Tumor Necrosis Rate Adjusted by Tumor Volume Change Is a Better Predictor of Survival of Localized Osteosarcoma Patients

Background We assessed whether new parameter that considers both tumor volume change and necrosis rate predicts metastasis-free survival of localized osteosarcoma patients. We also evaluated relationship between tumor volume change and necrosis rate or metastasis-free survival. Methods We retrospectively reviewed 151 patients with stage II osteosarcoma who were treated with surgery and neoadjuvant chemotherapy. The tumor volume change was measured and calculated based on pre- and postchemotherapy magnetic resonance images. The mean metastasis-free interval was 83.1 months. We calculated adjusted tumor necrosis rate as following formula: 100–(100–necrosis rate) × postchemotherapy/prechemotherapy tumor volume. Survival and logistic regression analyses were used to evaluate the correlation among size parameters, tumor necrosis rate and survival. Results The 5-year metastasis-free survival rate of 151 patients was 71.4% (95% CI, 67.7–75.1%). American Joint Committee on Cancer (AJCC) stage IIB (RR 2.27; 95% CI, 1.11–4.62; P = 0.025) and poor adjusted tumor necrosis rate (RR 2.02; 95% CI, 1.05–3.89; P = 0.035) independently correlated with metastasis-free survival period. Further, tumor volume change independently correlated with necrosis rate. Decreased tumor volume could predict good response, with sensitivity of 80.2%, specificity of 68.6%, and positive predictive value (PPV) of 74.7%. Increased or stable tumor volume could predict poor response, with sensitivity of 68.6%, specificity of 80.2%, and PPV of 75.0 %. Conclusion The necrosis rate adjusted by the tumor volume change is an independent prognostic factor in osteosarcoma. This adjusted tumor necrosis rate may serve as a basis for risk-adapted therapy in combination with other prognostic factors.     

The determination of sensation-dependent bladder emptying time in patients with complete spinal cord injury above T11

STUDY DESIGN: Retrospective investigation using urodynamic studies and medical records. OBJECTIVE: To evaluate the safety of sensation-dependent bladder emptying in complete spinal cord injury (SCI) patients, based on the preservation of the desire to void. SETTING: Spinal Cord Injury Unit, Yonsei Rehabilitation Hospital, Seoul, Korea. METHODS: This study was performed retrospectively on 79 complete SCI patients with lesions above T11, who had preserved the desire to void during conventional urodynamic studies. Patients were classified according to detrusor compliance and maximal bladder capacity. The clinical and urodynamic characteristics of each group were analyzed. RESULTS: Forty-five (57.0%) patients were classified as group A and 34 (43.0%) patients were classified as group B. There were no significant differences in clinical features, such as voiding methods and the presence of autonomic dysreflexia between the two groups. Compared with group B, there were significantly more areflexic neurogenic bladder cases in group A (P<0.05). There were significantly higher maximal detrusor pressures in group B (P<0.05). There were significantly more cases with the preservation of the strong desire to void in group B (P<0.05). CONCLUSION: Not all patients with discomplete SCIs accepted the use of sensation-dependent bladder emptying. The safe use of sensation-dependent bladder emptying will be determined based on the results of urodynamic studies.     

Dysfunction in configural face processing in patients with schizophrenia

BACKGROUND: Face recognition has important implications for patients with schizophrenia, who exhibit poor interpersonal and social skills. Previous reports have suggested that patients with schizophrenia have deficits in their ability to recognize faces, and because face recognition relies heavily on information about the configuration of faces, we hypothesized that patients with schizophrenia would have specific problems in processing configural information. METHODS: We measured the performance of 20 patients with schizophrenia and 20 normal subjects in a face-discrimination task, using upright and inverted pairs of face photographs that differed in featural or configural information. RESULTS: The patients with schizophrenia showed disproportionately poorer performance in discriminating configural compared with featural face sets. CONCLUSION: The result suggests that the face-recognition deficit in schizophrenic patients is due to specific impairments in configural processing of faces.     

Deficit of theory of mind in individuals at ultra-high-risk for schizophrenia

BACKGROUND: Although a deficit in social cognition is regarded as an early indicator of schizophrenia, few studies have investigated social cognition in ultra-high-risk (UHR) individuals. METHODS: Our investigation involved subjects at UHR for psychosis (N=33) and an age- and IQ-matched healthy control (HC) group (N=36). Two types of theory of mind (ToM) tasks and a neuropsychological test battery were measured. RESULTS: Compared to the HC group, the UHR group performed significantly worse for ToM tasks, with the effect size at an intermediate level (0.64-0.68). Furthermore, the UHR group showed impaired performance in the executive and working memory tests, but not verbal memory tests. These deficits for ToM tests observed in the UHR group were significantly correlated with set-shifting tasks. CONCLUSIONS: Deficits in social cognition may be modest at the prodromal stage of schizophrenia and may be attributed to prefrontal dysfunction. To prevent or delay transition to psychosis, there is a need for specific preventive strategies targeting social functioning for the UHR group.     

Medical comorbidities predict the need for colectomy for complicated and recurrent diverticulitis

Objective

The objective of this study was to identify risk factors for recurrent or complicated diverticulitis requiring colectomy.

Methods

A total of 112 patients were admitted to the West Haven Veterans Affairs Medical Center with the diagnosis of colonic diverticular disease from January 1998 to December 2006. Patients' records were assessed for demographics, past medical history, and physical and biochemical features of presentation. Student t tests, analysis of variance, and chi-square analysis were used to compare binary and categoric data.

Results

The medical records of 112 patients admitted to the West Haven Veterans Affairs hospital with the diagnosis of diverticulitis were analyzed retrospectively. A total of 97.3% were male (n = 109), with a mean age of 63.3 years, and a significant smoking history greater than 30 pack-years was present in 70.5% (n = 79) of patients. Eighty-four percent (n = 94) of patients presented with localized abdominal pain and 69.6% (n = 78) had abdominal tenderness without peritoneal signs. Computed tomography was performed in 85.7% (n = 96) of cases. A total of 23.2% (n = 26) of patients proceeded to laparotomy, with free perforation being the most common indication (38.4%, n = 12) followed by a history of 2 or more antecedent attacks of diverticulitis (23.1%, n = 6). Analysis of variance showed that serum albumin levels were significantly lower in the group undergoing colectomy compared with those who did not (3.4 vs 4.1 mg/dL; P = .016). The need for colectomy owing to complicated or recurrent attacks correlated with glucocorticoid use (P < .001) and a history of chronic obstructive pulmonary disease (P < .038), but not with diabetes mellitus, collagen vascular disease, or inflammatory bowel disease.

Conclusions

The rules regarding the treatment of diverticulitis are evolving. Comorbid conditions such as hypoalbuminemia, chronic obstructive pulmonary disease, and glucocorticoid use may predispose patients to recurrent or complicated attacks of diverticulitis requiring colectomy. Stratification and reduction of risks may reduce the overall morbidity and mortality of diverticulitis.     

Identification of mitochondrial FoF1-ATP synthase involved in liver metastasis of colorectal cancer

Liver metastasis is a major cause of poor survival of colorectal cancer patients. In order to identify the proteins associated with liver metastasis in colorectal cancer, we carried out two-dimensional gel electrophoresis-based comparative proteomic analysis of normal colon mucosa, primary colon cancer tissue and corresponding metastatic tumor tissue in liver. The proteins identified were further validated by immunohistochemical analysis of 67 quadruplet samples of normal colon primary colorectal cancer and normal liver-synchronous liver metastasis, and 251 colorectal cancers as well as in vitro invasion assay of the human colon cancer cell line, SNU-81. From proteomic assessment, the mitochondrial FoF1-ATP synthase (ATP synthase) alpha-subunit was identified as a protein that is upregulated in liver metastasis compared with the primary tumor. Immunohistochemical analyses confirmed a significant increase in the expression of ATP synthase alpha- and d-subunits in synchronous liver metastasis compared with primary tumor and normal mucosa, respectively. ATP synthase alpha- and d-subunits were overexpressed in 197 (78.5%) and 190 (75.7%), respectively, of the 251 colorectal cancers. The alpha- and d-subunits were significantly associated with liver metastasis (P < 0.05) as well as low histological grade (P < 0.0001). The d-subunit also correlated with venous invasion (P = 0.026) and distant metastasis (P = 0.032). In stage III cancers, d-subunit expression was independently associated with poor survival (P = 0.017). Furthermore, transfection of small interfering RNA targeted to ATP synthase alpha- and d-subunits resulted in decreased in vitro invasiveness of the human colon cancer cell line. Our overall findings demonstrate that increased ATP synthase is associated with liver metastasis of colorectal cancer.     

Differential expression of ribosomal proteins in a human metastasis model identified by coupling 2-D liquid chromatography and mass spectrometry

BACKGROUND: Proteomic profiling of an experimental tumor metastasis model has the potential to identify gene products that can influence this fatal phenotype of tumor cells. In this study, we focused on the notoriously difficult to assess ribosomal protein component of a pair of cell lines which originate from the same tumor but have opposite metastatic capabilities. MATERIALS AND METHODS: Cell lysate proteins were separated using a two-dimensional liquid chromatographic system directly coupled to an ESI-TOF mass spectrometer for accurate intact protein MW analysis. Characterization of distinct post-translational modifications and sequence variation within several ribosomal proteins was obtained using monolithic capillary LC/MS/MS, MALDI-MS and -MS/MS. RESULTS: The combination of these techniques enabled the identification of 45 unique ribosomal proteins, several of which were differentially expressed in metastatic M4A4 cells. CONCLUSION: The described proteomic profiling approach enables the identification of phenotype-associated ribosomal proteins for subsequent functional analyses and disease biomarker development.     

Activation of the renin-angiotensin system within podocytes in diabetes

The autocrine and paracrine activation of the renin-angiotensin system (RAS) within cells of the kidney plays a role in the overall pathophysiology of the renal disease due to diabetes. In this study, we focus on components of the RAS in the podocyte as these cells are important in the pathogenesis of glomerulosclerosis and proteinuria. Immortalized mouse podocytes were exposed to media containing normal glucose (NG) or high glucose (HG) for in vitro studies. In vivo studies utilized kidney tissue obtained from rats treated for 3 months with streptozotocin to induce diabetes. Angiotensinogen (AGT) and the angiotensin II (AII) type 1 receptor mRNA and protein were significantly increased in the podocytes cultured under the high glucose conditions. Both angiotensins I and II levels were significantly higher in cell lysates and the conditioned media of cells grown in high glucose. There were no differences in renin activity, angiotensin-converting enzyme level, or AII type 2 receptor level. Glomerular AGT and AII type 1 receptor assessed by means of immunohistochemistry were increased in diabetic rats compared with the control rats. Other measured components of the RAS within the glomeruli were not different. We suggest that increased AGT, an attendant increase in AII and increased AII type 1 receptor in podocytes experiencing diabetic conditions play an important role in the pathogenesis of diabetic nephropathy.