Sentinel Lymph Node Mapping in Breast Cancer Patients Through Fluorescent Imaging Using Indocyanine Green: The INFLUENCE Trial.

OBJECTIVE: The aim was to compare the (sentinel) lymph node detection rate of indocyanine green (ICG)-fluorescent imaging versus standard-of-care 99m Tc-nanocoilloid for sentinel lymph node (SLN)-mapping. BACKGROUND: The current gold standard for axillary staging in patients with breast cancer is sentinel lymph node biopsy (SLNB) using radio-guided surgery using radioisotope technetium ( 99m Tc), sometimes combined with blue dye. A promising alternative is fluorescent imaging using ICG. METHODS: In this noninferiority trial, we enrolled 102 consecutive patients with invasive early-stage, clinically node-negative breast cancer. Patients were planned for breast conserving surgery and SLNB between August 2020 and June 2021. The day or morning before surgery, patients were injected with 99m Tc-nanocolloid. In each patient, SLNB was first performed using ICG-fluorescent imaging, after which excised lymph nodes were tested with the gamma-probe for 99m Tc-uptake ex vivo, and the axilla was checked for residual 99m Tc-activity. The detection rate was defined as the proportion of patients in whom at least 1 (S)LN was detected with either tracer. RESULTS: In total, 103 SLNBs were analyzed. The detection rate of ICG-fluorescence was 96.1% [95% confidence interval (95% CI)=90.4%-98.9%] versus 86.4% (95% CI=78.3%-92.4%) for 99m Tc-nanocoilloid. The detection rate for pathological lymph nodes was 86.7% (95% CI=59.5%-98.3%) for both ICG and 99m Tc-nanocoilloid. A median of 2 lymph nodes were removed. ICG-fluorescent imaging did not increase detection time. No adverse events were observed. CONCLUSIONS: ICG-fluorescence showed a higher (S)LN detection rate than 99m Tc-nanocoilloid, and equal detection rate for pathological (S)LNs. ICG-fluorescence may be used as a safe and effective alternative to 99m Tc-nanocoilloid for SLNB in patients with early-stage breast cancer.

Current View of Diagnosing Small Fiber Neuropathy.

Small fiber neuropathy (SFN) is a disorder of the small myelinated Aδ-fibers and unmyelinated C-fibers [5, 6]. SFN might affect small sensory fibers, autonomic fibers or both, resulting in sensory changes, autonomic dysfunction or combined symptoms [7]. As a consequence, the symptoms are potentially numerous and have a large impact on quality of life [8]. Since diagnostic methods for SFN are numerous and its pathophysiology complex, this extensive review focusses on categorizing all aspects of SFN as disease and its diagnosis. In this review, sensitivity in combination with specificity of different diagnostic methods are described using the areas under the curve. In the end, a diagnostic work-flow is suggested based on different phenotypes of SFN.

An Ex Vivo Phantom Validation Study of an MRI-Transrectal Ultrasound Fusion Device for Targeted Prostate Biopsy.

OBJECTIVES: To evaluate the ex vivo accuracy of an MRI-TRUS fusion device for guiding targeted prostate biopsies, to identify the origin of errors, and to evaluate the likelihood that lesions can be accurately targeted. MATERIALS AND METHODS: Three prostate phantoms were used to perform 27 biopsies using transperineal MRI-TRUS fusion. All phantoms underwent 3-T MRI. The prostate contour and nine lesions were delineated onto the MRI. A 3D-US dataset was generated and fused with the MRI. Per lesion, one needle was virtually planned. The postbiopsy needle location was virtually registered. The needle trajectory was marked using an MRI-safe guidewire. Postinterventional MRI was performed. The coordinates of the lesion on preinterventional MRI, the virtually planned needle, the virtually registered needle, and the marked needle trajectory on postinterventional MRI were documented and used to calculate the planning error (PE), targeting error (TE), and overall error (OE). Using the OE in the transversal plane, an upper one-sided tolerance interval was calculated to assess the likelihood that a biopsy needle was on target. RESULTS: In the transversal plane, the mean PE, TE, and OE were 1.18, 0.39, and 2.33 mm, respectively. Using a single biopsy core, the likelihood that lesions with a diameter of 2 mm can be accurately targeted is 26%; lesions of 3 mm 61%; lesions of 4 mm 86%; lesions of 5 mm 96%; and lesions of 6 mm 99%. The likelihood of accurate sampling increases if more biopsy cores are used. CONCLUSION: MRI-TRUS fusion allows for accurate sampling of MRI-identified lesions with an OE of 2.33 mm. Lesions with a diameter of 3 mm or more can be accurately targeted. These results should be considered the lower limit of in vivo accuracy.

The quality of 5-aminolevulinic acid-induced photodynamic diagnosis and transurethral resection of bladder tumors: does the urologist play a role?.

INTRODUCTION: The aim of this study is to evaluate the quality of photodynamic diagnosis (PDD) and transurethral resection of bladder tumors (TURBT) among different urologists. PATIENTS AND METHODS: The selected data consists of 194 patients, 268 5-aminolevulinic acid (5-ALA)-induced PDD procedures and 934 biopsies. Tumors were resected and biopsies were taken from suspicious areas under guidance of white light endoscopy and 5-ALA-induced fluorescence cystoscopy. The quality of PDD was determined by evaluating the mean number of tumors resected by 5 urologists and, thereafter, assessing the time to recurrence between groups. RESULTS: Urologist 1 took 37% more biopsies (p < 0.001) and diagnosed 42% more tumors (p = 0.005) and 46% more false positives (p < 0.001) from bladders compared to urologists 2, 3, 4 and 5 together. The mean time to bladder cancer recurrence for all recurrences within 0-18 months was 11.0 months for operator 1 and 8.3 months for the other urologists (p = 0.01). CONCLUSIONS: The resecting urologist appears to be an important factor for the quality of standard and PDD-assisted TURBT. Learning curve programs may be required with experienced surgeons accompanying those with less experience.

Navigated laparoscopy--liver shift and deformation due to pneumoperitoneum in an animal model.

BACKGROUND: Precise laparoscopic liver resection requires accurate planning and visualization of important anatomy such as vessels and tumors. Combining laparoscopic ultrasound with navigation technology could provide this. Preoperative images are valuable for planning and overview of the procedure, while intraoperative images provide an updated view of the surgical field. PURPOSE: To validate the accuracy of navigation technology based on preoperative images, we need to understand how much the liver shifts and deforms due to heartbeat, breathing, surgical manipulation and pneumoperitoneum. In this study, we evaluated liver tumor shift and deformation due to pneumoperitoneum in an animal model. METHODS: Tumor models were injected into the liver of the animal, and 3D CT images were acquired before and after insufflation. Tumor shifts and deformation were determined. RESULTS: The results showed significant tumor position shift due to pneumoperitoneum, with a maximum of 28 mm in cranio-caudal direction. No significant tumor deformation was detected. Small standard deviations suggest rigid body transformation of the liver as a whole, but this needs further investigation. CONCLUSION: The findings indicate a need for anatomic shift correction of preoperative images before they are used in combination with LUS guidance during a laparoscopic liver resection procedure.

In vivo bladder cancer diagnosis by high-volume Raman spectroscopy.

We studied the feasibility of Raman spectroscopy for the diagnosis of bladder cancer in vivo. Since the invasion stage is crucial for the treatment choice, a high-volume based Raman probe was used to investigate the potential of determining the invasiveness of bladder cancer. High quality spectra were obtained from suspicious and nonsuspicious bladder locations during the procedure of transurethral resection of bladder tumors (TURBT) with collection times of 1-5 s. Multivariate analysis was used to generate the classification models. The algorithm was able to distinguish bladder cancer from normal bladder locations with a sensitivity of 85% and a specificity of 79%. The Raman spectra of bladder cancer stages showed a gradual increase in the intensity of specific amino acid peaks and, most likely, an increase in the intensity of DNA peaks.

Photodynamic diagnosis (5-aminolevulinic acid) of transitional cell carcinoma after bacillus Calmette-Guérin immunotherapy and mitomycin C intravesical therapy.

BACKGROUND: Photodynamic diagnosis (PDD) is a technique that enhances the detection of occult bladder tumors during cystoscopy using a fluorescent dye. OBJECTIVE: To study the differential effects of bacillus Calmette-Guérin (BCG) and mitomycin C (MMC) intravesical therapy on the false-positive rate of PDD of bladder cancer. DESIGN, SETTING, AND PARTICIPANTS: This study included 552 procedures and 1874 biopsies. INTERVENTION: Tumors were resected and biopsies were taken from suspicious areas, under guidance of white-light endoscopy and 5-ALA (5-aminolevulinic acid)-induced fluorescence cystoscopy. MEASUREMENTS: The influence of intravesical BCG immunotherapy and intravesical MMC chemotherapy on pyuria, inflammation, and PDD specificity was examined in univariate analyses. RESULTS AND LIMITATIONS: BCG significantly results in inflammation (odds ratio [OR]: 1.53, p=0.002), leukocyturia (OR: 1.84, p=0.034), and false positives in PDD (OR: 1.49, p=0.001). However, a single BCG instillation within 3 mo before PDD is most likely not associated with increased false-positive rates (OR: 0.35, p=0.26). Leukocyturia normalizes within 6 wk after the last BCG instillation, but PDD specificity is reduced up to 3 mo. CONCLUSIONS: BCG is an important predictor for false positives in PDD (5-ALA). More than one BCG instillation within 3 mo before fluorescence cystoscopy decreases the specificity of PDD.

Imaging techniques for research and education of thermal and mechanical interactions of lasers with biological and model tissues.

A setup based on color Schlieren techniques has been developed to study the interaction of energy sources, such as lasers, with biological tissues. This imaging technique enables real-time visualization of dynamic temperature gradients with high spatial and temporal resolution within a transparent tissue model. High-speed imaging techniques were combined in the setup to capture mechanical phenomena such as explosive vapor, cavitation bubbles, and shock waves. The imaging technique is especially used for qualitative studies because it is complex to obtain quantitative data by relating the colors in the images to temperatures. By positioning thermocouples in the field of view, temperature figures can be added in the image for correlation to colored areas induced by the temperature gradients. The color Schlieren setup was successfully used for various studies to obtain a better understanding of interaction of various laser, rf, and ultrasound devices used in medicine. The results contributed to the safety and the optimal settings of various medical treatments. Although the interaction of energy sources is simulated in model tissue, the video clips have proven to be of great value for educating researchers, surgeons, nurses, and students to obtain a better understanding of the mechanism of action during patient treatment.

Neodymium:yttrium aluminum garnet surgical laser versus bipolar electrocoagulation for laparoscopic ovariectomy in dogs.

OBJECTIVE: To compare use of neodymium:yttrium aluminum garnet (Nd:YAG) surgical laser and bipolar electrocoagulation (BEC) for laparoscopic ovariectomy (OVE) in dogs. STUDY DESIGN: Prospective clinical trial. ANIMALS: Female dogs (n=72). METHODS: Laparoscopic OVE by Nd:YAG laser (600 microm optical fiber, contact mode) in 36 dogs was compared with laparoscopic OVE by bipolar electro-coagulating grasping forceps. Dogs were paired (laser, electrocoagulation) matched for breed, age, body weight, obesity, and number of heat cycles. Duration of predetermined surgery times and total surgical time were compared between groups. Occurrence of intra- and postoperative complications and their effect on surgical duration were evaluated. RESULTS: Laser surgery resulted in a higher incidence of intraoperative mesovarial bleeding (12 times; 9 dogs) compared with electrosurgery (4 times; 3 dogs). Use of laser caused a 2 minute delay for transection of the left ovary compared with electrosurgery. Postoperative complication rates and convalescence were similar for both groups. CONCLUSIONS: BEC reduced surgical time and intraoperative mesovarial bleeding compared with laser resection. CLINICAL RELEVANCE: Although the laser was effective for laparoscopic OVE, bipolar electrosurgical laparoscopic OVE remained the method of choice.

Cost aspects of transurethral resection of the prostate, contact laser prostatectomy, and electrovaporization.

OBJECTIVES: To compare the costs of transurethral resection of the prostate (TURP), contact laser prostatectomy (CLP), and electrovaporization in men with lower urinary tract symptoms associated with benign prostatic hyperplasia. METHODS: We conducted a randomized controlled trial that included men with lower urinary tract symptoms who met the criteria of the International Scientific Committee on benign prostatic hyperplasia. Subjective changes were quantified using questionnaires validated by the American Urological Association. The maximal free urinary flow rate was estimated. Morbidity and mortality were registered. These parameters were measured at regular intervals for up to 1 year and once during long-term follow-up. A cost analysis together with a sensitivity analysis was performed on the basis of a follow-up of 12 months. RESULTS: A total of 50 men were randomized to TURP, 45 to laser treatment, and 46 to electrovaporization. The subjective and objective changes were very similar during the 12 months of follow-up. The costs were highest for CLP (1885 dollars), followed by TURP (1707 dollars), and were lowest for electrovaporization (1489 dollars). However, the length of hospital stay decreased during the trial more for CLP and electrovaporization than for TURP. Recalculations demonstrated almost equal costs for CLP and TURP (1697 dollars and 1643 dollars, respectively) and the lowest costs for electrovaporization (1386 dollars). CONCLUSIONS: Electrovaporization has a better cost-effectiveness than CLP and TURP in patients with lower urinary tract symptoms associated with benign prostatic hyperplasia. CLP and TURP showed very similar cost-effectiveness ratios.