Does Ovary-Sparing Hysterectomy lead to decrease in ovarian reserve?

Clinical pearls:

• Women who underwent ovarian sparing hysterectomy have a greater decrease in levels of antimüllerian hormone as compared to women with intact reproductive organs and this decrease is independent of baseline levels.
• These women on an average achieve menopause 1.9 years earlier than those with no surgery. 
• The highest number of hysterectomies are performed on women aged 40-44 making them susceptible to premature menopause and increasing their risk for CVD, osteoporosis and psychological problems. 

The decision to spare the ovaries or remove it during hysterectomy is often very difficult to make in everyday gynecology practice. The potential benefit of removing the ovaries for eliminating the risk of ovarian cancer has to be balanced against the cardiovascular and anti-osteoporotic benefits gained by sparing them.

Prophylactic Oophorectomy along with hysterectomy in low risk women results in early death, fatal and nonfatal cardiac disease, osteoporosis and neurologic complications.[1] A study results showed that for women who have a hysterectomy with ovarian conservation at ages 50 to 54 with being at average risks for chronic diseases, the chances of surviving to age 80 was 62.46% vs 53.88% if ovaries were not spared. [2]  

This 8.5% difference was advocated to far less women dying because of CVD (15.95% vs. 7.57%) and hip fracture (4.96% vs. 3.38%) far exceeding the mortality of .47% women dying because of ovarian cancer in patients whom ovaries were left behind at the time of benign hysterectomy.

But, recent research and evidence indicate that women who underwent ovarian sparing hysterectomy entered menopause very quickly as compared to women with intact reproductive organs.[3] [4]

A recent Prospective Research on Ovarian Function study (PROOF) published in May, 2016 issue of obstetrics and gynecology compared the levels of antimüllerian hormone in women undergoing hysterectomy before and after the surgery.

PROOF is a prospective cohort study of large ethnically divert women who underwent ovarian sparing hysterectomy and racially and age matched controls conducted between 2004-2007 and followed through 2009.

Median Baseline levels of antimüllerian were comparable in both the groups before the study subjects underwent hysterectomy, but at a median of 366 days’ follow up post hysterectomy, the study group has almost twice decrease in antimüllerian hormone levels (−40.7% compared with −20.9%; P<.001) and were more likely to have nondetectable levels (12.8% compared with 4.7%; P=.02) compared with the referent group.

These large decrease could be explained by assuming that hysterectomy disrupts the blood flow to ovaries or removes the paracrine /endocrine stimulus from the uterus hastening the ovarian senescence due to follicular depletion.

It was also observed that black women were more predisposed to decrease in antimüllerian hormone as compared to white women. This finding is comparable to previous other related studies which concluded that reproductive aging varies according to race and ethnicity and black women have lower baseline antimüllerian levels and also show greater percentage decline.

The study had limitation of only studying a subset of cohort, but was done to eliminate other confounding factors.

To conclude, women who underwent hysterectomy with ovaries left intact, have a greater decrease in levels of antimüllerian hormone as compared to women with intact reproductive organs and this decrease is independent of baseline levels.

If hysterectomy is leading to decreased ovarian reserve and earlier menopause, then this has very important public health ramifications. Hysterectomy is the most common surgery in gynecology worldwide and second most common operation performed in US with approximately 600,000 hysterectomies are performed each year.

The highest number of Hysterectomies are performed on women aged 40-44 making them susceptible to premature menopause and increasing their risk for CVD, osteoporosis and psychological problems.

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[1]Keshavarz H, Hillis H, Kieke BA, Marchbanks P. Hysterectomy surveillance—United States, 1994–1999. Atlanta (GA): Centers for Disease Control and Prevention; 2002. Available at:http://www.cdc.gov/mmwr/preview/mmwrhtml/ss5105a1.htm.

[2] http://www.pharllc.com/wp-content/uploads/2013/03/Parker-Contemp-Obstet-Gynecol-2006.pdf accessed on June 29, 2016.

[3]  Ahn EH, Bai SW, Song CH, Kim JY, Jeong KA, Kim SK, et al.. Effect of hysterectomy on conserved ovarian function. Yonsei Med J 2002;43:53–8.

[4] Farquhar CM, Sadler L, Harvey SA, Stewart AW. The association of hysterectomy and menopause: a prospective cohort study. BJOG 2005;112:956–62

Aspirin guide app launched that aid physicians in clinical decision making: Who should be put on low dose aspirin?

The Aspirin Guide app

The beneficial role of  low dose aspirin for secondary  prevention of cardiovascular event and stroke after a primary event is backed by large clinical trial data, reviews and meta-analysis.

Physicians face a more challenging question in clinical practice- who should be put on daily low dose aspirin to prevent first cardiovascular event or stroke so that the benefits outweigh the risks of GI bleeding.

The US Preventive Services Task Force (USPSTF) recently issued clinical guidelines for use of  aspirin as preventive medication. It advises  “initiating low-dose aspirin use for the primary prevention of cardiovascular disease (CVD) and colorectal cancer (CRC) in adults aged 50 to 59 years who have a 10% or greater 10-year CVD risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years ” with a recommendation ‘B’.

The decision to start aspirin for men and women aged 60-69 who have a 10% or greater 10-year CVD risk is individualized according to each patient and it received a lower level ‘C’ recommendation.

But, Physicians find it’s very time consuming to implement and requires them to  make two different calculation. First they have to calculate the CVD and stroke risk and then refer a table that  gives you the bleeding risk.

 Brigham and Women’s Hospital, Harvard Medical School has launched an app named ‘aspirin guide’ which helps physician decide that which patient can be safely started on low dose aspirin balancing the risks and benefits.

The app comes with several unique features including:

It has the US Preventive Services Task Force recent guidelines for the use of aspirin for. primary prevention.

It calculates a 10 year cardiovascular disease risk score based on series of inputs the physician provides about patient’s medical statistics. Based on the score and the bleeding risk, the app can aid in decision making in prescribing aspirin.

The summary of decision making can be mailed to the physician and patient.

It also have sex specific guidelines incorporated, so that according to the earlier  guidelines  and RCTs even women  65 and older can be put on therapy if they are not at high risk for GI bleeding.

The app also have an algorithm flow chart for shared decision making that can be easily followed.

The app is developed by  Dr JoAnn Manson, professor of medicine at Harvard Medical School and Brigham and Women's Hospital, Dr. Samia Mora, MD, MPH is a cardiologist and cardiovascular epidemiologist and Jeffery  Manson is a computer programmer who develops  medical  apps.

Reference:

https://itunes.apple.com/nz/app/aspirin-guide/id1117434628?mt=8

http://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/aspirin-to-prevent-cardiovascular-disease-and-cancer

Bibbins-Domingo K, on behalf of the U.S. Preventive Services Task Force. Aspirin Use for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2016;164:836-845. doi:10.7326/M16-0577

Smaller “Occiput-spine angle” during first stage of labor increases risk of operative delivery-a new sonographic parameter to assess fetal head deflexion.

Occiput-spine angle
courtesy http://onlinelibrary.wiley.com/doi/10.1002/uog.14342/full

Clinical Pearls:

• Fetal deflexion in first stage of labor is directly correlated with higher chances of operative  delivery.
• A new sonographic parameter of Occiput-spine angle < 125 predicts high chances of prolonged labor and operative intervention.
• This finding is easily reproducible in subsequent observations.
• This parameter cannot be measured in  frank occiput posterior positions due to  technical limitations.

According to a population based study labor dystocia is the most common indication for primary cesarean section, followed by abnormal fetal CTG, fetal malpresentation, multiple gestation, and suspected fetal macrosomia.[1]

Fetal deflexed cephalic malpresentation is responsible for nearly 30% cases of labor arrest leading to operative intervention. The degree of fetal head extension results in variety of malpresentation including sinciput, brow, and face.[2]

The diagnosis of labor dystocia and fetal cephalic malpresentation is traditionally made by digital examination, but use of ultrasound is increasingly made in labor ward to support the clinical diagnosis especially in face and brow presentations. [3] [4]

A recent study published in July issue of American Journal of obstetrics and Gynecology [5] aimed to determine whether ultrasound measurements quantifying occiput-spine angle can be used as a parameter to determine the course, outcome and operative intervention in labor.

Study was conducted at maternity units of one of the oldest university in Europe at Bologna and Parma from January 2014 to April 2015. In this prospective cross-sectional study 108 pregnant women who presented with uncomplicated singleton pregnancies at term gestation of 37 weeks or beyond were recruited as study participants. The inclusion criteria were regular and active uterine contraction, with cervical dilatation between 3-6 cm, fetal head station at 0. Patients with occipital posterior position and PROM > 24 hours were excluded from the study.

A 2 dimensional sagittal sonogram of fetal head and cervical spine was taken and stored. On the image an offline measurement of the angle formed between the two lines drawn tangential to occipital bone and first vertebra was performed to quantify the  position of fetal head.                           

The results of the ultrasound were not known to the obstetrician who managed the labor. The labor outcome, mode of delivery and the result of ultrasound examination were correlated retrospectively.

After accounting for other confounding factors and excluding cesarean deliveries for non-reassuring FHS, multivariate logistic regression was performed. 

It was seen that out of 108 study subjects, spontaneous vaginal delivery occurred in 79 patients. Of the remaining patients  10 required vacuum assistance and 19 has to undergo cesarean section. The patients needed vacuum or cesarean section because of  labor arrest in 19 patients and nonreassuring fetal heart rate in 10 patients.

Multivariable logistic regression analysis showed that narrow occiput-spine angle values (OR 1.08; 95% CI 1.00−1.16; P = .04) and nulliparity (OR 16.06; 95% CI 1.71−150.65; P = .02) were independent risk factors for operative delivery. A larger occiput-spine angle width (i.e., >125°) showed to be significantly associated with a shorter duration of labor (hazard ratio = 1.62; 95% CI 1.07−2.45; P = .02).

This is a very important first study that correlated  fetal head deflexion objectively in the first stage of labor and  its impact on  labor outcome. The occiput spine angle in the first stage was directly related to the station of the fetal head, the deeper the head the greater the angle.

Cases that required intervention ,all had smaller occiput-spine angle at a similar station indicating diminished flexion of the fetal head. In all those fetuses with occiput-spine angle <125°, the duration of labor was considerably prolonged.

Other similar studies were conducted in the past but none measured the fetal deflexion quantitatively and the findings were not reproducible. About 30-50% of fetuses occupy a frank occiput posterior position in early first stage of labor and the measurements cannot be assessed in such cases. A  recent study have shown that in such patients the chances of operative delivery are quite high.

The study described a new sonographic parameter of occiput-spine angle that can predict with accuracy the chances of operative intervention. Fetuses with deflexed head resulting in smaller occiput-spine angle (<125°) are at increased risk for operative delivery.

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[1] http://www.ajog.org/article/S0002-9378(14)00055-6/fulltext

[2] Jacobson, L.J. and Johnson, C.E. Brow and face presentations. Am J Obstet Gynecol. 1962; 84:1881–1886

[3]Ghi, T., Maroni, E., Youssef, A. et al. Intrapartum three-dimensional ultrasonographic imaging of face presentations: report of two cases. Ultrasound Obstet Gynecol. 2012; 40: 117–118

[4] Lau, W.L., Cho, L.Y., and Leung, W.C. Intrapartum translabial ultrasound demonstration of face presentation during first stage of labor. J Obstet Gynaecol Res. 2011; 37: 1868–1871

[5] Ghi T, Bellussi F, Azzarone C, et al. The “occiput–spine angle”: a new sonographic index of fetal head deflexion during the first stage of labor. Am J Obstet Gynecol 2016;215:84.e1-7.

Abnormally invasive placenta---Can we predict and do better?

Clinical Pearls:

• Previous cesarean section or uterine surgery is the single most important predisposing factors for Abnormally Invasive placenta.
• One cesarean section increases the risk of AIP seven fold in subsequent pregnancy.
• History of post-partum hemorrhage is also a risk factor for AIP and increases the risk 6 fold in current pregnancy.
• In 70% of cases, the diagnosis of AIP was missed during antenatal period.
• Increasing clinician awareness for incidence of AIP in the high risk patients leads to increased diagnosis in antenatal period.
• Avoiding unnecessary cesarean section is the only way to decrease the incidence of AIP.  

Lowering the Cesarean section rate in the population is the only most effective way in reducing the incidence of Abnormally invasive placenta(AIP) is the conclusion of a large, population based cohort study from the Nordic countries.

The Nordic Obstetric Surveillance Study (NOSS) required obstetricians’ collaboration in reporting AIP, uterine rupture, excessive blood loss and peripartum hysterectomy from 2009-2012. Due to paucity of cases at a single hospital the data was pooled and validated by National Health Registries. 

The data was analyzed and identified 205 cases of AIP amounting to an incidence of 3.4 per 10,000 deliveries.

The study was published in the current issue of British Journal of Obstetrics and Gynecology(BJOG).[1]

The study goal was to gauge the prevalence, risk prediction, predisposing factors, antenatal suspicion, maternal morbidity and birth complications in cases of AIP.

The study confirmed the association between AIP and previous cesarean section or any other previous uterine surgeries like endometrial ablation, and in vitro fertilization. The risk of AIP in subsequent pregnancy is seven fold with one prior Cesarean section to 56-fold after three or more CS.

Placenta previa was the single most important risk factor identified in nearly half of the pregnancies.

 In addition, patient who had postpartum hemorrhage in previous pregnancy have 6 times the risk of AIP in current pregnancy as compared to patients who did not have PPH.

An antenatal diagnosis of AIP can strikingly reduce the complication rate but in nearly two-third of patients (70%) of patients the diagnosis was missed. Of these, 39% had prior CS and 33% had placenta praevia.

Increased awareness about the risk factors among clinicians can raise the index of suspicion and led to more and more patients being diagnosed in prenatal period. Clinicians performing Ultrasound(USG) should have high index of suspicion in high risk women with previous uterine surgery or a placenta over uterine scar. These women should be offered additional sonography.

Nordic countries have lower rates of AIP than US, perhaps due to lower rate of cesarean section and high order cesarean births or better obstetrics facilities. 

But, the only sure way to decrease the incidence of AIP is to avoid unnecessary cesarean delivery, especially the first cesarean section.

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[1] Thurn L, Lindqvist PG, Jakobsson M, Colmorn LB, Klungsoyr K, Bjarnadóttir RI, Tapper AM, Børdahl PE, Gottvall K, Petersen KB, Krebs L, Gissler M, Langhoff-Roos J, Källen K. Abnormally invasive placenta—prevalence, risk factors and antenatal suspicion: results from a large population-based pregnancy cohort study in the Nordic countries. BJOG 2015; DOI: 10.1111/1471-0528.13547.

ACOG updates recommendations for preventing obstetric lacerations during vaginal delivery.

Clinical Pearls:

• Recommends against routine episiotomy, advises restrictive use of episiotomy
• Warm compress during pushing led to decreased incidence of third-degree and fourth-degree lacerations.
• No single birthing position helps in decreasing perineal lacerations.
• Suture material used is absorbable synthetic ones with continuous suturing.
• Full thickness external anal sphincter repair should be done end-to-end or overlap with a single dose of antibiotics at the time of repair.
• Vaginal delivery is an appropriate, safe option for women who have experienced severe obstetric lacerations during previous pregnancies unless she had anal incontinence, wound infection or repeat surgery.
• Does not recommend the routine use of endoanal ultrasonography immediately after labor to detect occult OASIS.

ACOG states that 53% to 79% of patients will have some type of lacerations during vaginal deliveries but most of them will not hamper the functional outcome.[1] Most of these are first and second degree lacerations, but third and fourth degree lacerations resulting in obstetric anal sphincter injuries (OASIS) can occur in 11% of patients.

A new practice Bulletin  “Prevention and Management of Obstetric Lacerations at Vaginal Delivery,"  was released by ACOG  on June 22, 2016 replacing  Practice Bulletin #71, “Episiotomy,” and Committee Opinion #647, “Limitations of Perineal Lacerations as an Obstetric Quality Measure.”

"The previous bulletin did not focus on the broader concept of perineal lacerations and anal sphincter injury. This was developed to be much more comprehensive and to reaffirm to physicians that episiotomy is not recommended as routine part of delivery." Said co-author Sara Cichowski. MD.

The bulletin advises obstetrics practitioner against the routine use of episiotomy to decrease perineal lacerations, instead take other measures to mitigate the risk.

A review involving 8 trials and 11,651 randomized women have concluded that warm compress on the perineum during pushing is associated with decreased incidence of perineal trauma.[2] (Level A recommendation). Perineal massage, either during first stage or during the second stage of labor, can decrease muscular resistance and reduce the likelihood of laceration. Many other trials have confirmed the benefit of perineal massage but ACOG did not recommend perineal support due to lack of sufficient information and clinical methods.

Based on clinical data ACOG recommends restrictive use of episiotomy as compared to routine use. A systemic review[3] found many benefits of restrictive use over routine use like severe perineal trauma, less suturing and fewer healing complications. Both fared equal for severe vaginal/perineal trauma, dyspareunia and urinary incontinence.

The bulletin quotes "Current data and clinical opinion suggest that there are insufficient objective evidence-based criteria to recommend episiotomy, especially routine use of episiotomy, and that clinical judgment remains the best guide for use of this procedure." [4]

National Episiotomy rates have steadily decreased since 2006, when ACOG guidelines did not recommend routine episiotomy. Data shows that in 2000, 33% of women received episiotomy which has come down to 12% in 2012.

Data on timing of giving episiotomy was sparse as also its benefit or harm in cases of shoulder dystocia or operative vaginal delivery.

Clear consensus also could not be reached on any single birthing position and delayed pushing after full dilatation leading to decreased perineal lacerations and episiotomy.  

Minor tears of anterior vaginal wall and labia can be left to heal by itself after achieving hemostasis while periurethral, periclitoral and large labial laceration with bleeding should be repaired. Clinicians are advised to use clinical judgement when it comes to repair first- or second-degree lacerations due to lack of evidence.

The choice of suture material should be continuous absorbable synthetic ones, such as polyglactin. Full thickness external anal sphincter repair should be done end-to-end or overlap with a single dose of antibiotics at the time of repair. (Level A recommendation).

ACOG also states that majority of women with obstetric anal sphincter injuries (OASIS) deliver vaginally in subsequent pregnancies. Cesarean delivery may be offered to women who with history of OASIS if she experienced anal incontinence, wound infections, repeat surgery or psychological trauma.

“Without question, a vaginal delivery is an appropriate, safe option for women who have experienced severe obstetric lacerations during previous pregnancies,” opined Sara Cichowski, MD, who co-authored the new guidelines. “However, women who have anal incontinence or who have suffered significant physical or emotional trauma as a result of previous experiences may find that a cesarean delivery is the right choice for them.”[5]

It also does not recommend the routine use of endoanal ultrasonography immediately after labor to detect occult OASIS, but advocates that a trained clinical research fellow should examine the patient before the suturing perineal tear by the attending physician. Detection of overt OASIS have a learning curve and improves with education and training.

The bulletin also provided recommendations for long term monitoring and pelvic floor exercises.

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[1] http://www.acog.org/About-ACOG/News-Room/News-Releases/2016/Ob-Gyns-Can-Prevent-and-Manage-Obstetric-Lacerations

[2] http://www.ncbi.nlm.nih.gov/pubmed/22161407

[3] http://www.ncbi.nlm.nih.gov/pubmed/19160176

[4] http://journals.lww.com/greenjournal/Abstract/2016/07000/Practice_Bulletin_No__165___Prevention_and.46.aspx

[5] http://www.acog.org/About-ACOG/News-Room/News-Releases/2016/Ob-Gyns-Can-Prevent-and-Manage-Obstetric-Lacerations

Plant based therapies and menopausal symptoms: A Systematic Review and Meta-analysis

According to data by North American Menopause Society (NAMS) about 6000 US women transition into menopause every day. With ever increasing life expectancy in western world (79.7 years) it is expected that by the year 2020 number of US women older than 51 will be 50 million and the corresponding statistics worldwide is 1.1Billion. [1]

Women who have undergone surgical menopause are more likely to use Hormone replacement therapy as compared to women with natural menopause. About 75% of women who undergo surgical menopause use HRT at some time, 50% of those with a hysterectomy only had used HRT and only 30% of women with natural menopause had used HRT.[2]

About 80% of women experience Vasomotor symptoms as they transition into menopause and according to the Study of Women's Health Across the Nation (SWAN)[3] these symptoms last average 7.4 years after menopause.

Many women opt for menopausal hormone therapy (MHT) to relieve the vasomotor symptoms, especially after the current research have shown it to be safe in women within 10 years of menopause and no contraindication. MHT have many adverse effects in older postmenopausal women (over age 60 years) and is not generally indicated.

Because of the concern for safety, many women are turning towards plant based herbal remedies often called as “Bioidentical hormones”. These are synthesized from soy and plant extract and modified to be structurally similar to endogenous hormones. A recent Systematic Review and Meta-analysis published in the recent edition of Journal of American Medical Association (JAMA)^[4] sought to determine the effectiveness of these therapies in relieving vasomotor symptoms and vaginal dryness.

Two independent reviewers extracted data from Ovid MEDLINE, EMBASE, and Cochrane Central, searching for eligible studies that were published before March 27,2016. A total of 62 studies were identified, including 6653 individual women. The main outcome studied were Hot flashes, night sweats, and vaginal dryness. The time range of therapy extended between 4 weeks to 2 years, the average being about 12 weeks.

Out of 62 studies, only 36 studies used plant based phytoestrogens, the rest used other herbal and Chinese herbal medicines.

As compared to placebo use of phytoestrogen was seen to decrease number of hot flashes per day (pooled mean difference of changes -1.31, 95% CI -2.02 to -0.61) and vaginal dryness score (pooled mean difference -0.31, 95% CI -0.52 to -0.10) but no difference was seen in daily night sweat score between the two treatment regimen. 

Dr. Oscar H. Franco, MD, of Erasmus University Medical Center in Rotterdam, The Netherlands, who is the lead researcher also and colleagues also attempted to determine the individual effects of plant based treatments like all forms of soy isoflavones, Black Cohosh and Chinese and non-Chinese medicinal herbs.

Red leaf clover and soy isoflavones were not found much effective in hot flashes. No definitive evidence regarding its active ingredients and concerns over safety and side effects were also important issues regarding its use in clinical practice.

Studies including Chinese herbal medicines and other herbal remedies lacked sufficient power to perform meta- analysis but the results were inconsistent and did not show any association.

The study had several limitations including the reporting of the hot flashes being itself subjected to recall bias, methodological deficiencies, limited generalizability, and inconsistent composition of phytoestrogen used.

The authors cautioned that the results should be interpreted in light of the limitations and further rigorous well designed randomized, placebo-controlled, double-masked trial with large women from different racial/ethnic background and menopausal status that could be followed up for years is required before any conclusion can be drawn.

Current evidence does suggest that the composite and individual specific phytoestrogen use was associated with moderate reduction in night sweats and vaginal dryness but has no effect on hot flashes.

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[1] http://www.menopause.org/docs/2012/cg_a.pdf?sfvrsn=2

[2] http://www.cdc.gov/nchs/data/misc/hrt_booklet.pdf

[3] http://www.swanstudy.org/

[4] http://jama.jamanetwork.com/article.aspx?articleid=2529629

[5] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566363/

Osteoporosis drug can prevent the development of breast cancer in women who are BRCA1 mutation carriers.

Individuals who carry a mutation in breast cancer susceptibility gene(BRCA1) are highly prone to develop breast cancer.  As compared to general population who have 8% chance of developing breast cancer, women who harbor this germline mutation have a 55-65% chance of developing breast cancer by the age 70.[1]

These women frequently undergo prophylactic risk reducing surgeries ( (bilateral prophylactic mastectomy and bilateral prophylactic salpingo-oophorectomy) to minimize the chances of developing breast cancer.[2]

Scientist around the world are long looking for chemoprevention to reduce the risk of cancer in BRCA1 mutation carriers. Currently Tamoxifen is in use for chemoprevention.  

 A recent paper published in Nature[3] offers a breakthrough for millions of next generation women with BRCA1 mutation carrier. Researchers are already considering it as ‘holy grail’ of breast cancer prevention.

Denosumab is a human monoclonal antibody for the treatment of osteoporosis. It is also a RANKL signaling inhibitor, RANK⁺ and RANK⁻  are two subsets of luminal progenitors present in the histological normal breast tissue of BRCA1 mutation carriers. RANK⁺ cells are highly proliferative, have grossly aberrant DNA repair and bear a molecular signature similar to that of basal-like breast cancer. Denosumab inhibited the RANK⁺ signaling and stopped the progesterone induced proliferation of pre-neoplastic cells and also tissues from breast biopsies of BRCA1 mutation carriers. The same effect was also seen in mouse model of mammary tumorigenesis. Denosumab is already in use for treatment of osteoporosis and for patients with bone metastasis of breast cancer. 

Geoff Lindeman, a clinician-scientist at the Walter and Eliza Hall Institute and a co-author of the study said "Over the last few years, it has become increasingly clear from the work of several groups that RANK ligand, which switches on RANK, is an important regulator of cell growth in the breast. We have now been able to pinpoint the precise culprit cells and were very excited to see that they express the RANK protein."

As a part of pilot study three women were also treated with Denosumab and the results are encouraging days Dr. Lindeman.

Dr. Francisco Esteva (researcher at NYU Langone Medical Center and a part of the pilot study) and his colleagues are looking forward to conducting large scale clinical trials. "The new study does not change any management or clinical use of any drugs at this point, but it provides data that can be tested in a clinical trial," he said. "The data are compelling."

He also added that we are looking at least 10 years down the lane, but it offers hope for future generations of women.

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[1]http://ww5.komen.org/BreastCancer/InheritedGeneticMutations.html

[2] http://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet

[3] http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.4118.html#access

New obesity treatment device AspireAssist approved by FDA

Image courtesy:Aspire Bariatrics

One more gadget added to the armamentarium of obesity treatment device as FDA approves  The AspireAssist device[1]. This device uses a surgically placed tube in the stomach to drain about 30% of the content after every meal. AspireAssist, is created by Segway inventor Dean Kamen and a team of bariatricians and was patented in 2013[2].

It is not a short term procedure and is not indicated in patients who are moderately obese. Its main indication is in patients aged 22 and older, with BMI between 35-55 and who have failed to achieve and maintain weight through non-surgical procedure.

The short OPD procedure consists of endoscopically placing a tube in the stomach through a small incision in the abdomen. A small disc shaped port valve is connected to the tube and it lies outside the abdominal skin flushed with the body. The patient is taught to drain the content of the stomach 20-30 minutes after a meal into toilet. For optimal weight loss the patients should drain the contents atleast 3 times daily[3].

AspireAssist is in use in parts of Europe since late 2011. In a trial of 111 study participants who received AspireAssist and lifestyle modification vs 60 control participants who only received lifestyle modification, AspireAssist patients lost 3 times the body weight by simple lifestyle modification only.

All the patients are monitored closely as it requires shortening of the tube as patients lose weight and abdominal girth. Frequent electrolyte checkup and nutritional supplement are required, along with dietary and life style modification. The patient is also taught the hygiene of the abdominal port.

Side effects of the tube include diarrhea, indigestion, nausea and vomiting.

The risks associated with AspireAssist include risk of the surgical procedure and risk associated with the abdominal port. Surgical risk includes sore throat, pain, abdominal bloating, indigestion, bleeding, infection, nausea, vomiting, sedation-related breathing problems, inflammation of the lining of the abdomen, sores on the inside of the stomach, pneumonia, unintended puncture of the stomach or intestinal wall and death. 

A number of complications associated with the abdominal port requires removal of the tube and closing the port. Patient may present with abdominal discomfort or pain, irritation, hardening or inflammation of the skin around the site where the tube is placed, leakage, bleeding and/or infection around the site where the tube is placed and device migration into the stomach wall.

Contraindication to AspireAssist includes diagnosed bulimia, diagnosed binge eating disorder, night eating syndrome, certain types of previous abdominal surgery, pregnancy or lactation, inflammatory bowel disease or stomach ulcers. Certain systemic conditions like uncontrolled hypertension, serious pulmonary or cardiovascular disease, coagulation disorders, chronic abdominal pain also places the patients at high risk for abdominal surgery.

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[1] http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm506625.htm

[2] http://www.popsci.com/gadgets/article/2013-01/segway-inventor-patents-gadget-sucks-food-directly-out-stomach

[3] http://www.aspirebariatrics.com/about-the-aspireassist/

No evidence of congenital anomalies with Zika infection in third trimester.

The first outbreak of Zika virus occurred in South America occurred in Brazil in May 2015 subsequently in October Columbia confirmed 156 cases of Zika in 13 municipalities.[1]  Neurological abnormalities and other adverse pregnancy outcomes are associated with Zika infection in first and second trimester of pregnancy.

A recent surveillance report from the Colombian Instituto Nacional de Salud (INS) suggested that Zika infection in the last trimester of pregnancy does not cause any structural fetal defect. The report of this study was published in recent online edition of New England Journal of Medicine.[2]

A total of 65,726 cases of ZVD were reported in Colombia during the study period from August 9, 2015, through April 2, 2016. Out of these 2485 (4%) were found positive on RT-PCR assay. Zika infection was widespread in Colombia with 11,944 pregnant women affected, of which 1484 (12%) were confirmed on RT-PCR assay.

Out of 11,944 infected pregnant women, INS had complete data on for a subgroup of 1850 women correlating gestational age and the onset of symptoms of Zika infection. Out of these 1850 women, 616 women got infection in third trimester and in nearly 89-90% of these women no congenital anomalies were detected at birth.

The remaining women were infected in first and second trimester, so they still had ongoing pregnancy when the cut-off date of the study was reached. 

The number of cases reported in the study does not show the true magnitude of the Zika infection as the surveillance system does not include asymptomatic women or those women who do not go to healthcare provider.

The authors stressed the importance of healthcare providers in educating the patients about the vector and sexual mode of transmission of the Zika infection.

The INS and CDC jointly are implementing intensified surveillance in places with Zika infections to determine the full spectrum of disease in mother and infants in relation to gestational age at infection. 

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[1] http://www.who.int/emergencies/zika-virus/history/en/

[2] http://www.nejm.org/doi/full/10.1056/NEJMoa1604037#t=article