Neuroinvasive Bacillus cereus Infection in Immunocompromised Hosts: Epidemiologic Investigation of 5 Patients With Acute Myeloid Leukemia.

Background: Bacillus cereus is a ubiquitous gram-positive rod-shaped bacterium that can cause sepsis and neuroinvasive disease in patients with acute leukemia or neutropenia. Methods: A single-center retrospective review was conducted to evaluate patients with acute leukemia, positive blood or cerebrospinal fluid test results for B cereus, and abnormal neuroradiographic findings between January 2018 and October 2022. Infection control practices were observed, environmental samples obtained, a dietary case-control study completed, and whole genome sequencing performed on environmental and clinical Bacillus isolates. Results: Five patients with B cereus neuroinvasive disease were identified. All patients had acute myeloid leukemia (AML), were receiving induction chemotherapy, and were neutropenic. Neurologic involvement included subarachnoid or intraparenchymal hemorrhage or brain abscess. All patients were treated with ciprofloxacin and survived with limited or no neurologic sequelae. B cereus was identified in 7 of 61 environmental samples and 1 of 19 dietary protein samples-these were unrelated to clinical isolates via sequencing. No point source was identified. Ciprofloxacin was added to the empiric antimicrobial regimen for patients with AML and prolonged or recurrent neutropenic fevers; no new cases were identified in the ensuing year. Conclusions: B cereus is ubiquitous in the hospital environment, at times leading to clusters with unrelated isolates. Fastidious infection control practices addressing a range of possible exposures are warranted, but their efficacy is unknown and they may not be sufficient to prevent all infections. Thus, including B cereus coverage in empiric regimens for patients with AML and persistent neutropenic fever may limit the morbidity of this pathogen.

Mycobacterium abscessus Cluster in Cardiac Surgery Patients Potentially Attributable to a Commercial Water Purification System.

BACKGROUND: Nontuberculous mycobacteria are water-avid pathogens that are associated with nosocomial infections. OBJECTIVE: To describe the analysis and mitigation of a cluster of Mycobacterium abscessus infections in cardiac surgery patients. DESIGN: Descriptive study. SETTING: Brigham and Women's Hospital, Boston, Massachusetts. PARTICIPANTS: Four cardiac surgery patients. INTERVENTION: Commonalities among cases were sought, potential sources were cultured, patient and environmental specimens were sequenced, and possible sources were abated. MEASUREMENTS: Description of the cluster, investigation, and mitigation. RESULTS: Whole-genome sequencing confirmed homology among clinical isolates. Patients were admitted during different periods to different rooms but on the same floor. There were no common operating rooms, ventilators, heater-cooler devices, or dialysis machines. Environmental cultures were notable for heavy mycobacterial growth in ice and water machines on the cluster unit but little or no growth in ice and water machines in the hospital's other 2 inpatient towers or in shower and sink faucet water in any of the hospital's 3 inpatient towers. Whole-genome sequencing confirmed the presence of a genetically identical element in ice and water machine and patient specimens. Investigation of the plumbing system revealed a commercial water purifier with charcoal filters and an ultraviolet irradiation unit leading to the ice and water machines in the cluster tower but not the hospital's other inpatient towers. Chlorine was present at normal levels in municipal source water but was undetectable downstream from the purification unit. There were no further cases after high-risk patients were switched to sterile and distilled water, ice and water machine maintenance was intensified, and the commercial purification system was decommissioned. LIMITATION: Transmission pathways were not clearly characterized. CONCLUSION: Well-intentioned efforts to modify water management systems may inadvertently increase infection risk for vulnerable patients. PRIMARY FUNDING SOURCE: National Institutes of Health.

A Flexi-PEGDA Upconversion Implant for Wireless Brain Photodynamic Therapy.

Near-infrared (NIR) activatable upconversion nanoparticles (UCNPs) enable wireless-based phototherapies by converting deep-tissue-penetrating NIR to visible light. UCNPs are therefore ideal as wireless transducers for photodynamic therapy (PDT) of deep-sited tumors. However, the retention of unsequestered UCNPs in tissue with minimal options for removal limits their clinical translation. To address this shortcoming, biocompatible UCNPs implants are developed to deliver upconversion photonic properties in a flexible, optical guide design. To enhance its translatability, the UCNPs implant is constructed with an FDA-approved poly(ethylene glycol) diacrylate (PEGDA) core clad with fluorinated ethylene propylene (FEP). The emission spectrum of the UCNPs implant can be tuned to overlap with the absorption spectra of the clinically relevant photosensitizer, 5-aminolevulinic acid (5-ALA). The UCNPs implant can wirelessly transmit upconverted visible light till 8 cm in length and in a bendable manner even when implanted underneath the skin or scalp. With this system, it is demonstrated that NIR-based chronic PDT is achievable in an untethered and noninvasive manner in a mouse xenograft glioblastoma multiforme (GBM) model. It is postulated that such encapsulated UCNPs implants represent a translational shift for wireless deep-tissue phototherapy by enabling sequestration of UCNPs without compromising wireless deep-tissue light delivery.

Mechanistic Evaluation of Bioorthogonal Decaging with trans-Cyclooctene: The Effect of Fluorine Substituents on Aryl Azide Reactivity and Decaging from the 1,2,3-Triazoline.

Bioorthogonal prodrug activation/decaging strategies need to be selective, rapid and release the drug from the masking group upon activation. The rates of the 1,3-dipolar cycloaddition between a trans-cyclooctene (TCO) and a series of fluorine-substituted azido-PABC self-immolative spacers caging two model drugs, and subsequent release from the 1,2,3-triazoline are reported. As the number of fluorine substituents on the PABC linker increases from one to four, the rate of cycloaddition increases by almost one order of magnitude. Using a combination of fluorescence, 1H/19F NMR, and computational experiments, we have been able to determine how substituents on the PABC ring can influence the degradation rates and also the product distribution of the 1,2,3-triazoline. We have also been able to determine how these substituents influence the rate of imine hydrolysis and 1,6-self-immolation decaging rates of the generated anilines. The NMR and computational studies demonstrate that fluorine substituents on the aromatic ring lower the transition state energy required for converting the triazoline to the imine or aziridine intermediates via extrusion of diatomic nitrogen, and that in the case of a tetrafluoro substituted aromatic ring, it is the imine hydrolysis and 1,6-self-immolation that is rate-limiting. This knowledge further enhances the understanding of factors which influence the stability of triazolines, and enables potential applications of fluorinated aromatics, in particular, perfluorinated aromatics, in synthetic chemistry and sustained-release drug delivery systems.

Quantifying inadvertent thermal bowel injury from the monopolar instrument.

BACKGROUND: Insulation defects are observed in 3-39 % of laparoscopic instruments. Electrosurgical injuries due to insulation defects or capacitive coupling remain an issue in laparoscopic surgery with a prevalence of 0.6-5 per thousand cases. Shielded instruments with active electrode monitoring (AEM) have been postulated to prevent these injuries. The benefit of these instruments has not been quantified. Most bowel injuries are unrecognized intra-operatively. Injury is revealed only after the patient exhibits peritonitis symptoms and surgical intervention to repair the bowel is required. These injuries may result in devastating and costly complications or mortality. The extent of bowel injury possible with commonly used generator settings and associated energy output has never been histologically defined. Our objectives in this experimental study were: quantify and compare the energy released through insulation defects or capacitive coupling with standard unshielded monopolar versus shielded instruments with (AEM), determine energy required to cause a visible burn, and relate the histological burn depth to a given amount of energy. METHODS: Ex vivo porcine jejunum was used for tissue testing. An oscilloscope measured energy output from three common electrosurgical generators at recommended power settings with standard or AEM instruments with insulation defects and in capacitive coupling scenarios. Presence of a visible burn was noted, and depth of tissue damage for a given amount of energy was measured histologically. RESULTS: All samples that received ≥3.8 J of energy had visible burns. As little as 10 J caused full wall thickness burns. 3.8 J was exceeded at the 30- and 50-W power settings in every experimental scenario using standard monopolar instruments; AEM instruments never approached this much energy. CONCLUSIONS: Serious burn injury results from small amounts of energy leaked from standard instruments. AEM instruments appeared protective and did not leak sufficient energy to cause burn injuries to the bowel.

First-in-human evaluation of a hexon chimeric adenovirus vector expressing HIV-1 Env (IPCAVD 002).

BACKGROUND: We report the first-in-human safety and immunogenicity assessment of a prototype hexon chimeric adenovirus (Ad) serotype 5 (Ad5) vector containing the hexon hypervariable regions of Ad serotype 48 (Ad48) and expressing human immunodeficiency virus (HIV) type 1 EnvA. METHODS: Forty-eight Ad5 and Ad48 seronegative, HIV-uninfected subjects were enrolled in a randomized, double-blind, placebo-controlled, dose escalation phase 1 study. Four groups of 12 subjects received 10(9) to 10(11) viral particles (vp) of the Ad5HVR48.EnvA.01 vaccine (n = 10 per group) or placebo (n = 2 per group) at week 0 or weeks 0, 4, and 24. Safety and immunogenicity were assessed. RESULTS: Self-limited reactogenicity was observed after the initial immunization in the highest (10(11) vp) dose group. Responses in vaccinees included Ad48 neutralizing antibody (nAb) titers higher than Ad5 nAb titers, EnvA-specific enzyme-linked immunosorbent assay titers, and EnvA-specific enzyme-linked immunospot assay responses, and these responses generally persisted at week 52. At week 28 in the 10(9), 10(10), and 10(11) vp 3-dose groups, geometric mean EnvA enzyme-linked immunosorbent assay titers were 5721, 10 929, and 3420, respectively, and Ad48 nAb titers were a median of 1.7-fold higher than for Ad5. CONCLUSIONS: Ad5HVR48.ENVA.01 was safe, well tolerated, and immunogenic at all doses tested. Vector-elicited nAb responses were greater for Ad48 than Ad5, confirming that Ad-specific nAbs in humans are primarily, but not exclusively, directed against the hexon hypervariable regions. Clinical Trials Registration. NCT00695877.

First-in-human evaluation of the safety and immunogenicity of a recombinant adenovirus serotype 26 HIV-1 Env vaccine (IPCAVD 001).

BACKGROUND: We report the first-in-human safety and immunogenicity assessment of a prototype Ad26 vector-based human immunodeficiency virus (HIV) vaccine in humans. METHODS: Sixty Ad26-seronegative, healthy, HIV-uninfected subjects were enrolled in a randomized, double-blinded, placebo-controlled, dose-escalation phase 1 study. Five groups of 12 subjects received 10(9)-10(11) vp of the Ad26-EnvA vaccine (N = 10/group) or placebo (N = 2/group) at weeks 0 and 24 or weeks 0, 4, and 24. Safety and immunogenicity were assessed. RESULTS: Self-limited reactogenicity was observed after the initial immunization at the highest (10(11) vp) dose. No product-related SAEs were observed. All subjects who received the Ad26-EnvA vaccine developed Ad26 NAb titers, EnvA-specific enzyme-linked immunosorbent assays (ELISA) titers, and EnvA-specific enzyme-linked immunospot assays (ELISPOT) responses. These responses persisted at week 52. At week 28 in the 10(9), 10(10), 10(11) vp 3-dose and the 10(10) and 5 × 10(10) vp 2-dose groups, geometric mean EnvA ELISA titers were 6113, 12 470, 8545, 3470, and 9655 and mean EnvA ELISPOT responses were 397, 178, 736, 196, and 1311 SFC/10(6) peripheral blood mononuclear cells, respectively. CONCLUSION: This Ad26 vectored vaccine was generally safe and immunogenic at all doses tested. Reactogenicity was minimal with doses of 5 × 10(10) vp or less. Ad26 is a promising new vaccine vector for HIV-1. CLINICAL TRIALS REGISTRATION: NCT00618605.

Single-injection HPLC method for rapid analysis of a combination drug delivery system.

Developing combination drug delivery systems (CDDS) is a challenging but necessary task to meet the needs of complex therapy regimes for patients. As the number of multi-drug regimens being administered increases, so does the difficulty of characterizing the CDDS as a whole. We present a single-step method for quantifying three model therapeutics released from a model hydrogel scaffold using high-performance liquid chromatography (HPLC). Poly(ethylene glycol) dimethacrylate (PEGDMA) hydrogel tablets were fabricated via photoinitiated crosslinking and subsequently loaded with model active pharmaceutical ingredients (APIs), namely, porcine insulin (PI), fluorescein isothiocyanate-labeled bovine serum albumin (FBSA), prednisone (PSE), or a combination of all three. The hydrogel tablets were placed into release chambers and sampled over 21 days, and APIs were quantified using the method described herein. Six compounds were isolated and quantified in total. Release kinetics based on chemical properties of the APIs did not give systematic relationships; however, PSE was found to have improved device loading versus PI and FBSA. Rapid analysis of three model APIs released from a PEGDMA CDDS was achieved with a direct, single-injection HPLC method. Development of CDDS platforms is posited to benefit from such analytical approaches, potentially affording innovative solutions to complex disease states.

Duration of postoperative dressing after mini-open carpal tunnel release: a prospective, randomized trial.

PURPOSE: In this prospective, randomized, controlled study, we hypothesized that there would be no difference in short-term functional, subjective, and blinded wound outcome measures between patients treated after mini-open carpal tunnel release (CTR) with a postoperative bulky dressing for 2 weeks and those with dressing removal and placement of an adhesive strip after 48 to 72 hours. METHODS: A total of 94 consecutive patients underwent mini-open CTR and placement of a bulky dressing and were randomized to either bandage removal at 48 to 72 hours with placement of an adhesive strip or continuation of the postoperative dressing until initial follow-up at approximately 2 weeks. We evaluated patient demographics, Levine-Katz scores, range of motion, strength, and a blinded assessment of wound healing at approximately 2 weeks and between 6 and 12 weeks. We conducted paired and independent sample t-tests to evaluate for statistical significance. RESULTS: There was no significant difference in Levine-Katz scores between groups at either the first follow-up or final visit. One patient with a longer dressing duration had evidence of a wound dehiscence. CONCLUSIONS: Removal of a bulky dressing after mini-open CTR and replacement with an adhesive strip at 48 to 72 hours causes no wound complications and results in equal short-term clinical and subjective outcome measures compared with using a bulky dressing for 2 weeks. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.

Electrosurgery in gastrointestinal endoscopy: principles to practice.

An electrosurgery generator unit is a critical piece of equipment in any therapeutic endoscopy setting. Electrosurgery generators produce high-frequency alternating electric current and differ from electrocautery units in that both cutting and coagulation effects can be achieved. This ability to cut and coagulate at the same time makes electrosurgery an ideal therapeutic tool for gastrointestinal endoscopy. Although education and familiarity with these devices are accepted as the primary avenue to the safest and most effective clinical outcomes, concise information linking the basic properties of electrosurgery directly to clinical practice is not widespread. The following are the aims of this article: (i) to relate the fundamental electrosurgical principles to commonly performed procedures such as snare polypectomy, hot biopsy, sphincterotomy, bipolar hemostasis, and argon plasma coagulation, and (ii) to provide practical suggestions for the use of these devices on the basis of an understanding of electrosurgical principles and the available clinical data.

A pharmacogenomic study of docetaxel and gemcitabine for the initial treatment of advanced non-small cell lung cancer.

BACKGROUND: Pharmacogenomic profiling is an attractive strategy for individualizing chemotherapy. Several genetic polymorphisms predict the survival of patients with non-small cell lung cancer treated with platinum-based chemotherapy. This phase II clinical trial was performed using a non-platinum-based chemotherapy doublet. The impact of previously identified polymorphisms on clinical outcomes was assessed. METHODS: Patients with advanced non-small cell lung cancer who had not received previous chemotherapy were treated with docetaxel 40 mg/m2 on days 1 and 8 and gemcitabine 800 mg/m2 days 1 and 8 every 21 days until disease progression or unacceptable toxicity. A pretreatment blood sample was obtained, and genomic DNA was analyzed for polymorphisms in DNA repair and metabolic genes. RESULTS: Forty-nine patients were enrolled and evaluated for response and survival. The overall radiographic response rate was 38%, and the median survival was 8.6 months. Nonhematologic toxicity was generally mild. Two treatment related deaths occurred: one due to neutropenic sepsis during the first cycle and one due to pulmonary edema after 12 cycles of treatment. Polymorphisms in XPD, XRCC1, and XRCC3 did not significantly predict survival, but trends similar to those reported for platinum-based chemotherapy were observed. The wild-type XPD genotype was associated with prolonged survival and a significantly higher risk of grade 4 neutropenia (p = 0.02). CONCLUSION: This regimen of docetaxel and gemcitabine is well tolerated and active for the treatment of advanced non-small cell lung cancer. The impact of XPD polymorphisms on hematologic toxicity is similar to what has been reported for platinum-based chemotherapy.

Phase III trial of paclitaxel plus carboplatin with or without tirapazamine in advanced non-small-cell lung cancer: Southwest Oncology Group Trial S0003.

PURPOSE: Tumor hypoxia confers chemotherapy resistance. Tirapazamine is a cytotoxin that selectively targets hypoxic cells. We conducted a phase III clinical trial to determine whether the addition of tirapazamine to paclitaxel and carboplatin offered a survival advantage when used in the treatment of patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Of 396 patients registered, 367 eligible patients were randomly assigned to either arm 1 (n = 181), which consisted of treatment every 21 days with paclitaxel 225 mg/m2/3 h, carboplatin (area under the curve = 6), and tirapazamine 260 mg/m2 in cycle 1 (which was escalated, if tolerable, to 330 mg/m(2) in cycle 2), or arm 2 (n = 186), which consisted of paclitaxel and carboplatin as in arm 1 with no tirapazamine. RESULTS: Patient characteristics were similar between the two arms. There were no statistically significant differences in response rates, progression-free survival, or overall survival. Patients on arm 1 had significantly (P < .05) more abdominal cramps, fatigue, transient hearing loss, febrile neutropenia, hypotension, myalgias, and skin rash and were removed from treatment more often as a result of toxicity than patients in arm 2 (26% v 13%, respectively; P = .003). More than 40% of patients did not have the tirapazamine dose escalated, primarily because of toxicity. The trial was closed early after an interim analysis demonstrated that the projected 37.5% improvement in survival (8 v 11 months median survival) in arm 1 was unachievable (P = .003). CONCLUSION: The addition of tirapazamine to paclitaxel and carboplatin does not result in improved survival in advanced NSCLC compared with paclitaxel and carboplatin alone but substantially increases toxicity.

Ablation of stage T1/T2 prostate cancer with permanent interstitial temperature self-regulating rods.

PURPOSE: To determine if stage T(1)/T(2) prostate cancer can be treated safely and effectively with interstitial thermal ablation. PATIENTS AND METHODS: Twenty patients with biopsy-confirmed prostate cancer were enrolled in the protocol. The average age was 71.0 years, and the pretreatment prostate specific antigen (PSA) concentration ranged from 2.5 to 10.7 ng/mL and the Gleason sum from 3 to 7. An array of small biocompatible magnetic alloy rods was placed in the patients percutaneously in a procedure analogous to the placement of brachytherapy seeds. Rods were placed end-to-end and no further than 1 cm apart; rods extended to the capsule and were placed at the capsule in the rectal grove. The rods are temperature self-regulating and heat to 70 degrees C when placed in an alternating magnetic field. Each patient was treated in a coil system that supplies a uniform magnetic field throughout the patient's pelvis for a single 60-minute session. Urethral cooling and rectal temperature monitoring was performed. Serial PSA was followed, and biopsy was performed 1 year post-treatment. RESULTS: Immediately after treatment, most PSA values increased dramatically but then fell to <1.0 ng/mL within 8 weeks. After 1 year, five patients had positive biopsies; these patients had significantly lower rodimplant densities. Eight patients reported erectile dysfunction, but none reported incontinence. Other complications were minor. CONCLUSION: The data suggest that this technique is well tolerated and safe and may be useful in certain patients with T(1)/T(2) prostate cancer.

Use of interstitial temperature self-regulating thermal rods in the treatment of prostate cancer.

Several groups are investigating a new technique for thermal treatment of the prostate involving permanent implantation of small biocompatable rods in a procedure similar to brachytherapy. The rods are then heated by an extracorporeal alternating magnetic field. The rods are composed of an alloy of palladium and cobalt such that they are temperature self-regulating; the regulated temperature is set during manufacture. Clinically, rods with a regulating temperature in the hyperthermia range are being employed as an adjuvant to external-beam radiation. Rods with a regulation temperature in the thermal ablation range are being used in two patient groups: those with newly diagnosed stage T(1) or T(2) prostate cancer and those who have localized recurrent disease after external-beam radiation. Early data appear promising.

Ferromagnetic self-regulating reheatable thermal rod implants for in situ tissue ablation.

BACKGROUND AND PURPOSE: Ferromagnetic compounds, when placed in a radiofrequency magnetic field, develop an electrical current. When placed in tissue, resistance to the transmission of the electrical current leads to heating of the tissues next to the ferromagnetic compound. The Curie temperature is a transition point at which the development of a particular temperature within the material results in loss of its magnetic properties; as such, when this temperature is reached, there is cessation of current, and thus heat production stops. Our goal was to examine the ablative impact of permanently implanted palladium and cobalt self-regulating temperature rods on solid abdominal and pelvic organs. These rods were designed to develop a maximum temperature of 70 degrees C. MATERIALS AND METHODS: In 16 pigs, renal, hepatic, uterine, and pancreatic ferromagnetic rods were placed using a template. The rods were delivered in 1-cm parallel rows of two rods each in order to ablate 7 g of tissue. The animals were subsequently treated in an extracorporeal magnetic field of 50 gauss rms at a frequency of 50 kHz. The position of the rods was confirmed by fluoroscopy before the animal was put in the magnetic field. The animals received one or two treatment sessions. Intralesional and extralesional temperatures were measured continuously. Serum chemistry was analyzed before surgery, after each treatment, and at the time of harvest. Two weeks following therapy, the treated tissues were harvested and examined histopathologically. RESULTS: In all tissues with properly aligned rods, the temperature of the tissue surrounding the rods exceeded 50 degrees C. Histologic review showed confluent tissue necrosis in 7 of 9 kidneys (78%), 6 of 9 livers (67%), 1 of 3 pancreases (33%), and 1 of 3 uterine specimens (33%). Necrosis extended for 2 mm beyond the periphery of the rods. All failures were secondary to technical misalignment of the rods, which occurred because of our attempt to treat more than one organ in each animal. CONCLUSIONS: Ferromagnetic rods, when properly aligned in a magnetic field, create well-defined areas of necrosis. There are no skip areas of viable tissue within the treated area, and there is a precipitous fall-off of injury just outside the area of treatment. Also, because the rods can be reactivated at any time, recurrent lesions within the same site can be treated. This form of minimally invasive in situ ablative therapy appears promising. Clinical trials in the kidney and in other abdominal and pelvic organs are pending.

A field-focusing device to increase power output of ThermoRod trade mark implants for thermal ablation of tissue.

Induction heating of small, cylindrical ferromagnetic implants (1.4 cm long and 1 mm in diameter) is a method for treating deep-seated tumors. These implants, or ThermoRods trade mark, are placed within a lesion in 1-cm(2) arrays and are exposed to an alternating magnetic field. The implants absorb energy from that field and transfer it as heat to the surrounding tissue. Each ThermoRod trade mark offers approximately 400 mW of power, and to kill cells, the target temperature must be greater than 42 degrees C. In this work, a magnetic field-focusing device is employed to concentrate the induced magnetic flux toward a local region near the base of the prostate to increase the power output of proximal ThermoRods trade mark. This, in turn, allows for more complete thermal ablation of lesions near the base of the prostate where the heat-sink characteristics of the bladder can cause significant power losses. Boundary element analysis and in vitro testing have shown that the use of a ferrofluid-based field-focusing device can lead to a significant increase in power output of approximately 25% and 13%, respectively, of proximal ThermoRods trade mark. These preliminary results indicate that the incorporation of such a ferrofluid-based focusing device into ThermoRod trade mark treatments is promising for the avoidance of significant power loss and for assuring complete thermal ablation of prostatic lesions.

Interstitial thermal therapy in patients with localized prostate cancer: histologic analysis.

OBJECTIVES: To examine, by way of histologic examination, the destruction of excised prostate glands treated with thermal ablation. Thermal ablation treatment with permanently implanted temperature self-regulating rods is being used in the treatment of localized prostate cancer. METHODS: Four patients with biopsy-proven prostate cancer, who had been scheduled for routine radical prostatectomy with a gland size of less than 70 g, Gleason sum of 7 or less, and prostate-specific antigen values less than 10.0 ng/mL, were implanted with 70 degrees C rods under ultrasound and fluoroscopic control. The patients were then given multiple thermal treatments. Glands were removed and histologically analyzed to access the thermal destruction. RESULTS: Histologic examination revealed confluent thermal destruction within the rod array when the rods were placed end-to-end and no farther than 1 cm apart. Little necrosis was seen outside the array. To ensure the necessary destruction, the rods must be placed at the capsule, including posteriorly near the rectum. The results indicated that energy levels greater than 40 W-min/g of tissue should be used. This can be achieved by implanting 1.5 rods/g of prostate and treating the patient for 60 minutes. In 3 of the 4 patients, no residual cancer was found in the gland after thermal treatment. CONCLUSIONS: Histologic examination has aided in determining the implant density and treatment time and, therefore, the necessary energy, for adequate necrosis. The technique demonstrates the ability to destroy the prostate adequately, including tissue at the capsule. This new procedure appears promising in the treatment of localized prostate cancer.

Interpreting measures of treatment effect in cancer clinical trials.

The efficacy of a new cancer regimen is usually assessed by analyzing outcomes such as tumor response and overall survival. Many publications summarizing results of cancer clinical trials report measures such as odds ratios and hazard ratios, as these are the estimators of treatment effect obtained from regression models used to analyze the data. However, these measures are sometimes misinterpreted, as they are not necessarily familiar to many readers. The most common mistake is to interpret both measures as relative risks, an interpretation that can lead to an incorrect impression of the impact of the treatment on response and survival.