Polo-like kinase 1 is essential for the first mitotic division in the mouse embryo.

Polo-like kinase 1 (PLK1), a member of the serine/threonine protein kinases family, is involved in multiple steps of mitotic progression. It regulates centrosome maturation, mitotic spindle formation, and cytokinesis. While studied extensively in somatic cells, little is known about PLK1 activities in the mammalian preimplantation embryo. We examined the role of PLK1 in the one-cell mouse embryo. Western blotting showed that the PLK1 protein content increased significantly during the S-phase of the one-cell stage and declined during the first mitotic division. Activation of PLK1 preceded nuclear envelope breakdown (NEBD) in both pronuclei at the entry to first embryo mitosis. Immunofluorescence revealed the presence of phosphorylated, active PLK1 (pThr(210) -PLK1) in both male and female pronuclei, and in the microtubule-organizing centers (MTOCs) shortly before NEBD. During the first mitotic metaphase, pThr(210) -PLK1 accumulated at the spindle poles and was also associated with condensed chromosomes. Inhibition of PLK1 activity with a specific PLK1 inhibitor, BI 2536, at the one-cell stage induced the formation of a bipolar spindle that displayed disordered microtubular arrangements and dislocated, condensed chromosomes. Although such embryos entered mitosis, they did not complete mitosis and arrested at metaphase. Time-lapse recording revealed progressive misalignment of condensed chromosomes during first mitotic metaphase. These data indicate that PLK1 activity is not essential for entry into first mitosis, but is required for the events leading up to metaphase-anaphase transition in the one-cell mouse embryo.

Role of N-terminal pro B-type natriuretic peptide in identifying patients at high risk for adverse outcome after emergent non-cardiac surgery.

BACKGROUND: Patients undergoing emergency surgery continue to be at very high risk, but accurate risk identification for the individual patient remains difficult. This study tested the usefulness of perioperative N-terminal pro B-type natriuretic peptide (NT-proBNP) for in-hospital and long-term risk stratification. METHODS: We conducted a prospective single-centre observational cohort study in an Austrian university hospital. Two hundred and ninety-seven consecutive patients >50 yr of age undergoing a variety of emergency non-cardiac procedures were included. The primary endpoint was a composite of non-fatal myocardial infarction (MI), acute heart failure, or death between index surgery and 3 yr follow-up. The secondary endpoint was in-hospital major adverse cardiac events (MACE), defined as non-fatal MI, acute heart failure, or cardiac death. RESULTS: During a median follow-up of 34 months (inter-quartile range: 16-39), 31% of subjects reached the primary endpoint. A preoperative NT-proBNP ≥725 pg ml(-1) was associated with a 4.8-fold univariate relative risk [95% confidence interval (CI): 3.1-7.6] and a postoperative NT-proBNP ≥1600 pg ml(-1) was associated with a four-fold univariate relative risk (95% CI: 2.7-6.2) for reaching the primary endpoint. Moreover, preoperative NT-proBNP remained a significant and independent (hazards ratio 1.91, 95% CI 1.08-3.37, P=0.027) predictor in a multivariate Cox proportional hazards model. A preoperative NT-proBNP ≥1740 pg ml(-1) was associated with a 6.9-fold univariate relative risk (95% CI: 3.5-13.4) for MACE during the index hospital stay, but did not remain significant in a multivariate logistic regression model. CONCLUSIONS: Preoperative NT-proBNP can help identify patients at high risk for adverse long-term outcome after emergency surgery.

Sensitivity and specificity of bispectral index for classification of overt hepatic encephalopathy: a multicentre, observer blinded, validation study.

BACKGROUND: The severity of hepatic encephalopathy is currently graded clinically using West Haven criteria and psychometric tests. OBJECTIVE: To assess the discriminative power of the bispectral index (BIS) monitor to classify the degree and progression of hepatic encephalopathy. DESIGN: A consecutive, multicentre, observer blinded validation study. SETTING: Medical University of Graz (Graz, Austria), Zhejiang University First Affiliated Hospital (Hang Zhou, China), and Cairo University (Cairo, Egypt). PATIENTS: 28 consecutive patients with hepatic encephalopathy were first enrolled at Medical University of Graz as a test set. The estimated BIS cut off values were subsequently tested in a validation set of 31 patients at Zhejiang University First Affiliated Hospital and 26 patients at Cairo University; 18 patients were reassessed later in a longitudinal study. Fifteen of 85 patients (18%) were excluded from the final analysis (11 became too agitated with high electromyographic activity; four fell asleep during the recording). RESULTS: Applying the Austrian BIS cut off values of 85, 70, and 55 for discriminating West Haven grades 1 to 4 yielded agreement between BIS classification and West Haven grades in 40 of the 46 validation patients (87%), and in 16 of the 18 follow up patients (89%). Mean (SD) BIS values differed significantly between patients with West Haven grade 1 (90.2 (2.5)), grade 2 (78.4 (6.6)), grade 3 (63.2 (4.8)), and grade 4 (45.4 (5.0)). CONCLUSIONS: BIS is a useful measure for grading and monitoring the degree of involvement of the central nervous system in patients with chronic liver disease.

Influence of acute normovolaemic haemodilution on bispectral index monitoring and propofol dose requirements.

BACKGROUND: Numerous medical and physiological conditions that might alter electroencephalography (EEG), such as hypoglycaemia, hypothermia or hypovolaemia, were shown to result in the bispectral Index (BIS) indicating an incorrect hypnotic state. Recently, acute normovolaemic haemodilution (ANH) was shown to be associated with significant impairment of cognitive functions that could alter EEG and consequently BIS monitoring, an EEG derived parameter. METHODS: In a randomised clinical study, we assessed the effect of ANH on BIS monitoring before induction and after propofol target controlled infusion (TCI) anaesthesia in 45 unmedicated patients randomly allocated to ANH with oxygen insufflation (oxygen group), ANH with air insufflation (air group), or control group. RESULTS: With ANH, mean BIS values briefly declined in the oxygen group (82+/-4) and air group (84+/-3) before returning to baseline values. The loss of consciousness time was significantly shorter, with fewer propofol TCI dose requirements, and BIS was significantly higher in the oxygen group (1.3+/-0.5 min, 2.41+/-0.15 microg/ml, 73+/-7) and air group (1.2+/-0.6 min, 2.44+/-0.17 microg/ml, 75+/-5), compared with the control group (1.7+/-0.4 min, 2.75+/-0.17 microg/ml, 61+/-5), respectively. Whereas, there was no significant difference in BIS values between the oxygen group (38+/-7), air group (36+/-5) and control group (40+/-6) at propofol TCI 4 microg/ml anaesthesia maintenance. CONCLUSIONS: BIS values briefly declined with ANH before returning to baseline values before anaesthesia induction. Despite transient ANH enhancement of propofol effect during induction, there was no significant difference in BIS values with or without ANH during propofol maintenance of anaesthesia.

Effects of borneol and thymoquinone on TNBS-induced colitis in mice.

Components of plant essential oils have been reported to have health benefit properties, including antioxidative, anti-tumour, antimicrobial, anti-stress, and immunomodulative activities. We examined the anti-inflammatory effects of thymoquinone, the active ingredient in the volatile oil of Nigella sativa seeds, and borneol, the active component of Salvia officinalis essential oil, on TNBS-induced colitis in mice. Thymoquinone was added to the commercial diet at a concentration of 0.05 % and borneol at two concentrations (0.09% and 0.18%) and fed to ICR mice 5 days before induction of TNBS colitis. Seven days after TNBS administration the mice were killed and macroscopic and histological scores were evaluated. Cytokine mRNA expression in colonic tissue was assessed using quantitative realtime RT-PCR. We did not detect any significant changes in macroscopic and histological scores between experimental and control groups, but we observed a significant decrease in proinflammatory cytokine (IL-1beta and IL-6) mRNA expression in colon tissue in the 0.09% and 0.18% borneol-treated groups of mice in comparison to the control group. Surprisingly, we were not able to confirm anti-inflammatory effects of thymoquinone in TNBS colitis. In conclusion, our data show that borneol is able to significantly suppress proinflammatory cytokine mRNA expression in colonic inflammation, although no significant morphological changes are visible.

Direct electron imaging in electron microscopy with monolithic active pixel sensors.

A new imaging device for dynamic electron microscopy is in great demand. The detector should provide the experimenter with images having sufficient spatial resolution at high speed. Immunity to radiation damage, accumulated during exposures, is critical. Photographic film, a traditional medium, is not adequate for studies that require large volumes of data or rapid recording and charge coupled device (CCD) cameras have limited resolution, due to phosphor screen coupling. CCD chips are not suitable for direct recording due to their extreme sensitivity to radiation damage. This paper discusses characterization of monolithic active pixel sensors (MAPS) in a scanning electron microscope (SEM) as well as in a transmission electron microscope (TEM). The tested devices were two versions of the MIMOSA V (MV) chip. This 1M pixel device features pixel size of 17 x 17 microm(2) and was designed in a 0.6 microm CMOS process. The active layer for detection is a thin (less than 20 microm) epitaxial layer, limiting the broadening of the electron beam. The first version of the detector was a standard imager with electronics, passivation and interconnection layers on top of the active region; the second one was bottom-thinned, reaching the epitaxial layer from the bottom. The electron energies used range from a few keV to 30 keV for SEM and from 40 to 400 keV for TEM. Deterioration of the image resolution due to backscattering was quantified for different energies and both detector versions.

Effects of selected plant essential oils on the growth and development of mouse preimplantation embryos in vivo.

Plant essential oils (EOs) have been reported to have health benefit properties and their preventive and therapeutic use in animals is expected to increase in the future. We evaluated the influence of five essential oils obtained from plant species which are known to have positive antimicrobial, antioxidative and anti-inflammatory effects--sage EO from Salvia officinalis L. (Lamiaceae), oregano EO from Origanum vulgare L. (Lamiaceae), thyme EO from Thymus vulgaris L. (Lamiaceae), clove EO from Syzygium aromaticum L. (Myrtaceae) and cinnamon EO from Cinnamomum zeylanicum Blume (Lauraceae) on the growth and development of mouse preimplantation embryos in vivo. Essential oils were added to commercial diet at concentrations of 0.25% for sage EO, thyme EO, clove EO, cinnamon EO and 0.1% for oregano EO, and fed to ICR female mice for 2 weeks ad libitum. Females were then mated with males of the same strain. Embryos obtained on Day 4 of pregnancy at the blastocyst stage were stained by morphological triple staining (Hoechst, PI, Calcein-AM) and evaluated using fluorescent microscopy. The effects of essential oils were estimated by the viability of embryos, number of nuclei and distribution of embryos according to nucleus number. Cinnamon EO significantly decreased the number of nuclei and the distribution of embryos according to nucleus number was significantly altered. Sage EO negatively influenced the distribution of embryos according to nucleus number. Clove and oregano EOs induced a significantly increased rate of cell death. Only thyme EO had no detectable effects on embryo development. In conclusion, none of the essential oils had any positive effect on embryo development, but some of them reduced the number of cells and increased the incidence of cell death.

Expression of IGF-I, IGF-II, and IGF-IR in gallbladder carcinoma. A systematic analysis including primary and corresponding metastatic tumours.

AIMS: The insulin-like growth factor (IGF) system has been implicated in tumour development and progression. This study was designed to analyse the expression of the IGF-I receptor (IGF-IR) and its ligands (IGF-I, IGF-II) in gallbladder cancer. METHODS: IGF-I, IGF-II, and IGF-IR immunoreactivity was investigated in 57 gallbladder carcinomas and corresponding lymph node (n = 11) and hepatic (n = 7) metastases using a tissue microarray technique and correlated with tumour stage, grade, and patient outcome. RESULTS: Cancer tissue allowing a reliable evaluation of IGF-I, IGF-II, and IGF-IR was present in 55 of 57 primary tumours and 17 of 18 metastases. IGF-I and IGF-II immunoreactivity was seen in 25 and 14 of the 55 primary tumours, in addition to six and three of the 17 metastases, respectively. No associations with tumour stage, grade, or prognosis were detected. IGF-IR was expressed in 52 of 55 primary tumours and all 17 metastases. IGF-IR staining intensity decreased with tumour cell dedifferentiation. Moreover, IGF-IR expression in less than 50% of cancer cells was an independent marker of poor prognosis in multivariate analysis (risk ratio, 4.0; 95% confidence interval, 1.4 to 11.2; p = 0.01). CONCLUSIONS: The expression of IGF-IR and its ligands provides evidence for the existence of an auto/paracrine loop of tumour cell stimulation in gallbladder cancer and makes this type of cancer a candidate for therapeutic strategies aimed at interfering with the IGF pathway. The recognition of IGF-IR as a new independent prognostic biomarker may help to identify patients who might benefit from adjuvant treatment.

Patterns of invasion and histological growth as prognostic indicators in urothelial carcinoma of the upper urinary tract.

The biological significance of squamous and glandular differentiation and different patterns of invasion in upper urinary tract urothelial carcinoma is unclear. We reviewed 268 cases of consecutive upper urinary tract carcinomas with respect to the presence of squamous and/or glandular differentiation and different patterns of invasion (nodular, trabecular, and infiltrative) and correlated data with patient outcome. Squamous or glandular differentiation occurred in 47/268 (18%) tumors and its presence correlated with high tumor stage (P<0.001) and grade (P<0.001). Invasive patterns were nodular in 49/227 (22%), trabecular in 95/227 (42%), and infiltrative in 83/227 (37%) tumors. The nodular pattern prevailed in low stage (P<0.001) and low-grade (P<0.001) tumors, whereas the infiltrative pattern prevailed in high stage (P<0.001) and high-grade (P<0.001) tumors. Multivariate analysis proved that tumor stage (P<0.001) and the infiltrative pattern (P<0.001) are independent predictors of metastasis-free survival, whereas tumor grade and squamous and glandular differentiation lacked independent influence on patient outcome. In conclusion, the infiltrative pattern of invasion significantly correlated with advanced disease and poor patient outcome. In contrast, the presence of squamous and/or glandular invasion did not prove independent influence on patient outcome. The pattern of invasion should be commented upon separately in the pathology report.

In-hospital cardiac resuscitation outside the ICU by nursing staff equipped with automated external defibrillators--the first 500 cases.

BACKGROUND: Since nursing staff in the hospital are frequently the first to witness a cardiac arrest, they may play a central role in the effective management of in-hospital cardiac arrest. In this retrospective study the first 500 in-hospital cardiac arrests in non-monitored areas, which were treated initially by nursing staff equipped with automated external defibrillators (AEDs) are reported. METHODS AND RESULTS: Between April 2001 and December 2004, 500 in-hospital cardiac arrest calls were made: there were false arrests in 61 patients, so a total of 439 patients (88%) were evaluated using the Utstein style of data collection. ROSC occurred in 256 patients (58%), 125 (28%) were discharged from hospital and 95 (22%) were still alive 6 months after discharge. Among the 73 patients with VF/VT 63 (86%) had ROSC, 34 (47%) were discharged from hospital and 28 (38%) were alive after 6 months. The chance of survival was not influenced by the time between the call of the arrest team and the 1st defibrillation but was slightly higher with physicians as in-hospital first responders (p=0.078). In contrast, 366 patients with non-VF/VT, 193 (53%) had ROSC, but only 91 (25%) were discharged from hospital and 67 (18%) were alive after 6 months. The risk of dying was significantly higher in patients with non-VF/VT (p<0.001), and there was a trend to a higher risk ratio in patients older than 65 years and in patients with non-witnessed cardiac arrest (p=0.056 and 0.079, respectively). CONCLUSION: This observational study supports the concept of hospital-wide first responder resuscitation performed by nursing staff before the arrival of the CPR-team. Among these patients survival rate was higher in those with VF/VT defibrillated at an early stage. Consequently, it may be assumed that patients may die unnecessarily due to sudden cardiac arrest if proper in-hospital resuscitation programmes are not available.

Induction of stathmin expression during liver regeneration.

Stathmin is a 19 kDa cytoplasmic phosphoprotein proposed to act as a relay for signals activating diverse intracellular regulatory pathways. After two-thirds partial hepatectomy, the concentration of stathmin reached a peak between 48 and 72 hours, comparable to the levels observed in neonatal liver, at about 10 times the basal adult level. Stathmin then decreased to basal levels within 7 days, more rapidly than during postnatal tissue development (7 weeks), with no detectable change in its phosphorylation state. Interestingly, the mRNA for stathmin reached a peak much earlier than the protein, at 24 hours posthepatectomy, and decreased to a still detectable level until 96 hours after hepatectomy. Altogether, the present results further support the generatility of the implication of stathmin in regulatory pathways of cell proliferation and differentation during normal tissue development and posttraumatic regeneration.

Different effects of abciximab and cytochalasin D on clot strength in thrombelastography.

Maximum amplitude (MA) in thrombelastography (TEG) consists of a plasmatic and a platelet component. To assess the magnitude of the plasmatic component, pharmacological approaches have been proposed to eliminate the platelet component. We evaluated the individual and combined effects of abciximab and cytochalasin D on the MA of TEG. Whole blood, platelet-rich plasma (PRP) and homologous platelet-poor plasma (PPP) from 20 healthy volunteers were spiked with abciximab or cytochalasin D or a combination of both and TEGs performed. Abciximab and cytochalasin D decreased MA in all samples. MA of whole blood (18.6 +/- 3.1 mm) and PRP (33.7 +/- 3.5 mm) spiked with abciximab or cytochalasin D alone (15.0 +/- 2.9 mm and 25.0 +/- 4.0 mm) were significantly higher when compared with abciximab and cytochalasin D combined (10.4 +/- 3.0 and 20.2 +/- 3.5 mm). While MA of PRP and homologous PPP were significantly (P < 0.001) different after individual administration of abciximab and cytochalasin D, combination of both abolished this difference (20.2 +/- 3.5 mm and 20.4 +/- 3.7 mm, P = 0.372). In whole blood of critically ill patients or patients undergoing major surgery there was also a significant difference of MA between abciximab alone and in combination with cytochalasin D (16.5 +/- 11.3 mm and 11.3 +/- 7.7 mm, P < 0.001). This indicates that in contrast to individual administration of abciximab or cytochalasin D, a combination of both compounds eliminates the platelet-specific effect on MA of TEG tracings.

Efficacy of folinic versus folic acid for the correction of hyperhomocysteinemia in hemodialysis patients.

The effectiveness of intravenous folinic acid or intravenous folic acid for the treatment of hyperhomocysteinemia of hemodialysis patients is unknown. In a randomized, controlled, double-blind trial, 66 hemodialysis patients were administered either 15 mg of folic acid or an equimolar amount (16.1 mg) of folinic acid intravenously three times weekly. Normalization of total homocysteine (tHcy) plasma levels after 4 weeks of treatment was achieved in 10 patients (30.3%) in the folic-acid group and 6 patients (18.2%; P: = 0.389) in the folinic-acid group (normalization at any time during the study period in 39.4% and 33.3% of the patients; P: = 0.798). The relative reduction in tHcy plasma levels at week 4 was 32.2% in the folic-acid group and 34.1% in the folinic-acid group. A high baseline tHcy plasma concentration (P: = 0.00001), methylenetetrahydrofolate reductase (MTHFR) 677TT/1298AA genotype (P: = 0.03540), and low red blood cell folate concentrations (P: = 0.02285) were associated with a better relative response to treatment. Normalization of tHcy plasma levels was dependent on a lower baseline tHcy level (P: = 0.01976), younger age (P: = 0.00896), and MTHFR 677TT/1298AA or 677CT/1298AC genotypes (P: = 0.00208 and P: = 0.02320, respectively). A 4-week course of intravenous folinic acid is not superior to intravenous folic acid in reducing elevated tHcy plasma levels in hemodialysis patients. The response to treatment is predicted by tHcy plasma level, red blood cell folate content, and MTHFR genotype.

Positive end-expiratory pressure and the damaged right ventricle. An experimental open versus closed chest study.

Hemodynamic changes after isolated impairment of right ventricular function (produced by increasing afterload by temporary banding of the pulmonary artery) were studied in 22 ventilated pigs during increased levels of positive end-expiratory pressure (4, 8, 12, and 16 cm H2O). In the open chest group, application of positive end-expiratory pressure produced only a slight decrease of cardiac index. After right ventricular damage a decrease of cardiac index of more than 25% occurred only when higher levels of positive end-expiratory pressure were applied. In contrast to the open chest group, the closed chest group showed more distinct cardiovascular responses after positive end-expiratory pressure. In the damaged right ventricle with a positive end-expiratory pressure of 16 cm H2O, right ventricular end-diastolic pressure increased more than 100%. With positive end-expiratory pressure, cardiac index decreased 34% before and 47% after right ventricular damage. We conclude that positive end-expiratory pressure induces a more pronounced decrease in cardiac index if right ventricular function is impaired. During open chest conditions with lower levels of positive end-expiratory pressure, these changes are only small, however, and probably irrelevant. During closed chest conditions, the hemodynamic changes are much more pronounced. High right ventricular end-diastolic pressures resulting from impaired right ventricular contractility as well as from high levels of positive end-expiratory pressure may have an impact on biventricular function and right ventricular coronary driving pressure.

Noninvasive measurement of pulmonary vascular resistances by assessment of cardiac output and pulmonary transit time.

RATIONALE AND OBJECTIVES: Pulmonary vascular resistance is of special interest in many diseases. Usually it is determined invasively by catheterization, but cardiac output and pulmonary transit time can be ascertained by several noninvasive methods. METHODS: Fourteen heart recipients (age 34-71 years) were examined by electron-beam CT of the heart. Cine and flow studies were performed using a total of 60 mL of contrast and a breath-hold of 20 seconds. RESULTS: A mathematical model for calculating pulmonary vascular resistances from noninvasively measured cardiac outputs and pulmonary transit times was developed. Right-sided heart catheterization served as the reference method. CONCLUSIONS: The formula created seems to allow a clinically valid estimate of pulmonary vascular resistance from noninvasively acquired data.

New measurement of the rare decay K+ --> pi(+)&mgr;(+)&mgr;(-)

More than 400 K+-->pi(+)&mgr;(+)&mgr;(-) events were observed in a rare K+ decay experiment at the Brookhaven Alternating Gradient Synchrotron. Normalized to the K+-->pi(+)pi(+)pi(-) decay, the branching ratio is determined to be [9.22+/-0.60(stat)+/-0. 49(syst)]x10(-8). This branching ratio and the &mgr;&mgr; mass spectrum is in very good agreement with the measurement of the K+-->pi(+)e(+)e(-) decay, but deviates significantly from the previous measurement.

Prostaglandin E1 reduces the frequency of rejection after heart transplantation.

This retrospective study was carried out to evaluate the effect of prostaglandin E1 on the frequency of rejection in 36 heart transplant recipients who survived orthotopic heart transplantation for 60 days or longer. The therapy for both groups was the same except group 1 (n = 12) was given PGE1 for 6 to 14 days. Indication for the PGE1 was right ventricular mismatch or failure. The prostaglandin administration started during the transplantation procedure. The dosage was 28 to 64 ng/kg/min and was tapered down from 14.7 to 32 ng later. No major side effects related to PGE1 have been observed. During the first 60 days after heart transplantation, in the group treated with prostaglandin, rejection grade 2 or higher was evident in 0.91 biopsies/patient versus 2.2 in nontreated patients, (p less than 0.05). A prolonged interval free from rejection (p less than 0.05) was observed in the patients treated with prostaglandin.

Are heterogenous results of EGFR immunoreactivity in renal cell carcinoma related to non-standardised criteria for staining evaluation?

AIMS: To assess whether heterogeneity of epidermal growth factor receptor (EGFR) immunoreactivity in renal cell carcinoma (RCC) is related to non-standardised criteria for staining evaluation. METHODS: EGFR expression was investigated in 132 primary and 55 metastatic conventional RCCs using a tissue microarray technique. RESULTS: Overall, membranous and/or cytoplasmic EGFR immunostaining was present in 123 of 132 (93%) primary and 49 of 53 (92%) metastatic RCCs, with extensive immunoreactivity (> 50% of tumour cells) in 110 of 132 (83%) primary tumours and 39 of 53 (73%) metastases. Cytoplasmic staining was associated with high tumour stage and high tumour grade. In addition, strong membranous staining (score 3+) prevailed in high grade RCCs. Cytoplasmic immunostaining was associated with an unfavourable prognosis, whereas overall (cytoplasmic and membranous) immunoreactivity and intensity of membranous staining were not. CONCLUSIONS: Different methods of immunohistochemical evaluation led to different results, strengthening the need for standardisation, especially against a background of rapidly evolving EGFR targeted cancer treatment strategies.

Palliation of advanced esophageal carcinoma by photodynamic therapy and irradiation.

BACKGROUND: We wanted to determine the role of photodynamic therapy in a multimodal approach for the treatment of patients with advanced cancer of the esophagus. METHODS: We reviewed the cases of 119 patients with nonresectable esophageal carcinoma who underwent endoluminal palliation. Twenty-one patients required initial dilation and tumor obliteration with a neodymium: yttrium-aluminum-garnet laser prior to therapy. Forty-four patients received photodynamic therapy followed by brachyradiotherapy, and 75 patients were treated with brachyradiotherapy. In both groups, some patients also received external-beam irradiation. RESULTS: Photodynamic therapy produced a significant difference in relieving stenosis caused by tumor stenosis (mean, 6.6 mm; p = 0.0000). The dysphagia score improved by one to three levels in all patients, with a significant difference in favor of PDT (p = 0.0003). The mean number of overall treatment sessions was four (range, one to seven). The rate of major complications was 9.2%. Four esophageal perforations occurred, three after intervention and one spontaneously 5 months later. Four esophagorespiratory tract fistulas developed several months after combined PDT and irradiation. The mean overall survival was 7.7 months, and analysis of variance revealed a significant difference in favor of PDT and external-beam irradiation (p = 0.0129 and p = 0.0001, respectively). CONCLUSIONS: Photodynamic therapy has been shown to be an effective palliative treatment of advanced esophageal cancer. However, proper patient selection is necessary to prevent serious complications.