Radical Hysterectomy

The evolution of the radical hysterectomy encompasses nearly 2500 years and is among the most fascinating stories in surgical oncology. Some writings on cervical cancer have survived from antiquity. Hippocrates of Cos (460–370 BC) attempted trachelectomy but noted that nothing he did could eradicate the disease.¹ In the mid-fifth century, Byzantine physician Aëtius of Amida used vaginal irrigation with herbal compounds to relieve pain caused by cervical cancer.¹ Ambroise Paré recommended cervical amputation, which was performed in 1652 by Tulpius.¹ Father of American gynecology J. Marion Sims (1813–1883) used galvanocaustic loops to amputate and cauterize a cervical cancer.²

John Hunter (1728–1793), founder of the Royal College of Surgeons of England, was 19 years of age when he traveled from Glasgow to London to study and subsequently work with his brother William Hunter, a graduate of Edinburgh University.¹ Although J. Hunter had no formal medical training, he became the leading anatomist and one of the country’s finest surgeons through self-education and training. Among his many prosected specimens are specimens of advanced cervical cancer demonstrating the natural history and route of spread locally within the pelvis.

The spectacular rise of the Johns Hopkins Hospital and School of Medicine began in the late 1890s with the recruitment of 40-year-old William Osler (1849–1919; later Sir William) and 31-year-old Howard Atwood Kelly (1858–1943), both members of the University of Pennsylvania faculty. They joined famous surgeon William Halstead (aged 37 years) and distinguished pathologist William H. Welch (1850–1934; aged 38 years) to form the nucleus that spearheaded the development of Johns Hopkins into the world class institution it is today.

John Goodrich Clark (1867–1927) completed his training at the University of Pennsylvania and interned at a local Philadelphia hospital for 2 years before coming to Johns Hopkins.³ Originally he had been granted a residency position with Osler; however, upon arriving in Baltimore, Maryland, he was told that position had been committed to another physician. Osler sent him to Kelly who had an opening in gynecology. Thus, but a quirk of fate, Clark became a gynecologist rather than an internist.

Kelly assigned Clark to develop a more radical surgical approach for the treatment of cervical cancer. At a pathologic examination of 20 cases of cervical cancer treated by hysterectomy, Clark found that the disease had extended beyond the margins of resection in 15 cases.³ Influenced by the surgical doctrines of Halsted, he began considering an en bloc radical hysterectomy for cervical cancer. Clark was familiar with the combined operation described in 1894 by the German surgeon A. Mackenrodt who extensively used actual cautery to destroy the local growth at its primary site before dissecting free the upper vagina and suturing it over the cervix.⁴ He credited Mackenrodt’s procedure as the first step toward wider extirpation of the pelvic tissues along with the uterus.

The year 1895 turned out to be critical in the development of the surgical attack on cervical cancer. In March, the German surgeon Reis presented the anatomic theory of what would become the modern radical hysterectomy, calling for systematic removal of pelvic lymph nodes.⁵ Independently, Clark at Johns Hopkins,⁶ Rumpf in Berlin,⁷ and Wilhelm Latzko (1863–1945)⁸ in Vienna performed the first radical hysterectomies. Clark had his case on April 26, 1895, when he was just a second-year resident and the sole author of a manuscript that described the operation. He wrote, “The faults common to all methods of removal of the uterus are (1) the broad ligaments are cut too close to the uterus, and (2) too small portions of the vagina are removed.”⁶

Citing the unacceptable surgical mortality of abdominal surgery, Austrian surgeon Friedrich Schauta (1849–1919) advocated a vaginal approach to radical hysterectomy.⁹ Schauta made use of the experience of the Czech surgeon K. Pawlik who performed his first simple vaginal hysterectomy in a patient with cervical cancer in 1880 and, then, in 1889 reported 3 radical vaginal hysterectomies.¹⁰ Although Pawlik is credited as having performed the very first radical vaginal hysterectomy, Schauta was the first to systematically perform it. His first extensive radical vaginal hysterectomy was performed in 1901. The German Chair of Gynecology at the Berlin Charite, Walter Stoeckel (1871–1961), extensively modified Schauta’s operation,¹¹ and the Austrian gynecologist Isodor Alfred Amreich (1885–1972)¹² extended the radicality of the procedure for the treatment of more advanced cervical and endometrial carcinomas.

Although Schauta was already a professor in Innsubruck at 32 years of age and would soon develop an international reputation during his lifetime, he had the misfortune of having to live in the shadow of his pupil, the Viennese surgeon Ernst Wertheim (1864–1920).^13,14,15 Wertheim was critical of the vaginal procedure for its failure to include an assessment of the lymph nodes. An intense rivalry developed between Schauta and Wertheim regarding the operative approach and their disagreement caused considerable antagonism between them.

Ultimately, Wertheim would modify and popularize the operation, describing his abdominal radical hysterectomy in a 1900 manuscript.¹³ Wertheim advocated removal of the adjacent medial portion of the parametria and the upper part of the vagina and any adjacent enlarged pelvic lymph nodes. He was extremely disciplined and demanding with a difficult disposition, nervously performing surgery without surgical gloves for fear of losing sensitivity in his fingertips. His published experience was impressive in magnitude, follow-up, and descriptions of complications. In 1912, Wertheim published a monograph that included more than 500 cases, with an overall mortality rate of 10%.¹⁵ Due to the influenza pandemic, Wertheim died on February 15, 1920, at 56 years of age. Schauta had died 1 year earlier and the 2 men were buried side-to-side.

In 1944, the surgical approach to treatment of early-stage cervical cancer was revisited by Joe Vincent Meigs (1892–1963) of Harvard Medical School and the Massachusetts General Hospital.^16,17,18 He initiated a full-scale research program and visited surgeons in Europe and was impressed with the logic of Wertheim’s procedure. Acknowledging the 1934 report by Frederick J. Taussig (1872–1943) of Washington University Medical School, in which a survival benefit was obtained when pelvic lymphadenectomy was added to standard radiotherapy for cervical cancer,¹⁹ Meigs developed a modified Wertheim operation to include more extensive removal of the parametria and complete bilateral pelvic lymphadenectomy. In his initial series of 47 patients, he observed positive lymph nodes in 17%.²⁰ The series was extended to include 100 patients in which the operative mortality rate was 1%, with 5-year survival rates of 81.1% for stage 1 and 61.8% for stage 2 cancers.²¹ Although fistulas remained a significant obstacle to widespread endorsement of radical hysterectomy, the mortality associated with the procedure was virtually eliminated with the availability of antibiotics, blood transfusion, and specially trained gynecologic surgeons. It is ironic that the operation is often called the Wertheim operation in the United States, where as many European surgeons refer to it as the Meigs operation.

Two decades earlier on the other side of the world, Wertheim’s operation was further modified in 1921 by renowned Japanese surgeon Hidakazu Okabayashi.^22,23,24 He did not propose his operation as a new technique but more as a modification of the operation performed by his teacher, Professor Takayama, who had perfected the original Wertheim procedure by operating on 200 cases each year.²² Okabayashi placed emphasis on the extended radicality of extirpation of the parametrium. His 1932 film of the procedure was discovered in 2007 and demonstrates an even more radical operation, with a complete separation of the deep layer of the vesicouterine ligament, thus enabling the surgeon to perform an extensive resection of the parametrium and the lateral paravaginal tissue.²⁵ This essential step enabled the surgeon to completely separate the bladder from the uterus and the lateral side of the cervix and vagina, allowing sufficient transection of the vagina at the required level, as necessary.

Since its publication in 1974, the operative classification of Piver, Rutledge, and Smith has been used widely to assess the radicality of an abdominal cervical cancer operation.²⁶ This system describes 5 classes of radical (or extended) hysterectomy, classes I to V. Class II or modified radical hysterectomies with bilateral pelvic lymphadenectomy are indicated for microinvasive carcinomas (International Federation of Gynecology and Obstetrics [FIGO] IIA, occult IB1), while class III or Wertheim-Meigs radical hysterectomy with bilateral pelvic lymphadenectomy is the standard treatment for patients with early stage, visible lesions (FIGO IB1–IB2; some IIA1). The Piver classification was not designed to accommodate vaginal radical hysterectomy, nerve-sparing, or minimally invasive procedures.

In 1961, Kobayashi from Tokyo University modified Okabayashi’s radical hysterectomy and identified the principles for prevention of bladder dysfunction.²⁷ Kobayashi preserved the pelvic splanchnic nerves by separating the vascular part and the neural part of the cardinal ligament during resection of the parametrial tissues.²⁷ In recent years, the nerve-sparing radical hysterectomy has been expertly rendered by Okabayashi’s direct descendent and successor, Fujii.²⁸

Radical Trachelectomy for Fertility Preservation

Daniel Dargent (1937–2005) was the French pioneer of both the radical trachelectomy to preserve fertility and the use of the sentinel node concept for surgical staging in cervical cancer. Dargent resurrected the anatomic principles of Schauta’s radical vaginal hysterectomy and combining that with the surgical modality of laparoscopy, he performed the first successful systematic conservative surgical approach for invasive cervical cancer in 1994.²⁹ The radical vaginal ­trachelectomy, involving the removal of the cervix, surroundingparametria, and upper vagina, was preceded by laparoscopic bilateral pelvic lymphadenectomy.³⁰ In a seminal paper ­published in 2000, Dargent reported on a series of 56 patients scheduled for the procedure, of whom 47 successfully underwent it.³¹ The disease distribution ranged from IA1 to IIB. At a mean follow-up of 52 months, 2 recurrences (4%) were observed. Subsequent pregnancies resulted in 25% late miscarriages and 13 healthy livebirths. Dargent’s operation has emerged as the standard of care for women with early cervical cancer who wish to preserve fertility.

Pelvic Exenteration

In his colorful remembrance of Alexander Brunschwig (1901–1969), Boronow notes that, although his immigrant parents from the Alsace Lorraine area gave him little in the way of material things, they gifted him with superb intellect.³² Following the 1935 publication of the first report of a successful 2-stage procedure for radical en bloc resection of the duodenum and head of the pancreas for a growth of the ampulla of Vater by Whipple, Parsons, and Mullins,³³ the first “one-stage” Whipple was published by Brunschwig in 1939.³⁴ He was appointed Chief of Gynecology at the Memorial Hospital for Cancer and Allied Disease in New York in 1947, where he turned his attention to the problem of cervical cancer. He noted that treatment was primarily with radiation therapy and local failures were frequent, as were fistulae, both from uncontrolled cancer and from radiation injury. Brunschwig hypothesized that ultra-radical dissection of organs in the pelvic area may eradicate recurrent cervical cancer. It was in his sentinel publication in 1948,³⁵ which contained his first 22 cases, that Brunschwig carefully described the en bloc removal of the uterus, cervix, vagina, parametria, the entire internal iliac complex, rectum, bladder, and sometimes, the distal ureters. Bilateral pelvic and aortocaval lymphadenectomies typically preceded the extirpative phase, and creation of a wet colostomy, and occasionally vaginal reconstruction, immediately followed. This concept was met with an enormous credibility gap. His colleague Hugh Barber recalled, “Many in high places regarded this as a thoughtless form of mutilation, with limited chance of success for palliation, much less cure. The criticism was frequent, harsh, and bitter. Even the moral right to carry out such extensive surgery was questioned. Dr. Brunschwig had an extremely sensitive nature and was easily hurt. It took every measure of his strength, courage, and dedication to continue.”³² The operation was regarded as “the most radical surgical attack so far described for pelvic cancer” and, at the time of Brunschwig’s initial publication, the operative mortality rate was 23%. Brunschwig himself described the procedure as “brutal and cruel, but one that saved lives.”³² His technique for fecal and urinary diversion was the so-called “wet colostomy” (bilateral ureterocolostomy) and Boronow recalls that, when scrubbing with him, he would select the naval as the site for the stoma.³² During his time, operations were often glorified by names that seem oddly out of place in today’s politically correct world.³² Brunshwig’s total pelvic exenteration was called the “All-American”; an anterior exenteration was a “North American,” and a posterior exenteration was, of course, a “South American.”³² With improvements in critical care, antibiotics, hyperalimentation, thromboembolism prophylaxis, and advances in surgical technique (subjects that Brunschwig published extensively on),^36,37,38 the morbidity and mortality rates have dramatically improved, with current operative mortality rates below 5%, major perioperative complication rates of 30% to 44%, and overall 5-year survival rates as high as 60%.