Cytopathologic characteristics and differential diagnostic considerations of osteolytic myxopapillary ependymoma

Myxopapillary ependymoma (MPE) is a rare variant of conventional ependymoma found predominantly in the sacrococcygeal region in young adults and characterized by its distinct epithelial and stromal components (WHO grade I designation). MPE with extensive osteolysis is extremely uncommon and only up to 40 cases have been documented. A case is presented here in which imprint smears of a sacral tumor in an 18‐year‐old man revealed complex papillary structures, small loose clusters, or cord‐like structures of bland tumor cells embedded in a myxoid or mucinous background. The tumor cells possessed uniformly round nuclei with a smooth nuclear outline, fine granular chromatin, and small nucleoli. Slender cytoplasmic fibrillary processes and occasional intracytoplasmic vacuoles were observed. A cytologic diagnosis of a MPE was suggested and histochemical and immunohistochemical studies were conducted on formalin‐fixed, paraffin‐embedded material. Immunohistochemically, the tumor cells showed diffuse and strong membranous and cytoplasmic staining for cytokeratin AE1/AE3, glial fibrillary protein, and S‐100 protein, but negative for epithelial membrane antigen, pan‐neuroendocrine markers (i.e., NSE, chromogranin A, synaptophysin), or brachyury. The proliferative index with MIB‐1 was around 10%. The diagnosis of osteolytic MPE was confirmed based on cytopathologic, histopathological, immunohistochemical results, radiologic findings, and the location of the tumor. We demonstrated here the cytopathological features of osteolytic MPE with emphasis on differential diagnostic considerations. Diagn. Cytopathol. 2014;42:778–783. © 2013 Wiley Periodicals, Inc.     

A new spray-type adhesion barrier (AdSpray) improves condition for surgical treatment in the reversal of Hartmann procedure: A case report

Rationale:Hartmann procedure (HP) often causes severe postoperative adhesions in the pelvic space; therefore, the reversal of Hartmann procedure (RHP) is a challenging surgery. A new spray-type antiadhesion agent, AdSpray, has been reported to be useful in three-dimensional fields such as the liver. However, there are no reports of its use in HP. We present a case of a male patient with rectal cancer who underwent laparoscopic HP with AdSpray to prevent postoperative adhesions.Patient concerns:A 52-year-old man presented with melena and constipation.Diagnosis:Colonoscopy revealed an almost obstructive type II tumor at the rectosigmoid colon, and histopathological examination revealed moderately differentiated adenocarcinoma. Enhanced abdominal computed tomography revealed slightly enlarged regional lymph nodes but no ascites around the tumor, and there was no metastasis to the liver or lungs. Therefore, we diagnosed clinical stage T4aN1bM0 rectosigmoid colon cancer. Intraoperatively, a metastatic tumor of the liver surface and a high degree of valve retention in the oral colon were identified.Interventions:After performing laparoscopic HP with AdSpray, we scheduled a laparoscopic RHP with staged hepatic surgery for synchronous liver metastasis from colorectal cancer 1 month later.Outcomes:No postoperative inflammatory adhesions were observed in the pelvis or around the rectal stump, allowing us to perform RHP by a single-incision laparoscopic surgery from the stoma site without any problem. The operation time for RHP was 80 minutes; the patient was in good general condition after the operation, and he was discharged on postoperative day 7.Lessons:In laparoscopic HP, Adspray was easy to use for three-dimensional fields such as the pelvis and effectively prevented postoperative inflammatory adhesions. Thus, RHP may become less risky and be performed more as a minimally invasive surgery.     

Non–clinical efficacy,safety and stable clinical cell processing of induced pluripotent stem cell‐derived anti–glypican‐3 chimeric antigen receptor‐expressing natural killer/innate lymphoid cells

The use of allogeneic, pluripotent stem‐cell‐derived immune cells for cancer immunotherapy has been the subject of recent clinical trials. In Japan, investigator‐initiated clinical trials will soon begin for ovarian cancer treatment using human leukocyte antigen (HLA)‐homozygous‐induced pluripotent stem cell (iPSC)‐derived anti–glypican‐3 (GPC3) chimeric antigen receptor (CAR)‐expressing natural killer/innate lymphoid cells (NK/ILC). Using pluripotent stem cells as the source for allogeneic immune cells facilitates stringent quality control of the final product, in terms of efficacy, safety and producibility. In this paper, we describe our methods for the stable, feeder‐free production of CAR‐expressing NK/ILC cells from CAR‐transduced iPSC with clinically relevant scale and materials. The average number of cells that could be differentiated from 1.8‐3.6 × 10⁶ iPSC within 7 weeks was 1.8‐4.0 × 10⁹. These cells showed stable CD45/CD7/CAR expression, effector functions of cytotoxicity and interferon gamma (IFN‐γ) production against GPC3‐expressing tumor cells. When the CAR‐NK/ILC cells were injected into a GPC3‐positive, ovarian‐tumor‐bearing, immunodeficient mouse model, we observed a significant therapeutic effect that prolonged the survival of the animals. When the cells were injected into immunodeficient mice during non–clinical safety tests, no acute systemic toxicity or tumorigenicity of the final product or residual iPSC was observed. In addition, our test results for the CAR‐NK/ILC cells generated with clinical manufacturing standards are encouraging, and these methods should accelerate the development of allogeneic pluripotent stem cell‐based immune cell cancer therapies.     

The impact of visceral obesity on surgical outcomes of laparoscopic surgery for colon cancer

Purpose

Although obesity is considered as a risk factor for postoperative morbidity in abdominal surgery, its effect on the outcomes of laparoscopic-assisted colectomy (LAC) is still unclear. The technical difficulty and risk factor for postoperative complication in LAC are thought to be influenced by visceral obesity. The aim of this prospective study was to evaluate the impact of visceral fat on the surgical outcomes of LAC.

Methods

Between April 2005 and December 2010, consecutive patients with preoperatively diagnosed colon cancer, excluding medium and low rectal cancer, who underwent LAC, were enrolled. Their visceral fat area (VFA) and body mass index (BMI) were prospectively collected. The VFA was assessed by Fat Scan software. The patients were classified into two groups as follows: VFA nonobese with VFA <100 cm² (VNO) and VFA obese with VFA ≧100 cm² (VO). The predictive factors for surgical complications of LAC were evaluated by univariate and logistic regression analyses.

Results

A total of 338 consecutive patients were enrolled in this study. Of the 338 patients, 194 (57.4 %) and 138 (42.6 %) were classified into the VNO and VO groups, respectively. Logistic regression analysis showed that high BMI (≧25 kg/m²) and VO independently predicted the incidence of overall postoperative complications (p?=?0.040 and 0.007, respectively). VO was more highly related to the incidence of overall postoperative complications, anastomotic leakage (p?=?0.021), and surgical site infection (SSI) (p?=?0.013) than high BMI.

Conclusions

VFA is a more useful parameter than BMI in predicting surgical outcomes after LAC.     

Clinical analysis of the patients with hemodialysis associated with intracerebral hematoma

We treated 64 hemodialysis patients with cerebral hemorrhage over an 18-year period between 1986 and 2003. Clinical features, prognostic factors, and therapeutic strategy were reviewed in these cases. Thirty of the cases were in the 13-year period between 1986 and 1998, and 34 cases, in the 5-year period between 1999 and 2003. In recent years, the incidence of cerebral hemorrhage has risen with the increase in the number of hemodialysis patients. There were 21 patients with at least a 10-year history of hemodialysis. The underlying cause of renal failure was diabetic nephropathy in 25 patients and glomerulonephritis in 24 patients. The most frequent sites of bleeding were the basal ganglia and thalamus, the cerebellum being involved in only one patient. Many patients had severe bleeding with hematomas greater than 61 ml. Outcome assessment by the Glasgow Outcome Scale showed 24 patients with good recovery, 8 with moderate disability, 4 with severe disability, and 28 who died. Good recovery was seen more often in patients in their 50s and 60s, whereas death occurred more often in patients aged 70 and older. Although there is now less morbidity than previously, the prognosis is not uniformly favorable in all cases. Factors associated with a poorer prognosis included mixed hemorrhage, hematomas greater than 61 ml, and age 70 and older. Hematoma size and age were particularly important prognostic factors. Improved management and prognosis in these patients requires acute intensive treatment similar to that for hypertensive cerebral hemorrhage.     

Elevated Von Willebrand factor propeptide for the diagnosis of thrombotic microangiopathy and for predicting a poor outcome

Thrombotic microangiopathy (TMA) is associated with vascular endothelial cell injury and is sometimes linked with poor outcome. Von Willebrand factor (VWF) propeptide (VWFpp) is considered to be a marker of vascular endothelial cell injury. The plasma levels of VWF, VWFpp, and thrombomodulin (TM) were evaluated for their use in the diagnosis of TMA in 75 patients with TMA. There were 30 TMA patients with marked decreases in ADAMTS13 (TMA/ADAMTS13) and 45 without the decrease (TMA/other). The plasma levels of TM, VWF, and VWFpp values were significantly high in patients with TMA, especially TMA/other group. The plasma levels of TM and VWFpp were significantly high in non-survivor with TMA. In the TMA/other group, the plasma levels of VWFpp were negatively correlated with ADAMTS13 activity. The plasma levels of TM correlated with the renal function, but the plasma levels of VWFpp did not. A ROC analysis indicated that VWFpp and TM were useful markers for the prediction of a poor outcome. These findings suggest that VWFpp is an useful marker for the diagnosis of TMA and for the prediction of poor outcome.     

Leg Muscle Strength Correlates with Gait Performance in Advanced Parkinson Disease

Objective Leg muscle strength (LMS) is decreased in early-stage Parkinson disease (PD) patients and is associated with slower walking and falls. However, LMS in advanced PD has not been well investigated. The purpose of this study was to evaluate LMS in advanced PD patients and its effects on gait performance, activities of daily living, and the cognitive function. Methods The medical records of 132 patients with idiopathic advanced PD [Hoehn and Yahr (H&Y) stages 3 and 4] with a mean disease duration of 9.6 years were retrospectively reviewed. Leg extensor muscle strength of the patients was measured using a Strength Ergo 240. The associations between the LMS and gait performance, Barthel index, H&Y stage, and Mini-Mental State Examination (MMSE) score were analyzed. Results A Spearman''s correlation analysis showed that LMS was correlated with the sex, age, age of disease onset, H&Y stage, Barthel index, MMSE score, and gait parameters. A multivariable linear regression analysis for identifying predictors of LMS showed that the gait velocity (β=0.377), Barthel index (β=0.281), sex (β=-0.187), and disease duration (β=-0.155) were significant. A receiver operating characteristic curve analysis for discriminating between H&Y stage 3 and 4 was performed for LMS; the area under the curve was 0.774 (95% confidence interval=0.696-0.851). Conclusions LMS was strongly associated with multiple domains of clinical characteristics, especially gait velocity and the Barthel index. Our study also suggested that LMS can be a predictor of PD progression.