Prenatal diethylstilbestrol exposure and human genital tract abnormalities

Herbst AL, Scully RE, Robboy SJ, DES research 1979

foetus image
Nonneoplastic abnormalities including vaginal adenosis, cervical eversion (ectropion), and transverse cervical and vaginal ridges are frequent in the DES-exposed population, particularly if the drug was administered early in pregnancy.

1979 Study Abstract

The incidence of clear cell adenocarcinoma of the vagina and cervix associated with intrauterine exposure to diethylstilbestrol DES and similar compounds during the first half of pregnancy has increased. Ninety percent of these cancers have occurred in patients 14 years of age or older.

Although these carcinomas are exceedingly rare, nonneoplastic abnormalities including vaginal adenosis, cervical eversion (ectropion), and transverse cervical and vaginal ridges are frequent in the exposed population, particularly if the drug was administered early in pregnancy. Current evidence favors a disturbance in development of the müllerian duct as the explanation of these changes.

Whether DES is only a teratogen or also a carcinogencerviccervi is unknown, as is the possible role of other factors in the development of cancer. An increased incidence of cancer among exposed males has not been documented.

Sources and more information
  • Prenatal diethylstilbestrol exposure and human genital tract abnormalities, Herbst AL, Scully RE, Robboy SJ. 1979 May;(51):25-35. NCBI PMID: 481577.
More DES DiEthylStilbestrol Resources

Alopecia cancer treatment side effect: from uncomfortable to life-changing

I survived cancer – but drugs left me with permanent alopecia

Shirley Ledlie was left with persistent significant Alopecia following breast cancer treatment with Taxotere drug. Image credit The Telegraph.

Studies show that long term hair loss, which can be caused by a cocktail of certain cancer drugs, has significant impact of quality of survival. Why isn’t more known about it?

Shirley Ledlie long-term Alopecia’s cause – significant and permanent hair loss – was a drug called Taxotere (Docetaxel), which, when combined into a “cocktail” with other chemotherapy drugs, causes “male pattern baldness“…

Read I survived cancer – but drugs left me with permanent alopecia,
The Telegraph, 03 Sep 2015.

The Whistleblower

A shocking expose of the healthcare industry by one of its most successful executives

The-Whistleblower book cover image
A shocking expose of the healthcare industry by one of its most successful executives.

Confessions of a Healthcare Hitman

This is a shocking expose of the healthcare industry by one of its most successful executives. “The Whistle Blower” will shock everyone. It begins in 2003 when Pfizer takes over Pharmacia and details the insidious techniques Pfizer used to terminate more than 10,000 Pharmacia employees. It reveals illegal, and even criminal business practices at Pharmacia, which the author brought to light during the Pfizer acquisition, resulting in the FBI, the FDA’s Enforcement Division, the Justice Department, the New York State Attorney General and the Securities and Exchange Commission all calling him in for questioning over the course of the following year. However, in the post-Enron world of federal sanctions for retaliation against whistleblowers, he couldn’t be fired or demoted, although he lost his department and was moved to an office next to corporate security. This is the story of one senior industry executive who set out to change the entire pharmaceutical industry for the better, fighting on the behalf of American consumers for lower priced drugs. To win this battle, he testified before congress and wrote this book, which exposes the drug industry’s darkest and most closely guarded secrets.

Clear cell adenocarcinoma of the vagina and cervix secondary to intrauterine diethylstilbestrol exposure

Recurrent CCA has been observed as long as 20 years after primary therapy

image of CCAC
Factors that may increase the risk are maternal history of prior miscarriage, exposure to DES in early gestation, a fall season of birth, and prematurity. Recurrent CCA has been observed as long as 20 years after primary therapy emphasizing the importance of prolonged follow-up..

1990 Study Abstract

Intrauterine diethylstilbestrol (DES) exposure is associated with an increased risk for the development of clear cell adenocarcinoma (CCA) of the vagina and cervix.

The age of the DES-exposed patients has varied from 7 to 34 years with the highest frequency from 14 to 22 years. The risk among the exposed is small and is on the order of 1 per 1,000.

Factors that may increase the risk are maternal history of prior miscarriage, exposure to DES in early gestation, a fall season of birth, and prematurity. Pregnancy does not appear to influence adversely the tumor characteristics or prognosis of patients who have developed these malignancies.

Criteria for appropriate local therapy of small clear cell adenocarcinomas of the vagina are presented. Recurrent CCA has been observed as long as 20 years after primary therapy emphasizing the importance of prolonged follow-up..

Sources and more information
  • Clear cell adenocarcinoma of the vagina and cervix secondary to intrauterine exposure to diethylstilbestrol, Herbst AL, Anderson D, Semin Surg Oncol. 1990;6(6):343-6. NCBI PMID: 2263810.
More DES DiEthylStilbestrol Resources

The European Commission, the meetings with companies, and the corporate lobby bias

ALTER-EU writes to President Juncker re: corporate lobby bias

This post content is published by ALTER-EU, a coalition of over 200 civil society groups and trade unions concerned with the influence of corporate lobbyists on the political agenda in Europe

Alliance for Lobbying Transparency
ALTER-EU sent a letter from to EU Commission President Juncker, based on analysis of the lobby meetings held by high-level officials in the Commission between 1 December 2014 and 23 June 2015. ALTER-EU regrets that 75% of EU Commission lobby meetings are w/ith companies despite Juncker promising balance.

Executive summary / policy recommendations:

  1. Lobbyists representing businesses and trade associations make up 75 per cent of all high-level meetings and more than 80 per cent in certain areas such as financial regulation or the internal market. yet the Commission has committed to deliver balance in stakeholder representation. We conclude that the only effective way to achieve this is by limiting the number of meetings with big business lobbyists and increasing access by other stakeholders, including civil society organisations.
  2. After the largely successful introduction of the meeting ban at the highest Commission levels, ALTER-EU calls upon President Juncker to extend the ban on meeting unregistered lobbyists to all levels of the Commission as a significant proportion of lobbying happens with Commission officials below the highest level.
  3. For almost all commissioners, there is a discrepancy between their published agendas and the lobby meetings registered on the Commission websites, suggesting many meetings listed in the agenda were not reported afterwards. All commissioners must publish a complete list of their lobby meetings in a timely manner.
More information:
  • Who is meeting whom? The lobby meetings of the new European Commission, alter-eu, June 24, 2015. Full PDF.
  • ALTER-EU writes to President Juncker re: corporate lobby bias, alter-eu, 4 th September 2015

Childhood cancer not a death sentence any longer, but a life sentence still

Cancer Risk in Childhood Cancer Survivors Continues for Decades

This post content is published by National Cancer Inst, the U.S. government’s lead agency for cancer research

Long-term survivors of childhood cancer may need careful monitoring for a second cancer.

Survivors of childhood cancer have an elevated risk of developing second, distinct cancers into their forties and beyond, according to a new study.

Several studies have documented childhood cancer survivors’ increased risk of developing a second cancer, but this new study is among the first to assess this risk for survivors in their fifth and sixth decades of life. Although cancer risk increases with age, the study showed that childhood cancer survivors who were older than 40 had a more than twofold increased risk of developing a second cancer than would be expected in the general population.

The findings were published August 10 in the Journal of Clinical Oncology (JCO).

Led by Lucie Turcotte, M.D., of the University of Minnesota Medical Center, the study used data on more than 14,000 participants in the long-running NCI-supported Childhood Cancer Survivor Study (CCSS) who were initially diagnosed between 1970 and 1986.

Nearly 3,200 participants in this CCSS cohort were 40 or older when the study’s last participant survey was conducted. Among these individuals, 615 cancers were diagnosed, more than two-thirds of which (419) were nonmelanoma skin cancers.

Participants also had an increased risk for breast cancer, followed by kidney cancer, sarcoma, and thyroid cancer. Long-term survivors also had an increased risk for benign tumors.

Overall, approximately 16 percent of the survivors in this analysis developed a subsequent cancer between ages 40 and 55. The incidence of cancer in these survivors was similar regardless of whether they had also been diagnosed with a second tumor (benign or malignant) before age 40, the authors reported.

Second cancers in survivors are often linked to prior treatments, and in this study both radiation therapy and treatment with a platinum-containing chemotherapy drug were significantly associated with substantially increased risks of a subsequent cancer after age 40.

Many survivors included in the study had Hodgkin lymphoma as children (30 percent), in part because this cancer is usually diagnosed at an older age than other common childhood cancers, so they were more likely to already have reached their fifth and sixth decades of life.

High-dose radiation therapy directed at the chest was a standard treatment for Hodgkin lymphoma during the study’s time period. This “clearly influenced” the types of second malignant cancers seen in the study, wrote Mark Applebaum, M.D., and Susan Cohn, M.D., in an accompanying editorial in JCO.

Nearly 60 percent of Hodgkin lymphoma survivors had a malignant or benign tumor diagnosed after age 40, they continued, largely because these survivors had such a high incidence of breast cancer.

Overrepresentation of Hodgkin lymphoma survivors in the study is a limitation, agreed Julia Rowland, Ph.D., director of NCI’s Office of Cancer Survivorship.

“But the findings also show that for those diagnosed with specific kinds of cancer as children, their second cancer risk doesn’t go away,” Dr. Rowland said.

Dr. Turcotte agreed. “Our findings are probably going to be the most important for Hodgkin lymphoma survivors,” she said. “It tells us that anybody who got high-dose radiation should continue to undergo close observation as they get older.”

Although studies of more near-term outcomes in childhood cancer survivors have shown an increased risk of lung, colorectal, and head and neck cancer, the risk of such cancers was not increased in the long term in this JCO study. That may be, Dr. Turcotte said, because rates of these particular cancers are higher in the general population among people in this same age range, obscuring any potential excess risk in long-term survivors.

The study results affirm that the overall approach to monitoring health has to be different for childhood cancer survivors, Dr. Rowland stressed.

She recounted a recent conversation with a long-term childhood cancer survivor. “And she said, ‘Childhood cancer isn’t necessarily a death sentence any longer,’” Dr. Rowland recalled. “‘But it is a life sentence.’ That’s an important point to remember for our youngest cancer survivors.”

Sources and more information
  • Cancer Risk in Childhood Cancer Survivors Continues for Decades,
    NCI, August 31, 2015.
  • Childhood Cancer Survivor Study: An Overview, NCI, April 21, 2015.
  • Risk of Subsequent Neoplasms During the Fifth and Sixth Decades of Life in the Childhood Cancer Survivor Study Cohort, NCBI PMID: 26261260, J Clin Oncol. 2015 Aug 10. pii: JCO.2015.60.9487.

The hidden “cocktail effect” of endocrine disruptors revealed

Synergistic activation of human pregnane X receptor by binary cocktails of pharmaceutical and environmental compounds

EDCs-cocktail-effect
Interaction network of ligands with residues of the LBP (grey); red dashed lines highlight the interactions between EE2 and TNC resulting in a mutual stabilization of the compounds in the LBP. Colour code: red, oxygen; blue, nitrogen; yellow, sulphur; green, chlorine; black dashed lines, hydrogen bonds.

2015 Study Abstract

Humans are chronically exposed to multiple exogenous substances, including environmental pollutants, drugs and dietary components. Many of these compounds are suspected to impact human health, and their combination in complex mixtures could exacerbate their harmful effects. Here we demonstrate that a pharmaceutical oestrogen and a persistent organochlorine pesticide, both exhibiting low efficacy when studied separately, cooperatively bind to the pregnane X receptor, leading to synergistic activation. Biophysical analysis shows that each ligand enhances the binding affinity of the other, so the binary mixture induces a substantial biological response at doses at which each chemical individually is inactive. High-resolution crystal structures reveal the structural basis for the observed cooperativity. Our results suggest that the formation of ‘supramolecular ligands’ within the ligand-binding pocket of nuclear receptors contributes to the synergistic toxic effect of chemical mixtures, which may have broad implications for the fields of endocrine disruption, toxicology and chemical risk assessment.

Sources and more information
  • Synergistic activation of human pregnane X receptor by binary cocktails of pharmaceutical and environmental compounds, Nature Communications 6, Article number: 8089 doi:10.1038/ncomms9089, 03 September 2015

Epilepsy in pregnancy and reproductive outcomes: a systematic review and meta-analysis

Significant association of epilepsy, exposure to antiepileptic drugs, and adverse outcomes exists in pregnancy

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A small but significant association of epilepsy, exposure to antiepileptic drugs, and adverse outcomes exists in pregnancy. Image via Lucie Otto-Bruc.

2015 Study Abstract

Background
Antenatal care of women with epilepsy is varied. The association of epilepsy and antiepileptic drug exposure with pregnancy outcomes needs to be quantified to guide management. We did a systematic review and meta-analysis to investigate the association between epilepsy and reproductive outcomes, with or without exposure to antiepileptic drugs.

Methods
We searched MEDLINE, Embase, Cochrane, AMED, and CINAHL between Jan 1, 1990, and Jan 21, 2015, with no language or regional restrictions, for observational studies of pregnant women with epilepsy, which assessed the risk of obstetric complications in the antenatal, intrapartum, or postnatal period, and any neonatal complications. We used the Newcastle-Ottawa Scale to assess the methodological quality of the included studies, risk of bias in the selection and comparability of cohorts, and outcome. We assessed the odds of maternal and fetal complications (excluding congenital malformations) by comparing pregnant women with and without epilepsy and undertook subgroup analysis based on antiepileptic drug exposure in women with epilepsy. We summarised the association as odds ratio (OR; 95% CI) using random effects meta-analysis. The PROSPERO ID of this Systematic Review’s protocol is CRD42014007547.

Findings
Of 7050 citations identified, 38 studies from low-income and high-income countries met our inclusion criteria (39 articles including 2 837 325 pregnancies). Women with epilepsy versus those without (2 809 984 pregnancies) had increased odds of spontaneous miscarriage (OR 1·54, 95% CI 1·02–2·32; I2=67%), antepartum haemorrhage (1·49, 1·01–2·20; I2=37%), post-partum haemorrhage (1·29, 1·13–1·49; I2=41%), hypertensive disorders (1·37, 1·21–1·55; I2=23%), induction of labour (1·67, 1·31–2·11; I2=64%), caesarean section (1·40, 1·23–1·58; I2=66%), any preterm birth (

Interpretation
A small but significant association of epilepsy, exposure to antiepileptic drugs, and adverse outcomes exists in pregnancy. This increased risk should be taken into account when counselling women with epilepsy.

Sources and more information

Big money and close ties behind Big Pharma’s Brussels lobby efforts

Policy prescriptions: the firepower of the EU pharmaceutical lobby and implications for public health

EU-pharmaceutical-lobby
A new report released today reveals the dramatic extent of the pharmaceutical industry’s lobbying efforts towards EU decision-makers, with the industry spending an estimated 15 times more than civil society actors working on public health or access to medicines.

This post content is published by Corporate Europe Observatory (CEO) – challenging the influence of big business and business lobby groups in EU policy making.

Policy prescriptions: the firepower of the EU pharmaceutical lobby and implications for public health‘ by Corporate Europe Observatory probes the privileged access to decision-making in Brussels enjoyed by the sector and facilitated by a lobby spend of around €40 million, extensive meetings with policy-makers, and presence in advisory groups. Under-reporting and the continued avoidance by some of the EU’s voluntary lobby transparency system mean that overall industry spending may be much higher than the transparency register reveals.

The report shows that Big Pharma enjoys a staggering number of meetings with European Commission departments and officials. For example, influential EU pharmaceutical trade association, the European Federation of Pharmaceutical Industries and Associations (EFPIA), had over 50 meetings with the Juncker Commission in its first four and a half months of office.

“The large-scale efforts of big pharmaceutical companies to mould EU policy to their own commercial benefit and their privileged access to EU decision-makers are deeply worrying. Strong measures are needed to avoid capture of EU health policy by Big Pharma, beginning with full transparency over industry lobbying and ending of privileged access,” says CEO researcher and author of the report, Rachel Tansey.

The study examines some of Big Pharma’s channels of influence in the EU and exposes concrete examples of EU law and policies that have been targeted or shaped by the industry. These include rules around clinical trials’ data transparency, trade secrets, and the negotiation of the EU-US trade deal, the Transatlantic Trade and Investment Partnership (TTIP).

It also puts pharma lobby group EFPIA in the spotlight, examining its goals, tactics, access and influence, including a critique of the EU’s multi-billion euro public-private partnership with EFPIA, the ‘Innovative Medicines Initiative’.

How Does Google Plan to Transform Healthcare?

Is Google reaching for the moon when it comes to healthcare innovation?

Forget the “sky’s the limit”, Google is reaching for the moon when it comes to healthcare innovation…

Sources and more information