Central Nervous System Outcomes of Lazertinib Versus Gefitinib in EGFR-Mutated Advanced NSCLC: A LASER301 Subset Analysis.

INTRODUCTION: Lazertinib, a third-generation mutant-selective EGFR tyrosine kinase inhibitor, improved progression-free survival compared with gefitinib in the phase 3 LASER301 study (ClinicalTrials.gov Identifier: NCT04248829). Here, we report the efficacy of lazertinib and gefitinib in patients with baseline central nervous system (CNS) metastases. METHODS: Treatment-naive patients with EGFR-mutated advanced NSCLC were randomized one-to-one to lazertinib (240 mg/d) or gefitinib (250 mg/d). Patients with asymptomatic or stable CNS metastases were included if any planned radiation, surgery, or steroids were completed more than 2 weeks before randomization. For patients with CNS metastases confirmed at screening or subsequently suspected, CNS imaging was performed every 6 weeks for 18 months, then every 12 weeks. End points assessed by blinded independent central review and Response Evaluation Criteria in Solid Tumors version 1.1 included intracranial progression-free survival, intracranial objective response rate, and intracranial duration of response. RESULTS: Of the 393 patients enrolled in LASER301, 86 (lazertinib, n = 45; gefitinib, n = 41) had measurable and or non-measurable baseline CNS metastases. The median intracranial progression-free survival in the lazertinib group was 28.2 months (95% confidence interval [CI]: 14.8-28.2) versus 8.4 months (95% CI: 6.7-not reached [NR]) in the gefitinib group (hazard ratio = 0.42, 95% CI: 0.20-0.89, p = 0.02). Among patients with measurable CNS lesions, the intracranial objective response rate was numerically higher with lazertinib (94%; n = 17) versus gefitinib (73%; n = 11, p = 0.124). The median intracranial duration of response with lazertinib was NR (8.3-NR) versus 6.3 months (2.8-NR) with gefitinib. Tolerability was similar to the overall LASER301 population. CONCLUSIONS: In patients with CNS metastases, lazertinib significantly improved intracranial progression-free survival compared with gefitinib, with more durable responses.

Laparoscopic uncontained power morcellation-induced dissemination of ovarian endodermal sinus tumors: A case report.

BACKGROUND: Endodermal sinus tumors (ESTs), which arise primarily in children and adolescents, account for 20% of malignant ovarian germ cell tumors, but constitute only 1% of all ovarian malignancies. Treatment of ESTs consists of surgical staging with fertility-sparing surgery and chemotherapy. CASE SUMMARY: A 15-year-old nulliparous patient was diagnosed with disseminated ovarian ESTs after laparoscopic unilateral salpingo-oophorectomy using uncontained power morcellation for treatment of a ruptured solid adnexal mass in another hospital. Exploratory laparotomy; total abdominal hysterectomy, right salpingo-oophorectomy, and lymphadenectomy were performed with optimal debulking, and surgical stage 3C was assigned to the patient. CONCLUSION: In 2014, the Food and Drug Administration noted that power morcellation was probably associated with a risk of disseminating suspected cancerous tissue. Furthermore, the use of power morcellation to remove solid adnexal mass is considered a contraindication because of the potential for a malignant tumor. This case report aims to warn of the dangers of using uncontained power morcellation to treat solid adnexal masses.

Impact of the Timing of Rocuronium Injection after Propofol Administration on Temporal Summation of Pain in Gynecologic Laparoscopic Surgery: A Prospective and Controlled Study.

Purpose: Temporal summation of pain, which is defined as the perception of greater pain evoked by repetitive painful stimuli, varies among individuals. This study aimed at determining the impact of the timing of rocuronium after induction with propofol on the temporal summation of pain. Methods: One hundred patients aged 19-60 years underwent gynecologic laparoscopic surgery. Patients were randomly assigned to one of the two groups: group PRi received immediate injections of rocuronium after propofol administration and group PRd received rocuronium injections when the bispectral index score (BIS) decreased to <60 after propofol administration. The grade of rocuronium-induced withdrawal movement (RIWM) according to the timing of propofol injection, the incidence and severity of propofol injection pain (PIP), rescue analgesics, visual analog scale (VAS) score after surgery for postoperative pain, patient-controlled analgesia (PCA) opioid consumption, association between PIP and the grade of RIWM, and associations between PIP, the grade of RIWM, and postoperative pain outcomes were measured. Results: The differences between the incidence and severity of PIP in the two groups were not significant. The grade of the RIWM in the PRd group was significantly reduced compared with the PRi group. Rescue analgesics, severity for postoperative pain, and PCA opioid consumption were not significant. Correlations between the incidence and severity of PIP and the grade of RIWM were weakly negative. Correlations between the grade of RIWM and pain outcomes were moderately positive, but correlations between the severity for PIP and the postoperative pain outcomes were negligible. Conclusion: The timing of rocuronium administration after propofol injection played a role in reducing RIWM. The grade of RIWM was significantly related to pain outcomes compared with the severity of PIP. Therefore, delayed rocuronium injection after induction with propofol reduced temporal summation of pain.

Endometriosis-induced massive hemoperitoneum misdiagnosed as ruptured ectopic pregnancy: a case report.

BACKGROUND: Endometriosis, an estrogen-dependent inflammatory disease, is commonly observed in gynecologic practice. Spontaneous hemoperitoneum is a rare but serious complication of endometriosis. Most cases of endometriosis-induced hemoperitoneum are attributable to a ruptured endometrioma or utero-ovarian vessel hemorrhage. We report a case of massive hemoperitoneum secondary to intra-abdominal bleeding from the peritoneal endometriotic deposits with spontaneous abortion that was misdiagnosed as a ruptured ectopic pregnancy. CASE PRESENTATION: A 36-year-old Korean woman was admitted to our hospital for acute abdominal pain and vaginal bleeding. She was suspected of ruptured ectopic pregnancy on the basis of a positive serum human chorionic gonadotropin test result and ultrasonographic evidence of pelvic fluid collection. During hospitalization, her symptoms deteriorated with peritoneal irritation sign on physical examination, hypotension, and tachycardia. Emergency exploratory laparoscopy was performed and revealed active bleeding from the peritoneal endometriotic deposit, which was treated with laparoscopic electrocoagulation. The patient's postoperative course was uneventful. Spontaneous abortion was diagnosed on the basis of decreased serial serum human chorionic gonadotropin level estimation. CONCLUSIONS: Although rare, gynecologists should consider endometriosis-induced hemoperitoneum with spontaneous abortion in the differential diagnosis in women of reproductive age presenting with a positive serum human chorionic gonadotropin test result and acute abdomen with intra-abdominal bleeding.

Isolated tubal torsion in the third trimester of pregnancy managed with simultaneous salpingectomy and cesarean section.

Isolated tubal torsion is an uncommon cause of acute abdomen in pregnancy. Tubal torsion may occur in the absence of adnexal disease. Diagnosing tubal torsion is especially difficult in pregnancy because no precise preoperative radiological and biochemical investigations have been conducted. Most patients are diagnosed during surgery. Here, I present a case of isolated tubal torsion in a pregnant woman at 35 weeks and 6 days of gestation that was managed with salpingectomy and cesarean section simultaneously.

Randomized controlled trial of the efficacy and safety of self-adhesive low-level light therapy in women with primary dysmenorrhea.

OBJECTIVE: To evaluate the efficacy and safety of low-level light therapy in women with primary dysmenorrhea. METHOD: A multicenter prospective, randomized, double-blind, placebo-controlled clinical trial including patients 18-35 years of age with primary dysmenorrhea was undertaken at two university hospitals in South Korea between October 2011 and September 2012. Patients were randomized using a computer-generated sequence to receive low-level light therapy using the Color DNA-WSF device or to receive placebo treatment with a dummy device. The severity of menstrual pain, assessed using a visual analog scale, was the primary outcome and was evaluated at baseline and during every menstrual cycle for 3 months following treatment. Patients who received more than one application of treatment (with a Color DNA-WSF or placebo device) were included in analyses. Patients and investigators were masked to the treatment assignments. RESULTS: Overall, 44 patients were assigned to each group. At the final study visit, the reduction in scores using a visual analog scale was significantly greater in patients who received low-level light therapy (n=41; 4.34±2.22) than among those in the control group (n=38; 1.79±1.73; P<0.001 when adjusted for age) No serious adverse events occurred. CONCLUSION: Low-level light therapy could be an effective, safe treatment modality for women with primary dysmenorrhea. Clinical Trials.gov: NCT02026206.

Recurrent ovarian steroid cell tumor, not otherwise specified managed with debulking surgery, radiofrequency ablation, and adjuvant chemotherapy.

Steroid cell tumors, not otherwise specified, are infrequently encountered ovarian neoplasms, which constitute <0.1% of all ovarian tumors. Most of these tumors are unilateral, and almost one-third of all cases are reportedly malignant. However, because most of these tumors are diagnosed in the early stage, and do not recur or metastasize, little is known about their response to therapies such as chemotherapy or radiation. Here, we present a rare case of recurrent steroid cell tumor, not otherwise specified that showed a complete response after debulking surgery, radiofrequency ablation, and adjuvant chemotherapy.

Interaction between postoperative shivering and hyperalgesia caused by high-dose remifentanil.

BACKGROUND: High-dose remifentanil-based anesthesia is associated with opioid-induced hyperalgesia (OIH) and postanesthetic shivering (PAS). These effects can be prevented by N-methyl-d-aspartate (NMDA) receptor antagonists. This study aimed to investigate correlations between OIH and PAS caused by high-dose remifentanil and the effects of low-dose ketamine on OIH and PAS. METHODS: Seventy-five patients scheduled for single-port laparoscopic gynecologic surgery were randomly allocated into three groups, each of which received intraoperative remifentanil: group L at 0.1 µg/kg/min; group H at 0.3 µg/kg/min; and group HK at 0.3 µg/kg/min plus 0.25 mg/kg ketamine just before incision, followed by a continuous infusion of 5 µg/kg/min ketamine until skin closure. RESULTS: PAS, postoperative tactile pain threshold, and the extent of hyperalgesia in group H were significantly different (P < 0.05) than in the other two groups. PAS was significantly correlated with OIH, including mechanically evoked pain such as postoperative tactile pain threshold (r = -0.529, P = 0.01) (r = -0.458, P = 0.021) and the extent of hyperalgesia (r = 0.537, P = 0.002) (r = 0.384, P = 0.031), respectively, in group H and group HK. Notably, both groups were treated with high-dose remifentanil. Tympanic membrane temperature, time to first postoperative analgesic requirement, postoperative pain scores, analgesic consumption, and cumulative patient-controlled analgesia volume containing morphine were comparable in all three groups. CONCLUSIONS: OIH, including the enhanced perception of pain, and PAS were both associated with high-dose remifentanil, were significantly correlated and were attenuated by a low dose of ketamine. This suggests that a common mechanism in part mediated through activation of the central glutamatergic system (e.g., NMDA receptors), underlies the two effects caused by high doses of remifentanil.

Prx1 modulates the chemosensitivity of lung cancer to docetaxel through suppression of FOXO1-induced apoptosis.

The expression levels of Prx1 are frequently elevated in several human cancers, including lung cancer and may confer increased resistance to treatment. In this study, we investigated the role of Prx1 in docetaxel-induced apoptosis in A549 lung cancer cells. To test whether Prx1 knockdown affected the sensitivity of A549 cells to docetaxel treatment, we generated short hairpin RNA (shRNA) constructs targeting Prx1 and analyzed the effect of Prx1 knockdown on growth and apoptosis. Tumor growth was evaluated in scrambled shRNA- or shPrx1-infected A549 cell tumors receiving docetaxel treatment. In addition, mechanistic information was gathered by western blot analysis from cell lysates of scrambled- and shPrx1-infected A549 cells pretreated with or without LY294002 and subsequently treated with docetaxel. We found that Prx1 knockdown resulted in enhanced docetaxel-induced cytotoxicity in a dose-dependent manner. In vivo, the growth rate of shPrx1-infected A549 tumors was significantly reduced compared to that of scrambled shRNA-infected A549 tumors. Prx1 knockdown also augmented the inhibitory effects of docetaxel on tumor growth. Prx1 knockdown increased the apoptotic potential through activation of the caspase cascade and suppressed docetaxel-induced phosphorylation of Akt and its substrate forkhead box O1 (FOXO1). Moreover, treatment with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 reduced the phosphorylation of FOXO1 and increased the cytotoxicity of docetaxel in A549 cells. Our findings suggest that Prx1 may modulate the chemosensitivity of lung cancer to docetaxel through suppression of FOXO1-induced apoptosis.

Effects of menopausal hormone therapy on uterine myoma in menopausal women.

OBJECTIVES: The aim of the present study is to evaluate the long term effects of estrogen-progestogen therapy (EPT) on uterine myomas volume in postmenopausal women. METHODS: We performed a retrospective analysis on postmenopausal women with asymptomatic uterine myoma during the period between April, 2008 and September, 2012. Postmenopause was defined as amenorrhea for longer than a year or serum follicle stimulating hormone levels higher than 40 IU/L. The volume of the myoma was assessed by transvaginal ultrasonography for every 6 months after administration of EPT. RESULTS: Thirty-eight women were included in the study, with 32 in the EPT group and 6 in the control group. Overall, uterine myoma volume (mean ± standard deviation, cm(3)) in the EPT group was 19.5 ± 24.6 at baseline, and those at 6 and 12 months were 24.7 ± 35.1 and 28.5 ± 56.4, respectively. Myoma volume did not change significantly with EPT, and these changes were not significantly different from the control group. Myoma volume changes were not significantly different in the subgroups according to the route of estrogen administrations and the method of progestogen administrations. Clinically significant volume increases during one year of EPT was noted in 28.1% (9/32), however, only one showed transient increases. CONCLUSION: Our results suggest that treating postmenopausal woman with EPT on a long-term basis does not increase the volume of uterine myomas.

The Relationship between Uterine Myoma Growth and the Endocrine Disruptor in Postmenopausal Women.

OBJECTIVES: To investigate the number of leiomyoma patients-exposed to bisphenol A (BPA) and to observe whether the serum concentration of BPA is related to leiomyoma growth. METHODS: A total of 158 patients were recruited for this study. Leiomyoma patients were divided into three groups, mild (n = 48), moderate (n = 32) and severe (n = 28), according to the size of leiomyomas. The control (n = 30) group was defined as having no leiomyomas. Transvaginal ultrasonography was used to identify and measure the leiomyomas. Serum BPA concentrations were measured by enzyme-linked immunosorbent assay. RESULTS: BPA was detected in 87.0% out of a total of 158 samples, and in 86.0% out of 108 leiomyoma patients. In detail, the detection rates of serum BPA were 88.0% in the control group, 77.2% in the mild group, 90.0% in the moderate group and 96.0% in the severe group. The mean BPA concentration in the control group was 0.558 ± 0.097 ng/mL, the leiomyoma groups, the mean BPA concentrations were 0.274 ± 0.063 ng/mL (mild), 0.346 ± 0.064 ng/mL (moderate) and 0.647 ± 0.039 ng/mL (severe) (P = 0.0003). Values represent the mean ± standard error. CONCLUSION: The detection rates of serum BPA in the control and leiomyoma groups were 88.0% and 86.0%, respectively. However, there was no significant difference in the serum BPA concentrations between the control and leiomyoma groups. To verify the effect of BPA on leiomyoma growth, a close and sequential monitoring is recommended for people who are at risk for uterine leiomyoma.

The effects of magnesium sulfate infiltration on perioperative opioid consumption and opioid-induced hyperalgesia in patients undergoing robot-assisted laparoscopic prostatectomy with remifentanil-based anesthesia.

BACKGROUND: Opioids not only exert an antinociceptive effect, but also modulate central N-methyl-D-aspartate (NMDA) receptors, resulting in hyperalgesia and acute opioid tolerance. This study was aimed to investigate the effect of the NMDA receptor antagonist, magnesium in preventing remifentanil-induced hyperalgesia. METHODS: For this study, 75 patients scheduled for robot-assisted laparoscopic prostatectomy were randomly allocated into three groups of patients whose incision sites were infiltrated: Group M, with 25% magnesium sulfate 80 mg/kg; Group S, with the same volume of saline under remifentanil-based anesthesia, and Group D, with the same volume of saline under desflurane based anesthesia. All three groups were infiltrated into incision sites after pneumoperitoneum. Intraoperative evaluation included mean remifentanil dose, and postoperative evaluation included pain severity at time intervals of 30 min, 6, 12, 24 and 36 hours, time to first postoperative analgesic requirement, and analgesic dosage required during 24 hours. RESULTS: Mean remifentanil doses during the intraoperative periods in group M were significantly lower than those in group S (P < 0.001). The time to first postoperative analgesic requirement in postoperative period in groups M and D was significantly longer than that in group S (P < 0.001). Visual analog scale scores for pain in groups M and D were significantly lower than those in group S for 12 hours after operation. CONCLUSIONS: A relatively high dose and continuous infusion of remifentanil were associated with opioid induced hyperalgesia. Wound infiltration with magnesium sulfate decreased opioid consumption and reduces opioid induced hyperalgesia.