Mechanically Tunable Hollow Silica Ultrathin Nanoshells for Ultrasound Contrast Agents.

Perfluoropentane (PFP) gas filled biodegradable iron-doped silica nanoshells have been demonstrated as long-lived ultrasound contrast agents. Nanoshells are synthesized by a sol-gel process with tetramethyl orthosilicate (TMOS) and iron ethoxide. Substituting a fraction of the TMOS with R-substituted trialkoxysilanes produces ultrathin nanoshells with varying shell thicknesses and morphologies composed of fused nanoflakes. The ultrathin nanoshells had continuous ultrasound Doppler imaging lifetimes exceeding 3 hours, were twice as bright using contrast specific imaging, and had decreased pressure thresholds compared to control nanoshells synthesized with just TMOS. Transmission electron microscopy (TEM) showed that the R-group substituted trialkoxysilanes could reduce the mechanically critical nanoshell layer to 1.4 nm. These ultrathin nanoshells have the mechanical behavior of weakly linked nanoflakes but the chemical stability of silica. The synthesis can be adapted for general fabrication of three-dimensional nanostructures composed of nanoflakes, which have thicknesses from 1.4-3.8 nm and diameters from 2-23 nm.

Glutathione metabolism in patients with non-small cell lung cancers.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in the United States. Because NSCLC is highly chemoresistant, it is, usually not treatable. Altered glutathione (GSH) metabolism is thought to be one major mechanism of chemoresistance, and GSH levels are reported to be elevated in NSCLC. The main objective of this study is to delineate the potential mechanisms involved in elevation of tissue GSH, including extraction from the circulation by NSCLC. Twenty consecutive patients with NSCLC were enrolled. At the time of lobectomy, pulmonary artery and vein were identified, and blood flow was measured by an electromagnetic probe. Subsequently, blood samples were drawn from pulmonary artery, the vein draining the tumor-bearing lobe, and a normal lobe. Immediately after lobectomy, tumor and lung specimens were snap frozen. NSCLC tumor specimens had higher levels of GSH compared with lung tissue (20.8 +/- 9.4 versus 11.6 +/- 3.0 nmol/mg protein, respectively; P < 0.05). The tumor demonstrated higher activity of the enzyme gamma-glutamyl transpeptidase, a membrane-bound enzyme involved in transmembrane uptake of GSH, than lung tissue (41.9 +/- 26.4 versus 22.4 +/- 12.3 units/mg protein, respectively; P < 0.05). Also, the tumor-bearing lobe showed elevated extraction of GSH and two of its component amino acids compared with lung tissue (GSH uptake: 0.60 +/- 0.67 versus 0.20 +/- 0.40 microM/min, respectively; P < 0.05). NSCLC tumors are able to extract circulating GSH and its constituent amino acids to synthesize intracellular GSH. Increased activity of gamma-glutamyl transpeptidase may be one mechanism underlying increased GSH uptake by NSCLC.

Pretreatment with IFN-gamma decreases infectious complications after partial hepatectomy in the rat.

Infectious postoperative complications occur commonly after hepatectomy and may lead to a long hospital stay or death. The potential beneficial effects of interferon-gamma (IFN-gamma) in this setting were evaluated in a model of hepatectomy and sepsis in rodents. Incidence of bacterial translocation was measured in animals on days 1, 2, and 5 after partial hepatectomy. Macrophage function was quantified by in vitro tumoricidal activity and superoxide anion (O2-) production. Survival after partial hepatectomy and cecal ligation and puncture (CLP) was recorded. After partial hepatectomy, bacterial translocation was decreased on days 1 and 2 in animals pretreated with IFN-gamma (p < 0.05). Macrophages from animals treated with IFN-gamma had higher in vitro tumoricidal activity and production of O2- (p < 0.05). Hepatectomized animals pretreated with IFN-gamma had an increased survival after CLP (p < 0.05). IFN-gamma may be useful in decreasing the incidence of infectious complications after partial hepatectomy.

Critical care of patients with cancer. Surgical considerations.

Surgical evaluation of and therapy for the critically ill cancer patient continue to present significant challenges despite, or perhaps in part because of, an ongoing technologic refinement of therapeutic modalities within a modern ICU.

Advanced age does not contribute to increased risks or poor outcome after major abdominal operations.

Elderly patients are still frequently denied major operations out of concerns over increased morbidity. The impact of advanced age on morbidity, mortality, and late outcomes after major gastric and pancreatic resections was studied by retrospective review with Chi square and regression analysis. Between July 1987 and June 2000, 179 patients underwent a major gastrectomy or pancreatectomy procedure at the City of Hope Cancer Center. There were 96 males and 83 females with a median age of 64 years (range 17-97) and elderly subsets more than 70 (n = 53) and more than 80 (n = 18) years of age. Diagnoses included gastric cancer (n = 83, 46%), pancreatic or periampullary cancer (n = 78, 44%), and benign pancreatic (n = 11, 6%) or gastric (n = 7, 4%) conditions. Age >70 years was correlated with more complex underlying medical conditions (P = 0.001) and gastrectomy for cancer (P = 0.01). None of four in-hospital deaths or 11 90-day lethal events occurred in patients >70 years of age (P = 0.005). Overall complications (35% vs 49%) and major complications (25% vs 37%) were less frequent in the older patient group [P = not significant (NS)]. Median intensive care unit stay (3 vs 2 days) and hospital stay (12 vs 12.5 days) were similar (P = NS). Pancreatoduodenectomy, gastrectomy for "benign" indications, and splenectomy--but not age--were significant prognostic variables for increased complications and longer hospital stay (at P < 0.05). At a median follow-up of 13 months (20 for survivors) the median survival after resection for gastric cancer (30 vs 16 months) or pancreatic/periampullary cancer (30 vs 23 months) was not inferior in elderly patients (P = NS). Five-year disease-free survival was superior in gastric cancer patients >70 years (59% vs 26%, P = 0.03) but not for pancreatic cancer. Advanced age under current clinical selection criteria does not impose increased hazards beyond disease- and procedure-related risk factors for patients undergoing gastrectomy or pancreatectomy; no patient should be denied these operations on the basis of age criteria alone.

Children's participation in household labor: Child socialization versus the need for household labor.

Despite the scarcity of studies of children's participation in housework, it has been established that children contribute a significant amount of total household labor. However, research on why some children contribute more than others has yielded ambiguous results. Using data from the National Survey of Families and Households(J. A. Sweet, L. Bumpus, and V. Call [1988], working paper NSFH-1, Center for Demography and Ecology, University of Wisconsin, Madison), this study tests two competing theories of children's labor participation. The first, dealing with child socialization,proposes that parents assign household chores to children as a socializing experience (e.g., to promote responsibility). The second posits that children are used as a labor source whenever structural constraints prevent adults from performing the necessary chores, and alter the demand for household labor.The results indicate that children average 7 hours of housework per week, representing 12% of all household labor. Both theories receive support, yet the pragmatic aspects of households (e.g., adult labor force participation) receive greater confirmation.

Outcome of palliative operations for malignant bowel obstruction in patients with peritoneal carcinomatosis from nongynecological cancer.

BACKGROUND: Malignant bowel obstruction (MBO) secondary to peritoneal carcinomatosis carries a grave prognosis. We evaluated clinicopathologic factors that predict outcomes after palliative operations for MBO. METHODS: Data on patients undergoing laparotomy for palliation of gastrointestinal MBO at City of Hope between 1995 and 2000 were retrospectively collected. Successful palliation was defined as the ability to tolerate solid food (TSF). RESULTS: Sixty-three patients underwent operative treatment. In 20 patients, MBO was the first presentation of disease; for others, the median disease-free interval was 15 months. The complication rate was 44%, and postoperative mortality was 15%. The median length of stay was 12 days. Twenty-nine patients (45%) were discharged from the hospital on a regular diet; 22 (76%) continued to eat until their last follow-up. Median survival was 90 days. Univariate factors for longer survival were TSF on discharge, colorectal primary, and nonmetastatic status at first diagnosis. Patients with ascites and whose cancer first presented with MBO had an inferior survival. Noncolorectal primary remained a multivariate predictor for decreased survival. TSF was predicted by the absence of ascites, an obstruction not involving the small bowel, and a preoperative albumin of >3.0 mg/dl. Multiple logistic regression analysis yielded presence of ascites and small-bowel obstruction as predictors of inability to TSF. CONCLUSIONS: Only one third of patients with MBO from peritoneal carcinomatosis will have prolonged postoperative palliation with significant, but acceptable, treatment-related morbidity. TSF at discharge is a useful predictor of continued palliation for most patients. Patients with colorectal cancer may have superior survival outcome and better palliation; others are at risk for poor outcomes, especially in the presence of ascites and MBO of small bowel. In these patients, highly selective use of laparotomy is recommended.

Oral L-2-oxo-4-thiazolidine reduces bacterial translocation after radiation in the Fischer rat.

Glutathione (GSH) is important in protecting rapidly dividing intestinal cells against free radicals generated following radiation. L-2-Oxo-thiazolidine (OTZ) promotes GSH synthesis through increased cysteine delivery. We hypothesize that oral supplementation with OTZ will augment GSH levels and decrease the incidence of bacterial translocation after abdominal radiation, and these effects will be abrogated by treating with a blocker of GSH synthesis, buthionine sulfoximine (BSO). Fischer rats received by oral gavage either OTZ (OTZ/rad), OTZ plus BSO (OTZ/BSO/rad), or saline (sal/rad) 4 hr prior to and 18 hr after radiation. One group underwent saline gavage and no radiation (ctl/sal). On Day 4, animals were sacrificed and mesenteric lymph nodes (MLN) were cultured. Liver and jejunum were removed for GSH analysis by HPLC. Nonradiated, ctl/sal had higher levels of hepatic and jejunal GSH than ctl/rad (13.0 +/- 1.2 vs 9.7 +/- 1.5, 11.2 +/- 1.0 vs 7.8 +/- 2.5 micromol/g dry wt, P < 0.05). Supplementation with OTZ (OTZ/rad) increased hepatic and jejunal GSH levels but treatment with OTZ and BSO (OTZ/BSO/rad) eliminated this benefit (12.0 + 2.6 vs 9.5 + 1.7, 10.1 + 2.4 vs 5.9 + 1.3 micromol/g dry wt, P < 0.05). Ctl/rad had a high rate of positive MLN cultures (80%) compared to ctl/sal and OTZ/rad (10 and 30%, P < 0.05). Treatment with OTZ and BSO (OTZ/BSO/rad vs OTZ/rad, 70 and 30%, P < 0.05) reversed the benefit of OTZ supplementation. This study demonstrated whole abdominal radiation depleted both hepatic and jejunal levels of GSH. Uniquely, OTZ supplementation restored hepatic and jejunal levels of GSH and decreased rate of bacterial translocation.

Surgeon variability in treating nonpalpable breast cancer: surgical oncology as a value-added specialty.

BACKGROUND: Several studies have demonstrated a relatively low rate of breast conservation surgery (BCS) in the United States. Few have analyzed the impact of individual surgeon variability on the outcome of the procedure, and none have contrasted surgical oncologists versus general surgeons in the treatment of nonpalpable breast cancer. METHODS: A blinded review was done of 409 excisions for nonpalpable breast cancer performed by 11 board-certified general surgeons (GS, n = 221) and one surgical oncologist (SO, n = 185) in a teaching institution. We compared surgical margins, need for reexcision, and breast conservation rates. RESULTS: Although there were no significant differences in patient and tumor characteristics, there were surprising differences between the GS and SO, especially related to surgical margins and final treatment. The SO has a significantly higher rate of frozen section compared to GS (81% vs. 64%, P < 0.01) and a lower rate of positive margin at the time of original biopsy (25% vs. 41%, P < 0.01). These differences translated into lower necessity for reexcision of tumor (18% vs. 48%, P < 0.01) and higher rate of BCS (88% vs. 70%, P < 0.01). CONCLUSION: This study demonstrates marked differences among trained general surgeons. The additional experience of a surgical oncologist is valuable, because fewer positive margins lead to a higher likelihood of breast preservation and decreased costs related to fewer additional operative procedures.

Multifocal extremity sarcoma: an uncommon and controversial entity.

BACKGROUND: The primary site of metastasis from extremity sarcomas is the lung. When patients with extremity sarcoma present with the disease in more than one site but not in the lung, the question of whether the disease is multifocal or metastatic is difficult to resolve. METHODS: We reviewed 1423 patients admitted with extremity sarcoma from 1982 through 1996. Patient demographics, primary site, other sites, local recurrence, distant metastasis, and survival were analyzed. Statistics were by Fischer exact test, chi 2, Kaplan-Meier method, and log-rank test where appropriate. RESULTS: Sixteen (1%) patients were identified with multifocal disease out of 1423 patients with extremity sarcoma. There was no difference in sex, age, size, grade, depth, and margins between multifocal and unifocal disease. In a mean follow-up time of 57 months, 50% had local recurrence of primary tumor, 80% had distant metastasis, and only 30% were alive at the time of the analysis. Whereas 21% of all patients with solitary disease develop lung metastasis, 63% of patients with apparent multifocal disease develop lung metastasis. The 5-year disease-specific survival of patients with multifocal disease was not different from that of all patients presenting with metastatic disease to lung. CONCLUSION: Whether multifocal disease exists or is merely a form of metastasis is unproven by this analysis, but the outcome is the same. Management algorithms should suggest treating patients with multifocal disease as if it is metastatic disease.