Differences in gut integrity following abdominal surgery according to the magnitude of the surgical stress

BACKGROUND: An increase in serum diamine oxidase (DAO) activity reflects intestinal mucosal damage. This was used to estimate the effect of surgical stress after elective abdominal surgery on gut integrity. METHODS: Patients with gastrointestinal tract cancers were placed in either group T (transthoracic esophagectomy for esophageal cancer, n = 9) or group L (laparotomy, n = 10). The serum DAO activity was measured pre-operatively, and on postoperative days 1, 3, and 8. RESULTS: Transthoracic esophagectomy was associated with a more extensive stress than the operations in group L, as measured by the intra-operative blood loss, the amount of blood transfused, and the operative time (P = 0.007, P = 0.0002, P = 0.0011, respectively). Following surgery, the serum DAO activity was decreased markedly in all patients in group T. In contrast, the activity was unchanged in group L (P = 0.04). CONCLUSIONS: The severity of the surgical insult plays a significant role in the decrease in serum DAO activity. These results suggest that surgical stress influences gut integrity following elective abdominal surgery.     

A novel compound RS-0466 reverses beta-amyloid-induced cytotoxicity through the Akt signaling pathway in vitro

In order to determine whether 5-[bis(carboxymethyl) amino]-2-carboxy4-cyano-3-thiopheneacetic acid distrontium salt (S12911-2) inhibits bone resorption by acting on the differentiation and/or function of osteoclasts, its effects were assessed on the 1,25-dihydroxyvitamin D(3)-induced expression of carbonic anhydrase II and vitronectin receptor in chicken bone marrow cells, and on the resorbing activity of authentic rat osteoclasts cultured on bone slices. S12911-2 dose-dependently inhibited, after a 6-day exposure, the expression of carbonic anhydrase II and vitronectin receptor in stimulated osteoclasts (46% and 40%, respectively, at 10(-3) M Sr(2+), P<0.05). A pre-incubation of bone slices with S12911-2 induced a dose-dependent inhibition of bone resorbing activity from 32% at 10(-4) M Sr(2+) to 66% at 10(-3) M Sr(2+) (P<0.05 in each case). A continuous incubation (10(-3) M Sr(2+)) induced a greater inhibition of bone resorbing activity (73%, P<0.05). The inhibition of bone resorption obtained specifically with S12911-2 is related to an inhibition of the differentiation and resorbing activity of the osteoclasts.     

Development of Acute Adult T-cell Leukemia Following PD-1 Blockade Therapy for Lung Cancer

Immune checkpoint inhibitors (ICIs) are widely used for the treatment of various cancers. However, paradoxical exacerbation of neoplasms, referred to as “hyperprogressive disease,” has been reported in a proportion of patients treated with anti-programmed cell death-1 (PD-1)/PD-1 ligand (PD-L1) blockade. We herein report a case of acute adult T-cell leukemia (ATL) that developed shortly after the administration of nivolumab, a PD-1 inhibitor, to treat non-small-cell lung cancer. There were no signs of ATL before the administration of nivolumab, and seropositivity for human T-cell leukemia virus type-1 (HTLV-1) was confirmed after the development of acute ATL. We speculate that nivolumab likely contributed to the development of acute ATL.     

Brain regions associated with Brunnstrom and functional independence measure scores in patients after a stroke: a tract-based spatial statistics study

[Purpose] We aimed to assess diffusion tensor fractional anisotropy to outline the brain regions associated with the long-term motor and cognitive functional outcomes of patients with stroke. [Participants and Methods] Eighty patients from our previous study were enrolled. Fractional anisotropy maps were acquired on days 14–21 after stroke onset, and tract-based spatial statistics were applied. Outcomes were scored using the Brunnstrom recovery stage and Functional Independence Measure motor and cognition components. Fractional anisotropy images were assessed in relation to outcome scores using the general linear model. [Results] For both the right (n=37) and left (n=43) hemisphere lesion groups, the corticospinal tract and the anterior thalamic radiation were most strongly associated with the Brunnstrom recovery stage. In contrast, the cognition component involved large regions encompassing the anterior thalamic radiation, superior longitudinal fasciculus, inferior longitudinal fasciculus, uncinate fasciculus, cingulum bundle, forceps major, and forceps minor. The results for the motor component were intermediate between those for the Brunnstrom recovery stage and those for the cognition component. [Conclusion] Motor-related outcomes were associated with fractional anisotropy decreases in the corticospinal tract, whereas cognitive outcomes were related to broad regions of association and commissural fibers. This knowledge will help scheduling appropriate rehabilitative treatments.     

Applicability of automated tractography during acute care stroke rehabilitation

[Purpose] To assess the clinical applicability of a novel automated tractography tool named XTRACT during acute stroke rehabilitation. [Participants and Methods] Three patients with left hemisphere stroke were sampled. Diffusion tensor images were acquired on the second week, and automated tractography was then applied. Tractography images and fractional anisotropy (FA) values in the corticospinal tract (CST) and arcuate fasciculus (AF) were assessed in relation to hemiparesis and aphasia. [Results] Patient 1 was nearly asymptomatic; FA in the left CST was 0.610 and that in the AF was 0.509. Patient 2 had severe hemiparesis and mild motor aphasia. Tractography images of the CST and AF were blurred; FA in the left CST was 0.295 and that in the AF was 0.304. Patient 3 showed no hemiparesis or aphasia at initial assessment. Tractography image of the CST was intact but that of the AF was less clear; FA in the left CST was 0.586 and that in the AF was 0.338. Considering the less clear images of the AF and lower FA value in Patients 2 and 3, further examinations for aphasia were performed, which revealed agraphia. [Conclusion] Visualization and quantification of neural fibers using automated tractography promoted planning acute care rehabilitative treatment in patients with stroke.     

Successful preoperative chemotherapy with S-1 plus low-dose cisplatin for advanced gastric cancer with synchronous liver metastases: report of 2 cases

We report 2 cases of advanced gastric cancer with synchronous liver metastases who were successfully downstaged using S-1 plus low-dose cisplatin chemotherapy followed by surgical resection. S-1 was administered orally (80 mg/m(2)/day) twice daily for 14 consecutive days, and cisplatin (15 mg/m(2)) was infused over 1 h on days 1 and 8. Successful downstaging of the hepatic metastases was confirmed by imaging analyses; however, neither patient showed a complete response of the primary lesion in the stomach. Toxicities, according to the WHO criteria, were mild. The patients underwent surgical resection within 4 weeks after the last chemotherapy. Postoperatively, they were discharged without complications and received adjuvant chemotherapy. Both patients remained alive and well at 17 and 12 months after surgery, respectively, without recurrence. These cases provide further evidence that S-1 plus low-dose cisplatin chemotherapy enables downstaging of advanced gastric cancer and a subsequent potentially curative resection without serious complications.     

Excessive fibrinolysis detected with thromboelastography in a case of amniotic fluid embolism: fibrinolysis may precede coagulopathy

Journal of Thrombosis and Thrombolysis - Amniotic fluid embolism (AFE) is a catastrophic condition in the peripartum period and still remains as a leading cause of maternal death. Although over 80%...     

The use of personalized biomarkers and liquid biopsies to monitor treatment response and disease recurrence in locally advanced rectal cancer after neoadjuvant chemoradiation

Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the mainstay treatment for locally advanced rectal cancer. Variable degrees of tumor regression are observed after nCRT and alternative treatment strategies, including close surveillance without immediate surgery, have been investigated to spare patients with complete tumor regression from potentially adverse outcomes of radical surgery. However, clinical and radiological assessment of response does not allow accurate identification of patients with complete response. In addition, surveillance for recurrence is similarly important for these patients, as early detection of recurrence allows salvage resections and adjuvant interventions. We report the use of liquid biopsies and personalized biomarkers for monitoring treatment response to nCRT and detecting residual disease and recurrence in patients with rectal cancer. We sequenced the whole-genome of four rectal tumors to identify patient-specific chromosomal rearrangements that were used to monitor circulating tumor DNA (ctDNA) in liquid biopsies collected at diagnosis and during nCRT and follow-up. We compared ctDNA levels to clinical, radiological and pathological response to nCRT. Our results indicate that personalized biomarkers and liquid biopsies may not be sensitive for the detection of microscopic residual disease. However, it can be efficiently used to monitor treatment response to nCRT and detect disease recurrence, preceding increases in CEA levels and radiological diagnosis. Similar good results were observed when assessing tumor response to systemic therapy and disease progression. Our study supports the use of personalized biomarkers and liquid biopsies to tailor the management of rectal cancer patients, however, replication in a larger cohort is necessary to introduce this strategy into clinical practice.