The 46-year-old plaintiff first presented to her primary care physician (PCP) on April 23, 2013, for a cough that had lasted 3 days. She reported incontinence, dribbling, and an inability to hold her urine after heavy menstruation. 

She also reported abdominal pain. Her PCP urged her to go to an ob/gyn for a work-up, with the differential possibly being endometriosis versus ruptured cyst. The impression was that the patient had recurrent stress urinary incontinence but the ob/gyn was concerned that it could turn into physical incontinence, given the woman’s gynecologic issues and age. 

 to send her for an ultrasound (U/S) of the pelvis, which was performed on May 1, 2013. The U/S revealed a very large uterine fibroid (7x7 cm).

On May 5, 2013, the plaintiff presented to nonparty hospital with complaints of lower abdominal pain and vaginal bleeding that had lasted for 2 days. She reported bright red blood with multiple clots that increased throughout the day and her diagnosis with a 7x7-cm uterine fibroid by her PCP but said she did not have an ob/gyn. 

On exam, she reported that she had a history of heavy menses secondary to the fibroid. Transvaginal (TVUS) confirmed multiple fibroids, the largest being 8.7 cm, and an enlarged uterus (8.5 x 12.2 cm). The impression was leiomyoma of the uterus. The woman was sent home in stable condition that night because she felt better, with a directive to follow up with an ob/gyn that week.

The plaintiff saw her PCP on July 23, 2013, for the start of preoperative medical clearance for a hysterectomy. She was cleared for surgery. 

, she reported incontinence and dribbling and that she could not hold her urine after menstruating. The assessment was vaginal bleeding, with abdominal pain secondary to the abdominal fibroids.

On or about August 26, 2013, the plaintiff presented to Defendant Hospital A for a laparoscopic hysterectomy by 

, secondary to bleeding fibroids. The plaintiff’s history included a cesarean delivery, open cholecystectomy, bilateral breast reduction, and treatment for a miscarriage. During the hysterectomy, she sustained a bladder injury. 

An intraoperative cystoscopy confirmed a 2-cm tear near the vaginal cuff. Two double-J ureteral stents were placed by Defendant urologist, who recommended that she be transferred to Defendant Hospital B. The woman’s bladder was not repaired intraoperatively; instead she was transferred after Defendant ob/gyn A spoke with 

On August 27 at 11:40 p.m., the plaintiff was transferred from Defendant Hospital A to Defendant Hospital B with an admitting diagnosis of injury to the bladder and urethra and open wound. The admitting physician was Defendant ob/gyn B, who attempted conservative management; for 48 hours, the patient was stable without any issues. 

On August 29, a decision was made to perform a cystoscopy to further evaluate the bladder injury. Defendant ob/gyn B’s operative report indicated that informed consent was obtained. A cystogram was performed using 200 mL of fluid without obvious contrast extravasation. The plaintiff’s Foley catheter was removed and the two previously placed double-J stents were identified and noted to be in good position. 

A cystoscopy then was performed, and at the level of the trigone in the posterior portion of the bladder, an area consistent with the intraoperative injury was found. The same was noted to have granulating tissue but no obvious tear or extraperitoneal leak was seen. 

, Defendant ob/gyn B decided “to not proceed with a formal repair” and instead, decided to continue to conservatively manage the plaintiff. 

The Foley catheter was replaced and the report concluded with a comment that the patient was to follow up in the office within the next 2 weeks for a repeat cystoscopy and removal of the double-J stents that had been placed. In the Postoperative Acute Care Unit, she received 2 units of blood. Discharge was on August 30.

A day later, the plaintiff was readmitted to Defendant Hospital B complaining of no urine output from the Foley catheter for 12 hours, lower abdominal pain, and difficulty breathing. The catheter was changed in the ER without relief of symptoms, so the plaintiff was admitted. 

On U/S, her bladder was small with fluid around it. A computed tomography (CT) scan showed that the Foley catheter was out of the bladder and in the peritoneum. The catheter was repositioned and conservative management was attempted. 

 the patient had desaturations in oxygen to the 80s and was found to have bilateral pulmonary embolisms (PEs). Dopplers came back negative for deep vein thrombosis. 

Because of the woman’s history of PEs, a removable inferior vena cava filter was placed by vascular surgery. An intravenous (IV) Heparin drip also was started. The plan was to stabilize the patient medically and then take her to the operating room (OR) for an open bladder repair.

On September 3, repair surgery was undertaken by Defendant ob/gyn B. The procedure was described as an open complex cystorrhaphy with a repair of bladder injury and placement of a suprapubic tube. Per the OR report, “due to the location of the injury at the level of the trigone, a decision was made to perform an intravesical repair.” 

As a result, a cystotomy was performed in the dome of the bladder. The injury was noted to be at the trigone between both ureteral orifices. A suprapubic catheter was placed and the plan was to monitor the patient, transition her back to a heparin drip and eventually warfarin, with the hopes of discharging her a few days thereafter. Postoperatively, the plaintiff had bouts of tachycardia. 

She remained on a heparin drip. Transthoracic echocardiography showed evidence of some right heart strain. Heparin was changed to enoxaparin sodium. The suprapubic tube eventually drained clear urine and the patient was discharged on September 6 with the suprapubic tube to the Foley catheter and a three-way, 24-French Foley to leg bag.

On September 13, the plaintiff followed up with Defendant ob/gyn B at his office. On exam, the doctor found her to be doing well with a suprapubic tube and the Foley catheter in place. He planned to keep the catheters in for the next 2 weeks and the note indicated she would be following up with her PCP regarding management of her warfarin level. 

Defendant ob/gyn B planned to perform a cystogram at the next visit and perhaps remove the Foley catheter but he intended to leave the suprapubic tube in for another few weeks. 

The plaintiff went to her PCP on September 24 for complaints of a urinary tract infection (UTI) with abrupt onset. 

Her symptoms concluded voiding scant amounts while urinating and the last occurrence was a few weeks before, and burning pain. Diagnosis was acute cystitis, UTI and she was started on sulfamethoxazole/trimethoprim. 

A note written by Defendant ob/gyn B about the patienht’s return visit on September 27, repeated the history and said that the patient is “doing well with no complaints other than minimal pain from the Foley.” 

A cystogram was performed and no evidence of extravasation was noted. The Foley catheter was removed but the suprapubic tube was left in place. When plaintiff returned to Defendant ob/gyn B’s office a week later, a cystogram showed no evidence of extravasation and the suprapubic tube was removed. The bilateral stents were left in place and the patient was directed to return in 3 weeks for their removal. In addition, she was placed on more antibiotics as a result of a complaint of dysuria. 

On October 8, the plaintiff was seen by her PCP for a complaint of 4-day lumbar radicular syndrome, pain 4/10. She also reported frequent urination, incontinence, dribbling, and painful urination. She reported that the pain started after the catheter was removed. 

 that she return to the urologist for catheter placement versus further evaluation. On October 10, the plaintiff was transferred to Defendant Hospital B with complaints of nausea, vomiting, and flank pain and a diagnosis of pyelonephritis. A Foley catheter was placed and she was started on IV antibiotics. A CT scan showed bilateral moderate hydronephrosis with left perinephric stranding.

On October 12, Defendant ob/gyn B brought the patient back to the OR for a cystoscopy, during which he removed the bilateral stents. A cystogram was performed and again no contrast extravasation was seen. 

Thereafter, a cystoscopy was performed. The report noted that the “entire mucosa was extensively observed” and in the area of the previous repair, debris and granulation tissue were noted. Both ureteral orifices were easily identified, and both the right and left ureteral stents were noted to be calcified with debris. 

It was felt that the stents might be a possible source for the UTI, so they were removed. The plan was to monitor the plaintiff over the next 12 hours to see if there was any improvement. The Foley catheter was removed and she passed a trial of void so she was discharged on October 13. 

An appointment with Defendant ob/gyn B was made for October 25 butthen rescheduled to November 22. 

, the plaintiff was 1 month post-removal of the stents, appeared to be doing well save for the complaint of increasing nocturia every 1 1/2 to 2 hours during the evenings as well as frequency throughout the day. Defendant ob/gyn B performed a physical exam and found nothing out of the ordinary except for some costovertebral angle tenderness. 

Under “Impression” he called the plaintiff a woman with “significant lower urinary tract symptoms” and indicated that while a urine dipstick showed some white blood cells, there was no obvious UTI. A culture was sent and the patient was placed on solifenacin to see if this would improve her nocturia. She was directed to return in 4 weeks for a repeat uroflow and postvoid residual (PVR) but she did not.

On August 21, 2014, the plaintiff saw her PCP with complaints of frequent urination as well as vaginal bleeding between periods or after sex. She also reported that this began after surgery. She reported being treated with solifenacin with good results. 

She was given another prescription for the drug, 10 mg daily. The plaintiff returned to Defendant ob/gyn B on September 3 (10 months after her last visit) for the final time. The purpose of the visit was for a new onset of urinary incontinence. In his note, Defendant ob/gyn B recited the woman’s history of the complex bladder injury and repair, the pulmonary embolus. 

He also mentioned her “bleeding issues” (hypercoagulability), for which she was under the care of a hematologist. The plaintiff reported that she had been feeling well over the preceding 6 months and it was only 2 weeks prior when she started to notice the urinary incontinence. 

She denied any other urinary issues but did report that she was having some pelvic pain. A urine dipstick done in the office was within normal limits and the patient was scheduled for further evaluation with flexible cystoscopy. She did not return.

On October 30, the woman saw her PCP with complaints of bladder discomfort and UTI symptoms. 

She did not feel her complaints were socially unacceptable, but had leaking when she laughed, sneezed, and coughed. She also reported urinary frequency but no pain with incontinence. The diagnosis was UTI, acute cystitis. 

The plaintiff went back to her primary doctor on February 27, 2016. His note reported that she presented for urinary incontinence and indicated that the woman was status-post multiple bladder procedures with new incontinence. 

 to reorder medication for incontinence and that she should follow up with urology and urological studies. On July 18, the woman was seen by her primary care physician for lesions found on her rib cage via a CT chest. She had no complaints of dysuria, frequency, urgency, nocturia, hematuria or incontinence. 

 The PCP referred the plaintiff for a bone scan to rule out metastatic disease, which was performed on July 28. On July 29, The PCP notified the woman that the results were normal.

The plaintiff argued that the defendants delayed diagnosing a fibroid uterus, menorrhagia, and anemia and delayed treating fibroids and performing a hysterectomy. 

The plaintiff’s side further alleged that the defendants negligently performed a laparoscopic hysterectomy, delayed timely treatment of complex bladder injury, failed to diagnose said injury intraoperatively, failed to diagnose and treat or prevent bladder damage, delayed surgery, failed to have appropriate surgical specialists available, failed to assess risk factors for a PE, caused a PE, and failed to properly place a Foley catheter.

They contended that the bladder injury was diagnosed by defendants just after the hysterectomy was completed and during the cystoscopy of August 29, 2013. They argued that good and accepted medical practice required immediate repair of the hole in the plaintiff’s bladder. 

They contended that the delay placed the plaintiff at risk for further complications including the worsening of her condition, worsening of the hole, reopening of the hole, incomplete closure, additional procedures, infection, increased risk of urinary incontinence and/or frequency and pain.

Our urology expert was able to defend Defendant ob/gyn B. The plaintiff’s injury, the cystotomy, occurred during the hysterectomy on August 26, 2013. He confirmed that any delay in performing surgery to repair the cystotomy did not cause further injury to the woman. Moreover, incontinence—her alleged injury—pre-existed the surgery. 

, any complaint that she was now at an increased risk because she was treated conservatively made no medical sense. In fact, she would be at an increased risk if she had surgery. Furthermore the repair itself was undertaken in a standard fashion and expertly performed.

The gynecology expert advised that the approximate 2-day delay in repairing the patient’s bladder injury made no difference. On August 29, Defendant ob/gyn B performed a cystogram and a cystoscopy to assess the extent of the plaintiff’s injury. 

The cystogram showed no evidence of leakage and the cystoscopy confirmed the finding. While some healing tissue was found, no perforation was found and there was no extravasation of dye. Defendant ob/gyn B directly visualized the area, and it appeared to be healing. 

Given the complexity of the repair that would have been necessary due to the injury’s location, Defendant ob/gyn B decided to treat the plaintiff conservatively. Our expert opined that the prudent course was to let her continue to heal as she appeared to be healing on her own, and not subject her to a further complicated surgery. 

, although there is variation from patient to patient, but if a patient does not have a leak and is healing, treatment is conservative. Waiting for evidence of a leak for 2 days did not cause or contribute to subsequent urinary issues.

At Defendant ob/gyn B’s deposition, it became evident that the plaintiff really had no claims against him and was hoping, by naming him as a defendant and taking his deposition, that he would implicate the co-defendants. 

To the extent that the plaintiff found it necessary to have him testify that the injury to the bladder occurred at the prior institution, he accomplished his purpose. To the extent he had hoped that ob/gyn B would offer comment that the injury to the bladder was caused by negligence, he was unsuccessful. 

, he testified that he had no knowledge of how the injury occurred other than learning that it happened during the surgery undertaken at the codefendant Hospital.

This case was interesting because we essentially knew from the time of our client’s deposition forward that the plaintiff was not focusing on his actions or inactions and that so long as we maintained our defense posture, we were likely to extract him from the case if and when our codefendant settled. 

We were certainly prepared to defend his care at trial if it came to that. 

 to have the case fully worked up and evaluated to ensure you are in your best position to defend whatever allegations–credible or otherwise–are advanced. 

Ob/gyn B was prepared to not only defend his care but also not to offer opposing counsel any testimony that could implicate his codefendants and further the plaintiff’s somewhat specious claims.

, coordinating defenses should be the primary objective for the trial.

The importance of intervention: When was this baby in trouble? 

 the question of fetal well-being as demonstrated on the FHR tracing is significant. 

Articles

Allegations in this complex case include negligence in performing laparoscopic hysterectomy and delaying treatment of bladder injury.

Did delay in bladder repair cause urologic issues?

Vulvovaginitis may be infectious or non-infectious in etiology, and it is often underdiagnosed or misdiagnosed. Chronic or recurrent vulvovaginitis is frustrating to patients and a burden to the health care system. 

The three types of infectious vulvovaginitis most commonly seen in reproductive-age women are bacterial vaginosis (BV), vulvovaginal candidiasis (VVC) and trichomoniasis. 

Other differential diagnoses to consider include herpes simplex infection, allergic reaction to irritants and non-infectious vaginitis such as lichen planus, genitourinary syndrome of menopause (GSM), and desquamative inflammatory vaginitis (DIV). 

Infection and/or inflammation of the vulva and vagina are associated with itching, burning, irritation, dyspareunia, and abnormal and/or malodorous vaginal discharge.

This article focuses on the diagnosis and treatment of recurrent and chronic cases.

All patients who present with complaints suggestive of vulvovaginitis should have a complete history; physical examination of the vulva, vagina and perianal area; saline microscopy (including pH, 10% potassium hydroxide (KOH) whiff test) if available; point-of-care testing if available; and culture and molecular diagnosis testing as needed.

History should include relationship of symptoms to sexual intercourse, menstrual cycle, use of feminine products and practices, over-the-counter medications, and medical and medication history.

On examination, patients with BV may have a malodorous grey, creamy or thin homogeneous discharge whereas patients with VVC may present with evidence of inflammation such as erythema, edema, fissures, or excoriations in moderate to severe cases, while patients with trichomoniasis may exhibit signs of inflammation like erythema.

Patients with GSM may show signs of vulvovaginal atrophy while patients with DIV may show signs of inflammation (Figures 1 to 4). Vaginal samples should be obtained from the posterior fornix in BV and lateral vaginal wall in VVC and microscopy performed. (Table 1).

Office based testing of the vaginal discharge using pH test, 10% KOH and saline microscopy is preferred if available. This approach may provide immediate diagnosis, and treatment can be initiated. 

The United States Food and Drug Administration (FDA)-approved commercially available tests (point-of-care test or molecular diagnostics) can be used as alternatives.

BV, the most common cause of abnormal vaginal discharge in reproductive-age women is characterized by abnormal vaginal flora, decreased or absent lactobacilli, and an increased number of anaerobes and facultative anaerobes. 

It is a dysbiosis, and some of the associatedbacteria include 

BV is associated with increased risk of pelvic inflammatory disease; increased risk of acquisition and transmission of sexually transmitted infections (STIs); adverse obstetric and gynecologic outcomes such as preterm labor, preterm birth, and chorioamnionitis; and vaginal cuff cellulitis post-hysterectomy. 

Patients may describe the malodorous discharge as “rotten egg or fishy” and worse after sexual intercourse or a menstrual period. The diagnosis is usually clinical (Table 1). 

Presence of three of four Amsel criteria is needed to make the diagnosis

Gram stain with Nugent score is the gold/reference standard used in research settings, while Amsel criteria are used in clinical setting. 

Although microscopy is preferred and cost effective, it may not be available in all clinical settings and data evaluating US Food and Drug Administration (FDA)-approved commercially available tests have acceptable performance against the reference standards.

FDA-approved commercially available tests can be used to diagnose BV but should be interpreted alongside patient history and examination.

Recurrent bacterial vaginosis (RBV) is defined as three or more episodes in 12 months.6,12 Recurrence rate is high, and often involves frequent telephone calls and visits to the clinic; multiple treatments are prescribed in the absence of curative therapy.

Bradshaw et al. reported recurrence rates of 58% over a 12-month period in women treated with oral metronidazole for 7 days. In their study, recurrence was associated with prior history of BV, lack of hormonal contraceptive use, having the same sex partner throughout the study duration, and having female sex partners.

Other factors that have been associated with recurrence include douching, frequent sexual intercourse without condoms, and failure to reestablish a 

-predominant vaginal flora. It has also been suggested that formation of a vaginal biofilm in BV could be one of the factors in RBV.

Women with RBV should be appropriately treated based on the Centers for Disease Control and Prevention (CDC) recommended conventional therapy of nitroimidazole or clindamycin administered orally or vaginal and offered additional suppressive therapy with 0.75% metronidazole intravaginal gel twice weekly for 4 months.

In a multicenter study, Sobel et al randomized patients with RBV to twice- weekly intravaginal metronidazole gel or placebo for 16 weeks after initial treatment. He documented that during 28-week follow-up, recurrence was less in the suppressive therapy group. 

Recurrence occurred in 51% of treated women compared with 75% of women receiving placebo.16 Patients should be educated about the risk of possible yeast infection during the suppressive therapy phase.

Another option for RBV is a combination of oral nitroimidazole with intravaginal boric acid as the induction phase, followed by suppression therapy. Reichman et al treated women who met criteria with either tinidazole or metronidazole 500 mg orally twice daily for 7 days followed by intravaginal boric acid 600 mg at bedtime for 21 days as the induction phase.

Asymptomatic patients then proceeded to the maintenance phase of intravaginal metronidazole gel twice weekly. In this study, the cure rate was 92% at 7 weeks, 88% at 12 weeks, and 50% at 36 weeks. We have modified the suppression therapy in our clinical practice, and documented success with 0.75% metronidazole intravaginal gel once a week for 4 months.

VVC is the second most common cause of vulvovaginitis. Although

 is the most common cause of VVC (85%-90%), other non- albicans candida (NAC) (

) could be colonizers or pathogenic.12,17

Diagnosis should not be based on clinical findings alone due to lack of specificity; symptoms of external dysuria, itching, and burning are not always sufficient to make a diagnosis.

Clinical features may include curd-like vaginal discharge.

On examination, patients may have erythema, edema, fissures, or excoriations. Microscopy with or without addition of 10% KOH may reveal fungal elements. Fungal culture is helpful in patients with clinical features suggestive of VVC but who have a negative saline microscopy.

 It is also helpful in patients who have failed therapy or those with suspected resistance to commonly used anti-fungals.

 FDA-approved molecular testing is commercially available for providers who do not have access to microscopy. 

Some molecular testing has rapid turnover, but may not give speciation and sensitivities. Although fungal culture results may take a week to be returned, they may be needed to plan treatment.

RVVC isdefined as at least three symptomatic episodes in 12 months.19 Risk of recurrence is increased in patients who frequently take antibiotics, are chronic users of corticosteroids, on prolonged immunosuppressant (e.g. transplant patients) or immunosuppressed patients (uncontrolled HIV/AIDS), have uncontrolled or poorly controlled diabetes, or have azole-resistant or non- 

Patients with RVVC would benefit from maintenance therapy after the induction treatment phase has been successfully completed.

 should have sensitivity testing performed and be treated based on the results. 

Sobel et al and Marchaim et al have documented success with compounded medications in patients with azole resistance and those who have failed multiple doses of first-line medications.

In patients with azole-resistant VVC, treatment options include intravaginal boric acid 600 mg daily for 14-21 days, intravaginal 15.5% flucytosine vaginal cream (5 g) daily for 14 days, and intravaginal amphotericin B 50-mg vaginal suppository daily for 14 days. 

It is important to consider other differential diagnosis of vulvovaginal itch. All that itches is not yeast and patients with persistent itching despite treatment should be referred to a specialist. 

Examples of vaginal specialist-recommended regimens for RVVC include:

Fluconazole 150 mg orally every 72 hours x 3 doses; followed by fluconazole orally 150 mg weekly x 6 months or miconazole 1200 mg vaginally weekly x 6 months (for patients who prefer vaginal route for maintenance therapy).

Itraconazole 200 mg orally twice daily x 3 days followed by itraconazole orally, 100-200 mg daily for 6 months.

Trichomoniasis is the most common non-viral STI in women worldwide.

 It is associated with reproductive morbidity and increased risk of HIV acquisition and transmission. Patients may be asymptomatic or present with abnormal yellow –green vaginal discharge, inflammatory symptoms such as itching, burning, and dyspareunia. 

On examination, there may be erythema of the vulva, vagina and “strawberry cervix.” Microscopy, if available, may reveal motile trichomonads; other diagnostic modalities include point-of-care testing or FDA-approved commercially available molecular testing. 

Nucleic acid amplification testing (NAAT) is recommended for diagnosis of trichomoniasis.

Treatment of the patient and her sex partner(s) is recommended.

 Nitroimidazole is the drug of choice. Treatment is usually a single 2-g dose of metronidazole or tinidazole.

Kissinger et al, in a randomized trial of single-dose 2-g metronidazole versus 7 days of metronidazole, showed that the 7-day oral-dose metronidazole is the preferred treatment for trichomoniasis treatment in non-HIV-infected women.

Reinfection is more common than treatment failure, but patients suspected to have failed treatment or who have nitroimidazole resistanceshould be referred to an infectious disease specialist. 

Patients with nitroimidazole allergy should be referred for desensitization. CDC offers resistance testing by request. Health providers can access the CDC website and contact the office in charge for this service.

In women who fail 2 g metronidazole without evidence of reinfection, metronidazole 500 mg orally twice daily x 7 days is recommended. If treatment fails, tinidazole or metronidazole 2 g orally for 5 days is then recommended. 

If persistent infection is documented despite the previous therapy without evidence of reinfection, there are case series and reports documenting success using high-dose tinidazole and compounded paromomycin in management of refractory trichomoniasis, as follows:

Tinidazole 500 mg orally 4 times daily for 1 week OR

Tinidazole 500 mg orally 4 times daily PLUS Tinidazole 500 mg vaginally twice daily x 14 days OR

Tinidazole 1 g orally 3 times daily plus 5 g of compounded 5% intravaginal paromomycin nightly X 14 days.

We have had success in our clinical practice with use of 5 g of 5% compounded paromomycin alone x 14 days in three patients who were allergic to nitroimidazole. 

Of significance, the compounded creams could be irritants to the skin and should be inserted inside the upper and mid third of the vagina at bedtime. 

Patients should apply an emollient as barrier to the vulva, and refrain from all sexual intercourse while using compounded vaginal medications. Compounded medications are also expensive.

A review of chronic/recurrent vulvovaginitis would not be comprehensive without a discussion of the two commonly encountered non-infectious causes: GSM and DIV.

DIV, a diagnosis of exclusion, is a chronic vulvovaginitis that is poorly understood.

 It occurs mostly in perimenopausal and postmenopausal women, and may be associated with low estrogen levels. 

Diagnosis is usually clinical with patients complaining of copious yellow–green discharge. They may describe the discharge as thick, “sticky,” mucoid staining of their underwear. Patients sometimes wear panty liners or sanitary pads due to the volume or discoloration of their undergarments. 

They may complain of itching, pain, burning, and sometimes dyspareunia. On examination, the vulva maybe erythematous, friable and may bleed on contact. 

The vagina may be erythematous and purulent yellow-green discharge noted. Microscopy shows sheets of white blood cells and parabasal cells maybe present if the patient is hypoestrogenic.

At least one symptom (vaginal discharge, dyspareunia, pruritus, pain, irritation or burning)

Leukorrhea +/- parabasal cells on microscopy

Management involves counseling and education about this poorly understood condition. 

Initial treatment is 2% intravaginal clindamycin for 4 to 6 weeks. Patient who fail to respond to vaginal clindamycin may repeat treatment with 10% intravaginal compounded hydrocortisone for the same duration. 

Patient education should include the possibility of failed therapy and relapse. Presence of parabasal cells indicates a hypoestrogenic state and vaginal estrogen twice a week should be included in the regimen. 

Patients who relapse should be referred to a vaginal specialist.

GSM is often seen in postmenopausal patients or hypoestrogenic women such as those who are breastfeeding or who have undergone menopause due to surgery or exposure to chemotherapy or radiation. 

Patients may present with vaginal dryness, pain, itching, thin watery discharge, and dyspareunia.

 On examination, the vagina may be pale, with loss of elasticity. Vaginal pH is elevated in symptomatic patients. 

Microscopy may show some parabasal cells, paucity of normal vaginal epithelial cells, and lack of lactobacilli. 

Management should include evaluation for secondary bacterial and fungal infections and treatment.

First-line management is with vaginal lubricants and moisturizers.

Patients who remain symptomatic and have no contraindications to use of hormones may benefit from systemic or vaginal hormones. In our practice, we usually start with vaginal estrogen in various formulations or vaginal dehydroepiandrosterone before considering systemic formulations.

1. Stockdale CK, Boardman L. Diagnosis and treatment of vulvar dermatoses. 

2. Sobel JD, Reichman O, Misra D, Yoo W. Prognosis and treatment of desquamative inflammatory vaginitis. 

3. Koumans EH, Sternberg M, Bruce C, et al. The prevalence of bacterial vaginosis in the United States, 2001-2004; associations with symptoms, sexual behaviors, and reproductive health. 

4. Anderson MR, Klink K, Cohrssen A. Evaluation of vaginal complaints. 

5. 2015 STD Treatment Guidelines. https://www.cdc.gov/std/tg2015/default.htm. Accessed January 20, 2020.

6. Bradshaw CS, Morton AN, Hocking J, et al. High Recurrence Rates of Bacterial Vaginosis over the Course of 12 Months after Oral Metronidazole Therapy and Factors Associated with Recurrence. 

7. Amsel R, Totten PA, Spiegel CA, Chen KCS, Eschenbach D, Holmes KK. Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations. 

8. Cartwright CP, Lembke BD, Ramachandran K, et al. Development and validation of a semiquantitative, multitarget PCR assay for diagnosis of bacterial vaginosis. 

9. Cartwright CP, Lembke BD, Ramachandran K, et al. Comparison of nucleic acid amplification assays with BD affirm VPIII for diagnosis of vaginitis in symptomatic women. 

Recurrent or chronic vulvovaginitis is frustrating to patients and a burden to the health care system. Here is a guide to addressing it.

Practical approach to recurrent vulvovaginitis

 shows that these laws are not associated with an increased understanding of the clinical implications of breast density.

The study assessed the association of residing in a state with a DBN law and a woman’s awareness and knowledge about breast density through survey responses. The survey also looked at breast cancer anxiety. 

The internet survey was conducted in 2018 with participants in KnowledgePanel®, an online research panel. Participants were English-speaking women between ages 40 and 59 without a personal history of breast cancer who had received at least one screening mammogram (N = 1928; survey completion rate 68.2%). 

The four main measures of the survey were: 1) reported history of increased breast density; 2) knowledge of the increased risk of breast cancer from dense breasts; 3) knowledge of the masking effect of dense breasts on mammography and 4) breast cancer anxiety.

Based on weighted analysis, 41.3% of women reported a history of increased breast density. A much higher proportion of survey participants who lived in states with DBN reported having increased breast density compared with women who reported living in states with no law (43.6% vs 32.7%, 

In multivariable regression, women residing in a DBN state were more likely to report increased breast density (OR 1.70, 95% CI 1.34-2.17), as were older women, women with a high school education or higher, and with public or private insurance (compared with no insurance).

Black and Hispanic women were less likely than white women to report having increased breast density. Only 23.0% of women overall know that increased breast density was associated with a higher risk of breast cancer and 68.0% of women understood that dense breasts decreased the sensitivity of mammography. 

However, the authors found no difference between women from DBN and non-DBN states for these outcomes, or for breast cancer-related anxiety.

Based on their findings, the authors suggest that state DBN laws are not associated with increased understanding of the clinical implications of breast density. 

Furthermore, they found that women with lower education may be less likely to benefit from DBN laws. 

Ultimately, the authors believe that the clinical implications of a dense breast finding are “complex and personalized and require a conversation between a woman and her provider.”

Kyanko KA, Hoag J, Busch SH, et al. Dense breast notification laws, education, and women’s awareness and knowledge of breast density: A nationally representative survey. 

. August 2020. doi:10.1007/s11606-019-05590-7

Currently, 38 states and the District of Columbia have enacted dense breast notification (DBN) laws mandating that mammogram results include language informing women of risks related to dense breasts. 

Breast density laws and patient knowledge

Since the discovery of PARP inhibitors (PARPi) in 2005, there has been rapid clinical development of five different agents (olaparib, rucaparib, niraparib, veliparib, talazoparib), leading to seven indications approved by the US Food and Drug Administration (FDA) across breast and ovarian cancer.

In 2014, olaparib became the first PARPi approved by the FDA for use as treatment of recurrent ovarian cancer, followed by rucaparib in 2016 and niraparib in 2019. 

Over this same time period, the FDA approved all three of these PARPi for a different indication – as maintenance therapy intended to prolong the disease-free interval following chemotherapy. 

Across different drugs and clinical settings, use of PARPi has resulted in a prolonged period without cancer recurrence – or disease-free interval – particularly among patients with 

2 mutations, owing to their mechanism of action.

PARPi are a class of oral targeted therapy whose effect is dependent upon a tumor’s inability to repair its DNA. The PARP1 and PARP2 proteins are instrumental in repairing DNA single-strand breaks, which prevents formation of double-strand breaks at the time of DNA replication. 

PARPi block this repair process and thus dramatically increase the number of double strand breaks. Cells can typically repair these resultant double strand breaks in an error-free fashion using the homologous recombination (HR) pathway, but when the pathway is defective, PARPi result in cell death. 

This homologous recombination deficiency (HRD) is frequently a result of a germline or somatic mutation in a gene involved in the HR pathway, notably 

2, but can also be detected in tumors in the absence of such mutations. 

With germline and somatic testing, patients with genetic mutations or tumors with HRD can be identified as those who may derive significant clinical benefit from PARPi use.

With more than 20 trials of PARPi in ovarian cancer alone, there is a growing body of literature on the common side effects of these drugs and their management, as well as their unique financial challenges. 

Ongoing clinical questions being addressed include how best to predict patient response to PARPi therapy, combat drug resistance, and determine the optimal setting(s) for use in individual patients.

Many of the adverse events (AEs) encountered with use of PARPi are shared across agents. Most patients experience some degree of nausea and fatigue. Serious hematologic side effects can occur with any PARPi, and myelosuppressive effects can be exacerbated when these drugs are combined with other therapies. 

Dose reductions are often necessary in the event of a serious side effect, and if they persist, the drug may need to be discontinued. Of note, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are serious but rare AEs occurring in up to 1% of patients and they have been associated with several different PARPi. 

Embryo-fetal toxicity has been documented in animal studies with exposure to PARPi. These drugs should not be used in pregnant patients, and pregnancy should be avoided for 6 months following last exposure.

Olaparib was the first PARPi to be developed thus is the most extensively studied. The most common AEs with olaparib are fatigue, nausea, and vomiting, which occur in 60% to 75% of patients across studies. 

Serious hematologic AEs can occur in 10% to 20% of patients (anemia, neutropenia), and rarely patients experience severe fatigue (4%).

 Olaparib in combination with vascular endothelial growth factor (VEGF) inhibitors such as bevacizumab or cediranib can increase the rate of hypertension, fatigue, diarrhea, abdominal pain, and small bowel obstruction.

The AE profile of rucaparib is similar to that of olaparib, with nausea and fatigue occurring in more than 70% of patients, and severe anemia in about one-fifth of patients. 

An isolated transaminitis is a unique AE with rucaparib use, resulting in mild to moderate elevations of alanine transaminase (ALT) and aspartate transaminase (AST) noted in one-third of patients and more serious elevations in approximately 10% of patients. Rash and photosensitivity were other specific yet uncommon mild AEs.

Myelosuppression is more frequent among patients taking niraparib, with significantly more thrombocytopenia in particular compared to other PARPi (up to 60% of patients). Notable serious AEs with niraparib are also hematologic, with significant anemia being the most common (25%-30%), followed by thrombocytopenia (20%-30%) and neutropenia (10%-20%). 

Mild nausea and fatigue are seen at rates similar to those in olaparib and rucaparib, and mild constipation can be encountered as well.

Although not FDA-approved for use in the United States, veliparib has shown some efficacy as both monotherapy and in combination with other cancer-directed treatments in numerous trials. Gastrointestinal (GI) AEs were similar to other PARPi, and severe AEs were relatively uncommon.

Talazoparib is only FDA-approved for treatment in patients with advanced breast cancer who have germline BRCA mutations (Table 1). Although fatigue and GI AEs are milder with talazoparib relative to other PARPi, severe hematologic AEs occur in up to 55% of patients.

All PARPi require close monitoring with weekly complete blood count with differential for the first month of therapy, which can be done once a month thereafter, if the patient is stable. A complete metabolic panel should be obtained at baseline and periodically thereafter. 

Across different drugs and clinical settings, use of PARPi has resulted in a prolonged period without cancer recurrence.

Vol 65 No 04

Did delay in bladder repair cause urologic issues?

Practical approach to recurrent vulvovaginitis

Breast density laws and patient knowledge

PARP inhibitors: Choosing what to use in epithelial ovarian cancer

Can a healthier diet reduce menopause symptoms?