Humidity-enhanced sub-ppm sensitivity to ammonia of covalently functionalized single-wall carbon nanotube bundle layers.

A low-cost method for carbon nanotubes (CNTs) network production from solutions on flexible polyethylene naphthalate substrates has been adopted to prepare high quality and well characterized SWCNT bundle layers to be used as the active layer in chemiresistor gas sensors. Two types of SWCNTs have been tested: pristine SWCNTs, deposited from a surfactant solution, and covalently functionalized SWCNTs, deposited from a dimethyl-acetamide solution. The humidity effects on the sensitivity of the SWCNTs network to NH3 have been investigated. The results show that relative humidity favors the response to NH3, confirming recent theoretical predictions. The COOH-functionalized sample displays the largest response owing to both its hydrophilic nature, favoring the interaction with H2O molecules, and its largest surface area. Compared to data available in the literature, the present sensors display a remarkable sensitivity well below the ppm range, which makes them quite promising for environmental and medical applications, where NH3 concentrations (mostly of the order of tens of ppb) have to be detected.

Simple preoperative risk scale accurately predicts perioperative mortality following esophagectomy for malignancy.

Surgery remains one of the major treatment options available to patients with esophageal cancer, with high mortality in certain cohorts. The aim of this study was to develop a simple preoperative risk scale based on patient factors, hospital factors, and tumor pathology to predict the risk of perioperative mortality following esophagectomy for malignancy. The Nationwide Inpatient Sample database was used to create the risk scale. Patients who underwent open or laparoscopic transhiatal and transthoracic esophageal resection were identified using International Classification of Diseases, 9th edition codes. Patients <18 years and those with peritoneal disease were excluded. Multivariate logistic regressions were used to define a predictive model of perioperative mortality and to create a simple risk scale. From 1998 to 2011, a total of 23 751 patients underwent esophagectomy. The observed overall perioperative mortality rate for this cohort was 7.7%. Minimally invasive techniques, and operations performed in higher volume centers were protective, whereas increasing age, comorbidities and diagnosis of squamous cell carcinoma were independent predictors of mortality. Based on this population, a risk scale from 0-16 was created. The calibration revealed a good agreement between the observed and risk scale-predicted probabilities. A set of sensitivity/specificity analyses was then performed to define normal (score 0-7) and high risk (score 8-16) patients for clinical practice. Mortality in patients with a score of 0-7 ranged from 1.3-7.6%, compared with 10.5-34.5% in patients with a score of 8-16. This simple preoperative risk scale may accurately predict the risk of perioperative mortality following esophagectomy for malignancy and can be used as a clinical tool for preoperative counseling.

Maternal perinatal undernutrition modifies lactose and serotranferrin in milk: relevance to the programming of metabolic diseases?

A close link between intrauterine growth restriction and development of chronic adult diseases such as obesity, diabetes, and hypertension has been established both in humans and animals. Modification of growth velocity during the early postnatal period (i.e., lactation) may also sensitize to the development of metabolic syndrome in adulthood. This suggests that milk composition may have long-lasting programming/deprogramming metabolic effects in the offspring. We therefore assess the effects of maternal perinatal denutrition on breast milk composition in a food-restricted 50% (FR50) rat model. Monosaccharides and fatty acids were characterized by gas chromatography, and proteins were profiled by surface-enhanced laser desorption/ionization-time-of-flight analysis in milk samples from FR50 and control rat dams. Milk analysis of FR50 rats demonstrated that maternal undernutrition decreases lactose concentration and modulates lipid profile at postnatal day 10 by increasing the unsaturated fatty acids/saturated fatty acids and diminishes serotransferrin levels at postnatal day 21. Our data indicate that maternal perinatal undernutrition modifies milk composition both quantitatively and qualitatively. These modifications by maternal nutrition open new perspectives to identify molecules that could be used in artificial milk to protect from the subsequent development of metabolic diseases.

Experimental and theoretical study of electronic structure of lutetium bi-phthalocyanine.

Using Near Edge X-Ray Absorption Fine Structure (NEXAFS) Spectroscopy, the thickness dependent formation of Lutetium Phthalocyanine (LuPc2) films on a stepped passivated Si(100)2×1 reconstructed surface was studied. Density functional theory (DFT) calculations were employed to gain detailed insights into the electronic structure. Photoelectron spectroscopy measurements have not revealed any noticeable interaction of LuPc2 with the H-passivated Si surface. The presented study can be considered to give a comprehensive description of the LuPc2 molecular electronic structure. The DFT calculations reveal the interaction of the two molecular rings with each other and with the metallic center forming new kinds of orbitals in between the phthalocyanine rings, which allows to better understand the experimentally obtained NEXAFS results.

Breast carcinoma metastatic to the gallbladder and urinary bladder.

We present a patient with a history of infiltrating lobular breast carcinoma that metastasized to both the biliary and urinary tract after a ten year disease-free period following mastectomy and chemoradiotherapy. The patient presented with acute cholecystitis; imaging and histopathology revealed infiltrating lobular carcinoma of the gallbladder and urinary bladder. This report emphasizes the importance of long-term follow up in patients with a history of breast cancer and maintaining a high degree of suspicion for diagnosis of metastatic disease.

Clinically-relevent orthotopic metastatic models of pancreatic cancer imageable with fluorescent genetic reporters.

This article describes authors' cumulative experience with the development and preclinical application of clinically-relevant, metastatic orthotopic mouse models of pancreatic cancer made imageable with genetic reporters. These models utilize the human pancreatic cancer cell lines which have been genetically engineered to selectively express high levels of green fluorescent protein (GFP) or red fluorescent protein (RFP). Tumors with fluorescent genetic reporters are established subcutaneously in nude mice, and fragments of the subcutaneous tumors are then surgically transplanted onto the pancreas. Loco-regional tumor growth and distant metastasis of these orthotopic implants occurs spontaneously and rapidly throughout the abdo-men in a manner consistent with clinical human disease. Highly specific, high-resolution, real-time quantitative fluorescence imaging of tumor growth and metastasis may be achieved in vivo without the need for contrast agents, invasive techniques, or expensive imaging equipment. A high correlation between florescence optical imaging, magnetic resonance imaging, and ultrasound in these models has been demonstrated. Transplantation of RFP-expressing tumor fragments onto the pancreas of GFP- or cyan fluorescent protein-expressing transgenic mice was used to facilitate visualization of tumor-host interaction between the pancreatic cancer cells and host-derived stroma and vasculature. Such in vivo models have enabled visualization in real time and acquisition of images of the progression of pancreatic cancer in the live animal, the models also demonstrate the real-time antitumor and antimetastatic effects of several novel therapeutic strategies on pancreatic malignancy. These fluorescent models are therefore powerful and reliable tools with which to investigate metastatic human pancreatic cancer and novel therapeutic strategies directed against it.

Road soil retention of Pb leached from MSWI bottom ash.

Municipal solid waste incinerator (MSWI) bottom ash may be used as a road construction material; it potentially contains however a sizable quantity of heavy metals, which under the effect of rainfall infiltration through the road structure can be leached out from the material and infiltrate into the underlying soil. An eco-compatibility assessment of MSWI bottom ash reuse in road construction applications necessitates examining the solubility and retention of heavy metals in road soils. This study is dedicated to Pb transfer, sorption and desorption (NEN 7341 standard test) within various soils. These experiments yield results relative to the interaction between road soils and an MSWI bottom ash leachate representative of a "fresh" product, with a high leaching potential. For the soils investigated, the sorption of lead varies between 90% and 99%. For an extraction at pH 7, Pb release is very low (<2%) for all soils, while at pH 4 leaching varies between 4% and 47%. This work shows that Pb may be fixed by some types of road soil in mostly stable forms.

OBP-401-GFP telomerase-dependent adenovirus illuminates and kills high-metastatic more effectively than low-metastatic triple-negative breast cancer in vitro.

We previously described the development of a highly-invasive, triple-negative breast cancer (TNBC) variant using serial orthotopic implantation of MDA-MB-231 human breast cancer in nude mice. The isolated variant is highly invasive in the mammary gland and metastasized to lymph nodes in 10 of 12 mice compared with 2 of 12 of the parental cell line. OBP-401 is a telomerase-dependent cancer-specific, green fluorescent protein (GFP)-expressing adenovirus. OBP-401 was used to infect parental MDA-MB-231P cells and high-metastatic MDA-MB-231H and MDA-MB-231HLN isolated from a lymph node metastasis and MDA-MB-231HLM isolated from a lung metastasis. Time-course imaging showed that OBP-401 labeled MDA-MB-231HP, MDA-MB-231HLN, and MDA-MB-231HLM cells more brightly than MDA-MB-231 parental cells. OBP-401 killed MDA-MB-231H, MDA-MB-231HLN, and MDA-MB-231HLM cells more efficiently than MDA-MB-231P parental cells. These results indicate that OBP-401 could infect, label and then kill high-metastatic MDA-MB-231 more efficiently than low-metastatic MDA-MB-231.

Adenovirus-mediated wild-type p53 gene transfer down-regulates vascular endothelial growth factor expression and inhibits angiogenesis in human colon cancer.

Recent studies have indicated that angiogenesis may be regulated, in part, by p53 tumor suppressor gene function. We hypothesized that wild-type p53 replacement would down-regulate vascular endothelial growth factor (VEGF) expression and inhibit angiogenesis. KM12L4 and SW620, human colon cancer cell lines with p53 mutations, were transduced with a replication-defective adenoviral vector containing the wild-type p53 gene (Ad5/CMV/p53). Reverse transcription-PCR confirmed the presence of p53 in Ad5/CMV/p53-transduced cells. Transduction of colon cancer cells with wild-type p53 decreased VEGF RNA expression compared with that of controls. The decrease in VEGF expression in SW620 cells was dose dependent, with a 49% decrease observed at a multiplicity of infection of 50, and a 71% decrease observed at a multiplicity of infection of 100. Similar effects were seen in KM12L4 cells. VEGF supernatant protein levels were significantly reduced compared with those in nontransduced controls 48 h after the introduction of wild-type p53. Ad5/CMV/p53 inhibited tumor cell-induced angiogenesis in vivo. Restoration of wild-type p53 expression may decrease tumor growth by inhibiting the angiogenic response. These findings may explain, in part, the bystander effect seen with p53 tumor suppressor gene therapy.

Methioninase cancer gene therapy with selenomethionine as suicide prodrug substrate.

In this study, we report a novel approach to gene-directed enzyme prodrug therapy for cancer. This gene therapy strategy exploits the toxic pro-oxidant property of methylselenol, which is released from selenomethionine (SeMET) by cancer cells with the adenoviral-delivered methionine alpha,gamma-lyase (MET) gene cloned from Pseudomonas putida. In MET-transduced tumor cells, the cytotoxicity of SeMET is increased up to 1000-fold compared with nontransduced cells. A strong bystander effect occurred because of methylselenol release from MET gene-transduced cells and uptake by surrounding tumor cells. Methylselenol damaged the mitochondria via oxidative stress and caused cytochrome c release into the cytosol, thereby activating the caspase cascade and apoptosis. Adenoviral MET-gene/SeMET treatment also inhibited tumor growth in rodents and significantly prolonged their survival. Recombinant adenovirus-encoding MET gene-SeMET treatment thereby offers a new paradigm for cancer gene therapy.

Methioninase gene therapy of human cancer cells is synergistic with recombinant methioninase treatment.

Results obtained over the past 40 years have demonstrated that tumor cells of all types tested have an elevated growth requirement for methioninase compared with normal cells. Recombinant methioninase (rMETase) cloned from Pseudomonas putida has been found previously to be an effective antitumor agent attributable to deprivation of the extracellular methionine source of the tumor. To degrade intracellular methioninase, we have now developed an adenoviral vector inserted with the P. putida methioninase (MET) gene (rAd-MET). The in vitro efficacy of rAd-MET was tested on the OVCAR-8 human ovarian cancer cell line, the HT1080 human fibrosarcoma cell line, and human normal fibroblasts. rAd-MET transduction of OVACAR-8 and HT1080 resulted in high levels of methioninase expression up to 10% or more of the total protein of the cells, depending on the multiplicity of infection. The IC50 of rAd-MET for OVCAR-8 cells in 96-well plates was approximately 2 x 106 plaque-forming units (pfu)/well. The IC50 of control adenovirus (control-rAd) was 4 x 10(7) pfu/well, 20 times higher than rAd-MET. In the presence of the IC50 of 2 x 10(6) pfu/well of rAd-MET, the addition of 0.025 units/ml of rMETase, which is 25% of the IC50, resulted in a 90% inhibition of tumor cell number. This indicated that rAd-MET enhanced the efficacy of rMETase. In contrast, 2 x 10(6) pfu/well of control-rAd in combination with 0.025 units/ml of rMETase had an efficacy of only 10% inhibition of cell number. The synergistic effect of the combination of rMETase and rAd-MET was quantitated by calculating the combination index (CI). The CIs for all combinations of rAd-MET and rMETase tested on OVCAR-8 were <0.7 with a mean of 0.5, indicating synergy. Similar synergy of rAd-MET and rMETase was seen on HT1080 human fibrosarcoma cells with a mean of 0.74. In contrast, the CIs of all combinations of rMETase and control adenovirus concentrations tested on both cell lines had a mean CI of approximately 1, which indicated that this combination had only an additive effect. The normal fibroblasts, on the other hand, appeared relatively resistant to the MET gene because in the presence of rMETase, 2.5 x 10(7) pfu/well of rAd-MET or control rAd had almost an identical effect on cell survival. The selectively strong synergy of rAd-MET and rMETase on cancer cells allows reduced levels of each agent to be used, thus decreasing potential side effects.

Recombinant adenovirus expressing wild-type p53 is antiangiogenic: a proposed mechanism for bystander effect.

Angiogenesis is required for the growth and progression of malignancies. Recent studies have demonstrated that genetic alterations may accompany acquisition of the angiogenic phenotype. The tumor suppressor gene p53 is most frequently mutated in human cancers and is also known to be a transcriptional regulator of a variety of genes. Here, we investigated the antiangiogenic effect of the wild-type p53 (wt-p53) gene transfer on a human non-small cell lung cancer cell line. Mutant p53-expressing H226Br non-small cell lung cancer cells were transduced with the wt-p53 gene using a recombinant adenoviral vector (Ad5CMVp53) and applied to semiquantitative reverse transcription-PCRs for the detection of altered mRNA expression of angiogenic and/or antiangiogenic factors. In vivo neovascularization assay of Ad5CMVp53-infected cells was then performed using a membrane-diffusion chamber system s.c. transplanted in nu/nu mice. We also evaluated the effect of Ad5CMVp53-infected H226Br cells on nontransduced tumor cells in vivo by s.c. inoculating mixture of cells into nu/nu mice. Ad5CMVp53 infection markedly inhibited the expression of an angiogenic factor, vascular endothelial growth factor, and increased the expression of a novel antiangiogenic factor, brain-specific angiogenesis inhibitor 1, resulting in reduced neovascularization in vivo. Mixing experiments showed that tumor cells transduced with the wt-p53 gene inhibited the in vivo tumor growth of adjacent nontransduced cells. Our data suggest that a recombinant adenovirus expressing the wt-p53 gene is antiangiogenic, which may explain, in part, the mechanism of the bystander effect induced by the wt-p53 gene transfer on adjacent tumor cells.

Color-coding cancer and stromal cells with genetic reporters in a patient-derived orthotopic xenograft (PDOX) model of pancreatic cancer enhances fluorescence-guided surgery.

Precise fluorescence-guided surgery (FGS) for pancreatic cancer has the potential to greatly improve the outcome in this recalcitrant disease. To achieve this goal, we have used genetic reporters to color code cancer and stroma cells in a patient-derived orthotopic xenograft (PDOX) model. The telomerase-dependent green fluorescent protein (GFP)-containing adenovirus OBP-401 was used to label the cancer cells of a pancreatic cancer PDOX. The PDOX was previously grown in a red fluorescent protein (RFP) transgenic mouse that stably labeled the PDOX stroma cells bright red. The color-coded PDOX model enabled FGS to completely resect the pancreatic tumors including stroma. Dual-colored FGS significantly prevented local recurrence, which bright-light surgery or single-color FGS could not. FGS, with color-coded cancer and stroma cells has important potential for improving the outcome of recalcitrant-cancer surgery.

Human pancreatic adenocarcinomas express parathyroid hormone-related protein.

PTH-related protein (PTHrP) is expressed in many common malignancies such as breast and prostate cancer and can regulate their growth. Little is known, however, about the role of PTHrP in pancreatic adenocarcinoma. To study PTHrP in pancreatic exocrine cancer, we studied its expression in pancreatic cancer cell lines and surgical specimens. Eight human pancreatic adenocarcinoma cell lines were evaluated: AsPC-1, BxPC-3, Capan-1, CFPAC-1, MIA PaCa-2, PANC-1, PANC-28, and PANC-48. Murine monoclonal antibodies to the amino-terminal (1-34), mid-region (38-64), and carboxyl-terminal peptides (109-141) of PTHrP were used to identify cellular PTHrP and secreted PTHrP, including Western blotting and immunocytochemical staining for PTHrP from each cell line. Cellular PTHrP was detected in all cell line extracts by both Western blotting and immunoassay. CFPAC-1, derived from a pancreatic liver metastasis, had the highest concentration of PTHrP, and MIA PaCa-2, derived from primary pancreatic adenocarcinoma, had the lowest. PTHrP was localized by immunocytochemical staining in the cytoplasm in all but one cell line, and both nuclear and cytoplasmic immunostaining were observed in the MIA PaCa-2 and PANC-1 cells. Secretion of PTHrP into cell medium was also observed for each cell line and paralleled intracellular PTHrP levels. Evidence for differential processing of PTHrP expression was provided by studies demonstrating different patterns of PTHrP among the cell lines when assessed by PTHrP immunoassays directed against different PTHrP peptides. In specific, PTHrP secretion measured by a PTHrP-(38-64) assay was highest for BxPC-3, whereas the highest levels of secreted PTHrP-(109-141) occurred in CFPAC-1 and PANC-1. Growth of AsPC-1 cells was stimulated in a dose-dependent manner by PTHrP-(1-34). Immunostaining from archival tissue of patients with pancreatic adenocarcinoma revealed strong PTHrP expression in all 14 specimens. All patients were eucalcemic preoperatively. These results demonstrate that PTHrP is commonly expressed in pancreatic cancer. Our data suggest that PTHrP may have growth-regulating properties in pancreatic adenocarcinoma cells, but further studies are required.

Cytotoxicity, apoptosis, and viral replication in tumor cells treated with oncolytic ribonucleotide reductase-defective herpes simplex type 1 virus (hrR3) combined with ionizing radiation.

The viral ribonucleotide reductase (rR)-defective herpes simplex type-1 (HSV-1) virus (hrR3) has been shown previously to preferentially replicate in and kill tumor cells. This selectivity is associated with tumor cell up-regulation of mammalian rR. Ionizing radiation (IR) is currently used in the therapy of many malignancies, including glioblastoma, cervical carcinoma, and pancreatic carcinoma. IR has been shown to up-regulate mammalian rR in tumor cells and appears to increase the efficacy of at least one non-rR-deleted HSV-1 strain in an in vivo tumor model. Here, we test the hypothesis that a single therapeutic radiation fraction will increase the replication and toxicity of hrR3 for malignant cell lines in vitro. PANC-1 pancreatic carcinoma, U-87 glioblastoma, and CaSki cervical carcinoma cell lines were treated with varying doses of IR and subsequently infected with hrR3 or KOS (wild-type HSV-1 strain). Cell survival was then measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and trypan blue exclusion cytometry. At 72 hours posttreatment, irradiation with 2 Gy reduced survival from 100% to 76% in noninfected cells, from 61% to 48% in KOS-infected cells, and from 39% to 27% in hrR3-infected PANC-1 cells. As such, analysis of variance indicated that the toxicity of the two modalities was additive. Similar additivity was seen in U-87 MG and CaSki cells. Absolute survival of hrR3-infected or KOS-infected PANC-1 cells decreased as a function of time after treatment (24-72 hours) and multiplicity of infection (MOI) (0.05-5.0). However, the relative decrease in survival with the addition of IR to hrR3 or KOS in PANC-1 cells was not markedly affected by altering MOI (0.05-5.0), time (24-72 hours), radiation dose (2-20 Gy), or cell culture conditions (confluent/growth arrested). We used fluorescence-activated cell sorter analysis with the cationic lipophilic dye DiOC6 to quantify a reduction in mitochondrial membrane potential that'is associated with apoptosis. Fluorescence-activated cell sorter analysis indicated increased apoptosis in both hrR3- and IR-treated cells at 48-72 hours, with hrR3 alone producing the most induction. Viral yields from PANC-1 cells after irradiation and infection were examined. No significant differences were seen between irradiated and nonirradiated cells in viral replication, with hrR3 producing single-step titers of 3.1 +/- 0.9 x 10(5) and 4.0 +/- 1.2 x 10(5) plaque-forming units/mL in nonirradiated and irradiated cells. Thus, complementary toxicity was seen between IR and hrR3 or KOS, regardless of cell type, time, MOI, IR dose, or culture conditions, without evidence of augmented apoptosis or viral replication.

Antimetastatic efficacy of adjuvant gemcitabine in a pancreatic cancer orthotopic model.

Gemcitabine is a promising new agent that has been recently studied for palliation of advanced (stage IV) unresectable pancreatic cancer. We hypothesized that adjuvant gemcitabine would reduce recurrence and metastases following surgical resection of pancreatic cancer. To test this hypothesis, we evaluated gemcitabine on a green fluorescent protein (GFP) transductant of the human pancreatic cancer cell line BxPC-3 (BxPC-3-GFP) using surgical orthotopic implantation (SOI) in nude mice. GFP enabled high resolution fluorescent visualization of primary and metastatic growth. Five weeks after SOI, the mice were randomized into three groups: Group I received exploratory laparotomy only. Group II underwent surgical resection of the pancreatic tumor without further treatment. Group III underwent tumor resection followed by adjuvant treatment with gemcitabine, 100 mg/kg every three days for a total of four doses, starting two days after resection. The mice were sacrificed at thirteen weeks following implantation and the presence and location of recurrent tumor was recorded. Gemcitabine reduced the recurrence rate to 28.6% compared to 70.6% with resection only (P = 0.02) and reduced metastatic events 58% in the adjuvant group compared to resection only. This study, demonstrating that gemcitabine is effective as adjuvant chemotherapy post-pancreatectomy, suggests this new indication of the drug clinically.

Chronologically-specific metastatic targeting of human pancreatic tumors in orthotopic models.

Pancreatic cancer is a highly metastatic disease that responds poorly to currently-available treatment. In order to better visualize and understand the chronology and specificity of metastatic targeting of pancreatic cancer, two human pancreatic cancer cell lines, expressing green fluorescent protein (GFP), were studied in orthotopic models. MIA-PaCa2-GFP and BxPC-3-GFP tumor fragments were transplanted by surgical orthotopic implantation (SOI) to the nude mouse pancreas for fluorescence visualization of the chronology of pancreatic tumor growth and metastatic targeting. BxPC-3-GFP tumors developed rapidly in the pancreas and spread regionally to the spleen and retroperitoneum as early as six weeks. Distant metastases in BxPC-3-GFP were rare. In contrast, MIA-PaCa-2-GFP grew more slowly in the pancreas but rapidly metastasized to distant sites including liver and portal lymph nodes. Regional metastases in MIA-PaCa-2-GFP were rare. These studies demonstrate that pancreatic cancers have highly specific and individual 'seed-soil' interactions governing the chronology and sites of metastatic targeting.

Gene therapy and pancreatic cancer.

Adenocarcinoma of the pancreas is associated with a short survival due to frequent delays in diagnosis and the lack of effective systemic therapies. Advances in understanding the molecular basis of pancreatic cancer have allowed identification of molecular targets which are amenable to therapeutic intervention. Such targets include p53, K-ras, p16, and DPC-4. Gene therapy involves the transfer of genetic constructs which alter the neoplastic potential of the cancer cell. Vectors used in gene transfer include viral and non-viral methods. Presently, gene therapy of pancreatic cancer is limited to pre-clinical studies using in vitro and in vivo models. However, the initial results from these pre-clinical studies have been encouraging and will form the basis for clinical studies of gene transfer in patients with pancreatic cancer.

Splenectomy in the accelerated or blastic phase of chronic myelogenous leukemia: a single-institution, 25-year experience.

BACKGROUND: Patients in the accelerated or blastic phases of chronic myelogenous leukemia (CML) often have painful splenomegaly and secondary thrombocytopenia. We tested the hypothesis that splenectomy can be performed with minimal complications in advanced CML, thereby alleviating pain, reversing thrombocytopenia, and minimizing transfusion requirements. METHODS: We reviewed the records of 53 patients in the accelerated or blastic phases of CML who underwent splenectomy between 1970 and 1995 at the U. T. M. D. Anderson Cancer Center. RESULTS: Twenty-eight patients were in accelerated phase and 25 in blastic phase at the time of splenectomy. The most common indications for splenectomy were symptomatic splenomegaly (median splenic weight, 1000 gm; range, 120 to 6700 gm) or thrombocytopenia (platelet count less than 100,000/microliter) or both. There was 1 death within 30 days of splenectomy. The preoperative platelet count increased 3.72-fold +/- 0.53-fold (mean +/- SEM) by postoperative day 7 (p < 0.001; paired t test). Patients with transfusion-dependent thrombocytopenia had significantly fewer platelet and red blood cell transfusions in the 6 months after splenectomy than in the 6 months before splenectomy (p = 0.016; sign test). CONCLUSIONS: Splenectomy can be performed with minimal morbidity and mortality in advanced CML, thereby relieving symptomatic splenomegaly, reversing thrombocytopenia, and minimizing transfusion requirements.

Improved sentinel lymph node localization in patients with primary melanoma with the use of radiolabeled colloid.

BACKGROUND: The purpose of this study was to determine whether the sentinel lymph node (SLN) localization technique, which uses blue dye and 99mTc-labeled sulfur colloid, provides advantages over blue dye alone in the management of patients with stages I and II cutaneous melanoma. METHODS: The records of 626 consecutive patients with melanoma who underwent lymphatic mapping and SLN biopsy between 1991 and 1997 at the M.D. Anderson Cancer Center were reviewed. Lymphatic mapping was performed with isosulfan blue dye alone (n = 252) or in combination with 99mTc-labeled sulfur colloid accompanied by a hand-held gamma probe (n = 374). SLNs were defined as those that stained blue or demonstrated increased focal radiotracer uptake. RESULTS: SLN identification rates improved from 87% (dye alone) to 99% (dye and colloid) (P < .0001) with the combined technique in all anatomic sites examined. The mean number of SLNs harvested from each basin was significantly greater in the patients mapped with dye and colloid (1.74 vs 1.31; P < .0001). Occult metastatic disease was identified in 17.5% of all patients and did not significantly differ between groups. In 92% of patients who had at least one positive SLN and were mapped with both agents, lymphatic metastases were identified in the SLN that contained the greatest radiotracer uptake. CONCLUSIONS: SLN identification is enhanced by the addition of radiolabeled sulfur colloid and intraoperative use of the hand-held gamma probe and may identify SLNs missed by the blue dye alone. These data support the combined use of radiolabeled sulfur colloid and blue dye in lymphatic mapping procedures to improve the nodal staging of stages I and II melanoma.