Intraoperative radiotherapy in the treatment of neuroblastoma: Report of a pilot study

Background: External beam radiotherapy in advanced neuroblastoma is limited by the volume of normal radiosensitive tissues included in the radiation field. Limitations to external radiation are the late effects to these tissues. Intraoperative radiotherapy (IORT) delivers a single high-radiation dose to a tumor while displacing normal tissues that would have been included in an external field. Standard external radiotherapy can still be done after boost IORT. Methods: Eight advanced-stage neuroblastoma patients who received IORT as part of their multimodality therapy were reviewed to identify the impact of IORT on operative time, complications, and tumor control in the treatment field. The IORT was accomplished by patient transport from the OR to the radiation therapy suite; these were separated by three floors. Results: IORT added 30–75 min to the operative procedure. Tumors in the resection/IORT fields showed no evidence of disease (one), stable tumor size (six), and tumor recurrence (one). Two complications were identified: a urinary fistula and CO₂ retention, which was detected and corrected before the IORT. Neither of these complications was related to the IORT. Two patients who had subsequent tumor resection after IORT demonstrated tumor differentiation to ganglioneuromatous tissue. Conclusions: IORT usually can be completed in less than an hour. No IORT-associated complications were identified. IORT along with maximal tumor resection, external radiation, and chemotherapy enhances local tumor control.Presented in part at the 47th Annual Symposium of The Society of Surgical Oncology, Houston, TX, March 17–20, 1994.     

Intraperitoneal Versus Interpleural Morphine or Bupivacaine for Pain after Laparoscopic Cholecystectomy

Background: Opioids can produce peripheral analgesic effects by activation of opioid receptors on sensory nerves. This study was designed (1) to examine a novel route of opioid administration, the intraperitoneal injection; (2) to compare this to interpleural application, and (3) to compare opioid with local anesthetic effects under both conditions.

Methods: At the end of laparoscopic cholecystectomy, 110 patients received the following injections in a double-blind, randomized manner: Group 1 (n = 18) was given intraperitoneal morphine (1 mg in 20 ml saline) and 20 ml intravenous saline. Group 2 (n = 17) received intraperitoneal saline and 1 mg intravenous morphine. Group 3 (n = 15) received 20 ml 0.25% intraperitoneal bupivacaine and intravenous saline. Group 4 (n = 20) received interpleural morphine (1.5 mg in 30 ml saline) and 30 ml intravenous saline. Group 5 (n = 20) received interpleural saline and 1.5 mg intravenous morphine. Group 6 (n = 20) received 30 ml 0.25% interpleural bupivacaine and intravenous saline. Postoperative pain was assessed using a visual analog scale, a numeric rating scale, and the McGill pain questionnaire. Pain localization, supplemental analgesic consumption, vital signs, and side effects were recorded for 24 h.

Results: Neither intraperitoneal nor interpleural morphine produced significant analgesia after laparoscopic cholecystectomy (P > 0.05, Kruskal-Wallis test), whereas interpleural bupivacaine was effective (P < 0.05, Kruskal-Wallis test, up to 6 h postoperatively) but not intraperitoneal bupivacaine (P > 0.05, Kruskal-Wallis test). Shoulder pain was not prevalent in the majority of patients during the first 6 h. By 24 h, about half of the patients complained of shoulder pain, which was rated "low" by about one-third of all patients. No significant side effects occurred.     

A breast feeding education and promotion program: Effects on knowledge,attitudes, and support for breast feeding

This study was undertaken to determine the effects of a partner-support, incentive-baed educational program on breast feeding knowledge, attitudes and support and to examine the relationship between feeding intentions and feeding behavior among low-income women. Women who expressed a willingness to participate in the intervention were randomly assigned to intervention and usual breast feeding (control) groups. Sixty-eight primipara women, with expected due dates between May and December, 1992, volunteered to participate in the study. Of these, 34 were randomly assigned to each of the two groups. Approximately 81 percent of the women completed the study, leaving n=29 in the control group and n-26 in the intervention group. The intervention consisted of special incentives (prizes) for women and their partners to participate in several breast feeding education and promotion activities. Intervention group women and their partners experienced positive changes in breast feeding knowledge and attitudes. Furthermore, the intervention seemed to have influenced more women in the treatment group to breast feed despite their prenatal feeding intentions. In addition, the partners of intervention group women were perceived to be more supportive of, breast feeding than control group partners. These findings suggest that incentives, such as donated prizes, can be used to attract lower socioeconomic group women and their partners to breast feeding promotion interventions. Participation in such interventions can produce positive changes in breast feeding knowledge, attitudes, and support, and can have a dramatic effect in promoting breast feeding.This study was supported through contract no. 59-3198-1-050 from the Food and Nutrition Service, U.S. Department of Agriculture.     

A stereological analysis of the lateral geniculate nucleus in adult Macaca nemestrina monkeys

The Cavalieri method and the optical fractionator were employed to estimate the volume and neuron numbers, respectively, of the dorsal lateral geniculate nucleus (dLGN) in seven adult male pigtail monkeys (Macaca nemestrina). Unbiased estimates were selectively obtained for the parvocellular (P), magnocellular (M), and interlaminar plus superficial (I + S) layers of the nucleus. The dLGN had a mean volume of 56.5 mm3, and contained on average 1.79 million neurons. The P layers contributed 64% of the volume and 83% of the neurons in the dLGN; the corresponding proportions for the other layers were 13% and 9% (M), and 23% and 8% (I + S). Interindividual variability was large for neuron counts, which varied within a two-fold range, and lower for volume estimates. Since no published data are available for the pigtail dLGN, the present results are compared with quantitative studies of the dLGN in other macaque species, placing special emphasis in the discussion of the methodologies used.     

Tissue potassium,selenium, and iron levels associated with gastric cancer progression

The contents of 10 minor and trace elements in histologically confirmed gastric adenocarcinomas and their corresponding normal gastric mucosal tissues obtained from 39 patients at the time of gastric resection were simultaneously determined by instrumental neutron activation analysis. Specimens were irradiated by reactor neutrons and subsequently subject to direct analysis using a high-resolution HPGe -spectrometer. Univariate analysis revealed that gastric cancer tissues had significantly higher concentrations of Fe, K, Mg, Na, Rb, Se, and Zn than normal gastric mucosal tissues. However, multivariate analysis found that Fe, K, and Se were independent elements that associated with gastric cancer. Upon further evaluation of their clinical significance, we found a high tissue K level was related to lymphatic duct metastasis. High Se tissue levels were linked to intestinal type adenocarcinoma. A positive correlation was found between high Fe levels and vascular involvement. These findings suggest that Fe and K are associated with gastric cancer progression. Se is involved in carcinogenesis of stomach in high-risk areas. The mechanisms that underlie the corresponding pathohistological features deserve further study.     

Totally laparoscopic aortobifemoral bypass grafting in an experimental model: Description of technique with initial surgical results

Our aim was to examine the feasibility of a totally laparoscopic insertion of a bifurcated aortofemoral bypass graft in a canine model and to compare the surgical results with those in control animals undergoing standard grafting and laparoscopic-assisted bypass procedures. Using a six-port approach, we exposed and cross clamped the aorta, tunneled a bifurcated Dacron graft, and performed an end-to-end aortic anastomosis while maintaining pneumoperitoneum by means of CO₂. Proximal anastomoses were performed with 4/0 double-ended continuous Prolene sutures and distal anastomoses were performed through standard groin incisions. Total operating and aortic cross-clamp times were measured as was the total blood loss for each procedure. Clinical outcome was also documented. Eight female laboratory-bred hounds underwent successful totally laparoscopic aortobifemoral bypass grafting, eight underwent open grafting, and eight underwent laparoscopic-assisted bypass. Mean operating time was 193 minutes in the animals undergoing totally laparoscopic insertion vs. 156 minutes in the open group and 180 minutes in the laparoscopic-assisted group. Aortic cross-clamping time was also significantly longer at 87 minutes vs. 43 minutes (p < 0.001)=" in=" the=" totally=" laparoscopic=" group,=" but=" blood=" loss=" was=" less.=" all=" eight=" laparotomy=" and=" laparoscopic-assisted=" dogs=" were=" still=" alive=" with=" no=" complications=" at=" 28=" days,=" whereas=" three=" of=" the=" eight=" in=" the=" totally=" laparoscopic=" group=" showed=" evidence=" of=" temporary=" paraplegia.=" this=" experimental=" study=" demonstrates=" that=" a=" totally=" laparoscopic=" approach=" can=" be=" used=" to=" insert=" a=" bifurcated=" aortofemoral=" bypass=" with=" a=" proximal=" end-to-end=" anastomosis=" but=" currently=" does=" not=" save=" time=" and=" may=" increase=" the=" risk=" of=" neurologic=">Presented at the Twentieth Annual Meeting of the Peripheral Vascular Surgery Society, New Orleans, La., June 10, 1995.     

Pay Status as a Predictor of Outcome in Surgical Treatment of Obesity

Background: Higher complication rates and lower success in surgery for severe obesity have been reported for patients with government pay status. We examined the effect of pay status upon outcome in surgical treatment of obesity. Methods: This was an observational study from an aggregate data set of individual patient information. Government pay status (G) was defined as full or partial medical care payment through Medicare, Medicaid, or Veterans Administration. Payment entirely by private insurance was defined as private (P). Operations were classified as either simple (S, gastric restriction) or complex (C, gastric restriction with small bowel bypass). Two measures of outcome, perioperative complication rate and weight loss success (≤50% excess weight), were examined to determine pay status effect. Results: More G than P patients were treated with simple procedures (79% vs 51%, p < 0.05). Perioperative complication rates were more common for G than P patients (14.4% vs 9.1%, p < 0.05). One-year weight loss success was higher for P than G, regardless of operation type. Conclusion: Pay status should be included in characterization of patient groups and in the analysis of results when effectiveness of surgical treatment for severe obesity is reported.     

Comparative Pharmacology of Cisatracurium (51W89), Atracurium, and Five Isomers in Cats

Background: Atracurium has four chiral centers and the marketed product is a mixture of ten optical and geometric isomers. Six of the isomers were prepared and evaluated for neuromuscular blocking activity and autonomic effects in anesthetized cats. This study reports the comparative pharmacology of the six isomers and atracurium that led to the selection of one isomer, cisatracurium (Nimbex, 51W89) for clinical development.

Methods: Purpose bred cats, anesthetized with alpha-chloralose (80 mg/kg) and pentobarbital sodium (7 mg/kg) administered intraperitoneally, were used in this study. Neuromuscular blocking effects were assessed from the effects on the tibialis anterior twitch evoked at 0.15 Hz. Inhibition of the autonomic nervous system was assessed from the effects on the nictitating membrane contraction, in response to preganglionic sympathetic nerve stimulation and the bradycardia/vasodepressor responses to vagal nerve stimulation. Cardiovascular effects and plasma histamine concentrations were determined after a bolus injection of cisatracurium or atracurium.

Results: Like atracurium, all six isomers produced dose-dependent neuromuscular block (NMB). The calculated ED95 NMB values varied approximately tenfold (43+/-2 micro gram/kg-488+/-56 micro gram/kg). The "R-series" isomers were more potent than the corresponding "S series" isomers. With the exception of the S,Trans-S', Trans isomer, the NMB effects, i.e., onset times (range 2.6+/-0.2 min to 4.7+/-0.3 min) and total durations (range 9.9+/- 1.4 min to 14+/-0.9 min), of the other five isomers were very similar to that of atracurium. The former isomer had a relatively short duration of action. The 25-75% recovery times after cisatracurium at 1x ED sub 95 (4.4+/-0.4 min), 4x ED95 (4.5+/-0.4 min), and continuous infusions lasting at least 60 min that maintained 95-99% NMB (4.8+/-0.4 min) indicated a noncumulative effect. The vagal ID50: NMB ED95 ratios for atracurium and the six isomers ranged from 2 to 27. The sympathetic ID25: NMB ED95 ranged from 2.7 to 60. Atracurium and all of the isomers, except cisatracurium, produced cardiovascular effects after intravenous bolus administration at large doses (700-4,800 micro gram/kg). In contrast to atracurium, there were no changes in plasma histamine concentrations associated with the administration of doses of cisatracurium equivalent to 60x the NMB ED95 (62+/-8 micro gram/kg).     

Molecular diagnosis of exocrine pancreatic cancer using a percutaneous technique

Background: The K-ras oncogene is activated by point mutations at codon 12 in most patients with exocrine pancreatic cancer. Mutant-enriched polymerase chain reaction (PCR) amplification can enhance the detection of mutated K-ras. This technique was applied to patients undergoing percutaneous fine-needle aspiration (FNA) biopsy of suspect pancreatic lesions. Methods: Twenty-five patients underwent percutaneous FNA of the pancreas for cytologic and molecular analysis. After preparing cytologic smears, the 22-gauge needle and syringe used for FNA were rinsed in RPMI-1640. The specimen was centrifuged, and DNA was extracted from the supernatant and subjected to mutant-enriched PCR using appropriate mismatched primers that introduce a BstNI restriction endonuclease cleavage site at codon 12 of wild-type, but not mutant, K-ras. After digestion with BstNI, the DNA was reamplified. To increase assay sensitivity, the final five PCR cycles were completed incorporating 5 μCi of (α-32P)dCTP. The DNA was then redigested and subjected to gel electrophoresis and autoradiography. Results: The median amount of DNA retrieved per specimen was 3.33 μg. Mutant K-ras was detected as a band of 143 bps; residual wild-type DNA was seen as a 114-bp fragment. Twenty-one of 25 specimens demonstrated mutated K-ras DNA. Two patients with nondiagnostic cytology results had mutated K-ras DNA; adenocarcinoma of pancreatic origin was confirmed in both cases after pancreatectomy. Conclusion: The molecular diagnosis of pancreatic cancer through identification of mutations in K-ras can be readily performed on specimens obtained by percutaneous FNA. As aggressive multimodality management of this disease becomes more common, pretreatment analysis of molecular determinants may have greater clinical significance. Presented at the 48th Cancer Symposium of The Society of Surgical Oncology, Boston, Massachusetts, March 23–26, 1995.     

A Field Test of the Sweat Patch

The sweat patch is a new, noninvasive method designed to estimate the ethanol consumption of drinking subjects. It consists of salt-impregnated absorbent pads protected by a plastic chamber with attached water-tight adhesive. The patch reportedly collects transepidermal fluid at a steady rate for up to 10 days. Recent laboratory research has indicated a linear relationship between the concentration of ethanol in transepidermal fluid and mean concentration of ethanol in blood. Levels of ethanol in the sweat patch allowed identification of persons drinking at least 0.5 g of ethanol/kg/day with 100% sensitivity and specificity. The study reported here was conducted to test the field effectiveness of this sweat patch in normal, active research subjects. First, several pretests were conducted to determine the optimal location of the patch on the body and its fluid uptake at various sites. A laboratory experiment using nonalcoholic subjects was conducted to replicate previous work, and methods of measuring ethanol concentration in the patch were refined. A field test of the patch was then carried out. Healthy active volunteers drank a single "moderate" dose of ethanol (0.5 g of ETOH/kg of body weight) and then remained abstinent for the next 3 days. A week later, a "heavy" dose (1.0/kg of body weight) was consumed. Only a trace of ethanol was detected in any of the patches worn in either experiment. The patch did not measure ethanol in the transepidermal fluid under field conditions. Thus, further design modifications and pilot testing are required before the full benefits of this unobtrusive measure of drinking can be realized.