Preparing a liquid crystalline dispersion of carbon nanotubes with high aspect ratio.

We successfully prepared a surfactant-assisted carbon nanotube (CNT) liquid crystal (LC) dispersion with double-walled CNTs (DWCNTs) having a high aspect ratio (≈1378). Compared to dispersions of single-walled CNTs (SWCNTs) with lower aspect ratio, the transition concentrations from isotropic phase to biphasic state, and from biphasic state to nematic phase are lowered, which is consistent with the predictions of the Onsager theory. An aligned DWCNT film was prepared from the DWCNT dispersion by a simple bar-coating method. Regardless of the higher aspect ratio, the order parameter obtained from the film is comparable to that from SWCNTs with lower aspect ratios. This finding implies that precise control of the film formation process, including a proper selection of substrate and deposition/drying steps, is crucial to maximize the CNT-LC utilization.

Streptavidin-Conjugated Oxygen-Doped Single-Walled Carbon Nanotubes as Near-Infrared Labels for Immunoassays.

Single-walled carbon nanotubes (CNTs) are promising candidates for near-infrared (NIR) fluorescent labels in diagnostic fields. We report a complex of oxygen-doped CNT (o-CNT) and streptavidin (SA) for preparing CNT-based NIR labels with a high reaction efficiency in immunoassays. This complex specifically binds to biotin molecules by conjugating a linker molecule of phospholipid polyethylene glycol (PL-PEG) to SA (o-CNT-SA). The immunoprecipitation reaction efficiency between o-CNT-SA and biotin reaches 79.3% when the surface of o-CNTs is uniformly covered with SA-conjugated PL-PEG. The strong affinity between SA and biotin is useful for preparing CNT-based sensitive NIR fluorescent labels.

Liquid Crystalline Behaviors of Single-Walled Carbon Nanotubes in an Aqueous Sodium Cholate Dispersion.

Controlling the alignment of single-walled carbon nanotubes (SWCNTs) on the macroscopic scale is critical for practical applications because SWCNTs are extremely anisotropic materials. One efficient technique is to create an effective SWCNT dispersion, which shows a liquid crystal (LC) phase. A strong acid treatment can realize SWCNT liquid crystalline dispersions. However, strong acids pose a substantial safety risk, which renders the process unfit for mass production. Herein, an isolated SWCNT dispersion displaying an LC behavior is prepared using sodium cholate without an acid treatment, and its phase transition behaviors are systematically investigated across the isotropic to biphasic to nematic phases. As the SWCNT concentration increases, the dispersion undergoes an isotropic-to-nematic phase transition in which the spindle-shaped LC droplets, or the so-called tactoids, and the Schlieren textures can be observed in the intermediate biphasic state and the nematic phase, respectively. The arrangements of SWCNTs in the tactoids and the Schlieren structures are directly investigated by polarized optical microscopy. The clear LC behaviors of the CNT dispersion suggest that the CNT orientations can be controlled by the normal surfactant-assisted method, which is a crucial advantage for the liquid-phase processing of CNT fibers and films.

Recurrent membranous nephropathy with a possible alteration in the etiology: a case report.

BACKGROUND: Phospholipase A2 receptor 1 (PLA2R1) and thrombospondin type-1 domain-containing 7A (THSD7A) are the two major pathogenic antigens for membranous nephropathy (MN). It has been reported that THSD7A-associated MN has a higher prevalence of comorbid malignancy than PLA2R1-associated MN. Here we present a case of MN whose etiology might change from idiopathic to malignancy-associated MN during the patient's clinical course. CASE PRESENTATION: A 68-year-old man with nephrotic syndrome was diagnosed with MN by renal biopsy. Immunohistochemistry showed that the kidney specimen was negative for THSD7A. The first course of corticosteroid therapy achieved partial remission; however, nephrotic syndrome recurred 1 year later. Two years later, his abdominal echography revealed a urinary bladder tumor, but he did not wish to undergo additional diagnostic examinations. Because his proteinuria increased consecutively, corticosteroid therapy was resumed, but it failed to achieve remission. Another kidney biopsy was performed and revealed MN with positive staining for THSD7A. PLA2R1 staining levels were negative for both first and second biopsies. Because his bladder tumor had gradually enlarged, he agreed to undergo bladder tumor resection. Pathological examination indicated that the tumor was THDS7A-positive bladder cancer. Subsequently, his proteinuria decreased and remained in remission. CONCLUSIONS: This case suggests that the etiology of MN might be altered during the therapeutic course. Intensive screening for malignancy may be preferable in patients with unexpected recurrence of proteinuria and/or change in therapy response.

Prevalence of chronic postsurgical pain after thoracotomy and total knee arthroplasty: a retrospective multicenter study in Japan (Japanese Study Group of Subacute Postoperative Pain).

We performed a multicenter observational study to assess the prevalence and risk factors of persistent pain after lung cancer surgery and total knee arthroplasty (TKA) in the Japanese population. After receiving Ethics Committee approval, a retrospective chart review was performed for patients who underwent surgery at seven university hospitals in Japan in 2013. A total of 511 patients who underwent lung cancer surgery and 298 patients who underwent TKA were included. The prevalence of chronic postsurgical pain (CPSP) at 3 and 6 months was 18 and 12% after lung surgery and 49 and 33% after TKA, respectively. The prevalence of analgesic use at 3 and 6 months was 16 and 9% after lung surgery and 34 and 22% after TKA, respectively. In both groups, preoperative analgesic use was associated with CPSP. Anesthetic methods or techniques during both types of surgery did not significantly affect the prevalence of CPSP. This is the first study in which the prevalence of CPSP after lung surgery and TKA in Japanese population was extensively evaluated in a multicenter trial. Further prospective studies are needed to confirm the prevalence of CPSP in the Japanese population and to identify risk factors and prevention methods.

[A Case of Resected Combined Pancreatic Mixed Ductal Adenocarcinoma and Neuroendocrine Tumor].

A 63-year-old man was followed-up for diabetes mellitus. During follow-up, computed tomography(CT)showed dilatation of the main pancreatic duct in the tail of the pancreas. Abdominal enhanced CT revealed a 25 mm tumor in the body of the pancreas. Endoscopic ultrasound-fine needle aspiration(EUS-FNA)was performed, and the pathological diagnosis was adenocarcinoma. Therefore, based on the diagnosis of pancreatic body carcinoma, distal pancreatectomy with splenectomy was performed. The postoperative course was uneventful. Histological and immunohistochemical examination revealed that the tumor consisted of a ductal carcinoma and a neuroendocrine component. Therefore, combined pancreatic tumor (fT3N1M0, StageⅡB)was diagnosed. The patient subsequently received postoperative adjuvant chemotherapy(S-1 100mg/ day), and survived without recurrence 6 months after the operation. We report this case of combined pancreatic tumors with a review of the literature.

[A Case of Resected Metachronous Cholangiocarcinoma after Pancreaticoduodenectomy].

The patient was a 79-year-old woman, who had undergone pancreaticoduodenectomy(PD)for lower bile duct carcinoma in our hospital(pT3N0H0P0M0, fStage III ). Four years 6 months after the initial operation, abdominal CT revealed left bile duct expansion and hilar bile duct thickening. Therefore, based on the diagnosis of perihilar cholangiocarcinoma originating from the left hilar duct, we performed left lobectomy with caudate lobectomy and biliary tract reconstruction. The surgical specimen showed a tumor in the left hilar bile duct. Histopathological diagnosis of the tumor was a moderately differentiated adenocarcinoma(pT2aN0H0P0M0, fStage II ). Surgical margins were histologically negative. Since the tumor was located away from the anastomosed site of the cholangiojejunostomy, we determined that the tumor was not a recurrence but a metachronous cholangiocarcinoma. The postoperative course was uneventful. The patient survived without recurrence 2 years after the second operation. The possibility of heterochronic biliary carcinomas should be considered during follow-up evaluation. We report this case of metachronous cholangiocarcinoma that occurred 4 years 6 months after PD, with a review of the literature.

[A Case of an IgG4-Related Inflammatory Pseudotumor of the Liver Showing Enlargement That Was Difficult to Differentiate from Hepatic Cancer].

A 60-year-old man was admitted for a liver mass(S3), which rapidly increased in size during intraductal papillary mucinous neoplasm(IPMN)follow-up. Although EOB-MRIwas performed, the mass could not be accurately diagnosed as hepatic cancer. Thus, we performed a lateral segmentectomy. In the resected specimen, a solid tumor mass was clearly bound in segment 3 of the liver. Since histopathology revealed no malignant cells and many IgG4-positive cells, we confirmed the diagnosis as IgG4-related inflammatory pseudotumor of the liver. IgG4-related diseases occur in various organs in the body, and they are known to associate with autoimmune pancreatitis and sclerosing cholangitis, but an IgG4-related inflammatory pseudotumor of the liver is a rare disease. It is often difficult to distinguish from hepatic cancer and surgical resection is performed.

[A Case of Xanthogranulomatous Cholecystitis That Changed Over Time and Was Difficult to Distinguish from Advanced Gallbladder Cancer].

A 70-year-old man was referred because of suspected gallbladder cancer and gallstones. Contrast-enhanced CT, EOB-MRI and PET-CT could not completely rule out gallbladder cancer. The patient preferred follow-up without surgery. At 4 months after initial examination, the gallbladder wall thickening showed improvement, but appeared worse at 9 months after initial examination. Therefore, we decided to perform surgery. Since malignant findings were not observed on rapid intraoperative pathology, we performed a cholecystectomy and right hemicolectomy because of inflammation in the transverse colon. Pathological examination diagnosed xanthogranulomatous cholecystitis. The imaging appearance of xanthogranulomatous cholecystitis varies, and also changes over time, making it difficult to distinguish from advanced gallbladder cancer. We experienced a case of xanthogranulomatous cholecystitis that changed over time, and report this case with a review of the literature.

[Resected Focal Nodular Hyperplasia That Was Difficult to Differentiate from Hepatocellular Carcinoma--A Case Report].

We report a case of a 62-year-old woman with a growing liver tumor that was difficult to differentiate from hepatocellular carcinoma (HCC). Abdominal CT revealed a hypervascular tumor (36 mm in diameter) in segment 3 of the liver that showed early enhancement and which had grown from 30 mm to 36 mm over the previous year. A fatty liver and gallstones were also detected. Magnetic resonance imaging (MRI) showed high intensity staining of the tumor on both T1- and T2-weighted images, and EOB-MRI revealed a mass that showed high signal intensity in the hepatobiliary phase. The imaging findings were not typical for HCC; however, the possibility of malignancy could not be ruled out due to the enlargement of the mass. Therefore, in February 2015, we performed a laparoscopic left lateral segmentectomy with cholecystectomy. After a good postoperative course, the patient was discharged from the hospital 11 days after surgery. Histological assessment revealed the tumor was focal nodular hyperplasia (FNH).

Psychological Barriers to the Use of Opioid Analgesics for Treating Pain in Patients With Advanced Recurrent Cancer: A Multicenter Cohort Study.

Background: We aimed to gain insight into psychological barriers toward initiation of strong opioid analgesic use in patients with advanced recurrent cancer. Methods: This study included 46 patients who were prescribed with opioid analgesics for advanced recurrent cancer. The primary outcome was psychological barriers assessed using the Japanese version of the Barriers Questionnaire-II (JBQ-II). The secondary outcomes were psychological changes and pain relief one week after the induction of strong opioid analgesics. Results: The mean age of participants was 63.6 years. Furthermore, 26.1% had an Eastern Cooperative Oncology Group (ECOG) performance status of ≥3. The mean JBQ-II total score was 1.97 (95% confidence interval: 1.75-2.19). At the initiation of opioid therapy, there was no difference in the total scores between the baseline and one week later. Nevertheless, there was a significant difference in the subscale "disease progression" score (mean 2.97 vs. 2.59, difference in means 0.38, standard error 0.16, p = 0.026). Personalized Pain Goal (PPG) was achieved in about half of the participants, and a trend toward a higher score in the subscale "harmful effects" (concern about adverse events) was observed in those who did not achieve PPG. Conclusion: This study showed that patients with advanced recurrent cancer have psychological barriers to opioid induction. The relationship between the presence of psychological barriers before and after induction of opioid analgesics and the speed of pain improvement was determined. The results may provide fundamental information for prospective intervention studies to develop individualized education programs for patients with psychological barriers to opioids.Clinical Trial Registration Number UMIN000042443.

[HER2 testing for advanced recurrent gastric cancer in a general hospital].

The Japanese gastric cancer treatment guidelines(published as a web supplement for version 3)recommend the implementation of HER2 testing prior to the selection of chemotherapy. Since we had not yet implemented HER2 immunohistochemistry(IHC)methods for gastric cancer, we tried to compare the HER2 testing results from a reference laboratory(ref lab) and our hospital(in-house). The HER2 concordance rates were calculated between the results from in-house and ref lab using 26 cases(31 samples)which were from patients with advanced, metastatic unresectable, or Stage IV resectable gastric cancer. The HER2 expression(in-house/ref lab)was distributed as follows: negative/negative, 18 cases; negative/equivocal, 2 cases; negative/positive, 1 case;equivocal/equivocal, 2 cases; and positive/positive, 3 cases. The concordance rate was 88. 4%(23/26), and the mismatch rate was 11. 6%(3/26)between in-house and ref lab. Although IHC test results with in-house and ref lab had been generally consistent, it is still necessary to improve and standardize diagnostic accuracy in the near future.

Multi-laboratory evaluation of immunoaffinity LC-MS-based glucagon-like peptide-1 assay.

Background: Although the fit-for-purpose approach has been proposed for biomarker assay validation, practical data should be compiled to facilitate the predetermination of acceptance criteria. Methods: Immunoaffinity LC-MS was used to analyze glucagon-like peptide-1 as a model biomarker in six laboratories. Calibration curve, carryover, parallelism, precision, relative accuracy and processed sample stability were evaluated, and their robustness among laboratories was assessed. The rat glucagon-like peptide-1 concentrations in four blinded samples were also compared. Results: The obtained results and determined concentrations in the blinded samples at all laboratories were similar, with a few exceptions, and robust, despite the difference in optimization techniques among laboratories. Conclusion: The results provide insights into the predefinition of the acceptance criteria of immunoaffinity LC-MS-based biomarker assays.

Psychological barriers to the use of opioid analgesics for treating pain in patients with advanced recurrent cancer (BAROC): protocol for a multicentre cohort study.

INTRODUCTION: Opioid analgesics are essential for treating cancer pain. However, patients are sometimes reluctant to use them because of concerns about addiction and dependence. Rapid pain relief following opioid administration may help overcome the psychological barriers to opioid analgesic use. This study aims to determine the relationship between psychological resistance to strong opioid analgesic use and pain amelioration speed in patients with advanced recurrent cancer. METHODS AND ANALYSIS: This ongoing, multicentre, observational study enrols patients aged 20 years or older with distant metastasis or advanced recurrent cancer receiving strong opioid analgesics for cancer pain for the first time. All participants, both inpatient and outpatient, were recruited from five Japanese hospitals. We are investigating the relationship between psychological barriers at the start of treatment and pain relief during the first week of treatment in these patients. The primary outcome is the Japanese version of the Barriers Questionnaire-II score at baseline. The secondary outcomes are the relationships between psychological barriers to strong opioid analgesic use and changes in pain over time. The participants are asked to fill out an electronic patient-reported outcome daily during the first week of treatment. The sample size was determined based on the number of patients in the year prior to study commencement who used strong opioid analgesics, met the eligibility criteria and could be expected to consent to participate in the study. ETHICS AND DISSEMINATION: The study protocol was approved by the ethics committee (approval ID B200600091) of Yokohama City University on 24 August 2020. The protocol has been reviewed by the institutional review boards at the four participating study sites. The results will be published in a peer-reviewed journal and will be presented at a relevant meeting. TRIAL REGISTRATION NUMBER: UMIN000042443.

Three-dimensional nuclear luminance analysis in well-differentiated adenocarcinoma of the lung.

OBJECTIVE: Well-differentiated papillary adenocarcinoma of the lung (G1 cancer cells) is difficult to distinguish from benign bronchial columnar epithelial cells with reactive atypia (benign cells) in many cases because nuclear atypia is mild. We focused on the 3-dimensional presence of nuclei in cell smears. Several images focused on the nucleus were acquired, and the nuclear luminance was measured and analyzed. STUDY DESIGN: One hundred G1 cancer cells and benign cells (nuclei), respectively, were selected from those on a bronchial brushing preparation for cytology. Images of 41 layers were acquired at 0.25-µm intervals in each cell, and the nuclear luminance was measured (a total of 8,400 images). RESULTS: There were more focus positions in the G1 cancer cell nuclei, showing a 3-dimensional nucleus, compared to benign cells, and the 3-dimensional variation in the coefficient of variation (CV) of nuclear luminance at the focus position was smaller in G1 cancer than in benign cells, showing a significant difference. CONCLUSION: The G1 cancer cells' nuclear structure was more 3-dimensional, and the chromatin distribution was homogeneous. The three-dimensional variation in the nuclear luminance CV could be numerically presented, which might be an objective index for cancer diagnosis.

Prevalence of neuropathic pain in terminally ill patients with cancer admitted to a general ward: a prospective observational study.

OBJECTIVES: To determine the prevalence of neuropathic pain among terminally ill patients with cancer admitted to a general ward, using the International Association for the Study of Pain algorithm. METHODS: This prospective observational study was conducted at a tertiary care center. We enrolled terminally ill patients with cancer admitted to the general ward between September 2018 and September 2019. On the day of consultation with our palliative care team, pain management clinicians examined and diagnosed neuropathic pain using the International Association for the Study of Pain diagnostic criteria. RESULTS: A total of 108 patients were enrolled during the study period. The median age was 69 years (interquartile range [IQR] 58.3-76.8 years), 72 patients (66.7%) were men, and the median survival time was 33 days (IQR 14.3-62 days). Of the 108 patients, 33 (30.6%) had neuropathic pain. Patients with neuropathic pain had more severe pain than those without neuropathic pain. CONCLUSIONS: The prevalence of neuropathic pain in terminally ill patients with cancer admitted to a Japanese general ward was 30.6%. Further studies are warranted to elucidate whether the accurate diagnosis of neuropathic pain can improve pain control and/or patient conditions.

[Spontaneous regression of mucosa-associated lymphoid tissue lymphoma of the lung].

We report a case of mucosa-associated lymphoid tissue (MALT) lymphoma of the lung that regressed spontaneously. An 82-year-old man was referred to our hospital because of an abnormal chest shadow. Chest CT scans showed soft tissue components along the periphery of the left main bronchus. Bronchoscopy showed an edematous and protruding lesion. Pathological findings showed diffuse invasion of small lymphoid cells of B-cell origin in the submucosal layers. These cells formed lymphoepithelial lesions. Southern blot hybridization demonstrated monoclonality and immunoglobulin heavy-chain gene rearrangement. We diagnosed MALT lymphoma of the lung. Spontaneous regression was found clinically 16 days after the first tumor biopsy for diagnosis by bronchoscopy. Autofluorescence imaging (AFI) 8 months after the first biopsy showed a decrease in magenta color. Immunohistochemical staining showed marked decrease in CD20 + B cells and an increase in the proportion of T cells, the majority of which were CD4 + T cells. No relapse of these lesions was detected 20 months after the first visit. It may be possible to closely follow up pulmonary MALT lymphoma without immediate treatment.

[Effectiveness of oral tramadol hydrochloride for chronic non-malignant pain].

BACKGROUND: Tramadol hydrochloride is a centrally acting analgesic agent with two distinct mechanisms of action, a weak opioid agonist and an inhibitor of monoamine neurotransmitter reuptake, which produces significant analgesic effect synergistically. Though tramadol was approved in 1978 in Japan, it has rarely been used in clinical settings compared to foreign countries, e.g. Germany and USA. The aim of this study is to investigate effectiveness of oral tramadol for chronic non-malignant pain in Japan. METHODS: Tramadol was orally administered to patients with refractory non-malignant pain. Effects and adverse effects of tramadol were assessed about one month after the start of the administration. RESULTS: Out of 17 patients using tramadol daily, tramadol was found to be significantly effective in 4 patients (23.5%) and moderately effective in 8 patients (47.1%) from the viewpoint of pain relief as well as improvement of activities of daily livings. Side effects were reported by 7 patients (41.2%), which included nausea, constipation, and dizziness, but none of the side effects were serious. CONCLUSIONS: Tramadol is a useful option to treat non-malignant chronic pain, especially considering its very low abuse potential and a more acceptable side effect profile compared to non-steroidal anti-inflammatory drugs and opioids.

Classic Hodgkin lymphoma with osseous involvement mimicking Langerhans cell histiocytosis in a child.

Hodgkin lymphoma (HL) commonly presents superficial lymphadenopathy. In addition, HL cells can arise in various organs including the liver and spleen as an extranodal lymphoma. HL in bone is unusual at the initial diagnosis, although some cases show late-stage localization of lymphoma cells to bone. We report the rare case of a young patient with cranial bone classic HL, presumably originating from the skull without any involvement of lymph nodes. As the main clinical manifestation was only tumor mass in the skull without osteoscopic pain, the tentative diagnosis of Langerhans cell histiocytosis was histologically confirmed by an excisional biopsy. Before the final pathological diagnosis as classic HL, we noticed several small lesions in extranodal regions through systemic surveys, suggesting that the cranial lesion appeared antecedent to those lesions. This is a rare and instructive case of cranial bone HL for which a histological diagnosis has been meticulously made.

An ancillary method in urine cytology: Nucleolar/nuclear volume ratio for discrimination between benign and malignant urothelial cells.

BACKGROUND: The essential of urine cytology for the diagnosis and the follow-up of urothelial neoplasia has been widely recognized. However, there are some cases in which a definitive diagnosis cannot be made due to difficulty in discriminating between benign and malignant. This study evaluated the practicality of nucleolar/nuclear volume ratio (%) for the discrimination. METHODS: Using Papanicolaou-stained slides, 253 benign urothelial cells and 282 malignant urothelial cells were selected and divided into a benign urothelial cell and an urothelial carcinoma (UC) cell groups. Three suspicious cases and four cases in which discrimination between benign and malignant was difficult were prepared for verification test. Subject cells were decolorized and stained with 4',6-diamidino-2-phenylindole for detection of the nuclei and the nucleoli. Z-stack method was performed to analyze. RESULTS: When the cutoff point of 1.514% discriminating benign urothelial cells and UC cells from nucleolar/nuclear volume ratio (%) was utilized, the sensitivity was 56.0%, the specificity was 88.5%, the positive predictive value was 84.5%, and the negative predictive value was 64.4%. Nuclear and nucleolar volume, number of the nucleoli, and nucleolar/nuclear volume ratio (%) were significantly higher in the UC cell group than in the benign urothelial cell group (P <0.001). In the verification test using the nucleolar/nuclear ratio (%), four of the seven cases were concordant with the final diagnosis. CONCLUSION: This study analyzed the nuclear and nucleolar volume to establish an index for discrimination of benign and malignant urothelial cells, providing possible additional information in urine cytology. Diagn. Cytopathol. 2016;44:483-491. © 2016 Wiley Periodicals, Inc.