Stage at diagnosis of colorectal cancer through diagnostic route: Who should be screened?

Background: Colorectal cancer (CRC) is a global health concern, with advanced-stage diagnoses contributing to poor prognoses. The efficacy of CRC screening has been well-established; nevertheless, a significant proportion of patients remain unscreened, with > 70% of cases diagnosed outside screening. Although identifying specific subgroups for whom CRC screening should be particularly recommended is crucial owing to limited resources, the association between the diagnostic routes and identification of these subgroups has been less appreciated. In the Japanese cancer registry, the diagnostic routes for groups discovered outside of screening are primarily categorized into those with comorbidities found during hospital visits and those with CRC-related symptoms. Aim: To clarify the stage at CRC diagnosis based on diagnostic routes. Methods: We conducted a retrospective observational study using a cancer registry of patients with CRC between January 2016 and December 2019 at two hospitals. The diagnostic routes were primarily classified into three groups: Cancer screening, follow-up, and symptomatic. The early-stage was defined as Stages 0 or I. Multivariate and univariate logistic regressions were exploited to determine the odds of early-stage diagnosis in the symptomatic and cancer screening groups, referencing the follow-up group. The adjusted covariates were age, sex, and tumor location. Results: Of the 2083 patients, 715 (34.4%), 1064 (51.1%), and 304 (14.6%) belonged to the follow-up, symptomatic, and cancer screening groups, respectively. Among the 2083 patients, CRCs diagnosed at an early stage were 57.3% (410 of 715), 23.9% (254 of 1064), and 59.5% (181 of 304) in the follow-up, symptomatic, and cancer screening groups, respectively. The symptomatic group exhibited a lower likelihood of early-stage diagnosis than the follow-up group [P < 0.001, adjusted odds ratio (aOR), 0.23; 95% confidence interval (95%CI): 0.19-0.29]. The likelihood of diagnosis at an early stage was similar between the follow-up and cancer screening groups (P = 0.493, aOR for early-stage diagnosis in the cancer screening group vs follow-up group = 1.11; 95%CI = 0.82-1.49). Conclusion: CRCs detected during hospital visits for comorbidities were diagnosed earlier, similar to cancer screening. CRC screening should be recommended, particularly for patients without periodical hospital visits for comorbidities

Quasi-direct Cu–Si3N4 bonding using multi-layered active metal deposition for power-module substrate

Tatsumi H., Moon S., Takahashi M., et al. Quasi-direct Cu–Si3N4 bonding using multi-layered active metal deposition for power-module substrate. Materials and Design 238, 112637 (2024); https://doi.org/10.1016/j.matdes.2024.112637.The advancement of power modules demands more reliable insulating circuit substrates. Traditional substrates, comprising Cu and Si3N4, are produced using active metal brazing (AMB). However, AMB substrates have reliability concerns owing to electrochemical migration and void formation from brazing filler metals. This study introduces a quasi-direct Cu–Si3N4 bonding technique using a Ti/Al bilayer active metal deposition at the bonding interface. A sputtered Ti/Al bilayer was formed on the Si3N4 surface, then heated and pressurized the sputtered Si3N4 substrate with Cu sheets in vacuum to bond each other without voids or delamination. The Ti/Al layers reacted with Si3N4 and Cu, forming a 300 nm intermediate layer. TEM observations show this layer contains segregated Ti–N and Cu–Al phases, with a good lattice match to Si3N4 and Cu–Al. Temperature-cycling tests on the Cu/Si3N4/Cu substrate revealed delamination caused by increased tensile stress at the periphery of the bonding area due to asymmetrical Cu patterns. This novel quasi-direct Cu–Si3N4 bonding technique addresses issues of electrochemical migration and void formation seen in AMB substrates, offering a reliable bonding interface for power electronic substrates

Cancer activity and bleeding events post-PCI

Purpose : Limited data exist about clinically relevant bleeding events related to antiplatelet therapy after percutaneous coronary intervention (PCI) in cancer patients. We investigated the risk factors for clinically relevant bleeding events in patients with cancer after PCI with stent implantation. Patients and Methods : Patients with solid cancer subjected to first PCI were divided into active (n = 45) and non-active cancer groups (n = 44). The active group included non-operable patients on treatment or with metastasis ; the non-active included those already subjected to or for whom radical surgery was planned within 3 months after the index PCI. Results : During a median follow-up of 2.2 years, 11 bleeding events occurred, with only one occurring in the non-active cancer group. Half of them occurred during the dual-antiplatelet therapy (DAPT) period, and the rest occurred during single-antiplatelet therapy (SAPT) period. Kaplan-Meier analysis showed significantly more bleeding events in the active cancer group (p = 0.010). Multivariate Cox regression hazard analysis revealed cancer activity as a significant independent risk factor for bleeding (p = 0.023) ; but not for three-point major adverse cardiovascular events. Conclusion : Clinically relevant bleeding risk after PCI was significantly lower in non-active cancer. Active cancer group had clinically relevant bleeding during both DAPT and SAPT periods

Unilateral lung transplantation using right and left upper lobes: An experimental study

Objective: The shortage of organ donors is a serious problem in Japan. The right and left upper lobes of rejected extended-criteria lungs have the potential to be used for downsized lung transplantation; however, the 2 upper lobes are too small for a size-matched recipient. The present study investigated the feasibility of unilateral transplantation using the right and left upper lobes. Methods: After harvesting the heart-lung block from donor swine, a left lung graft was created using the right and left upper lobes and transplanted into the left thoracic space of the recipient swine (group A, n = 5). We then evaluated graft function for 6 hours and compared these results with those of a control group (group B, n = 5), in which orthotopic left lung transplantation had been performed. Results: The mean partial pressure of oxygen in the arterial blood gas after reperfusion was 507 mm Hg in group A and 463 mm Hg in group B (P = .2). The mean pulmonary arterial pressure was 30.3 mm Hg in group A and 27.5 mm Hg in group B (P = .4). The mean airway pressure was 6.4 mm Hg in group A and 6.2 mm Hg in group B (P = .7). Conclusions: Our results suggest that unilateral left lung transplantation using the right and left upper lobes is technically and functionally feasible for size-matched recipients. In addition, this technique enables the use of rejected lungs if the upper lobes are still intact

再発性甲状腺癌のリンパ節転移におけるTc-99m MDPの集積(Tc-99m MDP Accumulation in Lymph Node Metastases of Recurrent Thyroid Cancer)(英語)

金沢医科大学 放射線科原著論文/症例報

Successful management of hyperammonemia with hemodialysis on day 2 during 5-fluorouracil treatment in a patient with gastric cancer: a case report with 5-fluorouracil metabolite analyses

Ozaki, Y., Imamaki, H., Ikeda, A. et al. Correction to: Successful management of hyperammonemia with hemodialysis on day 2 during 5‑fluorouracil treatment in a patient with gastric cancer: a case report with 5‑fluorouracil metabolite analyses. Cancer Chemotherapy and Pharmacology (2020) 86:693-699.Purpose: Hyperammonemia is an important adverse event associated with 5-fluorouracil (5FU) from 5FU metabolite accumulation. We present a case of an advanced gastric cancer patient with chronic renal failure, who was treated with 5FU/leucovorin (LV) infusion chemotherapy (2-h infusion of LV and 5FU bolus followed by 46-h 5FU continuous infusion on day 1; repeated every 2 weeks) and developed hyperammonemia, with the aim of exploring an appropriate hemodialysis (HD) schedule to resolve its symptoms. Methods: The blood concentrations of 5FU and its metabolites, α-fluoro-β-alanine (FBAL), and monofluoroacetate (FA) of a patient who had hyperammonemia from seven courses of palliative 5FU/LV therapy for gastric cancer were measured by liquid chromatography–mass spectrometry. Results: On the third day of the first cycle, the patient presented with symptomatic hyperammonemia relieved by emergency HD. Thereafter, the 5FU dose was reduced; however, in cycles 2–4, the patient developed symptomatic hyperammonemia and underwent HD on day 3 for hyperammonemia management. In cycles 5–7, the timing of scheduled HD administration was changed from day 3 to day 2, preventing symptomatic hyperammonemia. The maximum ammonia and 5FU metabolite levels were significantly lower in cycles 5–7 than in cycles 2–4 (NH3 75 ± 38 vs 303 ± 119 μg/dL, FBAL 13.7 ± 2.5 vs 19.7 ± 2.0 μg/mL, FA 204.0 ± 91.6 vs 395.9 ± 12.6 ng/mL, mean ± standard deviation, all p < 0.05). After seven cycles, partial response was confirmed. Conclusion: HD on day 2 instead of 3 may prevent hyperammonemia in 5FU/LV therapy

Structural basis for PPARγ transactivation by endocrine-disrupting organotin compounds

Harada, S., Hiromori, Y., Nakamura, S. et al. Structural basis for PPARγ transactivation by endocrine-disrupting organotin compounds. Sci Rep 5, 8520 (2015). https://doi.org/10.1038/srep08520

Involvement of mTOR pathway in neurodegeneration in NSF-related developmental and epileptic encephalopathy

Membrane fusion is mediated by soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. During neurotransmitter exocytosis, SNARE proteins on a synaptic vesicle and the target membrane form a complex, resulting in neurotransmitter release. N-ethylmaleimide-sensitive factor (NSF), a homohexameric ATPase, disassembles the complex, allowing individual SNARE proteins to be recycled. Recently, the association between pathogenic NSF variants and developmental and epileptic encephalopathy (DEE) was reported; however, the molecular pathomechanism of NSF-related DEE remains unclear. Here, three patients with de novo heterozygous NSF variants were presented, of which two were associated with DEE and one with a very mild phenotype. One of the DEE patients also had hypocalcemia from parathyroid hormone deficiency and neuromuscular junction impairment. Using PC12 cells, a neurosecretion model, we show that NSF with DEE-associated variants impaired the recycling of vesicular membrane proteins and vesicle enlargement in response to exocytotic stimulation. In addition, DEE-associated variants caused neurodegenerative change and defective autophagy through overactivation of the mTOR pathway. Treatment with rapamycin, an mTOR inhibitor, or overexpression of wild-type NSF ameliorated these phenotypes. Furthermore, neurons differentiated from patient-derived induced pluripotent stem cells showed neurite degeneration, which was also alleviated by rapamycin treatment or gene correction using genome editing. Protein structure analysis of NSF revealed that DEE-associated variants might disrupt the transmission of the conformational change of NSF monomers and consequently halt the rotation of ATP hydrolysis, indicating a dominant negative mechanism. In conclusion, this study elucidates the pathomechanism underlying NSF-related DEE and identifies a potential therapeutic approach