and control.

Scientific understanding of cancer advanced significantly in the 19th century with the advent of the modern microscope. In 1804, Laennac provided the initial description of melanoma, followed by Jacob's identification of basal cell carcinoma in 1827, and Bowen's recognition of squamous cell carcinoma in situ, marking pivotal moments in the development of scientific oncology. Arthur Jacob, an Irish physician, termed the skin tumor presently identified as basal cell carcinoma (BCC) “Ulcus rodens” (4). In 1900, the Hungarian Physician István Krompecher (1905–1983) described BCC as a malignant, locally invasive, and destructive cancer and named it “Carcinoma epitheliale adenoides”; he then went on to pioneer the classification of skin tumors using histogenetic principles, three years later coining the term “Basalzellenkrebs”, a term indicating that the tumor originated in the basal layer of the epidermis or hair follicle.

During the 19th century, Surgical Oncology was flourishing in Europe: several unimaginable surgical procedures were successfully performed, to establish technical advancements and set the foundation for modern practice.

Theodor Billroth (1829-1894) was a distinguished German surgeon and a devoted amateur musician. He assumed the esteemed position of professor of surgery at the University of Vienna in 1867. Having significantly mitigated the threat of fatal surgical infections through his ground-breaking work and in collaboration with his peers, Billroth shifted his focus to the forefront of surgery. He delved into the pioneering realm of altering or removing organs previously deemed inaccessible.

A pioneer in adopting the "white coat" attire, Billroth achieved numerous surgical milestones. In 1872, he conducted the inaugural oesophagectomy, excising a segment of the oesophagus and skillfully joining the remaining parts. The following year, in 1873, he executed the maiden laryngectomy, entirely removing a cancerous larynx. Billroth also pioneered rectal cancer excision, having performed 33 such operations by 1876. By 1881, his expertise had rendered intestinal surgery nearly routine.

Undoubtedly, his most renowned achievement remains the first successful gastrectomy for gastric cancer. On January 29, 1881, after numerous unsuccessful attempts, Billroth performed the inaugural successful resection for antral carcinoma on Therese Heller. Despite her passing almost four months later due to liver metastases, this ground-breaking operation marked a milestone in surgical history. In this procedure, Billroth closed the greater curvature side of the stomach and anastomosed the lesser curvature to the duodenum, a technique still recognized as the Billroth I operation to this day (5).

There has been a long-lasting history of cross-contamination between the Old Continent and North America: a remarkable example is represented by a pioneering surgeon in thoracic surgery, Franz John A. Torek (1861-1938). The son of German immigrants to the USA, he worked in the German (now Lenox Hill) Hospital in New York City. In 1913 he performed the first thoracic esophagectomy for cancer, and the patient survived for 12 years (6).

Celsus (AD 178) stands as the pioneering figure credited with the initial documentation of a surgical procedure for the removal of lower lip cancer, marking a significant milestone in the history of head and neck surgery. Following in his footsteps, Abulcasis (1013-1107) and Avicenna (980-1036) further advanced the field by reporting on the excision of lip tumors, advocating for a method where the lip was intentionally left open to heal through secondary intention. However, it was Robert Liston (1794-1847) who is attributed with introducing the innovative V excision technique in 1837, a landmark development in surgical practice. In his seminal work "Practical Surgery" (1837). Liston documented a range of operations, including those for tumors affecting the lip, tongue, jaws, thyroid, and parotid gland, solidifying his legacy as a pioneer in the field of surgery.

Billroth's first successful total laryngectomy for cancer was performed in 1873; this warrants mention in this listing of historical surgical accomplishments.

Theodor Kocher of Berne (1841-1917) was a Swiss physician and medical researcher who received the 1909 Nobel Prize in Physiology or Medicine for his work in the physiology, pathology, and surgery of the thyroid. Among his many accomplishments are the introduction and promotion of aseptic surgery and scientific methods in surgery, specifically reducing the mortality of thyroidectomies below 1% in his operation, with a report of 100 such operations in 1883.

During the era when Prague was under the auspices of the Austro-Hungarian Empire, it boasted the third-largest university clinic in the German-speaking world. In the spring of 1880, an esteemed invitation beckoned Kocher to assume a professorial role in Prague, a moment of immense prestige for him. Encouragement poured in from numerous colleagues, particularly those abroad, urging him to accept, while peers and medical practitioners in Bern, his hometown, fervently implored him to remain.

Kocher, astutely leveraging the Prague offer, skilfully negotiated for enhancements to the university clinic under the auspices of the Bernese government. Remarkably, his stipulations were met with full acquiescence; the government pledged to commence construction of the new Inselspital building the following year, augmented his allowance for surgical instruments and literature, and expanded the capacity of beds designated for Kocher at the new Inselspital. In light of these developments, Kocher resolved to remain in Bern, a decision met with gratitude from many Bernese and Swiss students and professionals. He cited the affection of his students among his primary motivations for his choice. Notably, in a heart-warming display of appreciation, university students orchestrated a torchlight procession on June 8, 1880, in homage to Kocher's contributions. Such dramatic advancements were made possible by the discovery of ether (1842), nitrous oxide (1844), and chloroform (1847).

The surgical management of uterine cancer remained a focal point in both Germany and Austria. Ernst Wertheim of Vienna (1864-1920) refined the radical hysterectomy for cervical cancer, initially outlined by John G. Clark of the Johns Hopkins Hospital in 1895. This intricate procedure entailed the removal of the uterus, parametrium, tissues surrounding the upper vagina, and pelvic lymph nodes, while preserving the ovaries.

In subsequent years, Victor Bonney (1872–1953) of England upheld this tradition and conducted over 500 such surgeries, contributing significantly to the advancement of gynecological oncology. Bonney developed a keen interest in conservative surgical approaches and emerged as a trailblazer in the realm of less invasive procedures, notably ovarian cystectomy for the removal of ovarian cysts and myomectomy for excising fibroids. Through his pioneering work, Bonney facilitated the preservation of fertility for numerous women of reproductive age, significantly expanding treatment options and improving outcomes in gynaecological surgery.

One of the most pivotal oncological advancements at the turn of the century was the revelation of the effects of radiation. Madame Curie's discovery of radium in 1898 introduced a promising new treatment modality to the field. For the first time, the concept of multimodal treatment emerged, offering a potential breakthrough in locoregional cancer therapy.

With extensive surgical procedures associated with high morbidity and mortality rates, the outlook for cancer treatment was bleak, amplifying hope for this innovative approach. Cancers amenable to various forms of applicators or needle insertions, such as cervical cancer, head and neck cancer, and breast cancer, were among the first to undergo this pioneering treatment method.

Equipment capable of producing low-voltage therapeutic X-rays was also accessible during this period. However, while modern techniques in radiation therapy transformed the landscape of these treatments, local side effects, toxicities, and the constraints associated with radiation therapy in the first half of the twentieth century often resulted in dissatisfaction with this approach. In clinical scenarios where surgery seemed a viable alternative, the limitations of radiation therapy sometimes outweighed its benefits.

The advent of plasma and whole-blood transfusion capabilities, coupled with the discovery of antimicrobial agents, rendered more extensive surgical operations increasingly feasible. During the first half of the century, radiation technology appeared to be a suboptimal substitute for the surgical management of cancer. Consequently, more radical operative procedures emerged as the new beacon of hope for cancer treatment.

Extensive removal of the affected area, plus all the surrounding tissue and draining nodes was accepted as the standard for most cancers as in the case of breast cancer. With the introduction of anaesthesia and strict aseptic techniques, a radical surgical management became standard: the Halsted radical mastectomy prevailed in the first half of the 20th century. The American surgeon William Halsted (1852–1922) performed the first radical mastectomy in 1882, removing the mammary gland, the underlying chest muscle (including pectoralis major and minor) as well as the nodes of the axilla. The long-term survival of breast cancer patients quoted at the end of the 19th century was only in the 5% to 10% range, but the Halsted surgical method increased the cure rate to more than 40%.

Several decades later, deriving its scientific basis from the Lymphatic Permeation Theory, the English surgeon William Sampson Handley (1872-1962) influenced the development of cancer surgery. In 1906 he published Cancer of the Breast and its Operative Treatment which created his reputation with the wider medical establishment; the foundation for less demolitive surgical management was set. David H. Patey (1899 -1977), a British surgeon at the Middlesex Hospital in London, began performing a modified radical mastectomy in 1932 and used it routinely after 1936. This approach of less mutilating mastectomy techniques was a revolutionary departure from the previous time-honored and proven methods espoused by Halsted and his surgical pupils in that it preserved the pectoralis muscle and the chest wall skin.

Recently, one more step towards the preservation of the mammary gland, and with it the respect of cosmetic outcomes and patient-centred care, was marked by the advancements proposed by Umberto Veronesi.

The Milanese team was also pivotal in developing the sentinel node technique, to reduce the morbidity of unnecessary axillary dissection. While Armando Giuliano in the US initially used blue dye to map sentinel nodes, Giovanni Paganelli in Milan proposed nuclear medicine techniques and introduced them into clinical practice. Parallelly, the same European Institute of Oncology team introduced the ROLL (Radio Occult Lesion Localisation) technique for non-palpable lesions in the early nineties: ROLL was vastly adopted worldwide before the introduction of isotope seeds, magnetic tracers, and other innovative techniques. Postoperative radiotherapy in intended to provide the sterilization of residual cancer cells in the operative area, while irradiating of the whole mammary gland might be avoided. A new technique was therefore developed at the EIO during the last decade of the nineties’’. Intra-operative radiotherapy (IORT) of a breast quadrant after the removal of the primary carcinoma consisted of a mobile linear accelerator (linac) with a robotic arm used to deliver electron beams, producing energies from 3 to 9 MeV. Through a perspex applicator, the radiation is delivered directly to the mammary gland. Skin margins are stretched out of the radiation field to spare the skin from the radiation, while an aluminium-lead disc is placed between the gland and the pectoralis muscle to protect the thoracic wall. Different dose levels were tested from 10 to 21 Gy without important side-effects. The IORT treatment was very well accepted by all patients and a new avenue was opened to further improve the outcomes of patients undergoing breast conservation.

As European surgeons were progressively downscaling breast cancer surgery over the years, both for the mammary gland and the axilla, it became obvious that cosmetic results were also to be considered and improved, without compromising oncologic control of the disease.

The collaboration with plastic surgeons became a standard in the early eighties and new reconstructive procedures were developed, initially for immediate reconstruction at the time of mastectomy. The next step was introducing plastic surgery techniques for breast conserving surgery (oncoplastic surgery). Krishna B. Clough, a French surgeon from Paris, set its foundation in the late eighties; he then provided a classification and quadrant-per-quadrant atlas for oncoplastic surgery. He demonstrated that these techniques not only allowed reshaping of the breast, but extended breast conservation options by permitting extensive glandular resections for breast-conserving therapy of breast carcinomas, either primarily or after neo-adjuvant treatment.

The modern management of rectal cancer was markedly influenced by Ernest Miles; although attempts at radical removal of cancers of the rectum had been performed earlier, it was not until 1908 that the English surgeon Sir William Ernest Miles (1869-1947) reported a rational technical approach, improving the efficacy, safety, and efficiency of an operation which is still performed nowadays in line with his predicaments; through post-mortem dissection of postoperative patients as well as those with inoperable disease, Miles determined that the lymphatic drainage of the rectum consisted of three separate pathways leading from the rectum: upward, lateral and downward. Based on his findings, he concluded that pelvic colon excision with adequate mesenteric lymphadenectomy was needed to prevent recurrence from proximal lymphatic spread.

John Percy Lockhart-Mummery (1875–1957) was a British surgeon at St. Mark’s Hospital, London. He established sigmoidoscopy as a primary diagnostic tool for disease of the large bowel; he devised a classification for Familiar Polyposis, which led to the Polyposis Registry, the foundation of clinical genetic investigations, which he started with Dukes in 1924, keeping data on people with inherited multiple polyps. Cuthbert Dukes (1890–1977), a pathologist was credited for the classification of colorectal cancer. In 1932 he published his seminal paper on the staging of rectal cancer. His work has stood the test of time as a result of its simplicity and its role in influencing therapeutic strategies. Additionally, his staging system is an accurate prognostic indicator and a predictor of operative mortality. The original work was a breakthrough in the understanding and management of colorectal cancer. St. Mark’s Hospital became the cradle of the modern management of colorectal disease across the 20th century. Sir Alan Parks was practising there in the mid to late 1970s when he pioneered the surgical procedure for forming an ileo-anal pouch (Jpouch); technical details were first published in the British Medical Journal in 1978. It was developed as an alternative to the ileostomy, avoiding the discomfort of a stomal opening (where incontinent intestinal waste is emptied into a bag worn by the patient) and attempting to restore anorectal continence. More recently Wendy Atkin (1947–2018) was instrumental in promoting screening campaigns for colorectal cancer, with an increased effectiveness when compared to faecal occult blood tests. Once-only-sigmoidoscopy/colonoscopy campaigns have been promoted internationally.

These surgical and pathological milestones were set up in London, but one more British surgeon should be mentioned for his contribution toward the improvement of rectal cancer outcomes: Professor William Heald, in close collaboration with pathologist Philip Quirke, introduced the concept of the 'Holy Plane' of rectal surgery. The identification and careful handling of the optimal dissection plane surrounding the mesorectum, allowed for improving local control of the disease and significant reduction of local recurrences.

The trial that first demonstrated the benefit of 5-session radiotherapy alone was led by Cornelis Van de Velde and Corrie Marijnen in the Netherlands. The British school almost simultaneously confirmed the same results, enriching them with in-depth analyses of the operative specimens, the leader being radiotherapist David Sebag Montefiore and pathologist Phil Quirke in the UK.

Important technical contributions also came from France where Rolland Parc, a surgeon based at Hǒpital Saint‐Antoine, Paris; he improved surgical results by proposing a modification of Parks' colo‐anal anastomosis, where the J‐shaped colic reservoir is then anastomosed to the anal canal.

The new treatment paradigm of better local control with a long course of preoperative radio-chemotherapy, compared to the North American approach of postoperative radiotherapy in locally advanced rectal cancers, switched the current international practice. The credit for this goes to the German team led by Dr. Rolf Sauer and Professor Claus Rödel, who conducted several additional randomized trials clarifying how to combine the new drugs with long-course radiotherapy.

Scandinavian researchers produced a sequence of randomized/prospective studies, demonstrating the feasibility and effectiveness of short-course preoperative radiotherapy with delayed surgery for rectal cancer. This was intended to achieve the resectability of locally advanced neoplasms, where removal entails major pelvic demolition, high operative morbidity and mortality, compromised quality of life, and poor oncological outcomes. The leading figures of this revolution were Lars Pahlman and Bengt Glimelius.

Such European technical advancements in the field of surgery and radiotherapy greatly contributed to downscaling the management of colorectal cancer; a further attempt to minimize demolitive surgery combines chemo-radio in managing rectal cancers. Cornelius van De Velde, a Dutch Surgeon from Leiden, was instrumental in establishing a network of international specialists and setting up a “real life” good quality dataset, the Watch & Wait Database: the long-term outcomes of clinical complete responders after neoadjuvant treatment for rectal cancer were recently published on the Lancet.

The past half a century has seen a paradigm shift, from aggressive and demolitive surgery, to the realization that multimodal treatment, technological advances, and minimally invasive techniques can reduce the need for, radical surgery, together with its detrimental effects. Preservation of the form, function, and patient’s quality of life without any survival disadvantage, has become the new target. Today's surgeons, besides mastering technical skills, are highly trained medical professionals and together with oncologists, radiologists, scientists, anaesthetists and nurses, have made cancer surgery a safe and effective routine (7).

We have now gathered redundant evidence showing how those cancer patients who are treated by a Surgical Oncologist, instead of a General Surgeon, have a 20% better cure rate; despite this, the European community has been slow in acknowledging the achievement and promoting Surgical Oncology. This is in contrast with North America where the cancer program expanded in 1965 with the formation of the multidisciplinary Commission on Cancer. The Commission on Cancer began CME courses on cancer care for all general surgeons as well as developing special surgical oncology educational presentations. The American Board of Surgery submitted a formal request to the American Board of Medical Specialties (ABMS) to establish a certificate in Complex General Surgical Oncology. The request was approved on 23 March 2011: the certificate of Complex General Surgical Oncology was awarded to candidates after they had passed a written qualifying exam and an oral certifying exam (8). The first cohort of surgical oncology fellows took the written exam in 2014 and the oral certifying exam in February 2015 to become the first board-certified surgical oncologists. This is 75 years after the ‘‘the Founding Five’’ members of the James Ewing Society envisioned the importance of this activity. A similar step is highly recommended in the EU, to improve knowledge, homogenise standards, and offer all cancer patients with state-of-the-art Surgical Oncology.

References

McAleer S. A history of cancer and its treatment. Ulster Med J. 2022 Sep; 91(3): 124–129.

https://www.cancer.org/cancer/understanding-cancer/history-of-cancer/cancer-treatment-surgery.html

Hajdu SI. A note from history: landmarks in history of cancer, part 1 Cancer 2011 Mar 1;117(5):1097-102.

Jacob A. Observations respecting an ulcer of peculiar character, which attacks the eyelids and other parts of the face. Dublin Hospital Rep Commun Med Surg. 1827;4:232–239.

Weil, Peter H.; Buchberger, Robert (1999-07-01). "From Billroth to PCV: A Century of Gastric Surgery". World Journal of Surgery. 23 (7): 736–742

Dubecz A., Schwartz SI. Franz John A. Torek Annals Thoracic Surgery Volume 85, ISSUE 4, P1497-1499, April 2008

Wyld L, Audisio RA, Poston GJ. The evolution of cancer surgery and future perspectives Nat Rev Clin Oncol 2015 Feb;12(2):115-24

Michelassi F. Update on the American Board of Surgery subspecialty certificate in Complex General Surgical Oncology. Ann Surg Oncol. 2013; 20:2103–5