Randomized clinical trial of negative pressure wound therapy as an adjunctive treatment for small-area thermal burns in children.

BACKGROUND: The efficacy of negative pressure wound therapy (NPWT) in the acute management of burns remains unclear. The purpose of this trial was to compare standard Acticoat™ and Mepitel™ dressings with combined Acticoat™, Mepitel™ and continuous NPWT to determine the effect of adjunctive NPWT on re-epithelialization in paediatric burns. METHODS: This two-arm, single-centre RCT recruited children with acute thermal burns covering less than 5 per cent of their total body surface area. The primary outcome was time to re-epithelialization. Blinded assessments were performed using photographs captured every 3-5 days until discharge. Secondary measures included pain, itch, grafting, perfusion and scar management referrals. RESULTS: Some 114 patients were randomized. Median time to re-epithelialization was 8 (i.q.r. 7-11) days in the NPWT group and 10 (8-14) days in the control group. In a multivariable model, NPWT decreased the expected time to wound closure by 22 (95 per cent c.i. 7 to 34) per cent (P = 0·005). The risk of referral to scar management was reduced by 60 (18 to 81) per cent (P = 0·013). Four participants in the control group and one in the NPWT group underwent grafting. There were no statistically significant differences between groups in pain, itch or laser Doppler measures of perfusion. Adverse events were rare and minor, although NPWT carried a moderate treatment burden, with ten patients discontinuing early. CONCLUSION: Adjunctive NPWT hastened re-epithelialization in small-area burn injuries in children, but had a greater treatment burden than standard dressings alone. Registration number: ACTRN12618000256279 ( http://ANZCTR.org.au).

ANTECEDENTES: La eficacia del tratamiento de las heridas con presión negativa (negative pressure wound therapy, NPWT) en el tratamiento agudo de las quemaduras sigue sin estar claro. El propósito de este ensayo clínico fue comparar los apósitos estándar del tipo Acticoat™ y Mepitel™ con la combinación de Acticoat™, Mepitel™ y NPWT continua para determinar el efecto de la adición de NPWT en la reepitelización de las quemaduras en pediatría. MÉTODOS: Ensayo controlado y aleatorizado, con dos brazos y unicéntrico, que reclutó niños con quemaduras térmicas agudas que afectaban < 5% de la superficie corporal total. El resultado primario fue el tiempo hasta la reepitelización. Se realizaron evaluaciones a ciegas utilizando fotografías tomadas cada 3-5 días hasta el alta hospitalaria. Las medidas secundarias incluían dolor, picor, injerto, perfusión y derivación para el tratamiento de las cicatrices. RESULTADOS: Se aleatorizaron un total de 114 pacientes. La mediana de tiempo hasta la reepitelización fue 8 días (rango intercuartílico, interquartile range, IQR 7-11) en el grupo NPWT y 10 días (8-14) en el grupo control. En el modelo multivariable, el uso de NPWT disminuyó los días previstos hasta el cierre de la herida en un 22% (i.c. del 95% 7-34%; P = 0,005). El riesgo de ser derivado para el tratamiento de la cicatriz se redujo en un 60% (18-81%; P = 0,013). Cuatro participantes en el grupo control y uno en el grupo NPWT fueron sometidos a injertos. No hubo diferencias estadísticamente significativas en el dolor, picor, o mediciones de la perfusión con Doppler laser. Los eventos adversos fueron raros y menores, aunque NPWT conllevó una carga de tratamiento moderada con 10 pacientes que lo suspendieron precozmente. CONCLUSIÓN: El tratamiento complementario de la herida con presión negativa acelera el tiempo hasta la reepitelización en quemaduras de pequeña extensión en niños, pero implica una mayor carga de tratamiento.

Susceptibility of channel catfish, Ictalurus punctatus (Rafinesque), to Edwardsiella ictaluri challenge following copper sulphate exposure.

Channel catfish, Ictalurus punctatus (Rafinesque), with or without a preliminary 24 h exposure to 2 mg copper sulphate L(-1), were challenged with 7.5 x 10(6) colony forming units L(-1) of Edwardsiella ictaluri to determine the effect of copper sulphate on disease resistance. Catfish previously exposed to copper sulphate were significantly more resistant to the bacterial challenge than those not exposed. Catfish not exposed to copper sulphate suffered 35.5% mortality while catfish exposed to copper sulphate experienced 14.1% mortality. Copper concentrations were the same in tank waters of both exposed and control fish at the time of challenge, eliminating the possibility that copper in the water may have been toxic to bacteria. Copper concentrations in freeze dried and ground tissues of unexposed, exposed, and purged channel catfish were highest in fish before copper sulphate exposures suggesting that elevated tissue levels of copper were not responsible for the increased resistance to bacterial challenge. Competition for sites of bacterial attachment to gill or epithelial cells may account for the reduction in mortality; although this is not supported by the low copper content of fish tissue after copper exposure.

Channel catfish virus gene expression in experimentally infected channel catfish, Ictalurus punctatus (Rafinesque).

Channel catfish virus (CCV) produces an acute haemorrhagic disease in fingerling channel catfish and establishes latent infection in fish that survive the primary infection. This study investigated CCV gene expression in tissues of experimentally infected fish. Reverse transcriptase polymerase chain reaction assays were developed for detection of transcripts expressed by each of the CCV direct repeat region genes in CCV-infected channel catfish ovary cells and in tissues of infected fish. Immediate-early, early and late gene transcripts were detected in the blood, brain, kidney and liver tissues of acutely infected catfish demonstrating active viral replication in multiple tissues during the early stages of CCV infection. However, there was no evidence for viral replication by 24 days post-infection in tissues of fish that survived the acute disease. Viral latency-associated transcripts encoded by CCV direct repeat genes were not detected in latently infected catfish. The results of this study provide a foundation for further studies to investigate the molecular basis of CCV pathogenesis and latency.

Toxicity of copper in an oxic stream sediment receiving aquaculture effluent.

Sediments were collected from a stream (upstream, outfall and downstream) receiving copper laden catfish pond effluent to assess toxicity to non-target biota. No significant reduction in Hyalella azteca survival or growth (10 d), or Typha latifolia germination and root and shoot growth (7 d) were observed after exposure to upstream and outfall sediments. A significant reduction in H. azteca survival was observed after exposure to the downstream sediment sample; however, no reduction in T. latifolia germination or seedling growth was detected. Bulk sediment copper concentrations in the upstream, outfall and downstream samples were 29, 31, and 25 mg Cu/kg dry weight, respectively. Interstitial water (IW) concentrations ranged from 0.053 to 0.14 mg Cu/l with 10 d IW toxicity units > or = 0.7. Outfall samples were amended with additional concentrations of copper sulfate so that bulk sediment measured concentrations in the amended samples were 172, 663, 1245, and 1515 mg Cu/kg dry weight. Survival was the most sensitive endpoint examined with respect to H. azteca with a no observed effects concentration (NOEC) and lowest observed effects concentration (LOEC) of 1245 and 1515 mg Cu/kg, respectively. NOEC and LOEC for T. latifolia root growth were 663 and 1245 mg Cu/kg, respectively. IW copper concentrations were > or = 0.86 mg Cu/l with H. azteca intersitial water toxicity unit (IWTU) concentrations > or = 1.2. Sequential extraction qualitatively revealed the carbonate and iron oxide fractions which accounted for a majority of the copper binding. In this instance, the copper which was applied to catfish ponds does not appear to be adversely impacting the receiving stream system.

Effects of the oxidant potassium permanganate on the expression of gill metallothionein mRNA and its relationship to sublethal whole animal endpoints in channel catfish.

Potassium permanganate is an oxidant heavily used in fish culture. The effects of this compound were examined utilizing molecular (Metallothionein) and whole animal endpoints following an 8-week exposure to nominal concentrations of 0.5 (daily) and 1.0 and 2.0 mg/L (on alternate days) of potassium permanganate (PM). In order to measure MT, a complementary DNA clone of metallothionein (MT) was cloned and sequenced from the liver of channel catfish treated with a single injection of cadmium chloride (10 mg/kg). The cDNA was obtained by reverse transcriptase polymerase chain reaction (RT-PCR), using 3' rapid amplification of cDNA ends (RACE) technique. No significant correlation was observed with gill MT expression or sublethal endpoints indicative of toxicity (weight, length, condition index [CI], or liver somatic index [LSI). MT mRNA expression in gill was significantly reduced only after 8 weeks in the 2.0 mg/L treatment. Decreases in CI were observed in males at all time points after 4 weeks, at the 2.0 mg/L treatment concentration, with a NOEC of 1 mg/L. Reductions in LSI that were not dose dependent were also observed in both males and females throughout the 8-week study and no consistent reduction in weight gain or length was observed. These data demonstrate that minimal changes in sublethal effects occur in fish following 0.5-2.0 mg/L PM treatment after 4 weeks, but recovery from adverse effects is observed by 8 weeks, suggesting that acute (typically less than 1 week) treatment of channel catfish with PM would not significantly affect fish health.

Detection of channel catfish virus DNA in latently infected catfish.

Channel catfish virus (CCV) disease is an acute haemorrhagic disease in juvenile channel catfish (Ictalurus punctatus). While fish that survive primary CCV infection are suspected of being carriers of CCV, little is known concerning CCV latency. In this report, fingerling catfish were infected with CCV by experimental immersion challenge. Infected fish displayed clinical signs of CCV disease, but 22% of infected fish survived the acute disease. At 140 days post-infection, PCR analysis detected CCV DNA in the blood, brain, intestines, kidney, liver and peripheral blood leukocytes of latently infected fish. Further analysis indicated the CCV genome may exist as circular or concatemeric DNA during virus latency. This study, employing an experimental model of CCV disease, confirms that CCV establishes a latent infection of channel catfish.

Surgical resection of stage IIIA and stage IIIB non-small-cell lung cancer after concurrent induction chemoradiotherapy. A Southwest Oncology Group trial.

UNLABELLED: Recent studies suggest that preoperative induction chemotherapy +/- radiotherapy can improve the historically poor resectability and survival of patients with stage IIIA non-small-cell lung cancer, but sometimes with significant associated morbidity and mortality. Such treatment has not been studied in stage IIIB non-small-cell lung cancer, usually considered unresectable. This multiinstitutional phase II trial tested the feasibility of concurrent preoperative chemoradiotherapy for stages IIIA and IIIB non-small-cell lung cancer. METHODS: Eligible patients had pathologically documented T1-4 N2-3 disease (without pleural effusions). Induction therapy was cisplatin, 50 mg/m2, days 1, 8, 29, and 36 plus VP-16, 50 mg/m2, days 1 to 5, and 29 to 33 plus concurrent radiotherapy (4500 cGy, 180 cGy fractions). Resection was attempted 3 to 5 weeks after induction if the response was stable, partial, or complete. Complete nodal mapping at thoracotomy was required. RESULTS: One hundred forty-six patients were entered. This interim analysis is based on the first 75 eligible patients for whom complete surgical data are available. There were 49 men and 26 women, median age 58 years (range 32 to 75 years). Sixty-eight of (91%) patients were eligible for operation, and 63 of 75 patients (84%) underwent thoracotomy. Fifty five of 75 patients (73%), including 12 of 16 with a stable response, had a complete resection. Four of 63 patients died postoperatively (6%). Approximately one third required a "complex" resection, for example, lobectomy plus chest wall or spine resection, but mean operating time was 3.2 hours and mean blood loss was less than 1000 ml for both stages IIIA and IIIB. Complete pathology data are currently available from 53 patients: 11 (21%) had no residual tumor; 20 (30%) had rare microscopic foci of residual cancer. The 2-year survival is 40% for both stages IIIA and IIIB. CONCLUSIONS: This combined modality therapy has been well tolerated and has been associated with high response and resectability rates in both stage IIIA and stage IIIB non-small-cell lung cancer. Current survival is significantly better than survivorship among historical control patients and provides a firm basis for subsequent phase III clinical trials.

The role of fast neutron radiation therapy in the management of advanced salivary gland malignant neoplasms.

Fifty-three patients with locally advanced salivary gland malignant neoplasm were treated with fast neutron radiation therapy. All patients received treatment for gross inoperable, residual unresectable, or recurrent disease--clinical situations in which results using photon irradiation were suboptimal. With a median follow-up of 42 months and a minimum follow-up of 1 year, locoregional tumor control in the treatment field was achieved in 92% (48 of 52) of patients. An additional eight patients had regional failures outside the treatment field, resulting in an overall locoregional tumor control rate of 77% (40 of 52). The 5-year actuarial locoregional control rates were 65% overall and 75% in patients with node-positive disease. Grouping patients according to prior treatment status, actuarial 5-year locoregional control rates were 92% for patients treated definitively (without a prior surgical procedure), 63% for those treated postoperatively for gross residual disease, and 51% for those treated for recurrent disease after a surgical procedure. The P values associated with these differences were 0.12 and 0.01, respectively. There were no instances of radiation-induced facial nerve damage. This study suggests that neutron irradiation alone should be the therapy of choice in the treatment of advanced-stage salivary gland tumors and that surgery should be limited to those patients in whom disease-free margins can be obtained. The potential morbidity of a debulking surgical procedure before neutron irradiation is not warranted by an improvement in loco-regional control over that achievable with neutron therapy alone.

Reirradiation for recurrent cerebral astrocytoma.

We describe a case of reirradiation for symptomatic, recurrent, inoperable cerebral astrocytoma grade II. Symptomatic and radiographic response were obtained with no evidence of radiation induced brain injury three years following reirradiation. The factors affecting radiation injury and indications for reirradiation are discussed. Repeat radiotherapy is a useful treatment option in selected patients with recurrent brain tumors.

Current use of electron beam therapy in the United States.

Owing to their physical characteristics, electron beams are a crucial component in radiotherapy of human tumors. Besides their main indications (skin cancers, head and neck tumors, breast, chest wall recurrence, low pelvic tumors) other types and sites of malignancies are to be considered: skin lymphomas, soft tissue sarcomas, Kaposi's sarcoma in AIDS patients, as well as Intra Operative Radiotherapy.

Transient and chronic neurological complications of fast neutron radiation for adenocarcinoma of the prostate.

The records of 132 patients participating in clinical trials using fast neutron (n = 94), mixed neutron and photon (n = 16), or conventional photon (n = 22) irradiation for primary management of prostatic cancer were retrospectively reviewed to assess treatment-related neurological complications. With a median follow-up of 14 months (range 1 to 101 months), 31/132 patients (26 neutron, 3 mixed beam, 2 photon) have experienced either sciatica beginning during or shortly after treatment, or diminished bladder or bowel continence that developed at a median time of 6.5 months following treatment. Sciatica responded to oral steroids and was usually self-limited, whereas sphincter dysfunction appears to be permanent. Pre-treatment risk factors for complications included a history of hypertension, diabetes, cigarette smoking or peripheral vascular disease, with 81% of affected patients having one or more risk factors compared with 55% of unaffected patients (p = 0.01). Seven patients have moderate (5) or severe (2) residual problems, all in the cohorts receiving neutrons (6/7) or mixed beam therapy (1/7).

The role of prophylactic cranial irradiation in regionally advanced non-small cell lung cancer. A Southwest Oncology Group Study.

Lung cancer is the most common malignant disease in the United States. Only the few tumors detected very early are curable, but there has been some progress in the management of more advanced non-small cell lung cancer, particularly in regionally inoperable disease. Prevention of central nervous system relapse is an important issue in this group of patients because brain metastases ultimately develop in 20% to 25% of them. Seventy-three patients with regionally advanced non-small cell lung cancer were entered into a Phase II trial of neutron chest radiotherapy sandwiched between four cycles of chemotherapy including cisplatin, vinblastine, and mitomycin C. Prophylactic cranial irradiation was administered concurrently with chest radiotherapy (3000 cGy in 10 fractions in 15 patients; 3600 cGy in 18 fractions in the remaining 50 patients). Patients underwent computed tomographic scan of the brain before treatment and every 3 months after treatment. The initial overall response rate was 79%, but 65 of the 73 patients have subsequently died of recurrent disease. Median follow-up is 9 months for all 73 patients and 26 months for eight long-term survivors. No patient who completed the prophylactic cranial irradiation program had clinical or radiologic brain metastases. Toxic reactions to prophylactic cranial irradiation included reversible alopecia in all patients, progressive dementia in one patient, and possible optic neuritis in one patient. Both of these patients received 300 cGy per fraction of irradiation. The use of prophylactic cranial irradiation has been controversial, but its safety and efficacy in this trial supports its application in a group of patients at high risk for central nervous system relapse. Further evaluation of prophylactic cranial irradiation in clinical trials for regionally advanced non-small cell lung cancer is warranted.

Neutron radiation therapy for unresectable non-small-cell carcinoma of the lung. A review.

Over 200 patients have been entered in five studies investigating the use of fast neutron radiation therapy in the treatment of non-small-cell carcinomas of the lung since 1983. The results of these studies have been inconsistent. Most studies did not show survival rates or local control advantages over standard photon radiation therapy. Side effects from studies employing mixed photon-neutron treatment plans or clinically oriented, high-energy cyclotrons were seen to be comparable to those of standard courses of radiation therapy, representing a considerable improvement over those studies utilizing low-energy cyclotrons for a full course of radiation therapy, which resulted in unacceptably high complication rates. A new phase III study utilizing high-energy isocentric neutron beams has been designed and implemented, and over 100 patients have been entered to date. The current status of fast neutron radiation therapy in the treatment of non-small-cell lung cancer is reviewed.

Neutron radiotherapy for malignant gliomas.

Neutron radiotherapy has been used for patients with malignant gliomas for over a decade; a substantial number of patients have been treated to date. Pathologic analysis of surgical specimens posttreatment and autopsy specimens have documented an increased antitumor effect of neutrons against malignant gliomas, compared with photon irradiation. However, results of neutron trials to date have not shown a survival advantage over conventional radiotherapy for these patients. This article reviews current surgical, radiotherapeutic, and chemotherapeutic approaches to these tumors, the rationale for neutron treatment, and the results of trials of neutron radiotherapy conducted to date for patients with malignant gliomas.

Fast neutron radiotherapy for sarcomas of soft tissue, bone, and cartilage.

The basic radiobiological rationale for the use of fast neutron radiotherapy in the treatment of classically radioresistant tumors such as soft tissue sarcomas, osteogenic sarcomas, and chondrosarcomas is reviewed. There are no definitive randomized studies comparing high and low linear energy transfer radiotherapy for these tumor systems, but a review of published series is highly suggestive of a therapeutic advantage for fast neutrons. For soft tissue sarcomas, the local control rate is 53% (158 of 297) with fast neutrons, compared with 38% (49 of 128) with photons/electrons; for osteogenic sarcomas, the local control rate is 55% (40 of 73) with fast neutrons, compared with 21% (15 of 73) with photons/electrons; and for chondrosarcomas, the local control rate is 49% (25 of 51) with fast neutrons, compared with 33% (10 of 30) with photons/electrons. An ongoing clinical trial for these tumors is also described.

Cyclophosphamide, vincristine, cisplatin, VP-16 and radiation therapy in extensive small-cell lung cancer. A Southwest Oncology Group Study.

Patients with extensive small-cell lung cancer were given induction chemotherapy consisting of cyclophosphamide, vincristine, cisplatin, and etoposide (COPE) every 3 weeks for four cycles. Responding patients then received chest and elective whole-brain irradiation. Patients presenting with brain metastases received therapeutic brain irradiation during the first cycle of chemotherapy. No maintenance therapy was given, but two late intensification cycles of COPE were given at weeks 24 and 48. Among the 34 evaluable patients, the response rate to induction chemotherapy was 59%, with 10% achieving a complete response (CR) and 49%, a partial response (PR). Of the 18 patients who completed chest irradiation, 3 achieved a CR, producing an overall CR rate of 18%. Five patients completed the projected course of treatment. The median duration of response for all patients was 8 months (range, 2-30+ months) and the median survival was 9 months (range, 1-30+ months). Complete responders had a median response duration of 9 months and a median survival of 11 months. This regimen produced significant myelosuppression, with 5 neutropenic deaths (13%) occurring in the 38 patients evaluable for toxicity; an additional 16% required hospitalization for fever while neutropenic. Only six patients (13%) had nadir platelet counts of less than 50,000/mm3 with no episodes of thrombocytopenic hemorrhage. Nausea, vomiting, and neurotoxicity were mild to moderate in all patients. One patient with no evidence of disease died of radiation pneumonitis at 6 months. While producing significant toxicity, this regimen did not result in a CR rate or survival advantage that would suggest its superiority over standard regimens for small-cell lung cancer.

Combined intracavitary and external beam irradiation for superficial transitional cell carcinoma of the bladder: an alternative to cystectomy for patients with recurrence after intravesical chemotherapy.

A total of 17 patients with superficial transitional cell carcinoma of the bladder underwent treatment with pelvic external beam irradiation followed by an intracavitary 137cesium implant via a triple lumen Foley catheter. Of these patients 11 had recurrent and multifocal superficial cancer, with 8 having relapse after prior intravesical chemotherapy. External beam doses of 3,600 to 5,066 cGy. were followed by implant doses delivering 2,000 to 3,200 cGy. to the bladder mucosa, with the sum of external and intracavitary doses totaling 6,500 to 7,500 cGy. Of 15 patients evaluable with a median followup of 48 months, and including 13 followed for more than 2 years, 11 (73 per cent) remain free of disease, 3 (20 per cent) have recurrence in the bladder but have retained the bladder and only 1 has required cystectomy. All 4 failures occurred in the subgroup of 8 patients who had received prior intravesical chemotherapy. This bladder-sparing approach is well tolerated, is an alternative to cystectomy in patients with recurrent superficial transitional cell carcinoma of the bladder and in our series has salvaged 50 per cent (4 of 8) of the patients even after failure of intravesical chemotherapy.

Soft-tissue changes after head and neck radiation: CT findings.

To identify possible soft-tissue changes of the head and neck after radiation therapy, 102 CT scans from 78 patients with head and neck tumors were reviewed to assess (1) skin thickening, (2) epiglottic thickening, (3) stranding of subcutaneous fat, and (4) stranding of deep cervical fat. Scans were obtained after radiation therapy alone (10 cases), after radiation and surgery (27 cases), after surgery alone (24 cases), or before either surgery or radiation (41 cases). Skin thickening, epiglottic thickening, and stranding of subcutaneous fat were seen more frequently after radiation therapy than before such treatment. However, skin thickening and stranding of subcutaneous fat were sometimes also associated with tumor involvement and/or previous surgery, while epiglottic thickening was only occasionally associated with tumor involvement. Stranding of deep cervical fat was noted with increased frequency after radiation or surgery, but postradiation effects could not be reliably distinguished from postsurgical or tumor effects. We conclude that soft-tissue changes of the head and neck on CT may commonly be associated with previous radiation therapy, but these postradiation effects are not always distinguishable from postsurgical effects or tumor.

Improved radiotherapy treatment planning for spinal cord tumors using gadolinium enhanced MR imaging.

Primary intramedullary spinal cord tumors are frequently difficult to localize for radiation treatment planning. Conventional imaging techniques, including unenhanced magnetic resonance (MR) scans, cannot clearly distinguish residual tumor from surrounding normal spinal cord. Recently, contrast agents have been developed for MR that have considerable promise for improving tumor volume definition. This report describes the impact of contrast-enhanced MR on the treatment planning process for four patients with primary spinal cord tumors and discusses the significance of this technique for patients with these neoplasms.