Durvalumab with etoposide and carboplatin for patients with extensive-stage small cell lung cancer and interstitial lung disease: A multicenter, open-label prospective trial.

OBJECTIVES: Certain guidelines recommend caution when administering immunotherapy in patients with pre-existing interstitial lung disease (ILD) owing to the high incidence of pneumonitis induced by anti-cancer therapy. A prospective clinical trial assessing the safety of chemoimmunotherapy in patients with small-cell lung cancer (SCLC) and pre-existing ILD is warranted. Therefore, this study evaluated the safety and efficacy of chemoimmunotherapy in patients with extensive-stage (ES)-SCLC and mild idiopathic interstitial pneumonia (IIP). METHODS: In this multicenter prospective trial, patients with ES-SCLC and pre-existing mild chronic fibrosing IIP were recruited. Mild IIP was defined as the exclusion of poor pulmonary function, a definite usual interstitial pneumonia (UIP) pattern, and positivity for autoantibodies in blood tests. The patients received durvalumab, etoposide, and carboplatin every three weeks (induction phase), followed by 1,500 mg durvalumab every four weeks (maintenance phase). The primary endpoint was severe pneumonitis-free rate. RESULTS: Twenty-one patients were included in the analysis. Among them, 13 patients displayed a probable UIP pattern, whereas eight patients exhibited an indeterminate for UIP pattern. Two patients (9.5 %) had pneumonitis of any grade during the induction phase; one had Grade 1 and the other had Grade 5 pneumonitis. No other patient developed pneumonitis during the maintenance phase. The severe pneumonitis-free rate was 95.2 % (95 % confidence interval (CI): 77.3-99.2 %). The median progression-free survival was 5.5 months (95 % CI: 3.6-6.4 months). Median overall survival was 10.7 months (95 % CI: 6.0 months to not reached). CONCLUSIONS: Chemoimmunotherapy is a feasible treatment approach for patients with ES-SCLC and mild IIP.

The role of secondary imaging in children aged under 24 months with proven skull fracture on initial computed tomography scan.

To assess the clinical significance of repeated head imaging in children with minor blunt force head trauma who underwent computed tomography (CT), limited to those who exclude with very low risk of important traumatic brain injury. We conducted a retrospective cohort study of children aged under 24 months with minor head trauma who underwent repeated head imaging and initial CT scans according to the Pediatric Emergency Care Applied Research Network (PECARN) rules. We enrolled 741 children and 110 with skull fracture (SF). Of the 96 patients with SF on initial CT who received head magnetic resonance imaging (MRI) a few days later, 36 (37.5%) patients' initial CT findings revealed intracranial injury in addition to SF. The number of children who exhibited new intracranial findings on follow-up MRI among those with isolated SF without intracranial damage and those with SF and intracranial injury on initial CT was 25/60 (40.7%) and 14/36 (38.9%), respectively. Subcutaneous hematoma on arrival and intersection with the coronal suture and lines of fracture were significantly associated with new intracranial findings. Four children with SF and intracranial injury on initial CT received neurosurgical intervention. No intervention was needed for those with isolated SF. We demonstrated that a proportion of children with head trauma had new findings on follow-up MRI, particularly in those without very low risk of clinically important traumatic brain injury. Patients who exhibit new intracranial MRI findings that satisfy the PECARN rules may not require neurosurgical intervention if their initial CT finding is isolated SF.

Endoscopic ultrasonography for microvascular imaging without contrast enhancement in the differential diagnosis of pancreatic lesions.

OBJECTIVES: Detective flow imaging endoscopic ultrasonography (DFI-EUS) is a recent imaging modality developed for detecting fine vessels without the need for ultrasound contrast agents. The aim of the present study was to evaluate the utility of DFI-EUS for solid pancreatic lesions and to compare the diagnostic ability for pancreatic cancer (PC) between DFI-EUS, directional power Doppler (eFLOW) EUS, and contrast-enhanced harmonic (CH)-EUS. METHODS: Patients with a pancreatic lesion who underwent DFI-EUS, eFLOW-EUS, and CH-EUS between March 2019 and November 2023 were retrospectively enrolled. Final diagnoses were confirmed by pathologic examination of EUS-guided tissue acquisition and/or resected specimens. Lesions were categorized into the three patterns of poor, mild, and rich vascularity on DFI-EUS and eFLOW-EUS, and hypo-, iso-, and hypervascular on CH-EUS. PC was defined as a poor pattern on DFI-EUS and eFLOW-EUS, and a hypovascular pattern on CH-EUS. RESULTS: The final diagnoses of 90 examined tumors were PC (n = 57), inflammatory mass (n = 6), autoimmune pancreatitis (n = 13), neuroendocrine tumor (n = 9), and others (n = 5). The sensitivity, specificity, and accuracy for diagnosis of PC were 93%, 82%, and 88%, respectively, on DFI-EUS, 97%, 42%, and 77% on eFLOW-EUS, and 95%, 89%, and 92% on CH-EUS. The accuracy of DFI-EUS was significantly superior to eFLOW-EUS (P = 0.005), but no significant difference was found between DFI-EUS and CH-EUS. CONCLUSION: DFI-EUS is more sensitive for depicting vasculature than eFLOW-EUS, and has higher diagnostic sensitivity for PC. Evaluation of vascularity on DFI-EUS is useful for the differential diagnosis of pancreatic lesions without the need for intravenous contrast agent.

Perioperative surveillance of myocardial injury after non-cardiac surgery in patients with hip fracture: A retrospective cohort study.

Myocardial injury after non-cardiac surgery is due to ischaemia either during non-cardiac surgery or within 30 days after it. Our surveillance protocol includes hip fracture template and high-sensitivity troponin stratification, as recommended in European countries. Our retrospective study cohort included surgical patients for hip fracture at our hospital in Japan. The primary outcome was the rate of myocardial injury after non-cardiac surgery in comparison to patients managed with (213) and without (176) hip fracture template. The hip fracture template was used more in patients with myocardial injury after non-cardiac surgery than those without myocardial injury after non-cardiac surgery. When hip fracture template was used, patients had a higher likelihood of myocardial injury after non-cardiac surgery after adjusting for age, time to operation, diabetes mellitus, and chronic kidney disease (odds ratio 41.3; 95% confidence interval: 12.1, 259.6). Patients with myocardial injury after non-cardiac surgery had higher in-hospital mortality than those without myocardial injury after non-cardiac surgery, even in adjusted analysis. There was a high detection rate of myocardial injury after non-cardiac surgery when patients with hip fractures were managed with hip fracture template. Myocardial injury after non-cardiac surgery was associated with in-hospital mortality.

Repeat endoscopic submucosal dissection close to the initial endoscopic submucosal dissection scar for superficial esophageal squamous cell carcinoma.

BACKGROUND: Repeat endoscopic submucosal dissection for metachronous recurrence of esophageal squamous cell carcinoma close to previous endoscopic submucosal dissection scars is challenging. Therefore, this study evaluated the efficacy and safety of repeat endoscopic submucosal dissection for recurrent esophageal squamous cell carcinoma. METHODS: The study included 1680 patients. After propensity score matching, esophageal endoscopic submucosal dissection-related outcomes were compared between the post-endoscopic submucosal dissection scar group (n = 91) and first endoscopic submucosal dissection group (n = 910). The Kaplan-Meier method and log-rank tests were used to compare both groups' survival and local recurrence curves. RESULTS: After propensity score matching, the two groups showed no significant difference in en bloc resection rate (97.80% vs. 99.56%, p = 0.096), treatment time (64.75 min vs 61.33 min, p = 0.448), recurrence rate (3.30% vs. 2.20%, p = 0.458), and stricture rate (7.69% vs. 4.07%, p = 0.110). However, the perforation rate was higher in the post-endoscopic submucosal dissection scar group than in the first endoscopic submucosal dissection group (4.40% vs. 1.10%, p = 0.031). The 5-year overall survival rates in the post-endoscopic submucosal dissection scar and first endoscopic submucosal dissection groups were 88.6% and 89.0%, respectively. CONCLUSIONS: Repeated esophageal endoscopic submucosal dissection for recurrent esophageal squamous cell carcinoma yielded satisfactory clinical outcomes and survival rates. Therefore, repeat endoscopic submucosal dissection may effectively treat esophageal squamous cell carcinoma recurrence close to the initial endoscopic submucosal dissection scars.

Usefulness of Clinical Frailty Scale for Comprehensive Geriatric Assessment of Older Heart Failure Patients.

Background: Comprehensive geriatric assessment (CGA) is a multidisciplinary diagnostic process to identify the physical, psychological, and social functions of patients with frailty. The Clinical Frailty Scale (CFS) might aid in effectively identifying older patients with heart failure (HF) and frailty who would then reap maximum benefits from the CGA. Methods and Results: A single-centre prospective cohort study that enrolled consecutive hospitalised patients (age ≥75 years) with HF was conducted. The Barthel index (BI), Mini Mental State Examination (MMSE), the Charlson comorbidity index (CCI), and the COntrolling NUTritional (CONUT) for CGA was used. Among 190 enrolled patients (mean age, 85.4 years; 47.9% male), all-cause mortality (primary endpoint) occurred in 45 patients and HF-related rehospitalization (secondary endpoint) in 59 patients within 1 year. The cumulative incidence of all-cause mortality was significantly higher in the high CFS group (low 6.3%, high 30.5%, P<0.001). However, the cumulative incidence of HF-related rehospitalization was not significantly different (low 26.3%, high 32.0%, P=0.304). The multivariable analysis revealed that the CFS group was independently associated with the risk of all-cause mortality. CFS showed a strong correlation with the BI and moderate correlation with the MMSE. Conclusions: The CFS was associated with all-cause mortality within 1 year and was correlated with frailty domains of CGA.

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.

Efficacy of the traction method for gastric endoscopic submucosal dissection: a randomized controlled trial (with videos).

BACKGROUND AND AIMS: To overcome the technical difficulties associated with gastric endoscopic submucosal dissection (ESD), a novel traction device that can alter the direction of traction was developed. This study compared the efficacy and safety of conventional ESD versus those of traction-assisted gastric ESD. METHODS: Patients with a single gastric epithelial neoplasm were randomized to receive conventional (n = 75) or traction-assisted (n = 73) gastric ESD. The primary outcome was ESD procedure time. RESULTS: There were no differences between the conventional and traction-assisted groups with respect to treatment results or adverse events. The mean procedure time was similar for both groups (78.9 vs 88.3 minutes, respectively; P = .3); however, times for the traction device tended to be shorter for lesions in the lesser curvature of the upper or middle stomach (84.6 vs 123.2 minutes; P = .057). CONCLUSIONS: Traction-assisted ESD for lesions in the lesser curvature of the upper or middle stomach were shorter, thereby reducing the procedure time of conventional ESD. (Clinical trial registration: University Hospital Medial Information Network Clinical Trials Registry, identifier 000044450.).

Safety of skipping the tract dilation step for EUS-guided biliary drainage in patients with unresectable malignant biliary obstruction (with video).

BACKGROUND: Thin delivery system stents can be inserted directly without the need for a tract dilation step and are expected to reduce bile leakage during endoscopic ultrasound-guided biliary drainage (EUS-BD). The present study retrospectively compared the safety and efficacy of EUS-BD using a thin metal stent (< 7.5 Fr) with those of EUS-BD using a conventional stent (≥ 7.5 Fr). METHODS: The present study enrolled 112 patients who underwent EUS-BD using metal stents for unresectable malignant biliary obstruction between April 2016 and July 2022. The primary endpoint was the rate of adverse events (AEs). The secondary endpoints were clinical success rate, procedure time, procedure success rate in the absence of the tract dilation step, recurrent biliary obstruction rate, time to biliary obstruction, and overall survival. Risk factors associated with early AEs were also evaluated. RESULTS: The rate of early AEs was significantly lower (12% vs. 35%, P = 0.013) and the procedure success without the tract dilation step was significantly higher (82% vs. 33%, P < 0.001) in the thin than in the conventional delivery system stent group. None of the other secondary endpoints differed significantly between the two groups. Multivariate analysis showed that employing the tract dilation step during EUS-BD was a significant independent risk factor for early AEs (skipping vs. employing; HR, 9.66; 95% CI, 1.13-83.0, P = 0.028). CONCLUSION: Employing the tract dilation step during EUS-BD was a significant risk factor for early AEs. Metal stents with a delivery diameter < 7.5 Fr can be inserted directly without the tract dilation step, resulting in lower early AE rates.

Mannitol versus furosemide in patients with thoracic malignancies who received cisplatin-based chemotherapy using short hydration: A randomized phase II trial.

BACKGROUND: Mannitol is exclusively recommended in the National Comprehensive Cancer Network guidelines for diuresis in cisplatin (CDDP)-based chemotherapy. The utility of furosemide, a widely used and convenient diuretic, thus requires clarification. METHODS: This is a prospective, single-centered, open-label, noninferiority phase II study. Patients with thoracic malignancies who planned to receive CDDP-based chemotherapy were randomly assigned to receive either mannitol (arm A) or furosemide (arm B). The primary end point was set as the proportion of patients who experienced any grade of "creatinine (Cr) increased" based on the upper limit of the normal range (ULN) during the first cycle as assessed by Common Terminology Criteria for Adverse Events Version 4.0. Secondary end points were Cr increased based on the baseline value during the first cycle, Cr increased after the completion of CDDP, and the proportion of patients with phlebitis. RESULTS: Between April 2018 and March 2022, 115 patients were enrolled and 106 were analyzed. Any grade of Cr increased based on the ULN during the first cycle was 17.3% (arm A) and 24.1% (arm B), respectively (p = 0.34). Therefore, the primary end point was not met. After completion of chemotherapy, any grade of Cr increased was observed in 23.1% (arm A) and 31.5% (arm B), respectively. However, the actual serum Cr level and Cr clearance during the courses were not different between the arms. Phlebitis occurred more frequently in arm A (28.8%) than arm B (16.7%). CONCLUSIONS: Mannitol should remain the standard diuresis in CDDP-based chemotherapy assessed by conventional CTCAE grading, but furosemide can be room for consideration when assessed by actual serum Cr level and Cr clearance.

Impact of Flagging/Risk Stratification System on Complications in Hospitalist Hip Fracture Co-management: Retrospective Cohort Study.

Purpose: Hip fractures are associated with high morbidity and mortality, the rates of which can be improved by comprehensive care. To improve hospitalist co-management of hip fractures, we designed and implemented hip fracture template (HFT), a flagging and risk stratification algorithm system. It includes consideration of perioperative management and preventative measures against hip fractures. We examined its effect on morbidity in patients with hip fractures and the factors associated with complications. Methods: We conducted a retrospective cohort study of patients who underwent surgery for hip fracture. The primary outcome was the perioperative complication rate, comparing patients managed with and without HFT. Multivariate analysis was adjusted for age, gender, and any significant variables shown in univariate analysis. Results: HFT was used in 121 patients and not used in 147 patients. In univariate analysis, patients were less likely to have complications if HFT was used (19.0% vs. 29.9%, P = 0.047), but there was no difference in length of stay (17 days vs. 17 days, P = 0.27) or in-hospital-mortality (0.8% vs. 0.7%, P = 1.00) between the groups. In adjusted analysis, patients managed by HFT had lower likelihood of complications (OR 0.55, 95% CI 0.31-0.98). Among patients managed by HFT, those with revised cardiac risk index (RCRI) ≥ 1 were more likely to have complications in both univariate (42.1% vs. 14.7%, P = 0.01) and adjusted analysis (OR 3.37, 95% CI 1.03-10.84). Conclusion: Patients with hip fractures managed with HFT were less likely to have complications, especially those with RCRI ≥ 1, suggesting benefits of using HFT.

Protocol for a Multi-Center Confirmatory Trial to Evaluate the Differential Diagnostic Performance of Contrast-Enhanced Ultrasonography Using Perflubutane in Patients with a Pancreatic Mass: A Multicenter Prospective Study.

For pancreatic masses, an evaluation of their vascularity using contrast-enhanced ultrasonography can help improve their characterization. This study was designed to evaluate the utility and safety of contrast-enhanced transabdominal ultrasonography (CE-TUS) and endoscopic ultrasonography (CE-EUS) in the diagnosis of pancreatic masses including solid or cystic masses. This multi-center comparative open-label superiority study is designed to compare Plain (P)-TUS/EUS alone with P-TUS/P-EUS plus CE-TUS/CE-EUS. Three hundred and one patients with a total of 232 solid pancreatic masses and 69 cystic masses were prospectively enrolled. The primary endpoints are to compare the diagnostic accuracy between P-TUS/P-EUS alone and P-TUS/P-EUS plus CE-TUS/CE-EUS for both the TUS and EUS of solid pancreatic masses, and to compare the diagnostic accuracy between P-EUS alone and P-EUS plus CE-EUS in cystic pancreatic masses. The secondary endpoints are to compare the diagnostic sensitivity and specificity of P-TUS/P-EUS alone and P-TUS/P-EUS plus CE-TUS/CE-EUS for pancreatic solid/cystic masses, and the accuracy of P-TUS alone and P-TUS plus CE-TUS for pancreatic cystic masses. Other secondary endpoints included comparing the diagnostic sensitivity, specificity, and accuracy of CE-TUS, CE-EUS and CE-computed tomography (CT) for solid/cystic pancreatic masses. The safety, degree of effective enhancement, and diagnostic confidence obtained with CE-TUS/CE-EUS will also be assessed.

Phase II study of S-1 plus docetaxel as first-line treatment for older patients with advanced gastric cancer (OGSG 0902).

BACKGROUND: Although there is insufficient evidence for the treatment of older patients with advanced gastric cancer, fluorouracil combined with platinum chemotherapy has been recognized as a standard first-line treatment for such populations in Japan despite the lack of efficacy and toxicity data. METHODS: Patients aged 75 years or older with advanced gastric cancer were enrolled. S-1 plus docetaxel (docetaxel: 40 mg/m2, day 1; S-1: 80 mg/m2, days 1-14; q21 days) was repeated every 3 weeks. The primary endpoint was overall response rate. Secondary endpoints were safety, progression-free survival, time to treatment failure, and overall survival. The sample size was calculated as 30 under the hypothesis of an expected response rate of 40% and a threshold response rate of 20%, at a power of 90% and a two-sided alpha value of 5%. RESULTS: From February 2010 to January 2015, 31 patients were enrolled and assessed for efficacy and toxicity. The response rate was 45.2% (95% CI 27.3%-64.0%; p = 0.001) and it exceeded the expected response rate set at 40%. Median progression-free survival was 5.8 months, the 1-year survival rate was 58.1%, and the median survival time was 16.1 months. The major grade 3/4 adverse events were neutropenia (58%), febrile neutropenia (13%), anemia (10%), anorexia (10%), and fatigue (6%). CONCLUSIONS: These findings indicate that S-1 plus docetaxel as first-line treatment for older patients is feasible and that it has promising efficacy against advanced gastric cancer.

Effect of istradefylline on postural abnormalities in patients with Parkinson's disease: An association study of baseline postural angle measurements with changes in Unified Dystonia Rating Scale total score.

In our previous study, istradefylline treatment in patients with Parkinson's disease (PD) improved postural abnormalities (PAs), as seen from a decrease in the mean Unified Dystonia Rating Scale (UDRS) total score from week 0 to week 24. A subgroup analysis based on baseline clinical characteristics investigated the association between improvement in the UDRS total score and istradefylline treatment. However, the association between an objective assessment of PAs and improvement in the UDRS total score is unclear. This ad hoc analysis investigated the association between improvement in the UDRS total score after istradefylline treatment and baseline trunk and neck angles, objective assessments of PAs, measured from patients' photographs taken in the previous study. The patients (n = 31) were stratified into groups based on the trunk forward flexion angle (TFFA), trunk lateral flexion angle (TLFA), and neck flexion angle (NFA) values at baseline. From week 0 to week 24, significant improvements in the UDRS total score were found in median percent change (-8.33% [interquartile range: -43.97, 0.00], P = 0.039) in patients with equal to or above the median TFFA values, and in median change (-|1.50 [-9.25, 0.00], P = 0.015) and median percent change (-13.33% [-50.47, 0.00], P = 0.009) in patients with equal to or above the median TLFA values. Patients with more advanced PAs showed more consistent improvements in the UDRS total score with istradefylline. Baseline TFFA and TLFA values, which are objective values, may be useful to assess the istradefylline effectiveness in patients with PD and PAs.

Impact of sarcopenia on recurrent biliary obstruction after EUS-guided biliary drainage in patients with malignant biliary obstruction.

BACKGROUND AND AIMS: Sarcopenia is an important prognostic factor for cancer patients. The aim of this study was to assess the ability of sarcopenia to predict recurrent biliary obstruction (RBO) in patients with unresectable cancer after EUS-guided biliary drainage (EUS-BD). METHODS: The study enrolled 113 patients who underwent EUS-BD using the self-expandable metal stent (SEMS) for unresectable malignant biliary obstruction (MBO) between April 2016 and December 2021 at Wakayama Medical University Hospital. The skeletal muscle index at the third lumbar spine level (L3) was calculated from computed tomography images. We analyzed the cumulative incidence of RBO at 180 days after stent insertion. Univariate and multivariate analyses were performed to identify variables significantly associated with RBO. RESULTS: Seventy-six patients were assigned to the sarcopenia group, and 37 were assigned to the non-sarcopenia group. The 180-day cumulative incidence of RBO was 11% in the non-sarcopenia group and 29% in the sarcopenia group (p = 0.034). The time to RBO was significantly shorter for the sarcopenia group (p = 0.028; Gray's test). Multivariate analyses identified sarcopenia as an independent prognostic factor for RBO (present vs absent; HR 4.61; 95% CI 1.76-12.10, p = 0.001). The rates of biliary sludge/food impaction were significantly higher in the sarcopenia group for the causes of RBO (p = 0.048). There were no significant differences between the sarcopenia and the non-sarcopenia groups with respect to related EUS-BD adverse events. CONCLUSION: Sarcopenia is an independent indicator of RBO in patients with MBO who receive EUS-BD with SEMS.

Effects of postoperative oral elemental nutritional supplement on skeletal muscle loss after gastrectomy for gastric cancer.

BACKGROUND: We previously showed that daily nutritional intervention with an oral elemental diet (ED) at 300 kcal/day for 6-8 weeks postoperatively decreased the percentage of body weight loss (%BWL), and that the effect was maintained for 1 year. This post hoc analysis aimed to determine whether this intervention decreased skeletal muscle mass loss 1-year post-gastrectomy. METHODS: Data from consecutive, untreated patients with histopathologically confirmed stage I-III gastric adenocarcinoma who planned to undergo total gastrectomy (TG) or distal gastrectomy (DG) and were enrolled in a previously published randomized trial were used. The primary endpoint was the percentage of skeletal muscle mass index (%SMI) loss from baseline at 1 year postoperatively, based on abdominal computed tomography images obtained preoperatively and at 1 year postoperatively. RESULTS: The overall median %SMI loss was lower in the ED versus control group, but the difference was not significant. The difference in %SMI loss in the ED and control groups was greater in patients with TG (10.1 vs. 13.0; P = 0.12) than in those with DG (5.5 vs. 6.8; P = 0.69). A correlation was observed between %BWL and %SMI loss in both groups (ED group, coefficient 0.591; control group, coefficient 0.644; P < 0.001 for both). Type of gastrectomy (coefficient 7.38; P = 0.001) and disease stage (coefficient - 6.43; P = 0.04) were independent predictors of postoperative skeletal muscle mass loss. CONCLUSION: ED administration for 6-8 weeks following gastrectomy had no inhibitory effect on skeletal muscle loss at 1 year postoperatively. CLINICAL TRIAL REGISTRATION: UMIN000023455.

K-ras gene mutation analysis to diagnosis pancreatic adenocarcinoma from endoscopic ultrasound-guided tissue acquisition; a systematic review and meta-analysis.

BACKGROUND: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) has high sensitivity for the pathological diagnosis of pancreatic masses, but also a high false-negative rate. K-ras gene mutations occur in over 75 % of pancreatic ductal adenocarcinomas (PDAC), and this meta-analysis evaluated the utility of detecting K-ras gene mutations from EUS-TA specimens for the diagnosis of PDAC. METHODS: Relevant studies in PubMed, the Cochrane Library, and Web of Science were systematically searched. Meta-analysis was performed on data from the selected studies using a bivariate model to provide pooled values of sensitivity, specificity, and their 95 % confidence intervals (CIs). RESULTS: This meta-analysis included 1521 patients (from 10 eligible studies) who underwent EUS-TA with K-ras gene mutation analysis for diagnosis of pancreatic solid masses. The pooled estimates of sensitivity and specificity were 76.6 % (95 % CI, 70.9-81.5 %) and 97.0 % (95 % CI, 94.0-98.5 %), respectively, for pathological diagnosis, 75.9 % (95 % CI 69.5-81.4 %) and 95.3 % (95 % CI, 92.3-97.2 %) for K-ras gene mutation analysis, and 88.7 % (95 % CI 87.1-91.7 %) and 94.9 % (95 % CI, 91.5-97.0 %) for pathological diagnosis in combination with K-ras gene mutation analysis. The sensitivity for diagnosis of PDAC was significantly higher for pathological diagnosis in combination with K-ras gene mutation analysis than for pathological diagnosis or K-ras gene mutation analysis alone (both, p < 0.001). There was no difference in specificity between pathological diagnosis in combination with K-ras gene mutation analysis and both either (p = 0.234, 0.945, respectively). CONCLUSIONS: K-ras gene mutation analysis in combination with to pathological diagnosis of EUS-TA increases the accuracy of differential diagnosis of PDAC.

A Phase II Study of High-Flow Nasal Cannula for Relieving Dyspnea in Advanced Cancer Patients.

CONTEXT: The efficacy and tolerability of high-flow nasal cannula (HFNC) for relieving dyspnea in advanced cancer patients with limited prognosis requires elucidation. OBJECTIVES: The primary aim of this trial was to assess the efficacy and tolerability of HFNC regarding dyspnea including severe as well as moderate for longer durations in patients under palliative care. METHODS: In this prospective study, hospitalized patients with advanced cancer who had dyspnea at rest (numeric rating scale, NRS≥3) and hypoxemia were enrolled. They were treated with HFNC for five days in the respiratory unit. Primary endpoint was mean change of modified Borg scale at 24 hours. Key secondary endpoints consisted of mean changes in modified Borg scale during the study period and feasibility (Trial Identifier, UMIN000035738). RESULTS: Between February 2019 and February 2022, 25 patients were enrolled and 21 were analyzed. Twenty patients used inspired oxygen and the mean fraction of inspired oxygen (FiO2) was 0.34 (range, 0.21-1.0). At baseline, mean NRS (dyspnea) was 5.9 (range, 3-10). Median survival time was 19 days (range, 3-657). The mean change of modified Borg scale was 1.4 (80% confidence interval [CI]: 0.8-1.9) at 24 hours, 12 patients (57%) showed 1.0 points improvement of modified Borg scale. Within two hours, 15 patients showed 1.0 points improvement of modified Borg scale and such early responders were likely to maintain dyspnea improvement for 24 hours. Nineteen patients could continue HFNC for 24 hours and 11 patients completed five days of HFNC. CONCLUSION: To our knowledge, this trial is the first prospective study to assess the five-day efficacy and tolerability of HFNC for dyspnea in patients under palliative care. Although this did not reach the prespecified endpoint, about half of the patients showed 1.0 point improvement, a minimally clinically important difference (MCID) in the chronic lung disease. HFNC can be a palliative treatment option in advanced cancer patients with dyspnea.

Adverse events of self-expandable metal stent placement for malignant distal biliary obstruction: a large multicenter study.

BACKGROUND AND AIMS: Endoscopic placement of self-expandable metal stents (SEMSs) for malignant distal biliary obstruction (MDBO) may be accompanied by several types of adverse events. The present study analyzed the adverse events occurring after SEMS placement for MDBO. METHODS: The present study retrospectively investigated the incidence and types of adverse events in patients who underwent SEMS placement for MDBO between April 2018 and March 2021 at 26 hospitals. Risk factors for acute pancreatitis, cholecystitis, and recurrent biliary obstruction (RBO) were evaluated by univariate and multivariate analyses. RESULTS: Of the 1425 patients implanted with SEMSs for MDBO, 228 (16.0%) and 393 (27.6%) experienced early adverse events and RBO, respectively. Pancreatic duct without tumor involvement (P = .023), intact papilla (P = .025), and SEMS placement across the papilla (P = .037) were independent risk factors for acute pancreatitis. Tumor involvement in the orifice of the cystic duct was an independent risk factor for cholecystitis (P < .001). Use of fully and partially covered SEMSs was an independent risk factor for food impaction and/or sludge. Use of fully covered SEMSs was an independent risk factor for stent migration. Use of uncovered SEMSs and laser-cut SEMSs was an independent risk factor for tumor ingrowth. CONCLUSIONS: Pancreatic duct without tumor involvement, intact papilla, and SEMS placement across the papilla were independent risk factors for acute pancreatitis, and tumor involvement in the orifice of the cystic duct was an independent risk factor for cholecystitis. The risk factors for food impaction and/or sludge, stent migration, and tumor ingrowth differed among types of SEMSs.

Efficacy and safety of neoadjuvant nab-paclitaxel plus gemcitabine therapy in patients with borderline resectable pancreatic cancer: A multicenter single-arm phase II study (NAC-GA trial).

Background: Nab-paclitaxel plus gemcitabine is a standard treatment for metastatic/locally advanced pancreatic cancer. The effectiveness of neoadjuvant therapy with nab-paclitaxel plus gemcitabine (GnP-NAT) in patients with borderline resectable pancreatic cancer (BRPC) remains unclear. Patients and Methods: This single-arm phase II trial included 61 patients with BRPC that were treated with two cycles of GnP-NAT, (nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2), on days 1, 8, and 15 over a 4-week period, which comprised one cycle. The primary endpoint was overall survival time. In the absence of disease progression, patients underwent planned pancreatectomy. Results: Median overall survival, the primary endpoint, was 25.2 months, and the median recurrence-free survival was 12.3 months. The overall rate of grade 3/4 events was 73.8%. One patient, who had a history of radiation therapy for past esophageal cancer, died from exacerbation via pneumonia. The overall resection rate was 73.8% (n = 45), and the R0 resection rate was 63.9% (n = 39). Overall, postoperative complications were found in 19 patients (42%) with 24 events, and nine patients (20%) with nine events ≥ grade IIIa, based on Dindo's classification. Conclusions: This protocol treatment is thought to be a feasible, safe, and promising treatment regimen, but we caution against its use in patients with a history of interstitial lung disease and/or prior pulmonary irradiation. The survival data from this study suggest the need for further investigations of GnP-NAT efficacy in patients with BRPC, as well as prospective evaluation of adverse events. Clinical Trial Registration: UMIN Clinical Trials Registry, UMIN000024154 and ClinicalTrials.gov, NCT02926183.