Hiromi Ugaki

PIK3CA gene mutations and amplifications in uterine cancers, identified by methods that avoid confounding by PIK3CA pseudogene sequences

PIK3CA codes for a Class IA p110-alpha catalytic subunit of the PI3Ks (phosphatidylinositol 3-kinases) that regulate various signaling pathways important for neoplasia, including cell proliferation, motility, adhesion, and survival. Pro-oncogenic mutations in exons 9 and 20 of the PIK3CA gene have been frequently observed in numerous types of human malignancies. Amplification of the PIK3CA gene has been reported in uterine cervical cancers. In this study, we have done in depth analysis of uterine cervical and endometrial cancers for PIK3CA gene mutations and amplifications. In uterine cervical cancers, PIK3CA mutations were found in 3 of 22 cases (14%), all of them in exon 9. In endometrial cancers, a similar incidence of mutations was found, in 3 of 29 cases (10%), however they were all within exon 20. Amplification of the PIK3CA gene was also detected in 2 out of 22 (9%) cervical cancers and 3 out of 29 (10%) endometrial cancers. In this study, we were unable to find a clear association between PIK3CA mutations and gene amplifications, nor with tumor histological subtypes or staging. Mutations and amplifications of the PIK3CA gene are relatively infrequent in human cervical and endometrial cancers; however, PIK3CA gene alteration may still play a role in some subset of uterine cancers.

Concurrent Weekly Nedaplatin, External Beam Radiotherapy and High-Dose-Rate Brachytherapy in Patients with FIGO Stage IIIb Cervical Cancer: A Comparison with a Cohort Treated by Radiotherapy Alone

Objectives: The aim of this study was to evaluate whether nedaplatin-based concurrent chemoradiotherapy (CCRT) using high-dose-rate intracavitary brachytherapy (HDR-ICBT) is superior to radiotherapy (RT) alone in patients with FIGO stage IIIb cervical cancer. Methods: The records of 41 consecutive women treated either with nedaplatin-based CCRT using HDR-ICBT (n = 20) or RT alone (nonrandomized control group, n = 21) for stage IIIb cervical cancer were retrospectively reviewed. The activity and toxicity were compared between the two treatment groups. Progression-free survival (PFS) and overall survival (OS) were the main endpoints. Results: The 5-year overall survival rates in the CCRT and RT groups were 65 and 33.3%, respectively. The median OS of the CCRT and RT groups were 60 and 29 months, respectively. CCRT was significantly superior to RT alone with regard to PFS (p = 0.0015) and OS (p = 0.0364). The frequency of acute grade 3–4 toxicity was significantly higher in the CCRT group than in the RT group. However, no statistically significant difference was observed with regard to severe late toxicity. Conclusions: Nedaplatin-based concurrent chemoradiotherapy was safely performed and significantly improved the prognosis of patients with FIGO stage IIIb cervical cancer. This treatment can be considered as an alternative to cisplatin-based chemoradiotherapy in this patient population.

Intraoperative frozen section assessment of myometrial invasion and histology of endometrial cancer using the revised FIGO staging system.

Objectives: The objective of this study was to assess the value of intraoperative frozen section (IFS) diagnosis for myometrial invasion and histology of endometrial cancer using the revised International Federation of Gynecology and Obstetrics (FIGO) staging system. Methods: The medical records of 303 patients with endometrial cancer who underwent surgery with intraoperative diagnosis at the Osaka University Hospital between January 1999 and December 2008 were reviewed. Intraoperative frozen section diagnosis was retrospectively analyzed for the accuracy rates of myometrial invasion and histology compared with the final diagnosis and with preoperative prediction by magnetic resonance imaging (MRI) and endometrial curettage. Results: When using the previous FIGO staging system, the accuracy rate of IFS for the diagnosis of myometrial invasion was 77%, whereas the accuracy rate of preoperative prediction by MRI was 54%. However, using the newly revised FIGO staging system for myometrial invasion, the accuracy rate of IFS was 87% and the preoperative prediction by MRI was 82%. The accuracy rate of IFS for the diagnosis of histology was 71%, whereas the accuracy rate of preoperative prediction by endometrial curettage was 68%. Conclusion: Although under the previous FIGO staging system IFS diagnosis was significantly more accurate than preoperative prediction by MRI, when using the newly revised FIGO staging system, there are no significant differences between the values of preoperative and intraoperative diagnoses. The accuracy of IFS, however, trends to be slightly better than the preoperative procedures of MRI and endometrial surface biopsy. Thus, IFS diagnosis is still useful for directing primary operative management.

Luteoma-induced fetal virilization

A pregnancy luteoma represents an unusual response of ovarian stromal cells to the altered hormonal levels of pregnancy. It is a distinctive non‐neoplastic lesion characterized by solid proliferations of luteinized cells resulting in a tumor‐like ovarian enlargement. Most patients are asymptomatic; the ovarian enlargement is usually discovered incidentally at cesarean section or during postpartum tubal ligation. We report a typical case that we found at cesarean section to be associated with a virilized infant who manifested clitoromegaly and labial fusion. We detected an increased level of testosterone in the maternal patient. We concluded that the ovarian luteoma induced the fetal virilization.

Spontaneous Uterine Perforation of Pyometra Presenting as Acute Abdomen

Pyometra is the accumulation of pus in the uterine cavity, and spontaneous perforation of pyometra resulting in generalized diffuse peritonitis is extremely uncommon. We report a rare case of diffuse peritonitis caused by spontaneous perforation of pyometra. A 66-year-old postmenopausal woman with diffuse abdominal pain and vomiting was admitted to our institution. She had a history of mixed connective-tissue disease and had been taking steroids for 20 years. Under a diagnosis of generalized peritonitis secondary to perforation of the gastrointestinal tract or uterus, supravaginal hysterectomy and bilateral salpingo-oophorectomy were performed. Unfortunately, wound dehiscence and infection occurred during the postoperative course, which were exacerbated by her immunocompromised state. Despite intensive care and a course of antibiotics, the patient died of multiple organ failure resulting from sepsis on the 36th postoperative day. Although correct diagnosis, early intervention, and proper treatment can reduce morbidity and mortality of spontaneous perforation of pyometra, if severe infection occurs, this disease can be life threatening for immunocompromised hosts.

Safety and efficacy of lower-dose unfractionated heparin for prophylaxis of deep vein thrombosis and pulmonary embolism in an Asian population.

The objective of this study is to analyze the tolerance and efficacy of the subcutaneous administration of a reduced 2500-unit low-dose unfractionated heparin given for an efficacious, yet Asian population-sensitive, prophylaxis for deep vein thrombosis and fatal pulmonary embolism. Eighty-seven Japanese patients were operated on either for abdominal or pelvic complications or both, as well as for gynecologic conditions including ovarian, cervical, and corpus cancers. Thirty-two of the patients were administered the experimental low dose of unfractionated calcium heparin for prophylaxis. The 2500 units of low-dose unfractionated heparin were given subcutaneously 2 h preoperatively and again 12 h postoperatively. Other standard methods of mechanical prophylaxis, including graduated compression stockings and intermittent pneumatic compression, were performed. Fifty-five of the patients were not administered heparin, but did receive the same standard mechanical graduated compression stockings and intermittent pneumatic compression prophylaxis. We compared the surgical and postsurgical complications noted for low-dose unfractionated heparin patients with the results of those who received no heparin prophylaxis and analyzed this data using the Mann–Whitney U-test. There was no significant difference in the mean of the blood loss volumes. There were also no significant differences found in the perioperative bleeding complications between the two groups. However, three (3/55; 6%) of the patients in the no-heparin group suffered a symptomatic pulmonary embolism, although none were fatal. There were no pulmonary embolism onsets in the heparin prophylaxis group. We feel that we have provided evidence that several serious complications, such as perisurgical hemorrhage, deep vein thrombosis, fatal pulmonary embolism, and increased postoperative recovery times, can be prevented by prophylaxis with 2500-unit low-dose unfractionated heparin.

Contents Vol. 69, 2010

M.A. Belfort, Provo, Utah J. Bornstein, Nahariya H.L. Brown, Durham, N.C. C. Chapron, Paris J. de Haan, Maastricht G.A. Dekker, Adelaide J.A. Deprest, Leuven K. Hecher, Hamburg S. Kahhale, São Paulo H. Kliman, New Haven, Conn. T.F. Kruger, Tygerberg J.A. Kuller, Raleigh, N.C. M.J. Kupferminc, Tel Aviv H. Minkoff , Brooklyn, N.Y. J. Moodley, Congella J.M. Mwenda, Nairobi H. Odendaal, Tygerberg J.T. Repke, Hershey, Pa. Founded 1895 as ‘Monatsschrift für Geburtshilfe und Gynäkologie’, continued 1946–1969 as ‘Gynaecologia’ and 1970–1977 as ‘Gynecologic Investigation’