A case of cardiac metastasis of neuroendocrine tumor with 2-year follow-up.

A 55-year-old male underwent surgery for thymus gland tumors six years previously, and for lung and pancreas tumors three years previously, which were pathologically diagnosed as neuroendocrine tumors (NETs). During routine medical checkups, a giant negative T-wave was observed on the electrocardiogram. Echocardiography revealed a tumor at the apex. A surgical biopsy was performed; the tumor was diagnosed as a cardiac metastasis of NETs, and chemotherapy was initiated. Two years later, echocardiography confirmed that the tumor had not increased in size. A 2-year follow-up of NETs cardiac metastasis is rare; we therefore report this case. Learning objective: Neuroendocrine tumors are considered slowly progressing tumors, but despite the presence of cardiac metastasis, accurate diagnosis and appropriate treatment have allowed the patient to survive the disease for more than two years.

Cardio-Ankle Vascular Index and Left Atrial Reverse Remodeling After Ablation for Atrial Fibrillation.

Arterial stiffness has been reported to cause left atrial (LA) remodeling due to increased left ventricular filling pressure, resulting in atrial fibrillation (AF). This study aimed to evaluate the association between LA reverse remodeling (LARR) after AF ablation and cardio-ankle vascular index (CAVI), an indicator of arterial stiffness.This study included 333 patients with AF (171 with paroxysmal AF and 162 with nonparoxysmal AF) and LA enlargement (LA volume index ≥ 34 mL/m2) who underwent AF ablation between December 2008 and July 2021. CAVI was evaluated preoperatively during AF (n = 155, 46.5%) or sinus rhythm (n = 178, 53.5%). Participants were divided into groups with LARR (n = 133, 39.9%) and without LARR (n = 200, 60.1%) according to whether the degree of decrease in LA volume index on transthoracic echocardiography 6 months after ablation was ≥ 15% or < 15%, respectively.Sinus rhythm was maintained in 168 (50.5%) patients within 3-6 months after the index procedure. Univariate analysis revealed that preoperative CAVI (7.80 ± 1.22 versus 8.57 ± 1.09, P < 0.001) was significantly lower, and the maintenance of sinus rhythm (61.6% versus 43.0%, P = 0.0011) was higher in the group with LARR. Multivariate logistic regression analysis revealed that preoperative CAVI was independently associated with LARR (odds ratio, 0.60, 95% confidence interval, 0.46-0.78, P < 0.001).In patients with AF and LA enlargement, CAVI is independently associated with LA reverse remodeling after catheter ablation.

The Kagoshima-DVT Score Is a Useful Predictive Model for Cancer-Associated Thrombosis in Patients With Gastrointestinal Cancer.

Background: Cancer-associated thrombosis (CAT) is a common complication of cancer and has received increasing attention; the Khorana Risk Score (KRS) is a recommended but insufficient risk assessment model for CAT. We propose a novel Kagoshima-DVT score (KDS) to predict preoperative deep vein thrombosis (DVT). This scoring method scores D-dimer ≥1.5 µg/mL, age ≥60 years, female sex, ongoing glucocorticoids, cancer with high risk of DVT, and prolonged immobility. The purpose of this study was to compare the performance of the KDS and KRS in predicting CAT in patients with gastrointestinal cancer. Methods and Results: In all, 250 patients without a history of thrombosis who received their first chemotherapy for gastrointestinal cancer were divided into low- (48.0%), intermediate- (38.8%), and high-risk (13.2%) groups for CAT development by the KDS. The patients' median age was 67 years and 63.2% were men. In all, 61 (27.1%) patients developed CAT (17.6%, 35.3%, and 36.4% of patients in the low-, intermediate, and high-risk groups, respectively; log-rank P=0.006). The area under the time-dependent receiver operating characteristic curve for CAT occurrence within 1 year was larger for the KDS than KRS (0.653 vs. 0.494). Conclusions: A high KDS at the start of first chemotherapy is a risk indicator for CAT development during chemotherapy. Moreover, the KDS is more useful than the KRS in predicting CAT risk.

A new pre-test probability score for diagnosis of deep vein thrombosis in patients before surgery.

BACKGROUND: Venous thromboembolism is a serious perioperative complication. We developed a new pre-test probability score for predicting deep vein thrombosis (DVT) before surgery. METHODS: Whole leg ultrasonography was performed on 973 inpatients and outpatients with suspected DVT based on a preoperative D-dimer cut-off value of ≥ 1 µg/ml. We allocated two-thirds (n = 651) of the study participants to a derivation cohort and one-third (n = 322) to a validation cohort. The pre-test probability model was developed from the derivation cohort data. RESULTS: The pre-test probability model for DVT assigned 2 points to D-dimer ≥ 1.5 µg/mL and 1 point each to age ≥ 60 years, female sex, ongoing glucocorticoid therapy, prolonged immobility, and cancer with high risk of DVT. The area under the curve of the pre-test probability score was 0.72 and 0.70 in the derivation and validation cohorts, respectively. The rates of DVT according to pre-test probability scores in the derivation and validation cohorts were 7% and 6% in the low (score = 0-2), 23% and 22% in the intermediate (score = 3-4), and 47% and 50% in the high probability group (score ≥ 5), respectively (p < 0.0001). CONCLUSIONS: The pre-test probability score (Kagoshima-DVT score) was helpful in detecting preoperative DVT in both inpatients and outpatients. We identified low probability group to reduce whole-leg ultrasonography and high probability group to detect more DVT before surgery.

Influence of Diabetes Mellitus on Surgical Outcomes in Patients with Cervical Myelopathy: A Prospective, Multicenter Study.

STUDY DESIGN: Multicenter, prospective study. PURPOSE: To investigate the effects of diabetes mellitus (DM) on surgical outcomes in patients with cervical myelopathy. OVERVIEW OF LITERATURE: To date, few studies have investigated the influence of postoperative blood glucose or glycated hemoglobin (HbA1c) levels on surgical outcomes. METHODS: The participants were patients who underwent surgery for the treatment of cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament. The 61 cases were evaluated preoperatively and 1 year postoperatively using the Japanese Orthopaedic Association (JOA) scores and the JOA Cervical Myelopathy Evaluation Questionnaire (JOACMEQ). The study variables included fasting blood glucose and HbA1c levels measured preoperatively and at 1 week, 4 weeks, and 1 year postoperatively; the F-wave conduction velocity, latency, rate of occurrence, and M-wave latency in the ulnar and tibial nerves were measured preoperatively and at 1 year postoperatively. The patients were divided into a group without diabetes (N group, 42 patients) and a group with diabetes (DM group, 19 patients). We then assessed the associations between the surgical outcomes and each of the study variables. RESULTS: JOA scores significantly improved in both groups; however, no significant between-group differences were found. There was no significant improvement in the JOACMEQ scores, which assessed cervical function, upper and lower limb function, and bladder function in both groups. We then subdivided the DM group into those with a good control of HbA1c after 1 year (DMG group, 12 patients) and those with HbA1c deterioration after 1 year (DMB group, seven patients), prior to comparing the surgical outcomes. The JOACMEQ scores for upper and lower limb function significantly improved in the DMG group (p<0.01). Compared with the DMB group, there were no significant increases in upper or lower limb function scores in the DMG group. CONCLUSIONS: Poor glycemic control might prevent postoperative functional recovery of the spinal cord.

Transient dual-luciferase assay combined with a glucocorticoid-inducible system for rice protoplasts.

We describe a transient dual-luciferase assay combined with a glucocorticoid-inducible system for rice protoplasts. Luciferase genes were efficiently induced by adding 0.1 µM of dexamethasone to the protoplast suspension, the activity of the luciferases reaching a maximum 6 h after induction. This assay system is applicable to studying the translation efficiency of rice by using the luciferase gene harboring tandem copies of an interesting codon at the 5' end.

Clinical features and surgical outcomes of lumbar spinal stenosis in patients aged 80 years or older: a multi-center retrospective study.

INTRODUCTION: With increased aging of the population, spine surgeons have more opportunity to treat elderly patients for lumbar spinal stenosis (LSS). The purpose of this study was to clarify the clinical features and surgical outcomes for LSS in the elderly aged 80 years or older. MATERIALS AND METHODS: We retrospectively reviewed 702 consecutive patients with LSS who underwent decompression surgery without fusion between 2006 and 2010. Patients with other conditions that could affect functional status were excluded from this study. Of the remaining 304 patients, 241 with LSS whose condition could be evaluated 6 months at least after surgery were analyzed. The mean follow-up period was 14.4 months (range 6-60 months). There were 144 males and 97 females aged 45-93 years old (average: 72.2 years old). Patients were divided into two age groups: 80 years or older (Group A, 46 patients) and under 80 years of age (Group B, 195 patients). We evaluated differences in the clinical features and surgical outcomes between the two groups. RESULTS: There were no significant differences in surgical levels, the number of operation levels, operation times, or the amount of intraoperative bleeding between Groups A and B. The percentages of patients with comorbidities were 73.9 % in Group A and 60.0 % in Group B, which were not significantly different. There were no significant differences in Japanese Orthopaedic Association scores preoperatively, 6 months postoperatively, and at the final follow-up between the two groups. Furthermore, recovery ratios 6 months postoperatively and at final follow-up were similar between the two groups. The percentages of patients with postoperative complications were 19.6 % in Group A and 13.3 % in Group B, which were not significantly different. CONCLUSIONS: This multi-center retrospective study demonstrated that the benefits and risks of decompression surgery for LSS were similar between patients aged over 80 years and those under 80 years. Therefore, decompression surgery is a reasonable treatment even for elderly patients aged over 80 years.

Prompt surgical management for spinal fracture in the elderly aged over 90 years with diffuse idiopathic skeletal hyperostosis to extend their healthy lifespan.

There is a possibility that the patients with diffuse idiopathic skeletal hyperostosis (DISH) increase with aging of the population and progressive lengthening of life expectancy in developed countries. In the patients with DISH, even a trivial vertebral fracture may actually turn out to be a three-column injury because mechanical stress is applied to the fracture site due to the lever arm effect. Under these circumstances, even a prolonged strict immobilization often results in failure. Recently, elderly people increasingly wish to maintain physical abilities. We present three patients aged over 90 years with DISH sustaining lower thoracic vertebral fracture after minor trauma. Long fusion involving three vertebral levels above and below the fracture site was performed with pedicle screw system, and vertebroplasty was carried out by transpedicular filling with hydroxyapatite blocks. The patients' activities of daily living were maintained close to the pre-injury level 1 year and 9 months, 2 years and 3 months, and 1 year after surgery, respectively. Many reports have recommended surgery over conservative treatments at vertebral fracture complicating DISH; however, there has been no report of vertebral fracture in patients aged over 90 years with DISH. Satisfactory results were obtained by surgical treatment in our three patients despite their age. We recommend posterior fusion with vertebroplasty just after injury for vertebral fracture in the elderly patients of advanced age with DISH to extend their healthy lifespan.

Geminin expression in small lung adenocarcinomas: implication of prognostic significance.

Geminin is an important molecule which plays a role in cell cycle regulation, and this has been considered to be a useful biomarker of cell proliferation. The purpose of this study was to evaluate the pathological and prognostic significance of geminin expression in small lung adenocarcinoma (AC). We performed Western blot analysis of five human lung AC cell lines and immunohistochemistry on 100 surgically resected specimens of lung AC with a diameter less than 3 cm. We counted the number of positively stained tumor cells, and calculated the labeling indices (LIs). Geminin proteins were variably detected in all five cell lines examined on Western blotting. The mean LIs for geminin, Ki-67, and MCM7 were 7.5%, 12.3%, and 18.5%, respectively. The geminin LIs were associated with some clinicopathological profiles including gender, histological grade, subtypes, N-status, p-factor, and tumor stage. A significantly worse prognosis was noted in the higher geminin LIs group than in the lower group (p < 0.01). Multivariate Cox regression analysis also confirmed that geminin LIs was an independent prognostic marker in stage IA lung AC patients. These results suggest that geminin is overexpressed in small lung ACs, and geminin LIs might be a useful prognostic indicator in patients with lung AC.

Geminin, Ki67, and minichromosome maintenance 2 in gastric hyperplastic polyps, adenomas, and intestinal-type carcinomas: pathobiological significance.

BACKGROUND: Geminin negatively regulates Cdt1 and induces the formation of prereplicative complexes by loading mini-chromosome maintenance proteins (Mcm) onto chromatin and limiting DNA replication to once per cell cycle. Recent studies have suggested that geminin expression is a marker of the S/G2/M phase of the cell cycle and is associated with a poor prognosis in various human malignancies. This study aimed to clarify the pathobiological role of geminin in intestinal-type gastric carcinoma, and its relationships with minichromosome maintenance 2 (Mcm2) and Ki67 expression. METHODS: We performed western blot analysis of seven human gastric cancer cell lines, and immunohistochemical analysis of 72 gastric mucosal lesions and 128 surgically removed advanced intestinal-type gastric carcinomas. Double-labeling immuno-fluorescence was performed to identify the coexpression of geminin and Ki67. RESULTS: Geminin was detected in all cell lines. Geminin labeling indices (LIs) in hyperplastic polyps, low-grade adenomas, high-grade adenomas, and intestinal-type adenocarcinomas were 3.9%, 10.5%, 18.6%, and 27.2%, respectively. The equivalent LIs for Ki67 and Mcm2 were 17.7%, 42.2%, 52.6%, and 59.7%; and 26.7%, 70.0%, 67.8%, and 77.8%, respectively. Double-labeling immunofluorescence revealed coexpression of geminin and Ki67 in both normal and tumor cells. The LI for geminin was significantly correlated with N stage, International Union Against Cancer (UICC) stage, Mcm2 LI, and Ki67 LI. Patients in stages I-IV and stage III with higher LIs for geminin (>25%) had significantly worse prognoses (P < 0.05 and P < 0.04, respectively). Univariate Cox regression analysis indicated that the overall survival of stage I-IV tumors was significantly correlated with high geminin LIs (relative risk [RR] = 1.94; P = 0.04). CONCLUSIONS: Geminin expression might reflect the biological nature of gastric intramucosal neoplasms and could be a possible prognostic marker in advanced intestinal-type gastric carcinomas.

Minichromosome maintenance-7 and geminin are reliable prognostic markers in patients with oral squamous cell carcinoma: immunohistochemical study.

BACKGROUND: Minichromosome maintenance (MCM) proteins act as the origin licensing machinery that regulates initiation of DNA replication. Geminin is a licensing repressor and prevents reinitiation of DNA replication by blocking reloading of MCM proteins at replication origins. Recent studies have proposed that MCM7 and geminin may be sensitive proliferative and prognostic markers of various malignant tumors. This study aimed to analyze the expression of MCM7 and geminin to clarify pathobiological significance in human oral squamous cell carcinomas (OSCCs). METHODS: We performed immunohistochemical analysis on 10 specimens of normal oral epithelia, 50 lesions with dysplasia and 113 OSCCs. Labeling indices (LIs) for MCM7, geminin and Ki-67 were evaluated, comparing with clinicopathological profiles. RESULTS: The mean LIs for MCM7 were 29.2% for normal epithelia, 32.2% for dysplasias, and 51.1% for OSCCs; the value was significantly higher in the last than in the former two (P < 0.01). The mean LIs for geminin were 6.8% for normal epithelia, 9.2% for dysplasias, and 21.3% for OSCCs; the value was significantly higher in the OSCCs (P < 0.01). The MCM7 LIs were correlated with the histological grade of OSCCs, in which the highest LIs were noted in the poorly differentiated type (P < 0.01). The survival rate was significantly lower in patients with a higher MCM7 LI (>49.5%) than in those with a lower LI (P < 0.05) at stage III-IV. However, the survival rate in the patients with a higher geminin LI (>19.5%) was significantly higher than in those with a lower LI (P < 0.05) at stage IV.

Prognostic significance of Minichromosome maintenance protein 7 and Geminin expression in patients with 109 soft tissue sarcomas.

Minichromosome maintenance complex (MCM2-7) and Geminin are important in the prevention of DNA re-replication in the cell cycle, and are also prognostic markers for numerous human malignancies. The present study examined Minichromosome maintenance protein 7 (MCM7) and Geminin expression in human soft tissue sarcomas (STSs) to clarify their correlation to the clinicopathological factors. Immunohistochemistry was performed to detect the expression of MCM7, Geminin and Ki-67 on paraffin-embedded sections of 109 STSs. Labeling indices (LIs) of the molecules were evaluated in the tumors. Higher LIs of MCM7, Geminin and Ki-67 were significantly correlated with distant metastasis (P<0.01), histological grade (P<0.01) and poor prognosis (P<0.01), respectively. LIs of MCM7 and Geminin were significantly correlated with Ki-67 LIs, (MCM7/Ki-67: rs=0.745, P<0.01 and Geminin/Ki-67: rs=0.604, P<0.01). Multivariate analyses showed that the higher LIs of Geminin, but not MCM7 and Ki-67, were shown to be an independent factor of poorer prognosis (relative risk 2.72, P=0.013). The immunohistochemical expression of MCM7 and Geminin may be novel and useful markers for evaluating the prognosis in patients with human STS.