Subcallosal and Heubner artery infarcts following surgical repair of an anterior communicating artery aneurysm: a causal relationship with postoperative amnesia and long-term outcome

Since the 1950s, amnesia or memory impairment has been repeatedly reported in patients following surgical repair of anterior communicating artery (ACoA) aneurysms. Postoperative infarctions following surgical repair of ACoA aneurysms are classified as involvement of the subcallosal artery (the largest unpaired perforator of the ACoA), the recurrent artery of Heubner (RAH), or a combination of both. Postoperative amnesia can seriously affect the patient’s quality of life, thus prompting physicians to discuss the symptomatology of the three infarction patterns. We made the following speculations regarding the causal relationship between the infarction pattern and postoperative amnesia. First, postoperative amnesia is most likely caused by an infarction in the territory of the subcallosal artery, particularly in the column of the fornix, a constituent of the Papez neuronal circuit. Second, infarction in the RAH territory alone is unlikely to cause significant amnesia. Third, infarcted foci in the RAH territory, when associated with a subcallosal artery infarction, can cause considerable frontal dysfunction due to impaired frontostriatal circuits in patients with postoperative amnesia, with resultant worsening of the long-term outcome or quality of life.     

Automated histological classification of whole-slide images of gastric biopsy specimens

Background

Automated image analysis has been developed currently in the field of surgical pathology. The aim of the present study was to evaluate the classification accuracy of the e-Pathologist image analysis software.

Methods

A total of 3062 gastric biopsy specimens were consecutively obtained and stained. The specimen slides were anonymized and digitized. At least two experienced gastrointestinal pathologists evaluated each slide for pathological diagnosis. We compared the three-tier (positive for carcinoma or suspicion of carcinoma; caution for adenoma or suspicion of a neoplastic lesion; or negative for a neoplastic lesion) or two-tier (negative or non-negative) classification results of human pathologists and of the e-Pathologist.

Results

Of 3062 cases, 33.4% showed an abnormal finding. For the three-tier classification, the overall concordance rate was 55.6% (1702/3062). The kappa coefficient was 0.28 (95% CI, 0.26–0.30; fair agreement). For the negative biopsy specimens, the concordance rate was 90.6% (1033/1140), but for the positive biopsy specimens, the concordance rate was less than 50%. For the two-tier classification, the sensitivity, specificity, positive predictive value, and negative predictive value were 89.5% (95% CI, 87.5–91.4%), 50.7% (95% CI, 48.5–52.9%), 47.7% (95% CI, 45.4–49.9%), and 90.6% (95% CI, 88.8–92.2%), respectively.

Conclusions

Although there are limitations and requirements for applying automated histopathological classification of gastric biopsy specimens in the clinical setting, the results of the present study are promising.

     

Feasibility of endoscopic resection using bipolar snare for nonampullary duodenal tumours in familial adenomatous polyposis patients

The management of duodenal and colorectal tumours is important in patients with familial adenomatous polyposis (FAP). Endoscopic resection (ER) should be carefully performed because the risk of complications during or after (ER) of nonampullary duodenal tumours is higher than that of stomach or colorectal lesions in general. Thus, we evaluated the feasibility of endoscopic resection using bipolar snare (ERB) for nonampullary duodenal tumours in FAP patients. Eleven FAP patients who underwent ERB for nonampullary duodenal tumours at our hospital between October 2013 and December 2016 were retrospectively analysed based on clinicopathological features. ER was generally indicated for endoscopically diagnosed tumours >?20 mm, biopsy-confirmed high-grade dysplasia or carcinomas >?10 mm, and multiple tumours. Nineteen endoscopic treatments were performed and 134 nonampullary duodenal tumours were resected. The median patient age at initial treatment was 40 years (range 20–64), and median size of the largest tumour in each procedure was 16 mm (range 9–40). Of the 101 pathologically evaluated lesions, 10 tumours were high-grade tubular adenomas, 87 were low-grade tubular adenomas, 1 was an adenocarcinoma, and 3 were non-neoplastic mucosal polyps. No intraoperative or delayed perforations were observed. Melena was encountered in one patient and managed without emergent endoscopic intervention. ERB for nonampullary duodenal tumours of FAP patients is feasible and effective, even for large lesions with high-grade dysplasia. Long-term outcomes of ERB, including local recurrence and prognosis, should be monitored.     

Established gastric cancer cell lines transplantable into C57BL/6 mice show fibroblast growth factor receptor 4 promotion of tumor growth

Previously no mouse gastric cancer cell lines have been available for transplantation into C57BL/6 mice. However, a gastric cancer model in immunocompetent mice would be useful for analyzing putative therapies. N‐Methyl‐N‐nitrosourea (MNU) was given in drinking water to C57BL/6 mice and p53 heterozygous knockout mice. Only 1 tumor from a p53 knockout mouse could be cultured and the cells s.c. transplanted into a C57BL/6 mouse. We cultured this s.c. tumor, and subcloned it. mRNA expression in the most aggressive YTN16 subline was compared to the less aggressive YTN2 subline by microarray analysis, and fibroblast growth factor receptor 4 ( FGFR4) in YTN16 cells was knocked out with a CRISPR/Cas9 system and inhibited by an FGFR4 selective inhibitor, BLU9931. These transplanted cell lines formed s.c. tumors in C57BL/6 mice. Four cell lines (YTN2, YTN3, YTN5, YTN16) were subcloned and established. Their in vitro growth rates were similar. However, s.c. tumor establishment rates, metastatic rates, and peritoneal dissemination rates of YTN2 and YTN3 were lower than for YTN5 and YTN16. YTN16 established 8/8 s.c. tumors, 7/8 with lung metastases, 3/8 with lymph node metastases and 5/5 with peritoneal dissemination. FGFR4 expression by YTN16 was 121‐fold higher than YTN2. FGFR4‐deleted YTN16 cells failed to form s.c. tumors and showed lower rates of peritoneal dissemination. BLU9931 significantly inhibited the growth of peritoneal dissemination of YTN16. These studies present the first transplantable mouse gastric cancer lines. Our results further indicate that FGFR4 is an important growth signal receptor in gastric cancer cells with high FGFR4 expression.     

MR imaging and clinical features associated with intraoperative hemorrhage during laparoscopic myomectomy

Laparoscopic myomectomy may become a cause to increase intraoperative hemorrhage. The purpose of this investigation was to study the relationship between clinical features, MR imaging findings and intraoperative hemorrhage during laparoscopic myomectomy. This study included 126 patients clinically and pathologically diagnosed as uterine leiomyoma between 2010 and 2015. These findings were statistically compared between significant intraoperative hemorrhage group (greater than 300?ml) and nonsignificant intraoperative hemorrhage group (less than 300?ml). Correlation between the maximum diameter of resected leiomyomas and the maximum diameter leiomyomas on MR imaging were also evaluated. Significant hemorrhage group showed larger maximum diameter of resected leiomyoma (p?=?0.01), larger maximum diameter of leiomyoma on MR imaging (p?=?0.01) and have cellular leiomyomas on MR imaging more frequently (p?=?0.03) than nonsignificant intraoperative hemorrhage group. The maximum diameter of resected leiomyomas significantly correlated with that of leiomyomas on MR imaging (Spearman’s rho?=?0.797, p?<?0.001). The cutoff value of maximum diameter of uterine leiomyoma on MR imaging between both groups was 7.27?cm. The MR imaging findings of a large uterine leiomyoma (more than about 7.3?cm) may predict significant intraoperative blood loss during laparoscopic myomectomy.     

Colorimetric chemosensitivity testing using sulforhodamine B

A colorimetric chemosensitivity test was investigated using sulforhodamine B (SRB), which stains protein synthesized by cells, as an end-point marker. Four cultured cell lines, 9 human tumor xenografts serially transplanted into nude mice, and 14 fresh surgical specimens were subjected to this assay. The optimal conditions for the assay were 3–5 × 10⁴ cells per well in a 96-microplate, an SRB concentration of 4%, and an incubation time of more than 10 minutes. When mitomycin C, doxorubicin, cisplatin, and 5-fluorouracil were assessed by the SRB assay, the concentration-effect curves revealed a sharp slope between plateaux at low and high concentrations, suggesting that this assay has an excellent sensitivity which can assess the effect of drugs as “all or none.” Although this high sensitivity resulted in good reproducibility of the assay for cultured cell lines, the predictive rate of the SRB assay for the chemosensitivity of human tumor xenografts in vivo was limited to 63.9%. As a result, this SRB assay is thought to be useful for evaluating the chemosensitivity of cultured cells as all or none, since it can assess directly cellular protein synthesis, which is one of the most important parameters of cell renewal, with excellent sensitivity. © 1993 Wiley-Liss, Inc.     

Identification of K-ras Oncogene Mutations in the Pure Pancreatic Juice of Patients with Ductal Pancreatic Cancers

Pancreatic cancer is detected on the basis of morphological changes delineated by means of various image-diagnostic methods. However, differentiation between chronic pancreatitis and pancreatic cancer, especially at the early stage, is not always simple when based upon the morphological changes alone. Therefore, we attempted to elucidate K- ras mutations in the sediment of pure pancreatic juice (PPJ) containing exfoliated ductal pancreatic cancer cells. PPJ was collected endoscopically from 20 patients with pancreatic cancer (PC) and 18 patients with chronic pancreatitis (CP). Polymerase chain reaction and allele specific oligonucleotide dot blot hybridization for K- ras mutations were performed with the DNA extracted from these samples. A K- ras mutation at codon 12 was identified in the PPJ of 11/20 (55%) of the patients with PC. On the other hand, the same mutation was not identified in the PPJ of any patient with CP. Moreover, K- ras mutations at codons 13 and 61 were not recognized in the PPJ of any patient with either PC or CP. These findings suggested that the presence of a K- ras mutation at codon 12 in PPJ would be useful in confirming the diagnosis of PC.     

IL-5 production by CD4+ T cells of asthmatic patients is suppressed by glucocorticoids and the immunosuppressants FK506 and cyclosporin A

IL-5 was produced in vitro by peripheral blood mononuclear cells(PBMC) of mite-sensitive atopic patients upon challenge withspecific allergen, while PBMC of healthy controls produced essentiallyno IL-5. Stimuli delivered by the combination of phorbol esterand Ca²⁺ ionophore induced marked IL-5 production by PBMC obtainedfrom atopic and non-atoplc asthmatics, suggesting that bothprotein kinase C and Ca²⁺ Influx are required for IL-5 production.CD2- or CD4-bearlng cell depletion almost completely removedIL-5-produclng cells while CD8-bearing cell depletion ratherenriched them. These findings indicate that CD4⁺ T cells arethe principal source of IL-5 in PBMC. The capacity of PBMC ofatopic asthmatics, non-atopic asthmatics and healthy controlsto produce IL-2, IL-4, IL-5 and IFN- was compared, to find thatcytokine-producing capacities other than that of IL-5 (IL-2,IL-4 and IFN-) were not significantly different among the threegroups. Dexamethasone, FK506 and cyclosporin A suppressed IL-5production in vitro in a dose-dependent manner. Clear dose-dependentsuppression of IL-5 gene expression by FK506 was also observed.Treatment of asthmatic patients with inhaled glucocorticoid(beclomethasone dipropionate) ameliorated clinical symptoms,improved lung function and markedly suppressed IL-5 productionby PBMC, suggesting the essential role of IL-5 in the pathogenesisof bronchial asthma and the clinical importance of its regulation.     

Predictability of tricuspid annular plane systolic excursion for the effectiveness of tolvaptan in patients with heart failure

Background

There is no echocardiographic predictor of the effectiveness of tolvaptan in patients with heart failure (HF). The aim of this study was to investigate the echocardiographic predictor of responders to tolvaptan in patients with HF.

Methods

This observational study consisted of 62 consecutive in-hospital patients with HF who received tolvaptan with volume overload despite standard therapies. The echocardiography data were obtained within 1 week before the administration of tolvaptan. Tolvaptan responders were defined as those having a body weight decrease from baseline >1 kg on the morning of day 8.

Results

The mean age of the 62 patients was 75.1 ± 13.9 years, and 45 patients (72.6%) were considered to be responders. Tricuspid annular plane systolic excursion (TAPSE) was significantly higher (17.1 ± 3.8 vs. 13.0 ± 3.9 mm; p = 0.0004) and the tricuspid valve regurgitation pressure gradient (33.3 ± 14.6 vs. 44.9 ± 12.2 mmHg; p = 0.007) and estimated right atrium pressure (7.8 ± 4.2 vs. 10.3 ± 4.5 mmHg; p = 0.043) were significantly lower in the Responder group than in the Non-responder group. In a multivariate logistic regression analysis, TAPSE was found to be an independent predictor of response (odds ratio 1.28; 95% confidence interval 1.03–1.60). According to the receiver operating characteristics analysis, the area under the curve of TAPSE was the largest among the parameters measured by echocardiography. The cut-off value for TAPSE to predict responders was determined to be 17.0 mm (sensitivity = 56.8%, specificity = 94.1%).

Conclusions

TAPSE is a simple predictor of the effectiveness of tolvaptan in patients with HF.