Usefulness of diffusion-weighted magnetic resonance imaging for evaluating the effect of hemostatic radiotherapy for unresectable gastric cancer

There are several reports that vouch for the usefulness of diffusion-weighted image (DWI) in making a diagnosis before treatment. However, no study has evaluated the effect of radiotherapy (RT) for unresectable gastric cancer. In the present case report, we evaluated the effectiveness of RT using DWI. An 81-year-old man was hospitalized with a broken bone and then diagnosed with advanced gastric cancer with breeding. He had chorionic renal failure and surgery was impossible. Further, contrast-enhanced computed tomography and magnetic resonance imaging (MRI) were not performed due to renal failure, whereas palliative RT was performed. We followed up the patient using blood test and MRI (DWI) to estimate whether bleeding had stopped or not after radiotherapy. Hemostasis effect was found after 2 weeks of RT. In DWI examination, there was a decrease in the tumor signal intensity 30 days after RT. Similarly, at day 60, the tumor signal intensity further decreased on DWI and the blood test results indicated no progression of anemia. At 4 months after the RT, the patient died because of respiratory failure without any bleeding. DWI is useful not only for the initial diagnosis but also for evaluating the effectiveness of RT.Trial registration: National clinical study registered number: UMIN000026362

Successful treatment of unresectable advanced rectal cancer with liver metastases by hemostasis re-irradiation of the rectal cancer and palliative low-dose whole-liver radiation therapy: a case report.

A 72-year-old man was admitted to the hospital with fatigue. Colonoscopy revealed a 50 × 50 mm rectal tumor with bleeding. Based on close inspection, he was diagnosed with unresectable advanced rectal cancer with multiple liver metastases. Chemotherapy was administered as 10 cycles of bevacizumab + mFOLFOX6 and 7 cycles of bevacizumab + FOLFIRI. Nine months later, he presented with hematochezia and progression of anemia. It was difficult to stop the bleeding via endoscopy. He underwent radiation therapy (39 Gy in 13 fractions), and hemostasis was confirmed. Then, further chemotherapy was performed with 3 cycles of bevacizumab + FOLFIRI and 2 cycles of TAS102. However 14 months after the initial visit, he presented with right hypochondralgia and abdominal fullness due to the progression of multiple liver metastases. Palliative low-dose whole-liver radiation therapy (WLRT) (30 Gy in 10 fractions) was performed. He developed Grade 2 nausea, but his right hypochondralgia reduced, liver dysfunction improved, and he successfully completed radiotherapy. At approximately the same time his anemia progressed, and colonoscopy revealed recurrent bleeding from the tumor. Re-irradiation (15 Gy in 5 fractions) of the rectal tumor was carried out and a blood transfusion was performed for the bleeding. He was discharged after confirmation the anemia had not progressed. Few reports have been published on the use of both palliative re-irradiation to stop bleeding from rectal cancer and palliative low-dose WLRT. Based on our experience with this case, we believe that palliative radiotherapy can be useful in treating patients with a poor prognosis

Protective effect of the Japanese traditional medicine juzentaihoto on myelosuppression induced by the anticancer drug TS-1 and identification of a potential biomarker of this effect

Abstract Background TS-1 is an oral anticancer drug containing a 5-fluorouracil derivative (Tegafur) that is widely used in Japan for the treatment of cancer, especially gastrointestinal tumors. Frequently, however, TS-1 therapy has to be discontinued because of leukopenia. If it were possible to predict the development of bone marrow suppression before the white blood cell (WBC) count had actually decreased, treatment could be improved by strict dosage control and/or the prophylactic administration of hematopoietic drugs. Juzentaihoto (JTT), a traditional Japanese medicine (Kampo), has been reported to activate hematopoiesis and reduce the side effects associated with chemotherapy and radiotherapy. Here, we 1) evaluate the efficacy of JTT in alleviating myelosuppression induced by TS-1 therapy in mice, and 2) explore biomarkers that reflect both induction by TS-1 and alleviation by JTT of bone marrow suppression using a proteomics approach. Methods Ten mg/kg of TS-1 was administered to Balb/c mice with or without 1 g/kg of oral JTT for 3, 5 and 7 days. WBC count and ratio of CD34+ bone marrow cells (BMCs) were estimated by flow cytometry. Plasma samples were analyzed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI TOF-MS). A biomarker candidate from SELDI profiling was identified using a combination of cation exchange spin column purification, SDS-PAGE, enzymatic digestion and LC-MS/MS. Results After administration of TS-1, a significant decrease in WBC count and CD34+ BMC ratio were observed at days 5 and 3, respectively. JTT treatment improved WBC count on day 7 and CD34+ BMC ratio on days 5 and 7. SELDI analysis highlighted three protein peaks that had increased on day 3 after treatment with TS-1 but remained unchanged in mice co-treated with JTT. One of the three peaks, m/z 4223.1, was further investigated and identified as a specific C-terminal fragment of albumin. Conclusion This study indicates that bone marrow suppression by treatment with TS-1 in mice might be improved by coadministration of JTT. A C-terminal fragment of albumin was identified as a candidate biomarker for predicting TS-1-induced myelosuppression. However, the sensitivity and specificity of the biomarker candidate must be validated in future clinical studies.</p

Dynamic regulation of plasma matrix metalloproteinases in human diabetic ketoacidosis

Background: Diabetic ketoacidosis (DKA) in children is associated with cerebrovascular-related complications. We recently reported that DKA facilitates leukocyte adherence to the brain microvascular endothelium. Adhered leukocytes can release enzymes that instigate vascular dysfunction. Our aims were to measure plasma levels of leukocyte-derived matrix metalloproteinases (MMPs) from DKA patients and to correlate plasma MMP concentrations with DKA severity. Methods: Plasma was obtained from children with type 1 diabetes, either in DKA (n = 16) or insulin controlled (CON; n = 16). Antibody microarray and gelatin zymography were used to quantify plasma MMPs and their endogenous tissue inhibitors (TIMPs). MMP concentrations were correlated with DKA severity (blood pH). Quantitative PCR of leukocyte mRNA was used to help determine the origin of plasma MMPs. Results: DKA was associated with altered plasma levels of ↓MMP-2 (P \u3c 0.001), ↑MMP-8 (P \u3c 0.001), ↑MMP-9 (P \u3c 0.05), and ↑TIMP-4 (P \u3c 0.001), as compared with CON. Elevated MMP-8 and MMP-9 were both positively correlated with DKA severity (P \u3c 0.05). DKA was associated with increased leukocyte mRNA for MMP-8, MMP-9, and TIMP-4 (P \u3c 0.005). Conclusion: MMPs are dynamically regulated during DKA. Plasma MMP-8 and MMP-9 concentrations correlate with DKA severity and are known to degrade brain microvascular endothelial cell tight junctions. Thus, leukocyte-derived MMPs might contribute to DKA-associated cerebrovascular complications

CXCL1/CXCL8 (GROα/IL-8) in human diabetic ketoacidosis plasma facilitates leukocyte recruitment to cerebrovascular endothelium in vitro

Diabetic ketoacidosis (DKA) in children is associated with intracranial vascular complications, possibly due to leukocyte-endothelial interactions. Our aim was to determine whether DKA-induced inflammation promoted leukocyte adhesion to activated human cerebrovascular endothelium. Plasma was obtained from children with type 1 diabetes either in acute DKA or in an insulin-controlled state (CON). Plasma concentrations of 21 inflammatory analytes were compared between groups. DKA was associated with altered circulating levels of ↑CXCL1 (GROα), ↑CXCL8 (IL-8), ↑IL-6, ↑IFNα2, and ↓CXCL10 (IP-10) compared with CON. These plasma analyte measurements were then used to create physiologically relevant cytokine mixtures (CM). Human cerebral microvascular endothelial cells (hCMEC/D3) were stimulated with either plasma (DKA-P or CON-P) or CM (DKA-CM or CON-CM) and assessed for polymorphonuclear leukocyte (PMN) adhesion. Stimulation of hCMEC/D3 with DKA-P or DKA-CM increased PMN adhesion to hCMEC/D3 under "flow" conditions. PMN adhesion to hCMEC/D3 was suppressed with neutralizing antibodies to CXCL1/CXCL8 or their hCMEC/D3 receptors CXCR1/CXCR2. DKA-P, but not DKA-CM, initiated oxidative stress in hCMEC/D3. Expression of ICAM-1, VCAM-1, and E-selectin were unaltered on hCMEC/D3 by either DKA-P or DKA-CM. In summary, DKA elicits inflammation in children associated with changes in circulating cytokines/chemokines. Increased CXCL1/CXCL8 instigated PMN adhesion to hCMEC/D3, possibly contributing to DKA-associated intracranial vascular complications