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1.
J Gynecol Oncol ; 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38178702

ABSTRACT

OBJECTIVE: In Japan, perioperative prophylaxis of pulmonary embolism (PE) in gynecologic cancer patients with preoperative asymptomatic venous thromboembolism (VTE) has not been well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-arm clinical trial to investigate the prevention of postoperative symptomatic PE onset by seamless anticoagulant therapy from the preoperative period to 4 weeks after surgery instead of using intermittent pneumatic compression. METHODS: Anticoagulant therapy was started immediately after asymptomatic VTE diagnosis and stopped preoperatively according to the rules of each institution. Unfractionated heparin administration was resumed within 12 hours postoperatively, and this was followed by the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle was continued for 28 days. Primary outcome was the occurrence of symptomatic PE in 28 days postoperatively. Secondary outcomes were the incidence of VTE-related events in 28 days and 6 months postoperatively and protocol-related adverse events. RESULTS: Between February 2018 and September 2020, 99 patients were enrolled; of these, 82 patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube, or peritoneal cancer; 21 for endometrial cancer; and 3 for cervical cancer. No symptomatic PE was observed within 28 days postoperatively; two patients had bleeding events (major bleeding and clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increased alanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase). CONCLUSION: The multifaceted perioperative management for gynecologic malignancies with asymptomatic VTE effectively prevented postoperative symptomatic PE. TRIAL REGISTRATION: JRCT Identifier: jRCTs031180124.

2.
World Neurosurg ; 183: e796-e800, 2024 03.
Article in English | MEDLINE | ID: mdl-38218438

ABSTRACT

BACKGROUND: Recent literature suggests that sagittal imbalance is a risk factor for adjacent segment disease following fusion surgery. This study explored the influence of pelvic incidence minus lumbar lordosis (PI-LL) mismatch on the mid-term results and reoperation rate after single-level posterior lumbar interbody fusion (PLIF). METHODS: The participants of this study included 253 patients (80 men and 173 women; mean age 68.2 years) who underwent L4-5 single-segment PLIF. Preoperative PI-LL mismatch was defined as a PI-LL of 30° or greater. The patients were divided into 2 groups according to the presence or absence of PI-LL mismatch (PI-LL mismatch group; group M, Control group; group C), and the clinical outcomes and radiographic parameters were compared. RESULTS: Of the 253 cases, 25 were classified in group M and 228 in group C. The Japanese Orthopaedic Association score at 5 years postoperatively was 23.0 ± 3.6 in group M and 23.5 ± 5.1 in group C, and the recovery rate was 66.2 ± 32.6% in group M and 64.6 ± 21.4% in group C and there was no significant difference in the recovery rate between the 2 groups. All radiographic parameters except sacral slope were significantly worse in group M. One patient (4.3%) in Group M and 18 patients (7.8%) in Group C required revision surgery at 2.4 years (range 0.0-5.0) and there was no significant difference in the revision rate between the 2 groups. CONCLUSIONS: The mid-term results of L4-5 single-level PLIF were compared with and without PI-LL mismatch, with the threshold defined as 30°; however, there were no significant differences in both the Japanese Orthopaedic Association recovery and reoperation rates between the 2 groups.


Subject(s)
Lordosis , Spinal Fusion , Male , Animals , Humans , Female , Aged , Lordosis/diagnostic imaging , Lordosis/surgery , Lordosis/etiology , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Retrospective Studies , Postoperative Complications/diagnostic imaging , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Spinal Fusion/methods
5.
Cancer Rep (Hoboken) ; 7(1): e1934, 2024 01.
Article in English | MEDLINE | ID: mdl-38013666

ABSTRACT

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.


Subject(s)
Ovarian Neoplasms , Progesterone , Female , Humans , Progesterone/pharmacology , Progesterone/physiology , Receptors, Progesterone/genetics , Receptors, Progesterone/metabolism , bcl-2-Associated X Protein , Progestins/pharmacology , Medroxyprogesterone Acetate/pharmacology , Ovarian Neoplasms/drug therapy , Genomics , Cell Death
6.
J Orthop Sci ; 29(2): 508-513, 2024 Mar.
Article in English | MEDLINE | ID: mdl-36894404

ABSTRACT

BACKGROUND: Because of the high incidence of major perioperative adverse events, spine surgery in dialysis patients should be recommended carefully after consideration of its risks and benefits. However, the benefits of spine surgery in dialysis patients remain unclear because of the lack of long-term outcomes. The purpose of this study is to elucidate the long-term outcomes of spine surgery in dialysis patients, focusing on activities of daily living (ADLs), life expectancy, and risk factors for postoperative mortality. METHODS: Data for 65 dialysis patients who underwent spine surgery at our institution and were followed up for a mean duration of 6.2 years were retrospectively reviewed. ADLs, number of surgeries, and survival times were recorded. The postoperative survival rate was calculated using the Kaplan-Meier method, and risk factors for postoperative mortality were investigated using a generalized Wilcoxon test and multivariate Cox proportional-hazards model. RESULTS: Compared with preoperative ADLs, ADLs significantly improved at discharge after surgery and at the final follow-up. However, 16 of the 65 patients (24.6%) underwent multiple surgeries, and 34 (52.3%) died during the follow-up period. Kaplan-Meier analysis revealed that the survival rate after spine surgery was 95.4% at 1 year, 86.2% at 3 years, 69.6% at 5 years, 59.7% at 7 years, and 28.7% at 10 years, and the overall median survival time was 99 months. Multivariate Cox regression analysis showed that a dialysis period of ≥10 years was a significant risk factor. CONCLUSIONS: Spine surgery in dialysis patients improved and maintained ADLs in the long term and did not shorten life expectancy. However, dialysis patients undergoing spine surgery require multiple surgeries more frequently, and a dialysis period of ≥10 years is a significant risk factor for postoperative mortality.


Subject(s)
Activities of Daily Living , Renal Dialysis , Humans , Retrospective Studies , Risk Factors , Life Expectancy , Postoperative Complications/epidemiology , Treatment Outcome
7.
J Obstet Gynaecol Res ; 50(3): 501-507, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38115203

ABSTRACT

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.


Subject(s)
Indazoles , Neoplasm Recurrence, Local , Ovarian Neoplasms , Piperidines , Female , Humans , Creatinine , Retrospective Studies , Ovarian Neoplasms/drug therapy
8.
Osong Public Health Res Perspect ; 14(5): 427-432, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37920898

ABSTRACT

BACKGROUND: As the population ages worldwide, including in Japan, there is a growing expectation for older adults to remain active participants in society. The act of sharing one's experiences and knowledge with younger generations through social engagement not only enriches the lives of older individuals, but also holds significant value for our society. In this study, we examined both positive and negative perceptions of older adults and investigated the correlation between these perceptions and generativity among older citizens. Additionally, we evaluated the impact of life satisfaction on these factors. METHODS: We conducted a survey of 100 older adults in Japan (mean age, 71.68 years) and utilized multiple regression analyses, using positive and negative perceptions of older adults, life satisfaction, and demographic factors as independent variables. The sub-categories of generativity-namely, generative action, concern, and accomplishment-were used as dependent variables. RESULTS: Participants who held a more positive perception of older adults demonstrated a higher level of generative actions and concerns. Additionally, participants who reported higher levels of life satisfaction also exhibited more generative actions, concerns, and accomplishments. Conversely, those who held a more negative perception of older adults were found to have higher levels of generative actions. CONCLUSION: Enhancing positive perceptions of older adults among them can boost the sub-categories of generativity. This study, which was conducted from an exploratory perspective, has several limitations, including a potential sampling bias. A more comprehensive examination of the relationship between perceptions of older adults and generativity is anticipated in future research.

9.
J Spine Surg ; 9(3): 269-277, 2023 Sep 22.
Article in English | MEDLINE | ID: mdl-37841797

ABSTRACT

Background: The importance of spinopelvic sagittal alignment for adjacent segment disease (ASD) after lumbar fusion surgery has been reported. However, no longitudinal cohort studies have determined the extent to which segmental alignment and spinopelvic global alignment can be achieved using 12° lordotic cages in posterior lumbar inter-body fusion (PLIF) and the extent to which the development of ASD can be prevented. The purpose of this study was to analyze changes in segmental and spinopelvic sagittal alignment after single-segment PLIF with 12° lordotic cages, to clarify the relationship between changes in segmental and spinopelvic sagittal alignment, and to report the incidence of ASD at 2 years postoperatively. Methods: Subjects in this 2-year prospective longitudinal cohort study were 28 patients who had undergone L4/5 PLIF using 12° lordotic cages. Incidence of operative ASD (O-ASD) was evaluated as clinical outcomes. Radiological measurements were examined preoperatively and at 3 months, 1 year and 2 years postoperatively. The following radiographic spinopelvic parameters were measured: segmental lordosis (SL) at L4/5; sagittal vertical axis (SVA); T1 pelvic angle (TPA); thoracic kyphosis (TK); lumbar lordosis (LL); sacral slope (SS); pelvic tilt (PT); and pelvic incidence (PI). With respect to radiological outcomes, changes in SL (ΔSL) and spinopelvic parameters and the incidence of radiological ASD (R-ASD) were evaluated. Correlations of ΔSL and changes in other spinopelvic parameters (ΔSVA, ΔTPA, ΔTK, ΔLL, ΔSS, ΔPT, and ΔPI-LL) between preoperatively and 3 months postoperatively were examined. Results: The follow-up rate was 100% (n=28) at 1 year postoperatively and 96.4% (n=27) at 2 years postoperatively. No cases of O-ASD were seen during 2 years of follow-up. Significant realignment was observed and maintained at 2 years postoperatively in almost all spinopelvic sagittal parameters (SL, SVA, TPA, LL, PT, PI-LL). Regarding the correlation between ΔSL and other parameters, significant correlations were detected with ΔSVA (r=-0.37, P<0.05) and ΔLL (r=0.538, P<0.01). Three cases (11.1%) showed R-ASD at 2 years postoperatively. Conclusions: PLIF with 12° lordotic cages for L4 degenerative spondylolisthesis improved SL and global sagittal realignment, and achieved satisfactory clinical outcomes with a low incidence of ASD during 2 years of follow-up.

10.
Taiwan J Obstet Gynecol ; 62(4): 559-561, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37407194

ABSTRACT

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.


Subject(s)
Pulmonary Embolism , Venous Thrombosis , Female , Humans , Middle Aged , Venous Thrombosis/etiology , Ovary/surgery , Ovary/blood supply , Pulmonary Embolism/etiology , Anticoagulants/therapeutic use , Tomography, X-Ray Computed/methods
12.
J Behav Ther Exp Psychiatry ; 79: 101822, 2023 06.
Article in English | MEDLINE | ID: mdl-36494217

ABSTRACT

BACKGROUND AND OBJECTIVES: Overgeneral autobiographical memory (OGM) has been shown to occur in depressed and previously depressed populations regardless of the emotional valence of cues. However, recent research has pointed out that the retrieval process underlying OGM, generative retrieval (i.e., retrieval requiring effort or additional information) or direct retrieval (i.e., memory that comes to consciousness without effort or additional information), may differ depending on the emotional valence of cues. We examined the hypotheses that a remitted MDD (major depressive disorder), group compared with a control group, would show (a) more direct retrieval of categoric memories for negative cues, (b) more generative retrieval of categoric memories for positive cues, and (c) less direct retrieval of specific memories for positive cues. METHODS: A remitted clinical MDD group (n = 21) and control group (n = 21) completed the Autobiographical Memory Test with minimal instruction, and were required to subjectively judge generative retrieval and direct retrieval. RESULTS: As expected, results showed that the remitted MDD group reported more frequent direct retrieval of categoric memory for negative cues and more generative retrieval of categoric memory for positive cues than the control group. LIMITATIONS: Our paradigm for distinguishing between generative and direct retrieval relied on subjective judgements. CONCLUSIONS: This extends the findings from student sample in previous studies to a help-seeking population. Increased availability of negative categoric memories and the attenuation of positive specific recall represent vulnerabilities for MDD. We discuss how these findings provide further rationale for memory therapeutics for MDD and refinement of those techniques.


Subject(s)
Depressive Disorder, Major , Memory, Episodic , Humans , Depressive Disorder, Major/psychology , Cues , Mental Recall , Emotions
13.
Exp Ther Med ; 23(6): 409, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35619629

ABSTRACT

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.

14.
J Obstet Gynaecol Res ; 48(4): 1046-1049, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35174580

ABSTRACT

Ovarian vein thrombosis (OVT) usually occurs on the right side in women with underlying conditions such as pelvic diseases and thrombophilia or during the postpartum period. Here, we present a patient with bilateral OVTs without underlying conditions. A 63-year-old woman without remarkable past or family histories complained of mild lower abdominal pain. Computed tomography revealed bilateral OVTs, with the right-sided thrombus nearly progressing into the inferior vena cava. The presence of symptoms and risk of thrombus extension/pulmonary embolism (PE) led us to administer an oral anticoagulant (rivaroxaban) promptly. Her symptom improved gradually and bilateral OVTs disappeared by 3 months without any evidence of PE. The present case suggests that OVT can occur in a woman without underlying conditions, and the use of an anticoagulant may be a treatment option in such a case.


Subject(s)
Pulmonary Embolism , Thrombosis , Venous Thrombosis , Female , Humans , Middle Aged , Ovary/blood supply , Vena Cava, Inferior , Venous Thrombosis/diagnosis , Venous Thrombosis/drug therapy
15.
Mol Clin Oncol ; 16(1): 14, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34881034

ABSTRACT

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.

16.
Mol Clin Oncol ; 15(6): 263, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34777799

ABSTRACT

A previous study by our group reported that removing a larger number of lymph nodes in patients with stage I ovarian clear cell carcinoma (OCCC) improved progression-free survival (PFS). The present study investigated whether clinical conditions, particularly the number of removed lymph nodes, are independent predictors of progression for stage II or higher OCCC and whether the significance of the number of removed lymph nodes differs according to FIGO stage for OCCC. A total of 113 patients with OCCC who had undergone surgery between January 1993 and December 2015 were retrospectively enrolled and the clinicopathological data were obtained from their medical records. Among patients with stage II or higher OCCC, PFS of those with no residual tumor or no lymph node metastasis was significantly better than that of those with residual tumor (P=0.023) or lymph node metastasis (P=0.035). Multivariate analysis revealed that no residual tumor was the only independent predictor for improved PFS of patients with stage II or higher. Regarding the number of removed lymph nodes, it did not significantly affect the PFS of patients with stage II or higher OCCC, whereas it improved the PFS of those with stage I, being an independent predictor of progression of stage I OCCC. In summary, although the number of removed lymph nodes was an independent predictor of progression for stage I OCCC, it was not for stage II or higher OCCC. The prognostic significance of the number of removed lymph nodes in OCCC may differ depending on the FIGO stage.

17.
World Neurosurg ; 154: e762-e769, 2021 10.
Article in English | MEDLINE | ID: mdl-34365048

ABSTRACT

OBJECTIVE: Only a few studies have addressed clinical outcomes of revision surgery for adjacent segment disease. The purpose of this study was to elucidate clinical outcomes of second (repeat) posterior lumbar interbody fusion (PLIF) by focusing on the relationship between clinical outcomes and spinopelvic parameters and predisposing factors requiring subsequent corrective long fusion after repeat PLIF. METHODS: We analyzed the data of 47 patients ≥40 years old who underwent repeat PLIF after single-segment PLIF owing to adjacent segment disease. The correlation between clinical outcomes and radiographic parameters was investigated. Patient demographics and radiographic parameters were compared between patients with and without subsequent corrective long fusion. RESULTS: Japanese Orthopaedic Association score at final follow-up was 13.4, and the recovery rate was 37.2%. All sagittal parameters except pelvic tilt and C7-central sacral vertical line at final follow-up showed weak to moderate (|r| = 0.30-0.56) correlation with clinical scores. Finally, 11% of patients required subsequent long corrective fusion. Pelvic incidence minus lumbar lordosis (PI-LL) mismatch (cutoff value of 27.5°) and thoracic kyphosis (cutoff value of 12.5°) before repeat PLIF were identified as predisposing factors for subsequent long corrective fusion. CONCLUSIONS: The clinical outcomes of repeat PLIF were inferior to outcomes of primary PLIF. Once PI-LL mismatch occurs after initial PLIF, it will be difficult to resolve the PI-LL mismatch during the second PLIF. To stop the chain of reoperations in patients whose preoperative PI-LL exceeds 27.5° before repeat PLIF, corrective long fusion may be a surgical option to consider.


Subject(s)
Lordosis , Pelvis/surgery , Reoperation , Spinal Fusion/adverse effects , Aged , Female , Humans , Incidence , Lumbar Vertebrae/surgery , Male , Preoperative Period , Reoperation/statistics & numerical data , Retrospective Studies , Treatment Outcome
18.
J Neurosurg Spine ; 35(4): 454-459, 2021 Jul 23.
Article in English | MEDLINE | ID: mdl-34298517

ABSTRACT

OBJECTIVE: Although several reports have described adjacent-segment disease (ASD) after posterior lumbar interbody fusion (PLIF), there have been only a few reports focusing on early-onset ASD occurring within 3 years after primary PLIF. The purpose of this study was to investigate the prevalence and postoperative pathologies of early-onset ASD and its relation with radiological parameters such as segmental lordosis (SL). METHODS: The authors reviewed a total of 256 patients who underwent single-segment PLIF at L4-5 for degenerative lumbar spondylolisthesis (DLS) and were followed up for at least 5 years. The definition of ASD was a symptomatic condition requiring an additional operation at the adjacent fusion segment in patients who had undergone PLIF. ASD occurring within 3 years after primary PLIF was categorized as early-onset ASD. As a control group, 54 age- and sex-matched patients who had not suffered from ASD for more than 10 years were selected from this series. RESULTS: There were 42 patients with ASD at the final follow-up. ASD prevalence rates at 3, 5, and 10 years postoperatively and at the final follow-up were 5.0%, 8.2%, 14.1%, and 16.4%, respectively. With respect to ASD pathologies, lumbar disc herniation (LDH) was significantly more common in early-onset ASD, while lumbar spinal stenosis and DLS occurred more frequently in late-onset ASD. Significant differences were detected in the overall postoperative range of motion (ROM) and in the changes in ROM (ΔROM) at L3-4 (the cranial adjacent fusion segment) and changes in SL (ΔSL) at L4-5 (the fused segment), while there were no significant differences in other pre- and postoperative parameters. In stepwise logistic regression analysis, ΔSL was identified as an independent variable (p = 0.008) that demonstrated significant differences, especially in early-onset ASD (control 1.1° vs overall ASD -2.4°, p = 0.002; control 1.1° vs early-onset ASD -6.6°, p = 0.00004). CONCLUSIONS: The study results indicated that LDH was significantly more common as a pathology in early-onset ASD and that ΔSL was a major risk factor for ASD, especially early-onset ASD.


Subject(s)
Intervertebral Disc Displacement/surgery , Lordosis/surgery , Lumbar Vertebrae/surgery , Spinal Fusion , Spondylolisthesis/surgery , Adult , Aged , Female , Follow-Up Studies , Humans , Lumbosacral Region/surgery , Male , Middle Aged , Postoperative Complications/diagnostic imaging , Risk Factors , Spinal Fusion/methods , Spinal Stenosis/surgery , Young Adult
20.
Cancer Med ; 10(8): 2732-2739, 2021 04.
Article in English | MEDLINE | ID: mdl-33710778

ABSTRACT

Vasohibin-1 (VASH1) is a VEGF-inducible endothelium-derived angiogenesis inhibitor, and vasohibin-2 (VASH2), its homolog, exhibits proangiogenic activity. VASH2 is expressed by various cancer cells and accelerates tumor angiogenesis and progression. VASH2 was recently shown to exhibit tubulin carboxypeptidase (TCP) activity related to microtubule functions. Paclitaxel (PTX), an effective chemotherapeutic agent that is widely used to treat ovarian cancer, inhibits microtubule depolymerization and may interact with VASH2. We herein established several VASH2 knockout ovarian cancer cell lines using the CRISPR/Cas9 genome editing system to examine the intracellular tubulin detyrosination status and PTX chemosensitivity. The knockout of VASH2 did not affect the proliferation or sphere-forming activity of ovarian cancer cells in vitro. A Western blot analysis of VASH2 knockout cells revealed the weak expression of detyrosinated tubulin and upregulated expression of cyclin B1. The knockout of VASH2 significantly increased chemosensitivity to PTX, but not to cisplatin in ovarian cancer cell lines. The knockout of VASH2 reduced TCP activity and increased cyclin B1 expression, resulting in increased PTX chemosensitivity in ovarian cancer cells. The inhibition of angiogenesis and regulation of microtubule activity may be achieved in ovarian cancer treatment strategies targeting VASH2.


Subject(s)
Angiogenic Proteins/genetics , Carboxypeptidases/metabolism , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Paclitaxel/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , CRISPR-Cas Systems , Carboxypeptidases/genetics , Cell Culture Techniques/methods , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Proliferation/genetics , Cyclin B1/metabolism , Female , Gene Knockdown Techniques , Humans , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Tubulin/metabolism , Tyrosine/genetics , Tyrosine/metabolism
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