Serum vascular endothelial growth factor predicts venous invasion in hepatocellular carcinoma: a prospective study

OBJECTIVE: To evaluate the correlation between serum vascular endothelial growth factor (VEGF) level and the clinicopathologic features in patients with hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: VEGF is an important angiogenic factor regulating tumor angiogenesis. A high serum VEGF level has been shown to be associated with tumor progression and metastasis in several human cancers, but its significance in HCC is unclear. The correlation between serum VEGF level and tumor pathologic features in patients with HCC has not been studied before. METHODS: Preoperative serum samples and tumor specimens were prospectively collected in 100 patients undergoing resection of HCC. Serum VEGF level was measured by enzyme-linked immunosorbent assay, and tumor VEGF expression was assessed by immunohistochemical study. Histopathologic examination was performed by a pathologist without prior knowledge of the serum VEGF level or tumor VEGF expression. RESULTS: Preoperative serum VEGF levels ranged from 15 to 1,789 pg/mL (median 269). When serum VEGF levels were compared between groups categorized by different clinicopathologic variables, significant correlation was found between a high serum VEGF level and absence of tumor capsule, presence of intrahepatic metastasis, presence of microscopic venous invasion, and advanced stage. There was a positive correlation between the serum VEGF level and tumor expression of VEGF as well as platelet count. When the 75th percentile serum VEGF level (500 pg/mL) was used as a cutoff level, the frequency of venous invasion in patients with a high serum VEGF level was significantly greater compared with patients with a low serum VEGF level. By multivariate analysis, a serum VEGF level of more than 500 pg/mL and tumor size more than 5 cm were independent preoperative factors predictive of microscopic venous invasion. During a median follow-up of 11.6 months, 48% of patients with a serum VEGF level of more than 500 pg/mL and 27% of those with a serum VEGF level of 500 pg/mL or less developed postoperative recurrence. CONCLUSIONS: These results show that a high preoperative serum VEGF level is a predictor of microscopic venous invasion in HCC, suggesting that the serum VEGF level may be useful as a biologic marker of tumor invasiveness and a prognostic factor in HCC.     

Dorzagliatin,a Dual-Acting Glucokinase Activator,Increases Insulin Secretion and Glucose Sensitivity in Glucokinase Maturity-Onset Diabetes of the Young and Recent-Onset Type 2 Diabetes

Glucokinase (GK, gene symbol GCK) maturity-onset diabetes of the young (MODY) is caused by heterozygous inactivating mutations in GK and impaired glucose sensing. We investigated effects of dorzagliatin, a novel allosteric GK activator, on insulin secretion rates (ISRs) and β-cell glucose sensitivity (βCGS) in GCK-MODY and recent-onset type 2 diabetes. In a double-blind, randomized, crossover study, 8 participants with GCK-MODY and 10 participants with type 2 diabetes underwent 2-h 12 mmol/L hyperglycemic clamps following a single oral dose of dorzagliatin 75 mg or matched placebo. Effects of dorzagliatin on wild-type and mutant GK enzyme activity were investigated using an NADP⁺-coupled assay with glucose-6-phosphate dehydrogenase in vitro. In GCK-MODY, dorzagliatin significantly increased absolute and incremental second-phase ISRs versus placebo but not the acute insulin response. Dorzagliatin improved βCGS in GCK-MODY with an upward and leftward shift in ISR-glucose response. Dorzagliatin increased basal ISRs in type 2 diabetes, with smaller changes in second-phase ISRs versus GCK-MODY. In vitro, dorzagliatin directly reduced the glucose half saturation concentration of wild-type GK and selected GK mutants to varying degrees. Dorzagliatin directly restored enzyme activity of select GK mutants and enhanced wild-type GK activity, thereby correcting the primary defect of glucose sensing in GCK-MODY.     

Monitoring of the neonate undergoing MR imaging: technical considerations. Work in progress

Instrument monitoring of vital signs in neonates undergoing magnetic resonance (MR) imaging can be difficult because of the unique environmental restrictions imposed by the imager. The authors present their experience with monitoring more than 50 newborn infants and discuss the interaction of monitoring devices with the MR imager. Several MR-compatible monitors allow continuous evaluation of body temperature, heart rate, blood pressure, and auscultation of heart sounds and respiration in mechanically ventilated infants. Signal-to-noise (S/N) ratio measurements taken during imaging of the head of an infant with these monitors in place did not differ appreciably from the ratio obtained during imaging without monitors. Tip angles should be optimized to account for widely varying head size among neonates, since adverse monitoring effects are significantly compounded by improper tip angle adjustment.     

Nasopharyngeal carcinoma in young patients

Seventy-one Chinese patients ranging in age from 9 to 20 years who had histologically verified nasopharyngeal carcinoma were reviewed. The presenting symptoms were often multiple, comprising nasal (77.5%) and ear (73.2%) symptoms, headache (60.6%), and neck swelling (63.4%). The median duration of these symptoms was 2 to 3 months, and 90.1% of the patients were Stage III or IV at presentation. All patients were treated primarily by radiotherapy. Forty-four of the 71 patients died of the disease; the median time to death was 18 months. Nasopharyngeal carcinoma in the young patients in Hong Kong does not appear to be different from that of the adult population in Hong Kong in terms of histology, pattern of relapse, and survival. Compared with the adult patients, however, the current series of young patients presented with more advanced-staged disease. The incidence of nasopharyngeal carcinoma in Hong Kong was compared with Chinese populations in other parts of the world, and the general pattern was comparable. The only postadolescent peak was found in the Chinese population of San Francisco.     

CT features of primary cerebral lymphoma in AIDS and non-AIDS patients

Computed tomographic study of six cases with primary cerebral non-Hodgkin lymphoma are reviewed. Three had a history of intravenous drug abuse and were diagnosed as having acquired immunodeficiency syndrome (AIDS). All cases presented with space occupying lesions in the frontal lobe with the exception of Case 4. Computed tomography demonstrated multiple lesions in AIDS cases whereas non-AIDS lesions were invariably single. The AIDS patients died within 1 year despite radiotherapy as compared with the non-AIDS patients.     

A prospective randomized study of abdominal rectopexy with and without sigmoidectomy in rectal prolapse.

Eighteen patients with full-thickness prolapse of the rectum were randomized to rectopexy alone (group 1) or with sigmoidectomy (group 2). Three months postoperatively, seven patients in group 1 and two in group 2 complained of severe constipation. One patient in group 1 and three patients in group 2 remained incontinent. The results of colonic marker studies showed a significant increase in the number of markers at day 5 for those in group 1 (preoperative, 7.7 +/- 2.6; postoperative, 14.6 +/- 2.2; t test, p less than 00.1) but no significant increase in group 2 (preoperative, 4.6 +/- 2.2; postoperative 6.8 +/- 2.3; t test, p less than 0.01). No significant changes or differences between the groups were seen in the anorectal angle on videoproctogram. The results of anorectal physiologic studies done postoperatively showed no differences between the groups in maximum resting pressure, sphincter length or saline solution infusion test; however, the patients in group 1 had a significantly greater rectal compliance (group 1, 0.24 +/- 0.02 millimeters mercury per milliliter; group 2, 0.1 +/- 0.02 millimeters mercury per milliliter; p less than 00.1). This may occur because the redundant loop of sigmoid colon causes hold-up of intestinal content and kinking at the junction between the sigmoid colon and the rectum.     

Cutaneous stimulation improves function of a chronic patient with cerebellar damage

The prognosis of cerebellar hemorrhage with brain stem compression is known to be poor, and patients who can usually survive are severely disabled with limited benefit from conventional rehabilitation. An innovative cutaneous stimulation was administered to a chronic patient (2 years after the incidence) who has severe ataxia, gait imbalance and limb spasticity caused by cerebellar hemorrhage. After 8 months of intervention, patient's function as evaluated by two functional measures has improved by 40%. In addition, the patient's ataxia and hypotonia have improved significantly in which he has regained the abilities to grasp objects, sit upright, control his equilibrium, and monitor an electric wheelchair. The present case study demonstrated a significant improvement of a chronic severely disabled patient who received the intervention 2 years after the accident, suggesting that the cutaneous stimulation may be a possible effective neurologic intervention.     

Operative choledochoscopy in patients with acute cholangitis: a prospective, randomized study

A prospective, randomized evaluation of operative choledochoscopy was carried out during emergency surgery in patients with acute cholangitis or acute suppurative cholangitis when conservative management had failed. After common bile duct exploration, 79 patients were randomized to have choledochoscopy and 78 patients to the control group. Laboratory and clinical parameters showed that choledochoscopy did not increase the incidence of septicaemia, acute pancreatitis, persistent cholangitis, postoperative wound sepsis, intraperitoneal sepsis and hospital mortality. The incidence of retained common bile duct stones detected by T tube cholangiography performed in the second postoperative week was significantly reduced (P less than 0.01) after choledochoscopy. Choledochoscopy detected stones missed by conventional common bile duct exploration in ten patients. It is concluded that choledochoscopy is a safe and effective technique in patients with acute cholangitis and acute suppurative cholangitis.