Clinicopathological features and outcome of surgical treatment of 149 patients with early (pT1) gastric cancer

BACKGROUND: Controversy exists concerning the definition of, treatment approach to, prognostic factors of and survival data on early gastric cancer. PATIENTS AND METHODS: 149 patients who underwent curative gastrectomy for carcinoma between 1972 and 2002 and were classified as having early gastric cancer (T1Nany) were included into a retrospective study. Patients were followed for a median of 5.5 years. RESULTS: We observed an increase in the incidence of early gastric cancer from 7.7% in the 1970s to 22.2% in the 1990s. None of the patients with mucosal tumors had lymph node metastases while 18 (20%) submucosal tumors were node positive. Multivariate analysis of all patients identified depth of tumor infiltration as the only independent risk factor for lymph node metastases. The analysis has shown that none of the clinicopathological features are reliable predictors of nodal status in patients with submucosal invasion. Patients with early gastric cancer had a very good prognosis, 10-year disease-specific survival was 80% or more in all subgroups of patients except for node-positive tumors. Depth of the tumor invasion, lymph node status as well as sex were found to be independent prognostic factors for overall survival. CONCLUSIONS: Early gastric cancer has a very good prognosis after standard surgery. Our data support the use of conservative limited surgical procedures for appropriate patients with mucosal gastric cancer. Patients with submucosal lesions require the same treatment approach as those with more advanced gastric cancer unless clinical usefulness of sentinel lymph node biopsy will be established.     

Application of novel hemostatic agent during laparoscopic partial nephrectomy

PURPOSE: We determined if QuikClot, a novel hemostatic agent made of a granulated mineral substance, could be used to control renal parenchymal bleeding and collecting system leakage during open and laparoscopic partial nephrectomy. MATERIALS AND METHODS: After obtaining renal hilar vascular control 2 domestic female pigs underwent bilateral open and 4 underwent unilateral laparoscopic partial nephrectomy. After excision of the lower pole without cautery the hemostatic agent was applied to the cut surface of the kidney and hilar vascular control was released. Additional QuikClot was added until complete hemostasis was achieved. One week postoperatively the animals were sacrificed and the operated kidneys were harvested for ex vivo retrograde pyelograms and histopathological analysis. RESULTS: All partial nephrectomies were performed without complication. Mean operative and warm ischemia times were 62 and 16 minutes, respectively. An average of 23% of renal mass by weight was resected with a mean blood loss of 73 ml per procedure. No cautery, additional hemostatic agents or techniques were used. No animal had clinical or radiographic evidence of urinoma or delayed hemorrhage. Histopathological analysis showed preservation of the renal parenchyma immediately beneath the QuikClot layer. CONCLUSIONS: In the porcine model QuikClot allowed the resection of large renal segments, while providing reliable hemostasis and closure of the renal collecting system. No deleterious effect on underlying renal parenchyma or surrounding tissues was observed.     

Enhancement of the efficacy of chemotherapy for lung cancer by simultaneous suppression of multidrug resistance and antiapoptotic cellular defense: novel multicomponent delivery system

The efficacy of chemotherapy of lung cancer is limited by the development of resistance in cancer cells during treatment. In most lung cancers, this resistance is associated with the overexpression of (a) multidrug resistance-associated protein (MRP) responsible for drug efflux from the cancer cells (pump resistance) and (b) BCL2 protein that activates antiapoptotic cellular defense (nonpump resistance). A novel liposomal proapoptotic anticancer drug delivery system was developed to enhance anticancer efficacy of the well-established drug doxorubicin (DOX). This multicomponent drug delivery system was tested on multidrug-sensitive and -resistant human small-cell lung cancer cells. The drug delivery system includes four components: (a) liposome as a carrier, (b) DOX as an inductor of apoptosis, (c) antisense oligonucleotides (ASOs) targeted to MRP1 mRNA as a suppressor of pump resistance, and (d) ASOs targeted to BCL2 mRNA as a suppressor of nonpump resistance. Intracellular internalization of ASOs and DOX; the influence of the proposed system on the expression of genes and proteins involved in the multidrug resistance, cytotoxicity, and apoptosis induction and antiapoptotic defense; and the activity of caspases were studied. It was found that the proposed liposomal delivery system successfully delivered ASOs and DOX to cell nuclei, inhibited MRP1 and BCL2 protein synthesis, and substantially increased the anticancer action of DOX by stimulating the caspase-dependent pathway of apoptosis in multidrug-resistant human lung cancer cells.     

Impaired gastric ulcer healing in diabetic rats: role of heat shock protein, growth factors, prostaglandins and proinflammatory cytokines

Gastric mucosa of diabetic rats is highly vulnerable to acute injury, but little is known about the influence of diabetic conditions on the healing of gastric ulcers. In this study, streptozotocin (70 mg/kg injected intraperitoneally) was used to induce diabetes mellitus in rats. Four weeks after streptozotocin injection, gastric ulcers were induced using the acetic acid method, and 10 days later, the healing rate and the gastric blood flow (GBF) were measured by planimetry and hydrogen (H(2))-gas clearance method, respectively. Six major groups of rats with gastric ulcers were used: (1) vehicle (saline); (2) streptozotocin alone; (3) insulin (4 IU/day intraperitoneally); (4) streptozotocin plus insulin; (5) pentoxifylline, an inhibitor of synthesis and release of tumor necrosis factor-alpha (TNF alpha); and (6) aspirin, a non-selective inhibitor of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), and rofecoxib, the highly selective COX-2. In the diabetic rats, a significant delay in ulcer healing ( approximately by 300%), accompanied by a decrease in the gastric mucosal blood flow was observed. The prolongation of the healing in diabetic animals was associated with an increase in gastric mucosal expression and release of TNFalpha, interleukin-1 beta (IL-1 beta), suppression of the vascular endothelial growth factor (VEGF), platelet endothelial cell adhesion molecule-1 (PECAM-1) and the mucosal overexpression of heat shock protein 70 (HSP 70). Administration of insulin reversed the delay in ulcer healing and significantly decreased the expression of IL-1 beta and TNF-alpha, while producing the rise in the expression of VEGF and PECAM. Pentoxifylline, an inhibitor of TNF-alpha, which by itself accelerated ulcer healing in non-diabetic rats, counteracted the increase in the area of gastric ulcer induced by streptozotocin, raised significantly gastric blood flow and suppressed the plasma TNF-alpha levels. Aspirin and rofecoxib, that significantly suppressed the mucosal prostaglandin E(2) generation in ulcer area, delayed significantly the rate of ulcer healing and decreased the GBF at ulcer margin in non-diabetic rats, and these changes were significantly augmented in diabetic animals. We conclude that: (1) Experimental diabetes dramatically impairs ulcer healing, depending upon the increased release of proinflammatory cytokines and the attenuation of angiogenesis that can limit the ulcer healing effects of locally produced HSP 70 and TNF-alpha. (2) Insulin reversed this impairment of ulcer healing in diabetic rats, mainly due to the enhancement of angiogenesis and reduction in expression of cytokines in the ulcer area. (3) Classic non-steroidal anti-inflammatory drugs such as aspirin prolonged ulcer healing under diabetic conditions due to suppression of endogenous prostaglandins and the fall in the microcirculation at the ulcer margin and these effects were mimicked by selective, so called "safe" COX-2 inhibitor, rofecoxib, suggesting that both COX isoforms are important sources of prostaglandins that are essential in the ulcer healing in diabetes.     

Intraoperative imaging in glioblastoma resection

The use of intraoperative imaging (IOI) in neurosurgical practice is proving to be yet another important advance in the evolution of brain tumor resection, particularly for the most common adult primary brain tumor--glioblastoma (GBM). The number of surgeons using IOI continues to increase, and the experience to date affords an opportunity to assess the value of the various techniques used for IOI.     

Chain-Breaking Antioxidant Capability of Some Beverages as Determined by the Clark Electrode Technique

The protective effects of red wine, tea, and coffee on cancer, atheroclerosis, and other diseases are attributed to the antioxidant activity (AOA) of polyphenols, which are abundant in those beverages. We present a rational procedure for determining the total chain-breaking AOA of beverages with the use of the Clark electrode technique. The procedure is based on the steady monitoring of oxygen consumption accompanying the chain peroxidation of methyl linoleate in Triton X-100 aqueous micelles induced by 2,2'-azobis(2-amidinopropan) dihydrochloride as a source of active free radicals. AOA was characterized by the number of kinetic chains (expressed in concentration units) that could be terminated by a beverage. The procedure was applied to determine the AOA of nine red wines and single samples of green and black teas, white wine, beer, and soluble coffee. The addition of any of the studied beverages to the testing system resulted in pronounced retardation of methyl linoleate oxidation. The period of increase in the oxidation rate with time caused by antioxidant consumption was preceded by a period when the oxidation rate was visibly decreased with time (increase in inhibition). The release of polyphenols from their complexes with other components of beverages was suggested as the most probable mechanism of this event, which was observed for the first time in this study.