Increase in creatinine levels associated with niraparib maintenance therapy in ovarian cancer.

AIM: In Japan, Niraparib maintenance therapy for primary and recurrent ovarian cancer was approved in September 2020 and is expected to improve the prognosis of ovarian cancer. However, the safety of niraparib maintenance therapy in Japanese patients has not been fully evaluated. METHODS: Patients with ovarian cancer (including fallopian tube and peritoneal cancer) treated with niraparib at Jichi Medical University Hospital from September 2020 to August 2022 were enrolled in this study. Patient background, starting dose, rates of interruption, reduction, or discontinuation, adverse events (AEs) during treatment, and estimated glomerular filtration rate (eGFR) trends were retrospectively analyzed. RESULTS: Twenty-nine patients received niraparib maintenance therapy during the study period, including 21 with primary cancer and 8 patients with recurrent cancer. Seventeen patients (58.6%) required dose interruptions and 16 patients (55.2%) required dose reductions. Only two patients (6.9%) discontinued treatment due to fatigue and nausea. The most frequent AE was creatinine increases in 18 patients (62.1%, all grades). Although eGFR levels decreased significantly after niraparib therapy compared to before niraparib therapy (59.3 vs. 50.3 mL/min/1.73 m2 , p < 0.001), the levels returned to pre-niraparib initiation levels after discontinuation of niraparib (64.6 vs. 64.6 mL/min/1.73 m2 , p = 0.96). Multivariate regression analysis showed that diabetes was independently associated with decreased eGFR (p = 0.013). CONCLUSIONS: Niraparib maintenance therapy frequently increased serum creatinine, but the change was reversible. Further studies are needed to determine the effects of niraparib on renal function in Japanese patients.

Activated neutrophils inhibit chemotactic migration of activated T lymphocytes to CXCL11 by multiple mechanisms.

Accumulation of T lymphocytes and neutrophils shows inversed association with the prognosis of cancer patients, suggesting infiltration of neutrophils and T cells might be differently regulated in tumor tissue. In this study, we stimulated neutrophils with PMA or LPS to produce neutrophil extracellular traps (NETs) and examined the effects on chemotactic migration of activated T cells to a representative T cell chemokine, CXCL11. Migration of the activated T cells was totally abrogated by PMA-stimulated neutrophils placed either in upper or lower chamber, which was mostly canceled by pretreatment with Catalase. Although LPS-stimulated neutrophils also inhibited T cell migration, depletion of NETs by ultracentrifugation or degradation of NETs with DNAse I restored T cell migration. Western blots showed that LPS-stimulated neutrophils thoroughly degraded CXCL11 with NETs dependent manner. Activated neutrophils inhibit T cell chemotaxis via multiple mechanisms including the release of H2O2 and chemokine degradation by NETs, which may suppress adaptive immunity.

Association between financial toxicity and health-related quality of life of patients with gynecologic cancer.

OBJECTIVES: Patients often struggle with their financial situation during cancer treatment due to treatment-related costs or loss of income. This resulting negative effect is called financial toxicity, which is a known as a side effect of cancer care. This study aimed to evaluate the association between financial toxicity and health-related quality of life among patients with gynecologic cancer using validated questionnaires. METHODS: In this multicenter study, patients with gynecologic cancer receiving anti-cancer drug treatment for > 2 months were recruited. Patients answered the COmprehensive Score for Financial Toxicity (COST) tool, EORTC-QLQ-C30, disease-specific tools (EORTC-QLQ-OV28/CX24/EN24), and EQ-5D-5L. Spearman's rank correlation coefficient was used to determine associations. RESULTS: Between April 2019 and July 2021, 109 cancer patients completed the COST questionnaire. The mean COST score was 19.82. Strong associations were observed between financial difficulty (r = - 0.616) in the EORTC-QLQ-C30 and body image (r = 0.738) in the EORTC-QLQ-CX24, while weak associations were noted between the global health status/quality of life (r = 0.207), EQ-5D-5L index score (r = 0.252), and several function and symptom scale scores with the COST score. CONCLUSIONS: Greater financial toxicity was associated with worse health-related quality of life scores, such as financial difficulty in gynecologic cancer patients and body image in cervical cancer patients as strong associations, and weakly associated with general health-related quality of life scores and several function/symptom scales.

Validity of the COmprehensive Score for financial Toxicity (COST) in patients with gynecologic cancer.

OBJECTIVE: Financial toxicity is a financial burden of cancer care itself, which leads to worse quality of life and higher mortality and is considered an adverse effect. The COmprehensive Score for financial Toxicity (COST) tool is a patient-reported outcome measurement used to evaluate financial toxicity. We aimed to validate the internal consistency and reproducibility of the COST tool in patients with gynecologic cancer. METHODS: In this multicenter study covering the period April 2019 to July 2021, using the COST tool in Japan, patients diagnosed with ovarian, cervical, or endometrial cancer receiving systemic anti-cancer drug therapy for more than 2 months were eligible. Patients with no out-of-pocket costs for direct medical costs were excluded. The patients answered the initial test and a retest, which was completed from 2 to 14 days after the initial test. Internal consistency and reproducibility were assessed using Cronbach's alpha and intraclass correlation coefficient (ICC), respectively. Cronbach's alpha ≥0.8 indicates good internal consistency, and ICC ≥0.8 is highly reliable. RESULTS: A total of 112 patients (ovarian: 50, cervical: 26, endometrial: 36) responded to the initial test, and 89 patients answered the retest from 2 to 14 days after the initial test. The median patient age was 58 (range, 28-78) years. The median COST score was 19. Cronbach's alpha showed good internal consistency at 0.83 (95% CI 0.78 to 0.87). The ICC at 0.850 (95% CI 0.777 to 0.900) showed high reliability. CONCLUSIONS: The COST tool has good internal consistency and reliable reproducibility in patients with gynecologic cancer in Japan. The COST tool quantifies financial toxicity in the insurance system, where patients have limited out-of-pocket direct medical costs. The results support the use of the COST tool in patients with gynecologic cancer.

Efficacy and toxicity of pegylated liposomal doxorubicin as therapy for recurrent ovarian cancer in relation to the number of previous chemotherapy regimens: Comparison with gemcitabine.

AIM: Pegylated liposomal doxorubicin (PLD) is one of the second-line chemotherapy regimens for platinum-resistant recurrent ovarian cancer, but in clinical practice, it is also used for third or subsequent lines of chemotherapy. There is no report on the efficacy and toxicity of PLD in relation to the number of previous chemotherapy regimens. The purpose of this study was to clarify these points and compare with the results of gemcitabine (GEM) therapy we reported previously. METHODS: We retrospectively reviewed the medical records of patients with platinum-resistant recurrent ovarian cancer who underwent two or more cycles of PLD therapy between July 2009 and March 2017 at our institution. We used our reported data of GEM for comparison analysis. RESULTS: Seventy-eight patients were enrolled in this study. The overall response rate was 19.2% and the disease control rate (DCR) was 53.8%. The DCR with 1, 2, 3, and 4 or more previous regimens was 53.8%, 48.6%, 63.6% and 66.7%, respectively. Grade 3/4 neutropenia and anemia developed in 59.0% and 12.8%, respectively. Grade 2 or higher hand -foot syndrome, stomatitis, and liver dysfunction developed in 25.6%, 25.6% and 2.6%, respectively. When the number of previous regimens was 3 or higher, the DCR of PLD was significantly higher than that of GEM (64.7% vs 30.8%, P = 0.037). CONCLUSION: The DCR did not decrease with a greater number of previous regimens. When the number of previous regimens was 3 or higher, PLD therapy had a superior DCR to GEM therapy. Toxicity was tolerable in PLD therapy.

A Prospective Randomized Comparison of Variable-Angle and Fixed-Angle Volar Locking Plating for Intra-Articular Distal Radius Fractures.

PURPOSE: To compare clinical and radiographic outcomes of using a variable-angle volar locking plate (VAVLP) with those of using a fixed-angle volar locking plate (FAVLP) for treating unstable intra-articular fractures of the distal radius. METHODS: One hundred twenty patients with unstable intra-articular fractures of the distal radius were randomized to open reduction and internal fixation with a VAVLP (n = 60) or an FAVLP (n = 60). Supplementary methods (eg., Kirschner wire fixation) were required in 4 patients with a VAVLP and 9 with an FAVLP. Clinical outcomes were evaluated at 6 weeks, 3 months, 6 months, and 1 year after surgery. Posteroanterior and lateral radiographs were used to measure standard radiographic parameters before surgery, in the immediate postoperative period, and at 1 year. Plate prominence and articular congruity were quantified using computed tomography at 6 months. RESULTS: There were no significant differences in any clinical outcome between the groups at any follow-up time. Volar tilt was significantly greater in patients treated with a FAVLP in the immediate postoperative period (8° vs 6°) and at 1 year (8° vs 5°). Although significant differences were not found in articular gap or stepoff between the 2 plates, the distal and volar prominence of the VAVLP was significantly greater than that of the FAVLP at 6 months. Significantly more patients treated with a VAVLP had a complication (38% vs 19%). However, most secondary surgeries were performed for hardware removal, and no patients from either group had complex regional pain syndrome or tendon rupture. CONCLUSIONS: Patients with intra-articular distal radius fractures can expect good functional and radiographic outcomes with VAVLP or FAVLP fixation. The VAVLP may be more prone to technical errors, leading to complications, whereas the FAVLP is more likely to require supplementary fixation. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.

New criteria for the omission of lymphadenectomy in endometrioid carcinoma.

OBJECTIVE: To establish new criteria for the omission of lymphadenectomy in patients with endometrioid carcinoma. METHODS: We retrospectively reviewed 185 cases of histologically confirmed endometrioid carcinoma by hysterectomy at Jichi Medical University Hospital between January 2006 and December 2011. We reviewed patient medical records to detect risk factors for lymph node metastasis to identify the optimum criteria for lymphadenectomy omission. RESULTS: Univariate analysis revealed risk factors for lymph node metastasis to be a large tumor size (volume index ≥40 cm³) (p<0.0001), tumor diameter >2 cm (p=0.0003), myometrial invasion ≥50% based on pre-operative MRI (p=0.0366), elevated serum CA125 (pre-menopausal value ≥70 U/mL, post-menopausal value ≥25 U/mL) (p=0.0004), and lymphadenopathy on pre-operative CT scans (p=0.0002). Multivariate analysis indicated that tumor volume index, tumor diameter, elevated serum CA125, and CT scans positive for lymphadenopathy were independent risk factors for lymph node metastasis. Thus, we set tumor diameter >2 cm, elevated serum CA125, and CT scans positive for lymphadenopathy as risk factors. In cases with no risk factors, the rate of lymph node metastasis was 2.1%, which rose to 8.9%, 30.4%, and 58.3% for those with one, two, and three risk factors, respectively. The rate of para-aortic lymph node metastasis rose from 0% to 2.5%, 10.9%, and 41.7% among those with zero, one, two, and three risk factors, respectively. CONCLUSIONS: We propose that lymphadenectomy can be omitted in cases of endometrioid carcinoma that do not have any of the following risk factors: tumor diameter >2 cm, elevated serum CA125, and a CT scan positive for lymphadenopathy. We believe that these new criteria will limit inter-institutional differences as they are all objective factors. Further, they are useful in predicting lymph node metastasis, including para-aortic lymph node metastasis, based on the number of risk factors present.

Targeting human vasohibin-2 by a neutralizing monoclonal antibody for anti-cancer treatment.

There are two members of the vasohibin (VASH) family, VASH1 and VASH2. VASH1 is expressed mainly in endothelial cells to inhibit angiogenesis, whereas VASH2 is expressed mainly in cancer cells to stimulate tumor growth. The aim of the present study was to establish neutralizing monoclonal antibody (mAb) against human VASH2 and apply it as an anti-cancer treatment. We previously raised mAb against several synthetic peptides of hVASH1, and found that one of them exhibited neutralizing activity against hVASH1. Because of the similarity in the amino acid sequences between VASH1 and VASH2, we hypothesized that they shared the bioactive center. When we mutated four amino acids within the region, the mutant VASH2 lost its pro-angiogenic activity. Therefore, we raised mAb against a synthetic peptide overlapping the mutated amino acids of hVASH2, and isolated one clone (1760) that almost completely inhibited the stimulatory effect of hVASH2 on the migration of and tube formation by endothelial cells. When we used this clone 1760 antibody for cancer treatment, the peritoneal injection of it inhibited both tumor growth and angiogenesis in a mouse xenograft model of human cancer cells. In terms of anti-tumor activity, 25 mg/kg of clone 1760 was equivalent to 5 mg/kg of bevacizmab. From these results, we propose the targeting of human VASH2 with neutralizing mAb as a new strategy for cancer treatment.

A rare case of intradural and extramedullary epidermoid cyst after repetitive epidural anesthesia: case report and review of the literature.

BACKGROUND: Spinal epidermoid cysts are benign tumors, which are rarely seen as an intradural extramedullary spinal cord tumor in the conus medullaris region. Acquired spinal epidermoid cysts are mostly caused by iatrogenic procedures, such as lumbar puncture, and the majority of acquired spinal epidermoid cysts have been reported below the L1 level, because lumbar puncture is usually performed around the iliac crest. Here, we report an extremely rare case of an epidermoid cyst that occurred as an intradural and extramedullary spinal cord tumor attached to the conus medullaris after repetitive epidural anesthesia. CASE PRESENTATION: A 67-year-old female presented with a low back pain and left sciatica. Although the patient had experienced occasional mild low back pain for several years, her low back pain markedly worsened 2 months before her visit, as well as newly developed left sciatica resulting in intermittent claudication. She had a history of several abdominal surgeries. All abdominal procedures were performed under general anesthesia with epidural anesthesia in her thoracolumbar spine. Magnetic resonance imaging of her lumbar spine demonstrated an intradural extramedullary spinal cord tumor at the T12-L1 level. Because her symptoms deteriorated, the tumor excision was performed using microscopy. Histological examination of the specimens demonstrated that the cyst walls lined with stratified squamous keratinizing epithelium surrounded by the outer layer of collagenous tissue with the absence of skin adnexa. A diagnosis of epidermoid cysts was confirmed. Her MRI showed complete resection of the tumor, and there was no recurrence at 2-year follow-up. CONCLUSIONS: In this case report, epidermoid cells might be contaminated into the spinal canal during repetitive epidural anesthesia. The patient was successfully treated by complete resection, and there was no recurrence at 2-year follow-up with a good clinical outcome. However, long-term follow-up is required for a potential risk of tumor recurrence.

Presence of Modic type 1 change increases risk of postoperative pyogenic discitis following decompression surgery for lumbar canal stenosis.

STUDY DESIGN: Multicenter retrospective study. BACKGROUND: Postoperative surgical site infection is one of the most serious complications following spine surgery. Previous studies do not appear to have investigated pyogenic discitis following lumbar laminectomy without discectomy. This study aimed to identify risk factors for postoperative pyogenic discitis following lumbar decompression surgery. METHODS: We examined data from 2721 patients undergoing lumbar laminectomy without discectomy in five hospitals from April 2007 to March 2012. Patients who developed postoperative discitis following laminectomy (Group D) and a 4:1 matched cohort (Group C) were included. Fisher's exact test was used to determine risk factors, with values of p < 0.05 considered statistically significant. RESULTS: The cumulative incidence of postoperative discitis was 0.29% (8/2721 patients). All patients in Group D were male, with a mean age of 71.6 ± 7.2 years. Postoperative discitis was at L1/2 in 1 patient, at L3/4 in 3 patients, and at L4/5 in 4 patients. Except for 1 patient with discitis at L1/2, every patient developed discitis at the level of decompression. The associated pathogens were methicillin-resistant Staphylococcus aureus (n = 3, 37.5%), methicillin-susceptible Staphylococcus epidermidis (n = 1, 12.5%), methicillin-sensitive S. aureus (n = 1, 12.5%), and unknown (n = 3, 37.5%). In the analysis of risk factors for postoperative discitis, Group D showed a significantly lower ratio of patients who underwent surgery in the winter and a significantly higher ratio of patients who had Modic type 1 in the lumbar vertebrae compared to Group C. CONCLUSIONS: Although further prospective studies, in which other preoperative modalities are used for the evaluation, is needed, our data suggest the presence of Modic type 1 as a risk factor for discitis following laminectomy. Latent pyogenic discitis should be carefully ruled out in patients with Modic type 1. If lumbar laminectomy is performed for such patients, more careful observation is necessary to prevent the development of postoperative discitis.

Vasohibin-1 expression inhibits advancement of ovarian cancer producing various angiogenic factors.

Vasohibin-1 (VASH1) is a negative feedback regulator of angiogenesis, the first to be discovered, and was identified in vascular endothelial growth factor (VEGF)-stimulated vascular endothelial cells. Vasohibin-1 inhibits abnormal vascularization induced by various angiogenic factors including fibroblast growth factor and platelet-derived growth factor (PDGF), in addition to VEGF. By focusing on this characteristic of VASH1, we investigated the antitumor effects of VASH1 expression on ovarian cancer cells that produce different angiogenic factors. By using a high VEGF-producing ovarian cancer cell line, SHIN-3, and a high PDGF-producing ovarian cancer cell line, KOC-2S, the cells were transfected with either a VEGF antagonist, soluble VEGF receptor-1 (sVEGFR-1, or sFlt-1), or VASH1 genes to establish their respective cellular expression. The characteristics of these transfectants were compared with controls. We previously reported that the expression of sFlt-1 inhibited tumor vascularization and growth of high VEGF-producing ovarian cancer cells, reduced peritoneal dissemination and ascites development, and prolonged the survival time of the host. However, in the current study, the expression of sFlt-1 had no such effect on the high PDGF-producing ovarian cancer cells used here, whereas VASH1 expression inhibited tumor vascularization and growth, not only in high VEGF-producing cells, but also in high PDGF-producing cells, reduced their peritoneal dissemination and ascites, and prolonged the survival time of the host. These results suggest that VASH1 is an effective treatment for ovarian cancer cells that produce different angiogenic factors.

Ovarian nongestational choriocarcinoma and associated adenocarcinoma with the same germ cell origin determined by a molecular genetic approach: A case report.

Ovarian non-gestational choriocarcinomas co-existing with adenocarcinoma are extremely rare and have been reported as epithelial ovarian carcinomas of a "non-germ cell origin" with "choriocarcinomatous differentiation". Although the cellular origin of non-gestational choriocarcinoma may be post-meiotic ovarian germ cells or the dedifferentiation of epithelial ovarian carcinoma, detailed genetic evidence has not yet been obtained to support this. We herein present a case of ovarian non-gestational choriocarcinoma co-existing with adenocarcinoma in a 29-year-old woman. The tumor rapidly increased in size and lung metastases appeared soon after parturition. We genetically demonstrated that the cellular origin of ovarian non-gestational choriocarcinoma was a post-meiotic germ cell derivation using a short tandem repeat analysis. The co-existing adenocarcinoma component was also shown to be of the same germ cell origin. These tumors showed the same homozygous pattern. A molecular genetic approach may be important for understanding the clinicopathological features of such tumors.

Radiation therapy for chemotherapy-resistant recurrent epithelial ovarian cancer.

OBJECTIVES: While radiation therapy is administered as a palliative treatment for recurrent ovarian cancer, it remains unclear whether it improves the prognosis. METHODS: The effects and adverse events of radiation therapy for patients with recurrent epithelial ovarian cancer were investigated using medical records. RESULTS: Herein, 46 subjects comprising 33 patients whose recurrent lesions were contained within the irradiation field (therapeutic radiation group; TRG) and 13 patients with some recurrent lesions outside the irradiation field (palliative radiation group; PRG) were included. The TRG achieved a response rate (RR) of 66%, a disease control rate (DCR) of 100%, a progression-free survival (PFS) of 10 months, and an overall survival (OS) of 20 months. The PFS after radiation therapy was significantly longer than that following chemotherapy received just before radiation therapy. The PFS of patients with recurrent intrapelvic lesions was longer than that of patients with some extrapelvic recurrence. There was no significant association between PFS after radiation therapy and the duration from the previous chemotherapy or histological type. The RR, DCR, PFS, and OS of the PRG were 30 and 90% and 2 and 6 months, respectively. Serious adverse events were rare. CONCLUSIONS: Radiation therapy is a potential option for chemotherapy-resistant, localized recurrent ovarian cancer. © 2014 S. Karger AG, Basel.

The role of non-genomic actions of progesterone and its membrane receptor agonist in ovarian cancer cell death.

BACKGROUND: Progesterone therapy is a relatively inexpensive treatment option for endometrial and breast cancers, with few side effects. Two signaling pathways usually mediate the physiological effects of progesterone, namely genomic and non-genomic actions. Genomic action occurs slowly via the nuclear progesterone receptor (PR), whereas the membrane progesterone receptor (mPR) induces rapid non-genomic action. AIMS: We investigated the effects of progesterone and various PR agonists on ovarian cancer cells. METHODS AND RESULTS: PR expression of six serous ovarian cancer cell lines was examined by western blotting, and mPR expression was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). PR-negative and mPR-positive ovarian cancer cells were exposed to progesterone and seven types of PR agonists (medroxyprogesterone acetate [MPA], dehydroepiandrosterone, dienogest, levonorgestrel, drospirenone, pregnenolone, and allopregnanolone) at 10-400 µM, and viable cell counts after exposure for 30 min were measured using the water-soluble tetrazolium (WST-1) assay. Ovarian cancer cell lines were exposed to 100 µM progesterone, and the expression of BAX, a pro-apoptotic protein, after 1-5 min was examined by western blotting. Western blotting detected no PR expression in the six serous ovarian cancer cell lines. In contrast, RT-qPCR detected mPR expression in all six serous ovarian cancer cell lines. Progesterone and MPA-induced cell death in all tested ovarian cancer cell lines in a concentration-dependent manner, whereas no effect was observed for other PR agonists. Western blotting revealed that pro-apoptotic protein BAX expression occurred 1 min after exposure to progesterone, suggesting that the cytocidal effects are mediated by rapid non-genomic action. CONCLUSION: Progesterone and MPA exhibited a rapid cytocidal effect on PR-negative ovarian cancer cells through non-genomic action. Progesterone and MPA could be novel adjuvant therapies for ovarian cancer.

Immune Checkpoint Inhibitor-induced Pancreatitis with Pancreatic Enlargement Mimicking Autoimmune Pancreatitis: A Case Report and Review of the Literature.

A 61-year-old woman was administered 35 cycles of pembrolizumab for the treatment of recurrent endometrial cancer, achieving a complete response. She presented with asymptomatic pancreatic enlargement and elevated hepatobiliary enzymes, but amylase and lipase levels were within the normal ranges. Intrapancreatic bile duct stenosis due to pancreatic enlargement was present, mimicking autoimmune pancreatitis on computed tomography performed before the onset of clinical manifestations. A histological examination of a biopsy specimen showed lymphocyte and plasma cell infiltration with dense fibrosis in the stroma. The patient was successfully treated with oral prednisolone. There were no manifestations of recurrent pancreatitis after tapering the prednisolone dose.

In vivo delivery of siRNA targeting vasohibin-2 decreases tumor angiogenesis and suppresses tumor growth in ovarian cancer.

Vasohibin-2 (VASH2) is a homolog of vasohibin-1 and exhibits pro-angiogenic activity. We recently reported that VASH2 is expressed in certain ovarian cancers and promotes tumor growth through angiogenesis. To further demonstrate the effectiveness of molecular targeting of VASH2 for anticancer treatment, we applied in vivo delivery of siRNA targeting VASH2 (siVASH2) using atelocollagen to a xenograft model of ovarian cancer. We inoculated mice s.c. with DISS and SKOV-3, two representative human ovarian serous adenocarcinoma cell lines. When tumors were measurable, we initiated treatment with control or siVASH2 mixed with atelocollagen, which enveloped the whole tumor. Treatment with siVASH2 significantly inhibited s.c. tumor growth by abrogating tumor angiogenesis. We confirmed that expression of VASH2 mRNA in the tumor was downregulated by siVASH2 treatment. In addition, the siVASH2-treated tumor contained more blood vessels covered with pericytes, indicating that knockdown of VASH2 contributes to the normalization of tumor blood vessels. Based on these results, VASH2 may be a promising molecular target for ovarian cancer treatment.

Ovarian vein thrombosis after bilateral adnexectomy in a symptomatic patient with concomitant pulmonary embolism: A case report.

OBJECTIVE: Ovarian vein thrombosis (OVT) after adnexectomy is usually asymptomatic, and pulmonary embolism (PE) has not been reported following this type of OVT. We present the case of a patient with symptomatic OVT after bilateral adnexectomy who experienced PE. CASE REPORT: A 52-year-old woman underwent total laparoscopic hysterectomy and bilateral adnexectomy for early stage endometrial cancer. On the 12th postoperative day, she presented with a fever of 38.7 °C. Computed tomography (CT) revealed bilateral OVT. Anticoagulant and antibacterial therapy was initiated; after five days, the fever subsided. On the 19th postoperative day, CT revealed a decrement in OVT; however, PE was observed. By the 60th postoperative day, PE disappeared. No deep vein thromboses were detected at any time. CONCLUSION: This case highlights that OVT, even after adnexectomy, can cause symptoms and PE can occur after this type of OVT. Anticoagulation therapy may be considered in such cases.

Shoulder internal rotation elbow flexion test for diagnosing cubital tunnel syndrome.

BACKGROUND: Shoulder internal rotation enhances symptom provocation attributed to cubital tunnel syndrome. We present a modified elbow flexion test--the shoulder internal rotation elbow flexion test--for diagnosing cubital tunnel syndrome. METHODS: Fifty-five ulnar nerves in cubital tunnel syndrome patients and 123 ulnar nerves in controls were examined with 5 seconds each of elbow flexion, shoulder internal rotation, and shoulder internal rotation elbow flexion tests before and after treatment (surgery in 18; conservative in others). For the shoulder internal rotation elbow flexion test position, 90° abduction, maximum internal rotation, and 10° flexion of the shoulder were combined with the elbow flexion test position. The test was considered positive if any symptom for cubital tunnel syndrome developed <5 seconds. Influence of the shoulder internal rotation elbow flexion test was evaluated by nerve conduction studies in 10 cubital tunnel syndrome nerves and 7 control nerves. RESULTS: The sensitivities/specificities of the 5-second elbow flexion, shoulder internal rotation, and shoulder internal rotation elbow flexion tests were 25%/100%, 58%/100%, and 87%/98%, respectively. Sensitivity differences between the shoulder internal rotation elbow flexion test and the other two tests were significant. Shoulder internal rotation elbow flexion test results and cubital tunnel syndrome symptoms were significantly correlated. Influence of the shoulder internal rotation elbow flexion test on the ulnar nerve was seen in 8 of 10 cubital tunnel syndrome nerves but not in controls. CONCLUSIONS: The 5-second shoulder internal rotation elbow flexion test is specific, easy and quick provocative test for diagnosing cubital tunnel syndrome.

Durable response after the discontinuation of pembrolizumab treatment due to an adverse event in a patient with advanced endometrial cancer: A case report.

The persistence of antitumor effects has been reported after the completion of treatment with immune checkpoint inhibitors (ICIs) for various types of carcinoma, such as malignant melanoma, exhibiting a durable response. A durable response has also been noted after the discontinuation of treatment at an early stage due to adverse events, including in renal pelvic cancer, pancreatic cancer and intrahepatic cholangiocarcinoma; however, to the best of our knowledge, a similar case report has not yet been published in the malignant gynecological tumor field. The present study described a patient with refractory advanced endometrial cancer in whom the administration of pembrolizumab was discontinued after the completion of the 7th course due to renal dysfunction; however, persistent tumor-reducing effects and decreases in the levels of tumor markers were noted for more than 18 months after the cessation of treatment. Pembrolizumab may be continuously administered to some patients for a long period, whereas a durable response is achieved by others even after its discontinuation at an early stage; therefore, difficulties are associated with selecting an appropriate duration of administration. Further studies are required to search for biomarkers that facilitate high-accuracy effect predictions, and to establish an optimal administration period in consideration of specific adverse reactions to ICIs and cost-effectiveness.

Response to and toxicity of weekly paclitaxel and carboplatin in patients with stage IIIC-IV ovarian cancer and poor general condition.

It has remained elusive whether standard chemotherapy regimens are safe for patients with ovarian cancer and poor general condition. The purpose of the present study was to assess the response to and toxicity of weekly paclitaxel and carboplatin (W-PC) in patients with ovarian cancer and poor general condition. The subjects were patients with ovarian cancer who received W-PC at Jichi Medical University Hospital (Shimotsuke, Japan) between January 2008 and December 2016. Patients who were ≥80 years old and/or had a performance status ≥3 and/or severe complications/underlying diseases were selected. Patients received paclitaxel (60 mg/m2) and carboplatin (area under the curve 2 mg/ml/min) on days 1, 8, and 15 of a 28-day cycle. Their medical records were retrospectively reviewed. A total of 31 patients were included in the study. Grade 3/4 neutropenia, anemia and thrombocytopenia developed in 18 (58%), 5 (16%) and 1 (3%) patients, respectively. Furthermore, three (10%) patients had a complete response (CR), 12 (39%) had a partial response (PR), 5 (16%) had stable disease and 11 (35%) had progressive disease. The overall response rate was 48% (15/31) and the disease control rate was 65% (20/31). The 5-year progression-free survival was 15% and the 5-year overall survival was 15%. A total of 9 patients survived for >40 months, one of whom survived without recurrence for 122 months. Performance status <3, a tumor response of CR or PR and >5 chemotherapy cycles were indicators of favorable prognosis. Only >5 chemotherapy cycles (vs. ≤5; P=0.002) was an independent good prognostic factor according to multivariate analysis. In conclusion, W-PC was tolerable and slightly effective in patients with ovarian cancer and poor general condition. W-PC may be one option for patients who are unable to receive standard chemotherapy regimens.