Hyperlipidemia as a risk factor for Trousseau syndrome-related cerebral infarction in patients with advanced gastrointestinal cancer

Trousseau syndrome-related cerebral infarction rarely occurs during chemotherapy in patients with gastrointestinal (GI) cancer, and its clinical features remain unclear. The present study aimed to examine the clinical features of Trousseau syndrome-related cerebral infarction developed during chemotherapy for GI cancer. The present retrospective cohort study consecutively enrolled 878 patients with unresectable GI cancer who received chemotherapy at the Multidisciplinary Treatment Cancer Center, Kurume University Hospital (Kurume, Japan) between April 2014 and March 2020. Patients with colorectal cancer (n=308) were the most common, followed by those with pancreatic (n=242), gastric (n=222) and biliary tract (n=59) cancer, neuroendocrine tumors (n=34) and duodenal cancer (n=11). Among the 878 patients, Trousseau syndrome-related cerebral infarction occurred in 8 (0.9%) patients with a median age of 70.5 years (range, 58–75 years), and 50% of the patients were male (4/8). In total, 3 patients had gastric cancer, 3 had pancreatic cancer and 2 had biliary tract cancer. A greater percentage of patients with Trousseau syndrome-related cerebral infarction had hyperlipidemia (38.0%) than those without (8.2%; P=0.005). Hyperlipidemia was a risk factor for occurrence of Trousseau syndrome-related cerebral infarction with an odds ratio of 7.009 (95% confidence interval, 1.785-27.513). Trousseau syndrome-related cerebral infarction developed during GI chemotherapy was rare and hyperlipidemia may predict its onset.     

Visualization of the photodegradation of a therapeutic drug by chemometric-assisted fluorescence spectroscopy

The fluorescence spectral fingerprint, also known as the excitation-emission matrix (EEM), is used to assess and visualize therapeutic drug photodegradation in combination with chemometrics. Examination of EEM-parallel factor analysis (PARAFAC) data showed that an individual component was easily separated from a mixture of photogenerated products of a heterocyclic pharmacophore, in this case, phenothiazine drugs (PTZs). Detailed investigations of both structure–EEM relationships and kinetics revealed that the components extracted from EEM–PARAFAC could be quantitatively attributed to such photogenerated products as phenothiazine sulfoxide and carbazole derivatives. EEM in combination with principal component analysis (PCA) could be used as a mapping tool to visualize information of the photodegradation process of PTZs. We also assessed the photostability of various types of PTZs containing side chains by using validated EEM–PARAFAC methodology.

Drug quality and assurance changes with time under the influence of a variety of environmental factors, such as light, temperature, and moisture.     

Two new isoflavanones from Erythrina costaricensis

Two new isoflavanones, 5,3′-dihydroxy-4′-methoxy-5′-(3-methyl-1,3-butadienyl)-2″,2″-dimethylpyrano[5,6:6,7]isoflavanone (1) and 5,3′-dihydroxy-5′-(3-hydroxy-3-methyl-1-butenyl)-4′-methoxy-2″,2″-dimethylpyrano[5,6:6,7]isoflavanone (2), together with two known isoflavonoids, cristacarpin, and euchrenone b₁₀, were isolated from the stems of Erythrina costaricensis. Their structures were established on the basis of spectroscopic evidence. These new compounds are rare isoflavanones, possessing both a 2,2-dimethylpyran substituent and a prenyl analog. The antibacterial activities of 1 and 2 against the methicillin-resistant Staphylococcus aureus were examined.     

First Japanese case of Pierson syndrome with mutations in LAMB2

Pierson syndrome (OMIM 609049) is typically characterized by congenital nephritic syndrome and peculiar ocular anomalies with microcoria. It is caused by mutations in LAMB2, which encodes laminin β2. Approximately 50 mutations of LAMB2 from approximately 40 unrelated families have been identified; however, most of them were from Western countries. Although three patients in Asia with mutations of LAMB2 have been reported, they were not typical cases. We report the first Japanese case of Pierson syndrome with proven causative LAMB2 mutations. She presented with congenital nephrotic syndrome and bilateral microcoria at birth, and developed end‐stage renal disease at 2 months of age. This is the first report of a typical case from Asia. LAMB2 analysis by direct sequencing revealed the compound heterozygous mutations c.3974_3975insA (p.N1325KfsX1331, maternal, novel) in exon 25 and c.4519C>T (p.Q1507X, paternal) in exon 27. The phenotype due to LAMB2 mutations appears to be similar between different ethnic groups.     

Label‐free multiphoton excitation imaging as a promising diagnostic tool for breast cancer

Histopathological diagnosis is the ultimate method of attaining the final diagnosis; however, the observation range is limited to the two‐dimensional plane, and it requires thin slicing of the tissue, which limits diagnostic information. To seek solutions for these problems, we proposed a novel imaging‐based histopathological examination. We used the multiphoton excitation microscopy (MPM) technique to establish a method for visualizing unfixed/unstained human breast tissues. Under near‐infrared ray excitation, fresh human breast tissues emitted fluorescent signals with three major peaks, which enabled visualizing the breast tissue morphology without any fixation or dye staining. Our study using human breast tissue samples from 32 patients indicated that experienced pathologists can estimate normal or cancerous lesions using only these MPM images with a kappa coefficient of 1.0. Moreover, we developed an image classification algorithm with artificial intelligence that enabled us to automatically define cancer cells in small areas with a high sensitivity of ≥0.942. Taken together, label‐free MPM imaging is a promising method for the real‐time automatic diagnosis of breast cancer.     

Hypoxic status in ovarian serous and mucinous tumors: relationship between histological characteristics and HIF-1α/GLUT-1 expression

Material and methods We analyzed the expression of hypoxia inducible factor-1α (HIF-1α) and glucose transporter-1 (GLUT-1) by immunohistochemistry in ovarian serous and mucinous tumors from the point view of the histological characteristics and acquisition of malignancy. A total of 102 ovarian tumors were examined, composed of 31 adenomas (serous 17 and mucinous 14), 32 borderline tumors (serous 13 and mucinous 19), and 39 adenocarcinomas (serous 21 and mucinous 18). Results The overall positive ratios were as follows: HIF-1α, 74% of adenomas, 91% of borderline tumors, and 100% of adenocarcinomas; and GLUT-1, 68% of adenomas, 95% of borderline tumors, and 100% of adenocarcinomas. Comparing serous tumors and mucinous tumors, there was no significant difference in the positive ratios of HIF-1α and GLUT-1 of adenomas, borderline tumors, and adenocarcinomas. However, both markers were more strongly expressed in serous adenocarcinomas (HIF-1α, 3 + 100%; GLUT-1, 3 + 76%) than in mucinous adenocarcinomas (HIF-1α, 3 + 61%; GLUT-1, 3 + 28%). The results of immunoblotting and mRNA expression level analyses corresponded with those of immunohistochemical expression profiles. DNA binding assay also demonstrated that HIF-1 is more commonly activated in serous adenocarcinomas than in mucinous adenocarcinomas. Conclusion HIF-1α and GLUT-1 expressions seemed to be coordinated to adapt ovarian tumor cells into hypoxic conditions in close association with the acquisition of malignancy. We consider that the relatively strong expression of both markers in serous tumors compared with mucinous tumors is related to the difference in their histological characteristics.     

A questionnaire about radiation safety management of the draining-water system at nuclear medicine facilities

We conducted a questionnaire survey about radiation-safety management condition in Japanese nuclear medicine facilities to make materials of proposition for more reasonable management of medical radioactive waste. We distributed a questionnaire to institutions equipped with Nuclear Medicine facilities. Of 1,125 institutions, 642 institutes (52.8%) returned effective answers. The questionnaire covered the following areas: 1) scale of an institution, 2) presence of enforcement of radiotherapy, 3) system of a tank, 4) size and number of each tank, 5) a form of draining-water system, 6) a displacement in a radioactive rays management area, 7) a measurement method of the concentration of medical radioactive waste in draining water system, 8) planned and used quantity of radioisotopes for medical examination and treatment, 9) an average displacement of hospital for one month. In most institutions, a ratio of dose limitation of radioisotope in draining-water system was less than 1.0, defined as an upper limitation in ordinance. In 499 hospitals without facilities of hospitalization for unsealed radioisotope therapy, 473 hospitals reported that sum of ratios of dose limits in a draining-water system was less than 1.0. It was calculated by used dose of radioisotope and monthly displacement from hospital, on the premise that all used radioisotope entered in the general draining-water system. When a drainage including radioactivity from a controlled area join with that from other area before it flows out of a institution, it may be diluted and its radioactive concentration should be less than its upper limitation defined in the rule. Especially, in all institutions with a monthly displacement of more than 25,000 m3, the sum of ratio of the concentration of each radionuclide to the concentration limit dose calculated by used dose of radioisotope, indicated less than 1.0.     

Risk Factors of Surgical Site Infection After Hepatectomy for Liver Cancers

Background  Risk factors of surgical site infection (SSI) after hepatectomy under the guideline of Centers for Disease Control and Prevention (CDC) are not well examined. Methods  Hospital records of consecutive patients who underwent hepatectomy without biliary reconstruction for liver cancers were reviewed retrospectively. Prophylactic antibiotics were given to patients just before skin incision and every 3 hours during the operations. Clinicopathological factors were compared between patients who developed SSI and those without it. Results  There were 405 patients identified, and the incidence of SSI was 23 cases (5.8%). In multivariate analysis, intraoperative bowel injury, blood loss >2000 ml, and age older than 65 years were significant risk factors of SSI after hepatectomy. Conclusions  Prophylactic antibiotics were necessary only during the operation for most patients who underwent hepatectomy without biliary reconstruction. However, patients with intraoperative bowel injury, blood loss >2000 ml, and age older than 65 years are at risk to develop SSI and might need additional administration of prophylactic antibiotics after surgery.     

Serum ornithine carbamyltransferase reflects hepatic damage in diabetic obese mice

Background and Aim: As ornithine carbamyltransferase (OCT) has proved to be a sensitive serum marker in the detection of hepatotoxicity in several models, it is important to confirm its application to the diagnosis of non‐alcoholic fatty liver disease. Methods: C57BL/6, KK‐Ta and KK‐Ay mice were fed a high‐fat diet for 8 weeks and serum enzyme markers were examined. Serum OCT and alanine aminotransferase (ALT) were also measured in diabetic obese ob/ob and db/db mice fed a normal diet. Liver damage in these mice was evaluated by the hepatic content of tumor necrosis factor‐alpha. Results: Serum levels of OCT increased in KK‐Ay fed a high‐fat diet compared with the normal diet‐fed group, whereas C57BL/6 and KK‐Ta mice were not affected. In ob/ob mice, the relative increase was always greater in OCT than in ALT. In contrast, in db/db mice, the relative increase was always greater in ALT. Hepatic tumor necrosis factor‐alpha was significantly elevated in ob/ob mice, but not in db/db mice. Conclusions: Serum OCT seemed to reflect tumor necrosis factor‐alpha‐mediated hepatic damage when compared with ALT in diabetic obese mice and could be useful in the application for non‐alcoholic fatty liver disease with features of metabolic syndrome, such as obesity and diabetes.     

The additive effect ofα-difluoromethylornithine (DFMO) and radiation therapy on a rat glioma model

Summary The effects of -difluoromethylornithine (DFMO), radiation and the therapy of their combination were investigated in rats bearing G-XII glioma. DFMO treatment as well as radiation therapy prolonged the survival period when compared to the results in non-treated control rats. The combination therapy showed a greater effect on the survival rate than the single therapies, the effect being additive. The concentration of putrescine, spermidine, andN ¹-acetylspermidine in tumor tissues was lowered by DFMO, while that of spermine was slightly elevated. Radiation decreased the concentration of all the polyamines, putrescine, spermidine, spermine andN ¹-acetylspermidine. The concomitant treatment with DFMO and radiation further decreased the concentrations of putrescine andN ¹-acetylspermidine in tumor tissues. The survival period of glioma-bearing rats is inversely correlated with the tissue levels of putrescine plusN ¹-acetylspermidine.Abbreviations DFMO -difluoromethylornithine - BrdUrd bromodeoxyuridine