22-gauge Co-Cr versus stainless-steel Franseen needles for endoscopic ultrasound-guided tissue acquisition in patients with solid pancreatic lesions.

BACKGROUND/AIMS: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) using Franseen needles is reportedly useful for its high diagnostic yield. This study compared the diagnostic yield and puncturing ability of EUS-TA using 22-gauge cobalt-chromium (CO-Cr) needles with those of stainless-steel Franseen needles in patients with solid pancreatic lesions. METHODS: Outcomes were compared between the 22-gauge Co-Cr Franseen needle (December 2019 to November 2020; group C) and stainless-steel needle (November 2020 to May 2022; group S). RESULTS: A total of 155 patients (group C, 75; group S, 80) were eligible. The diagnostic accuracy was 92.0% in group C and 96.3% in group S with no significant intergroup differences (p=0.32). The rate of change in the operator (from training fellows to experts) was 20.0% (15/75) in group C and 7.5% (6/80) in group S. Stainless-steel Franseen needles showed less inter-operator difference than Co-Cr needles (p=0.03). CONCLUSION: Both Co-Cr and stainless-steel Franseen needles showed high diagnostic ability. Stainless-steel Franseen needles are soft and flexible; therefore, the range of puncture angles can be widely adjusted, making them suitable for training fellows to complete the procedure.

Comparison of serum acylcarnitine levels in patients with myalgic encephalomyelitis/chronic fatigue syndrome and healthy controls: a systematic review and meta-analysis.

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome/systemic exertion intolerance disease (ME/CFS/SEID) is a condition diagnosed primarily based on clinical symptoms, including prolonged fatigue and post-exertional malaise; however, there is no specific test for the disease. Additionally, diagnosis can be challenging since healthcare professionals may lack sufficient knowledge about the disease. Prior studies have shown that patients with ME/CFS/SEID have low serum acylcarnitine levels, which may serve as a surrogate test for patients suspected of having this disease. This systematic review and meta-analysis aimed to investigate the differences in serum acylcarnitine levels between patients with ME/CFS/SEID and healthy controls. METHODS: This systematic review was conducted using PubMed and Ichushi-Web databases. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, we included all studies from the databases' inception until February 17, 2023, that evaluated blood tests in both patients with ME/CFS/SEID and healthy control groups. The primary endpoint was the difference in serum acylcarnitine levels between the two groups. RESULTS: The electronic search identified 276 studies. Among them, seven met the eligibility criteria. The serum acylcarnitine levels were analyzed in 403 patients with ME/CFS/SEID. The patient group had significantly lower serum acylcarnitine levels when compared with the control group, and the statistical heterogeneity was high. CONCLUSION: The patient group had significantly lower serum acylcarnitine levels when compared with the control group. In the future, the measurement of serum acylcarnitine levels, in addition to clinical symptoms, may prove to be a valuable diagnostic tool for this condition.

Efficacy for diagnoses of scirrhous gastric cancer and safety of endoscopic ultrasound-guided fine-needle aspiration: A systematic review and meta-analysis.

Scirrhous gastric cancer (SGC) is diagnosed using endoscopy and/or biopsy; however, SGC diagnosis remains challenging owing to its special growth form and morphologic features. Hence, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), which is minimally invasive and has a high proportion of diagnostic tissue, may be an alternative investigative modality for patients with suspected SGC. This systematic review and meta-analysis aimed to identify and evaluate the evidence for the efficacy and safety of EUS-FNA in patients with suspected SGC. We conducted a systematic review using the PubMed (MEDLINE) and Ichushi-Web (NPO Japan Medical Abstracts Society) databases and included all entries in which SGC was evaluated using EUS-FNA in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement from the databases' inception to October 10, 2022. The primary outcome was the proportion of SGC diagnosed using EUS-FNA. In addition, we analyzed the proportion of adverse events associated with EUS-FNA. The electronic search identified 1890 studies; overall, four studies met the selection criteria and reported data on EUS-FNA performed on 114 patients with suspected SGC. The overall diagnostic yield of EUS-FNA for SGC was 82.6% (95% confidence interval, 74.6-90.6%) and the statistical heterogeneity was 0% (I 2 = 0%), indicating a low heterogeneity. Furthermore, the EUS-FNA diagnostic proportion for SGC lymph node metastasis was 75-100%, indicating a high diagnostic performance. The adverse event rate of EUS-FNA was 0%. EUS-FNA may be an alternative investigation mode for SGC patients with negative esophagogastroduodenoscopy-biopsy results.

Management and Risk Factors for Pleural Effusion in Japanese Patients with Chronic Myeloid Leukemia Treated with First-line Dasatinib in Real-world Clinical Practice.

Objective Pleural effusion (PE) is a common adverse event that occurs during dasatinib therapy for chronic myeloid leukemia (CML). However, the pathomechanism of PE and appropriate management of Asian patients with CML have not been elucidated. This study investigated the incidence rate, risk, and appropriate management of PE in Asian patients with CML treated with dasatinib. Methods We retrospectively collected data on patients in the chronic phase of CML who received first-line dasatinib therapy and were registered in the CML-Cooperative Study Group database. Patients We identified 44 cases of PE in a series of 89 patients and analyzed previously reported risk factors and effective management of PE. Results A univariate analysis revealed that age, diabetes mellitus, chronic renal failure, hypertension, the history of cardiovascular events, and dasatinib dose were significantly associated with PE. A multivariate analysis revealed that age ≥65 years old was the only independent risk factor for PE. Dasatinib dose reduction and switching to a tyrosine kinase inhibitor showed a statistically significant difference in effectively reducing PE volume compared to single diuretic use. Conclusion Although further studies are warranted, our observations showed that advanced age is a significant risk factor for PE, and tyrosine kinase inhibitor dose reduction or replacement of dasatinib may be an effective management strategy for PE in Asian CML patients who received first-line treatment with dasatinib in real-world clinical practice.

Early dynamics of chronic myeloid leukemia on nilotinib predicts deep molecular response.

Chronic myeloid leukemia (CML) is a myeloproliferative disorder caused by the BCR-ABL1 tyrosine kinase. Although ABL1-specific tyrosine kinase inhibitors (TKIs) including nilotinib have dramatically improved the prognosis of patients with CML, the TKI efficacy depends on the individual patient. In this work, we found that the patients with different nilotinib responses can be classified by using the estimated parameters of our simple dynamical model with two common laboratory findings. Furthermore, our proposed method identified patients who failed to achieve a treatment goal with high fidelity according to the data collected only at three initial time points during nilotinib therapy. Since our model relies on the general properties of TKI response, our framework would be applicable to CML patients who receive frontline nilotinib or other TKIs.

Hazardous repeat bleeding after colorectal endoscopic submucosal dissection in a patient with immune thrombocytopenia: complete hemostasis using an over-the-scope clip.

A 76-year-old man diagnosed with early-stage colorectal cancer was referred to our hospital for endoscopic submucosal dissection (ESD). The patient had a low platelet count (31,000/µL) due to immune thrombocytopenia (ITP). The cancerous lesion was completely resected without any adverse events. A blood test performed 1 day post-ESD showed no progression of anemia and the initial postoperative course was uneventful. However, 7 days after ESD, dark red stools were observed, and we performed an emergency colonoscopy. We stopped the bleeding twice using hemoclips and hemostatic forceps. Since the patient's platelet count remained below 50,000/µL, we started thrombopoietin receptor agonist treatment with eltrombopag (12.5 mg/day) for thrombocytopenia. Although the platelet count increased, the patient experienced rebleeding for the fourth time and underwent an emergency colonoscopy, during which we used an over-the-scope clip (OTSC) to achieve hemostasis. No rebleeding occurred after OTSC intervention, and the platelet count stabilized at approximately 50,000/µL. We discharged the patient on Day 34 after ESD. Although the guidelines do not specify a target platelet count for performing ESD, a platelet count < 50,000/µL should be considered low. Furthermore, an OTSC may be useful for treating intractable bleeding.

Intraperitoneal Abscess as a Postoperative Complication of Gastric Endoscopic Submucosal Dissection.

We herein report a case of intraperitoneal abscess as a postoperative complication of gastric endoscopic submucosal dissection (ESD). A 70-year-old man who underwent ESD for early gastric cancer sought consultation for abdominal pain on postoperative day 28. Abdominal computed tomography revealed intraperitoneal abscess rupture. He underwent image-guided laparoscopic irrigation. His postoperative course was favorable, and he was discharged after 27 days. Intraoperatively, a white plaque adhering to the gastric wall was surrounded by a large pus volume and suspected to be ESD-associated. We present this case with a literature review of the association between intraperitoneal abscess and ESD.

The EUTOS long-term survival score predicts disease-specific mortality and molecular responses among patients with chronic myeloid leukemia in a practice-based cohort.

The European Treatment and Outcome Study (EUTOS) long-term survival (ELTS) score predicts disease-specific death in patients with chronic myeloid leukemia (CML) being treated with imatinib during the chronic phase (CP) of the disease. However, it is unclear whether the ELTS score predicts CML-related events or treatment responses. This study evaluated the predictive value of the ELTS score regarding prognosis and treatment response in patients with CML-CP. Clinical data were retrospectively obtained from patients enrolled in the CML Cooperative Study Group (CML-CSG), which included patients diagnosed with CML-CP from April 2001 to January 2016, and treated with any tyrosine kinase inhibitor (TKI) as first-line therapy. Among 342 eligible patients, the ELTS scores indicated low-, intermediate-, and high-risk in 74%, 21%, and 5% of patients, respectively. Patients with high ELTS scores had significantly higher disease-specific mortality and worse event-free survival, progression-free survival, and overall survival. Among four risk scores, including the Sokal, Hasford, EUTOS, and ELTS scores, risk stratification by the ELTS score had the highest predictive value in assessing patient prognosis, and also in treatment responses. In fact, the EUTOS and ELTS scores were able to predict the major molecular response within 12 months. Most importantly, the ELTS score was the only scoring system that predicted deep molecular response at any time, regardless of risk level (65.0%, 43.7%, and 23.5% in low-, intermediate-, and high-risk groups, respectively). Compared to other risk scores, the ELTS score was the most sensitive risk classification tool for the four endpoints of interest in this study, as well as molecular responses in patients with CML-CP.

Optimal treatment strategy with nilotinib for patients with newly diagnosed chronic-phase chronic myeloid leukemia based on early achievement of deep molecular response (MR4.5 ): The phase 2, multicenter N-Road study.

For patients who have chronic myeloid leukemia (CML), one of the primary treatment options is administration of nilotinib 300 mg twice daily (BID). In previous studies which compared outcomes associated with nilotinib or imatinib treatment, nilotinib achieved a higher rate of deep molecular response (MR). We conducted a phase II, open-label, multicenter study to investigate an intrapatient nilotinib dose-escalation strategy for patients with newly diagnosed chronic-phase (CP) CML based on early MR4.5 achievement. The primary study endpoint was achievement of MR4.5 by 24 months following the initiation of nilotinib 300 mg BID. Fifty-three patients were enrolled, 51 received nilotinib, and 37 completed the treatment. An increase in the nilotinib dose (to 400 mg BID) was allowed when patients satisfied our criteria for no optimal response at any time point. The median (range) dose intensity was 600 (207-736) mg/day. Of 46 evaluable patients, 18 achieved an optimal response and 28 did not. Of the latter, nine patients underwent dose escalation to 400 mg BID, and none achieved MR4.5 . The remaining 19 patients could not undergo dose escalation, 12 (63%) because of adverse events (AEs), and 7 (37%) for non-AE related reasons. Four of these patients achieved MR4.5 . The MR4.5 rate by 24 months was 45.7%. The progression-free, overall and event-free survival were each 97.6%. No new safety concerns were observed. Our findings support the use of continuous nilotinib at a dose of 300 mg BID for newly diagnosed patients with CML-CP.

Potential role for second­generation tyrosine kinase inhibitors in patients with chronic myeloid leukemia harboring additional clonal chromosome abnormalities: A retrospective CML Cooperative Study Group analysis.

Tyrosine kinase inhibitor (TKI) treatment is the standard of care for patients with chronic myeloid leukemia (CML). Even in the imatinib era, the presence of 'clonal chromosomal abnormalities' in the Philadelphia chromosome (CCA/Ph+) at diagnosis reportedly increased the risk of disease progression and predicted shorter survival. However, it remains unclear whether CCA/Ph+ is a poor prognostic marker in the era of new­generation TKIs. The data of patients with CML in the chronic phase (CP) that were extracted from the CML Cooperative Study Group database were retrospectively analyzed. Of the 328 eligible patients, 33 (10.1%) had CCA/Ph+, including 9 major route and 24 minor route aberrations. The characteristics of patients with and without CCA/Ph+ were similar; however, the proportion of blasts was higher among patients with CCA/Ph+. Notably, the survival rate of patients with CCA/Ph+ was not inferior to that of patients without CCA/Ph+, and there were no differences in responses to TKIs. All 9 patients with major route CCA/Ph+ attained a major molecular response (MMR) with no disease progression, and 8 ultimately achieved a deep molecular response. In particular, the median interval between TKI initiation and achievement of MMR was shorter in patients initially treated with a second­generation TKI than in those treated with imatinib (5 vs. 10 months). The present retrospective study, thus, revealed favorable treatment outcomes in CML­CP patients with CCA/Ph+ treated with second­generation TKIs. The data indicated that administering second­generation TKIs as first­line treatments is preferable in CML­CP patients with CCA/Ph+.

Comparison of the clinical outcomes of nilotinib and dasatinib therapies in newly diagnosed patients in the chronic phase of chronic myeloid leukemia: a retrospective analysis.

Treatment with a tyrosine kinase inhibitor (TKI) is the standard of care for patients with chronic myeloid leukemia (CML). The new-generation TKIs, nilotinib and dasatinib, are found to have deeper and faster treatment response rates compared to imatinib in the first-line setting. However, a direct comparison between nilotinib and dasatinib has never been reported previously. Our study aims to compare the outcomes and molecular responses achieved following the first-line use of these two agents in patients with CML-CP. The database of the CML Cooperative Study Group was reviewed and patients with CML in the chronic phase (CP) who were given nilotinib or dasatinib as first-line therapy were identified. Out of 361 patients with CML-CP enrolled in our database, 58 and 63 had been treated with conventional doses of nilotinib (300 mg twice daily) and dasatinib (100 mg once daily), respectively, as first-line therapy. The patient demographics did not show significant differences between the groups. The event-free survival rates did not differ between these two groups. The major molecular response (MMR) and the deep molecular response (DMR) rates by 6, 12, 18, and 24 months did not differ between groups. Among the three scoring systems, only the Hasford score could predict the achievement of DMR, and all of them failed to predict the achievement of MMR in the entire cohort. Our data suggest that both nilotinib and dasatinib have comparable efficacies and promising outcomes.

Features of vascular adverse events in Japanese patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: a retrospective study of the CML Cooperative Study Group database.

This study investigated the incidence rate and features of vascular adverse events (VAEs) in Japanese patients with chronic myeloid leukemia (CML) who were treated with tyrosine kinase inhibitors (TKIs). The analysis included 369 CML patients in the chronic or accelerated phases, selected from the CML Cooperative Study Group database; 25 events in 23 (6.2%) of these patients were VAEs. At the time of VAE incidence, nine patients were on treatment with imatinib, 12 with nilotinib, three with dasatinib, and one with bosutinib. VAE incidence comprised 13 cases of ischemic heart disease (IHD), eight of cerebral infarction (CI), and four of peripheral arterial occlusive disease (PAOD). IHD incidence rate in the study population was higher than that in the age-matched general population, particularly in nilotinib-treated patients, while CI incidence rate was almost equivalent. Compared with the Suita score, the SCORE chart and the Framingham score risk assessment tools detected more patients with high or very high risk of VAEs. In conclusion, incidence of IHD requires closer monitoring in nilotinib-treated patients. More detailed investigations for determining the most useful tool to predict VAE incidence and long-term analysis of therapy-related VAE cases are needed for improving safety during TKI therapy.

Incidence and outcome of second malignancies in patients with chronic myeloid leukemia during treatment with tyrosine kinase inhibitors.

We performed a retrospective study to evaluate the incidence of second malignancies (SMs) in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs). We analyzed data from 339 patients with CML who were extracted from the CML Cooperative Study Group database. The standardized incidence ratio (SIR) was calculated to assess the risk of SMs using data from the Cancer Registries in Japan. The median follow-up was 65 months. SMs developed in 14 patients (4.1%, 10 men, 4 women) after the start of TKIs. The median age was 69 years at the time of the CML diagnosis and 72.5 years at the time of the SM diagnosis. Ten patients were treated with imatinib, three with dasatinib, and one with nilotinib as the initial treatment. The SIR for all malignancies was 1.05 (95% CI 0.50-1.93) for men and 1.08 (95% CI 0.29-2.76) for women. The difference in the overall survival (OS) of patients with or without SMs was not statistically significant (5-year OS: 82.5% vs. 92.9%; p = 0.343). A subgroup analysis of 166 patients treated with second-generation TKIs (92 dasatinib, 74 nilotinib) showed that the SIRs for all malignancies were 1.33 (95% CI 0.36-3.41) for men and 0 for women. In conclusion, the incidence of SMs in CML patients during TKI treatment was the same as that in the general Japanese population. There was no evidence of an increase in the incidence of SMs during second-generation TKI treatment. Furthermore, the occurrence of SMs during TKI treatment did not affect the survival or mortality in our cohort.

Introduction of second-generation tyrosine kinase inhibitors may reduce the prognostic impact of high-risk patients, according to the European treatment and outcome study (EUTOS) score.

Our study aims to highlight the critical role of the introduction of second generation tyrosine kinase inhibitors (2nd TKIs) on the prognosis of patients with chronic myeloid leukemia (CML) in chronic phase (CML-CP), as determined by European Treatment and Outcome Study (EUTOS) system. Patients who were diagnosed with CML-CP before March 2009 were classified into the imatinib group, and those diagnosed after April 2009 were classified into the 2nd TKI group. EUTOS high-risk patients exhibited significantly worse outcomes in terms of event-free survival (EFS), progression-free survival (PFS), and CML-associated death than those considered to be low-risk. Risk stratification by EUTOS score was predictive of risk-associated clinical outcomes in patients classified into the imatinib group; however, the EUTOS score failed to predict the outcomes of patients classified into the 2nd TKI group. Our data suggest that the introduction of 2nd TKIs might have improved treatment outcomes, particularly in EUTOS high-risk patients.

Incidences and outcomes of therapy-related chronic myeloid leukemia in the era of tyrosine kinase inhibitors: Surveillance of the CML Cooperative Study Group.

This study was performed to investigate the features and outcome of patients with therapy-related chronic myeloid leukemia (TR-CML) who were treated with tyrosine kinase inhibitors (TKIs). The analysis included 308 patients with CML in the chronic phase who were extracted from the CML Cooperative Study Group database. Of these patients, 11 (3.6%) were identified as having TR-CML. No differences in age, sex, white blood cell count, hemoglobin level, platelet count, or European Treatment and Outcome Study risk were observed between patients with TR-CML vs. de novo CML. However, the responses of TR-CML patients to TKIs (6, 3, and 2 received imatinib, nilotinib, and dasatinib, respectively) were excellent; all achieved major or deep molecular response. Furthermore, the outcomes of TR-CML patients were relatively favorable; the 3-year event-free survival rates in the TR-CML and de novo CML patients were 100% and 94%, respectively; the difference was not statistically significant. In conclusion, our study showed that TR-CML patients could achieve a good clinical course with TKI therapy. Detailed investigations of TR-CML may provide new insights into CML biology.