Risk factors for developing post-thymectomy myasthenia gravis in patients with thymoma.

BACKGROUND: Thymectomy is required for the treatment of thymoma-associated myasthenia gravis (MG). However, MG may develop only after thymectomy, a condition known as post-thymectomy MG. This study aimed to investigate the risk factors for post-thymectomy MG in patients with thymoma. METHODS: We retrospectively identified 235 patients with thymoma who underwent thymectomy at a single hospital from January 2008 to December 2017: 44 with preoperatively diagnosed MG were excluded, leaving 191 patients in the final analysis. Univariable survival analyses using Cox proportional hazards regression model and Kaplan-Meier estimate were conducted to identify risk factors for post-thymectomy MG. RESULTS: Post-thymectomy MG developed in 4.2% (8/191) of the patients with thymoma between 18 days and 108 mo after surgery. Hazard ratios (HRs) of pre- and postoperative anti-acetylcholine receptor antibody (AChR-Ab) titers were 2.267 (P = .002) and 1.506 (P < .001), respectively. Patients with extended thymectomy had a low chance of post-thymectomy MG (HR 0.035, P = .007). Larger thymoma (HR, 1.359; P = .005) and type A or AB thymoma according to World Health Organization histological classification (HR, 11.92; P = .021) were associated with higher chances of post-thymectomy MG. Within the subgroup of preoperatively AChR-Ab seropositive patients, post-thymectomy MG developed in 22.2% (6/27). CONCLUSIONS: Pre- and postoperative AChR-Ab levels should be measured in patients with thymoma. A large thymoma and partial thymectomy appear to be associated with a higher probability of post-thymectomy MG.

Searching for an ideal cervical cancer screening model to reduce false-negative errors in a country with high prevalence of cervical cancer.

The purpose of this study was to develop an ideal cervical cancer screening model to reduce false-negative errors in Korea where there is a high prevalence of cervical cancer. We conducted a cross-sectional study including 33,531 women who underwent routine cervical cancer screening in Korea. Colposcopic examinations were performed after abnormal results on their screening tests. Diagnostic capacities including sensitivity, specificity, and false-negative rate of each screening scenario were analysed at the CIN1 or worse (CIN1+) threshold with colposcopic biopsy results considered the gold standard. A total of 4117 women had valid results for Papanicolaou (Pap) cytology, human papilloma virus (HPV) tests, cervicography, and colposcopically directed biopsy were included in this study. The disease prevalence of CIN1+ was 38.1%. Pap-alone resulted in the highest false-negative rate of 46.9%, followed by HPV-alone at 25.1%, cervicography-alone at 18.7%, Pap/HPV-combined at 15.0%, Pap/cervicography-combined at 6.9% and Pap/HPV/cervicography-combined at 2.9% in a sample of 1570 women with CIN1+ lesions. Therefore, cervicography demonstrated excellent performance for the detection of CIN or cervical cancer and markedly reduced false-negative errors when used in combination with Pap cytology and HPV tests.IMPACT STATEMENTWhat is already known on this subject? False-negative rate of Pap smears is as high as approximately 40-50%. Limitations of the Papanicolaou (Pap) test have led to the development of new screening programmes for cervical cancer, such as combination screenings with human papillomavirus (HPV) tests or cervicography.What do the results of this study add? Pap-alone resulted in the highest false-negative rate of 46.9%, followed by HPV-alone at 25.1%, cervicography-alone at 18.7%, Pap/HPV-combined at 15.0%, Pap/cervicography-combined at 6.9% and Pap/HPV/cervicography-combined at 2.9% in a sample of 1570 women with CIN1+ lesions.What are the implications of these findings for clinical practice and/or further research? Cervicography demonstrated excellent performance for the detection of CIN or cervical cancer and markedly reduced false negative errors when used in combination with Pap cytology and HPV tests.

Efficacy of vestibular rehabilitation and its facilitating and hindering factors from real-world clinical data.

Background and purpose: Customized vestibular rehabilitation improved dizziness and imbalance in several randomized controlled trials. In the present study, we determined the efficacy of customized vestibular rehabilitation using real-world observational data. Methods: In this retrospective observational study, we recruited 64 patients (median age = 60, interquartile range = 48-66.3) who completed the customized vestibular rehabilitation from January to December 2022. The outcomes of rehabilitation were evaluated using the dizziness handicap inventory (DHI) or vestibular disorders activities of daily living scale (VADL). The factors associated with outcomes were assessed with a generalized linear model, of which covariates included patients' age, sex, duration of illness, type of vestibular disorders, initial DHI and VADL scores, exercise compliance, and initial hospital anxiety and depression scale (HADS) scores. Results: After the median of 6 (4-6) weeks of rehabilitation, DHI and VADL scores significantly improved in patients with either peripheral or central vestibular disorders (Wilcoxon signed-rank test, p < 0.05). The initial DHI and VADL scores showed a positive while the sum of HADS scores showed a negative correlation with the outcome. In contrast, the age, sex, duration of illness, types of vestibular disorders, and exercise compliance did not affect the outcome. Discussion and conclusion: Customized vestibular rehabilitation is effective for central as well as peripheral disorders, especially when the symptoms are severe and the psychological distress is mild.

Loss of torsional quick eye movements during head roll in progressive supranuclear palsy: a new diagnostic marker.

BACKGROUND AND OBJECTIVES: Even though impaired horizontal and vertical saccades are well-known features of progressive supranuclear palsy (PSP), abnormalities of torsional quick phases of eye movements have not been defined in PSP and other Parkinsonian syndromes. This study aims to determine the diagnostic value of decreased torsional quick phases during head oscillations in the roll plane in patients with PSP. METHODS: Using video-oculography, we recorded the head and eye motion during passive head oscillations in the roll plane and determined the decrease of torsional quick phases in patients with PSP (n = 13) in comparison to normal controls (n = 13) and those with multiple system atrophy (MSA, n = 17) or idiopathic Parkinson's disease (PD, n = 6). RESULTS: Torsional quick phases were absent during the torsional vestibulo-ocular reflex (VOR) in 78.6% (11/13) of the patients with PSP, but only in 11.8% (2/17) of those with MSA and none with idiopathic PD or of normal controls (Chi-square tests, p < 0.001) while gains of the torsional VOR did not differ among the groups (Chi-square tests, p > 0.05). Furthermore, the torsional quick phases were smaller even when observed in patients with PSP. CONCLUSION: Loss of torsional quick phases is an early biological marker for diagnosis of PSP, and may be ascribed to degeneration of the rostral interstitial nucleus of the medial longitudinal fasciculus that contains the burst neurons for torsional as well as vertical saccades.

Genetic polymorphism of PRKCDBP is associated with an increased risk of endometrial cancer.

PRKCDBP is a putative tumor suppressor located at 11p15.4, where frequent genomic loss has been observed in human cancers. We explored the possible association between an intra-exonic single nucleotide polymorphism (SNP), rs1051992, that results in a Leu to Pro substitution, and risk for endometrial carcinogenesis. We assessed the genotype of rs1051992 in endometrial cancer tissues from 147 patients and normal endometrial tissue from 191 healthy individuals by restriction endonuclease PvuII-based genotyping. Allele frequencies in the cancer specimens were compared with those in the healthy controls. We also evaluated the association between polymorphisms at this locus and histopathological features of endometrial cancer.

Correlation between FDG uptake by PET/CT and the expressions of glucose transporter type 1 and hexokinase II in cervical cancer.

BACKGROUND: The aim of this study was to explore the association between 2-deoxy-2-F18-fluoro-D-glucose uptake and the expressions of glucose transporter type 1 (GLUT-1) and hexokinase II (HK-II) in the lymph nodes of patients with cervical cancer. METHODS: This prospective study included 20 women with International Federation of Gynecology and Obstetrics stage IB to stage IIA cervical cancer who underwent positron emission tomography (PET)-computed tomography (CT) (PET/CT) before surgical treatment. In 333 dissected lymph nodes (LNs) obtained, we examined the size, tumor involvement, and expressions of GLUT-1 and HK-II. These characteristics were compared with PET/CT and pathological findings. RESULTS: Pathological analysis found that 21% (70) of the 333 surgically dissected LNs were metastatic. Positron emission tomography/CT detected metastasis with 22.8% sensitivity and 98.5% specificity. The levels of GLUT-1 and HK-II expression in false-positive LNs were higher than those in pathologically confirmed negative nodes (P = 0.015 and P = 0.001, respectively). In metastatic LNs, PET/CT-positive nodes were significantly different from PET/CT-negative nodes in mean size (P = 0.043), tumor involvement (P = 0.008), and proportion of GLUT-1-positive tumor cells (P = 0.042). CONCLUSIONS: Our results indicate that overexpression of GLUT-1 and HK-II may be related to 2-deoxy-2-F18-fluoro-D-glucose uptake in false-positive tissues on PET/CT. In metastatic lymph nodes, the ability of PET/CT to detect cancer may depend on tumor involvement, lymph node size, and GLUT-1 expression.

Frequent inactivation of hSRBC in ovarian cancers by promoter CpG island hypermethylation.

OBJECTIVE: To explore the implication of human SRBC gene [serum deprivation response factor-related gene product that binds to the c-kinase (hSRBC)] abnormality in ovarian tumorigenesis. DESIGN: Retrospective study. SETTING: Medical center. SAMPLE: Twenty-two epithelial ovarian cancer and six normal ovary tissues. MEASURES: Mutation and altered expression of hSRBC gene. METHODS: hSRBC expression was characterized by polymerase chain reaction (PCR) analysis. Promoter CG dinucleotide (CpG) site methylation was determined using methylation specific PCR and bisulfite sequencing. RESULTS: Expression of hSRBC transcript was easily detectable in all normal tissues we examined, but 50% (two of four) of cancer cell lines and 41% (nine of 22) of primary carcinomas exhibited undetectable or substantially decreased expression. While genomic deletion or somatic mutations of the gene was not identified, its expression was reactivated in tumor cells by 5-aza-2'-deoxycytidine treatment, suggesting epigenetic inactivation of the gene in tumors. Promoter methylation was detected in all nine tumors with low expression but in only one of 13 (7.7%) tumors with normal expression. Bisulfite DNA sequencing analysis of 23 CpG sites within the promoter region revealed that the CpG sites are highly methylated in low-expressing tumors. In addition, promoter CpG sites methylation status showed a tight association with gene expression level. CONCLUSION: Our data demonstrate that epigenetic inactivation of hSRBC due to aberrant promoter hypermethylation is a common event and might be implicated in human ovarian tumorigenesis.

Pulmonary toxicity after a quick course of combinatorial vincristine, bleomycin, and cisplatin neoadjuvant chemotherapy in cervical cancer.

Pulmonary toxicity is one of the most serious adverse effects associated with a quick course of vincristine, bleomycin, and cisplatin neoadjuvant chemotherapy (NAC-VBP). The aim of this study was to evaluate pulmonary toxicity related to a quick course NAC-VBP. A total of consecutive 61 patients, who underwent at most 3 cycles of NAC-VBP every 10 days in the International Federation of Gynecology and Obstetrics (FIGO) stage IB-IIB cervical cancer from 1995 to 2007, were retrospectively analyzed. Of the 61 study subjects, 7 (11.5%) were identified to have pulmonary toxicity and 2 (3.3%) died of pulmonary fibrosis progression despite aggressive treatment and the use of a multidisciplinary approach. No factor predisposing pulmonary toxicity was identified. Initial symptoms were non-specific, but bronchiolitis obliterans organizing pneumonia and interstitial pneumonitis were characteristic findings by high-resolution computed tomography of the chest. The benefit of steroid therapy was uncertain and was associated with steroid-induced diabetes mellitus requiring insulin therapy in two patients. Fatal pulmonary toxicity is a major concern of a quick course NAC-VBP. In conclusion, these patients require special monitoring for bleomycin-induced pulmonary toxicity.

Successful laparoscopic management of primary omental pregnancy.

Omental pregnancy is an extremely rare type of ectopic pregnancy. We present a case in which a 26-year-old woman was admitted to the emergency room with abdominal pain. She was diagnosed with a ruptured ectopic pregnancy after a positive urinary pregnancy test and transvaginal ultrasound. Laparoscopic surgery showed intact pelvic organs and an ectopic mass on the omentum. The patient was treated successfully with laparoscopic partial omentectomy, and pathologic examination confirmed an omental pregnancy. As evidenced by this case, laparoscopy can be useful to diagnose and treat unusually located ectopic pregnancies.

Tacrolimus for Treating Orbital and Cranial Form of Idiopathic Inflammatory Pseudotumors.

BACKGROUND AND PURPOSE: Orbital and cranial form of idiopathic inflammatory pseudotumors (IIPs) are rare disorders with heterogeneous clinical presentations. Corticosteroids have been the first-line treatment for IIPs, but they are not always effective. METHODS: We reviewed the medical records of three patients with orbital or cranial form of IIP who were treated with tacrolimus as an adjuvant treatment. RESULTS: The three patients showed favorable outcomes with the addition of tacrolimus, which is a calcineurin inhibitor that inhibits T-cell activation and T-cell-dependent B-cell activation. CONCLUSIONS: Tacrolimus may be a safe and effective immunosuppressant for refractory or relapsing form of orbital or cranial IIPs.

Neoadjuvant chemotherapy in bulky stage IB-IIA cervical cancer: results of a quick course with vincristine, bleomycin, and cisplatin.

We retrospectively analyzed 51 consecutive patients with bulky International Federation of Gynecology and Obstetrics stage IB-IIA cervical cancer who were treated with vincristine (1 mg/m), bleomycin (25 mg/m; days 1-3), and cisplatin (50 mg/m) every 10 days between 1995 and 2005 to assess the efficacy and the safety of a quick course of neoadjuvant chemotherapy. A clinical response occurred in 37 patients (72.5%), including 7 patients (13.7%) with a complete response and 30 patients (58.8%) with a partial response; 13 patients (25.5%) had a stable disease, and 1 patient (2.0%) had a progressive disease. Among the 50 patients who were surgically explored, 42 patients had a radical hysterectomy with pelvic and para-aortic lymphadenectomy; radical surgery was aborted in 8 patients because of paracervical and para-aortic lymph node involvement. Hematologic toxicity was the most common adverse event with anemia occurring most frequently, followed by leukopenia. Importantly, pulmonary toxicity occurred in 7 patients, 2 of whom died of complications from pulmonary fibrosis 1 and 3 months after radical surgery. With a median follow-up of 53 months (range, 2-129 months), the estimated 2- and 5-year survival rates were 74.9% and 61.3%, respectively. In conclusion, the survival benefit of a quick course of neoadjuvant chemotherapy consisting of vincristine, bleomycin, and cisplatin may be uncertain despite the significant clinical response in bulky International Federation of Gynecology and Obstetrics stage IB2-IIA cervical cancer. Special care is required to monitor bleomycin-induced pulmonary toxicity.

Video-assisted thoracoscopic surgery for recurrent ovarian cancer with a metastatic mediastinal mass.

BACKGROUND: Although primary cytoreductive surgery is well accepted as a cornerstone of the management for epithelial ovarian cancer, the benefits of secondary cytoreduction in recurrent ovarian cancer remain unclear. Furthermore, no consensus has been reached regarding treatment strategies for extraperitoneal metastasis. CASE REPORT: A 29-year-old woman was admitted to our hospital due to suspected recurrent ovarian cancer. Four years previously, she had undergone primary debulking surgery which was followed by adjuvant chemotherapy consisting of paclitaxel (175 mg/m(2)) and carboplatin (area under the curve = 5) for 6 cycles due to an ovarian papillary serous adenocarcinoma stage IIIc. Preoperative evaluation revealed a palpable inguinal mass and multiple enlarged pelvic lymph nodes with a well-defined mediastinal mass on abdomino-pelvic and chest computed tomography. Secondary debulking combined with video-assisted thoracoscopic surgery (VATS) was performed. The patient had no discernable evidence of disease at her 18-month follow-up. CONCLUSION: VATS may be a reasonable option for secondary debulking in selected patients with isolated mediastinal metastasis.

Screening capacity and cost-effectiveness of the human papillomavirus test versus cervicography as an adjunctive test to Pap cytology to detect high-grade cervical dysplasia.

OBJECTIVE: This study compared the screening capacities and cost-effectiveness of the human papillomavirus (HPV) test versus cervicography as an adjunctive test to Papanicolaou (Pap) cytology to detect high-grade cervical neoplasia in Korea, a country with a high prevalence of cervical cancer. STUDY DESIGN: Of 33,531 Korean women who underwent cervicography as a screening test for cervical cancer between January 2015 and December 2016, we retrospectively analyzed the records of 4117 women who simultaneously or subsequently underwent Pap cytology, an HPV test, cervicography, and colposcopically directed biopsy. At a threshold of cervical intraepithelial neoplasia grade 2 or worse (CIN2+), based on colposcopic biopsy, we compared the diagnostic capacities and cost-effectiveness of these screening tools. RESULTS: The CIN2+ prevalence was 10.8% (446 of 4117 women) and the positive rate of high-risk HPV was 61.0% (2511 of 4117 women). Cervicography as an adjunctive to Pap cytology was a more sensitive test (97.5% vs 93.7%) with a higher odds ratio (15.65 vs 5.86) than the HPV test for detection of CIN2+ (P-value = 0.003). Moreover, the cost of cervicography co-testing was 23% less than that of HPV co-testing, decreasing the cost per patient with CIN2+ lesions from $1474 to $1135. CONCLUSION: Cervicography and Pap co-testing had superior screening capacity and cost-effectiveness for detection of preinvasive cervical lesions than HPV and Pap co-testing and may be an effective and cost-saving screening strategy in clinical practice in country with a high prevalence of cervical cancer.

Pulsed diode laser-based singlet oxygen monitor for photodynamic therapy: in vivo studies of tumor-laden rats.

Photodynamic therapy (PDT) is a promising cancer treatment that involves optical excitation of photosensitizers that promote oxygen molecules to the metastable O(2)(a(1)Delta) state (singlet oxygen). This species is believed to be responsible for the destruction of cancerous cells during PDT. We describe a fiber optic-coupled, pulsed diode laser-based diagnostic for singlet oxygen. We use both temporal and spectral filtering to enhance the detection of the weak O(2)(a-->X) emission near 1.27 microm. We present data that demonstrate real-time singlet oxygen production in tumor-laden rats with chlorin e6 and 5-aminolevulinic acid-induced protoporphyrin photosensitizers. We also observe a positive correlation between post-PDT treatment regression of the tumors and the relative amount of singlet oxygen measured. These results are promising for the development of the sensor as a real-time dosimeter for PDT.

In-vivo singlet oxygen dosimetry of clinical 5-aminolevulinic acid photodynamic therapy.

Photodynamic therapy (PDT) is a viable treatment option for a wide range of applications, including oncology, dermatology, and ophthalmology. Singlet oxygen is believed to play a key role in the efficacy of PDT, and on-line monitoring of singlet oxygen during PDT could provide a methodology to establish and customize the treatment dose clinically. This work is the first report of monitoring singlet oxygen luminescence in vivo in human subjects during PDT, demonstrating the correlation of singlet oxygen levels during PDT with the post-PDT photobiological response.

Pulsed diode laser-based monitor for singlet molecular oxygen.

Photodynamic therapy (PDT) is a promising cancer treatment. PDT uses the affinity of photosensitizers to be selectively retained in malignant tumors. When tumors, pretreated with the photosensitizer, are irradiated with visible light, a photochemical reaction occurs and tumor cells are destroyed. Oxygen molecules in the metastable singlet delta state O2(1Delta) are believed to be the species that destroys cancerous cells during PDT. Monitoring singlet oxygen produced by PDT may lead to more precise and effective PDT treatments. Our approach uses a pulsed diode laser-based monitor with optical fibers and a fast data acquisition system to monitor singlet oxygen during PDT. We present results of in vitro singlet oxygen detection in solutions and in a rat prostate cancer cell line as well as PDT mechanism modeling.

Acute Ischemic Stroke Mimicking Non-Convulsive Status Epilepticus.

Status epilepticus and stroke are occasionally characterized by indistinguishable symptoms. Diffusion-weighted imaging (DWI) could not only help differentiating seizure from stroke, but also assist in localizing a focus of seizure and reflect resolution of seizure. We report a case of non-convulsive status epilepticus that presented as acute ischemic stroke, mimicking the latter's clinical manifestations. A 77-year-old right-handed man visited the emergency room with complaints of impaired awareness and fluency with right hemiparesis. Moreover, he presented with first-onset focal to bilateral tonic-clonic seizure with eyeball deviation to the right for 1 minute. Magnetic resonance imaging showed hyperintensity on DWI with a reduced apparent diffusion coefficient (ADC) value in the left pulvinar and left temporo-occipital areas. However, eyeball deviation to the right was not matched with left hemispheric stroke. Electroencephalography (EEG) confirmed ictal discharges in the left temporal area, which were compatible with impaired awareness, ictal aphasia, and eyeball deviation to the right. In cases of conflicting results from neurological examination and DWI/ADC findings, clinicians should consider employing EEG for diagnosing and treating non-convulsive status epilepticus.