The gene encoding Bruton tyrosine kinase (Btk) is known to be mutated in human X chromosome-linked agammaglobulinemia and in the Xid mouse. This kinase was examined in B lymphocytes before and after antigen receptor ligation and also in pre-B cells. Btk was found to be catalytically activated and tyrosine phosphorylated in response to anti-IgM imulation in B cells. This kinase is also constitutively phosphorylated on tyrosine residues in pre-B cells. These findings point to a functional role for Btk in pre-antigen and antigen receptor signaling during B-cell development and provide a biochemical explanation for the X-linked genetic syndromes already linked to this kinase.Bruton tyrosine kinase (Btk) is a member of a small family of tyrosine kinases that share certain structural features, but whose biological roles are poorly understood. These kinases, which include Itk/Tsk in T lymphocytes (1, 2), TEC I and TEC II in liver cells as well as hematopoietic cells (3,4), and the DSrc28 kinase in Drosophila (5) (19).Anti-Btk Antibodies. Anti-Btk antibodies were raised in rabbits using a glutathione S-transferase (GST) Btk fusion as described by Tsukada et al. (7) followed by depletion over a GST-Sepharose immunoadsorbent and affinity purification using GST-Btk-Sepharose.Anti-Phosphotyrosine Immunoprecipitation and Anti-Btk Immunoblot Analysis. Anti-IgM crosslinking was performed and lysates from 5 x 107 cells (in 1% Nonidet P40) were prepared as described (19). Four-fifths of each lysate was used for the anti-phosphotyrosine immunoprecipitation step, using 50 ,ul of a 50% slurry of a monoclonal anti-phosphotyrosine antibody coupled to agarose (PY 20, Zymed).The remaining fifth of each lysate was immunoprecipitated with anti-Btk. Immunoprecipitates were washed four times with 0.2% Nonidet P40 in 10 mM Tris, pH 8.0/120 mM NaCl/0.4 mM EDTA, separated on a 10% polyacrylamide/ SDS gel, and transferred to an Immobilon-P membrane, and Btk was revealed by immunoblotting, using the ECL system (Amersham). In separate experiments, lysates were immunoprecipitated with anti-Btk as described above and an anti-phosphotyrosine immunoblot was performed as described (19).Assay for Catalytic Activation of Btk. WEHI 231 B cells (3 x 106) were used for each time point of the in vitro kinase assay. Cells (1.3 x 107) were stimulated with 2.5 pg of F(ab')2 anti-IgM (Zymed) in 100 ,l of serum-free RPMI medium at 37°C. At various time points lysates were made as described above and precleared using rabbit IgG and protein A-Sepharose. A portion of each lysate representing 3 x 106 cells was immunoprecipitated with anti-Btk, washed four times with the 0.2% Nonidet P-40 buffer described in the previous Abbreviations: Btk, Bruton tyrosine kinase; SH, Src homology. *To whom reprint requests should be addressed. 10606The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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Gynecologic emergencies include various diseases that result from adnexal and uterine disorders. Adnexal disorders may be classified into the following three categories: (a) disorders that cause hemorrhage (hemorrhagic ovarian cysts and ectopic pregnancies); (b) disorders related to adnexal tumors (adnexal torsion and rupture of ovarian tumors); and (c) disorders related to pelvic inflammatory disease, such as tubo-ovarian abscesses. Unusual adnexal torsion, such as massive ovarian edema, isolated fallopian tube torsion, and paraovarian cyst torsion, has also been described. Uterine disorders in gynecologic emergencies may be classified into two categories: (a) acute fibroid complications, including red degeneration of a uterine leiomyoma, torsion of subserosal myomas, and torsion of the uterus; and (b) causes of acute uterine bleeding, including retained products of conception and uterine arteriovenous malformations. Some gynecologic diseases are self-limited, while others cause infertility or life-threatening infection or bleeding if left untreated. Therefore, prompt and accurate diagnosis is important for appropriate life-saving treatment and for the preservation of fertility. The imaging findings are important when evaluating acute gynecologic diseases because the symptoms and physical examination findings are often nonspecific and limited. Ultrasonography is the first-line imaging modality; however, when a definitive diagnosis cannot be established, computed tomography (CT) and magnetic resonance (MR) imaging may narrow the differential diagnosis. Appropriate management requires radiologists to be familiar with the CT and MR imaging features of gynecologic emergencies. With respect to rare conditions, radiologists should take into account the representative findings presented in this article to increase diagnostic accuracy. RSNA, 2017.

This was a nation-wide retrospective study in Japan examining women who underwent radical hysterectomy for clinical stage IB-IIB cervical cancer with pelvic and/or para-aortic lymph node metastasis between 2004 and 2008. Time to recurrence or death and patterns of disease recurrence were compared based upon the adjuvant treatment pattern: whole pelvic radiotherapy alone (n = 253), concurrent chemoradiotherapy (CCRT, n = 502) and chemotherapy alone (n = 319). Women who received chemotherapy alone had similar recurrence (5-year rates, 36.6% vs. 34.1%, adjusted-hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.70-1.28, P = 0.72) and cervical cancer mortality (24.7% vs. 21.8%, adjusted-HR 0.96, 95% CI 0.67-1.38, P = 0.83) rates compared to those who received CCRT on multivariate analysis. However, when recurrence patterns were stratified, chemotherapy treatment was independently associated with decreased risk of distant recurrence (5-year cumulative rates, 19.2% vs. 24.6%, adjusted-HR 0.47, 95% CI 0.31-0.71, P < 0.001) but increased risk of local recurrence (23.9% vs. 14.3%, adjusted-HR 2.03, 95% CI 1.34-3.08, P = 0.001) compared to CCRT. Non-squamous histology, parametrial involvement and high lymph node ratio were independent predictors for local recurrence, and presence of multiple risk factors was associated with high 5-year cumulative local recurrence rate in the chemotherapy group: no risk factor 3.9%, single factor 14.2-22.1%, and multiple risk factors 27.8-71.9% (P < 0.001). In conclusion, while exhibiting different recurrence patterns, systemic chemotherapy may be as effective a postoperative treatment as radiation-based therapy in node-positive high-risk stage IB-IIB cervical cancer. When tumor exhibits certain risk factors, chemotherapy alone is likely insufficient for local control and adding pelvic irradiation to systemic chemotherapy is recommended in this subgroup.

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PURPOSE This phase III, multicenter, randomized, open-label study investigated the efficacy and safety of nivolumab versus chemotherapy (gemcitabine [GEM] or pegylated liposomal doxorubicin [PLD]) in patients with platinum-resistant ovarian cancer. MATERIALS AND METHODS Eligible patients had platinum-resistant epithelial ovarian cancer, received ≤ 1 regimen after diagnosis of resistance, and had an Eastern Cooperative Oncology Group performance score of ≤ 1. Patients were randomly assigned 1:1 to nivolumab (240 mg once every 2 weeks [as one cycle]) or chemotherapy (GEM 1000 mg/m2 for 30 minutes [once on days 1, 8, and 15] followed by a week's rest [as one cycle], or PLD 50 mg/m2 once every 4 weeks [as one cycle]). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate, duration of response, and safety. RESULTS Patients (n = 316) were randomly assigned to nivolumab (n = 157) or GEM or PLD (n = 159) between October 2015 and December 2017. Median OS was 10.1 (95% CI, 8.3 to 14.1) and 12.1 (95% CI, 9.3 to 15.3) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.0; 95% CI, 0.8 to 1.3; P = .808). Median PFS was 2.0 (95% CI, 1.9 to 2.2) and 3.8 (95% CI, 3.6 to 4.2) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.5; 95% CI, 1.2 to 1.9; P = .002). There was no statistical difference in overall response rate between groups (7.6% v 13.2%; odds ratio, 0.6; 95% CI, 0.2 to 1.3; P = .191). Median duration of response was numerically longer with nivolumab than GEM or PLD (18.7 v 7.4 months). Fewer treatment-related adverse events were observed with nivolumab versus GEM or PLD (61.5% v 98.1%), with no additional or new safety risks. CONCLUSION Although well-tolerated, nivolumab did not improve OS and showed worse PFS compared with GEM or PLD in patients with platinum-resistant ovarian cancer.

Background: Only few reports are available on the use of aortic balloon catheter for cesarean hysterectomy in placenta previa percreta. Case: A 32-year-old woman with placenta previa percreta underwent cesarean hysterectomy at 34 weeks of gestation. Before starting the surgery, an aortic occlusion balloon catheter (30 mm balloon, 5 Fr) was inserted. For total hysterectomy, the aortic balloon catheter was inflated and there was a sudden and dramatic reduction in blood loss, and the surgery was completed safely. An aortic occlusion was sustained for 80 min, with blood loss estimated at 3,200 ml. The postoperative course was uneventful. At 3 months after the operation, the mother and baby remained healthy. Conclusion: An aortic balloon is rapidly and easily inserted, and is an option for major hemorrhage in placenta previa percreta.