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Annals of Surgical Oncology Jul 2024The clinico-oncological outcomes of precursor epithelial subtypes of adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) are limited to small...
Precursor Epithelial Subtypes of Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasms (A-IPMN): Clinicopathological Features, Recurrence and Response to Adjuvant Chemotherapy.
BACKGROUND
The clinico-oncological outcomes of precursor epithelial subtypes of adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) are limited to small cohort studies. Differences in recurrence patterns and response to adjuvant chemotherapy between A-IPMN subtypes are unknown.
METHODS
Clincopathological features, recurrence patterns and long-term outcomes of patients undergoing pancreatic resection (2010-2020) for A-IPMN were reported from 18 academic pancreatic centres worldwide. Precursor epithelial subtype groups were compared using uni- and multivariate analysis.
RESULTS
In total, 297 patients were included (median age, 70 years; male, 78.9%), including 54 (18.2%) gastric, 111 (37.3%) pancreatobiliary, 80 (26.9%) intestinal and 52 (17.5%) mixed subtypes. Gastric, pancreaticobiliary and mixed subtypes had comparable clinicopathological features, yet the outcomes were significantly less favourable than the intestinal subtype. The median time to recurrence in gastric, pancreatobiliary, intestinal and mixed subtypes were 32, 30, 61 and 33 months. Gastric and pancreatobiliary subtypes had worse overall recurrence (p = 0.048 and p = 0.049, respectively) compared with the intestinal subtype but gastric and pancreatobiliary subtypes had comparable outcomes. Adjuvant chemotherapy was associated with improved survival in the pancreatobiliary subtype (p = 0.049) but not gastric (p = 0.992), intestinal (p = 0.852) or mixed subtypes (p = 0.723). In multivariate survival analysis, adjuvant chemotherapy was associated with a lower likelihood of death in pancreatobiliary subtype, albeit with borderline significance [hazard ratio (HR) 0.56; 95% confidence interval (CI) 0.31-1.01; p = 0.058].
CONCLUSIONS
Gastric, pancreatobiliary and mixed subtypes have comparable recurrence and survival outcomes, which are inferior to the more indolent intestinal subtype. Pancreatobiliary subtype may respond to adjuvant chemotherapy and further research is warranted to determine the most appropriate adjuvant chemotherapy regimens for each subtype.
PubMed: 38961040
DOI: 10.1245/s10434-024-15677-z -
Seminars in Nuclear Medicine Jul 2024Cardiac amyloidosis (CA) is caused by the misfolding, accumulation and aggregation of proteins into large fibrils in the extracellular compartment of the myocardium,... (Review)
Review
Cardiac amyloidosis (CA) is caused by the misfolding, accumulation and aggregation of proteins into large fibrils in the extracellular compartment of the myocardium, leading to restrictive cardiomyopathy, heart failure and death. The major forms are transthyretin (ATTR) CA and light-chain (AL) CA, based on the respective precursor protein. Each of them requires early diagnosis for a timely treatment initiation that will improve patient outcomes. For this, radionuclide imaging is essentially used as single-photon emission computed tomography (SPECT) with bone-avid radiotracers or as positron emission tomography (PET) with amyloid-binding radiotracers. Both offer unprecedented specificity for the diagnostic of CA. SPECT has even revolutionized the diagnosis of ATTR-CA by making it non-invasive. Indeed, SPECT has now entered the standard diagnostic pathway to CA and has led to earlier diagnosis of the disease. SPECT also modified the epidemiology of ATTR-CA, highlighting that the disease is much more frequent than previously believed, and showing that ATTR-CA plays a substantial role in HFpEF and aortic stenosis, particularly among elderly patients. In parallel, amyloid-binding radiotracers for PET have accumulated a substantial amount of evidence, but are not approved for clinical use in CA yet. Further studies are needed to refine acquisition protocols and validate results in broader populations. Unlike bone-avid SPECT radiotracers, PET radiotracers have been specifically created to bind to amyloid fibrils. Thus, PET is the only imaging method that is truly specific for amyloid deposits and very sensitive to any amyloid type. Indeed, PET can not only detect ATTR-CA, but also AL-CA and rare hereditary forms. For both SPECT and PET, advances in quantitation of myocardial uptake have generated more granular and reproducible findings, paving the way for progress in earlier diagnosis, risk stratification and therapeutic response monitoring. Encouraging findings have shown that SPECT and PET are sensitive to early CA when other diagnostic methods are negative. Both radionuclide imaging techniques can predict adverse outcomes, but more evidence is needed to determine how to use them in conjunction with usual prognostic staging scores. Studies on follow-up imaging after therapy suggested that SPECT and PET can capture myocardial changes in CA, but again, more data are needed to meaningfully interpret such changes. Based on all these promising results, radionuclide imaging has the potential to further impact the landscape of CA in diagnosis, prognosis and follow-up, but also to substantially contribute to the assessment of novel therapies that will improve the lives of patients with CA.
PubMed: 38960850
DOI: 10.1053/j.semnuclmed.2024.05.012 -
Journal of Nuclear Medicine : Official... Jul 2024Meta-[I]iodobenzylguanidine ([I]MIBG) scintigraphy with SPECT/CT is the standard of care for diagnosing and monitoring neuroblastoma. Replacing [I]MIBG with the new PET...
Meta-[I]iodobenzylguanidine ([I]MIBG) scintigraphy with SPECT/CT is the standard of care for diagnosing and monitoring neuroblastoma. Replacing [I]MIBG with the new PET tracer meta-[F]fluorobenzylguanidine ([F]MFBG) and further improving sensitivity and reducing noise in a new long-axial-field-of-view (LAFOV) PET/CT scanner enable increased image quality and a faster acquisition time, allowing examinations to be performed without sedation or general anesthesia (GA). Focusing on feasibility, we present our first experience with [F]MFBG LAFOV PET/CT and compare it with [I]MIBG scintigraphy plus SPECT/CT for imaging in neuroblastoma in children. A pilot of our prospective, single-center study recruited children with neuroblastoma who were referred for [I]MIBG scintigraphy with SPECT/CT. Within 1 wk of [I]MIBG scintigraphy and SPECT/low-dose CT, [F]MFBG LAFOV PET/ultra-low-dose CT was performed 1 h after injection (1.5-3 MBq/kg) without sedation or GA, in contrast to the 24-h postinjection interval needed for scanning with [I]MIBG, the 2- to 2.5-h acquisition time, and the GA often needed in children less than 6 y old. Based on the spirocyclic iodonium-ylide precursor, [F]MFBG was produced in a fully automated good manufacturing practice-compliant procedure. We present the feasibility of the study. In the first paired scans of the first 10 children included (5 at diagnosis, 2 during treatment, 2 during surveillance, and 1 at relapse), [F]MFBG PET/CT scan showed a higher number of radiotracer-avid lesions in 80% of the cases and an equal number of lesions in 20% of the cases. The SIOPEN score was higher in 50% of the cases, and the Curie score was higher in 70% of the cases. In particular, intraspinal, retroperitoneal lymph node, and bone marrow involvement was diagnosed with much higher precision. None of the children (median age, 1.6 y; range, 0.1-7.9 y) had sedation or GA during the PET procedure, whereas 80% had GA during [I]MIBG scintigraphy with SPECT/CT. A PET acquisition time of only 2 min without motion artifacts was the data requirement of the 10-min acquisition time for reconstruction to provide a clinically useful image. This pilot study demonstrates the feasibility of performing [F]MFBG LAFOV PET/CT for imaging of neuroblastoma. Further, an increased number of radiotracer-avid lesions, an increased SIOPEN score, and an increased Curie score were seen on [F]MFBG LAFOV PET/CT compared with [I]MIBG scintigraphy with SPECT/CT, and GA and sedation was avoided in all patients. Thus, with a 1-d protocol, a significantly shorter scan time, a higher sensitivity, and the avoidance of GA and sedation, [F]MFBG LAFOV PET/CT shows promise for future staging and response assessment and may also have a clinical impact on therapeutic decision-making for children with neuroblastoma.
PubMed: 38960713
DOI: 10.2967/jnumed.123.267256 -
[Rinsho Ketsueki] the Japanese Journal... 2024Many effective new agents for relapsed childhood acute lymphoblastic leukemia (ALL) are now becoming available, and international standard chemotherapy should be...
Many effective new agents for relapsed childhood acute lymphoblastic leukemia (ALL) are now becoming available, and international standard chemotherapy should be developed to optimize use of these agents. Randomized controlled trials (RCTs) are needed to establish a standard treatment, but few have been conducted for relapsed childhood ALL in Japan due to the small patient population. Participation in international RCTs is necessary to access sufficient patients for informative study results, but differences in approved drugs and healthcare systems between countries make this challenging. In 2014, the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) participated in an international study on standard-risk relapsed childhood ALL (IntReALL SR 2010) involving two RCTs and multiple drugs not approved in Japan, which was addressed by replacing the unapproved drugs with alternative approved drugs with the same or similar efficacy. This article discusses the historical background of treatment development for relapsed childhood ALL, our experience in participating in the IntReALL SR 2010 trial, and prospects for treating relapsed childhood ALL.
Topics: Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Child; Japan; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38960661
DOI: 10.11406/rinketsu.65.590 -
[Rinsho Ketsueki] the Japanese Journal... 2024Clinical trials with a solid strategy are indispensable for improving outcomes of rare childhood leukemias such as infant acute lymphoblastic leukemia (ALL) and ALL...
Clinical trials with a solid strategy are indispensable for improving outcomes of rare childhood leukemias such as infant acute lymphoblastic leukemia (ALL) and ALL associated with Down syndrome, and international collaboration contributes to trial success. I am part of a group conducting an international trial of ALL associated with Down syndrome in collaboration with Asian countries. Although we are meeting enrollment targets, there have been no enrollments outside Japan. We also planned a clinical trial in unclassifiable acute leukemia, but abandoned this effort due to a lack of consensus on the choice of treatment regimen. Many elements must fit together for an international trial to succeed, including not only the study's concept, theme, and objectives, but also the organization, the logistics, and, ultimately, trained professionals to carry it out. At the same time, of course, there is the need for appropriate timing and luck. International trials across countries with different cultures, social organizations, and medical systems require persistent effort and negotiation skills. Professional training and infrastructure development are necessary to make this possible.
Topics: Humans; Clinical Trials as Topic; International Cooperation; Asia; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 38960660
DOI: 10.11406/rinketsu.65.584 -
International Journal of Biological... Jul 2024Traditional plastics reshaped the society thanks to their brilliant properties and cut-price manufacturing costs. However, their protracted durability and limited... (Review)
Review
Traditional plastics reshaped the society thanks to their brilliant properties and cut-price manufacturing costs. However, their protracted durability and limited recycling threaten the environment. Worthy alternatives seem to be polyhydroxyalkanoates, compostable biopolymers produced by several microbes. The most common 3-hydroxybutyrate homopolymer has limited applications calling for copolymers biosynthesis to enhance material properties. As a growing number of researches assess the discovery of novel comonomers, great endeavors are dedicated as well to copolymers production scale-up, where the choice of the microbial carbon source significantly affects the overall economic feasibility. Diving into novel metabolic pathways, engineered strains, and cutting-edge bioprocess strategies, this review aims to survey up-to-date publications about copolymers production, focusing primarily on precursors origins. Specifically, in the core of the review, copolymers precursors have been divided into three categories based on their economic value: the costliest structurally related ones, the structurally unrelated ones, and finally various low-cost waste streams. The combination of cheap biomasses, efficient pretreatment strategies, and robust microorganisms paths the way towards the development of versatile and circular polymers. Conceived to researchers and industries interested in tackling polyhydroxyalkanoates production, this review explores an angle often underestimated yet of prime importance: if PHAs copolymers offer advanced properties and sustainable end-of-life, the feedstock choice for their upstream becomes a major factor in the development of plastic substitutes.
PubMed: 38960239
DOI: 10.1016/j.ijbiomac.2024.133575 -
International Journal of Biological... Jul 2024The construction of N, P co-doped hierarchically porous carbons (NPHPC) by a facile and green approach is crucial for high-performance energy storage but still an...
The construction of N, P co-doped hierarchically porous carbons (NPHPC) by a facile and green approach is crucial for high-performance energy storage but still an enormous challenge. Herein, an environment-friendly "in-situ co-doping, self-regulation-activation" strategy is presented to one-pot synthesize NPHPC using a phytic acid-induced polyethyleneimine/chitosan gel (PEI-PA-CS) as single precursor. NPHPC displayed a specific surface area of up to 1494 m g, high specific capacitance of 449 F g at 1 A g, outstanding rate capability and cycling durability in a wide temperature range (-20 to 60 °C). NPHPC and PEI-PA-CS electrolyte assembled symmetric quasi-solid-state flexible supercapacitor presents superb energy outputs of 27.06 Wh kg at power density of 225 W kg. For capacitive deionization (CDI), NPHPC also exhibit an excellent salt adsorption capacity of 16.54 mg g in 500 mg L NaCl solution at a voltage of 1.4 V, and regeneration performance. This study provides a valuable reference for the rational design and synthesis of novel biomass-derived energy-storage materials by integrating phytic acid induced heteroatom doping and pore engineering.
PubMed: 38960231
DOI: 10.1016/j.ijbiomac.2024.133346 -
International Journal of Biological... Jul 2024Ectoine, so-called tetrahydropyrimidine, is an important osmotic adjustment solute and widely applied in cosmetics and protein protectant. Some attempts have been made...
Ectoine, so-called tetrahydropyrimidine, is an important osmotic adjustment solute and widely applied in cosmetics and protein protectant. Some attempts have been made to improve the ectoine productivity. However, the strains with both high ectoine production capacity and high glucose conversion were still absent so far. Aim to construct a strain for efficiently producing ectoine, ectoine synthetic gene cluster ectABC from Pseudomonas stutzeri was overexpressed in E. coli BL21 (DE3). The ection production was improved by 382 % (ectoine titer increased from 1.73 g/L to 8.33 g/L) after the rational design of rate-limiting enzyme L-2,4-diaminobutyrate transaminase EctB (protein engineering) combined with the metabolic engineering that focused on the enrichment and conversion of precursors. The final strain YW20 was applied to overproduce ectoine in fed-batch fermentation and yield 68.9 g/L of ectoine with 0.88 g/L/h of space-time yield and the highest glucose conversion reported [34 % (g/g)]. From the fermentation broth, ectoine was purified with 99.7 % purity and 79.8 % yield. This study successfully provided an engineered strain as well as an efficient method for the industrial bio-synthesis and preparation of ectoine.
PubMed: 38960226
DOI: 10.1016/j.ijbiomac.2024.133612 -
The Science of the Total Environment Jul 2024In this study, the chemical mechanisms of O and nitrate formation as well as the control strategy were investigated based on extensive observations in Tai'an city in the...
In this study, the chemical mechanisms of O and nitrate formation as well as the control strategy were investigated based on extensive observations in Tai'an city in the NCP and an observation-constrained box model. The results showed that O pollution was severe with the maximum hourly O concentration reaching 150 ppb. Higher O concentration was typically accompanied by higher PM concentrations, which could be ascribed to the common precursors of VOCs and NO. The modeled averaged peak concentrations of OH, HO, and RO were relatively higher compared to previous observations, indicating strong atmospheric oxidation capacity in the study area. The RO production rate increased from 2.8 ppb h to 5 ppb h from the clean case to the heavily polluted case and was dominated by HONO photolysis, followed by HCHO photolysis. The contribution of radical-self combination to radical termination gradually exceeded NO + OH from clean to polluted cases, indicating that O formation shifted to a more NO-limited regime. The O production rate increased from 14 ppb h to 22 ppb h from clean to heavily polluted cases. The relative incremental reactivity (RIR) results showed that VOCs and NO had comparable RIR values during most days, which suggested that decreasing VOCs or NO was both effective in alleviating O pollution. In addition, HCHO, with the largest RIR value, made important contribution to O production. The Empirical Kinetic Modeling Approach (EKMA) revealed that synergistic control of O and nitrate can be achieved by decreasing both NO and VOCs emissions (e.g., alkenes) with the ratio of 3:1. This study emphasized the importance of NO abatement for the synergistic control of O and nitrate pollution in the Tai'an area as the sustained emissions control has shifted the O and nitrate formation to a more NO-limited regime.
PubMed: 38960186
DOI: 10.1016/j.scitotenv.2024.174405 -
The Science of the Total Environment Jul 2024There is considerable academic interest in the particle-ozone synergistic relationship (PO) between fine particulate matter (PM) and ozone (O). Using various synoptic...
Particle-ozone complex pollution under diverse synoptic weather patterns in the Yangtze River Delta region: Synergistic relationships and the effects of meteorology and chemical compositions.
There is considerable academic interest in the particle-ozone synergistic relationship (PO) between fine particulate matter (PM) and ozone (O). Using various synoptic weather patterns (SWPs), we quantitatively assessed the variations in the PO, which is relevant to formulating policies aimed at controlling complex pollution in the air. First, based on one-year sampling data from March 2018 to February 2019, the SWPs classification of the Yangtze River Delta (YRD) was conducted using the sum-of-squares technique (SS). Five dominant SWPs can be found in the YRD region, including the Aleutian low under SWP1 (occurring 45 % of the year), a tropical cyclone under SWP2 (21 %), the tropical cyclone and western Pacific Subtropical High (WPSH) under SWP3 (15.4 %), the WPSH under SWP4 (6.9 %), and a continental high pressure under SWP5 (3.1 %). The phenomenon of a "seesaw" between PM and O concentrations exhibited significant spatial heterogeneity, which was influenced by meteorological mechanisms. Second, the multi-linear regression (MLR) model and the partial correlation (PCOR) analysis were employed to quantify the effects of dominant components and meteorological factors on the PO. Meteorological variables could collectively explain only 33.0 % of the PM variations, but 58.0 % for O. O promoted each other with low concentrations of PM but was inhibited by high concentrations of PM. High relative humidity (RH) was conducive to the generation of PM secondary components and enhanced the radiative effects of aerosols and the negative correlation of PO. In addition, attention should be paid to assessing the combined effects of precursor levels, weather, and chemical reactions on the particle-ozone complex pollution. The control of O pollutants should be intensified in summer, while the focus should be on reducing PM pollutants in winter. Prevention and control measures need to reflect the differences in weather conditions and pollution characteristics, with a focus on RH and secondary components of PM.
PubMed: 38960176
DOI: 10.1016/j.scitotenv.2024.174365