Assessment of Mild Cognitive Impairment Using CogEvo: A Computerized Cognitive Function Assessment Tool.

INTRODUCTION/OBJECTIVES: To assess the utility of the computerized cognitive function assessment tool, CogEvo, as a screening tool for mild cognitive impairment in primary care, we explored the relationship between CogEvo performance, age, and the severity of cognitive dysfunction evaluated by the Mini-Mental State Examination (MMSE). METHODS: The observational cross-sectional study included 209 individuals' data (mean age 79.4 ± 8.9 years). We conducted a correlation analysis between CogEvo and MMSE scores, compared the performance among the 3 cognitive function groups (MMSE ≥ 28 group; MMSE24-27 group; MMSE ≤ 23 group) using the MMSE cut-off, and evaluated CogEvo's predictive accuracy for cognitive dysfunction through ROC analysis. RESULTS: Both total CogEvo and MMSE scores significantly decreased with age. A significant positive correlation was observed between total CogEvo and MMSE scores, but a ceiling effect was detected in MMSE performance. Significant differences were observed in the total CogEvo score, including orientation and spatial cognitive function scores, among the 3 groups. CogEvo showed no educational bias. ROC analyses indicated moderate discrimination between the MMSE ≥ 28 group and the MMSE24-27 and MMSE ≤ 23 groups. CONCLUSIONS: The computer-administered CogEvo has the advantage of not exhibiting ceiling effects or educational bias like the MMSE, and was found to be able to detect age-related cognitive decline and impairment.

Does Pathological T-Factor Affect Long-term Prognosis of Locally Advanced Colorectal Cancer Treated With Laparoscopic Multivisceral Resection?

BACKGROUND/AIM: Locally advanced colorectal cancer (LACC) has poor long-term outcomes. Our hypothesis was that the pathological tumor depth would affect postoperative outcomes in patients who underwent multivisceral resection with clear margins (R0). The aim of this study was to analyze short- and long-term outcomes in patients who underwent multivisceral resection for LACC, comparing between T3 and T4 stages. PATIENTS AND METHODS: This was a propensity score-matched, retrospective study. All 8,764 consecutive patients who underwent surgery for colorectal cancer between April 2007 and January 2021 at the Saitama Medical University International Medical Center were screened; 572 underwent multivisceral resection for LACC. We compared the T3 and T4 groups to evaluate outcomes. RESULTS: The 5-year disease-free survival (DFS) rates did not significantly differ between the two groups (hazard ratio=1.344, 95% confidence interval=0.638-2.907, p=0.33). The 5-year overall survival (OS) rates were significantly worse for the T4 group than for the T3 group (hazard ratio=3.162, 95% confidence interval=1.077-11.44), p=0.037). To determine the association between American Society of Anesthesiologists (ASA) score, transfusion, pathological T and OS, we performed univariate and multivariate analyses. ASA, transfusion, and pathological T-stage were associated with worse OS in univariate analysis (T4 vs. T3, respectively). CONCLUSION: Our study showed that postoperative complications and DFS of the T4 group were similar to those of the T3 group of locally advanced colorectal cancer treated with laparoscopic multivisceral resection. However, OS was worse in the T4 group compared with the T3 group. Multivariate risk factors for poor OS were ASA>2, transfusion, and T4 stage.

Risk Factors for Lymph Node Metastasis and Recurrence in T1 Colorectal Cancer: Analysis of 801 Patients in a Single Institute.

OBJECTIVE: To identify risk factors for lymph node metastasis and postoperative recurrence of pT1 colorectal cancer by clinicopathological study of surgically resected cases. METHODS: In 801 patients with pT1 colorectal cancer who underwent surgical resection with lymph node dissection between April 2007 and January 2021, we evaluated clinicopathological factors (age, gender, BMI, serum CEA level, tumor localization, additional resection after endoscopic treatment, operation time, blood loss, histological type, tumor size, vascular invasion, and central lymph node dissection). We performed univariate and multivariate analyses to examine risk factors for lymph node metastasis. We also examined risk factors for recurrence in 583 patients up to December 2017. RESULTS: Lymph node metastasis was observed in 100/801 patients (12.5%). Multivariate analysis of lymph node metastasis showed that patients with positive lymphatic invasion (odds ratio 2.57, 95% CI 1.62-4.04, P < .0001), positive venous invasion (odds ratio 2.31, 95% CI 1.48-3.61, P = .0002), and histologically poorly differentiated type (odds ratio 4.54, 95% CI 1.35-15.2, P = .014) were identified as risk factors. Postoperative recurrence was observed in 18/580 patients (3.1%). Risk factors for postoperative recurrence were also examined, including preoperative endoscopic treatment (odds ratio 3.59, 95% CI 1.18-10.9, P = .024), positive venous invasion (odds ratio 3.63, 95% CI 1.22-10.8, P = .021), positive lymph node metastasis (odds ratio 4.91, 95% CI 1.10-21.8, P = .037) were extracted as risk factors. DISCUSSION: In this study, venous invasion, lymphatic invasion, and histologically poorly differentiated type were identified as risk factors for lymph node metastasis in T1 colorectal cancer, and positive venous invasion, positive lymph node metastasis, and preoperative endoscopic treatment were identified as risk factors for recurrence. We hope that large prospective study will lead to the development of a more specific treatment strategy, including endoscopic treatment and additional surgical resection.

An Elastic Foot Orthosis for Limiting the Increase of Shear Modulus of Lower Leg Muscles after a Running Task: A Randomized Crossover Trial.

BACKGROUND: Excessive foot pronation may be attributed to an increasing burden on leg muscles during running, which might be a factor in medial tibial stress syndrome. We developed an elastic foot orthosis (EFO) that can decrease foot pronation and aimed to identify whether this orthosis could limit the increase in lower leg muscle hardness after running. METHODS: Twenty-one healthy volunteers participated in this randomized crossover trial with an elastic or sham foot orthosis (SFO). All volunteers ran on a treadmill for 60 min while wearing either orthosis. Muscle hardness of the posterior lower leg was assessed using shear wave elastography before and after running. The Wilcoxon signed rank test was used to compare muscle hardness between the two orthotic conditions. RESULTS: No significant differences were observed between the two orthotic conditions before running (p > 0.05). After running, the flexor digitorum longus (FDL) hardness in the EFO group was significantly lower than that in the SFO group (p < 0.01). No significant changes were observed in the other muscles. CONCLUSION: The results suggest that the EFO can restrict the increase in FDL hardness with running. The EFO may be an effective orthotic treatment for medial tibial stress syndrome.

Erratic and blood vessel-guided migration of astrocyte progenitors in the cerebral cortex.

Astrocytes are one of the most abundant cell types in the mammalian brain. They play essential roles in synapse formation, maturation, and elimination. However, how astrocytes migrate into the gray matter to accomplish these processes is poorly understood. Here, we show that, by combinational analyses of in vitro and in vivo time-lapse observations and lineage traces, astrocyte progenitors move rapidly and irregularly within the developing cortex, which we call erratic migration. Astrocyte progenitors also adopt blood vessel-guided migration. These highly motile progenitors are generated in the restricted prenatal stages and differentiate into protoplasmic astrocytes in the gray matter, whereas postnatally generated progenitors do not move extensively and differentiate into fibrous astrocytes in the white matter. We found Cxcr4/7, and integrin ß1 regulate the blood vessel-guided migration, and their functional blocking disrupts their positioning. This study provides insight into astrocyte development and may contribute to understanding the pathogenesis caused by their defects.

Short-term results of robot-assisted colorectal cancer surgery using Senhance Digital Laparoscopy System.

BACKGROUND: The Senhance Digital Laparoscopy System (Asensus Surgical Inc, Morrisville, NC, United States), which was introduced for the first time in Japan by our hospital, is a new surgical assistive robot following the da Vinci Surgical System. We herein report the short-term outcomes of 55 colorectal cancer surgery cases using this system at our hospital to assess the feasibility and safety of our procedures. MATERIALS AND METHODS: We retrospectively reviewed the patient backgrounds and surgical outcomes of 55 patients who underwent Senhance-assisted laparoscopic colorectal cancer surgery. RESULTS: The median age was 71 years. There were 31 males and 24 females, and the median body mass index was 23.1 kg/m2 . Fifteen patients had a history of abdominal surgery. The most common surgical technique was ileocecal resection (18 cases, 32.7%), followed by high anterior resection (11 cases, 20.0%). D2 or D3 dissection was performed in each operation, and D3 dissection was performed in 41 cases (74.5%). The median operative time was 240 minutes, the median blood loss was 5 mL, there were no intraoperative complications, and there were no cases of intraoperative blood transfusion. The median postoperative hospital stay was 7 days, which was comparable to conventional laparoscopic surgery. Postoperative complications of grade 2 or higher in the Clavien-Dindo classification were observed in two cases. CONCLUSION: The short-term results of 55 colorectal cancer surgery cases using the Senhance Digital Laparoscopy System were excellent and the system was introduced and surgery was safely performed.

The effectiveness of plasma miR-33a-5p as a predictive biomarker for the efficacy of colorectal cancer chemotherapy.

Several chemotherapeutic options are available for patients with metastatic colorectal cancer (mCRC), making it important to individualize treatment regimens. Individualization requires the clinical application of biomarkers for regimen selection, which is presently insufficient. miRNAs serve an important role in the control of biological processes in several types of cancer, acting as plasma biomarkers. The current study aimed to evaluate novel plasma microRNAs for predicting chemo-resistance in chemotherapy for patients with colorectal cancer (CRC) by employing a Toray 3D-Gene microRNA array-based approach, which compared plasma content before and during treatment. Specific miRNAs that acted as biomarkers of the fluoropyrimidine (FP) + oxaliplatin (OX) + bevacizumab (BEV) regime, a common first-line treatment for mCRC, were searched. The plasma samples of 110 patients with mCRC who had received the FP+OX+BEV regimen were subjected to microarray analyses using the 3D-Gene miRNA microarray platform, after which miRNAs levels were quantified via reverse transcription- quantitative PCR. Patients exhibiting complete response, partial response (PR) and reduced stable disease (SD) were defined as responders. Patients with extended SD and progression disease (PD) were defined as non-responders. Following microarray analysis, miR-33a-5p was selected as the candidate miRNA as it was upregulated in non-responder plasma samples. The expression of miR-33a-5p was upregulated in the non-responders (n=15) compared with the responders (n=95) (P=0.032). The high expression group demonstrated significantly poor progression-free survival (P<0.01). To evaluate whether miR-33a-5p can serve as a marker of chemo-resistance, miR-33a-5p expression levels were assessed at the following three time-points: Pre-point (before chemotherapy); PR-point (3-months after chemotherapy began); and PD-point (the time at which recurrence or progression was recorded). The results revealed that expression levels were significantly increased at the PD-point when compared with that at the pre-point (P=0.024). The current study determined that the miR-33a-5p expression level in the plasma may serve as a predictive marker of efficacy and as a biomarker of chemo-resistance.

[A Case Report of Postoperative Chylous Ascites after Laparoscopic Sigmoidectomy].

A female in her 70s was diagnosed as sigmoid colon cancer. Laparoscopic sigmoidectomy was performed. Chylous ascites was observed after starting oral intake. As we changed the patient's diet to a low fat diet, the chylous ascites disappeared. There are certain numbers of reports of the cases improved by fasting or only fat decreased meal. It is important to prevent this complications using appropriate surgical devices.

Validity and reproducibility of foot motion analysis using a stretch strain sensor.

BACKGROUND: Multi-segment foot analysis is traditionally challenging to perform while subjects are wearing footwear or a foot orthosis and is difficult to apply in the clinical setting. A recently developed stretch strain sensor (STR), that is thin and highly flexible, may solve this limitation because it does not require observation using a camera and is highly portable. RESEARCH QUESTION: This study aimed to examine the reproducibility and validity of foot motion analysis using the STR during walking and running by comparing it with a conventional motion capture system. METHODS: Twenty-one healthy participants were examined in this study. The STR was placed on the participant's foot in one of two locations in separate experiments (spring ligament; SL and navicular drop; ND methods). Foot kinematic data during walking and running were simultaneously recorded using the STR and a three-dimensional motion capture system. Intra-class correlation (ICC) was used to assess test-retest reproducibility of the STR method. Cross-correlation coefficient evaluated the similarity of the pattern of the signals between the two systems. Pearson and Spearman correlation analysis was used to evaluate the relationships between the STR measurement and angular excursion of the forefoot or hindfoot. RESULTS: The ICCs of the SL method were 0.95 and 0.96, and those of the ND method were 0.93 and 0.71 during walking and running, respectively. In the SL method, the pattern of the signals between the STR and forefoot frontal motion was strongly correlated. The STR measurement was significantly correlated with forefoot eversion excursion (walking: r=-0.67, running: r=-0.64, p < 0.01 each). In the ND method, the STR signal was not associated with forefoot and hindfoot kinematics. SIGNIFICANCE: Our results showed that the STR has acceptable reproducibility and validity of foot motion analysis. This system may enable measurement of foot motion while subjects are wearing shoes and outside the laboratory.

Prenatal ultrasonographic findings and fetal/neonatal outcomes of body stalk anomaly.

We studied 27 cases that were post or prenatally diagnosed with body stalk anomaly (BSA) using medical records of prenatal ultrasound findings, pregnancy outcomes, and fetal/neonatal prognosis during 1992 to 2018. Termination of pregnancy was chosen in 15 cases. Of the remaining 12 cases, seven were stillbirths and five were live births. Of seven stillbirths, intrauterine fetal demise occurred before onset of labor in four cases at 17 to 20th weeks of pregnancy. Pregnancy was continued in eight cases. Median gestational age of delivery was 33rd weeks of pregnancy. Median birth weight was 1198 g (range:482-1914 g). Vaginal delivery was chosen in six and caesarean delivery in two cases. Among six vaginally delivered cases, three (50%) fetuses were stillborn. All five live born neonates died within a few hours (16-133 minutes). Eighteen cases were confirmed as BSA postnatally by placental examination or autopsy at our hospital. Main prenatal ultrasonographic findings of them were abdominal wall defect (100%), absence of the umbilical cord (72%), abnormal spine (61%), and abnormal legs (50%). The most characteristic prenatal ultrasonography findings of BSA were the absence of free umbilical cord in the amniotic cavity and the presence of abdominal organs into the extraembryonic celom through abdominal wall defects. The autopsy showed severe pulmonary hypoplasia with the median lung/body weight ratio of 0.61% (range:0.34-0.85%). There were no cases of maternal morbidities. Our study provides important information about the pregnancy outcome and the fetal/neonatal outcome of BSA cases for the parents whose fetuses are diagnosed with BSA prenatally.

Prenatal diagnosis of Fraser syndrome caused by novel variants of FREM2.

Fraser syndrome (FS) involves multiple malformations and has a 25% recurrence risk among siblings. However, these malformations are difficult to detect prenatally, hampering prenatal diagnosis. Here, we describe a fetus with FS diagnosed using ultrasonography. Ultrasonography revealed congenital high airway obstruction syndrome and renal agenesis. Syndactyly of both hands and cryptophthalmos were noted postnatally, and the diagnosis was confirmed by genetic analysis, which showed novel compound heterozygous variants of FREM2.

Enhanced recovery after surgery program involving preoperative dexamethasone administration for head and neck surgery with free tissue transfer reconstruction: Single-center prospective observational study.

BACKGROUND: There are few reports on Enhanced Recovery After Surgery (ERAS)-based perioperative management following head and neck surgery with free tissue transfer reconstruction (HNS-FTTR). Here, we prospectively evaluated our ERAS program involving preoperative glucocorticoid administration in HNS-FTTR. METHODS: This prospective study included 60 patients who underwent HNS-FTTR at the Miyagi Cancer Center from June 2017 to December 2018. Their treatment plan included receiving perioperative management in accordance with our head and neck ERAS program. Major outcomes of hospitalization periods, early mobilization, early enteral nutrition, and patient satisfaction were assessed, and blood date and vital signs were compared with control patients who underwent HNS-FTTR from January 2014 to September 2016 at our institution before ERAS was implemented. RESULTS: The duration of hospital stay and the duration until completion of the discharge criteria was a median of 25 days and 17 days, respectively. Early mobilization was achieved in 86.0% of the patients at postoperative-day (POD)1 and 96.5% at POD2. Enteral nutrition was started in 80.1% at POD1 and 100% at POD2. Postoperative pain was controlled at mean VAS scores of 1.51-3.13. Clavien-Dindo grade II or higher postoperative complications were evident in 27.6% of the patients. The mean QOR40 score was 179.6 preoperatively, 146.1 at POD3, and 167.8 at POD7. Compared with the control group, there were significantly lower C-reactive protein levels, higher albumin levels, a lower body temperature, a lower neutrophil-to-lymphocyte ratio, less body weight fluctuation, and fewer incidences of decreased blood pressure in the ERAS group. CONCLUSION: Patients who underwent HNS-FTTR with ERAS-based perioperative management achieved early mobilization, early enteral nutrition, favorable pain control, remarkable recovery of patient satisfaction at POD7, and there was evidence of better hemodynamic stability and less inflammatory response compared with control patients.

Clonal array profiling of scFv-displaying phages for high-throughput discovery of affinity-matured antibody mutants.

"Antibody-breeding" approach potentially generates therapeutic/diagnostic antibody mutants with greater performance than native antibodies. Therein, antibody fragments (e.g., single-chain Fv fragments; scFvs) with a variety of mutations are displayed on bacteriophage to generate diverse phage-antibody libraries. Rare clones with improved functions are then selected via panning against immobilized or tagged target antigens. However, this selection process often ended unsuccessful, mainly due to the biased propagation of phage-antibody clones and the competition with a large excess of undesirable clones with weaker affinities. To break radically from such panning-inherent problems, we developed a novel method, clonal array profiling of scFv-displaying phages (CAP), in which colonies of the initial bacterial libraries are examined one-by-one in microwells. Progenies of scFv-displaying phages generated are, if show sufficient affinity to target antigen, captured in the microwell via pre-coated antigen and detected using a luciferase-fused anti-phage scFv. The advantage of CAP was evidenced by its application with a small error-prone-PCR-based library (~ 105 colonies) of anti-cortisol scFvs. Only two operations, each surveying only ~ 3% of the library (9,400 colonies), provided five mutants showing 32-63-fold improved Ka values (> 1010 M-1), compared with the wild-type scFv (Ka = 3.8 × 108 M-1), none of which could be recovered via conventional panning procedures operated for the entire library.

[Assessment for Local Treatment for Elderly Breast Cancer Cases].

The number of elderly breast cancer patients has been increasing recently nevertheless the optimal treatment for the elderly breast cancer patients still remains controversial. In this study, 21 primary breast cancer cases who were equal or older than 85 years old at our hospital were examined their clinical and pathological features. These 21 cases were divided into 2 group; Group A; ten cases who received operations, Group B; eleven cases who did not receive operations. T categories, M categories and clinical stages in Group B were significantly higher than those of Group A. The main causing reason why Group B cases had not received operations was that their primary breast cancer were too advanced to perform operation. Instead of operation, most Group B cases received endocrine therapy or radiotherapy. Group A cases received standard operative procedures including partial or total mastectomy and biopsies or dissection of axillary lymph nodes. Besides, their post- operative courses were good and safe. These results suggest that even for elderly patients, early diagnosis and treatment could improve their prognosis and quality of life. In addition, careful surveillances for elderly breast cancer patients, those who tend to stop attending regular check up to their hospital, should be considered for further assessment for characteristics of elderly breast cancer patients.

[A Case of Synchronous Double Lung Cancer Including Intestinal Adenocarcinoma Complicated with Colonic Adenoma].

The patient was a 73-year-old man who was referred to our hospital for increasing bilateral lung nodules. Video-assisted left S9-10 segmentectomy and right S1, S3 partial resection were performed separately for suspect of synchronous double lung cancer. Colonoscopy was performed because left lung tumor was difficult to distinguish between primary lung cancer and metastatic lung cancer. Colonoscopy did not find advanced cancer lesion. We diagnosed the left lung tumor as pT1b, cN0, cM0, Stage ⅠA2 intestinal adenocarcinoma. The right lung tumor was diagnosed as pT1c, cN0, cM0, Stage ⅠA3 papillary adenocarcinoma. Intestinal adenocarcinoma is a rare tissue subtype of lung adenocarcinoma and colonoscopy is useful modality for ruling out metastatic colorectal cancer.

[A Case of Ipsilateral Breast Cancer with Contralateral Axillary Node Recurrence after Right Breast Partial Mastectomy].

A female patient who was in her 50s visited our hospital complaining right breast tumor, 18 years after her right breast- conserving partial mastectomy with right axillary lymph nodes dissection. Ultrasonography revealed a right breast tumor and an enlarged lymph node at left axilla. Core needle biopsy(CNB)from the right breast tumor showed the recurrence of her breast cancer and fine-needle aspiration(FNA)from her left axillary lymph node showed Class Ⅴ. We concluded the recurrence of right breast cancer with left axillary metastasis. After neoadjuvant chemotherapy, she underwent right mastectomy and left axillary lymph node dissection. When the recurrence of residual breast is seen, the contralateral axillary lymph node might become a new sentinel lymph node.

Rupture of perivascular epithelioid cell neoplasm at 34 weeks' gestation: A nonendometriosis case of spontaneous hemoperitoneum in pregnancy.

Spontaneous hemoperitoneum in pregnancy (SHiP) has mainly been discussed in the context of endometriosis. With hormonal changes and enlargement of the uterus during pregnancy, tumors can also increase the chance of rupture and consequent SHiP. We report a case of a 30-year-old primiparous woman presented with sudden-onset intraabdominal hemorrhage at 34 weeks' gestation. The source of bleeding was rupture of a perivascular epithelioid cell neoplasm on the left round ligament of the uterus. The pregnancy ended with an uncomplicated, full-term, vaginal delivery. We performed an additional post-partum surgery to resect the left round ligament and transposition of the right ovary. In cases of SHiP, the possibility of a nonendometriosis origin should be considered. Preoperative imaging and histologic examinations of bleeding lesions are crucial for managing SHiP.

[A Case of Locally Advanced Breast Cancer Successfully Treated with Epirubicin/Cyclophosphamide].

A 66-year-old woman was referred to our hospital with the chief complaint of a huge exposed left breast mass with bleeding. Triple-negative invasive ductal carcinoma of the breast was diagnosed by core needle biopsy. Computed tomogra- phy showed axillary and infraclavicular lymph node metastases. Epirubicin/cyclophosphamide(EC)therapy was started. We reduced the dose to 80%during courses 2-4. After 4 courses of treatment, CT showed a complete response. We reduced the dose to 50% during courses 5-12 and stopped chemotherapy. Five years have passed without recurrence since the first treatment.

[A Case of Appendiceal Neuroendocrine Tumor Diagnosed after Appendectomy].

A 25-year-old woman visited our hospital with a complaint of right lower abdominal pain. As a result of the examination, she was diagnosed as having acute appendicitis. After conservative treatment, we planned an elective surgery. At 3 months after discharge, laparoscopic appendectomy was performed. We found a mass of 10mm in diameter at the body of the appendix. Histopathological examination revealed the proliferation of heteromorphic cells with small round nuclei. It was positive for chromogranin A and synaptophysin in immunostaining, so we made a diagnosis of NET G1. Tumor cells infiltrated beyond the intrinsic muscle layer, but no vascular invasion was observed, and the margin was negative. In accordance with the guidelines, we followed up the patient with imaging examination and did not find any signs of recurrence.

[A Case of Pancreatic Neuroendocrine Carcinoma Presenting Multiple Liver Metastasis as an Initial Manifestation for Which Diagnosis Confirmation Was Difficult].

A 67-year-old woman with a history of esophageal cancer(poorly-differentiated squamous cell carcinoma, pStageⅡ) was diagnosed with 2 liver tumors by regular checkup CT 10 years after her operation. We also observed elevated levels of tumor marker CEA. The tumors were suspected to be metastatic although no primary lesion was identified. We performed partial hepatectomy for diagnostic therapy. The pathological diagnosis was adenocarcinoma suggestive of metastatic tumors but the primary lesion remained unknown. Tumor marker levels were elevated 2 months after the operation and we detected a pancreatic tumor, multiple liver tumors, peritoneal dissemination, and para-aortic lymph node metastasis. Therefore, our clinical diagnosis was multiple metastases with primary pancreatic cancer and chemotherapy was performed. We conducted a thorough review of the diagnostic images and repeated the pathological analysis. Immunobiological staining showed that the tumor cells were positive for neuroendocrine markers such as chromogranin A, CD56, and Ki-67. We eventually diagnosed the liver tumors as metastasis from the pancreatic neuroendocrine carcinoma(Grade 3).