Needle fasciotomy for Dupuytren's contracture- a prospective cohort study of 58 fingers with a median follow-up of 6.5 years.

Needle fasciotomy (NF) is a minimally invasive treatment option for Dupuytren contractures, but long-term results have indicated a high recurrence rate. This prospective study was initiated to monitor the introduction of NF in a context where limited fasciectomy had been the only treatment option, and to investigate the long-term results. The inclusion criterion was a palpable cord with a Metacarpophalangeal (MCP) and/or Proximal interphalangeal (PIP) contracture in one or more fingers. Fifty-eight fingers in 42 patients (40 male and 2 female with a median age of 68 years) were treated by needle fasciotomy between November 2010 and March 2012, and were followed for a median of 6.5 years. The median total passive extension deficit (TPED) was 52° at baseline, but decreased significantly to 20° postoperatively. No severe adverse events such as nerve or tendon injuries were reported. At final-follow up of 48 fingers the median TPED was still significantly reduced to 23° for all fingers (p < 0.0001). Twenty-nine fingers retained full correction of the contracture, and in patients with recurrent contractures NF was preferred in 13 out of 17 patients. This study showed that needle fasciotomy is a safe procedure for Dupuytren's contracture, with excellent immediate reduction of the joint contracture and with a recurrence rate comparable to treatment by collagenase clostridium histolyticum (CCH).

Morphological patterns of the pretendinous cord in Dupuytren's disease: a predictor of clinical outcome?

The morphology of the pretendinous cord in Dupuytren's disease is poorly described in vivo and especially with respect to recurrence after treatment. This prospective study was designed to describe the morphology of Dupuytren's cords by ultrasound and to identify possible correlation between the ultrasonographic characteristics of these cords and the clinical outcomes two years after treatment. Thirty-nine patients with a contracture of at least 20° in the metacarpophalangeal (MCP) joint, who were scheduled for local treatment by either injectable collagenase clostridium histolyticum (CCH) or percutaneous needle fasciotomy (PNF), were examined by ultrasound. The echogenicity and position of the pretendinous cords in relation to flexor tendons and neurovascular bundles were categorized. The structure of the cords was described and characterized as predominantly nodular or fibrillar. All 39 patients were assessed clinically after two years. A majority of the patients (84%) had cords with nodular components, and six patients (16%) had fibrillar cords. After two years, the clinical results were compared to the ultrasonographic findings before treatment. Three patients had recurrent contracture, and a retrospective analysis showed that all of these patients had cords with mixed echogenicity and nodules before treatment. Fifteen patients had a palpable pretendinous cord, and all but one of these had cords with mixed echogenicity and nodular structure before treatment. This pilot study indicates that some ultrasonographic features of the Dupuytren's cord, such as mixed echogenicity and nodular structure, may predict recurrence after minimally invasive treatment for Dupuytren's contracture. However, a larger study in correlation with histological examination of the excised cords would be necessary to confirm the pathoanatomical significance of these ultrasonographic features.

Ultrasonographic examination of the ruptured cord after collagenase treatment or needle fasciotomy for Dupuytren's contracture.

Local treatment of Dupuytren's contracture, either by collagenase or needle fasciotomy, allows disruption of the pathological cord during forced extension. The purpose of this study was to investigate the cord before and after both treatments by ultrasound. A total of 39 patients with a minimum of 20° contracture in the metacarpophalangeal joint were included and randomized to treatment with either collagenase (20 patients) or needle fasciotomy (19 patients). The distance between the distal and the proximal parts of the ruptured cord was measured by ultrasound and the difference in passive joint movement before and after treatment was measured with a goniomenter. There were no significant differences between the collagenase and needle fasciotomy groups in the size of the rupture or gain of mobility. Most cords treated with collagenase and subsequent forced extension had the same ultrasonographic appearance as cords disrupted mechanically by needle fasciotomy. LEVEL OF EVIDENCE: III.

Impact of Comorbidity and Prescription Drugs on Haemorrhage in Cholecystectomy.

BACKGROUND: The purpose of the present study was to analyse the impact of patient-related risk factors and medication drugs on haemorrhagic complications following cholecystectomy. METHODS: All cholecystectomies registered in the Swedish population-based Register for Gallstone Surgery and ERCP (GallRiks) were identified. Risk factors for bleeding were assessed by linking data in the GallRiks to the National Patient Register and the Prescribed Drug Register, respectively. The risk of haemorrhage leading to intervention was determined by variable regression, and Kaplan-Meier analysis assessed survival rate following perioperative haemorrhage. RESULTS: A total of 94,557 patients were included between 2005 and 2015, of which 799 (0.8%) and 1192 (1.3%) patients were registered as having perioperative and post-operative haemorrhage, respectively. In multivariable analysis, an increased risk of haemorrhagic complications was seen in patients with cerebrovascular disease (p = 0.001), previous myocardial infarction (p = 0.001), kidney disease (p = 0.001), heart failure (p = 0.001), diabetes (p = 0.001), peripheral vascular disease (p = 0.004), and obesity (p = 0.005). Prescription of tricyclic antidepressant (p = 0.018) or dipyridamole (p = 0.047) was associated with a significantly increased risk of perioperative haemorrhage. However, this increase in risk did not remain significant following Bonferroni correction for mass significance. Perioperative haemorrhage increased the risk of death occurring within the first post-operative year [Hazard Ratio, (HR) 4.9, CI 3.52-6.93] as well as bile duct injury (OR 2.45, CI 1.79-3.37). CONCLUSION: The increased risk of haemorrhage associated with comorbidity must be taken into account when assessing patients prior to cholecystectomy. Perioperative bleeding increases post-operative mortality and is associated with an increased risk of bile duct injury.

Patients with triangular fibrocartilage complex injuries and distal radioulnar joint instability have reduced rotational torque in the forearm.

UNLABELLED: A total of 20 patients scheduled for wrist arthroscopy, all with clinical signs of rupture to the triangular fibrocartilage complex and distal radioulnar joint instability, were tested pre-operatively by an independent observer for strength of forearm rotation. During surgery, the intra-articular pathology was documented by photography and also subsequently individually analysed by another independent hand surgeon. Arthroscopy revealed a type 1-B injury to the triangular fibrocartilage complex in 18 of 20 patients. Inter-rater reliability between the operating surgeon and the independent reviewer showed absolute agreement in all but one patient (95%) in terms of the injury to the triangular fibrocartilage complex and its classification. The average pre-operative torque strength was 71% of the strength of the non-injured contralateral side in pronation and supination. Distal radioulnar joint instability with an arthroscopically verified injury to the triangular fibrocartilage complex is associated with a significant loss of both pronation and supination torque. LEVEL OF EVIDENCE: Case series, Level IV.

Incidence and risk factors for symptomatic venous thromboembolism following cholecystectomy.

BACKGROUND: The benefit of thromboembolism prophylaxis in cholecystectomy is controversial. This population-based study report on the incidence of and risk factors for symptomatic venous thromboembolism (VTE) after cholecystectomy. METHOD: All cholecystectomies registered in the Swedish Register of Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography (GallRiks) between 2006 and 2011 were reviewed. By linking patient data to the Swedish National Patient Register (NPR), the 30-day postoperative incidence of VTE (deep venous thrombosis [DVT] and/or pulmonary embolism [PE]) was identified. Age- and gender-standardized incidence ratio (SIR) for deep venous thrombosis (DVT) and pulmonary embolism (PE) were calculated. Multivariable analysis determined risk factors for VTE by calculating odds ratio (OR). RESULTS: Altogether 62,488 procedures were registered and postoperative VTE was seen in 154 (0.25%) patients. DVT was seen in 36 (0.06%) patients and PE in 25 (0.04%) patients within 30 days after surgery. The SIR for DVT was 22.2 (95% confidence interval (CI) 13.1-31.3) and for PE 5.6 (95% CI 2.3-8.9). Risk factors for VTE within 30 days after cholecystectomy were age >70 years (odds ratio [OR] = 2.69; 95% confidence interval [CI] 1.68-4.30), open cholecystectomy (OR = 1.95; CI 1.31-2.92), operation time >120 min (OR = 1.66; CI 1.18-2.35), acute cholecystitis (OR = 1.69; CI 1.18-2.42), and previous history of VTE (OR = 50.5; CI 27.3-92.8). Thromboembolism prophylaxis (TP) increased the risk for postoperative bleeding (OR = 1.72; 1.44-2.05). CONCLUSION: The incidence of VTE after cholecystectomy is low and thromboembolism prophylaxis (TP) increases the risk for postoperative bleeding. Patients with previous VTE events should be given TP when undergoing cholecystectomy.

Allopregnanolone and mood disorders.

UNLABELLED: Certain women experience negative mood symptoms during the menstrual cycle and progesterone addition in estrogen treatments. In women with PMDD increased negative mood symptoms related to allopregnanolone increase during the luteal phase of ovulatory menstrual cycles. In anovulatory cycles no symptom or sex steroid increase occurs. This is unexpected as positive modulators of the GABA-A receptor are generally increasing mood. This paradoxical effect has brought forward a hypothesis that the symptoms are provoked by allopregnanolone the GABA-A receptor system. GABA-A is the major inhibitory system in the brain. Positive modulators of the GABA-A receptor include the progesterone metabolites allopregnanolone and pregnanolone, benzodiazepines, barbiturates, and alcohol. GABA-A receptor modulators are known, in low concentrations to induce adverse, anxiogenic effects whereas in higher concentrations show beneficial, calming properties. Positive GABA-A receptor modulators induce strong paradoxical effects e.g. negative mood in 3-8% of those exposed, while up to 25% have moderate symptoms thus similar as the prevalence of PMDD, 3-8% among women in fertile ages, and up to 25% have moderate symptoms of premenstrual syndrome (PMS). The mechanism behind paradoxical reaction might be similar among them who react on positive GABA-A receptor modulators and in women with PMDD. In women the severity of these mood symptoms are related to the allopregnanolone serum concentrations in an inverted U-shaped curve. Negative mood symptoms occur when the serum concentration of allopregnanolone is similar to endogenous luteal phase levels, while low and high concentrations have less effect on mood. Low to moderate progesterone/allopregnanolone concentrations in women increases the activity in the amygdala (measured with fMRI) similar to the changes seen during anxiety reactions. Higher concentrations give decreased amygdala activity similar as seen during benzodiazepine treatment with calming anxiolytic effects. Patients with PMDD show decreased sensitivity in GABA-A receptor sensitivity to diazepam and pregnanolone while increased sensitivity to allopregnanolone. This agrees with findings in animals showing a relation between changes in alpha4 and delta subunits of the GABA-A receptor and anxiogenic effects of allopregnanolone. CONCLUSION: These findings suggest that negative mood symptoms in women with PMDD are caused by the paradoxical effect of allopregnanolone mediated via the GABA-A receptor.

Risk of bleeding associated with use of systemic thromboembolic prophylaxis during laparoscopic cholecystectomy.

BACKGROUND: The extent to which systemic perioperative thromboembolic prophylaxis affects peroperative and postoperative bleeding during cholecystectomy is not known. This article reports on risk of bleeding in a national cohort of cholecystectomies. METHODS: All cholecystectomies registered in the Swedish Register of Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography (GallRiks) between 2005 and 2010 were reviewed. Peroperative bleeding was defined as bleeding that could not be controlled by standard surgical techniques, necessitated conversion to an open procedure or required peroperative blood transfusion. Postoperative bleeding was defined as bleeding that necessitated reoperation, transfusion or a prolonged hospital stay. Risk estimates were performed using univariable and multiple logistic regression, and reported as odds ratios (ORs). RESULTS: A total of 51 621 procedures were registered in GallRiks. Some 48 010 patients were included in the analyses, of whom 21 259 (44·3 per cent) received thromboembolic prophylaxis. Peroperative bleeding complications occurred in 400 (1·9 per cent) and postoperative bleeding in 296 (1·4 per cent) given thromboembolic prophylaxis, compared with 189 (0·7 per cent) and 195 (0·7 per cent) respectively without thromboprophylaxis. After adjusting for age, sex, indication for surgery, American Society of Anesthesiologists grade, mode of admission, operative approach, duration of surgery and hospital volume, the OR for peroperative or postoperative bleeding complications in the group receiving prophylaxis was 1·35 (95 per cent confidence interval 1·17 to 1·55). However, in a subgroup analysis the risk was increased in laparoscopic surgery only. At 30-day follow-up, a total of 74 patients (0·2 per cent) had developed postoperative thromboembolism, 43 (0·2 per cent) of those who received thromboembolic prophylaxis compared with 31 (0·1 per cent) of those who did not. CONCLUSION: Thromboprophylaxis in patients undergoing laparoscopic cholecystectomy increased the risk of bleeding, but the occurrence of thromboembolic events was not significantly reduced. Identification of high- and low-risk patients is needed to guide clinical decisions regarding medical thromboprophylaxis.

Paradoxical effects of GABA-A modulators may explain sex steroid induced negative mood symptoms in some persons.

Some women have negative mood symptoms, caused by progestagens in hormonal contraceptives or sequential hormone therapy or by progesterone in the luteal phase of the menstrual cycle, which may be attributed to metabolites acting on the GABA-A receptor. The GABA system is the major inhibitory system in the adult CNS and most positive modulators of the GABA-A receptor (benzodiazepines, barbiturates, alcohol, GABA steroids), induce inhibitory (e.g. anesthetic, sedative, anticonvulsant, anxiolytic) effects. However, some individuals have adverse effects (seizures, increased pain, anxiety, irritability, aggression) upon exposure. Positive GABA-A receptor modulators induce strong paradoxical effects including negative mood in 3%-8% of those exposed, while up to 25% have moderate symptoms. The effect is biphasic: low concentrations induce an adverse anxiogenic effect while higher concentrations decrease this effect and show inhibitory, calming properties. The prevalence of premenstrual dysphoric disorder (PMDD) is also 3%-8% among women in fertile ages, and up to 25% have more moderate symptoms of premenstrual syndrome (PMS). Patients with PMDD have severe luteal phase-related symptoms and show changes in GABA-A receptor sensitivity and GABA concentrations. Findings suggest that negative mood symptoms in women with PMDD are caused by the paradoxical effect of allopregnanolone mediated via the GABA-A receptor, which may be explained by one or more of three hypotheses regarding the paradoxical effect of GABA steroids on behavior: (1) under certain conditions, such as puberty, the relative fraction of certain GABA-A receptor subtypes may be altered, and at those subtypes the GABA steroids may act as negative modulators in contrast to their usual role as positive modulators; (2) in certain brain areas of vulnerable women the transmembrane Cl(-) gradient may be altered by factors such as estrogens that favor excitability; (3) inhibition of inhibitory neurons may promote disinhibition, and hence excitability. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain.

Neurosteroid modulation of allopregnanolone and GABA effect on the GABA-A receptor.

The neurosteroid allopregnanolone (ALLO) or 3alpha-OH-5alpha-pregnane-20-one interacts with the GABA type A receptor chloride ion channel complex and enhances the effect of GABA. Animal and human studies suggest that ALLO plays an important role in several disorders including premenstrual syndrome, anxiety, and memory impairment. In contrast to ALLO, steroids with a hydroxy group in the 3beta position usually exert a reducing effect and have recently attracted interest due to their suggested role in counteracting the negative action of ALLO. In this study, five different 3beta-steroids were tested for their ability to modulate GABA-mediated chloride ion uptake in the absence and presence of ALLO in rat brain microsacs preparations. In addition, the effects of the 3beta-steroids and their interaction with ALLO were investigated by patch-clamp recordings of spontaneous inhibitory postsynaptic currents (sIPSCs) in rat hypothalamic neurons from the medial preoptic nucleus (MPN). All tested 3beta-steroids reduced the ALLO-enhanced GABA response in cerebral cortex, in hippocampus and in MPN. In cerebellum, only one had this effect. However, in the absence of ALLO, two of the 3beta-steroids potentiated GABA-evoked chloride ion uptake and prolonged the sIPSCs decay time, whereas the others had little or no effect. Therefore, it is possible that at least some 3beta-steroids can act as positive GABA(A) receptor modulators as well as negative modulators depending on whether or not ALLO is present. Finally, these results suggest that the 3beta-steroids could be of interest as pharmacological agents that could counteract the negative effects of ALLO.

Rapid non-genomic effect of glucocorticoid metabolites and neurosteroids on the gamma-aminobutyric acid-A receptor.

Glucocorticoids and neurosteroids, such as allopregnanolone and tetrahydrodeoxycorticosterone, are released during stress. A non-genomic effect of glucocorticoids has been established but is not yet fully understood. We have studied the effect of glucocorticoid metabolites on the gamma-aminobutyric acid (GABA) system. In these experiments we studied the effects of the glucocorticoid metabolites allotetrahydrocortisol, tetrahydrocortisol, allotetrahydrocortisone and tetrahydrocortisone in rat cortical microsacs. Our results showed that both these cortisol and cortisone metabolites reduce GABA-mediated chloride ion uptake. This reduction was not observed in the presence of allopregnanolone but allotetrahydrocortisol interacts with allopregnanolone, enhancing the allopregnanolone-stimulated potentiation of GABA-mediated chloride ion uptake. This enhanced effect was completely blocked by the addition of 30 microm of the 3beta-isomer of allopregnanolone, isoallopregnanolone. Our findings show that steroids released during stress interact with each other and GABA in the GABA system.

Amplitude and phase relationship between alpha and beta oscillations in the human electroencephalogram.

The relationship between the electro-encephalographic (EEG) alpha and beta oscillations in the resting condition was investigated in the study. EEGs were recorded in 33 subjects, and alpha (7.5-12.5 Hz) and beta (15-25 Hz) oscillations were extracted with the use of a modified wavelet transform. Power, peak frequency and phase synchronisation were evaluated for both types of oscillation. The average beta-alpha peak frequency ratio was about 1.9-2.0 for all electrode derivations. The peak frequency of beta activity was within 70-90 % of the 95 % confidence interval of twice the alpha frequency. A significant (p < 0.05) linear regression was found between beta and alpha power in all derivations in 32 subjects, with the slope of the regression line being approximately 0.3. There was no significant difference in the slope of the line in different electrode locations, although the power correlation was strongest in the occipital locations where alpha and beta oscillations had the largest power. A significant 1:2 phase synchronisation was present between the alpha and beta oscillations, with a phase lag of about pi/2 in all electrode derivations. The strong frequency relationship between the resting beta and alpha oscillations suggests that they are generated by a common mechanism. Power and phase relationships were weaker, suggesting that these properties can be modulated by additional mechanisms as well as be influenced by noise. A careful distinction between alpha-dependent and alpha-independent beta activity should be considered when making statements about the possible significance of genuine beta activity in different neurophysiological mechanisms.

Lactate dehydrogenase from the northern krill Meganyctiphanes norvegica: comparison with LDH from the Antarctic krill Euphausia superba.

Electrophoretic polymorphism of lactate dehydrogenase (LDH, EC 1.1.1.27) from abdominal muscle is reported in the northern krill Meganyctiphanes norvegica. In the population, from the Gullmarsfjord (west coast of Sweden), LDH was encoded for by two different Ldh-A* and -B* loci. The isoenzymes were named according to their electrophoretic mobilities. Ldh-A* locus was polymorphic. The allelic frequencies were a=0.99, a'=0.002, a"=0.004, a"'=0.004. The level of LDH polymorphism is low. Most individuals possess the same amount of two LDH homopolymers (LDH-A*(4) and LDH-B*(4)). The Meganyctiphanes norvegica LDH-A*(4) and LDH-B*(4) isoenzymes and the predominant LDH-A*(4) isoenzyme from Euphausia superba were purified to specific activities of 294, 306 and 464 micromol NADH min(-1) mg(-1), respectively. In both species the LDH isoenzymes were separated by chromatofocusing. All three isoenzymes are L-specific tetramers with molecular weight of approximately 160 kDa. Northern krill LDH-A*(4) has higher affinity for pyruvate and lactate and is more thermostable than LDH-B*(4). Both isoenzymes are inhibited significantly by high concentration of pyruvate but not lactate. Antarctic krill isoenzyme exhibits high substrate affinities, high NAD inhibition, high inhibition at 10 mM pyruvate, lack of lactate inhibition, and high heat stability and resembles northern krill LDH-A*(4) isoenzyme.

Low bit-rate efficient compression for seismic data.

Compression is a relatively new introduced technique for seismic data operations. The main drive behind the use of data compression in seismic data is the very large size of seismic data acquired. Some of the most recent acquired marine seismic data sets exceed 10 Tbytes, and in fact there are currently seismic surveys planned with a volume of around 120 Tbytes. Thus, the need to compress these very large seismic data files is imperative. Nevertheless, seismic data are quite different from the typical images used in image processing and multimedia applications. Some of their major differences are the data dynamic range exceeding 100 dB in theory, very often it is data with extensive oscillatory nature, the x and y directions represent different physical meaning, and there is significant amount of coherent noise which is often present in seismic data. Up to now some of the algorithms used for seismic data compression were based on some form of wavelet or local cosine transform, while using a uniform or quasiuniform quantization scheme and they finally employ a Huffman coding scheme. Using this family of compression algorithms we achieve compression results which are acceptable to geophysicists, only at low to moderate compression ratios. For higher compression ratios or higher decibel quality, significant compression artifacts are introduced in the reconstructed images, even with high-dimensional transforms. The objective of this paper is to achieve higher compression ratio, than achieved with the wavelet/uniform quantization/Huffman coding family of compression schemes, with a comparable level of residual noise. The goal is to achieve above 40 dB in the decompressed seismic data sets. Several established compression algorithms are reviewed, and some new compression algorithms are introduced. All of these compression techniques are applied to a good representation of seismic data sets, and their results are documented in this paper. One of the conclusions is that adaptive multiscale local cosine transform with different windows sizes performs well on all the seismic data sets and outperforms the other methods from the SNR point of view. All the described methods cover wide range of different data sets. Each data set will have his own best performed method chosen from this collection. The results were performed on four different seismic data sets. Special emphasis was given to achieve faster processing speed which is another critical issue that is examined in the paper. Some of these algorithms are also suitable for multimedia type compression.

Active breathing control (ABC) for Hodgkin's disease: reduction in normal tissue irradiation with deep inspiration and implications for treatment.

PURPOSE: Active breathing control (ABC) temporarily immobilizes breathing. This may allow a reduction in treatment margins. This planning study assesses normal tissue irradiation and reproducibility using ABC for Hodgkin's disease. METHODS AND MATERIALS: Five patients underwent CT scans using ABC obtained at the end of normal inspiration (NI), normal expiration (NE), and deep inspiration (DI). DI scans were repeated within the same session and 1-2 weeks later. To simulate mantle radiotherapy, a CTV1 was contoured encompassing the supraclavicular region, mediastinum, hila, and part of the heart. CTV2 was the same as CTV1 but included the whole heart. CTV3 encompassed the spleen and para-aortic lymph nodes. The planning target volume (PTV) was defined as CTV + 9 mm. PTVs were determined at NI, NE, and DI. A composite PTV (comp-PTV) based on the range of NI and NE PTVs was determined to represent the margin necessary for free breathing. Lung dose-mass histograms (DMH) for PTV1 and PTV2 and cardiac dose-volume histograms (DVH) for PTV3 were compared at the three different respiratory phases. RESULTS: ABC was well-tolerated by all patients. DI breath-holds ranged from 34 to 45 s. DMHs determined for PTV1 revealed a median reduction in lung mass irradiated at DI of 12% (range, 9-24%; n = 5) compared with simulated free-breathing. PTV2 comparisons also showed a median reduction of 12% lung mass irradiated (range, 8-28%; n = 5). PTV3 analyses revealed the mean volume of heart irradiated decreased from 26% to 5% with deep inspiration (n = 5). Lung volume comparisons between intrasession and intersession DI studies revealed mean variations of 4%. CONCLUSION: ABC is well tolerated and reproducible. Radiotherapy delivered at deep inspiration with ABC may decrease normal tissue irradiation in Hodgkin's disease patients.

Matched-pair analysis of conformal high-dose-rate brachytherapy boost versus external-beam radiation therapy alone for locally advanced prostate cancer.

PURPOSE: We performed a matched-pair analysis to compare our institution's experience in treating locally advanced prostate cancer with external-beam radiation therapy (EBRT) alone to EBRT in combination with conformal interstitial high-dose-rate (HDR) brachytherapy boosts (EBRT + HDR). MATERIALS AND METHODS: From 1991 to 1998, 161 patients with locally advanced prostate cancer were prospectively treated with EBRT + HDR at William Beaumont Hospital, Royal Oak, Michigan. Patients with any of the following characteristics were eligible for study entry: pretreatment prostate-specific antigen (PSA) level of >/= 10.0 ng/mL, Gleason score >/= 7, or clinical stage T2b to T3c. Pelvic EBRT (46.0 Gy) was supplemented with three (1991 through 1995) or two (1995 through 1998) ultrasound-guided transperineal interstitial iridium-192 HDR implants. The brachytherapy dose was escalated from 5.50 to 10.50 Gy per implant. Each of the 161 EBRT + HDR patients was randomly matched with a unique EBRT-alone patient. Patients were matched according to PSA level, Gleason score, T stage, and follow-up duration. The median PSA follow-up was 2.5 years for both EBRT + HDR and EBRT alone. RESULTS: EBRT + HDR patients demonstrated significantly lower PSA nadir levels (median, 0.4 ng/mL) compared with those receiving EBRT alone (median, 1.1 ng/mL). The 5-year biochemical control rates for EBRT + HDR versus EBRT-alone patients were 67% versus 44%, respectively (P <.001). On multivariate analyses, pretreatment PSA, Gleason score, T stage, and the use of EBRT alone were significantly associated with biochemical failure. Those patients in both treatment groups who experienced biochemical failure had a lower 5-year cause-specific survival rate than patients who were biochemically controlled (84% v 100%; P <.001). CONCLUSION: Locally advanced prostate cancer patients treated with EBRT + HDR demonstrate improved biochemical control compared with those who are treated with conventional doses of EBRT alone.

Interim report of image-guided conformal high-dose-rate brachytherapy for patients with unfavorable prostate cancer: the William Beaumont phase II dose-escalating trial.

PURPOSE: We analyzed our institution's experience treating patients with unfavorable prostate cancer in a prospective Phase II dose-escalating trial of external beam radiation therapy (EBRT) integrated with conformal high-dose-rate (HDR) brachytherapy boosts. This interim report discusses treatment outcome and prognostic factors using this treatment approach. METHODS AND MATERIALS: From November 1991 through February 1998, 142 patients with unfavorable prostate cancer were prospectively treated in a dose-escalating trial with pelvic EBRT in combination with outpatient HDR brachytherapy at William Beaumont Hospital. Patients with any of the following characteristics were eligible: pretreatment prostate-specific antigen (PSA) >/= 10.0 ng/ml, Gleason score >/= 7, or clinical stage T2b or higher. All patients received pelvic EBRT to a median total dose of 46.0 Gy. Pelvic EBRT was integrated with ultrasound-guided transperineal conformal interstitial iridium-192 HDR implants. From 1991 to 1995, 58 patients underwent three conformal interstitial HDR implants during the first, second, and third weeks of pelvic EBRT. After October 1995, 84 patients received two interstitial implants during the first and third weeks of pelvic EBRT. The dose delivered via interstitial brachytherapy was escalated from 5.50 Gy to 6.50 Gy for each implant in those patients receiving three implants, and subsequently, from 8.25 Gy to 9.50 Gy per fraction in those patients receiving two implants. To improve implant quality and reduce operator dependency, an on-line, image-guided interactive dose optimization program was utilized during each HDR implant. No patient received hormonal therapy unless treatment failure was documented. The median follow-up was 2.1 years (range: 0.2-7.2 years). Biochemical failure was defined according to the American Society for Therapeutic Radiology and Oncology Consensus Panel definition. RESULTS: The pretreatment PSA level was >/= 10.0 ng/ml in 51% of patients. The biopsy Gleason score was >/= 7 in 58% of cases, and 75% of cases were clinical stage T2b or higher. Despite the high frequency of these poor prognostic factors, the actuarial biochemical control rate was 89% at 2 years and 63% at 5 years. On multivariate analysis, a higher pretreatment PSA level, higher Gleason score, higher PSA nadir level, and shorter time to nadir were associated with biochemical failure. In the entire population, 14 patients (10%) experienced clinical failure at a median interval of 1.7 years (range: 0.2-4.5 years) after completing RT. The 5-year actuarial clinical failure rate was 22%. The 5-year actuarial rates of local failure and distant metastasis were 16% and 14%, respectively. For all patients, the 5-year disease-free survival, overall survival, and cause-specific survival rates were 89%, 95%, and 96%, respectively. The 5-year actuarial rate of RTOG Grade 3 late complications was 9% with no patient experiencing Grade 4 or 5 acute or late toxicity. CONCLUSION: Pelvic EBRT in combination with image-guided conformal HDR brachytherapy boosts appears to be an effective treatment for patients with unfavorable prostate cancer with minimal associated morbidity. Our dose-escalating trial will continue.

Fast adaptive wavelet packet image compression.

Wavelets are ill-suited to represent oscillatory patterns: rapid variations of intensity can only be described by the small scale wavelet coefficients, which are often quantized to zero, even at high bit rates. Our goal is to provide a fast numerical implementation of the best wavelet packet algorithm in order to demonstrate that an advantage can be gained by constructing a basis adapted to a target image. Emphasis is placed on developing algorithms that are computationally efficient. We developed a new fast two-dimensional (2-D) convolution decimation algorithm with factorized nonseparable 2-D filters. The algorithm is four times faster than a standard convolution-decimation. An extensive evaluation of the algorithm was performed on a large class of textured images. Because of its ability to reproduce textures so well, the wavelet packet coder significantly out performs one of the best wavelet coder on images such as Barbara and fingerprints, both visually and in term of PSNR.

Defining biochemical cure for prostate carcinoma patients treated with external beam radiation therapy.

BACKGROUND: The authors retrospectively reviewed their institution's long term experience with conventional external beam radiation therapy (RT) for localized prostate carcinoma to identify criteria associated with long term biochemical cure. METHODS: Between January 1987 and December 1994, 871 patients were treated with external beam RT alone for clinically localized prostate carcinoma at William Beaumont Hospital, Royal Oak, Michigan. All patients received only external beam RT to a median total dose of 66.6 grays (Gy) (range, 59.4-70.4 Gy). No patient received hormonal therapy unless treatment failure was documented. The median follow-up was 5.0 years (range, 0. 2-11.8 years). Biochemical failure was defined according to the American Society for Therapeutic Radiology and Oncology Consensus Panel definition. RESULTS: In the entire study group, 380 patients experienced biochemical failure at a median interval of 1.5 years after the completion of RT. The 5-year and 7-year actuarial rates of biochemical control were 50% and 48%, respectively. On multivariate analysis, a higher pretreatment prostate specific antigen (PSA) level, higher Gleason score, higher clinical T classification, higher nadir level, and shorter time interval to nadir all were associated significantly with biochemical failure (P < 0.001). The median intervals to biochemical failure for patients with pretreatment PSA levels /= 20.0 ng/mL were 2.2 years, 1.5 years, and 1.2 years, respectively (P < 0. 001). The median intervals to biochemical failure for patients with Gleason scores of 2-4, 5-7, and 8-10 were 1.8 years, 1.5 years, and 1.1 years, respectively (P < 0.001). Only 6 patients failed beyond 5 years after treatment even though 136 patients were at risk for failure beyond this point. When restricting analysis to 643 patients (74%) with >/= 3 years of PSA follow-up, the median nadir level for biochemically controlled patients was 0.6 ng/mL and occurred at a median interval of 1.9 years after RT versus a median nadir level of 1.3 ng/mL (P = 0.002) occurring at a median interval of 1.0 years (P < 0.001) in those patients who experienced biochemical failure. Patients were divided into subgroups based on their PSA nadir level and time to nadir. The 5-year actuarial biochemical control rates for patients with nadir values of /= 4.0 ng/mL were 78%, 60%, 50%, 20%, and 9%, respectively (P < 0.001). The 5-year actuarial biochemical control rates for patients who reached their nadir at < 1.0 years, 1.0-1.9 years, 2.0-2.9 years, and >/= 3.0 years were 30%, 52%, 64%, and 92%, respectively (P < 0.001). All 52 patients who achieved a nadir of /= 2.0 years to reach this nadir had biochemically controlled disease. CONCLUSIONS: These results suggest that a patient has a high likelihood of biochemical cure after treatment for prostate carcinoma with conventional doses of external beam RT if he has not demonstrated biochemical failure within 5 years of treatment. Patients with lower pretreatment PSA levels and lower Gleason scores may require longer follow-up than those with less favorable characteristics to achieve the same certainty of cure. Patients who achieve a PSA nadir /= 2.0 years to reach this nadir have the highest probability of cure.

Treatment outcome with adjuvant and salvage irradiation after radical prostatectomy for prostate cancer.

OBJECTIVES: To determine the factors associated with outcome by reviewing our institution's experience treating patients with external beam radiation therapy (RT) after radical prostatectomy. METHODS: Sixty-one patients received RT to the prostatic fossa after radical prostatectomy for prostate cancer (median dose 59.4 Gy). Thirty-eight patients received adjuvant RT within 6 months of surgery for adverse pathologic findings only. Therapeutic RT was administered to 23 patients either for a persistently elevated postoperative prostate-specific antigen (PSA) level (n = 2), a rising PSA level more than 6 months after surgery (n = 9), or a biopsy-proven local recurrence (n = 12). Preoperative and preradiation PSA values, Gleason score, pathologic findings, patient age, total RT dose, and indication for RT were analyzed for their impact on biochemical control. The median follow-up was 48 months. RESULTS: Patients treated with adjuvant RT achieved 3 and 5-year biochemical control rates of 84% and 67%, respectively. Multiple clinical, pathologic, and treatment-related factors were analyzed for an association with biochemical control. No variable was associated with 5-year outcome. The 5-year actuarial rate of biochemical control for patients treated with therapeutic RT was 16%. Multiple clinical, pathologic, and treatment-related factors were analyzed for an association with biochemical control. Only a pre-RT PSA level of 2 ng/mL or less was associated with an improved rate of biochemical control at 3 years (80% versus 27%, P = 0.001). However, at 5 years, this difference was not statistically significant. A separate analysis was performed to determine the prognostic factors associated with outcome for the entire group of patients. Only the indication for RT (adjuvant versus therapeutic) was associated with 5-year outcome. Patients treated with adjuvant RT had a statistically significant improvement in 5-year actuarial rates of biochemical control (67% versus 16%, P <0.001) and disease-free survival (66% versus 46%, P = 0.037) but not in overall survival. There were no statistically significant differences between patient groups with respect to age, preoperative PSA, Gleason score, pathologic T stage, median follow-up, and total RT dose. CONCLUSIONS: At our institution, patients treated with adjuvant RT after prostatectomy for adverse pathologic findings achieved excellent rates of biochemical control that were significantly better than that of similar patients treated therapeutically for persistent or rising PSA or clinical local recurrence.