Causal rule ensemble method for estimating heterogeneous treatment effect with consideration of prognostic effects.

We propose a novel framework based on the RuleFit method to estimate heterogeneous treatment effect in randomized clinical trials. The proposed method estimates a rule ensemble comprising a set of prognostic rules, a set of prescriptive rules, as well as the linear effects of the original predictor variables. The prescriptive rules provide an interpretable description of the heterogeneous treatment effect. By including a prognostic term in the proposed model, the selected rule is represented as an heterogeneous treatment effect that excludes other effects. We confirmed that the performance of the proposed method was equivalent to that of other ensemble learning methods through numerical simulations and demonstrated the interpretation of the proposed method using a real data application.

Hemispheric Lateralization in Older Adults Who Habitually Play Darts: A Cross-Sectional Study Using Functional Near-Infrared Spectroscopy.

Exercise training integrating physical and cognitive activities is gaining attention because of its potential benefits for brain health. This study focuses on exercise training using a dart game called Wellness Darts. Wellness Darts is a sport involving throwing darts and walking to pull them out of the board, memorizing the score, and subtracting this from the total score, thus requiring the simultaneous performance of two tasks: exercise and calculation. This is expected to maintain and improve cognitive function, and whether this continual darts training affects brain function is of great interest. Before conducting the longitudinal study revealing its effect on brain function, we aimed to cross-sectionally confirm the difference in hemispheric lateralization between expert and non-expert players. Functional near-infrared spectroscopy (fNIRS) was used to measure brain activity for three groups: an expert older group who practiced darts continually, a non-expert older control group, and a non-expert younger control group. Their brain activity patterns were quantified by the lateralization index (LI) and compared between groups. The results showed that the younger and the expert older groups had significantly higher LI values than the non-expert older group, and there was no difference between the expert older and the younger groups. Our results suggest that the Wellness Darts game possibly promotes hemispheric lateralization.

Leuconostoc mesenteroides subsp. strain NTM048 ameliorated nasal symptoms in patients with Japan cedar pollinosis: Randomized, double-blind, and placebo-controlled trial.

BACKGROUND: Lactobacillales including L mesenteroides have beneficial effects on human health, including improvement of psychological status and alleviation of allergic rhinitis. In mice, L mesenteroides subsp. strain NTM048 (NTM048) increased intestinal s-IgA. In humans, however, the effects of NTM048 on s-IgA secretion have been unclear. STUDY: This 16-week trial was performed using a double-blind, placebo-controlled, parallel group design. We aimed to establish whether Leuconostoc mesenteroides subsp. strain NTM048 increases the secretion of s-IgA in saliva. Forty healthy adults and forty patients with Japanese cedar pollinosis were recruited. Participants took either 2 test capsules including NTM048 (1010 CFU/day), or 2 placebo capsules per day, for 16 weeks. They were asked to collect their saliva and answered POMS2, a questionnaire about psychological status. The patients also answered questions about nasal symptoms. Blood samples were collected from the patients with Japanese Cedar pollinosis. Stool samples were collected at the start and on the last day of the trial. RESULTS: All subjects completed the trial. It was conducted during the season when Japanese cedar pollen is most scattered. Serum concentration of Japanese cedar pollen-specific IgE was > 2.0 UA/mL in patients with Japanese cedar pollinosis. The amount of s-IgA in saliva was not increased by NTM048 in overall subjects, and Japanese cedar pollen-specific IgE was not changed by NTM048 in patients with Japanese cedar pollinosis. The symptom of nasal blockage was improved by NTM048 12 weeks after the start of trial. post hoc analysis indicated a positive correlation between improving psychological status and the increase in occupation ratio of lactobacillus including NTM048. CONCLUSION: The amount of s-IgA in saliva was not increased by NTM048, but nasal blockage was improved by it. Psychological status might be improved if dosage of NTM048 is raised to the degree that NTM048 might be increased in the intestinal tract.

Rule ensemble method with adaptive group lasso for heterogeneous treatment effect estimation.

The increasing scientific attention given to precision medicine based on real-world data has led to many recent studies clarifying the relationships between treatment effects and patient characteristics. However, this is challenging because of ubiquitous heterogeneity in the treatment effect for individuals and the real-world data on their backgrounds being complex and noisy. Because of their flexibility, various machine learning (ML) methods have been proposed for estimating heterogeneous treatment effect (HTE). However, most ML methods incorporate black-box models that hamper direct interpretation of the relationships between an individual's characteristics and treatment effects. This study proposes an ML method for estimating HTE based on the rule ensemble method RuleFit. The main advantages of RuleFit are interpretability and accuracy. However, HTEs are always defined in the potential outcome framework, and RuleFit cannot be applied directly. Thus, we modified RuleFit and proposed a method to estimate HTEs that directly interpret the relationships among the individuals' features from the model. Actual data from an HIV study, the ACTG 175 dataset, was used to illustrate the interpretation based on the ensemble of rules created by the proposed method. The numerical results confirm that the proposed method has high prediction accuracy compared to previous methods, indicating that the proposed method establishes an interpretable model with sufficient prediction accuracy.

Clinical evaluation of needle-free electronic pneumatic hyaluronic acid injection treatment for facial atrophic acne scars: A prospective, randomized comparative trial.

Acne scars are common but difficult to treat, and an effective new treatment strategy is desired. This prospective, split-face randomized controlled trial was designed to compare the safety and efficacy of needle-free electronic pneumatic hyaluronic acid injection (EPI-HA) treatment for acne scars. Thirty Japanese subjects with moderate to severe facial atrophic acne scars underwent EPI-HA treatment on a randomized side of their face. Three treatment sessions were carried out at 1-month intervals, and the subjects were followed-up for 3 months after the final treatment. Three months after the final treatment, 48.3% of treated sides met the criteria for success, compared with 0% for the control sides (P < 0.0001). Rolling type scars were much improved compared with boxcar types and icepick types. Satisfaction (or better) was reported by 55.2% of subjects at the 3-month follow-up after the final treatment, which was similar to the physicians' assessment. Three-dimensional in vivo imaging analysis detected significant difference in scar reductions between the treated and control sides in the mean scar area, scar depth, and maximum depth of the biggest scar at 1 and 3 months after the final treatment (all P < 0.05). In conclusion, EPI-HA treatment significantly improved rolling facial atrophic acne scars in our Japanese subjects, with minimal side effects.

Estimation and visualization of heterogeneous treatment effects for multiple outcomes.

We consider two-arm comparison in clinical trials. The objective is to identify a population with characteristics that make the treatment effective. Such a population is called a subgroup. This identification can be made by estimating the treatment effect and identifying the interactions between treatments and covariates. For a single outcome, there are several ways available to identify the subgroups. There are also multiple outcomes, but they are difficult to interpret and cannot be applied to outcomes other than continuous values. In this paper, we thus propose a new method that allows for a straightforward interpretation of subgroups and deals with both continuous and binary outcomes. The proposed method introduces latent variables and adds Lasso sparsity constraints to the estimated loadings to facilitate the interpretation of the relationship between outcomes and covariates. The interpretation of the subgroups is made by visualizing treatment effects and latent variables. Since we are performing sparse estimation, we can interpret the covariates related to the treatment effects and subgroups. Finally, simulation and real data examples demonstrate the effectiveness of the proposed method.

Interpersonal brain synchronization during face-to-face economic exchange between acquainted dyads.

Interpersonal brain synchronization (IBS) has been observed during social interactions and involves various factors, such as familiarity with the partner and type of social activity. A previous study has shown that face-to-face (FF) interactions in pairs of strangers increase IBS. However, it is unclear whether this can be observed when the nature of the interacting partners is different. Herein, we aimed to extend these findings to pairs of acquaintances. Neural activity in the frontal and temporal regions was recorded using functional near-infrared spectroscopy hyperscanning. Participants played an ultimatum game that required virtual economic exchange in two experimental settings: face-to-face and face-blocked conditions. Random pair analysis confirmed whether IBS was induced by social interaction. Contrary to the aforementioned study, our results did not show any cooperative behavior or task-induced IBS increase. Conversely, the random pair analysis results revealed that the pair-specific IBS was significant only in the task condition at the left and right superior frontal, middle frontal, orbital superior frontal, right superior temporal, precentral and postcentral gyri. Our results tentatively suggested that FF interaction in acquainted pairs did not increase IBS and supported the idea that IBS is affected by 'with whom we interact and how'.

Thresholding Approach for Low-Rank Correlation Matrix Based on MM Algorithm.

BACKGROUND: Low-rank approximation is used to interpret the features of a correlation matrix using visualization tools; however, a low-rank approximation may result in an estimation that is far from zero, even if the corresponding original value is zero. In such a case, the results lead to a misinterpretation. METHODS: To overcome this, we propose a novel approach to estimate a sparse low-rank correlation matrix based on threshold values. We introduce a new cross-validation function to tune the corresponding threshold values. To calculate the value of a function, the MM algorithm is used to estimate the sparse low-rank correlation matrix, and a grid search was performed to select the threshold values. RESULTS: Through numerical simulation, we found that the false positive rate (FPR), interpretability, and average relative error of the proposed method were superior to those of the tandem approach. For the application of microarray gene expression, the FPRs of the proposed approach with d=2,3 and 5 were 0.128, 0.139, and 0.197, respectively, while the FPR of the tandem approach was 0.285. CONCLUSIONS: We propose a novel approach to estimate sparse low-rank correlation matrices. The advantage of the proposed method is that it provides results that are interpretable using a heatmap, thereby avoiding result misinterpretations. We demonstrated the superiority of the proposed method through both numerical simulations and real examples.

Do synbiotics really enhance beneficial synbiotics effect on defecation symptoms in healthy adults?: Randomized, double-blind, placebo-controlled trial.

GOALS: We examined whether synbiotics enhance improvement by probiotics. BACKGROUND: Probiotics, which are beneficial microbacteria, are a nutritional intervention for treatment of functional constipation or its tendency. Prebiotics, meanwhile, can promote the proliferation of probiotics in the gastrointestinal tract and enhance their beneficial effects. Synbiotics, a combination of probiotics and prebiotics, may be superior to probiotics in the treatment of defecation-related symptoms, but this requires elucidation. STUDY: This randomized, double-blind, placebo-controlled study enrolled 69 healthy adults with constipation tendency. Participants were allocated to either control, probiotics, or synbiotics groups and they recorded details of their defecations and their condition. The first 2 weeks were the observation period and the latter 2 weeks were the intervention period, in which participants took test foods. Probiotic foods included Bifidobacterium longum NT strain (1010 CFU/day), synbiotic foods included the NT strain (1010 CFU/day) and galactooligosaccharide (1 g/day). Placebo foods contained the vehicle only. Participants answered questionnaires (Patient Assessment on Constipation Symptoms [PAC-SYM], and one on dietary history) on the last day of each period. RESULTS: Nine participants withdrew consent, and 2 of the remaining 60 had missing data. Age, body mass index, and sex were not significantly different between the 3 groups. Frequency of bowel movements in the fourth week, the primary endpoint, was not increased in the probiotics or synbiotics groups compared with the control group, and the frequency of bowel movements and days with defecation were not changed by probiotics or synbiotics during the intervention period. Probiotics and synbiotics did not improve stool conditions, although incomplete defecation was improved by probiotics but not by synbiotics compared with placebo. PAC-SYM indicated that stool condition and total scores were improved by probiotics but not by synbiotics during the intervention compared with placebo. CONCLUSION: The probiotic strain Bifidobacterium longum NT can improve constipation symptoms, especially stool condition, but it does not increase bowel movement frequency in healthy adults with constipation tendency. Synbiotics treatment seemed to diminish this improvement of constipation induced by probiotics. This study indicates the possibility of attenuation of beneficial effects from probiotics by the use of synbiotics, contrary to synbiotics theory.

Predicting the Degree of Distracted Driving Based on fNIRS Functional Connectivity: A Pilot Study.

Distracted driving is one of the main causes of traffic accidents. By predicting the attentional state of drivers, it is possible to prevent distractions and promote safe driving. In this study, we developed a model that could predict the degree of distracted driving based on brain activity. Changes in oxyhemoglobin concentrations were measured in drivers while driving a real car using functional near-infrared spectroscopy (fNIRS). A regression model was constructed for each participant using functional connectivity as an explanatory variable and brake reaction time to random beeps while driving as an objective variable. As a result, we were able to construct a prediction model with the mean absolute error of 5.58 × 102 ms for the BRT of the 12 participants. Furthermore, the regression model with the highest prediction accuracy for each participant was analyzed to gain a better understanding of the neural basis of distracted driving. The 11 of 12 models that showed significant accuracy were classified into five clusters by hierarchical clustering based on their functional connectivity edges used in each cluster. The results showed that the combinations of the dorsal attention network (DAN)-sensory-motor network (SMN) and DAN-ventral attention network (VAN) connections were common in all clusters and that these networks were essential to predict the degree of distraction in complex multitask driving. They also confirmed the existence of multiple types of prediction models with different within- and between-network connectivity patterns. These results indicate that it is possible to predict the degree of distracted driving based on the driver's brain activity during actual driving. These results are expected to contribute to the development of safe driving systems and elucidate the neural basis of distracted driving.

Concordance rate of a four-quadrant plot for repeated measurements.

BACKGROUND: To assure the equivalence between new clinical measurement methods and the standard methods, the four-quadrant plot and the plot's concordance rate is used in clinical practice, along with Bland-Altman analysis. The conventional concordance rate does not consider the correlation among the data on individual subjects, which may affect its proper evaluation. METHODS: We propose a new concordance rate for the four-quadrant plot based on multivariate normal distribution to take into account the covariance within each individual subject. The proposed concordance rate is formulated as the conditional probability of the agreement. It contains a parameter to set the minimum concordant number between two measurement methods, which is regarded as agreement. This parameter allows flexibility in the interpretation of the results. RESULTS: Through numerical simulations, the AUC value of the proposed method was 0.967, while that of the conventional concordance rate was 0.938. In the application to a real example, the AUC value of the proposed method was 0.999 and that of the conventional concordance rate was 0.964. CONCLUSION: From the results of numerical simulations and a real example, the proposed concordance rate showed better accuracy and higher diagnosability than the conventional approaches.

Endoscopic ultrasonography shear wave as a predictive factor of endocrine/exocrine dysfunction in chronic pancreatitis.

BACKGROUND AND AIM: Chronic pancreatitis (CP) leads to permanent impairment of exocrine and endocrine functions. The endoscopic ultrasonography (EUS)-based Rosemont classification plays an important role in diagnosing CP. However, it is based on subjective judgment. In contrast, EUS shear wave measurement (EUS-SWM) has been established to be a precise method for evaluating tissue hardness. This study aimed to evaluate the utility of EUS-SWM in diagnosing CP and determining exocrine and endocrine dysfunctions. METHODS: We evaluated 40 patients who underwent EUS-SWM between January 2019 and January 2020. They were classified into the normal pancreas and early, probable, and definite CP groups following the Japan Pancreatic Society criteria. EUS-SWM value was compared between the normal pancreas group and the early, probable, and definite CP groups. The relationship between EUS-SWM value and exocrine/endocrine dysfunctions was also assessed. The cut-off value of EUS-SWM for diagnosing CP and exocrine/endocrine dysfunctions was investigated. RESULTS: The EUS-SWM value was positively correlated with the Japan Pancreatic Society criteria stages. The probable and definite CP groups had significantly higher EUS-SWM values than the normal group. The areas under the receiver operating characteristic curve for the diagnostic accuracy of EUS-SWM for CP, exocrine dysfunction, and endocrine dysfunction were 0.92, 0.78, and 0.63, respectively. The cut-off values of 1.96, 1.96, and 2.34 for diagnosing CP, exocrine dysfunction, and endocrine dysfunctions had 83%, 90%, and 75% sensitivity, respectively, and 100%, 65%, and 64% specificity, respectively. CONCLUSIONS: Endoscopic ultrasonography shear wave measurement provides objective assessment and can thus be an alternative diagnostic tool for diagnosing CP and exocrine/endocrine dysfunctions.

Optimization of therapeutic strategy for p16-positive oropharyngeal squamous cell carcinoma: Multi-institutional observational study based on the national Head and Neck Cancer Registry of Japan.

BACKGROUND: Although the American Joint Committee on Cancer TNM classification has been amended to include human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) as an independent entity, to the authors' knowledge the optimized de-escalating treatment modality has not been established to date. METHODS: The authors conducted a retrospective, nationwide, observational study in patients with HPV-related OPSCC who were treated from 2011 to 2014 in Japan to determine the best treatment modality. RESULTS: A total of 688 patients who were newly diagnosed with HPV-related OPSCC who were treated with curative intent at 35 institutions and had coherent clinical information and follow-up data available were included in the current study. In patients with T1-T2N0 disease (79 patients), both the 3-year recurrence-free survival and overall survival (OS) rates were 100% in the group treated with radiotherapy (RT) as well as the group receiving concurrent chemoradiotherapy (CCRT). The 3-year OS rates were 94.4% (for patients with T1N0 disease) and 92.9% (for patients with T2N0 disease) among the patients treated with upfront surgery. In patients with stage I to stage II HPV-related OPSCC, the 5-year recurrence-free survival and OS rates were 91.4% and 92%, respectively, in the patients treated with CCRT with relatively high-dose cisplatin (≥160 mg/m2 ; 114 patients) and 74.3% and 69.5%, respectively, in the patients treated with low-dose cisplatin (<160 mg/m2 ; 17 patients). CONCLUSIONS: Despite it being a retrospective observational trial with a lack of information regarding toxicity and morbidity, the results of the current study demonstrated that patients with T1-T2N0 HPV-related OPSCC could be treated with RT alone because of the equivalent outcomes of RT and CCRT, and patients with stage I to stage II HPV-related OPSCC other than those with T1-T2N0 disease could be treated with CCRT with cisplatin at a dose of ≥160 mg/m2 .

Preoperative Scoring System to Predict Prognosis in Patients Who Undergo Neoadjuvant Therapy for Pancreatic Cancer.

BACKGROUND/AIM: This study investigated the feasibility of an integrated scoring system of preoperative prognostic parameters using data from before/after neoadjuvant therapy in patients with borderline resectable pancreatic cancer (BRPC). PATIENTS AND METHODS: We constructed and analyzed a prognostic scoring system using factors that were previously reported to be significant prognostic indicators or predictors of histological response. RESULTS: We analyzed 28 consecutive patients with BRPC who underwent neoadjuvant therapy and subsequent surgical resection. Overall survival (OS) and recurrence free survival (RFS) were greater in patients with high scores (n=11) than in patients with low scores (n=17; log-rank test p=0.03/0.028). Pathological N0 status (p<0.05) and tumor cell destruction rate >50% (p<0.05) were found at a higher incidence among patients with high scores. CONCLUSION: OS and RFS can be predicted with an integrated scoring system that uses prognostic indices before/after neoadjuvant therapy for BRPC.

The usefulness of EUS-FNA with contrast-enhanced harmonic imaging of solid pancreatic lesions: A prospective study.

BACKGROUND AND AIM: Few studies have investigated endoscopic ultrasound-guided fine-needle aspiration with contrast-enhanced harmonic imaging (EUS-FNA-CHI) for diagnosing and adequately sampling pancreatic lesions. This study aimed to investigate the efficacy of EUS-FNA-CHI compared with that of endoscopic ultrasound-guided fine-needle aspiration with fundamental B mode imaging (EUS-FNA-FBI) for diagnosing solid pancreatic lesions. METHODS: Consecutive patients with solid pancreatic lesions were enrolled prospectively (UMIN 000024467). Only samples obtained during the first needle pass (EUS-FNA-FBI) and second needle pass (EUS-FNA-CHI) were used to compare the accuracy rate for diagnosing pancreatic lesions and rate of adequate sampling for histological evaluation. In patients with hypo-enhancing lesions on contrast-enhanced harmonic EUS (CH-EUS), subgroup analyses were performed. Patients were classified into those with a heterogeneous area in the whole lesion (whole group), those with a heterogeneous area with a non-enhancing area (non-enhancing group), and those with a heterogeneous area with a homogeneous area (homogeneous group). RESULTS: Ninety-three patients were enrolled. Overall, the rates of adequate sampling and sensitivity were significantly higher with EUS-FNA-CHI than with EUS-FNA-FBI (84.9% vs 68.8%, P = 0.003 and 76.5% vs 58.8%, P = 0.011, respectively). The adequate sampling rate and sensitivity were significantly higher with EUS-FNA-CHI than with EUS-FNA-FBI when the mass was > 15 mm. In the non-enhancing and homogeneous groups, the adequate sampling rate and sensitivity were significantly higher with EUS-FNA-CHI than with EUS-FNA-FBI. CONCLUSIONS: CH-EUS enables improved observation of pancreatic lesions and helps identify the target of EUS-FNA among different pathological areas of the lesions particularly of > 15 mm.

Subjective Loudness Using External Noise Reflects the Loudness and Distress of Tinnitus: A Cross-Sectional Study.

OBJECTIVES: Subjective tinnitus loudness has been measured using loudness matches, which compare tinnitus loudness with pure tones from an audiometer. When patients compare the sound pressure of certain noises with the tinnitus loudness, however, there may be remarkable differences from the measurements according to loudness matches. Subjective loudness (SubL) is an estimation of the sound pressure of tinnitus loudness by comparison of noises considered to be most similar to tinnitus loudness of patient. We examine whether SubL is inferior to loudness matches in measurement of subjective tinnitus loudness. DESIGN: Single-group cross-sectional study. PATIENTS: Included in this study were a clinical group of 111 patients with the chief complaint of subjective tinnitus. Seven of the 111 patients were excluded due to missing audiometry or questionnaire data. METHODS: Patients assessed the tinnitus loudness and related distress using visual analogue scales (VAS-L and VAS-S) and answered the Tinnitus Handicap Inventory (THI). Hearing acuity, tinnitus pitch, and loudness were then measured using an audiometer. RESULTS: VAS-L, VAS-S, and THI scores significantly correlated with loudness match using Goodwin's method (SL2) and SubL. Subgroup analysis based on patient ages indicated that all correlations of SL2 with VAS-L, VAS-S, and THI scores were no longer seen in patients more than 60 years of age. Meanwhile, SubL correlated with VAS-L, VAS-S, and THI scores in all subgroups. CONCLUSIONS: SubL was a good reflection of self-reported loudness and distress of tinnitus. It may therefore be a simple and easy means of assessing tinnitus loudness and associated distress during pre-examination without an audiometer.

Endoscopic sphincterotomy to prevent post-ERCP pancreatitis in patients with biliary neoplasms: a multicenter retrospective cohort study.

Background and aims Treatment of biliary neoplasms often involves multiple endoscopic retrograde cholangiopancreatography (ERCP)-related procedures. Endoscopic sphincterotomy (ES) may prevent post-ERCP pancreatitis (PEP). This retrospective, multicenter cohort study aimed to investigate the effectiveness of ES for prevention of PEP in patients with biliary neoplasm. Methods Patients with biliary duct neoplasm who underwent ERCP between January 2006 and December 2016 were enrolled. The frequency of PEP was compared between the ES and non-ES groups using propensity score analysis. The effectiveness of ES in subgroups of patients who underwent biliary duct stent placement, intraductal ultrasound (IDUS), and transpapillary biliary duct biopsy was analyzed by logistic regression. Results Of the 362 patients enrolled, 84 (23.2 %) developed PEP. Propensity score matching for PEP risk factors in 172 ERCP procedures showed that the frequency of PEP in the ES group was lower than that in the non-ES group (19.7 % vs. 33.7 %). Non-ES was also an independent risk factor for PEP in patients who underwent intraductal ultrasound and transpapillary biliary duct biopsy (RR = 4.54 and 5.26), but was not an independent risk factor for PEP in patients with biliary duct stents. In addition, there was no evidence that the frequency of PEP was statistically different between patients with plastic stents and metal stents in the ES and non-ES groups ( P  = 0.14 and 0.10). Conclusions ES is an effective technique to prevent PEP in patients with biliary neoplasms. In particular, ES is a safe technique to prevent PEP when performing IDUS and transpapillary biliary duct biopsy.

Diffusion-weighted MRI predicts the histologic response for neoadjuvant therapy in patients with pancreatic cancer: a prospective study (DIFFERENT trial).

PURPOSE: Pre-operative prediction of histological response to neoadjuvant therapy aids decisions regarding surgical management of borderline resectable pancreatic cancer (BRPC). We elucidate correlation between pre-/post-treatment whole-tumor apparent diffusion coefficient (ADC) value and rate of tumor cell destruction. We newly verify whether post-treatment ADC value at the site of vascular contact predicts R0 resectability of BRPC. METHODS: We prospectively reviewed 28 patients with BRPC who underwent diffusion-weighted magnetic resonance imaging before neoadjuvant chemotherapy and surgery. Correlation between the percentage of tumor cell destruction and various parameters was analyzed. Strong parameters were assessed for their ability to predict therapeutic histological response and R0 resectability. RESULTS: Pre-/post-treatment whole-tumor ADC value correlated with tumor cell destruction rate by all parameters (R = 0.630/0.714, P < 0.001/< 0.0001). The post-treatment cutoff value of ADC at the site of vascular contact for discriminating histological response of tumor destruction of ≤ 50% and tumor destruction of > 50% was determined at 1.42 × 10-3 mm2/s. It predicts R0 with 88% sensitivity, 50% specificity, and 61% accuracy. For histological response, the post-treatment whole-tumor ADC cutoff value for discriminating between tumor destruction of ≤ 50% and tumor destruction of > 50% was determined at 1.40 × 10-3 mm2/s. It predicts histological response with 100% sensitivity, 81% specificity, and 89% accuracy. It predicts R0 with 88% sensitivity, 70% specificity, and 75% accuracy. CONCLUSIONS: Post-treatment whole-tumor ADC value may be a predictor of R0 resectability in patients with BRPC. Tumor cell destruction rate is indicated by the difference between pre-/post-treatment ADC values. This difference is strongly affected by the pre-treatment ADC value. The cutoff value of ADC at the site of vascular contact could not discriminate R0 resectability.

Utility of Contrast-Enhanced Harmonic Endoscopic Ultrasonography for Early Diagnosis of Small Pancreatic Cancer.

This study aimed to assess whether contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS), compared to multidetector-row computed tomography (MDCT) and magnetic resonance imaging (MRI), is useful for early diagnosis of small pancreatic cancer (PC). Between March 2010 and June 2018, all three imaging modalities and surgery were performed for patients with a pancreatic solid lesion measuring ≤20 mm; diagnostic ability was compared among modalities. Fifty-one of 60 patients were diagnosed with PC (PC size in 41 patients: 11-20 mm; 10 patients: ≤10 mm). The sensitivity, specificity, and accuracy of CH-EUS, MDCT, and MRI for PC (11-20 mm) detection were 95%/83%/94%, 78%/83%/79%, and 73%/33%/68%, respectively. The diagnostic ability of CH-EUS was significantly superior compared with MDCT and MRI (p = 0.002 and p = 0.007, respectively). The sensitivity, specificity, and accuracy of CH-EUS, MDCT, and MRI for PC (≤10 mm) detection were 70%/100%/77%, 20%/100%/38%, and 50%/100%/62%, respectively. The diagnostic ability of CH-EUS tended to be superior to that of MDCT (p = 0.025). The sensitivity of MDCT for PC (≤10 mm) detection was significantly lower than that for PC (11-20 mm) detection (20% vs. 78%; p = 0.001). CH-EUS, compared to MDCT and MRI, is useful for diagnosing small PCs.

Utility of Elastography with Endoscopic Ultrasonography Shear-Wave Measurement for Diagnosing Chronic Pancreatitis.

Background/Aims: Rosemont classification (RC) with endoscopic ultrasonography (EUS) is important for diagnosing chronic pancreatitis (CP) but is based only on subjective judgement. EUS shear wave measurement (EUS-SWM) is a precise modality based on objective judgment, but its usefulness has not been extensively studied yet. This study evaluated the utility of EUS-SWM for diagnosing CP and estimating CP severity by determining the presence of endocrine dysfunction along with diabetes mellitus (DM). Methods: Between June 2018 and December 2018, 52 patients who underwent EUS and EUS-SWM were classified into two groups according to RC: non-CP (indeterminate CP and normal) and CP (consistent and suggestive of CP). The EUSSWM value by shear wave velocity was evaluated with a median value. The EUS-SWM value was compared with RC and the number of EUS features. The diagnostic accuracy and cutoff value of EUS-SWM for CP and DM and its sensitivity and specificity were calculated. Results: The EUS-SWM value significantly positively correlated with the RC and the number of EUS features. The EUS-SWM values that were consistent and suggestive of CP were significantly higher than that of normal. The area under the receiver operating characteristic (AUROC) curve for the diagnostic accuracy of EUS-SWM for CP was 0.97. The cutoff value of 2.19 had 100% sensitivity and 94% specificity. For endocrine dysfunction in CP, the AUROC was 0.75. The cutoff value of 2.78 had 70% sensitivity and 56% specificity. Conclusions: EUS-SWM provides an objective assessment and can be an alternative diagnostic tool for diagnosing CP. EUS-SWM may also be useful for predicting the presence of endocrine dysfunction.