Frequency and clinical features of deficient mismatch repair in ovarian clear cell and endometrioid carcinoma.

OBJECTIVE: To clarify the frequency of deficient mismatch repair (dMMR) in Japanese ovarian cancer patients, we examined microsatellite instability (MSI) status and immunohistochemistry (IHC) subtypes, including endometrioid carcinoma (EMC), clear cell carcinoma (CCC), or a mixture of both (Mix). METHODS: We registered 390 patients who were diagnosed with EMC/CCC/Mix between 2006 and 2015 and treated at seven participating facilities. For 339 patients confirmed eligible by the Central Pathological Review Board, MSI, IHC, and MutL homolog 1 methylation analyses were conducted. The tissues of patients with Lynch syndrome (LS)-related cancer histories, such as colorectal and endometrial cancer, were also investigated. RESULTS: MSI-high (MSI-H) status was observed in 2/217 CCC (0.9%), 10/115 EMC (8.7%), and 1/4 Mix (25%). Additionally, loss of MMR protein expression (LoE-MMR) was observed in 5/219 (2.3%), 16/115 (14.0%), and 1/4 (25%) patients with CCC, EMC, and Mix, respectively. Both MSI-H and LoE-MMR were found significantly more often in EMC (p<0.001). The median (range) ages of patients with MMR expression and LoE-MMR were 54 (30-90) and 46 (22-76) (p=0.002), respectively. In the multivariate analysis, advanced stage and histological type were identified as prognostic factors. CONCLUSION: The dMMR rate for EMC/CCC was similar to that reported in Western countries. In Japan, it is assumed that the dMMR frequency is higher because of the increased proportion of CCC.

Curcumin partly prevents ISG15 activation via ubiquitin-activating enzyme E1-like protein and decreases ISGylation.

The expression of the ubiquitin-like molecule interferon-stimulated gene 15 kDa (ISG15) and post-translational protein modification by ISG15 (ISGylation) are strongly activated by interferons or pathogen infection, suggesting that ISG15 and ISGylation play an important role in innate immune responses. More than 400 proteins have been found to be ISGylated. ISG15 is removed from substrates by interferon-induced ubiquitin-specific peptidase 18 or severe acute respiratory syndrome coronavirus 2‒derived papain-like protease. Therefore, maintaining strong ISGylation may help prevent the spread of coronavirus disease 2019 (COVID-19). However, it is unknown whether nutrients or chemicals affect ISGylation level. Curcumin is the major constituent of turmeric and functions as an immunomodulator. Here, we investigated the effect of curcumin on ISGylation. MCF10A and A549 cells were treated with interferon α and curcumin after which the expression levels of various proteins were determined. The effect of curcumin on ubiquitylation was also determined. Curcumin treatment was found to reduce ISGylation in a dose-dependent manner. The findings suggested that curcumin partly prevents disulfide bond-mediated ISG15 dimerization directly or indirectly, thereby increasing monomer ISG15 levels. Reduced ISGylation may also occur via the prevention of ISG15 activation by ubiquitin-activating enzyme E1-like protein. In conclusion, curcumin treatment was found to reduce ISGylation, suggesting that it may contribute to severe COVID-19. This is the first study to report a relationship between ISGylation and a food component.

Correlation of bone marrow 2-deoxy-2-[ 18 F]fluoro-D-glucose uptake with systemic inflammation in patients with newly diagnosed endometrial cancer.

OBJECTIVE: To clarify the relationship between 2-deoxy-2-[ 18 F]fluoro-D-glucose (FDG) uptake of bone marrow and systemic inflammation in patients with newly diagnosed endometrial cancer. METHODS: A total of 119 patients with untreated endometrial cancer underwent FDG PET/computed tomography (CT). For bone marrow FDG uptake, the mean standardized uptake value (SUVmean) of the five vertebrae (T11-12 and L3-L5) was measured and averaged (bone marrow SUV). The bone marrow-to-liver ratio (BLR) was calculated by dividing the bone marrow SUV by the SUVmean of the normal liver. FDG PET parameters were correlated with white blood cell count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and C-reactive protein (CRP), albumin, and hemoglobin levels. They were also correlated with FIGO stage. RESULTS: Bone marrow SUV and BLR showed significant positive correlations with white blood cell count, NLR, and CRP level and significant negative correlations with albumin level. BLR also showed a significant positive correlation with PLR. No significant differences in bone marrow SUV and BLR were apparent according to FIGO stage. CONCLUSION: Pretreatment FDG PET/CT in patients with newly diagnosed endometrial cancer may provide information on host systemic inflammation as assessed by bone marrow FDG uptake.

Diagnostic Laparoscopy for Ovarian Tumor Due to Salmonella Infection.

Ovarian abscess is thought to be caused by ascending infection. We experienced a case with ovarian abscess caused by Salmonella. The patient had been monitored for endometrial cysts at an outpatient clinic. She visited our hospital emergently with chief complaints of persistent fever and diarrhea. Although sexually transmitted disease was not suspected, she was diagnosed with pelvic inflammatory disease due to her high C-reactive protein (CRP) level and started antibacterial treatment. Two days later, diagnostic laparoscopy was performed for persisting CRP elevation, and she was diagnosed with ovarian abscesses due to Salmonella infection. As the patient had regularly eaten soft-boiled eggs and chicken, an association with her eating habits was strongly suspected as a cause. When a patient has symptoms of enteritis, preceding tubo-ovarian abscess should be considered the possibility of Salmonella infection. Early diagnosis and treatment are necessary for fertility preservation, and minimally invasive diagnostic laparoscopy is useful.

A New Technique for Seprafilm® That Can Be Practiced with a 5-mm Trocar.

Seprafilm® is an adhesion barrier sheet. However, it is difficult to handle it through a 5-mm trocar. We have devised a method of applying Seprafilm® safely and reliably through a 5-mm trocar by using a holder that comes with the film. We practiced this method in three cases of total laparoscopic hysterectomy for uterine leiomyoma. The quarter-pack is cut into three pieces. The film placed on the holder sheet was rolled up with forceps (or wrapped around forceps) and inserted into a 5 mm trocar. After application, the center of the short axis of the holder was pinched with a grasping forceps, and the holder was drawn out of the body through the trocar. Of the 36 pieces placed, Seprafilm® broke only in once. Insertion was successful in 100%, and the holder was successfully retrieved through the trocar in 92% (33/36) of the cases. The holder may be easily retrieved after application. This technique represents an extremely simple versatile application method in operations in which only 5-mm trocars can be used.

Uterine leiomyosarcoma well-controlled with eribulin mesylate.

Uterine leiomyosarcoma is a rare type of malignant gynecological tumor and has a poor prognosis; therefore, this tumor is often difficult to treat. Some new drugs have been approved during the past several years in Japan and are expected to be efficacious. Eribulin, one of these drugs, is a natural product of halichondrin B, which is isolated from a marine sponge. A recent clinical trial comparing eribulin with dacarbazine to target liposarcoma and leiomyosarcoma indicated that overall survival (OS) was prolonged by treatment with eribulin. We report a case of uterine progressive leiomyosarcoma that responded to eribulin. A 57-year-old woman was suspected of having leiomyosarcoma based on an endometrial biopsy and imaging examinations. Although the tumor grew toward the uterine artery on the right side of the uterine cervix, we performed a total abdominal hysterectomy and bilateral salpingo-oophorectomy to obtain an outcome of no gross residual disease. However, the margin of the right side of the uterine cervix was histologically positive, so leiomyosarcoma stage IIB (pT2bcN0cM0, FIGO2008) was diagnosed. Gemcitabine and docetaxel therapy was administered postoperatively. However, after three cycles, the residual tumor progressed. Other anticancer drugs were administered but were ineffective. We administered eribulin (1.4 mg/m2) as a fourth-line regimen, and the mass decreased by 32% after four cycles. However, the residual tumor continued to grow after eight cycles. The only adverse event associated with eribulin treatment was mild, grade 2 neutropenia. For our patient, eribulin was effective for her recurrent leiomyosarcoma. In selecting chemotherapy, there are currently no fixed guidelines; we should consider the characteristics and adverse events associated with each drug and patient performance status and comorbidities. In this patient, eribulin was associated with few adverse events, an easy route of administration and a good quality of life. Therefore, eribulin is expected to be efficacious for the treatment of gynecologic sarcoma.

HDLive Silhouette Inversion Mode in Diagnosis of Complete Hydatidiform Mole.

We present our experience of using the HDLive silhouette inversion mode to assess complete hydatidiform mole early in pregnancy. The HDLive silhouette inversion mode clearly depicted the number, size, and spatial position of molar vesicles, compared with conventional two-dimensional sonography or the HDLive inversion mode. Moreover, spatial relationships among molar vesicles, intrauterine anechoic fluid collection, and the uterine wall enabled the clear localization of the lesion. This technique provides new insights, and has the potential to supplement conventional two-dimensional sonography in the diagnosis of complete hydatidiform mole.

Three-Dimensional Color/Power Doppler Sonography and HD live Silhouette Mode for Diagnosis of Molar Pregnancy.

We present our experience of using new 3-dimensional color/power Doppler sonography (HDliveFlow; GE Healthcare Japan, Tokyo, Japan) with the HD live silhouette mode for diagnosing complete molar pregnancy in the first trimester and differentiating it from missed abortion with hydropic degeneration. In the case of a complete mole, color Doppler sonography showed numerous vesicles without blood vessels, whereas HDliveFlow with the HD live silhouette mode clearly depicted these vesicles forming a mass with the clear demarcation of its edges and showed no blood flow inside the mass. In contrast to the hydropic abortion, which appeared as some vesicles with many blood vessels around them on color Doppler sonography, HDliveFlow with the HD live silhouette mode showed some vesicles embedded within the abundant blood vessels. The spatial relationship between the vesicles and surrounding highly vascularized uterus could be shown on HDliveFlow with the HD live silhouette mode. This technique might be beneficial as an additional diagnostic tool along with conventional color/power Doppler sonography, and it facilitates the early discrimination of these cases in the first trimester of pregnancy.