Minodronic acid suppresses gonadotropin-releasing hormone agonist-induced bone remodeling biomarkers: a retrospective pilot study.

BACKGROUND: Estrogen deprivation therapy for myoma/adenomyosis decreases bone mineral density and can only be applied in the short term, as temporizing measures in the premenopausal woman. OBJECTIVE: To examine the effects of bisphosphonate minodronic acid on markers of bone turnover over a 6-month period in women receiving gonadotropin-releasing hormone agonist (GnRHa). METHODS: We retrospectively analyzed the medical records of 19 premenopausal patients with myoma/adenomyosis, who received GnRHa (leuprolide acetate, 1.88 mg/month or buserelin acetate, 900 µg/day) for 6 months from January 2014 to December 2014. Eight patients concomitantly received minodronic acid 50 mg every month during GnRHa therapy, and 11 treated with GnRHa alone. To compare these data in a case-controlled study, we analyzed an age-matched group of seven (premature or natural) menopausal women treated with minodronic acid. The primary outcome was percent changes in bone turnover markers in urine at 6 months. RESULTS: In menopausal women group, minodronic acid (50 mg once-monthly) for 6 months decreased urinary deoxypyridinoline (DPD) and cross-linked N-telopeptides of type 1 collagen (NTX). Women receiving a GnRHa had a significant increase in urinary DPD and TNX at 6 months while minodronic acid during GnRHa therapy improved urinary levels of DPD and NTX to near baseline. CONCLUSION: Minodronic acid treatment appears to be promising in women with secondary bone loss receiving GnRHa treatment.

New generation nonhormonal management for hot flashes.

Hot flashes are very common in women in menopause and can have a detrimental effect on quality of life. Hormone therapy (estrogen with or without progestin) remains the gold standard treatment for hot flashes, but concerns for the risk of hormone therapy have resulted in its decline and a demand for nonhormonal treatments with demonstrated efficacy for hot flashes. Several nonhormonal therapies have been tested in randomized placebo-controlled trials including nonpharmacologic approaches and pharmacologic nonhormonal agents. Among them, two classes of nonhormonal medications have been demonstrated to effectively alleviate hot flashes: γ-aminobutyric acid (GABA) analogs and selective serotonin reuptake inhibitors (SSRIs). This article discusses the superior efficacy of the newer nonhormonal prescriptions for the treatment of hot flashes when compared with estrogen replacement therapy, and provides some recommendations regarding use of them in peri- and postmenopausal women.

Exponential increase of the gestational-age-specific incidence of preeclampsia onset (COPE study): a multicenter retrospective cohort study in women with maternal check-ups at <20 weeks of gestation in Japan.

According to the 2004 Japanese definition, early-onset (EO) preeclampsia (PE) is defined as PE occurring at <32 weeks of gestation. This was based on the presence of "dual peaks" (30-31 and 34-35 weeks) in the prevalence of severe forms of hypertension. In contrast, the international definition adopted a cutoff of 34 weeks based on the consensus. Our aim was to investigate whether there were "dual peaks" in the gestational-age-specific incidence or prevalence of PE onset in pregnant women who underwent maternal check-ups at <20 weeks of gestation in a multicenter retrospective cohort study. Diagnoses of PE and superimposed preeclampsia (SPE) were based on the new Japanese definition. A total of 26,567 pregnant women with singleton pregnancy were investigated. The best fitting equations for the distribution of the onset of gestational-age-specific incidence (hazard) rates of PE/SPE, PE, and PE with severe hypertension (a systolic blood pressure ≥160 and/or a diastolic blood pressure ≥110 mmHg) were investigated using the curve estimation function in SPSS. PE/SPE occurred in 1.83% of the patients. EO-PE/SPE with onset at <32 and <34 weeks of gestation and preterm PE/SPE occurred in 0.38, 0.56, and 1.07% of the patients, respectively. Gestational-age-specific incidence rates of PE/SPE, PE, and PE with severe hypertension showed exponential increases, with very high R2 values (0.975, 0.976, and 0.964, respectively). There were no "dual peaks" in the prevalence rates of women with SPE/PE, PE, and PE with severe hypertension. In conclusion, the absence of "dual peaks" refutes the previous rationale of EO-PE being defined as PE at <32 weeks of gestation. Further studies to determine an appropriate definition of EO-PE/SPE are needed.

Beneficial effects of dienogest on uterine myoma volume: a retrospective controlled study comparing with gonadotropin-releasing hormone agonist.

PURPOSE: Uterine leiomyomas are the most common benign tumors of reproductive age women, but there is no effective medical therapy to data. Aim of this study was to examine and compare the efficacy of gonadotropin-releasing hormone agonist (GnRHa) versus dienogest in premenopausal women with uterine myoma. METHODS: We retrospectively analyzed the medical records of 55 premenopausal patients with endometriosis, who received dienogest (2 mg daily) for 6 months regarding coexistence of uterine myoma between January 2008 and June 2010. To compare these data in a case-control study, we analyzed a matched control group of 12 patients treated with leuprolide acetate (1.88 mg monthly) for 6 months having uterine myoma. RESULTS: Of the 55 patients treated with dienogest, six were associated with coexistent myoma node. Total myoma volume significantly decreased to 59.7 ± 7.0% of initial in dienogest group and 51.9 ± 5.5% in GnRHa group. Reduction rate in myoma volume was similar in both groups. CONCLUSION: Uterine myoma volume was successfully reduced by use of dienogest. Consideration of GnRHa disadvantages may lead to short- or long-term management of women with myoma who are to be managed transiently, and who wish to avoid surgical intervention, especially perimenopausal women.

Palmar fasciitis with polyarthritis-associated ovarian cancer: Case report and literature review.

Palmar fasciitis and polyarthritis (PFPA) is an uncommon disorder clinically characterized by rapidly developing bilateral arthritis of the hands and fasciitis of the palms. This cancer-associated syndrome, primarily linked to ovarian cancer, has also been associated with multiple different malignancies. PFPA symptoms usually precede the detection of ovarian cancer. In all patients from case series and single case reports described, ovarian cancer is already present at an advanced stage. Therefore, the authors aimed to present a case and systematically review available evidence on the association between PFPA and ovarian cancer, as gynecological oncologists. Awareness and recognition of PFPA may allow for earlier diagnosis and treatment of an occult ovarian cancer. The commitment of the attending gynecologists to become familiar with and identify rare diseases may lead to the detection at an early and curative stage and potentially life-saving therapeutic interventions.

Ovarian function following targeted anti-angiogenic therapy with bevacizumab.

Improvements in cancer therapy have enabled further insight into the long-term effects of treatment, including the highly prevalent gonadal failure. The focus of treatment has been shifted to the preservation of fertility, which may be achieved by preventing ovarian toxicity. To this end, new molecular-targeted agents, including monoclonal antibodies, have been developed and used in a standard procedure for managing different cancers. However, the prolonged antitumor activity of these drugs may cause the emergence of new toxic effects. The aim of the present review was to discuss the leading toxic effect of the anti-angiogenic agent bevacizumab on ovarian function in female patients of reproductive age, which may be observed and expected during in clinical practice. The majority of bevacizumab-induced side effects are expected to be transient and eliminated within the anticipated drug clearance time frame; however, fundamental investigations on these effects are required for generating more evidence-based practice guidelines.

Clinical benefits of metformin in gynecologic oncology.

Evidence has suggested that diabetes may contribute to the initiation and progression of specific types of cancer. Metformin, a biguanide, has become the preferred first-line therapy for the treatment of type 2 diabetes. Metformin is inexpensive, has a proven safety profile and is able to be safely combined with additional antidiabetic agents. In addition to the well-established antidiabetic effects of metformin, there has also been notable interest in its antitumor properties. The present review discusses the emerging role of metformin as an example of an existing drug, used worldwide in the treatment of diabetes, which has been demonstrated to exert significant in vitro and in vivo anticancer activities and has thus been investigated in clinical trials. In gynecologic oncology, metformin has been suggested to exhibit significant treatment efficacy against endometrial cancer. Three studies have demonstrated the potential therapeutic effects of metformin on the survival outcome of patients with ovarian cancer and in ovarian cancer prevention. However, this evidence was based on observational studies. Metformin has been shown to exert no statistically significant beneficial effect on cervical cancer incidence or mortality. By cancer site, the current limited insights highlight the need for clinical investigations and better-designed studies, along with evaluation of the effects of metformin on cancer at other sites.

Spontaneous perforation of pyometra presenting as acute abdomen and pneumoperitoneum mimicking those of gastrointestinal origin.

Gastrointestinal (GI) perforation accounts for over 90% of acute abdomen and pneumoperitoneum. The presence of pneumoperitoneum secondary to spontaneously perforated pyometra is an interesting yet confusing finding given the absence of gastrointestinal (GI) perforation, because pyometra is more common in postmenopausal women. We report an instructive case of diffuse peritonitis caused by spontaneous perforation of pyometra. A 70-year-old postmenopausal female was admitted to surgical emergency with signs of diffuse peritonitis. After resuscitation, an emergency laparotomy was performed because of suspicion of GI perforation. At laparotomy, about 2,000 mL of purulent fluid was found to be present in peritoneal cavity, while GI tract was intact. A rent with a diameter of 5 mm was found on anterior fundus of uterus. A total abdominal hysterectomy with a bilateral salpingo-oophorectomy was performed. Despite intensive care and a course of antibiotics, the patient died of multiple organ failure resulting from sepsis on postoperative day 16. Our case illustrates the importance of clinical knowledge of acute gynecological diseases, which are not uncommonly encountered by the general surgeon. Moreover, good appreciation of pelvic anatomy and close collaboration with gynecology and GI surgery colleagues is essential as operative intervention is often required.

Malignant neoplasia arising from ovarian remnants following bilateral salpingo-oophorectomy (Review).

Ovarian remnant syndrome (ORS) is a rare, but well-known gynecological complication, most often induced by difficult bilateral salpingo-oophorectomy (BSO) procedures that leave residual ovarian tissue on the pelvic wall. The most common preexisting conditions for this complication include endometriosis, pelvic inflammatory disease and prior abdominal surgery. The residual ovarian tissue may eventually cause malignant development. A total of 12 cases of malignant and benign tumors (clear cell adenocarcinoma in 1 case, mucinous-type tumors in 2, endometrioid-type tumors in 5, adenocarcinoma in 3 and border serous neoplasia in 1) and 21 benign cysts developing from an ovarian remnant have been described in the literature to date. Endometriosis, known to increase the risk of ovarian cancer, predisposes patients to ORS, with an incidence rate of 30 to 50% in ORS patients with ovarian carcinoma. Although the true incidence of ORS remains unknown, when endometriotic adhesions are diagnosed during BSO, the possibility of ORS and subsequent ovarian malignant transformation may mandate complete surgical resection.

Early diagnosis of malignant-transformed ovarian mature cystic teratoma: fat-suppressed MRI findings.

The most common form of malignant transformation developing from a mature cystic teratoma is squamous cell carcinoma, representing 80% of malignant transformations, while adenocarcinoma accounts for approximately 5%. Because of this rarity, few reports exist of preoperative diagnosis of this tumor by magnetic resonance imaging, in particular with fat suppression techniques. Here, we report magnetic resonance imaging findings and clinical features of a 79-year-old woman with mucinous adenocarcinoma arising from a mature cystic teratoma (measuring 5×6 cm), classified as surgical stage IA. Because of the poor prognosis of malignant transformation, when mature cystic teratomas are detected (even smaller than 5 cm tumor size) in postmenopausal women, serum tumor marker carcinoembryonic antigen levels and fat-suppressed magnetic resonance imaging may be potential indicators of malignant transformation.

Proposed medications for taxane-induced myalgia and arthralgia (Review).

Taxanes inhibit the disassembly of microtubules, which are involved in mitosis and axoplasmatic transport, and may cause the degeneration of peripheral, mainly small, sensory nerves. Peripheral neurotoxicity is a dose-limiting side-effect of taxanes. Neuroprotective agents may aid in the reduction of neurotoxicity, thus allowing the intensification of cytostatic therapy in patients. An increasing number of medications for the prevention of taxane-induced arthralgia and myalgia are becoming available to oncology teams. The most widely studied medications include so-called analgesics such as Shakuyaku-kanzo-to (a herbal medicine), corticosteroids and antihistamines. Arthralgias and myalgias (muscle spasms, fasciculations and prolonged contractions) may be extremely distressing for patients. New anti-epileptic drugs, particularly gabapentin and pregabalin, have proven to be safe and effective in the treatment of taxane-induced neurotoxicity. The aim of this review was to examine the topical choices available for the protective management of taxane-induced neurotoxicity monitored in preliminary case studies and clinical trials. At present, there is no standard of care for the prevention of taxane-induced arthralgia and myalgia. In combination with taxane-based chemotherapeutic regimens, these medical agents may be crucial in the treatment of a variety of types of cancer.

Pelvic tumors with normal-appearing shapes of ovaries and uterus presenting as an emergency (Review).

Abdominal pain with an associated pelvic mass is a common problem in everyday practice. Concerns about ectopic pregnancy, torsion of an enlarged ovary or malignancy usually dominate the diagnostic evaluation. On physical and imaging examination, when a palpable painful mass is present in the pelvis and the two ovaries and uterus are detected in their normal anatomical locations, the content and origin of the lesions may be significant in narrowing the pre-operative differential diagnosis. Thus, the emergent pelvic indications discussed in this review should be considered. The causes of acute abdominal pain are few in number and therefore an accurate diagnosis may be most frequently made at the time of exploratory laparotomy.

Transitional cell carcinoma of the ovary (Review).

Transitional cell carcinoma (TCC) of the ovary is a rare recently recognized subtype of ovarian epithelial cancer. Ovarian TCC has a modest response to chemotherapy, and metastatic TCC from the renal pelvis results in mortality. The clinical presentation is indistinguishable from other types of ovarian carcinoma. Histopathological examination remains the first tool used in the diagnosis of these heterogeneous tumors and in the separation of closely related tumors. Since it is generally accepted that surgical resection is the primary therapeutic approach, and patient outcomes following chemotherapy are better than for other types of ovarian cancers, it is a reasonable concept to detect tumors when they are still confined within the ovaries. Thus, the aim of this review was to describe typical cases of primary TCC, and to review the medical literature for information on TCC management in order to determine appropriate diagnostic methods and therapy.