Immediate versus expedient emergent laparotomy in unstable isolated abdominal trauma patients.

INTRODUCTION: Unstable abdominal trauma patients should be treated with emergent laparotomy. However, few studies have evaluated the association between time to surgery and survival in these patients. We aimed to assess the influence of time to laparotomy on outcomes in blunt and penetrating unstable abdominal trauma patients. METHODS: This retrospective study includes patients with abdominal injuries, systolic blood pressure <90mmHg on arrival, admitted in Israel during 2000-2018. Data regarding patients' characteristics, Injury Severity Score (ISS), Glasgow Coma Scale (GCS), time to surgery, length of hospital stay and mortality were collected via The Israeli National Trauma Registry. RESULTS: Overall, 69 blunt and 127 penetrating injury patients were included in the study. For blunt and penetrating trauma patients with ISS ≤14, no differences in outcome were found between patients who underwent laparotomy within 60min of admission and those who underwent laparotomy within 60-120min of admission. In patients with blunt trauma, ISS ≥16, and GCS <15, mortality was higher in the immediate laparotomy group (p = 0.004 and 0.049, respectively). CONCLUSIONS: In patients with a penetrating injury, no differences in mortality between immediate and expedient laparotomy were demonstrated. In patients with a blunt injury, with ISS ≥16 and GCS <15, mortality was higher among the immediate laparotomy group.

Dosimetric intercomparison for multicenter clinical trials using a patient-based anatomic pelvic phantom.

PURPOSE: To assess dose delivery accuracy to clinically significant points in a realistic patient geometry for two separate pelvic radiotherapy scenarios. METHODS: An inhomogeneous pelvic phantom was transported to 36 radiotherapy centers in Australia and New Zealand. The phantom was treated according to Phase III rectal and prostate trial protocols. Point dose measurements were made with thermoluminescent dosimeters (TLDs) and an ionisation chamber. Comprehensive site-demographic, treatment planning, and physical data were collected for correlation with measurement outcomes. RESULTS: Dose delivery to the prescription point for the rectal treatment was consistent with planned dose (mean difference between planned and measured dose - 0.1 ± 0.3% std err). Dose delivery in the region of the sacral hollow was consistently higher than planned (+1.2 ± 0.2%). For the prostate treatment, dose delivery to the prostate volume was consistent with planned doses (-0.49 ± 0.2%) and planned dose uniformity, though with a tendency to underdose the PTV at the prostate-rectal border. Measured out-of-field doses were significantly higher than planned. CONCLUSIONS: A phantom based on realistic anatomy and heterogeneity can be used to comprehensively assess the influence of multiple aspects of the radiotherapy treatment process on dose delivery. The ability to verify dose delivery for two trials with a single phantom was advantageous.

Radiotherapy dose-distribution to the perirectal fat space (PRS) is related to gastrointestinal control-related complications.

Traditionally rectal symptoms following pelvic/prostate radiotherapy are correlated to the dosimetry of the anorectum or a substructure of this. It has been suggested that the perirectal fat space (PRS) surrounding the rectum may also be relevant. This study considers the delineation and dosimetry of the PRS related to both rectal bleeding and control-related toxicity. Initially, a case-control cohort of 100 patients from the RADAR study were chosen based on presence/absence of rectal control-related toxicity. Automated contouring was developed to delineate the PRS. 79 of the 100 auto-segmentations were considered successful. Balanced case-control cohorts were defined from these cases. Atlas of Complication Incidence (ACI) were generated to relate the DVH of the PRS with specific rectal symptoms; rectal bleeding and control-related symptoms (LENT/SOM). ACI demonstrated that control-related symptoms were related to the dose distribution to the PRS which was confirmed with Wilcoxon rank sum test (p < 0.05). To the authors knowledge this is the first study implicating the dose distribution to the PRS to the incidence of control-related symptoms of rectal toxicity.

Modelling late stool frequency and rectal pain after radical radiotherapy in prostate cancer patients: Results from a large pooled population.

AIM: To investigate late gastrointestinal toxicity in a large pooled population of prostate cancer patients treated with radical radiotherapy. Normal tissue complication probability models were developed for late stool frequency and late rectal pain. METHODS AND MATERIALS: Population included 1336 patients, 3-year minimum follow-up, treated with 66-80Gy. Toxicity was scored with LENT-SOMA-scale. Two toxicity endpoints were considered: grade ⩾2 rectal pain and mean grade (average score during follow-up) in stool frequency >1. DVHs of anorectum were reduced to equivalent uniform dose (EUD). The best-value of the volume parameter n was determined through numerical optimization. Association between EUD/clinical factors and the endpoints was investigated by logistic analyses. Likelihood, Brier-score and calibration were used to evaluate models. External calibration was also carried out. RESULTS: 4% of patients (45/1122) reported mean stool frequency grade >1; grade ⩾2 rectal pain was present in the TROG 03.04 RADAR population only (21/677, 3.1%): for this endpoint, the analysis was limited to this population. Analysis of DVHs highlighted the importance of mid-range doses (30-50Gy) for both endpoints. EUDs calculated with n=1 (OR=1.04) and n=0.35 (OR=1.06) were the most suitable dosimetric descriptors for stool frequency and rectal pain respectively. The final models included EUD and cardiovascular diseases (OR=1.78) for stool frequency and EUD and presence of acute gastrointestinal toxicity (OR=4.2) for rectal pain. CONCLUSION: Best predictors of stool frequency and rectal pain are consistent with findings previously reported for late faecal incontinence, indicating an important role in optimization of mid-range dose region to minimize these symptoms highly impacting the quality-of-life of long surviving patients.

Surgical caseload and outcomes for women with invasive breast cancer treated in Western Australia.

We have assessed the outcomes for all women diagnosed with invasive breast cancer in Western Australia during 1989, 1994 and 1999, and compared the results for surgeons who treat 20 or more cases per year with those of surgeons who treat less. Women treated by high caseload surgeons were more likely to retain their breast (53.3% vs. 36.7%, p<0.001), have adjuvant radiotherapy (50.0% vs. 30.6%, p<0.001), and be alive after 4 years (1989, 86% vs. 82%; 1994, 89% vs. 84%; 1999, 90% vs. 79%, HR 0.71, p=0.03). Adjusting for age and year of diagnosis, women were not more likely to be treated with adjuvant chemotherapy (29.2% vs. 20.9%, p=0.28). In 1989 35% of women were treated by high caseload surgeons. By 1999 this had risen to 82%. The results confirm that women treated by high caseload surgeons have better outcomes.

Prevalence of HIV-1 DNA and p24 antigen in breast milk and correlation with maternal factors.

Breast milk specimens from human immunodeficiency virus type 1 (HIV-1)-seropositive and HIV-1-seronegative women were examined for the presence of HIV-1 p24 antigen by the antigen capture method and for viral DNA using the polymerase chain reaction. HIV-1 DNA was present in 70% of milk specimens collected from 47 HIV-seropositive women 0-4 days after delivery and in approximately 50% of specimens collected 6 and 12 months postpartum. p24 antigen, present in 24% of milk specimens collected from 37 seropositive women within the first 4 days postpartum, was not detected in any of the subsequent specimens. The presence of HIV-1 DNA or p24 antigen in milk was not significantly associated with maternal CD4 lymphocyte count, beta 2-microglobulin level, or fulfillment of the AIDS clinical case definition. Although the correlation of either HIV-1 proviral DNA or p24 antigen with the presence of infectious virus is not known, these data indicate the need for additional studies examining the role of breastfeeding in maternal-infant transmission of HIV-1.

Tangential breast irradiation: simple improvements.

A series of studies using phantom and in vivo dosimetry measurements with diodes and thermoluminescent dosimetry were undertaken to establish whether simple methods are available to obtain improvements in homogeneity of dose in the treated breast, and reductions of dose to tissues outside it, when using tangential 6MV photon fields. These studies confirmed that the use of an appropriate lung density correction factor in the planning process is likely to cause a reduction in the amount of wedge compensation predicted to be necessary to produce reasonable dose homogeneity in the central axis of the beam. This was shown to be of value in eliminating potential areas of overdosage in the chest wall medial and lateral to the breast mound, and also in reducing unwanted doses to the contralateral breast and lung. Further reductions in dose to contralateral breast were confirmed to occur when the majority, or all, of the wedge compensation predicted necessary is placed on the lateral field and when the lateral tangential field is angled anteriorly in such a way as to align the posterior beam edges. Skin does above, below, and over the breast mound were observed to depend critically upon angle of incidence of the beam, with its consequent effect upon electron build-up, and the position of the breast contour in the beam. Skin doses above and below the breast mound were shown to exceed over the mound itself. This differential effect was observed to increase with increasing wedge compensation. In some situations skin doses below the breast mound nearly reached prescribed dose within the breast. The design and use of simple lead attenuators to reduce these areas of high dosage is discussed.

Functional similarities and differences of AMPA and kainate receptors expressed by cultured rat sensory neurons.

Dorsal root ganglion neurons express functional AMPA and kainate receptors near their central terminals. Activation of these receptors causes a decrease in glutamate release during action potential evoked synaptic transmission. Due to differences in kinetic properties and expression patterns of these two families of glutamate receptors in subpopulations of sensory neurons, AMPA and kainate receptors are expected to function differently. We used embryonic dorsal root ganglion (DRG) neurons maintained in culture to compare functional properties of kainate and AMPA receptors. Most DRG neurons in culture expressed kainate receptors and about half also expressed AMPA receptors. Most AMPA and kainate receptor-expressing DRG neurons were sensitive to capsaicin, suggesting involvement of these glutamate receptors in nociception. When activated by kainate, AMPA receptors were capable of driving a sustained train of action potentials while kainate receptors tended to activate action potential firing more transiently. Glutamate elicited more action potentials and a larger steady-state depolarization in neurons expressing both AMPA and kainate receptors than in neurons expressing only kainate receptors. Adding to their more potent activation properties, AMPA receptors recovered from desensitization much more quickly than kainate receptors. Activation of presynaptic receptors by low concentrations of kainate, but not ATPA, caused a tetrodotoxin-sensitive increase in the frequency of spontaneous EPSCs recorded in dorsal horn neurons. By recording synaptic pairs of DRG and dorsal horn neurons, we found that activation of presynaptic kainate and AMPA receptors decreased evoked glutamate release from terminals of DRG neurons in culture. Our data suggest that the endogenous ligand, glutamate, will cause a different physiological impact when activating these two types of non-NMDA glutamate receptors at central or peripheral nerve endings of sensory neurons.

Bacillus Calmette-Guérin complications in children born to HIV-1-infected women with a review of the literature.

OBJECTIVE: To compare the risk of complications following Bacillus Calmette-Guérin (BCG) vaccination among children by maternal and infant HIV-1 infection status as part of an investigation of an outbreak of BCG complications. METHODS: A nonconcurrent cohort study of BCG complications among 125 infants born to HIV-1 seropositive and 166 infants born to HIV-1 seronegative mothers was conducted in Cité Soleil, Haiti. Infants were examined at regular intervals until 15 months of age, and complications from BCG were documented. An investigation of BCG vaccination practices was conducted. RESULTS: Mild or moderate complications occurred among 16 of 166 (9.6%) infants born to HIV-1 seronegative mothers compared with 4 of 13 HIV-1-infected infants (30.8%, P = .04) and 10 of 75 (13.3%, P = .39) uninfected infants born to HIV-1-infected mothers. No serious complications were noted. The outbreak of complications was associated with administration of 2.0 to 2.5 times the recommended dose of BCG vaccine. CONCLUSIONS: This and five other cohort studies indicate that there may be a small increased risk of complications following BCG vaccination among HIV-1-infected children, but the reactions are usually mild and the risk does not outweigh the benefits of BCG vaccination in populations at high risk of tuberculosis during infancy and childhood.

Factors influencing the degree of erythematous skin reactions in humans.

Dose-response relationships have been studied using an ordinal visual scale and reflectance spectrophotometry data from 123 treatment sites on 110 patients treated with 10 dose fractions over 12-14 days. Dose rates varied between 3 and 240 Gy/h and total doses of between 25 and 41 Gy were given using teletherapy apparatus. We found qualitative scoring of erythematous skin reactions to be subject to considerable inter- and intra-observer variation. Reflectance spectrophotometry provided more reproducible information, some of which was undetectable by naked eye. Baseline erythema readings were significantly higher in male patients and at anatomical sites of previous heavy UV exposure. In addition, a pronounced decline in erythema readings during the second week of therapy and 'reciprocal vicinity' (abscopal) effects adjacent to the field, undetected by the eye, were observed in a subset of patients. Meaningful dose-response relationships could be derived only from reflectance data with peak change from the pretreatment baseline measure providing the best discrimination. Peak erythema measures following treatment were found to depend on the age and gender of the patient as well as the treatment site and its baseline erythema measurement. This was independent of the total dose administered or the instantaneous dose rate at which it was delivered. The rate of erythema development was also dose rate dependent but only weakly dependent on the biological dose intensity (Gy equiv./day) of the treatment course. The data raise the question of whether irradiation-induced erythema is exclusively a secondary phenomenon occurring as a result of basal cell killing. The short repair half time value of 0.06 h obtained by direct analysis is perplexing and may reflect a dose rate-dependent physiological vasodilatory response to irradiation and/or a multi-component cellular repair process.

A phase III double-blind randomised study of rectal sucralfate suspension in the prevention of acute radiation proctitis.

BACKGROUND AND PURPOSE: A limited number of studies have suggested that oral sucralfate reduces the acute and late gastro-intestinal side-effects of pelvic radiotherapy and sucralfate enemas ameliorate symptoms of chronic proctitis. Sucralfate may act via local bFGF at the mucosal level in promoting angiogenesis and reducing epithelial associated microvascular injury. This multi-institutional study was designed to test the hypothesis that sucralfate given as an enema would have a significant protective effect against acute radiation induced rectal injury by direct application to the mucosa. MATERIALS AND METHODS: Eighty-six patients having radiotherapy for localised carcinoma of the prostate were randomised in a double-blind placebo-controlled study to receive either 15 ml of placebo suspension or 3 g of sucralfate in 15 ml suspension, given as a once daily enema during and for 2 weeks following radiotherapy. Assessment was based on the EORTC/RTOG acute toxicity criteria and a patient self-assessment diary. RESULTS: There was no significant difference between placebo and sucralfate for peak incidences of EORTC/RTOG proctitis. For the placebo and sucralfate arms 95 and 88% (difference 7 +/- 11%) suffered some degree of proctitis, with 71 and 61% (difference 10 +/- 19%) reaching grade 2, respectively. The median period to onset of grade 2 proctitis was 33.5 and 36 days, with the median duration being 9.5 and 15 days, respectively, again these difference being non-significant. Thirty-five and 37% of patients rated the effect of radiotherapy on bowel habit as 'a lot' with a moderate or severe effect on normal daily living in 52 and 49%, respectively. CONCLUSION: This study suggests that sucralfate given as a once daily enema does not substantially reduce the incidence of symptoms associated with acute radiation proctitis and its routine clinical use cannot be recommended. This cohort of patients will be followed to determine if any difference develops in relation to late toxicity.

Factors influencing outcome following radio-chemotherapy for oesophageal cancer. The Trans Tasman Radiation Oncology Group (TROG)

BACKGROUND AND PURPOSES: To define new directions, the Trans Tasman Radiation Oncology Group (TROG) has conducted a detailed analysis of its unrandomised experience with radio-chemotherapy in oesophageal cancer. METHODS AND PATIENTS: Since 1984, 373 patients with oesophageal cancer have been treated on three prospective, but unrandomised, protocols involving radiation with concurrent cisplatin and infusional fluorouracil. Centres in Australia and New Zealand have contributed patients. Reasons for case selection have been examined in detail and prognostic models have been examined in the light of biases exposed. RESULTS: Cause specific survival in 92 patients treated pre-operatively with 35 Gy, infusional fluorouracil and cisplatin was 25.5 +/- 6.0% at 5 years and similar to the 5 year expectations of 169 patients treated with 60 Gy and two courses of the same chemotherapy (23.8 +/- 4.7%). Analysis of failure in these groups suggests that local relapse precedes the development of metastases and competes as a cause for ultimate failure. Although patients treated surgically were less likely to relapse locally, survival was no better because more developed metastases. Some of the 112 patients treated "palliatively" with 30-35 Gy concurrent with chemotherapy without surgery have become long-term survivors with 5 year survival figure in this group 7.7 +/- 3.4%. Apart from variables related to disease stage and performance status at presentation, tumour site emerged as a strong predictor of outcome. Prognosis worsens the nearer the tumour is to the stomach. In addition, indications of a radiation dose response relationship emerged. CONCLUSIONS: Concurrent radio-chemotherapy protocols can improve outcome in patients fit enough to tolerate these approaches. New strategies remain necessary, however.

A combined modality approach to the management of oesophageal cancer.

This study aims to update the experience of multimodality approaches in the management of oesophageal cancer that have been adopted in several Australian and New Zealand hospitals. Between 1984 and 1985, 92 patients received pre-operative radiotherapy (30-36 Gy over 3 weeks) and one of two chemotherapy regimes (one or two courses of i.v. cisplatin 80 mg/m2 plus a 4-5 day continuous i.v. of fluorouracil 5-800 mg/m2/day) concurrently prior to surgery. Eighty-two patients (89%) underwent resection as planned. Operative specimens were microscopically free of residual tumour in 18 patients. Eight patients (9%) had treatment-related deaths: seven from surgery and one due to pre-operative chemoradiation. The Kaplan-Meier 5-year cause-specific survival estimates were 32.9 +/- 7.8% for the 58 patients with squamous cancer and 0% for the 32 with adenocarcinoma. Complete pathological response to the pre-operative regime was more common in females and was associated with a survival advantage. Five-year cause-specific survival expectation in patients who experienced a complete pathological response was 71.5 +/- 12.4%, whereas it was only 15.9 +/- 5.6% in patients who had residual cancer in their surgical specimens. Although less toxic the pre-operative regime utilizing only one cycle of chemotherapy was no less efficacious either in producing a complete pathological response or in terms of survival expectation. This uncontrolled pilot study has produced encouraging long-term results, especially for patients with squamous carcinoma that experienced a complete response to pre-operative synchronous chemoradiotherapy. A randomized controlled study comparing surgery alone with (one cycle) chemoradiation followed by surgery is now underway.

Phase I/II study of concurrent weekly carboplatin and radiation therapy in advanced head and neck cancer.

Thirty-two patients with locally advanced head and neck cancer have been treated with concurrent weekly carboplatin and conventional radiation therapy (RT) (2 Gy fractions 4-5 days/week to a total dose of 64-70 Gy over 7-8 weeks) in a Phase I/II study. Carboplatin was administered weekly during RT at doses of 75-150 mg/m2/wk as a 1-hour infusion. The maximum tolerated dose of carboplatin was 130 mg/m2/wk, with myelosuppression, predominantly neutropenia, being dose limiting. Other systemic toxicities were insignificant and no overlapping toxicity was evident. Ultimate locoregional control and survival probabilities were disappointing. It is suggested that either further studies using radiation and carboplatin at the dose 130 mg/m2/wk, or variations on dose and scheduling be performed prior to the instigation of Phase III studies.

Pelvic radiotherapy with concurrent 5-fluorouracil modulated by leucovorin for rectal cancer: a phase II study.

Combined modality treatment for cancer of the rectum has been shown to reduce recurrences and improve overall survival. We wished to find out if we could safely give concurrent radiotherapy and 5-fluorouracil (5-FU) modulated by leucovorin (LV) in 3 settings: pre-operatively, adjuvantly and in recurrent disease. A total of 39 patients were treated, 11 preoperatively, 17 adjuvantly and 11 with recurrent disease. There were 26 males and 13 females with a median age of 64 years. The median radiotherapy (RT) dose was 45 Gy/25 fractions/1.8 Gy per fraction (range 25-63 Gy). Chemotherapy consisted of LV 80 mg/m2 i.v. infusion over 1.5 hours followed by 5-FU 400 mg/m2 i.v. bolus, both given once a week. The median number of cycles was 8 (range 3-12). Diarrhoea was the main toxicity, and was encountered in 30 patients (77%): grade 1 in 3 (8%), grade 2 in 12 (30%), grade 3 in 11 (28%), and grade 4 in 4 (10%). This required 18 (46%) patients to have modifications to their RT (20% had breaks and 26% ceased at doses < 45 Gy). Nine patients (23%) had modifications in the chemotherapy (10% had breaks and 13% received < 6 cycles). Encouraging responses were seen in the preoperative setting. Concurrent RT and 5-FU/LV, as given in this schedule, results in an unacceptable incidence of diarrhoea, limiting both the total dose of RT and chemotherapy that can be delivered, particularly in patients who have had previous surgery.

Treatment and planning decisions in non-small cell carcinoma of the lung: an Australasian patterns of practice study.

Fourteen practising radiation oncologists were surveyed to assess their treatment and planning habits utilizing six sample cases of non-small cell carcinoma of the lung. Respondents were first given a general questionnaire, designed to evaluate their theoretical treatment and planning recommendations based on various tumour and patient related variables. Respondents then undertook a practical planning exercise utilizing planning CT and simulator radiographs for each of the six sample cases. Each case was accompanied by a brief history and report outlining specific tumour stage and non-stage related variables. The practical planning exercise was repeated on the second day of the survey utilizing different non-stage related variables but identical radiology and stage-related information. This design enabled firstly, a comparison of clinicians' intended policy and planning methods with actual policy and planning decisions, and secondly, an assessment of intra-clinician variability in decision making and planning practice. Good agreement was evident among clinicians with respect to general, non-case specific treatment policies; however, very significant variation occurred at an inter- and intra-clinician level and involved the entire treatment and planning process for individual cases. Despite identical treatment intent across identical radiological case pairings, clinicians chose widely differing margins and target volumes in their planning exercise. Treatment intent appeared to be influenced more by non-stage related variables rather than stage related information and radiological appearances per se. We have shown that experienced radiation oncologists do not adhere to stated case selection criteria and show inconsistencies in their treatment planning for non-small cell carcinoma of the lung.

High-frequency hearing loss in male farmers of Missouri.

Farmers are exposed to noise that is potentially hazardous to hearing. We measured the hearing of 161 male farmers and 75 male nonfarmers at the 1979 Missouri Farmers Association Agri-Fair and compared it with the hearing of 129 office workers from central Missouri. Fixed-level screening tests were conducted in both ears at three stimulus frequencies: 1000 and 2000 hertz at 20 decibels hearing level and 4000 hertz at 25 decibels hearing level. Audiometers were calibrated in accordance with the ANSI-1969 standard. The results show that farmers are at risk for hearing loss at 2000 and 4000 hertz when compared with office workers. The prevalence of hearing loss was greater for farmers at both frequencies in every decade age group from 25 to 64 years. Using screening failure at 2000 and 4000 hertz in both ears as a criterion for a loss that would affect communication ability, we found that the failure rate was 16.8 percent for farmers and 6.2 percent for office workers. As other investigators have found, the prevalence of high-frequency hearing loss in male nonfarmers who associate with farmers was nearly as great as for farmers.

Use of the Doppler ultrasonic flowmeter for pedicle flaps.

Summary--The Doppler ultrasonic flowmeter is presented as a method to help in flap outlining, transfer and return. When a directional flowmeter is added, this machine is extremely valuable for returning a flap at the earliest possible time. The Doppler is a safe, inexpensive, atraumatic, reliable instrument that can be learned in a very short time. We have found the Doppler to be very helpful in head and neck flaps.

Two non-parametric methods for derivation of constraints from radiotherapy dose-histogram data.

Dose constraints based on histograms provide a convenient and widely-used method for informing and guiding radiotherapy treatment planning. Methods of derivation of such constraints are often poorly described. Two non-parametric methods for derivation of constraints are described and investigated in the context of determination of dose-specific cut-points-values of the free parameter (e.g., percentage volume of the irradiated organ) which best reflect resulting changes in complication incidence. A method based on receiver operating characteristic (ROC) analysis and one based on a maximally-selected standardized rank sum are described and compared using rectal toxicity data from a prostate radiotherapy trial. Multiple test corrections are applied using a free step-down resampling algorithm, which accounts for the large number of tests undertaken to search for optimal cut-points and the inherent correlation between dose-histogram points. Both methods provide consistent significant cut-point values, with the rank sum method displaying some sensitivity to the underlying data. The ROC method is simple to implement and can utilize a complication atlas, though an advantage of the rank sum method is the ability to incorporate all complication grades without the need for grade dichotomization.