Safe and Accurate Laparoscopic Total Gastrectomy for Remnant Gastric Cancer With Severe Adhesions Using Indocyanine Green Fluorescence Imaging: Guidance in Detection of the Accurate Dissection Layer to Avoid Organ Injury.

Laparoscopic total gastrectomy (LTG) for remnant gastric cancer (RGC) requires advanced techniques due to severe postoperative adhesions and anatomic changes. We performed LTG in 2 patients with RGC using intraoperative indocyanine green (ICG) fluorescence imaging. Both cases previously underwent distal gastrectomy with Billroth-I reconstruction for gastric cancer and were subsequently diagnosed with early-stage gastric cancer of the remnant stomach. Indocyanine green (2.5 mg/body) was administered intravenously during surgery. The liver and common bile duct were clearly visualized during surgery using near-infrared fluorescence laparoscopy, and the adhesions between the hepatobiliary organs and remnant stomach were safely dissected. Laparoscopic total gastrectomy was successfully performed without complications, and the postoperative course was uneventful in both cases. Intraoperative real-time ICG fluorescence imaging allows clear visualization of the liver and common bile duct and can be useful in LTG for RGC with severe adhesions.

Neurodegenerative Disease Tauopathies.

Tauopathies are a diverse group of progressive and fatal neurodegenerative diseases characterized by aberrant tau inclusions in the central nervous system. Tau protein forms pathologic fibrillar aggregates that are typically closely associated with neuronal cell death, leading to varied clinical phenotypes including dementia, movement disorders, and motor neuron disease. In this review, we describe the clinicopathologic features of tauopathies and highlight recent advances in understanding the mechanisms that lead to spread of pathologic aggregates through interconnected neuronal pathways. The cell-to-cell propagation of tauopathy is then linked to posttranslational modifications, tau fibril structural variants, and the breakdown of cellular protein quality control.

Feasibility study of Internet video-based speech-language activity for outpatients with primary progressive aphasia.

BACKGROUND: Primary progressive aphasia is a clinical dementia syndrome secondary to neurodegenerative disease characterized by language-related difficulties. Currently, there is no effective treatment for language impairment in primary progressive aphasia. In the present study, we investigated the feasibility of Internet video-based speech-language activities for this condition. METHODS: Twenty-three people with primary progressive aphasia (pwPPA) participated in the study and were provided with twelve speech-language activity videos on a dedicated website, with three sessions per week. The group that chose to continue with participation after three months of intervention received Internet activities for one year. Cognitive domains associated with persistence, treatment motivation, and video difficulty settings were statistically analyzed. RESULTS: After three months, 17 out of 23 participants opted to continue with the activities. The ability to follow oral commands which was measured pre intervention was higher in the group that continued compared with those participants who discontinued activity. The scores of two Standard Language Test of Aphasia subtests, sentence repetition and narrative writing-associated with the ability to comprehend and produce sentence structure-were highly correlated with motivation, interest and concentration in activity. Participants with different levels of primary progressive aphasia progression could participate in the same video-based activities when high-frequency words were used in the video. CONCLUSIONS: Internet video-based speech-language activity at home has potential as a useful tool for future primary progressive aphasia treatment because it provides a cost-effective approach to intensive intervention and overcomes barriers associated with traditional therapy approaches.

Screening of Mild Cognitive Impairment Through Conversations With Humanoid Robots: Exploratory Pilot Study.

BACKGROUND: The rising number of patients with dementia has become a serious social problem worldwide. To help detect dementia at an early stage, many studies have been conducted to detect signs of cognitive decline by prosodic and acoustic features. However, many of these methods are not suitable for everyday use as they focus on cognitive function or conversational speech during the examinations. In contrast, conversational humanoid robots are expected to be used in the care of older people to help reduce the work of care and monitoring through interaction. OBJECTIVE: This study focuses on early detection of mild cognitive impairment (MCI) through conversations between patients and humanoid robots without a specific examination, such as neuropsychological examination. METHODS: This was an exploratory study involving patients with MCI and cognitively normal (CN) older people. We collected the conversation data during neuropsychological examination (Mini-Mental State Examination [MMSE]) and everyday conversation between a humanoid robot and 94 participants (n=47, 50%, patients with MCI and n=47, 50%, CN older people). We extracted 17 types of prosodic and acoustic features, such as the duration of response time and jitter, from these conversations. We conducted a statistical significance test for each feature to clarify the speech features that are useful when classifying people into CN people and patients with MCI. Furthermore, we conducted an automatic classification experiment using a support vector machine (SVM) to verify whether it is possible to automatically classify these 2 groups by the features identified in the statistical significance test. RESULTS: We obtained significant differences in 5 (29%) of 17 types of features obtained from the MMSE conversational speech. The duration of response time, the duration of silent periods, and the proportion of silent periods showed a significant difference (P<.001) and met the reference value r=0.1 (small) of the effect size. Additionally, filler periods (P<.01) and the proportion of fillers (P=.02) showed a significant difference; however, these did not meet the reference value of the effect size. In contrast, we obtained significant differences in 16 (94%) of 17 types of features obtained from the everyday conversations with the humanoid robot. The duration of response time, the duration of speech periods, jitter (local, relative average perturbation [rap], 5-point period perturbation quotient [ppq5], difference of difference of periods [ddp]), shimmer (local, amplitude perturbation quotient [apq]3, apq5, apq11, average absolute differences between the amplitudes of consecutive periods [dda]), and F0cov (coefficient of variation of the fundamental frequency) showed a significant difference (P<.001). In addition, the duration of response time, the duration of silent periods, the filler period, and the proportion of fillers showed significant differences (P<.05). However, only jitter (local) met the reference value r=0.1 (small) of the effect size. In the automatic classification experiment for the classification of participants into CN and MCI groups, the results showed 66.0% accuracy in the MMSE conversational speech and 68.1% accuracy in everyday conversations with the humanoid robot. CONCLUSIONS: This study shows the possibility of early and simple screening for patients with MCI using prosodic and acoustic features from everyday conversations with a humanoid robot with the same level of accuracy as the MMSE.

An autopsied FTDP-17 case with MAPT IVS 10 + 14C > T mutation presenting with frontotemporal dementia.

•We report the immunohistochemical and biochemical features of an FTDP-17 case with MAPT IVS 10 + 14C > T mutation.•Postmortem examination of the patient with bvFTD revealed diffuse neuronal and glial 4-repeat tau pathology similar to CBD.•The structure of tau filaments associated with MAPT IVS 10 + 14C > T mutation was characterized by electron microscopy.

Prognosis of hemodialysis patients undergoing surgery for gastric cancer: Results of a multicenter retrospective study.

BACKGROUND: Little is known about the survival outcomes of and predictive factors for survival in hemodialysis patients undergoing surgery for gastric cancer. METHODS: We performed a multicenter retrospective study from 9 institutions to investigate the survival outcomes of 75 hemodialysis patients with gastric cancer. Patient characteristics included demographic data, hemodialysis- and gastric cancer-related variables. Multivariate Cox hazards models were applied to determine independent predictors of poor overall survival and non-gastric cancer related death. RESULTS: Stage I disease was predominant (58.7%) in our series. The overall morbidity and the 30-day mortality rates were 25.3% and 1.3%, respectively. The 5-year overall survival rates of patients with pStages I, II, III, and IV disease were 59.2%, 42.9%, 32.3%, and 0%, respectively. Eleven (14.7%) patients died of gastric cancer, whereas many more (40.0%) died owing to causes other than gastric cancer. Non-gastric cancer-related death was especially prevalent in patients with pStages I (95.2%) and II (75.0%) disease. Multivariable analysis revealed advanced age, long duration of hemodialysis (> 5 years), total gastrectomy, and pStage IV disease to be independently associated with poor overall survival. Notably, advanced age, long duration of hemodialysis, and the presence of cardiovascular disease were all independent predictors of non-gastric cancer-related death. Patients with all 3 factors had very poor survival outcomes (3-year overall survival; 14.3%). CONCLUSION: The survival outcomes of hemodialysis patients with gastric cancer, especially those with early-stage gastric cancer, were clearly poor, largely owing to the increased risk of non-gastric cancer-related death. Preoperative comorbidities and hemodialytic features were useful for predicting long-term outcomes of this vulnerable population.

Intracellular dynamics of Ataxin-2 in the human brains with normal and frontotemporal lobar degeneration with TDP-43 inclusions.

TAR DNA-binding protein of 43 kDa (TDP-43) is a major component of intracellular aggregates formed in brains of the patients with frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS), which are correctively referred to as TDP-43 proteinopathies. A link between Ataxin-2 (ATXN2) and TDP-43 proteinopathies was established when intermediate CAG repeat expansions of ATXN2 gene were found to be associated with ALS and it was shown that ATXN2 modifies TDP-43 toxicity. Although ATXN2's contribution to TDP-43 proteinopathies has been mostly studied in ALS, recent studies have shown that intermediate repeat expansions of ATXN2 also influence the phenotype of FTLD by an unknown mechanism. To address this issue, we immunohistochemically and biochemically analyzed the intracellular dynamics of ATXN2 in brains of normal controls and FTLD-TDP cases. The immunohistochemical studies revealed that ATXN2 localized in the neuronal cytoplasm and proximal dendrites, and expressed widely and uniformly in normal human brains. A semi-quantitative immunofluorescent analysis of normal brains revealed that the cytoplasmic ATXN2 strongly associates with ribosomal protein S6 and poly-A binding protein 1 and partially overlaps with the endoplasmic reticulum marker Calnexin, suggesting a major role of ATXN2 in protein synthesis. The results of immunohistochemical and biochemical analyses of brains from FTLD-TDP cases showed the colocalization of ATXN2 and phosphorylated TDP-43 in the dystrophic neurites and the neuronal cytoplasmic inclusions in the hippocampal region, and a significant reduction of ATXN2 protein compared to controls. These results suggest that ATXN2 is involved in the pathological process of FTLD-TDP. It remains to be clarified whether reduced ATXN2 expression induces neurodegeneration by impairing protein synthesis or plays a neuroprotective role by attenuating the toxicity of TDP-43 aggregates in FTLD-TDP and other TDP-43 proteinopathies.

[A Case of a Huge, Mixed-Type IPMC with Suspected Rupture of the Omental Bursa That Was Effectively Treated with Gemcitabine plus Nab-Paclitaxel].

A 53-year-old woman was referred to our hospital because of upper abdominal pain and expansion of the pancreatic main duct. Enhanced computed tomography revealed expansion of the main pancreatic duct from the head to the tail; in addition, a 30 mm cystic tumor was observed in the pancreatic head and a 56 mm tumor was observed in the ventral side of the pancreatic body. Endoscopy revealed fistula formation in the duodenum of the Vater papilla on the oral side. The patient was diagnosed with an intraductal papillary mucinous carcinoma(IPMC). In addition, PET-CT revealed accumulation of FDG in the ventral side of the pancreatic body, and a disseminated nodule in the omental bursa was suspected. We administered 6 courses of gemcitabine plus nab-paclitaxel therapy, after which, the tumor in the ventral side of the pancreatic body disappeared. We then performed sub-stomach-preserving pancreatoduodenectomy. The results of abdominal cavity washing cytology were negative, and there were no disseminated nodules in the omental bursa. Therefore, we could perform R0 excision.

[The Clinical, Pathological, and Genetic Correlation in Frontotemporal Lobar Degeneration].

Frontotemporal lobar degeneration (FTLD) presents diverse clinical symptoms, including psychiatric, behavioral, and language symptoms. Pathologically, it is a collective term of heterogeneous neurodegenerative disorders characterized by deposits of aberrant proteins, including tau, TAR DNA-binding protein of 43kDa (TDP-43), and fused in sarcoma (FUS), predominately in frontotemporal lobes. Recent genetic research has identified several causal and susceptibility genes of FTLD. Moreover, there is an emerging correlation between the clinical-pathological phenotypes and genetic factors. Such knowledge would contribute to further clarification of the pathogenesis of FTLD and the development of novel therapeutic interventions.

Superior outcomes (but at higher costs) of non-operative management with interval appendectomy over immediate surgery in appendicitis with abscess: Results from a large adult population cohort.

INTRODUCTION: The aim of this study was to compare surgical outcomes and hospitalization costs between immediate surgery and non-operative management followed by interval appendectomy in adults presenting with appendicitis with abscess. METHODS: From 2003 to 2015, 3316 patients presented with appendicitis, including 101 who presented with appendicular abscess. Between 2003 and 2006, 33 patients with appendicular abscess were managed with emergency operations (emergency group). Non-operative management followed by interval appendectomy was implemented in 2007 and offered to 68 patients during the study period. Of these patients, 64 patients underwent the procedure (interval group), and 4 patients refused. RESULTS: Non-operative management was successful in 76.6% of cases (49/64 patients) in the interval group. Operative time and length of hospital stay were similar between the emergency and interval groups. In the interval group, blood loss, the need for extended resection, and overall postoperative morbidity were significantly lower than in the emergency group (P < 0.01, respectively). Medical costs for surgery in the interval group were lower than in the emergency group ($4512 vs $6888, P = 0.002), but this group's total medical costs were higher ($9591 vs $6888, P < 0.01). CONCLUSION: The interval strategy is associated with a reduced need for extended resection, lower postoperative morbidity, and a shorter length of hospital stay. However, total medical costs for the interval strategy are higher than those for emergency operations in cases of appendicular abscess in adults.

Hybrid fluorescent magnetic gastrojejunostomy: an experimental feasibility study in the porcine model and human cadaver.

BACKGROUND: Laparoscopic gastrojejunostomies are time consuming and require a specific training. Alternatively, sutureless anastomosis can be achieved using endoscopically delivered magnetic rings. Our aim was to assess the feasibility and reproducibility of an endo-laparoscopic gastrojejunostomy technique, using a pair of magnets coated with a near-infrared fluorescent biocompatible polymeric material. METHODS: Five pigs (3 acute and 2 survival models) and one human anatomical specimen were included. In the survival models, the distal ring was inserted into the duodenum endoscopically, and it was fixed to a thread clipped to the gastric mucosa. Twenty-four hours later, a two-port laparoscopy was performed using a near-infrared (NIR) laparoscope. The magnet position in the jejunum was detected with the transluminal fluorescence of the dye. Magnetic interaction with the metallic tip of the laparoscopic grasper allowed to capture the ring and bring the bowel loop to the future anastomotic site on the gastric wall. The proximal magnet was inserted into the stomach endoscopically and released when magnetic interaction started, allowing for a precise connection with the distal ring. The animals were followed up for 12 days and underwent control endoscopies and radiograms. In the acute animals, the anastomotic procedure was repeated 24 times. Finally, the procedure was performed in the human anatomical specimen. RESULTS: There were no technical problems, and magnetic connection could be precisely directed at both the anterior and posterior gastric walls. No complications occurred during the survival period and the anastomoses were patent on day 5. Transluminal fluorescence enabled a rapid detection of the magnet. CONCLUSIONS: Hybrid-reduced port magnetic gastrojejunostomy using a pair of fluorescently coated magnetic rings was feasible, reproducible, and easy to perform in both porcine and cadaver models.

Three-dimensional imaging improved the laparoscopic performance of inexperienced operators: a prospective trial.

BACKGROUND: Three-dimensional (3-D) high-definition (HD) stereovision and two-dimensional (2-D) ultra-high-resolution (4K) monitors have recently become available for laparoscopic surgery. The aim of this study was to compare laparoscopic performance between inexperienced participants using 3-D/HD and 2-D/4K monitors and those using conventional 2-D/HD monitors. METHODS: The study enrolled 66 participants with no previous surgical experience or medical training. They were randomly divided into three equal groups, each using a different type of monitor (2-D/HD, 2-D/4K, or 3-D/HD), to perform three phantom tasks using a laparoscopic simulator: Task 1, touching markers on a non-flat surface; Task 2, bimanual peg transfer; and Task 3, passing a straight rod through a loop. Each task was performed three times. The performance scores (operative time, path length of the forceps, and technical errors) were compared for each monitor type and by age group (< 30 vs. > 30 years). RESULTS: For all three tasks, scores using the 3-D monitor were significantly better than those using either 2-D monitor, with no difference between the 2-D/4K and 2-D/HD monitors. Using the 2-D monitors, the performance of Task 3 by the participants > 30 years was worse than that by the younger participants; however, there was no difference between the age groups when using the 3-D monitor. CONCLUSION: Participants with no prior experience using a 3-D monitor showed better laparoscopic performance than those using 2-D monitors, even with 4K resolution. This improvement was more marked in older participants, suggesting a greater loss of depth perception in a 2-D environment.

[Molecular analysis of the BCR-ABL1 fusion gene in a chronic myeloid leukemia patient with BCR-ABL1 International Scale-undetectable disease].

BCR-ABL1 International Scale (IS) measurement is an important technique used to monitor chronic myeloid leukemia (CML) when patients are treated with tyrosine kinase inhibitors. In very rare cases, the BCR-ABL1 IS measurement fails to detect BCR-ABL1 chimeric messages for unknown reasons. Such a situation was also experienced in our study; therefore, molecular analysis of BCR-ABL1 fusion gene was performed. A breakpoint in the ABL1 gene was identified in the middle of the a2 exon, leading to generation of chimeric messages lacking a nucleic acid sequence encoded by this exon (e14a3 chimeric message). The ABL1 a2 exon is critical for quantification of BCR-ABL1 chimeric messages with the measurement scales used in medical laboratories. Absence of this referred nucleic acid sequence was the reason why BCR-ABL1 IS measurement failed to detect the chimeric messages in our study. In the future, such rare cases of CML, with BCR-ABL1 chimeric messages not detected by standard IS measurements, in Japan should be collected and their molecular structures should be analyzed.

Handwriting Features of Multiple Drawing Tests for Early Detection of Alzheimer's Disease: A Preliminary Result.

Early detection of Alzheimer's disease (AD) has become increasingly important. Healthy monitoring technology focusing on behavioral changes is a promising approach in this vein. Among such technologies, handwriting features measured by digital tablet devices have attracted attention as potential indicators for detecting AD and mild cognitive impairment (MCI). However, previous studies have mainly investigated features in single tasks, and it remains unclear whether combining the features of multiple tasks could improve the performance of detecting AD and MCI. In this study, we investigated features in five representative tasks used in neuropsychological tests collected from 71 seniors including some diagnosed with MCI and AD. We found that our three-class classification model improved diagnosis accuracy by up to 11.3% by combining features of multiple tasks, for a final accuracy of 74.6%. We also suggested that drawing behaviors during multiple tasks might be useful for estimating disease progression simply by utilizing the labels of disease groups.

Multimodal Behavior Analysis Towards Detecting Mild Cognitive Impairment: Preliminary Results on Gait and Speech.

Behavioral analysis for identifying changes in cognitive and physical functioning is expected to help detect dementia such as mild cognitive impairment (MCI) at an early stage. Speech and gait features have been especially recognized as behavioral biomarkers for dementia that possibly occur early in its course, including MCI. However, there are no studies investigating whether exploiting the combination of multimodal behavioral data could improve detection accuracy. In this study, we collected speech and gait behavioral data from Japanese seniors consisting of cognitively healthy adults and patients with MCI. Comparing the models using single modality behavioral data, we showed that the model using multimodal behavioral data could improve detection by up to 5.9%, achieving 82.4% accuracy (chance 55.9%). Our results suggest that the combination of multimodal behavioral features capturing different functional changes resulting from dementia might improve accuracy and help timely diagnosis at an early stage.

Using Tablet-Based Assessment to Characterize Speech for Individuals with Dementia and Mild Cognitive Impairment: Preliminary Results.

Early detection of dementia as well as improvement in diagnosis coverage has been increasingly important. Previous studies involved extracting speech features during neuropsychological assessments by humans, such as medical pro- fessionals, and succeeded in detecting patients with dementia and mild cognitive impairment (MCI). Enabling such assessment in an automated fashion by using computer devices would extend the range of application. In this study, we developed a tablet-based application for neuropsychological assessments and collected speech data from 44 Japanese native speakers including healthy controls (HCs) and those with MCI and dementia. We first extracted acoustic and phonetic features and showed that several features exhibited significant difference between HC vs. MCI and HC vs. dementia. We then constructed classification models by using these features and demonstrated that these models could differentiate MCI and dementia from HC with up to 82.4 and 92.6% accuracy, respectively.

Hybrid endoluminal stapled pyloroplasty: an alternative treatment option for gastric outlet obstruction syndrome.

BACKGROUND: Gastroparesis is a rapidly increasing problem with sometimes devastating consequences. While surgical treatments, particularly laparoscopic pyloroplasty, have recently gained popularity, they require general anesthesia, advanced skills, and can lead to leaks. Peroral pyloromyotomy is a less invasive alternative; however, this technique is technically demanding and not widely available. We describe a hybrid laparo-endoscopic collaborative approach using a novel gastric access device to allow endoluminal stapled pyloroplasty as an alternative treatment option for gastric outlet obstruction. METHODS: Under general anesthesia, six pigs (mean weight 33 kg) underwent endoscopic placement of intragastric ports using a technique similar to percutaneous endoscopic gastrostomy. A 5 mm laparoscope was used for visualization. A functional lumen imagine probe was used to measure the cross-sectional area (CSA) and diameter of the pylorus before, after, and at 1 week after intervention. Pyloroplasty was performed using a 5 mm articulating laparoscopic stapler. Gastrotomies were closed by endoscopic clips, endoscopic suture, or combination. After 6-8 days, a second evaluation was performed. At the end of the protocol, all animals were euthanized. RESULTS: Six pyloroplasties were performed. In all cases, this technique was effective in achieving significant pyloric dilatation. The median pre-pyloroplasty pyloric diameter (D) and cross-sectional area (CSA) were 8 mm (4.9-11.6 mm) and 58.6 mm2 (19-107 mm2), respectively. After the procedure, these values increased to 13.41 mm (9.8-17.6 mm) and 147.7 mm2 (76-244 mm2), respectively (p = 0.0152). No important intraoperative events were observed. Postoperatively, all animals did well, with adequate oral intake and no relevant complications. At follow-up endoscopy, all incisions were healed and the pylorus widely patent. CONCLUSIONS: Hybrid endoluminal stapled pyloroplasty is a feasible, safe, and effective alternative method for the treatment of gastric outlet obstruction syndrome.

[Carcinosarcoma of the Esophagus That Presented as Esophageal Stenosis].

Esophageal carcinosarcoma is a rare malignant tumor. A 76-year-old man consulted near hospital about dysphagia. A gastrointestinal fiberscopy showed a stricture of the thoracic esophagus at approximately 34 cm from the incisor, and the macroscopic type of the tumor was 0-Ip. Biopsy results indicated carcinosarcoma. The patient underwent esophagectomy and regional lymphadenectomy with gastric tube reconstruction by laparoscopy-assisted surgery and thoracotomy. Pathological examination of the surgical specimen revealed that the majority of the tumor was composed of spindle-shaped atypical cells, but because a very small transitional area between squamous cell carcinoma and sarcoma was noted, a diagnosis of carcinosarcoma was made. The depth of invasion was small, and no region lymph node metastasis was detected. We classified the tumor as pT1b(SM)N0M0, pStage I. Immunohistochemically, the spindle-shaped sarcomatous cells displayed a posi- tive reaction to vimentin and cytokeratin AE1/AE3. Ki -67(MIB-1)labeling index was high. The patient was discharged after an uneventful postoperative course and remains well as an outpatient at his 6-month follow-up. We report this case with a review of the literature.