Brachytherapy boost for prostate cancer: Trends in care and survival outcomes.

PURPOSE: Androgen suppression combined with elective nodal and dose-escalated radiation therapy recently demonstrated an improved biochemical failure-free survival in men who received external beam radiation therapy (EBRT) plus a brachytherapy boost (BB) compared with dose-escalated external beam radiotherapy (DE-EBRT). We sought to analyze the factors predictive for use of EBRT + BB as compared with DE-EBRT and report resulting survival outcomes on a national level using a hospital-based registry. METHODS AND MATERIALS: We identified 113,719 men from the National Cancer Database from 2004 to 2013 with intermediate- or high-risk prostate cancer who were treated with EBRT + BB or DE-EBRT. We performed univariate and multivariate analyses of all available factors potentially predictive of receipt of treatment selection. Survival was evaluated in a multivariable model with propensity adjustment. RESULTS: For intermediate-risk patients, utilization of BB decreased from 33.1% (n = 1742) in 2004 to 12.5% (n = 766) in 2013 and for high-risk patients, utilization dropped from 27.6% (n = 879) to 10.8% (n = 479). Numerous factors predictive for use of BB were identified. Cox proportional hazards analysis was performed-adjusting for age, Charlson-Deyo comorbidity score, T stage, prostate-specific antigen, Gleason score, and sociodemographic factors-and demonstrated BB use was associated with a hazard ratio of 0.71 (95% confidence interval, 0.67-0.75; p < 0.0005) and 0.73 (95% confidence interval, 0.68-0.78; p < 0.0005) for intermediate- and high-risk patients, respectively. CONCLUSIONS: There has been a concerning decline in the utilization of BB for intermediate- and high-risk prostate cancer patients despite an association with improved on overall survival. Numerous factors predictive for use of BB have been identified.

Five year prostate-specific antigen outcomes after caesium prostate brachytherapy.

AIMS: To report 5 year prostate-specific antigen outcomes in men undergoing prostate brachytherapy with caesium 131 at a single institution. MATERIALS AND METHODS: All patients who underwent prostate brachytherapy with caesium 131 at our institution and had at least 24 months of follow-up were included in this study. The results are reported by risk group (low, intermediate and high) as well as by treatment received (monotherapy, combination therapy or trimodal therapy). The Phoenix definition (absolute nadir plus 2 ng/ml) was used to define biochemical freedom from disease (BFD). RESULTS: Four hundred and eighty-five patients underwent prostate brachytherapy with caesium 131 at our institution and 367 patients had at least 24 months of follow-up and were included in this analysis. Using the Phoenix criteria, 5 year actuarial BFD was 96.0% for patients in the low-risk category, 92.7% for patients in the intermediate-risk category and 82.9% for patients in the high-risk category. By treatment category, 95.7% of men treated with monotherapy had BFD, 84.9% of men treated with combination therapy had BFD and 92.0% of men treated with trimodal therapy had BFD. CONCLUSIONS: The present study showed that prostate brachytherapy with caesium 131 achieves excellent oncological outcomes at 5 years.

A first-in-human study of PDC31 (prostaglandin F2α receptor inhibitor) in primary dysmenorrhea.

STUDY QUESTION: What is the safe and pharmacodynamically active dose range for PDC31 (prostaglandin F2α receptor inhibitor) in patients with primary dysmenorrhea (PD)? SUMMARY ANSWER: The 1 mg/kg/h dose of PDC31 appears to be safe and potentially effective in reducing intrauterine pressure (IUP) and pain associated with excessive uterine contractility when given as a 3-h infusion in patients with PD. WHAT IS KNOWN ALREADY: PDC31 has previously been shown to reduce the duration and strength of PGF2α-induced contractions in human uterine myometrial strip models and to delay delivery in animal models of preterm labor. STUDY DESIGN, SIZE, DURATION: This was a prospective, multi-center, dose-escalating first-in-human Phase I study conducted from March 2011 to June 2012. A total of 24 women with PD were enrolled and treated with one of five doses (0.01, 0.05, 0.15, 0.3, 0.5 and 1 mg/kg/h) of PDC31 given as a 3-h infusion. Patients were observed for a further 24 h. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study was conducted at four hospitals in Europe in non-pregnant, menstruating women with PD. Women with PD (n = 24) received PDC31 infused over 3 h within 8-10 h of the onset of menstruation. IUP and pain monitoring through the visual analog scale (VAS) was assessed prior to, during and following the infusion. Patients were observed for dose-limiting toxicities and other adverse events. Pharmacokinetic samples were also taken to profile the drug. MAIN RESULTS AND THE ROLE OF CHANCE: A 3-h infusion of PDC31 was safe up to and including doses of 1 mg/kg/h. Most adverse events were mild (n = 15; 83.3%) and not considered associated with PDC31 (n = 14; 77.8%). PDC31 infusion decreased uterine activity based on IUP and pain (VAS) scores. IUP was decreased by 23% over all dose levels, reaching a minimum at 135-150 min. There appeared to be a dose-dependent effect on IUP, with the high dose group (1 mg/kg/h) showing the largest decrease in IUP. There was a statistically significant linear dose-effect and concentration-effect relationship for several IUP parameters over the evaluation period of 60-180 min. A dose differentiating effect on pain was seen with the two highest doses. PDC31 demonstrated uncomplicated, linear pharmacokinetics with a terminal half-life of ∼2 h. LIMITATIONS, REASONS FOR CAUTION: This was a first-in-human study and exposure to PDC31 was limited for safety reasons. As such, pharmacodynamic parameters were assessed at a two-sided Type I error of 20%, an appropriate level for the exploratory nature of this study without a placebo control arm. This limited the chance of false positive findings to one in five. WIDER IMPLICATIONS OF THE FINDINGS: Like PD, preterm labor is associated with prostaglandin-mediated uterine contractions; therefore, the findings of this study support further development of PDC31 as a treatment for both PD and preterm labor. STUDY FUNDING/COMPETING INTERESTS: This work was funded by PDC Biotech GmbH, Vienna, Austria. B.B., R.M.L., L.W., R.J.S., K.J.B. and C.F.S. received reimbursement for the conduct of this study from PDC Biotech GmbH. W.H., M.S. and R.P.S. are paid consultants for PDC Biotech GmbH. P.G. is a paid consultant and shareholder of PDC Biotech GmbH. TRIAL REGISTRATION NUMBER: NCT01250587 at www.clinicaltrials.gov.

The weekend effect: short-term mortality following admission with a hip fracture.

We retrospectively reviewed 2989 consecutive patients with a mean age of 81 (21 to 105) and a female to male ratio of 5:2 who were admitted to our hip fracture unit between July 2009 and February 2013. We compared weekday and weekend admission and weekday and weekend surgery 30-day mortality rates for hip fractures treated both surgically and conservatively. After adjusting for confounders, weekend admission was independently and significantly associated with a rise in 30-day mortality (odds ratio (OR) 1.4, 95% confidence interval (CI) 1.02 to 1.9; p = 0.039) for patients undergoing hip fracture surgery. There was no increase in mortality associated with weekend surgery (OR 1.2, 95% CI 0.8 to 1.7; p = 0.39). All hip fracture patients, whether managed surgically or conservatively, were more likely to die as an inpatient when admitted at the weekend (OR 1.4, 95% CI 1.02 to 1.80; p = 0.032), despite our unit having a comparatively low overall inpatient mortality (8.7%). Hip fracture patients admitted over the weekend appear to have a greater risk of death despite having a consultant-led service.

A rare report of foetal lingual cyst excised with harmonic scalpel.

Diagnosis of foetal lingual cysts is extremely rare. If large enough, it can compromise the upper oropharyngeal airway. A case of a large ventral lingual thyroglossal duct cyst mimicking a ranula was identified at 20 weeks of gestation and excised 11 weeks postnatally using the harmonic scalpel. The diagnosis and the benefit of ultrasonic dissection in the treatment of glossal lesions are reviewed.

SU-E-T-07: Edema Induced Changes in Tumor Cell Survival Fraction and Tumor Control Probability in 131Cs Permanent Prostate Implant Patients.

PURPOSE: The purpose of this study is to estimate the effect of edema, developed during implant procedure, on tumor cell surviving fraction(SF) and tumor control probability(TCP) in the patients of prostate cancer who underwent 131 Cs permanent seed implants. METHODS: The impact of edema on SF and TCP, was calculated using LQ equation extended to account for exponential nature of edema decay, dose delivered to dematous prostate and inhomogeneous dose distribution. Where (1) S(D)=(1/V)Σi=1n [Vpi{1+M0 exp(-λe t)}Si (D)] Si (D)=exp[-αRi (0)∫0t [exp(- λt)/{1+M0 exp(-λe t)}τ/3]dt -ßq(t){Ri (0)∫0t [exp(-λt)/{1+M0 exp(-λe t)}τ/3]dt }2 ] and (2) TCP=exp[-ρVpS(D)] Following parameters, α=0.15Gy-1 , ß=0.05Gy-2 , α/ß=3.0Gy, Tp=42days, µ=61.6d-1 and ρ=1×106 are used to calculate SF and TCP for 31 patients of 131 Cs permanent seed implants for edema half lives(EHL) ranging from 4 days to 34 days and for edemas of magnitudes(M0 ) varying from 5% to 60% of the actual prostate volume. RESULTS: The dose reductions in 131 Cs implants varied from 1.1% (for EHL=4 days and M0 =5%) to 32.3% (for EHL= 34 days and M0 = 60%). These are higher than the dose reduction in 125 I implants, which vary from 0.3% (for EHL= 4 days and M0 = 5%) to 17.5% (for EHL= 34 days and M0 = 60%). As edema half life increased from 4 days to 34 days and edema magnitude increased from 5% to 60% the SF increased by 4.57 log, and the TCP decreased by 0.80. CONCLUSIONS: Compensation of edema induced increase in the SF and decrease in the TCP in 131 Cs seed implants should be carefully done by redefining seed positions with the guidance of post needle plans. The presented model in this study can be used to estimate the SF or the TCP for pre plan or real time permanent prostate implants using day 0 post implant CT images.

Concurrent chemotherapy and intensity-modulated radiation therapy for anal carcinoma--clinical outcomes in a large National Cancer Institute-designated integrated cancer centre network.

AIMS: To report the clinical outcomes of patients with anal carcinoma treated with intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy in a large integrated academic-community cancer centre network. MATERIALS AND METHODS: Seventy-eight patients were treated with IMRT for anal carcinoma at 13 community cancer centres. IMRT planning for all centres was carried out at one central location. Sixty-five patients (83%) were T1-T2, 64% were N0, 9% were M1; five patients were HIV positive. All but one patient received concurrent chemotherapy. The median dose to the pelvis including inguinal nodes was 45 Gy. The primary site and involved nodes were boosted to a median dose of 55.8 Gy. All acute and late toxicities were scored according to the Common Terminology Criteria for Adverse Events, version 3.0. RESULTS: The median follow-up for the entire cohort was 16 months (range 0-72 months). Acute grade ≥3 toxicity included 27.7% gastrointestinal and 29.0% dermatological. Acute grade 4 haematological toxicity occurred in 12.9% of patients. Sixty-four (88.9%) patients experienced a complete response. The 2 year colostomy-free survival, overall survival, freedom from local failure and freedom from distant failure rates were 81.2, 86.9, 83.6 and 81.8%, respectively. CONCLUSIONS: Early results seem to confirm that IMRT used concurrently with chemotherapy for treatment of anal carcinoma is effective and well tolerated. This complex treatment can be safely and effectively carried out in a large integrated healthcare network.

Clinical and dosimetric factors associated with a prolonged feeding tube requirement in patients treated with chemoradiotherapy (CRT) for head and neck cancers.

BACKGROUND: Patients treated with chemoradiotherapy (CRT) for head and neck cancers often require feeding tubes (FTs) due to toxicity. We sought to identify factors associated with a prolonged FT requirement. PATIENTS AND METHODS: We retrospectively reviewed 80 patients treated with CRT for head and neck cancers. The pharyngeal constrictors (PCs), supraglottic larynx (SGL), and glottic larynx (GL) were contoured and the mean radiation doses and the volumes of each receiving >40, 50, 60, and 70 Gy (V40, V50, V60, and V70) were determined. RESULTS: A total of 33 of 80 patients required a FT either before or during the course of CRT. Fifteen patients required the FT for > or = 6 months. On univariate analysis, significant factors associated with a prolonged FT requirement were mean PC dose, PC-V60, PC-V70, SGL dose, SGL-V70, and advanced T3-T4 disease. Multivariate analyses found both PC-V70 and T3-T4 disease as significant factors .The proportions of patients requiring a FT > or = 6 months were 8% and 28% for treatment plans with PC-V70 <30% and > or = 30%, respectively. CONCLUSIONS: Increased radiation dose to the PCs is associated with a higher risk of a prolonged FT need. Dose sparing of the PC muscles may reduce this risk.

Do gastrointestinal transit parameters influence the pharmacokinetics of gefitinib?

The selective EGFR tyrosine kinase inhibitor, gefitinib has been shown to be active against certain human carcinomas. It had been noted that a proportion of volunteers consistently had lower gefitinib exposure following oral administration. The shape of the elimination profile in this subset was also different, showing a monophasic elimination pattern rather than the biphasic pattern observed in the majority of subjects. A gamma scintigraphic study was conducted to examine the relationship of gastrointestinal transit and drug absorption in a cohort of rapid clearance subjects (n=5) and normal profile volunteers (n=7). The fasted volunteer panel received a 250 mg gefitinib tablet labelled with [(111)In]-DTPA together with 240 mL [(99m)Tc]-labelled water. The rapid clearance cohorts were shown to have a faster mean gastric emptying T90 (37 min vs 74 min) and shorter small intestinal transit time (156 min vs 204 min), resulting in an earlier colonic arrival time (181 min vs 244 min). Mean plasma C(max) was lower (99.2 ng/mL vs 116 ng/mL) and AUC almost half in the rapid clearance group (2162+/-81 ngh/mL vs 4996+/-64 ngh/mL). These data suggest that gastrointestinal transit parameters play a role in the differences in the rapid clearance profile group, also contributing to the biphasic to monophasic switch. However, historical data show, at the recommended dose of 250 mg/day steady-state plasma concentrations adequate for clinical benefit are achieved in patients with non-small cell lung cancer.

Visual and computer software-aided estimates of Dupuytren's contractures: correlation with clinical goniometric measurements.

INTRODUCTION: Corrective surgery for Dupuytren's disease represents a significant proportion of a hand surgeon's workload. The decision to go ahead with surgery and the success of surgery requires measuring the degree of contracture of the diseased finger(s). This is performed in clinic with a goniometer, pre- and postoperatively. Monitoring the recurrence of the contracture can inform on surgical outcome, research and audit. PATIENTS AND METHODS: We compared visual and computer software-aided estimation of Dupuytren's contractures to clinical goniometric measurements in 60 patients with Dupuytren's disease. Patients' hands were digitally photographed. There were 76 contracted finger joints--70 proximal interphalangeal joints and six distal interphalangeal joints. The degrees of contracture of these images were visually assessed by six orthopaedic staff of differing seniority and re-assessed with computer software. RESULTS: Across assessors, the Pearson correlation between the goniometric measurements and the visual estimations was 0.83 and this significantly improved to 0.88 with computer software. Reliability with intra-class correlations achieved 0.78 and 0.92 for the visual and computer-aided estimations, respectively, and with test-retest analysis, 0.92 for visual estimation and 0.95 for computer-aided measurements. CONCLUSIONS: Visual estimations of Dupuytren's contractures correlate well with actual clinical goniometric measurements and improve further if measured with computer software. Digital images permit monitoring of contracture after surgery and may facilitate research into disease progression and auditing of surgical technique.

Comparison between real-time intra-operative ultrasound-based dosimetry and CT-based dosimetry for prostate brachytherapy using cesium-131.

The purpose of this study was to evaluate the correlation between real-time intra-operative ultrasound-based dosimetry (USD) and day 0 post-implant CT dosimetry (CTD) (131)Cs permanent prostate brachytherapy. Fifty-two consecutive patients who underwent prostate brachytherapy with (131)Cs were evaluated. Real time operating room planning was performed using VariSeed 7.1 software. Post-needle placement prostate volume was used for real-time planning. Targets for dosimetry were D(90) >110%, V(100) >90%, V(150) <50%, and V(200) <20%. The CT scan for post-operative dosimetry was obtained on day 0. The mean values for USD, CTD, and the linear correlation, respectively, were, for D(90): 114.0%, 105.61%, and 0.15; for V(100): 95.1%, 91.6%, and 0.22; for V(150): 51.5%, 46.4%, and 0.40; and for V(200): 15.8%, 17.9%, and 0.42. The differences between the mean values for USD and CTD for D(90) (p<0.01), V(100) (p<0.01), and V(150) (p<0.05) were statistically significant. For D(90), 30.8% of patients had a >15% difference between USD and CTD and 51.9% of patients had a >10% difference between these values. In contrast, the USD and CTD for V(100) were within 5% in 55.8% of patients and within 10% in 86.5% of patients. This study demonstrates a correlation between the mean intra-operative USD and post-implant day 0 CTD values only for V(200). Significant variation in D(90), V(150), and V(200) values existed for individual patients between USD and CTD. These results suggest that real-time intra-operative USD does not serve as a surrogate for post-operative CTD, and that post-operative CTD is still necessary.

Detection of cell-free fetal DNA in maternal urine.

OBJECTIVE: To evaluate the presence of cell-free fetal DNA signals in maternal urine as a potential source of material for non-invasive prenatal diagnosis. STUDY DESIGN: Patients referred to the regional fetal medicine unit who underwent prenatal diagnosis by chorionic villus sampling (CVS) were asked to give blood and urine immediately before the procedure. Maternal blood and urine were centrifuged at 10,000 g for 10 min. Plasma (1 mL) and urine (1 mL) supernatant were transferred to a clean tube and centrifuged again. The plasma (0.8 mL) and urine (0.8 mL) supernatant were removed without disturbing the cell pellet and stored at - 80 degrees C. Following DNA extraction, each sample was tested for the presence of Y chromosome associated DYS14 gene using real-time polymerase chain reaction (PCR). The total amount (maternal and fetal) of DNA in each sample was estimated using a quantitative real-time PCR assay. RESULTS: Twenty patients were enrolled in the study. CVS was performed at a median gestational age of 13 weeks (range 11 + 5 - 14 + 1). There were 12 male and 8 female fetuses, as confirmed by karyotype. Y chromosome DNA was not detected in any of the 20 samples of maternal urine, including 12 of the 20 samples in which Y chromosome DNA was detected in maternal plasma (all of whom were subsequently confirmed to be carrying a male fetus). There was considerable variation in the amount of total free DNA detected in maternal urine. CONCLUSIONS: Cell-free fetal DNA either was not present or did not amplify in maternal urine.

Internet use by patients with prostate cancer undergoing radiotherapy.

OBJECTIVES: To analyze the amount of Internet use, type of Internet use, and factors that predict Internet use by patients with prostate cancer. METHODS: A questionnaire evaluating the use of the Internet was given to 295 patients undergoing radiotherapy for prostate cancer in three different settings: an academic center (AC), a Veterans Affairs center (VA), and a community hospital. The study included 171 AC patients (58%), 104 VA patients (35%), and 20 community hospital patients (7%). RESULTS: The response rate to the questionnaire was greater than 99%. Overall, 128 (43%) of 295 patients had a home computer. This differed among the institutions, with 64% of AC patients and only 5% of VA patients having a home computer (P <0.0001). Overall, 94 (32%) of 295 patients used the Internet to access cancer information, with 48% of AC patients and 8% of VA patients using the Internet (P <0.0001). Seventeen percent of black patients (n = 113) had a home computer compared with 62% of white patients (n = 175; P <0.0001). Equal access to computers did not influence Internet use because, among those patients who had access to computers, black patients used the Internet less than did white patients (32% versus 61%, P <0.0001). Men 65 years of age or younger were more likely to use the Internet (45%) than those older than 65 years (28%; P = 0.004). Patients used many sites to access different types of information. CONCLUSIONS: A significant number of patients with prostate cancer access the Internet to obtain cancer information. Urologists and radiation oncologists should be familiar with this important resource to help patients access appropriate material.

Pressure-controlled inverse ratio ventilation after cardiac surgery.

BACKGROUND AND OBJECTIVE: Pressure-controlled inverse ratio ventilation was compared with controlled mechanical ventilation in patients after cardiac surgery. METHODS: Ten patients were ventilated after sternal closure using a Siemens Servo 900C ventilator to a target end-tidal PCO2 of 4.0 kPa. They were randomized to receive controlled mechanical ventilation or pressure-controlled inverse ratio ventilation. CO2-based data were recorded on a laptop personal computer, which together with arterial PCO2 permitted measurement of the respiratory dead space. Once measurements were complete the ventilator was switched to the other mode and new measurements taken. RESULTS: PaCO2 and VCO2 were virtually the same in both modes. Peak airway pressure (17.2 +/- 2.7 vs. 20.8 +/- 2.5 cmH2O, P < 0.01) and minute ventilation (4.9 +/- 1.1 vs. 5.3 +/- 1.1 cmH2O, P < 0.01) were less during pressure-controlled inverse ratio ventilation. Physiological dead space fraction (0.39 +/- 0.06 vs. 0.51 +/- 0.05, P < 0.001), airway dead space (56 +/- 15 vs. 81 +/- 15 mL, P < 0.001) and alveolar dead space fraction (0.25 +/- 0.07 vs. 0.31 +/- 0.09, P < 0.01) were all less during pressure-controlled inverse ratio ventilation. There were no differences in heart rate or mean arterial pressure. CONCLUSIONS: The prolonged inspiratory period and pressure-controlled flow pattern of pressure-controlled inverse ratio ventilation reduce the alveolar and airway dead spaces, and give lower peak airway pressures, compared with conventional ventilation, in cardiac surgical patients.

Lower gastrointestinal disease in women.

Gastrointestinal disease is common in women and therefore a commonly encountered entity in gynecologic practice. A new understanding of the underlying pathophysiology of the most common condition, irritable bowel syndrome, is changing both diagnosis and therapy.

Effects of cytokines and fluconazole on the activity of human monocytes against Candida albicans.

This study evaluates the effects of cytokines, used singly and in combination, on the microbicidal activity of human monocyte-derived macrophages (MDM) against intracellular Candida albicans in the presence and absence of fluconazole. In the absence of fluconazole, the addition of tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), gamma interferon (IFN-gamma), or IL-4 had no effect on the growth of C. albicans. In contrast, the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) resulted in decreased growth (P < 0.05), while the addition of IL-10 resulted in increased growth (P < 0.01). In the presence of fluconazole, only the addition of IFN-gamma resulted in an increase in the growth of C. albicans. In the presence or absence of fluconazole, all cytokine combinations except IFN-gamma plus GM-CSF caused significant decreases in growth (P < 0.01). IL-10 and IL-4 did not influence the activity of TNF-alpha or IL-1beta. In the absence or presence of C. albicans the addition of fluconazole, all of the cytokines studied, and combinations of fluconazole and selected cytokines caused increases in nitric oxide (NO) production (P < 0.01). Similar observations were made for superoxide (O(2)(-)) only in the presence of C. albicans. The greatest concentrations of NO and O(2)(-) were produced when C. albicans alone was present in the assays. Our results demonstrate that in the presence of low concentrations of fluconazole (0.1 times the MIC), selected cytokines and their combinations significantly increase the microbicidal activity of MDM against intracellular C. albicans.

Photodynamic therapy for mesothelioma.

Multiple trials of traditional cancer therapies for malignant pleural mesothelioma (including surgery, radiation therapy, and chemotherapy) have not convincingly demonstrated that any one treatment is superior to supportive care alone. Although there have been reports of long-term survivors who were treated with aggressive surgery combined with radiation and aggressive multi-agent chemotherapeutic regimens, these patient populations are highly selected and results cannot be generalized to a larger population. Despite attempts to use aggressive multimodality therapies, disease recurs in most patients. Local failure in particular is a large part of the natural history of mesothelioma, especially after surgery alone. Therefore, one of the major considerations in the development of new treatments is the inclusion of aggressive local therapies. Photodynamic therapy (PDT), a local treatment modality, is being evaluated as an adjuvant therapy to surgical resection. Clinical use of PDT requires the use of a photosensitizing agent and light of a wavelength specific to the absorption characteristics of the sensitizer in the presence of oxygen. The treatment effect of PDT is superficial, mostly because of the limited depth of light absorption in tissues. Therefore, it is theoretically an ideal treatment for tissue surfaces and body cavities after surgical debulking procedures. One theoretical advantage of PDT is that it can be used to treat the lung surface after a pleurectomy; therefore, patients may be treated with a pleurectomy rather than with an extrapleural pneumonectomy. Several studies have evaluated the efficacy of PDT in the treatment of mesothelioma. Clinical studies have not proven convincingly that the use of PDT is superior to the use of other adjuvant therapies or to surgery alone. The advent of newer photosensitizers and improved laser technology has led to a renewed interest in evaluating PDT. Additional studies are necessary to determine the role of PDT in the treatment of mesothelioma.

Pain and stress in the human fetus.

Invasive diagnostic and therapeutic techniques are increasingly applied to the fetus. It is not known if the fetus feels pain during such procedures, but the fetus does mount significant stress hormonal and circulatory changes in response to these from 18-20 weeks. Perinatal stress may have long-term neurodevelopmental implications. During open fetal surgery, maternal general anaesthesia provides fetal anaesthesia. However, in closed procedures, fetal analgesia presents difficulties. The optimal drug, dose, and route of administration remain to be determined.