Safety and feasibility of percutaneous abdominal lavage cytology screening (PACS) prior to surgical resection for pancreatic cancer.

PURPOSE: This study aimed to evaluate the feasibility, safety, diagnostic yield, and technical aspects of percutaneous abdominal lavage cytology screening (PACS) in patients with resectable pancreatic cancer. METHODS: This single-center, retrospective study included patients with resectable pancreatic cancer who underwent PACS before pancreatectomy between May 2022 and October 2023. The technical success rate, position of the drainage tube, volume of fluid administered, volume of fluid retrieved, fluid retrieval rate, and adverse events were evaluated. The cytological results of PACS were compared with those of surgical peritoneal lavage performed during pancreatectomy. RESULTS: Forty-four patients were enrolled in this study. The technical success rate for PACS was 100%. Drainage tube placement was outside the pouch of Douglas in all patients in the right-sided abdominal approach group (n = 10), whereas the placement was in the pouch of Douglas in all patients in the suprapubic approach group (n = 34). The mean volume of fluid administered, mean volume of fluid retrieved, and fluid retrieval rate were 185.0 ± 22.9 ml vs. 97.1 ± 32.0 ml (p < 0.001), 36.8 ± 25.6 ml vs. 50.5 ± 21.6 ml (p = 0.059), and 19.0 ± 12.4% vs. 54.9 ± 21.9% (p < 0.001) in the right abdominal approach and suprapubic approach groups, respectively. No adverse events were reported. The cytological results were benign in 42 patients; no discrepancy was observed in the results of surgical peritoneal lavage (n = 36). CONCLUSION: PACS is a feasible and safe procedure that can be performed before pancreatectomy in patients with resectable pancreatic cancer. the suprapubic approach may be ideal and PACS could be a screening method to detect carcinomatous peritonitis.

Pancreatic hamartoma: Possibility of a preoperative diagnosis via endoscopic ultrasound-guided fine-needle aspiration biopsy.

Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) is useful for preoperatively diagnosing various pancreatic tumors. Although there is a risk of complications, such as pancreatitis, this procedure achieves the crucial need of reducing unnecessary invasive surgery for benign lesions. Herein, we reported a surgically resected case of pancreatic hamartoma in the pancreatic head whose retrospective analysis revealed that the specimens obtained via EUS-FNAB contained hamartoma fragments. Pancreatic hamartoma is an extremely rare benign disease that is exceptionally difficult to diagnose before surgical resection owing to its rarity and lack of established imaging findings. To the best of our knowledge, the preoperative diagnosis of pancreatic hamartoma via EUS-FNAB specimens has not been reported to date. Herein, postoperative EUS-FNAB evaluation revealed a collection of pancreatic hamartoma lesions, although the initial diagnosis was pancreatic tissue with focal atrophy and fibrosis. Diagnosis using EUS-FNAB can be challenging owing to the very small sample size. If mature acini and ducts with fibrous stroma without islets are observed in the EUS-FNAB specimen, pancreatic hamartoma should be considered as a differential diagnosis. Thus, careful follow-up or reexamination of EUS-FNAB should be considered instead of surgery if a benign lesion is suspected preoperatively.

A case of medial pterygoid muscle metastasis of lung cancer presenting with trismus.

A man in his 60s with severe trismus was referred to our hospital. Based on computed tomography (CT), positron emission tomography/computed tomography (PET/CT), and biopsy, his initial diagnosis at another hospital was oropharyngeal cancer with cervical lymph node and distant metastases. After the review of the contrast-enhanced CT and reevaluated PET/CT images, we updated his diagnosis to left primary lung cancer that had metastasized to the cervical lymph nodes, bones, and skeletal muscles including the right medial pterygoid muscle. Since metastasis from primary lung cancer to the contralateral cervical lymph node is relatively rare, cervical lymph node metastases were thought to have originated from the metastatic lesion in the right medial pterygoid muscle. As metastases in the masticator muscles from lung cancer are rare, it is sometimes necessary to differentiate from primary head and neck lesions. Here, we report a rare case of lung cancer with the onset of trismus due to metastasis to the masticator muscle and perineural spread along the mandibular nerve.

Tumor Identification of Less Aggressive or Indolent Lymphoma With Whole-Body 11C-Acetate PET/CT.

PURPOSE: The aim of this study was to investigate the diagnostic performance of whole-body [C]acetate PET/CT in less aggressive or indolent lymphomas, wherein [F]FDG PET/CT would exhibit limited sensitivity. METHODS: Between September 2016 and May 2018, we prospectively evaluated 17 patients (9 men, 8 women; mean age [range], 71 [45-87] years) with pathologically proven less aggressive or indolent lymphomas according to Non-Hodgkin's Lymphoma Classification Project, using both [F]FDG PET/CT and [C]acetate PET/CT (performed on the same day). Detected nodal lesions were recorded according to the Ann Arbor classification. Extranodal (EN) lesions were also evaluated. We compared whole-body lesion detection between [F] FDG PET/CT and [C]acetate PET/CT using the McNemar test. RESULTS: In all patients, significantly more nodal and EN lesions were detected using [C]acetate PET/CT than [F]FDG PET/CT (nodal: 84 vs 64 regions; P < 0.001; EN: 26 vs 19 regions, P = 0.039). Bone lesions were detected in 8 and 5 patients using [C]acetate PET/CT and [F]FDG PET/CT, respectively (P = 0.25). Among the 14 patients (82.4%) who underwent bone marrow biopsy, bone marrow involvement was detected with sensitivities of 100% (6/6 patients) and 80% (5/6 patients) using [C]acetate PET/CT and [F]FDG PET/CT, respectively. Multiple areas of focal uptake in the spleen of 1 patient were exhibited on [F]FDG PET/CT but not [C]acetate PET/CT. CONCLUSIONS: [C]acetate PET/CT exhibited greater sensitivity than [F]FDG PET/CT for lesion detection in patients with less aggressive or indolent lymphomas, thus promising applicability as a physiological tracer in the study of such lesions.

Takayasu arteritis: clinical importance of extra-vessel uptake on FDG PET/CT.

BACKGROUND: [F-18]fluorodeoxyglucose positron emission tomography/computed tomography is routinely used for assessing Takayasu arteritis patients. However, extra-vessel [F-18]fluorodeoxyglucose uptake has not been evaluated in detail in these patients. We aimed to describe the extent and distribution of extra-vascular [F-18]fluorodeoxyglucose uptake on positron emission tomography/computed tomography in Takayasu arteritis patients. Seventy-three [F-18]fluorodeoxyglucose positron emission tomography/computed tomography scans from 64 consecutive Takayasu arteritis patients (59 women, mean age, 35.4 years; range, 13 to 71 years) and 40 scans from age-matched controls (36 women, mean age, 37.8 years; range, 13 to 70 years) were examined. We graded [F-18]fluorodeoxyglucose uptake in large vessels using a 4-point scale and evaluated extra-vessel findings. Factors correlated with disease activity were examined. We evaluated the relationship between disease activity according to the National Institutes of Health score with extra-vessel findings, as well as other inflammatory markers (e.g., white blood cell count and C-reactive protein level). RESULTS: Extra-vessel involvement was present in 50 of 73 (68.4%) scans, specifically at the following sites: lymph nodes, 1.4%; thyroid glands, 17.8%; thymus, 11.0%; spleen, 1.4%; vertebrae, 45.2%; and pelvic bones, 9.6%. Takayasu arteritis patients had higher [F-18]fluorodeoxyglucose uptake in the spine (P = 0.03) and thyroid glands (P = 0.003) than did controls; uptake in other regions was comparable between groups. Compared with inactive patients, those with active Takayasu arteritis had a higher number of [F-18]fluorodeoxyglucose uptake sites in the vasculature (P = 0.001). Finally, patients with a National Institutes of Health score of ≥ 1 had significantly higher extra-vascular involvement (P = 0.008). CONCLUSIONS: Extra-vessel [F-18]fluorodeoxyglucose uptake may be present in the context of Takayasu arteritis-related inflammatory processes. Information on extra-vascular [F-18]fluorodeoxyglucose uptake may be useful for detecting and evaluating inflammatory processes when interpreting positron emission tomography/computed tomography scans obtained from Takayasu arteritis patients.

Potential Suppressive Effects of Two C60 Fullerene Derivatives on Acquired Immunity.

The therapeutic effects of fullerene derivatives on many models of inflammatory disease have been demonstrated. The anti-inflammatory mechanisms of these nanoparticles remain to be elucidated, though their beneficial roles in allergy and autoimmune diseases suggest their suppressive potential in acquired immunity. Here, we evaluated the effects of C60 pyrrolidine tris-acid (C60-P) and polyhydroxylated fullerene (C60(OH)36) on the acquired immune response in vitro and in vivo. In vitro, both C60 derivatives had dose-dependent suppressive effects on T cell receptor-mediated activation of T cells and antibody production by B cells under anti-CD40/IL-4 stimulation, similar to the actions of the antioxidant N-acetylcysteine. In addition, C60-P suppressed ovalbumin-specific antibody production and ovalbumin-specific T cell responses in vivo, although T cell-independent antibodies responses were not affected by C60-P. Together, our data suggest that fullerene derivatives can suppress acquired immune responses that require T cells.

Regioselective addition of Grignard reagents to tosylazafulleroid and derivatization to 1,2-disubstituted [60]fullerene.

Grignard reagents (RMgBr: R = Et, p-tolyl) selectively attacked the ß-position of the bridgehead double bond of tosylazafulleroid through interaction of Mg with the S[double bond, length as m-dash]O group. The following [5,6] ring closure and C-N bond scission led to aryl/alkyl aminylfullerenes with 1,2-configuration. Tolyl-substituted aminylfullerene was further converted into 1,4-di(p-tolyl)fullerene on treatment in acidic toluene.

Oxidative deamination of azafulleroids into C60 by peracids.

Oxidation of azafulleroids with peracids regenerated C60 depending on the N-substituents. Alkyl-substituted azafulleroids preferred the oxidation of nitrogen to afford N-oxides as possible intermediates for C60 in moderate yields. Phenyl- and tosyl-substituted azafulleroids rather allowed the oxidation at the carbon cage. Theoretical calculations predicted the order of reactivity of azafulleroids as well as the relative N/C nucleophilicity.

Dramatic mechanistic change in acid-catalyzed arylation of azafulleroids depending on their ambident N/C basicity: formation of cyclopentene centered pentakisadduct.

Azafulleroid, amino-bridged [5,6]-open fullerene, has the ambident N/C basicity of the incorporated enamine moiety. Acid-catalyzed arylation of N-substituted azafulleroids proceeded via two types of initial N/C protonation to perform monoarylation or 1,4-bisarylation for the N-alkyl substituents and shuttlecock-type pentakisarylation for the N-phenyl substituent. The dramatic product change was explained by considering the possible mechanism as well as the DFT computational results.

Kinetic study of the Diels-Alder reaction of Li⁺@C60 with cyclohexadiene: greatly increased reaction rate by encapsulated Li⁺.

We studied the kinetics of the Diels-Alder reaction of Li(+)-encapsulated [60]fullerene with 1,3-cyclohexadiene and characterized the obtained product, [Li(+)@C60(C6H8)](PF6(-)). Compared with empty C60, Li(+)@C60 reacted 2400-fold faster at 303 K, a rate enhancement that corresponds to lowering the activation energy by 24.2 kJ mol(-1). The enhanced Diels-Alder reaction rate was well explained by DFT calculation at the M06-2X/6-31G(d) level of theory considering the reactant complex with dispersion corrections. The calculated activation energies for empty C60 and Li(+)@C60 (65.2 and 43.6 kJ mol(-1), respectively) agreed fairly well with the experimentally obtained values (67.4 and 44.0 kJ mol(-1), respectively). According to the calculation, the lowering of the transition state energy by Li(+) encapsulation was associated with stabilization of the reactant complex (by 14.1 kJ mol(-1)) and the [4 + 2] product (by 5.9 kJ mol(-1)) through favorable frontier molecular orbital interactions. The encapsulated Li(+) ion catalyzed the Diels-Alder reaction by lowering the LUMO of Li(+)@C60. This is the first detailed report on the kinetics of a Diels-Alder reaction catalyzed by an encapsulated Lewis acid catalyst rather than one coordinated to a heteroatom in the dienophile.

First synthesis and aggregation behaviour of periconjugated triazoliumfullerene.

Triazoliumfullerene was first prepared by the [3+2] cycloaddition of in situ generated 1,3-diaza-2-azoniaallene with fullerene and was characterized by the dispersed positive charge over the fullerene sphere associated with periconjugation. This new type of amphiphilic fullerene tended to form vesicles and crystalline aggregates after the casting of THF or MeOH solutions.

Ionic conductivity of [Li+@C60](PF6(-)) in organic solvents and its electrochemical reduction to Li+@C60(·-).

The ionic conductivity of [Li(+)@C60](PF6(-)) was measured in o-dichlorobenzene, and found to be higher than that of TBA(+)PF6(-). Electrochemical reduction of [Li(+)@C60](PF6(-)) without any supporting electrolyte gave the monovalent radical anion Li(+)@C60˙(-), as confirmed by the characteristic ESR signal and NIR absorption band.

Synthesis of a new class of fullerene derivative Li⁺@C60O⁻(OH)7 as a "cation-encapsulated anion nanoparticle".

Metal encapsulation into a cage and chemical modification on the outer surface of fullerenes endow them with some unique characteristic properties. Although the derivatization of endohedral fullerenes holds promise for producing novel new nano-carbon materials, there are few reports about such compounds. Herein, we report the synthesis of lithium encapsulated fullerenol Li(+)@C60O(-)(OH)7 using a fuming sulfuric acid method from [Li(+)@C60](PF6(-)) and characterization of its structure by IR, NMR, FAB mass spectroscopy, and elemental analysis. The hydroxylation of [Li(+)@C60](PF6(-)) is site-selective to preferentially give a single isomer (ca. 70%) with two minor isomers in marked contrast to the reaction of empty C60. We conclude from the analysis of radical species produced in the reaction of a C60 cage with fuming sulfuric acid that this unusual site-selective hydroxylation is caused by the lower HOMO level of Li(+)@C60 than that of empty C60. Furthermore, our results clearly indicate that the internal lithium cation is interacted with the introduced hydroxyl groups, and thus the properties of endohedral fullerenes can be controlled by the external modification of a fullerene cage.

Facile and exclusive formation of aziridinofullerenes by acid-catalyzed denitrogenation of triazolinofullerenes.

Variously substituted [6,6]closed aziridinofullerenes were exclusively obtained from acid-catalyzed denitrogenation of triazolinofullerenes without formation of relevant [5,6]open azafulleroids, which are the major products on noncatalyzed denitrogenation. The mechanistic consideration by DFT calculations suggested a reaction sequence involving initial pre-equilibrium protonation of the triazoline N(1) atom, generation of aminofullerenyl cation by nitrogen-extrusion, and final aziridination.

First kinetic evidence for the CH/π and π/π solute-solvent interaction of C60 in the Diels-Alder reaction with cyclohexadiene.

The first CH/π solute-solvent interaction of C(60) was evidenced by the kinetic solvent effects in the Diels-Alder reaction with 1,3-cyclohexadiene based on the evaluation of linear free energy relationship of log k(2) with empirical solvent polarity and basicity parameters, E(T)(30) and D(π), respectively.

Thermal [2+2] cycloaddition of morpholinoenamines with C60 via a single electron transfer.

The thermal reaction of C(60) with five- and six-membered morpholinocycloalkenes in refluxing toluene exclusively gave the [2+2] cycloadducts in high yields. However, a seven-membered homologue sluggishly reacted with C(60) because of the increasing steric hindrance. This cycloaddition reaction is likely to proceed via a single electron transfer (SET), a radical-coupling, and subsequent ion cyclization rather than the prior proton transfer between the radical ions.

Synthesis and regiochemistry of [60]fullerenyl 2-methylmalonate bisadducts and their facile electron-accepting properties.

A simple one-pot reaction using in situ chemically generated Na-naphthalenide as an electron reductant in the preferential generation of C(60)(2-) is described. Trapping of C(60)(2-) intermediate with 2 molar equiv of sterically hindered 2-bromo-2-methylmalonate ester afforded two singly bonded fullerenyl bisadducts C(60)[-CMe(CO(2)Et)(2)](2) in 35% and 7% yield, respectively. The regiochemistry of these two products was determined to be 1,4- and 1,16-bisadducts, respectively, by NMR, UV-vis-NIR, LCMS, and X-ray single crystal structural analysis. The minor 1,16-bisadduct 2 exhibits long wavelength absorption bands in the near-IR region and prominent electron-accepting characteristics as compared with those of the major 1,4-bisadduct and pristine C(60). As revealed by DFT calculation, we propose that the origin of these unusual characters of 2 arises from the moiety of [18pi]-trannulene, in close resemblance to that of the highly symmetrical emerald green 1,16,29,38,43,60-hexaadduct of C(60), EF-6MC(n). Accordingly, we anticipate a fast progressive formation of plausible 1,16-bisadduct-like intermediate moieties on a C(60) cage as the precursor structure leading to the formation of EF-6MC(n), by taking the corresponding regiochemistry and electronic properties into account.

Kinetics and regioselectivity in the Diels-Alder reaction of fulleroids vs. methanofullerene and C60.

Fulleroids, obtained from the 1,3-dipolar cycloaddition of fullerene with a diazoalkane, have a [5,6]-open methylene bridge and two highly twisted bridgehead double bonds. The [H,H]- and [H,CN]-substituted fulleroids were found to display significantly enhanced and regioselective Diels-Alder addition as compared with the [6,6] closed methanofullerene and C(60) with 2,3-dimethyl-1,3-butadiene, but reduced and nonregioselective addition with cyclopentadiene. NMR analysis of the 1:1 adduct and quantum calculations indicated that the high reactivity and the regioselective addition are due to pi-orbital misalignment at the bridgehead double bond.

Kinetic evidence for dihapto (eta(2)) pi-aryl participation in acid-catalyzed ring opening of diarylhomobenzoquinone epoxides.

The BF(3)-catalyzed ring-opening reaction of variously endo/exo m- and p-substituted diarylhomobenzoquinone epoxides proceeded through a transannular S(E)2-Ar cyclization of endo-aryl groups to give the tricyclic diketo-alcohols and cyclohexadienone spiro-linked tricyclic diketo-alcohols. Kinetics of these reactions has been investigated in CDCl(3) at 30 degrees C in order to elucidate the possible remote pi-aryl participation. The rates were significantly increased with increasing electron-donating ability of the endo-aryl substituents X (k(p-MeO)/k(p-CF3) = 8200) but only negligibly influenced by the distal exo-aryl substituents Y (k(p-MeO)/k(p-CF3) = 2.1). For the endo-X substituted series, an excellent linear free energy relationship, log k(rel)(endo) = -2.49sigma(ipso) - 1.62sigma(ortho) - 0.108 (R(2) = 0.98, n = 8), was attained using two modified site-dependent substituent parameters sigma(ipso) (using sigma(p)(+) for p-X and sigma(m) for m-X) and sigma(ortho) (using sigma(m) for p-X and sigma(p)(+) for m-X). This means that the dihapto(eta(2)) pi-coordination occurs in the pi-aryl participation, with the ipso pi-electron donation contributing 1.6 times more effectively than the ortho one. On the other hand, the distal exo-Y substituted series gave an acceptable Yukawa-Tsuno equation with small polar and resonance contributions; log k(rel)(exo) = -0.912(sigma(0) + 0.237Deltasigma(R)(+)) (R(2) = 0.96, n = 8). These kinetic substituent effects were compared with those of the acid-catalyzed pi-aryl assisted transannular S(E)2-Ar cyclization of the cyclobutene-fused diarylhomobenzoquinones. It was found that the geometrical characteristics of the vacant oxirane Walsh orbital and the cyclobutene antibonding orbital play a crucial role in the topological features of eta(2) pi-aryl participation.

Antimicrobial activity of fullerenes and their hydroxylated derivatives.

The antimicrobial activities of fullerene C60 and its derivatives against 6 kinds of bacteria and 2 kinds of fungi were evaluated. The tested samples were water-soluble fullerenes (polyvinylpyrrolidone (PVP)/C60, gamma-cyclodextrin (gamma-CD)/C60, and nano-C60) and 3 types of fullerenols (C60(OH)12, C60(OH)36.8H2O, and C60(OH)44.8H2O). Their activities were compared with those of (+)-catechin and hinokitiol from the viewpoint of future application to cosmetics. Although pristine C60 demonstrated no antimicrobial activity, fullerenols exhibited good antimicrobial activity against Propionibacterium acnes, Staphylococcus epidermidis, Candida albicans, and Malassezia furfur. In particular, C60(OH)44 exhibited a strong and wide-ranging antimicrobial activity comparable to that of catechin. This compound exhibits antimicrobial activity via inhibition of microbial cell growth and not via bactericidal activity.