Hepatic Arterial Infusion Chemotherapy Prior to Standard Systemic Chemotherapy in Patients with Highly Advanced Unresectable Liver Metastases from Colorectal Cancer: A Report of Three Patients

We administered hepatic arterial infusion chemotherapy (HAIC) prior to FOLFOX to three patients with unresectable liver metastases from colorectal cancer. The patients' disease state was found to be highly advanced based on both computed tomography findings and liver function tests. The treatment strategy included an initial administration of HAIC to control liver metastases and improve liver function in order to facilitate the subsequent safe administration of FOLFOX without drug loss. As the HAIC regimen, 1,000mg/m2 of 5-FU was administered weekly by continuous 5-h infusion after performing laboratory investigations through an implanted port-catheter system. After 3 HAIC cycles administered over 3 consecutive weeks, the mean alkaline phosphatase levels decreased from 969.3IU/l to 422IU/l due to shrinkage of the liver metastases. Thereafter, FOLFOX without drug loss could be safely initiated for all patients. Two patients succumbed 488 and 333 days after HAIC was initiated;the third patient is still alive and has been followed-up for 1215 days. The combined use of HAIC and standard systemic chemotherapy could be a feasible and efficacious treatment in highly advanced cases of liver dysfunction

“Hook and Roll Technique” Using an Articulating Hook Cautery to Provide a Critical View during Single-incision Laparoscopic Cholecystectomy

We describe a new simple and easy technique called the "Hook and roll technique" (HRT) that uses an articulating hook cautery to provide a critical view during single incision laparoscopic cholecystectomy (SILC). A 2-cm incision is made at the umbilicus to insert three 5-mm trocars or a multichannel port. After dissection of the serosa of the dorsal and ventral sides of the gall bladder, including Calot's triangle, the angled tip of the hook cautery is inserted between the cystic artery and duct with its tip placed dorsally. The tip is then rotated in a clockwise manner to avoid bile duct injury, allowing the connective tissue between them to be hooked, coagulated and cut. This procedure is repeated several times, followed by dissection between the cystic artery and the liver bed to achieve a critical view. From December 2008 to May 2011, 121 patients underwent SILC using HRT in our hospital without any serious complications. This technique is suitable for SILC, as it is consists of simple procedures that can be performed safely and easily, even by left hand in a cross-over approach, and it allows complete dissection of Calot's triangle to achieve a critical view without using any dissector under dangerous in-line viewing

The Endocannabinoid 2-Arachidonoylglycerol Produced by Diacylglycerol Lipase α Mediates Retrograde Suppression of Synaptic Transmission

SummaryEndocannabinoids are released from postsynaptic neurons and cause retrograde suppression of synaptic transmission. Anandamide and 2-arachidonoylglycerol (2-AG) are regarded as two major endocannabinoids. To determine to what extent 2-AG contributes to retrograde signaling, we generated and analyzed mutant mice lacking either of the two 2-AG synthesizing enzymes diacylglycerol lipase α (DGLα) and β (DGLβ). We found that endocannabinoid-mediated retrograde synaptic suppression was totally absent in the cerebellum, hippocampus, and striatum of DGLα knockout mice, whereas the retrograde suppression was intact in DGLβ knockout brains. The basal 2-AG content was markedly reduced and stimulus-induced elevation of 2-AG was absent in DGLα knockout brains, whereas the 2-AG content was normal in DGLβ knockout brains. Morphology of the brain and expression of molecules required for 2-AG production other than DGLs were normal in the two knockout mice. We conclude that 2-AG produced by DGLα, but not by DGLβ, mediates retrograde suppression at central synapses

RUNX1 transactivates BCR-ABL1 expression in Philadelphia chromosome positive acute lymphoblastic leukemia

The emergence of tyrosine kinase inhibitors as part of a front-line treatment has greatly improved the clinical outcome of the patients with Ph⁺ acute lymphoblastic leukemia (ALL). However, a portion of them still become refractory to the therapy mainly through acquiring mutations in the BCR-ABL1 gene, necessitating a novel strategy to treat tyrosine kinase inhibitor (TKI)-resistant Ph⁺ ALL cases. In this report, we show evidence that RUNX1 transcription factor stringently controls the expression of BCR-ABL1, which can strategically be targeted by our novel RUNX inhibitor, Chb-M'. Through a series of in vitro experiments, we identified that RUNX1 binds to the promoter of BCR and directly transactivates BCR-ABL1 expression in Ph⁺ ALL cell lines. These cells showed significantly reduced expression of BCR-ABL1 with suppressed proliferation upon RUNX1 knockdown. Moreover, treatment with Chb-M' consistently downregulated the expression of BCR-ABL1 in these cells and this drug was highly effective even in an imatinib-resistant Ph⁺ ALL cell line. In good agreement with these findings, forced expression of BCR-ABL1 in these cells conferred relative resistance to Chb-M'. In addition, in vivo experiments with the Ph⁺ ALL patient-derived xenograft cells showed similar results. In summary, targeting RUNX1 therapeutically in Ph⁺ ALL cells may lead to overcoming TKI resistance through the transcriptional regulation of BCR-ABL1. Chb-M' could be a novel drug for patients with TKI-resistant refractory Ph⁺ ALL

Laparoscopic repair of an abdominal incisional hernia above the pubis

　　Laparoscopic repair of a suprapubic hernia typically carries a high risk of recurrence, because fixation of the mesh in the peripubic area is difficult. We herein report a patient undergoing laparoscopic repair of a suprapubic hernia, along with a description of the surgical techniques employed. 　A 78-year-old woman visited our hospital with a chief complaint of swelling at the median hypogastric incision site after surgery for an ovarian cyst performed at age 25 years. Laparoscopic examination revealed the hernia orifice to be 3.5×3.0 cm in size and that the distance between the caudal margin of the hernia orifice and the pubis was 2.5 cm. Parietex composite mesh was used for fixation through all layers of the abdominal wall with non-absorbable sutures and tack fixation. On the pubic side, after the pubis had been exposed by separating it from the bladder, we performed mesh fixation through all layers of the abdominal wall immediately above the pubis with the sutures placed inside the mesh, combined with tack mesh fixation directly to the pubis. This procedure enabled definite fixation of the mesh. Six days after surgery, she was discharged without complications. To date, two years and five months after surgery, no recurrence has been observed

先天性心疾患根治術前患児の全身麻酔下での歯科治療 : 2症例について

Two child patients who have congenital heart disease were treated under general anesthesia for severe dental caries in order to prevent infectious endocarditis after the heart operation. Although both the caries treatment and the subsequent heart operation of these two cases were satisfactorily completed, the necessity of early and periodical oral management for these kinds of patients was strongly suggested. The pediatric dentistry department of a general hospital should play a role in building a close cooperation system between pediatricians and the local dental practitioners for the dental welfare of child patients who are susceptible to infectious disease

Mirrors Have a Modest Effect on Human Impulsivity

 Human behavior is affected by various social cues. Studies have revealed that cues of being watched affect both social and non-social behavior. A subsequent question is whether one’s own image in a mirror has a noticeable effect on behavior and decision-making. Previous studies suggest that people behave in accordance with social desirability in the presence of mirrors; however, the “mirror effect” is still controversial and researchers know little about the mechanism. To further investigate this effect, the current study examined whether mirrors influence impulsivity, a feature that is closely related to decision-making in both social and non-social situations. Participants completed a delay-discounting task in a mirror condition and a no-mirror control condition. We found that relative to the control condition, participant impulsivity increased in the mirror condition. This outcome may have been triggered when the participants’ private self-awareness, contrary to public self-awareness, was activated by the mirrors. Thus, mirror-induced self-awareness might have influenced decision-making as a non-social cue in our experiment. Considering the inconsistent results among previous and present studies, the mirror effect might be influenced by the cultural difference or experimental setting. Further investigation is needed to identify how people change their behavior and which aspects of self-awareness are influenced by mirrors.</jats:p