Prognostic Significance of VEGF Expression in Correlation With COX-2, Microvessel Density,and Clinicopathological Characteristics in Human Gastric Carcinoma

Background Many studies have shown that angiogenesis plays an important role in the process of cancer development and progression. Vascular endothelial growth factor (VEGF) has a potent angiogenic activity, and cyclooxygenase-2 (COX-2) supports angiogenesis by regulated production of angiogenic factors, including VEGF. The purpose of this study was to examine the expression of VEGF in combination with COX-2 and CD34, their correlation with various clinicopathological factors, and their prognostic significance in human gastric carcinoma. Methods Specimens from 169 patients with different grade and stage gastric carcinoma were investigated by immunohistochemistry for COX-2 and VEGF expression. Tumor microvessel density was assessed with CD34 immunostaining. Correlations between the expression of VEGF, COX-2, CD34, and various clinicopathological factors were studied. The effect of these proteins on patient survival was determined. Results COX-2 and VEGF were positively expressed in 36.7% and 50.3% of the patients, respectively. Positive correlation was found between VEGF and COX-2 and between VEGF and CD34. VEGF expression was correlated with depth of invasion; metastatic lymph nodes; lymphatic and venous invasion; and tumor, node, metastasis system stage. Patients with positive staining for VEGF showed far lower disease-free (64.9% vs. 81.3%) and overall (58.3% vs. 76.9%) survival rates than VEGF-negative patients. In multivariate analysis, only tumor location, depth of invasion, and lymph node metastasis were shown to be independent prognostic factors. Conclusions VEGF expression correlates with angiogenesis and tumor progression and is a valuable prognostic factor in patients with gastric carcinoma.     

Intraoperative Touch Preparation Cytology for Margin Assessment in Breast-Conservation Surgery: Does It Work for Lobular Carcinoma?

Background Breast carcinoma is the most frequently diagnosed malignancy in women of the North America. The combination of breast-conservation surgery and radiotherapy has become a standard of treatment for most breast cancers. It is critical to obtain clear margins to minimize local recurrence. The literature suggests that intraoperative touch preparation cytology (IOTPC) can be useful in evaluation of margins. Invasive lobular carcinoma (ILC) accounts for 10% to 15% of all breast cancers. Obtaining clear margins in ILC can be more challenging. Literature shows the positive margin rate for ILC to be as high as 60%. This report describes our experience with IOTPC for margin assessment in ILC by a single surgeon at Beth Israel Medical Center. The purpose of this study is to determine whether IOTPC is reliable for ILC. Methods A prospective review of 73 patients who underwent breast-conservation surgery with the use of IOTPC for margin assessment at Beth Israel Medical Center was performed. Pathology revealed ILC in 12 of these patients (16.4%), who are the subjects of this study. The lumpectomy specimens were oriented by the surgeon intraoperatively and were submitted fresh to pathology for cytologic assessment. IOTPC consisted of touching the corresponding margin onto the glass slide. The principle of this technique is that if cancer cells are present, they will stick to the slide, whereas fat cells will not. Six slides were prepared for each lumpectomy specimen. Air-dried samples were stained immediately by the Diff-Quik method and examined under the microscope by a cytopathologist. Results Twelve patients with ILC underwent breast-conservation surgery with IOTPC for assessment of 72 margins. Ten patients had lobular carcinoma only, and the remaining two patients had a combination of lobular and ductal carcinoma. There was a correlation between IOTPC and final pathology in 60 of 72 margins, which accounted for 83.3% of the cases. IOTPC for assessment of margins in patients undergoing breast-conservation surgery for ILC has a sensitivity of 8.3%, specificity of 98.3%, positive predictive value of 50%, and negative predictive value of 84.3%. Conclusions On the basis of our experience, IOTPC is of limited value for intraoperative assessment of margins for ILC. Poster presentation at the Sixth Annual Meeting of the American Society of Breast Surgeons, March 16–20, 2005, Los Angeles, California.     

Peripheral Arterial Occlusive Disease: Magnetic Resonance Imaging and the Role of Aggressive Medical Management

Atherosclerosis accounts for most peripheral arterial occlusive disease (PAD). Although many of the risk factors for atherosclerotic coronary artery disease (CAD) such as hyperlipidemia have been identified as risk factors for peripheral arterial disease, strong evidence is lacking that risk factor modification is effective in halting progression or improving outcomes. A better understanding is needed regarding the clinical and pathophysiologic responses to risk factor modification. This review describes current advances in the medical management for PAD including lipid modification antiplatelet therapy, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, exercise, and endovascular intervention. In addition, we discuss our active ELIMIT Trial (Effect of Lipid Modification on Peripheral Arterial Disease after Endovascular Intervention). We test the hypothesis that an aggressive regimen of serum lipid modification will inhibit the progression of atherosclerosis in femoral arteries and reduce the incidence of restenosis of femoral arteries following endovascular stenting by decreasing thrombosis and inflammation. This study will provide a novel strategy for retarding or preventing progression of atherosclerosis and re-stenosis of peripheral arterial disease following arterial revascularization procedures. Importantly, our magnetic resonance imaging studies will provide quantitative data on the vascular lesions in PAD. These studies will advance our understanding of the molecular mechanisms of inflammation and thrombosis associated with aggressive lipid modification. This work was presented at the Molecular Surgeon Symposium on Vascular Injury, Repair and Remodeling at the Baylor College of Medicine, Houston, Texas, May 15 and 16, 2006. The symposium was supported by a grant from the National Institutes of Health National Institute of Health (to C. Chen: R13 HL0836500).     

Quantitative Monitoring of Extracellular Matrix Production in Bone Implants by <Superscript>13</Superscript>C and <Superscript>31</Superscript>P Solid-State Nuclear Magnetic Resonance Spectroscopy

We used ³¹P and ¹³C solid-state nuclear magnetic resonance (NMR) spectroscopy to detect and analyze the major organic and inorganic components (collagen type I and bioapatite) in natural rabbit bone and β-tricalcium phosphate implants loaded with osteogenically differentiated mesenchymal stem cells. High-resolution solid-state NMR spectra were obtained using the magic-angle spinning (MAS) technique. The ³¹P NMR spectra of bone specimens showed a single line characteristic of bone calcium phosphate. ¹³C cross-polarization (CP) MAS NMR spectra of bone exhibited the characteristic signatures of collagen type I with good resolution for all major amino acids in collagen. Quantitative measurements of ¹³C-¹H dipolar couplings indicated that the collagen segments are very rigid, undergoing only small amplitude fluctuations with correlation times in the nanosecond range. In contrast, directly polarized ¹³C MAS NMR spectra of rabbit bone were dominated by signals of highly mobile triglycerides. These quantitative investigations of natural bone may provide the basis for a quality control of various osteoinductive bone substitutes. We studied the formation of extracellular bone matrix in artificial mesenchymal stem cell-loaded β-tricalcium phosphate matrices that were implanted into the femoral condyle of rabbits. The NMR spectra of these bone grafts were acquired 3 months after implantation. In the ³¹P NMR spectra, β-tricalcium phosphate and bone calcium phosphate could be distinguished quantitatively, allowing recording of the formation of the natural bone matrix. Further, ¹³C CPMAS allowed detection of collagen type I that had been produced in the implants. Comparison with the spectroscopic data from natural bone allowed assessment of the quality of the bone substitute material. J. S. and M. P. contributed equally to this study     

Role of Fibrin Glue as a Sealant to Esophageal Anastomosis in Cases of Congenital Esophageal Atresia with Tracheoesophageal Fistula

Objective The aim of this study was to characterize a successful approach for the management of infants with long-gap esophageal atresia (EA) with tracheoesophageal fistula (TEF). The goal was to preserve the native esophagus and minimize the incidence of esophageal anastomotic leaks using fibrin glue as a sealant over the esophageal anastomosis. Method A total of 52 patients were evaluated in this study. Only patients in whom, gap between the two ends of the esophagus was ≥ 2 cm were selected during January 2005 to January 2007. Patients were divided in two groups on the basis of block randomization. Group A comprised the patients in whom fibrin sealant was used as reinforcement on a primary end-to-end esophageal anastomosis; in group B, fibrin glue was not used. The two groups were compared in terms of esophageal anastomotic leak (EL), postoperative esophageal stricture (ES), and mortality. The statistical analysis was done using Fisher’s exact test and the chi-squared test. Result The number of anastomotic leaks in group A (glue group) was about one-fifth that in group B (no glue group). The incidence of ES was almost twice as high in group B as in group A. The mortality rate was almost threefold higher in group B (no-glue group). The higher incidence of EL and ES in group B compared to group A was statistically significant. Conclusion Thus, fibrin glue when used as an adjunct to esophageal anastomosis for primary repair of long-gap EA with TEF appears safe in the clinical setting and may lower the chances of esophageal leak and anastomosis-site strictures. Hence, it can diminish the mortality and morbidity of these patients.     

Optimization of Hyperthermic Intraperitoneal Chemotherapy With Oxaliplatin Plus Irinotecan at 43°C After Compete Cytoreductive Surgery: Mortality and Morbidity in 106 Consecutive Patients

Background Peritoneal carcinomatosis (PC), which has hitherto been regarded as a lethal entity, can now be cured with surgery (treating macroscopic tumor seeding) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) (treating residual microscopic disease). The purpose of this study was to analyze the morbidity and mortality of a particular approach associating optimal (R0–R1) cytoreduction, optimal HIPEC combining oxaliplatin and irinotecan, and an optimal homogeneous intraperitoneal temperature of 43°C. Methods A total of 106 consecutive patients were included in this prospective phase 2 study. After complete resection of the PC, HIPEC was performed by the Coliseum technique with oxaliplatin (360 mg/m²) combined with irinotecan (360 mg/m²) in 2 L/m² of 5% dextrose, over 30 minutes at a real intraperitoneal temperature of 43°C. During the hour preceding HIPEC, patients received 5-fluorouracil (400 mg/m²) and leucovorin (20 mg/m²) intravenously, resulting in tritherapy. Results Postoperative mortality and morbidity rates were 4% and 66%, respectively. The most frequent complications were digestive fistula (24%), lung infection (16%), and severe hematological toxicity (11%). Statistical correlation was evidenced between morbidity and the carcinomatosis score (P = .0008), the number of resected organs (P = .0001), the duration of surgery (P = .0001), and blood loss (P = .0001). Conclusions This new approach, optimized in three respects (complete cytoreduction, combination oxaliplatin with irinotecan, and high temperature) has resulted in a relatively high but acceptable incidence of adverse events considering the expected advantage for survival.     

Traumatic Injury of the Superior Mesenteric Vein: Ligate,Repair or Shunt?

Abstract We report a case of SMV injury in a critically ill patient. The patient was a 19-year-old woman involved in a motor vehicle collision. Her injuries included grade II splenic and renal lacerations, devascularized and lacerated right and transverse colon, a transected transverse mesocolon, a massive shear injury of her abdominal wall, and two partial SMV transections. At initial damage control laparotomy, the SMV was ligated, the devascularized bowel resected and a temporary abdominal closure applied. At re-operation, a mesocaval shunt using saphenous vein was employed. The shunt failed and the patient required a saphenous vein jump graft. Although visceral vascular injuries are rare, ligation of the SMV in a damage control situation is acceptable. This case study is the first to discuss appropriate treatment when interruption to a patient's collateral visceral venous drainage limits the surgeon’s ability to ligate. In these situations, bypass shunts may be successful.     

The association of anemia and hypoalbuminemia with accelerated decline in GFR among adolescents with chronic kidney disease

We sought to describe rates of kidney function decline and to identify modifiable risk factors for CKD progression in a multicenter prospective cohort study of adolescents with CKD aged 11 to 18 years seen semiannually for up to three years. Of the 23 subjects meeting inclusion criteria, the average estimated GFR was 51 ± 27 ml/min/1.73 m² (0.85 ± 0.45 ml/s/1.73 m²) at entry. The overall annualized decline in GFR was 5.6 ml/min/1.73 m² (0.093 ml/s/1.73 m²) per year (95% confidence interval [95% CI]: 1.9 to 9.3 [0.032 to 0.16]). The adjusted annualized decline in GFR was found to be accelerated in males, as well as among those over 15 years of age. The adjusted annualized decline in GFR was greater among those with either anemia (hematocrit below 36%), or hypoalbuminemia (albumin below 4 g/dl [40 g/L]). After adjustment, anemia was associated with an accelerated decline of 7.8 ml/min/1.73 m² (0.13 ml/s/1.73 m²) (95% CI: 3.3 to 12 [0.055 to 0.20]) and hypoalbuminemia was associated with an accelerated decline of 17 ml/min/1.73 m² (0.28 ml/s/1.73 m²) (95% CI: 11 to 22 [0.18 to 0.37]). Further study is needed to evaluate whether treatment of anemia or hypoalbuminemia, as outlined in current clinical care guidelines for CKD, may slow the progression of CKD in adolescents.     

Pelvic Ring Fractures: Utility of Clinical Examination in Patients with Impaired Consciousness or Tracheal Intubation

Abstract Objective: To define the diagnostic accuracy of clinical examination in patients with impaired consciousness or endotracheal intubation to detect pelvic ring fractures and to identify those with severe bleeding. Methods: Included in this prospective data collection with retrolective data analysis were a consecutive series of blunt trauma victims with either a Glasgow Coma Scale ≤ 13 or tracheal intubation. Clinical examination comprised testing for stability of the iliac wings. Results: From 784 subjects (injury severity score 23.3 ± 17.4) 93 patients (11.9%) were found to have a pelvic ring fracture. Clinical instability of the pelvic ring was found in 42 patients. There was only one false positive. Fifty-two fractures could not be identified by clinical examination, including nine fractures (17%) that required surgical fracture stabilization (sensitivity of clinical examination 44.1%). Seventeen fractures (18.3%) were associated with a blood loss larger than 20% of circulating blood volume. Sixteen of those were identified by clinical instability of the pelvic ring (sensitivity 94.1%, specificity 97.0%, positive predictive value 38.1%, negative predictive value 99.9%). Conclusions: Clinical examination for stability of the pelvis in this selected group of patients missed a significant number of pelvic ring fractures including fractures that require surgical stabilization. The finding of a clinically unstable identifies most of the patients with the pelvic ring fracture being a major source of bleeding. A stable pelvis makes pelvic ring fracture as being the source of bleeding quite unlikely.     

Internal Hernias: Clinical Findings,Management, and Outcomes in 49 Nonbariatric Cases

Internal hernia, the protrusion of a viscus through a peritoneal or mesenteric aperture, is a rare cause of small bowel obstruction. We report the clinical presentation, surgical management, and outcomes of one of the largest series of nonbariatric internal hernias. Ten-year retrospective review of patients at our institution yielded 49 cases of internal hernias. Majority of patients presented with symptoms of acute (75%) or intermittent (22%) small bowel obstruction. While 16% of CT scans were suspicious for internal hernia, in no cases the preoperative diagnosis of internal hernia was made. The most frequent internal hernias were transmesenteric (57.0%) and 34 hernias (69%) were caused by previous surgery. All internal hernias were reduced and the defects were repaired. Compromised bowel was present in 22 cases and 11 patients underwent small bowel resection. The mean postoperative hospitalization was 10.9 days. The overall mortality rate from our series is 2%, and the morbidity rate is 12%. Transmesenteric hernias, as complications of previous surgeries, are the most prevalent internal hernias. Preoperative diagnosis of internal hernia is extremely difficult because of the nonspecific clinical presentation. However, if discovered promptly, internal hernias can be repaired with acceptable morbidity and mortality. Poster presentation at Digestive Disease Week, May 22, 2006, Los Angeles, California, USA.