Circadian Disruption Accelerates Tumor Growth and Angio/Stromagenesis through a Wnt Signaling Pathway

Epidemiologic studies show a high incidence of cancer in shift workers, suggesting a possible relationship between circadian rhythms and tumorigenesis. However, the precise molecular mechanism played by circadian rhythms in tumor progression is not known. To identify the possible mechanisms underlying tumor progression related to circadian rhythms, we set up nude mouse xenograft models. HeLa cells were injected in nude mice and nude mice were moved to two different cases, one case is exposed to a 24-hour light cycle (L/L), the other is a more “normal” 12-hour light/dark cycle (L/D). We found a significant increase in tumor volume in the L/L group compared with the L/D group. In addition, tumor microvessels and stroma were strongly increased in L/L mice. Although there was a hypervascularization in L/L tumors, there was no associated increase in the production of vascular endothelial cell growth factor (VEGF). DNA microarray analysis showed enhanced expression of WNT10A, and our subsequent study revealed that WNT10A stimulates the growth of both microvascular endothelial cells and fibroblasts in tumors from light-stressed mice, along with marked increases in angio/stromagenesis. Only the tumor stroma stained positive for WNT10A and WNT10A is also highly expressed in keloid dermal fibroblasts but not in normal dermal fibroblasts indicated that WNT10A may be a novel angio/stromagenic growth factor. These findings suggest that circadian disruption induces the progression of malignant tumors via a Wnt signaling pathway

Multicenter safety study of mFOLFOX6 for unresectable advanced/recurrent colorectal cancer in elderly patients

<p>Abstract</p> <p>Background</p> <p>Combination chemotherapy with oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX) has become a standard regimen for colorectal cancer. An increase of adverse events with combination chemotherapy is predicted in elderly patients, and it remains controversial whether they should receive the same chemotherapy as younger patients. Accordingly, this study of modified FOLFOX6 (mFOLFOX6) therapy was performed to compare its safety between elderly and non-elderly patients.</p> <p>Methods</p> <p>We prospectively studies 14 non-elderly patients aged <70 years old and 8 elderly patients aged ≥ 70 years with unresectable advanced/recurrent colorectal cancer who received mFOLFOX6 therapy during the period from March 2006 to March 2007. Adverse events and the response to treatment were compared between the elderly and non-elderly groups.</p> <p>Results</p> <p>The main adverse events were neutropenia and peripheral neuropathy, which occurred in 62.5% (≥ grade 3) and 87.5% (≥ grade 1) of elderly patients. The grade and frequency of adverse events were similar in the elderly and non-elderly groups. In some patients with neutropenia, treatment could be continued without reducing the dose of oxaliplatin by deleting bolus 5-fluorouracil. A correlation was found between the cumulative dose of oxaliplatin and the severity of neuropathy, and there were 2 elderly and 3 younger patients in whom discontinuation of treatment was necessary due to peripheral neuropathy. The median number of treatment cycles was 10.0 and 9.5 in the non-elderly and elderly groups, respectively. The response rate was 60.0% in the non-elderly and 50.0% in the elderly group, while the disease control rate was 100% and 83.3% respectively, showing no age-related difference.</p> <p>Conclusion</p> <p>mFOLFOX6 therapy was well-tolerated and effective in both non-elderly and elderly patients. However, discontinuation of treatment was sometimes necessary due to peripheral neuropathy, which is dose-limiting toxicity of this therapy.</p

Damage control surgery for unstable thoracic wall injury

Damage control surgery (DCS) consists of three steps: an abbreviated initial operation, resuscitation in the ICU, and a planned reoperation. Although DCS for lung and heart injury have been established, there is no concept of DCS for the chest wall. We experienced a successful case, in which a DCS of chest wall lifting procedure and internal pneumatic stabilization were performed on the flail chest accompanied by a remarkable destruction of chest wall. As a result, the patient's abnormal breathing improved. Surgical fixations using KANI plate were performed at a later date. We suggest that the chest wall lifting procedure may be suitable as a DCS for thoracic cage destruction from severe chest wall injury. Keywords: Damage control surgery, Thoracic wall destruction, Rib fracture, Surgical stabilizatio

First establishment of a new table-rotated-type hybrid emergency room system

Abstract The hybrid emergency room (hybrid ER) system was first established in 2011 in Japan. It is defined as an integrated system including an ER, emergency computed tomography (CT) and interventional radiology (IVR) rooms, and operating rooms. Severe trauma patients can undergo emergency CT examinations and therapies (surgeries) without being transferred. The hybrid ER system is attracting attention because trauma resuscitation using this system has been reported to potentially improve the mortality rate in severe trauma patients. In August 2017, we established a new table-rotated-type hybrid ER to facilitate surgical functions. Herein, we introduce a new table-rotated-type hybrid ER consisting of an IVR–CT–operating room system and discuss its efficiency and feasibility for trauma resuscitation, including surgery and IVR. This system includes four new concepts: (1) to secure a wide working space during trauma resuscitation by reconsidering the arrangement of the C-arm, (2) ensure an air-conditioned operating room in the hybrid ER, (3) adopt an operating table but not interventional radiology table, and (4) prepare a trauma bay with three additional beds for multiple victims. This hybrid ER system also adopted the rotated-type table to secure a wide working space during the resuscitation phase. The C-arm was located away from the patients and placed on the wall opposite to the CT gantry, in contrast to that in previous systems. If patients needed an emergency IVR, the table was just rotated, and the IVR could be conducted immediately. This improvement can secure a wide working space in the hybrid ER. Moreover, the patient table was also a surgical operating table, and the hybrid ER system had an air-conditioned operating room (class 10,000). In the anticipation of many trauma patients being transported to the ER, a new trauma bay with three additional beds next to the hybrid ER was established, which also had an air-conditioned operating room. This new rotated-type hybrid ER system facilitates efficient surgical functions during trauma resuscitation and can secure a wide working space for the medical team to immediately perform resuscitative procedures and IVRs without delay