Justine Greene holds a photograph of her mother, Virginia Greene, in her office at Big Sisters in Vancouver. Greene’s mother and grandmother both died from ovarian cancer.
Photograph by: Ward Perrin , Vancouver Sun
B.C. is believed to be the first jurisdiction in the world with a prevention campaign based on a controversial change in surgical paradigm involving Fallopian tube removal
BY PAMELA FAYERMAN, VANCOUVER SUN FEBRUARY 22, 2013 9:53 AM
After losing her mother and grandmother to ovarian cancer, 39-year-old Justine Greene took what she and her doctors consider fate-altering, pre-emptive action — she had her Fallopian tubes removed.
The executive director of Big Sisters was emboldened by the BC Cancer Agency pronouncement that the majority of high-grade serous carcinomas — the most common and deadliest type of ovarian cancer — actually originates in the tubes, not the ovaries.
B.C. is believed to be the first jurisdiction in the world with a prevention campaign based on a controversial change in surgical paradigm involving Fallopian tube removal. Gynecologic oncologists and other B.C. experts recommend women consider Fallopian tube removal while undergoing hysterectomies or tubal ligations — otherwise, a potential cancer prevention measure could be missed. Tube removal, B.C. experts contend, is a straightforward procedure that shouldn’t cause surgical complications or other risks when being done by skilled obstetrician/gynecologists.
There is not yet any peer-reviewed evidence to prove the change in practice will prevent ovarian cancers, but if the theory is correct, it could represent the first big B.C.-led cancer prevention strategy since the 1950s, when the province became the first jurisdiction in the world to introduce a Pap smear program to dramatically reduce cervical cancer incidence.
“I do concur that if Dr. (Dianne) Miller (head of the BCCA gynecology oncology group, pictured above) and her team are correct, this would be a true breakthrough cancer prevention discovery made in B.C.,” said BCCA president Dr. Max Coppes.
The 2010 recommendation to about 225 gynecology surgeons in B.C. to use hysterectomies and tubal ligations — two common procedures in which Fallopian tubes are easily accessible — to remove the tubes was unprecedented. Traditionally, tubes were left behind during such operations, as a matter of surgical convenience, habit, or because of uncertainty about the effects of taking out another body part.
Greene was a featured speaker when B.C. experts pleaded with surgeons to adopt the new protocol. They justified the recommendation for change based on discoveries that the deadliest tumours start in the tubes, not the ovaries, as well as evidence gleaned from B.C. databases. The latter showed that 20 per cent of ovarian cancer patients had previously undergone a hysterectomy in which their Fallopian tubes were left in, raising suspicions that if the tubes had been taken out, patients may not have developed ovarian cancer.
As well, up to 15 per cent of ovarian cancer patients had had a previous tubal ligation, reinforcing the theory that complete removal of the tubes might have eliminated cancer risk.
While grieving the death of her high-profile mother — B.C. Business Council CEO Virginia Greene — Justine insisted her gynecologist take out her tubes while leaving her ovaries intact. As a self-described pragmatist, a “safer than safe kind of gal,” she wanted to ensure her child wouldn’t lose his mom to the same disease that had claimed her mother, and her grandmother before that.
She was certain she isn’t having more children, so her Fallopian tubes, whose sole function is for reproduction purposes, were no longer needed.
“I potentially changed my destiny on that day in March 2011, when I went in for the surgery at St. Paul’s Hospital that took all of 34 minutes. I don’t know that I’ve eliminated the entire risk, but at the moment I’m hedging my bets about doing what I can do to end the story of ovarian cancer in my family,” she said.
Greene didn’t fit the typical criteria for the new B.C. guideline on Fallopian tube removal — she wasn’t having a tubal ligation for sterilization purposes, nor was she having a hysterectomy. And even though she lost two female relatives to ovarian cancer, genetic testing on her mother didn’t turn up an inherited gene mutation that predisposes women to breast and ovarian cancers.
(The lifetime risk of ovarian cancer is 1.4 per cent in the general population, but in women with what are called BRCA gene mutations, it is 20 to 50 per cent).
No one was going to convince Greene there wasn’t some still-unknown genetic mutation affecting her family. Her gynecologist, Dr. Stephanie Rhone, agreed it was prudent to remove her Fallopian tubes, and when Greene is closer to menopause, she’ll get her ovaries removed, too.
“My mom would have supported my decision 100 per cent. She would have done this herself except she thought her mom died of colon cancer,” said Greene, noting that when geneticists did some medical detective work, they found an autopsy report on her grandmother showing her grandmother’s primary cancer was actually ovarian.
Like Greene, Kathy Cooper, a Lions Gate Hospital nurse and mother of two, has also had her Fallopian tubes removed, and so has her sister in Calgary.
“As an operating room nurse, I know how straightforward this is,” said Cooke. “So when my gynecologist offered it during our consultation about a tubal ligation, it was a no-brainer for me, given that it could protect me against ovarian cancer.
“I’ve been a nurse for eight years, and in that time, I’ve probably been in the OR for maybe 15 tubal ligations. Removing the tubes (instead of clipping them or tying them off) took maybe an extra 10 minutes. I wasn’t concerned at all about risks or complications, not at all.”
These women are but three of tens of thousands of Canadians swayed by the audacious, game-changing guidance from B.C.’s ovarian cancer experts regarding Fallopian tube removal for ovarian cancer prevention.
About two dozen B.C. ovarian cancer experts maintain there’s “indisputable” evidence that the tubes, not ovaries, are most often the initiating site for cancer. It’s a perspective shared by numerous leading scientists around the world. Yet there is no unanimity in the medical community on removal of tubes to reduce ovarian cancer risk.
It would appear, however, that the B.C. innovation is having a profound influence on doctors and patients across Canada. According to the Canadian Institutes for Health Information, the number of hospitalizations for Fallopian tube removal performed on B.C. women in 2008/2009 was 3,806, but it rose to 4,034 in 2009/10, 5,287 in 2010/11 and 6,133 in 2011/12. Across the nation, the number rose from 28,999 in 2008/2009 to 34,611 in 2011/12.
(The data does not distinguish between procedures done for cancer causes or cancer prevention, nor does it explain what proportion of the increases are related to the new surgery paradigm.)
Proponents of the practice, led by BC pathologist Dr. David Huntsman, pictured above, regard the new paradigm — and the study of it — as a “moral imperative.” Huntsman and his Ovarian Research Program (OvCaRe) colleagues fully concede it is an ambitious, as-yet-untested cancer prevention strategy, but one that shouldn’t be stalled since ovarian cancer is a disease killing too many women.
Ovarian cancer is the fifth most deadly cancer among women. About 2,600 Canadian women will be diagnosed with it this year (300 in B.C.) and 1,750 will die from it (220 in B.C.).
B.C. experts say there’s urgency behind the new protocol since there’s no way to screen for ovarian cancer in seemingly healthy women. Symptoms are often vague, and it’s usually detected in the advanced stage. It has the highest death rate of all gynecological cancers (up to 70 per cent) and has not seen any true advances for decades, in either curative or life-prolonging treatment.
“Some people have been early adopters of the practice (of removing tubes) we’re extolling. It’s gone viral in some places, and not in others,” said Dr. Dianne Miller, head of gynecologic oncology at the University of B.C. and BCCA.
Lower mortality rates
In medical jargon, the procedure touted by B.C. experts is called prophylactic, risk-reducing salpingectomy. Mathematical modelling by the BCCA has projected a 40-per-cent reduction in ovarian cancer deaths over the next 20 years through a combined, concerted effort involving removal of tubes during hysterectomies and tubal ligations and by referring more women for genetic testing to catch what are called BRCA gene mutation carriers who have a far higher risk of ovarian cancer.
If the new Fallopian tube removal protocol results in the projected 40-per-cent reduction in mortality, that would mean about 15,000 fewer Canadian deaths from ovarian cancer over 20 years.
About a third of women have hysterectomies or tubal ligations. Across Canada, there are nearly 50,000 hysterectomies done annually and about 70,000 tubal ligations. So there are plenty of opportunities to remove tubes and potentially — if the B.C. hunch is correct — prevent ovarian cancers. B.C. experts concede it will take decades to prove that tube removal will lower ovarian cancer rates in the general population.
The site of origin for high-grade serous carcinoma (HGSC) has been the subject of speculation for decades.
The hypothesis that cellular changes in the tubes can lead to cancer in the ovaries was proposed in a 1999 article by renowned scientist, Dr. Louis Dubeau. A 2006 Harvard University study by Dr. Chris Crum in the American Journal of Surgical Pathology found that numerous women with genetic (BRCA) mutations had cancer or pre-cancerous lesions in the ends of the tubes called the fimbria. The fimbria are distinguishable by their finger-like appendages which hover over the ovaries.
A 2006 Canadian study led by prolific Toronto scientist Dr. Steven Narod showed the risk of ovarian cancer was reduced 80 per cent in genetically susceptible women if they had their ovaries and Fallopian tubes removed. That study, in the Journal of the American Medical Association, concluded that both the tubes and ovaries should be removed, since either can be the site of origin for such cancer. Both organs must be “examined in fine detail to rule out microscopic disease.”
Up to 90 per cent of women who get ovarian cancer are not gene mutation carriers. But those with the risky mutations are far more likely to get ovarian cancer. Research done in such genetically susceptible women spawned the practice of removing ovaries and tubes to intercept the development of cancer.
A popular current theory is that ovarian cancer originates from tubal inflammation, infection or other irritants. The tubes themselves are tiny, but the fimbriated ends fans out to envelope the ovary. So there’s a lot of surface area at the end where there’s more potential for dangerous changes to cells.
Intriguingly, the incidence of ovarian cancer is higher in women who get pelvic inflammatory disease, while being lower in women who have had tubal ligations. The former hints at an inflammatory cause, and the latter suggests that when the tubes are closed off, there are fewer opportunities for inflammatory or infective factors. Hence, the lower rate of cancer in women who’ve had tubal ligations.
Dr. Barry Rosen, head of gynecologic oncology at the University of Toronto, gives plenty of credit to pathologists for hunting down the roots of ovarian cancer, by microscopically examining Fallopian tubes which had previously been considered inconsequential to the development of ovarian cancer.
“It seems logical now, but it’s embarrassing, really, that we didn’t put one and one together before. And that’s because nobody was looking closely enough into the tubes,” said Rosen in an interview at Toronto’s Princess Margaret Hospital.
Dr. Patricia Shaw, a professor at the University of Toronto and gynecology pathologist at the University Health Network pictured above, is recognized as a pioneer in the ovarian cancer field. The implicating role of the tubes, she said, harkens back to investigations on the tissue of women with genetic mutations who’d had their ovaries and tubes removed for cancer risk reduction reasons, a common strategy for those with a family history and who have tested positive for such gene mutations.
“We’d examine these tubes closely after they were removed and we were seeing precursor (pre-cancerous changes) lesions,” she said, in an interview at her office at Toronto’s Princess Margaret Hospital.
“I remember being at a meeting in 2002, and being shouted down by other doctors when I mentioned this. Doctors are very resistant to change, they’re a conservative bunch. Then Chris Crum published a manuscript promoting the concept (of Fallopian tubes as the site of origin) and that really got people talking.”
Shaw is most impressed by the B.C. approach: “You need clinical champions who are highly respected. Dianne Miller is that kind of person. And I have to confess I’m hugely envious of the Vancouver group. They’re kicking ass with their ovarian team.”
The B.C.-led innovation on tube removal got a boost in notoriety when Dr. Mark Heywood, head of gynecology at Vancouver General Hospital, was inaugurated in June, 2011, as president of the Society of Gynecologists of Canada (SOGC). In his guest editorial in the Journal of Obstetrics and Gynecology soon after, he declared his goal as president would be to make 2011/2012 “The Year of the Tube.”
“This will involve the promotion of taking what steps we can to reduce the incidence of HGSC (the most common epithelial ovarian cancer) which, the evidence strongly indicates, arises mostly from the tubal epithelium and not from the ovary,” he said, referencing a pivotal 2009 study in the International Journal of Gynecological Cancer by Vancouver and Toronto researchers.
“The strategy will be, in the short term, to promote removal of the tube whenever appropriate, at the time of hysterectomy and in tubal ligation in women over age 30,” Heywood added.
Around the same time Heywood’s editorial was published, the Society of Gynecologic Oncology and the Gynecologists of Canada issued a joint statement that was the “defining moment when everyone was onboard” with the logic of Fallopian tube removal for cancer prevention, said Elisabeth Ross, pictured here, the CEO of Ovarian Cancer Canada.
The pivotal, consensus statement (www.g-o-c.org) was seen by nearly 2,000 Canadian obstetrician/gynecologists. It read:
“Due to its cancer prevention potential, it is recommended that physicians discuss the risk and benefits of bilateral salpingectomy with patients undergoing hysterectomy or requesting permanent irreversible contraception.”
The next paragraph qualified it by noting the need for more evidence:
“Given that the total benefits and risk of this practice change have not been defined, a national ovarian cancer prevention study focused on Fallopian tube removal is a GOC priority.”
For a few years now, B.C. experts have been trying to get funding for such a long-term national or international study, so far without success.
But even in the absence of such research, not to mention that the idea of Fallopian tube removal to prevent ovarian cancer is still a concept in its infancy, Greene doesn’t regret having it done.
“I had a brief moment when I had to get over the fact that I took out a part of me that makes me female. But it was brief.”
Sun Health Issues Reporter
Tomorrow: Controversy as the B.C. Fallopian tube removal protocol comes under heavy scrutiny by circumspect North American experts who discuss potential risks and benefits.
Research costs for Pamela Fayerman’s series on ovarian cancer were partially offset by a health journalism grant from the Canadian Institutes of Health Research. Fayerman won the award for her proposal to do stories about Knowledge Transfer, the process by which medical research changes patient care. Future stories will look at other big, B.C.-based innovations.