Leiomyosarcoma of the sigmoid colon with multiple liver metastases and gastric cancer: a case report

BACKGROUND: Leiomyosarcoma (LMS) of the gastrointestinal tract is an extremely rare high-grade neoplasm with poor prognosis. For advanced LMS with distant metastasis, the decision as to the choice of the most appropriate therapeutic strategy, including chemotherapy and surgery, is difficult. Here, we present an unusual case of LMS of the sigmoid colon with liver metastases and gastric cancer. The survival of this patient was prolonged by a combined modality therapy involving chemotherapy and surgery. CASE PRESENTATION: A 66-year-old woman who had been diagnosed with advanced gastric cancer and multiple liver metastases was referred to our hospital. The initial treatment with docetaxel and S-1 considerably reduced both the gastric cancer and liver tumors; consequently we performed surgical resection. Pathological examination revealed that no viable tumor cells remained in the stomach and chemotherapy resulted in complete remission of the gastric cancer. The liver tumors were immunohistochemically diagnosed as LMS. A tumor of the sigmoid colon was subsequently discovered and the liver tumors were found to have recurred. The surgically resected sigmoid colon and liver tumors were all immunohistochemically diagnosed as LMS. These findings indicated that the multiple liver metastases arose from the LMS in the sigmoid colon, and that they were accompanied by advanced gastric cancer. We performed another surgical resection and administered chemotherapy to treat the recurring liver metastases. The patient survived for 4 years and 10 months after initial presentation at our hospital. CONCLUSION: Colonic LMS is rare and its joint occurrence with gastric cancer is extremely unusual. Although LMS is a high-grade neoplasm, a multimodal therapeutic approach can increase patient survival time even when multiple liver metastases are present

Optimization of the Combustion System of a Medium Duty Direct Injection Diesel Engine by Combining CFD modeling with Experimental Validation

The research in the field of internal combustion engines is currently driven by the needs of decreasing fuel consumption and CO2 emissions, while fulfilling the increasingly stringent pollutant emissions regulations. In this framework, this research work focuses on describing a methodology for optimizing the combustion system of compression ignition (CI) engines, by combining computational fluid dynamics (CFD) modeling, and the statistical Design of Experiments (DOE) technique known as Response Surface Method (RSM). As a key aspect, in addition to the definition of the optimum set of values for the input parameters, this methodology is extremely useful to gain knowledge on the cause/effect relationships between the input and output parameters under investigation. This methodology is applied in two sequential studies to the optimization of the combustion system of a 4-cylinder 4-stroke Medium Duty Direct Injection (DI) CI engine, minimizing the fuel consumption while fulfilling the emission limits in terms of NOx and soot. The first study targeted four optimization parameters related to the engine hardware including piston bowl geometry, injector nozzle configuration and mean swirl number (MSN) induced by the intake manifold design. After the analysis of the results, the second study extended to six parameters, limiting the optimization of the engine hardware to the bowl geometry, but including the key air management and injection settings. For both studies, the simulation plans were defined following a Central Composite Design (CCD), providing 25 and 77 simulations respectively. The results confirmed the limited benefits, in terms of fuel consumption, around 2%, with constant NOx emission achieved when optimizing the engine hardware, while keeping air management and injection settings. Thus, including air management and injection settings in the optimization is mandatory to significantly decrease the fuel consumption, by around 5%, while keeping the emission limits.Benajes Calvo, JV.; Novella Rosa, R.; Pastor Enguídanos, JM.; Hernández-López, A.; Hasegawa, M.; Tsuji, N.; Emi, M.... (2016). Optimization of the Combustion System of a Medium Duty Direct Injection Diesel Engine by Combining CFD modeling with Experimental Validation. Energy Conversion and Management. 110:212-229. doi:10.1016/j.enconman.2015.12.010S21222911

extubation failure due to subglottic stenosis

Background : This report describes a case of dynamic inspiratory airway collapse concomitant with subglottic stenosis in a patient who previously underwent tracheostomy that led to repeated post-operative extubation failure. Case presentation : A 43-year-old woman who had undergone tracheostomy 25 years previously was admitted to our intensive-care unit (ICU) after coronary artery bypass graft surgery. On postoperative day (POD) 0, she was extubated, but stridor was observed. We suspected upper airway obstruction and she was therefore reintubated. Before reintubation, urgent laryngotracheoscopy revealed dynamic inspiratory airway collapse and obstruction concomitant with subglottic stenosis. Preoperative computed tomography showed mild subglottic stenosis. Although intravenous corticosteroids were administered to prevent tracheal mucosal edema and a cuff leak test was confirmed to be negative, she developed extubation failure on POD6. On POD12, we performed tracheostomy to reduce mechanical irritation from the endotracheal tube. Mechanical ventilation was withdrawn and she discharged from the ICU. On POD33, her tracheostomy tube was removed and she remained clinically asymptomatic. Conclusions : We should be aware of the history of tracheostomy, especially at high tracheostomy sites, even in the absence of respiratory symptoms as risk factors for dynamic inspiratory airway collapse concomitant with subglottic stenosis contributing to repeated respiratory failure after extubation

GABAergic neurons in the preoptic area send direct inhibitory projections to orexin neurons

Populations of neurons in the hypothalamic preoptic area (POA) fire rapidly during sleep, exhibiting sleep/waking state-dependent firing patterns that are the reciprocal of those observed in the arousal system. The majority of these preoptic "sleep-active" neurons contain the inhibitory neurotransmitter GABA. On the other hand, a population of neurons in the lateral hypothalamic area (LHA) contains orexins, which play an important role in the maintenance of wakefulness, and exhibit an excitatory influence on arousal-related neurons. It is important to know the anatomical and functional interactions between the POA sleep-active neurons and orexin neurons, both of which play important, but opposite roles in regulation of sleep/wakefulness states. In this study, we confirmed that specific pharmacogenetic stimulation of GABAergic neurons in the POA leads to an increase in the amount of non-rapid eye movement (NREM) sleep. We next examined direct connectivity between POA GABAergic neurons and orexin neurons using channelrhodopsin 2 (ChR2) as an anterograde tracer as well as an optogenetic tool. We expressed ChR2-eYFP selectively in GABAergic neurons in the POA by AAV-mediated gene transfer, and examined the projection sites of ChR2-eYFP-expressing axons, and the effect of optogenetic stimulation of ChR2-eYFP on the activity of orexin neurons. We found that these neurons send widespread projections to wakefulness-related areas in the hypothalamus and brain stem, including the LHA where these fibers make close appositions to orexin neurons. Optogenetic stimulation of these fibers resulted in rapid inhibition of orexin neurons. These observations suggest direct connectivity between POA GABAergic neurons and orexin neurons. © 2013 Saito, Tsujino, Hasegawa, Akashi, Abe, Mieda, Sakimura and Sakurai

Real-world clinical outcomes of nivolumab and taxane as a second- or later-line therapy for recurrent or unresectable advanced esophageal squamous cell carcinoma

BackgroundNivolumab is approved in Japan as a second-line treatment for patients with advanced esophageal squamous cell carcinoma (ESCC) resistant to fluoropyrimidine and platinum-based drugs. It is also used in adjuvant and primary postoperative therapies. This study aimed to report real-world data on nivolumab use for esophageal cancer treatment.MethodsIn total, 171 patients with recurrent or unresectable advanced ESCC who received nivolumab (n = 61) or taxane (n = 110) were included. We collected real-world data of patients treated with nivolumab as a second- or later-line therapy and evaluated treatment outcomes and safety.ResultsMedian overall survival was longer and progression-free survival (PFS) was significantly longer (p = 0.0172) in patients who received nivolumab than in patients who received taxane as a second- or later-line therapy. Furthermore, subgroup analysis for second-line treatment only showed the superiority of nivolumab in increasing the PFS rate (p = 0.0056). No serious adverse events were observed.ConclusionsIn real-world practice, nivolumab was safer and more effective than taxane in patients with ESCC with diverse clinical profiles who did not meet trial eligibility criteria, including those with poor Eastern Cooperative Oncology Group performance status, comorbidities, and receiving multiple treatments

Minimally Invasive Surgery for Giant Oesophageal and Gastric Leiomyomas

Herein, we describe a case of a 41-year-old woman with two giant leiomyomas located in the lower thoracic oesophagus and gastric cardia that were treated by minimally invasive thoracoscopic and laparoscopic surgery. We first resected the gastric cardia and laparoscopically prepared a gastric tube, and then we resected the lower thoracic oesophagus and intrathoracically anastomosed the oesophagus and gastric tube using thoracoscopic surgery with the patient in the prone position. Two concurrent giant leiomyomas of the oesophagus and stomach are rare, and the choice of surgical procedure to address the tumour from the mediastinum into the abdominal cavity was particularly challenging. We selected a minimally invasive thoracoscopic approach with the patient in the prone position. This strategy seems effective for resecting these giant tumours in the lower thoracic oesophagus and gastric cardia

Adult Intussusception Due to Endometriosis Arising from the Uterine Tube: Report of a Case

Introduction: Endometriosis is a rare cause of intussusceptions in adults. Although intestinal endometriosis sometimes arises as a consequence of direct involvement of the pelvic organs with endometrial tissue, there is no report that this type of endometriosis causes ileocecal intussusception. Case presentation: Computed tomography assessment of a 40-year-old woman who presented with abdominal pain revealed ileocecal intussusceptions. The patient was managed by endoscopic reduction followed by laparoscopic resection. Adhesion between the right uterine adnexa and caecum was identified during surgery; therefore, combined resection of the uterine adnexa and ileocecum was performed. Pathological findings revealed that endometriosis, arising from the uterine tube and directly involving the cecal wall, had caused the intussusceptions. Conclusion: Although rare, endometriosis should be considered as part of a differential diagnosis of intussusception in adult women who present with abdominal pain. A preoperative diagnosis is sometimes difficult, therefore, surgical resection could be a reasonable strategy to achieve a precise diagnosis

Targeted therapy against Bcl-2-related proteins in breast cancer cells

INTRODUCTION: Bcl-2 and Bcl-xL confer resistance to apoptosis, thereby reducing the effectiveness of chemotherapy. We examined the relationship between the expression of Bcl-2 and Bcl-xL and chemosensitivity of breast cancer cells, with the aim of developing specific targeted therapy. METHODS: Four human breast cancer cell lines were examined, and the effects of antisense (AS) Bcl-2 and AS Bcl-xL phosphorothioate oligodeoxynucleotides (ODNs) on chemosensitivity were tested in vitro and in vivo. Chemosensitivity was evaluated by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay, and the antitumor effect was assessed in vivo by the success of xenograft transplantation into athymic mice. RESULTS: Treatment with AS Bcl-2 and Bcl-xL ODNs resulted in a sequence-specific decrease in protein expression, compared with controls. Treatment of BT-474, ZR-75-1, and MDA-MB-231 cells with AS Bcl-2 increased chemosensitivity to doxorubicin (DOX), mitomycin C (MMC), paclitaxel (TXL), and docetaxel (TXT). Transfection of the Bcl-2 gene into MDA-MB-453 cells decreased sensitivity to DOX and MMC. Treatment of MDA-MB-231, BT-474, and ZR-75-1 cells with AS Bcl-xL increased chemosensitivity to DOX, MMC and taxanes to a smaller extent than AS Bcl-2. This occurred in the setting of increased Bax and cleaved poly(ADP-ribose) polymerase, as well as decreased Bcl-2 and pAkt. AS Bcl-2 ODNs induced splenomegaly in association with increased serum IL-12, which was attenuated by methylation of the CpG motifs of AS Bcl-2; however, methylated CpG failed to negate the increased antitumor effect of AS Bcl-2. Bcl-2 and Bcl-xL, to a smaller extent, are major determinants of chemosensitivity in breast cancer cells. CONCLUSION: Targeted therapy against Bcl-2 protein with the use of AS ODNs might enhance the effects of chemotherapy in patients with breast cancer

Successful management of pelvic recurrence of MSI-High endometrial cancer by total pelvic exenteration followed by administration of pembrolizumab:A case report

Surgery can be curative treatment for pelvic locoregional recurrence of endometrial cancer; however, a cure is contingent on complete resection. Here, we report the case of a patient in whom recurrent endometrial tumor remained in the pelvis after resection; long-term control was achieved with postoperative administration of pembrolizumab.The patient had recurrent endometrial cancer of stage IA and was treated with chemotherapy and radiation, but tumor persisted in the pelvic cavity. We therefore attempted total pelvic exenteration, but the tumor was adherent to the pelvic wall and complete resection could not be achieved. However, postoperative administration of pembrolizumab controlled the residual tumor for more than two years without regrowth. We believe that since the resected tumor was MSI-High, the residual tumor responded well to pembrolizumab. It is not known whether cytoreductive surgery contributes to a long-term response to pembrolizumab, but at least in our patient, pembrolizumab appeared to be a very effective drug therapy for MSI-High endometrial cancer that was refractory to chemotherapy and radiotherapy