Breast Imaging and Density

Today we welcome Dr. David Edmonson, assistant professor in surgery and obstetrics and gynecology at the Warren Alpert Medical School of Brown University. Dr. Edmonson is an expert in breast disease and a surgical oncologist. Today he talks with us on imaging and breast density.

Mammography results can be classified into the BI-RADS (“Breast Imaging Reporting And Data System”) categories — it’s worthwhile to remember these categories and what the likelihood of malignancy is:

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Mammography will also often report breast density. Breast density can hinder the utility of mammography, and depending on your area of practice, may suggest or require additional study. Dr. Edmonson does note that breast density requirements do have limited data, but are the subject of active study.

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You can use risk models to help assess need for additional imaging: the Tyrer Cuzick or Gail models can be utilized, taking into account different risk factors.

To find out more about breast imaging and density, check out the immensely helpful DenseBreast-Info.org. On their website, there are multiple opportunities to expand your knowledge, including the CME opportunity Breast Density: Why It Matters as well as an FAQ for healthcare providers.

Preventing the Primary Cesarean, Part II

We’re re-visiting an old episode of ours on preventing the primary cesarean, with some more and differently focused information. We heard some great feedback from our last episode so we’re incorporating some of that here! This time around, we want to focus some more on how to promote normal labor and physiological birth! 

Let’s start off with talking about shared decision-making. This is a framework for taking situations with various individuals with different sets of knowledge, belief systems, and priorities and coming together to form a mutually satisfying plan to get everyone where they want to go. ACOG CO 587 reviews this in part, stating SDM can increase patient engagement and reduce risk with resultant improved outcomes, satisfaction, and treatment adherence.

Shared decision making can take the form of a variety of tools in prenatal care and on the labor floor:

1. Partograms - allowing patients to see where they are in their labor course compared to others.

2. Birth plans - providers and patients can come together early in their course of the pregnancy to identify patient goals and desires for their labor. Also allows recognition of some goals/desires may not be feasible due to the patient’s individual risk factors, pregnancy complications, etc. 

3. Patient education resources - we love www.birthtools.org, but there’s a number that exist (and some probably specific to your institution) that can help set expectations for the birthing process.

In identifying a patient’s desires in labor, one of the most common questions has to do with analgesia. Prental care is an excellent time to discuss both pharmacologic and non-pharmacologic options for coping. While epidurals are common in the USA, continuous labor support is another option for coping and also has been shown to reduce cesarean rates in trials. It can take on many forms, and be administered by anyone a laboring person trusts:

1. Physical support - positioning, use of touch, application of cold and heat and control of environment.

2. Emotional support - being present with the laboring woman, use of distraction.

3. Instructional/informational support - assistance with relaxation and breathing, using effective communication techniques.

4. Advocacy labor support - building trust, providing security and giving laboring women control.

Nutrition and hydration during labor is another common sticking point. It is very common for nutritional deprivation at NPO or clear liquid diets to occur in labor. This is for ostensibly, a good reason: fear of aspiration of stomach contents in the event for need for general anesthesia, or for vomiting due to decreased GI motility. However, a Cochrane review demonstrated no statistical difference in maternal or newborn outcomes related to type of birth or Apgar scores at five minutes. Nutritional deprivation provided no benefit or harm, and so evidence does not support nutritional deprivation. This review further stated that nutritional deprivation can cause maternal distress, unbalanced nutritional status, and increased pain in labor.

What about our original fear of aspiration? Current studies don’t show that nutritional deprivation ensure low stomach residue or acidity. When combined with decreased use of general anesthesia in modern obstetrics, concern for aspiration risk does not provide sound basis for implementation of withholding food or fluid from women in labor.

Next, let’s review the benefits of collaborative care models:

Labor is a team sport that contains the woman, her support person/people, her nurse, and provider (midwife/obstetrician/family practitioner). It shares the workload for this 24 hour in house care, providing a variety of perspectives on the case, in a mutually respectful environment. Now certainly, there are challenges to what sounds so harmonious: interdisciplinary mistrust, inconsistent communication, variable skill sets, scheduling logistics, hospital structure, to name a few. However, we know that this is evidence based! Studies where there have been 24 hour laborists and strip review and collaboration have led to significant decrease in NTSV rate. Why does it work? Well, it likely promotes consideration of alternative options, with experts of multiple perspectives and skill level.

Lastly, systems-based and structural design challenges may also contribute to cesarean. This work is nascent, but check out the awesome work by the folks at Ariadne Labs’ Delivery Decisions Initiative to learn more.

Group B Strep

Today’s episode covers the ACOG Committee Opinion on Group B Streptococcus, also known as GBS or Streptococcus agalactiae.

The OBG Project has a phenomenal summary of these new guidelines; we encourage you to check out their outline which was hugely helpful in preparing the podcast for today! And be sure to check out how you can get their premium product, OBG First, absolutely FREE if you’re a chief resident. Check out the sidebar to learn more!

Get to know Group B Strep

Streptococcus agalactiae or GBS is a common flora of the vagina and rectum of women, with a prevalence of colonization between 10-30%.  In newborns, two types of GBS-related disease exist:

• Late Onset Disease occurs between 7 days and 2-3 months after birth, and is characterized by sepsis, more commonly meningitis, and organ/soft tissue infection.

  • More commonly acquired by horizontal transmission from the mother; can also be acquired from hospital sources or individuals in the community.

  • Curious: late onset cases caused by placental ingestion with improper processing.

• Early Onset Disease is present within 7 days of birth.

  • Occurs secondary to vertical transmission; fetal/neonatal aspiration during labor process; or both. 

  • Manifestations of disease occur most likely within 12-48 hours after birth. 

  • Characterized by sepsis, pneumonia, and less commonly meningitis.

  • The most common cause of early-onset neonatal sepsis.

    • 72% of cases of Early Onset Disease occur in term newborns; however, mortality is markedly higher in premature infants (19.2% in premies vs 2.1% at term), and premature infants are more likely to require higher levels of intensive care intervention. 

  • When treating GBS in labor, this is what we are primarily aiming to prevent! 

• Risk factors for GBS Early Onset Disease:

  • Gestational age < 37 weeks

  • Very low birth weight

  • Prolonged rupture of membranes > 18 hours

  • Intraamniotic infection

  • Young maternal age

  • Black race

  • Heavy vaginal-rectal colonization or GBS bacteriuria (proxy for heavy colonization)

  • Previous newborn affected by GBS early onset disease

The Screening Recommendations

• Screening in the USA is universal, meaning this should be a standard part of prenatal care. 

  • ACOG recommends universal screening for vaginal-rectal colonization between 36’0 - 37’6.

    • These results are considered “valid” for 5 weeks — thus the majority of women will be captured with screening at 36’0 (assuming inductions for most women at 41’0). 

    • This is also recommended for women planning to deliver by cesarean.

• What about GBS bacteriuria?

  • If GBS bacteriuria is present in any amount at any time during pregnancy, this is considered a positive result (proxy for heavy colonization), and thus repeat screening is not necessary.

  • If asymptomatic GBS bacteriuria is present at >10^5 CFU/mL, treatment should be considered as you would for any other form of ASB. 

    • If at less than 10^5 CFU, no correlation has been found between treatment of this lower-level bacteriuria and improved maternal or neonatal outcomes; however, it should still be noted that this patient would be considered GBS positive.
      

• Screening may also occur at the time of admission for preterm labor and prelabor premature rupture of membranes (PPROM). 

  • In the case of prematurity, treatment should begin while awaiting screen results.

    • If the screen is positive and preterm labor resolves, the colonization should be considered positive for the remainder of the pregnancy.

    • If the screen is negative, re-screening should be performed after 5 weeks. 

• The gold standard for screening is obtaining a vaginal-rectal culture. 

  • Recently, nucleic acid amplification tests (NAAT) have also demonstrated promise in obtaining accurate, quick results.

    • Most accurate tests that perform similar to culture do require some culture time prior to the NAAT test performance; results generally aren’t available before 18-24 hours after screening occurs. 

      • NAAT tests that offer results in a shorter time period often have lower accuracy.

    • NAAT tests also do not have the ability to test antibiotic resistance, which is important in the case of a patient with known penicillin allergy.

      • If your patient has known penicillin allergy, the laboratory should be alerted so sensitivity testing can be performed.

  • Given this delay and with someone moving quickly in labor or preterm labor with no known GBS status, risk factor-based screening may also be employed to decide if treatment should be pursued in the absence of a screening result. 

    • If any of the risk factors are present, treatment should be pursued:

      • Prematurity or PPROM (< 36 weeks 6 days)

      • History of a prior newborn affected by GBS disease

      • Amniotic membrane rupture > 18 hours duration

      • Presence of intrapartum fever > 100.4F (38 C)

      • If known GBS positive result in a previous pregnancy (may engage in shared decision making in this clinical scenario).
        

Intrapartum Antibiotic Treatment 

• The gold standard for the treatment of GBS colonization intrapartum to reduce risk to neonates for early-onset disease is penicillin G. 

  • Dosed at a loading dose of 5 million units loading, then 2.5-3 million units IV every 4 hours until delivery.

  • Ampicillin is an acceptable alternative, with a loading dose of 2g IV followed by 1g IV every 4 hours. 

    • PCN is preferred as it has a narrower, more targeted spectrum of activity and lower likelihood of inducing resistance in other organisms.

  • For this reason, identification and history of penicillin allergy is super important to flush out in prenatal care! 

    • 80-90% of persons with reported PCN allergy are not truly allergic. 

      • Pruritic rash, urticaria (hives), immediate flushing, angioedema, respiratory distress, or anaphylaxis after PCN or cephalosporin administration is considered a high risk for true allergy.

      • Even with high risk persons, if PCN allergy testing has not been performed, it is recommended to do this — even in pregnancy!
        

  • When PCN allergy testing has not been performed, the allergy should be classified as “low” versus “high risk,” based on the symptoms just described.

    • If “low risk,” first generation cephalosporins such as cefazolin are recommended. 

      • Cefazolin has very low cross reactivity with penicillin for a 1st gen cephalosporin, and GBS remains highly susceptible to it. 

      • Dosed at 2g IV load, followed by 1g IV q8h until delivery.

    • If “high risk,” or an unknown risk with no allergy testing, susceptibility testing should be performed by the laboratory with screening.

      • Options for therapy will include clindamycin or vancomycin.

        • Clindamycin should only be utilized if culture results have shown susceptibilit.

          • Resistance to clindamycin in GBS is approximately 20%. 

          • Dosing: 900mg q8h until delivery 

        • Vancomycin has good activity against GBS.

          • High risk in creating resistant organisms (i.e., VRE) with widespread use, and thus every effort should be made to rule out penicillin allergy before its use.

          • Dosing: 20mg/kg IV q8h, with maximum of 2g per single dose.
            

• How long does it take the antibiotics to work?

  • All antibiotics used for GBS prophylaxis are time-dependent with respect to their ability to lower microbial load.

    • Studies done with PCN or ampicillin prophylaxis demonstrate that 4 or more hours pf prophylaxis is preferable, though 2 hours has been shown to reduce GBS count and decrease neonatal sepsis. 

    • That said, obstetric intervention should not be delayed solely to provide 4 hours of antibiotic administration., when it is indicated.

      • Examples of such interventions that should not otherwise be delayed include oxytocin administration, AROM, or cesarean.

That said, if interventions are not immediately indicated, the benefits of increased antibiotic exposure to reduce GBS exposure should be considered.

Bacteruria, UTI, and Pyelonephritis

Today, we’re going to review all the iterations of urine culture abnormalities in pregnancy. We screen urine cultures in the first trimester and many times again later on in pregnancy, and urinary symptoms are a common complaint.

Asymptomatic bacteriuria is when high levels of bacteria are in urine without associated symptoms. This occurs in 2-7% of pregnant women and typically occurs early in pregnancy.

Urinary tract infections can be broken down into two sub-categories:

1. Lower UTI, or acute cystitis is basically an infection of the bladder, with symptoms of dysuria, urinary frequency, and urgency. They occur in 1-2% of pregnant women.

2. Upper UTI, or acute pyelonephritis may have symptoms of simple cystitis, but include systemic symptoms of infection: flank pain, fevers, chills, nausea/vomiting and costovertebral angle (CVA) tenderness. They occur in 0.5-2% of pregnant women, and more commonly in the 2nd and 3rd trimesters.

Non pregnant women can experience asymptomatic bacteriuria as well as pregnant women. In the non pregnant patient, ASB can be quite prevalent, particularly as we age — over 20% in patients >80 years old. Multiple studies have shown that treatment of asymptomatic bacteriuria in the general, nonpregnant population does not reduce frequency of symptomatic infection or prevent adverse outcomes. Importantly, adhering to this principle helps with antibiotic stewardship.

Pregnant women, however, are different story. As many as 20-35% of pregnant women with asymptomatic bacteriuria will develop symptomatic cystitis or pyelonephritis if untreated, and risk is reduced by 70-80% with treatment. Asymptomatic bacteriuria is not only associated with pyelo, but also associated with adverse pregnancy outcomes, like preterm birth and low birth weight infants. Thus, versus other populations, ASB treatment is imperative in pregnancy.

The most common organisms implicated in these urinary infections include: 

• E. coli - about 70% 

• Klebsiella  - about 3% 

• Enterobacter - about 2% 

• Gram positive organisms (like GBS) = 10% 

Diagnosis and Screening Recommendations for ASB, Cystitis, and Pyelonephritis:

• Asymptomatic bacteriuria 

  1. Finding high-level bacterial growth on urine culture without symptoms consistent with a UTI.

  2. Recommendation per Infectious Disease Society of America to screen all pregnant women for asymptomatic bacteriuria at least once in early pregnancy (usually 12-16 weeks).

  3. Diagnostic criteria:

     1. Isolation of same bacterial strain greater than or equal to 10^5 colony-forming units/mL in two consecutive voided urine samples, or

     2. A single catheterized specimen with one bacterial species isolated in >/= 10^2 cfu/mL 

• Acute Cystitis 

  1. Symptoms as described above (dysuria, etc) with pyuria seen on urinalysis.

  2. Should be confirmed with urine culture, but with typical symptoms and pyuria, should start treating without the culture coming back.

  3. Cystitis should NOT involve systemic symptoms.

• Pyelonephritis 

  1. Can have all of the above (though dysuria may not always be present).

  2. Fevers, chills, flank pain, nausea/vomiting, CVA tenderness.

  3. Pregnant women can become VERY sick 

     1. Estimated that as many as 20% of pregnant women with pyelonephritis develop complications like septic shock syndrome or variants like ARDS.

     2. One study of 32,282 pregnant women in the general obstetric population with pyelo → 23% had anemia, 17% had bacteremia, 7% had respiratory insufficiency, and 2% had renal dysfunction.

  4. Diagnostic evaluation can include:

     1. Urinalysis, urine culture.

     2. CBC

     3. Possibly blood cultures and lactic acid if patient presents with sepsis.

     4. Imaging not routine, but in patients who are severely ill or who have symptoms of renal colic, diabetes, prior urologic surgery, immunosuppression, urosepsis, or repeated pyelo, imaging can help identify other complicating factors, ie. infected stone, renal abscess.

     5. Can consider CT, but ultrasound preferred due to decreased radiation exposure in pregnant women.

Treatment 

• Asymptomatic bacteriuria 

  1. Basic principle is to treat with antibiotics tailored to culture results and then follow up cultures to confirm sterilization of the urine.

  2. Possible antibiotics to consider include beta-lactams, nitrofurantoin, or fosfomycin.

  1. A short course is usually effective in eradicating asymptomatic bacteriuria,  although a single-dose regimens may not be as effective as slightly longer regimens. However, optimal duration of therapy is uncertain.

     1. The only exception is fosfomycin - a single dose can successfully treat bacteriuria.

  1. Follow up 

     1. Up to 30% of women fail to clear asymptomatic bacteriuria after short course therapy, so repeat culture is recommended about a week after finishing antibiotics.

     2. However, there isn’t a lot of data about if we should repeat another culture later on for repeat screening after treatment, or if this is even necessary.

     3. Similarly, not a lot of data about treating again if repeat culture is positive and for how long, though general consensus is to treat.

• Acute cystitis 

  1. Treatment is usually empiric because it’s hard to make someone wait until cultures are back.

  2. Same antibiotic treatment options as for asymptomatic bacteriuria.

  3. Again, treatment time is uncertain, but usually 3-7 day course as long as there are no symptoms/signs of pyelo (except fosfomycin, which is single-dose regimen).

  4. Follow-up repeat culture 7 days after antibiotic completion, as with ASB.

  5. If a woman has 2 or more episodes of recurrent cystitis in pregnancy, it is reasonable to start antibiotic prophylaxis:

     1. Cephalexin 250-500mg qHS or nitrofurantoin 50-100mg qHS depending on susceptibility of organisms on previous cultures.

• Pyelonephritis 

  1. Pregnant people need to be admitted because they are WAY more likely to get super sick compared to nonpregnant women.

  2. Parenteral antibiotics initially, then converted to oral antibiotics when woman has been afebrile for 24-48 hours.

  3. Empiric antibiotics:

     1. Broad spectrum beta-lactams - ie. ceftriaxone 

     2. If someone has ESBL (extended spectrum beta-lactamase) bacteria, can consider a carbapenem.

     3. Avoid fluoroquinolones and aminoglycosides in pregnancy.

  4. Oral antibiotics:

     1. Should usually be beta-lactams, or if second trimester, can consider trimethoprim-sulfamethoxazole (Bactrim).

     2. Do not use nitrofurantoin or fosfomycin because they do not achieve adequate levels in the kidney.

  5. Suppression/Prophylaxis:

     1. Should consider preventative therapy for the duration of pregnancy because recurrent pyelo during pregnancy occurs in 6-8% of women.

     2. Some practices continue antibiotic prophylaxis for six weeks postpartum, but the data is unclear to the benefit of this.

Endometrial Cancer

Today on the podcast we welcome Dr. Lindsey Beffa, clinical associate professor in the Division of Gynecologic Oncology at Women and Infants Hospital and the Warren Alpert Medical School at Brown University.

Endometrial cancer (or cancer of the endometrial lining) represents approximately 90% of uterine cancers overall. It’s the 4th most common cancer among US women and the most common GYN malignancy in the US. It has been increasing in incidence and has a peak incidence in women aged 60-70.

Type I Endometrial Cancer

These are low grade (1 or 2) cancers that generally have endometrioid histology. They overall have a favorable prognosis. When you think of endometrial cancer, this is probably what you imagine. They are estrogen-driven, have precursor lesions (EIN), and often present at an early stage.

Risk factors for type I cancers can be summarized with the type of tumor. These are estrogen-driven tumors. Thus, exogenous estrogen, or excess endogenous estrogen states, such as PCOS, chronic anovulatory states, obesity, diabetes mellitus, and rarely, granulosa cell tumors of the ovary that are estrogen secreting.

There are also genetic risk factors, including the Lynch syndrome, which is an autosomal dominant disorder of mismatch repair proteins. These are known as MLH 1, MSH 2, MSH 6, and PMS 2. Additionally, the Cowden syndrome is an autosomal dominant mutation of PTEN.

Type II Endometrial Cancer

On the other hand, these are high grade endometrioid or other aggressive histologies, such as clear cell or carcinosarcoma. These are fortunately much rarer but also have a less favorable prognosis. The risk factors for these are less clear, but do tend to appear in older, thinner patients; these tumors are additionally not estrogen-sensitive.

Presentation and Diagnosis

The most common presentation (75-90%) of endometrial cancer is abnormal uterine bleeding or postmenopausal bleeding. Additionally, abnormal Pap smears (AGC) or a thickened endometrial lining on ultrasound (>4mm postmenopausal) may prompt evaluation.

An endometrial biopsy is the simplest and very reliable way to achieve diagnosis, as long as >50% of the cavity is involved. If symptoms persist despite a negative biopsy, hysteroscopy and dilation and curettage should be performed.

Staging of Endometrial Cancer

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