Cerebral infarction caused by Trousseau syndrome associated with cervical cancer.

OBJECTIVE: The combination of cancer and hypercoagulable states is often called Trousseau syndrome. In particular, cerebral infarction caused by Trousseau syndrome is reported to have a poor prognosis. In gynecology, there are many reports of ovarian cancer and a few of uterine cancer. Since there has been no comprehensive report of Trousseau syndrome in cervical cancer, we aimed to summarize Trousseau syndrome in cervical cancer. METHODS: Cerebral infarction caused by cancer-related arterial thrombosis was defined as Trousseau syndrome. Patients with cervical cancer diagnosed at our hospital between January 2014 and December 2021 were retrospectively reviewed using the hospital's medical records. RESULTS: A total of 1,432 patients were included in the study. Trousseau syndrome occurred in 6 patients (0.4%). The mean age of patients with Trousseau syndrome was 63 years (range: 53-78 years). Of the 6 patients who developed Trousseau's syndrome, 4 patients had it before or during initial treatment, and 2 during recurrent/relapsed disease treatment. The 4 patients who developed the syndrome before or during initial treatment had advanced disease: 1 in stage IIIC and 3 in stage IVB. In all cases, the disease was associated with progressive distant metastasis. The median survival time from the onset of Trousseau syndrome was 1 month (range: 0-6 months). CONCLUSION: Cervical cancer causes Trousseau syndrome in cases of advanced disease with a short time between the onset of the syndrome and mortality.

Local Treatment Efficacy for Single-Area Squamous Cell Carcinoma of the Unknown Primary Site.

The prognosis for cancer of unknown primary site (CUP) is poor, and squamous cell carcinoma of the unknown primary site (SCCUP) is a rare histological type. CUP is often treated with aggressive multimodal treatments, while the treatment of single-area localized CUP remains controversial. We retrospectively reviewed the medical records of patients with CUP. SCCUP in women was classified according to several definitions. Based on the histologic type and site, they were classified into favorable and unfavorable subsets. We further divided SCCUP into two types (single and multiple areas) and reviewed treatment and efficacy. Among the 227 female CUP patients, 36 (15%) had SCCUP. The median age was 59.9 years (range, 31-90 years). Most patients (61.1%) had a good performance status. Of the SCCUP patients, 22 had cancer in a single area, and 14 in multiple areas. Single-area SCCUP was further divided into favorable (16 cases) and unfavorable subsets (6 cases). In the favorable subset, local treatment was predominant, and almost all cases had a good prognosis. Even in the unfavorable subset, local therapy was combined with systemic chemotherapy in only two cases, and four cases showed no recurrences. Local treatment may be effective for single-area SCCUP, even in the unfavorable subset.

Transperineal endoscopic approach with GelPOINT V-path in laparoscopic pelvic exenteration for postirradiated recurrent cervical cancer.

Pelvic exenteration (PE) is a highly invasive procedure associated with high morbidity and mortality rates. Laparoscopy is a promising option to reduce this invasiveness, and laparoscopic PE significantly reduces blood loss and shortens hospital stays. In the case of a large tumor with invasion to the surrounding organs, laparoscopic dissection around the pelvic floor is sometimes problematic owing to restrictions on handling instruments. To overcome these limitations, we performed a transperineal endoscopic approach using the GelPOINT V-path in addition to laparoscopic PE. This approach enabled dissection around the pelvic floor without the abovementioned obstacles under magnified visualization. As a result, we could dissect the pelvic floor precisely with a reduction of the dead pelvic space, which might contribute to reduced rates of postoperative complications while ensuring oncologic outcomes.

Efficacy of intra-abdominal cytoreductive surgery in advanced endometrial cancer with distant metastasis.

OBJECTIVE: The efficacy of intra-abdominal cytoreductive surgery in patients with endometrial cancer and distant metastasis is equivocal. We investigated the effectiveness of such surgical treatment and whether it should be performed before or after chemotherapy (CT). METHODS: This study included patients with an International Federation of Gynecology and Obstetrics stage IVB endometrial cancer who received initial treatment at our hospital between January 2006 and December 2017. RESULTS: We retrospectively reviewed 67 patients with stage IVB endometrial cancer with distant metastases and classified them into preceding surgery (PS, n=23), chemotherapy followed by a surgery (CS, n=27), and CT (n=17) groups. We examined the achievement of resection with [R (1)] or without [R (0)] intra-abdominal macroscopic residue and survival. The median survival time for R (0) was 44 (95% confidence interval [CI]=9-not available [NA]) months in the PS group and 27 (95% CI=11-NA) months in the CS group. The median survival time for R (1) was 9 (95% CI=0-24) months in the PS group and 12 (95% CI=7-19) months in the CS group. The similar prognosis in both groups was worse with R (1) than with R (0). The survival curve for R (1) in the resection groups was similar to that of the CT group. CONCLUSION: Achieving resection without intra-abdominal macroscopic residue for endometrial cancer with distant metastases, whether before or after CT, could extend patients' survival.

Impact of the coverage of risk-reducing salpingo-oophorectomy by the national insurance system for women with BRCA pathogenic variants in Japan.

To determine the impact of the coverage of risk-reducing salpingo-oophorectomy (RRSO) and mastectomy (RRM) as well as genetic testing for BRCA pathogenic variants by the national insurance system in Japan. We compared the clinical background of women who underwent RRSO at our institution before and after its coverage by the national insurance system. Those who underwent RRSO between January 2017 and December 2019 and between April 2020 and March 2022 were classified as Period. A and B, respectively. Overall, 134 women underwent RRSO during the study period. In Period A and B, 45 and 89 women underwent RRSO for the study period was 36 and 24 months, respectively. Compared with Period A, the number of women who underwent RRSO per month increased by threefold in Period B (p < 0.01). In addition, the number of women who underwent surgery for breast cancer along with RRSO increased in Period B (p < 0.01). Although the number of women who underwent concurrent RRM with RRSO in Period B increased, the difference was not statistically significant. Compared with Period A, the number of women diagnosed with BRCA pathogenic variant increased by 3.9-fold, and the proportion of women who underwent concurrent hysterectomy at the time of RRSO decreased from 66 to 7.9% in Period B (p < 0.01). Owing to the introduction of the national insurance system, the number of women who underwent RRSO and concurrent surgery for breast cancer at the time of RRSO increased in Japan.

Prognosis and adjuvant chemotherapy for patients with positive peritoneal cytology in stage IA endometrial cancer.

This study evaluated the influence of positive peritoneal cytology (PPC) on the prognosis of patients with stage IA endometrial cancer, and the usefulness of adjuvant chemotherapy in their treatment. We retrospectively analyzed the data of patients with stage IA endometrial cancer admitted in our hospital between 2005 and 2015. Among 989 patients who underwent peritoneal cytology, 135 (13.7%) had PPC. Multivariate analysis extracted several independent risk factors for recurrence in stage IA patients, including those with PPC. Adjuvant chemotherapy did not cause a significant difference in the 5-year relapse-free survival rate in patients with PPC (p = 0.78). Similarly, the 5-year recurrence-free survival rate with or without chemotherapy was not different among type II cancer patients (p = 0.11). However, the baseline risk of 5-year relapse-free survival without chemotherapy in patients with PPC and type II was very low (66.7%). While PPC was an independent risk factor for recurrence in stage IA endometrial cancer, adjuvant chemotherapy did not influence the survival rate in patients with PPC. While it is controversial whether adjuvant chemotherapy should be administered in stage IA uterine cancer with only PPC as a prognostic factor, it should be considered for early-stage patients who have multiple risk factors for recurrence.

Second fertility preservation surgery for early relapse of seromucinous borderline ovarian tumors.

•The initial diagnosis was endometriosis; however, the postoperative diagnosis was a seromucinous borderline ovarian tumor.•Women of reproductive age experienced an early relapse of seromucinous borderline ovarian tumor after surgery.•Transvaginal ultrasound was useful for early diagnosis of relapse.•A second fertility preservation surgery was performed, and fertility treatment without relapse was ongoing.

Laparoscopic Ureteral Reimplantation for the Management of Long-segment Ureteral Defect in Gynecologic Surgeries.

OBJECTIVE: To demonstrate techniques of laparoscopic ureteral reconstruction for long-segment ureteral defects in gynecologic surgeries. DESIGN: Step-by-step demonstration of a laparoscopic ureteral reimplantation using the Boari flap and ileal interposition. SETTING: Gynecologic diseases often involve the ureter; hence, knowledge of ureteral reconstruction techniques is imperative in gynecologic surgeries. The important aspect of ureteral reconstruction is to ensure tension-free anastomosis; therefore, various methods are required depending on the length of the ureteral defect [1]. The Boari flap and ileal interposition are preferred for repairing 8-cm to 12-cm and >12-cm ureteral defects, respectively. These methods have traditionally required large incisions [2,3]. Laparoscopic ureteral reimplantation using the Boari flap and ileal interposition has been reported to be as safe as the open technique and superior in terms of postoperative recovery in urologic surgeries [3,4]; however, to the best of our knowledge, it has not been reported in the field of gynecology. To our knowledge, this is the first report to demonstrate the techniques of laparoscopic Boari flap and ileal ureter replacement in gynecologic surgeries. The technique was approved by our institutional review board. INTERVENTIONS: The first case involved an intra-abdominal desmoid tumor, whereas the second case involved recurrent endometrial cancer. In both cases, long-segment ureteral resection was required to achieve complete tumor clearance. Laparoscopic ureteral reimplantation was performed successfully, without any complications, using the Boari flap in the first case and ileal interposition in the second. CONCLUSION: Laparoscopic ureteral reimplantation is technically feasible for the management of long-segment ureteral defects.

Nucleolar protein Nop25 is involved in nucleolar architecture.

Nop25 is a putative RNA binding nucleolar protein associated with rRNA transcription. The present study was undertaken to determine the crucial function of Nop25 in the nucleolus. When N-terminal amino acids of Nop25 were overexpressed as a dominant negative effector in cells, the nucleolus was fragmented into small components. Knockdown of Nop25 by RNA interference also induced drastic nucleolar fragmentation. These results suggest that Nop25 is involved in nucleolar architecture and maintenance. Although nucleolar fragmentation induced the dispersion of nucleolar proteins from the nucleolus, it did not lead to cell cycle arrest or apoptosis, suggesting no effect of nucleolar fragmentation on the transcription and processing of rRNA molecules and subsequent ribosome biogenesis. Studies on Nop25 may provide new information on nucleolar organization related to nucleolar architecture and function.

Mapping a nucleolar targeting sequence of an RNA binding nucleolar protein, Nop25.

Nop25 is a putative RNA binding nucleolar protein associated with rRNA transcription. The present study was undertaken to determine the mechanism of Nop25 localization in the nucleolus. Deletion experiments of Nop25 amino acid sequence showed Nop25 to contain a nuclear targeting sequence in the N-terminal and a nucleolar targeting sequence in the C-terminal. By expressing derivative peptides from the C-terminal as GFP-fusion proteins in the cells, a lysine and arginine residue-enriched peptide (KRKHPRRAQDSTKKPPSATRTSKTQRRRR) allowed a GFP-fusion protein to be transported and fully retained in the nucleolus. When the peptide was fused with cMyc epitope and expressed in the cells, a cMyc epitope was then detected in the nucleolus. Nop25 did not localize in the nucleolus by deletion of the peptide from Nop25. Furthermore, deletion of a subdomain (KRKHPRRAQ) in the peptide or amino acid substitution of lysine and arginine residues in the subdomain resulted in the loss of Nop25 nucleolar localization. These results suggest that the lysine and arginine residue-enriched peptide is the most prominent nucleolar targeting sequence of Nop25 and that the long stretch of basic residues might play an important role in the nucleolar localization of Nop25. Although Nop25 contained putative SUMOylation, phosphorylation and glycosylation sites, the amino acid substitution in these sites had no effect on the nucleolar localization, thus suggesting that these post-translational modifications did not contribute to the localization of Nop25 in the nucleolus. The treatment of the cells, which expressed a GFP-fusion protein with a nucleolar targeting sequence of Nop25, with RNase A resulted in a complete dislocation of the protein from the nucleolus. These data suggested that the nucleolar targeting sequence might therefore play an important role in the binding of Nop25 to RNA molecules and that the RNA binding of Nop25 might be essential for the nucleolar localization of Nop25.

Molecular cloning and characterization of Nop25, a novel nucleolar RNA binding protein, highly conserved in vertebrate species.

We report here the identification and characterization of a novel nucleolar RNA binding protein, referred to as Nop25 as based on its predicted molecular size and subcellular location. Nop25 homologues were widely discovered in diverse vertebrate species as hypothetical proteins, but not found in yeasts, plants and prokaryotic organisms. Nop25 was ubiquitously expressed in adult mouse organs and constitutively during mouse embryogenesis. Indirect immunofluorescence analysis with an anti-Nop25 antibody, as well as an experiment using a GFP-fused protein, demonstrated that Nop25 was localized in the nucleolus. Treatment of the cells with a low doses of actinomycin D caused Nop25 to translocate to the periphery of the nucleolus, suggesting that nucleolar localization of Nop25 is associated with rRNA transcription. Treatment of COS7 cells with RNase A resulted in a complete dissociation of Nop25 from the nucleolus, while in vitro binding assay demonstrated that Nop25 could bind directly to single-stranded nucleic acids. Further characterization of associated RNA molecules with Nop25 using immunoprecipitation experiment showed that Nop25 might bind to 28S rRNA. Studies on this novel nucleolar RNA binding protein may provide new information on the intricate nucleolar machinery as related to the transcription and processing of rRNA molecules and/or the subsequent assembly and maturation of ribosomes.

Functional expression of CCL6 by rat microglia: a possible role of CCL6 in cell-cell communication.

There is growing evidence that chemokines play important roles in the immune surveillance of central nervous system (CNS). In the CNS, microglia are primary immune effector cells and secrete various chemokines in response to their microenvironment. Using the RT-PCR procedure and indirect immunofluorescence analysis, we found that CCL6 (known as C10/MRP-1 in mouse) was expressed in rat primary microglia without any stimulation, but not in primary astrocytes, although both cell types expressed CCR1 mRNA, which is a receptor for CCL6. Furthermore, immunohistochemical analysis demonstrated that microglia produced CCL6 protein in a normal brain, suggesting that microglia may be the primary source of CCL6 in a normal brain. Recombinant rat CCL6 mediated the migration of microglia and astrocytes in vitro. The CCL6-mediated cell migration was blocked by treating the cells with LY294002, a PI3-kinase inhibitor and Western blot analysis showed that the phosphorylation of Akt could be induced by treating microglia with a recombinant CCL6, suggesting that CCL6 functions by activating the PI3-kinase/Akt pathway. A proinflammatory cytokine, interferon-gamma enhanced the expression of both CCL6 mRNA and protein in microglia, while other proinflammatory cytokines, interleukin-6 and tumor necrosis factor-alpha and an anti-inflammatory cytokine, transforming growth factor-beta exerted no effect on CCL6 expression in microglia. These findings suggest that CCL6 may be a mediator released by microglia for cell-cell communication under physiological as well as pathological conditions of CNS.