Blue Light Laser Results in Less Vocal Fold Scarring Compared to KTP Laser in Normal Rat Vocal Folds.

OBJECTIVES: Preliminary investigations suggest that a novel blue light (BL) laser with a wavelength of 445 nm is comparable to the commonly utilized potassium titanyl phosphate (KTP) laser (532 nm) for treatment of various laryngeal pathologies. The objective of the current study is to make a direct histological comparison of the degree of vocal fold scarring after either BL or KTP laser treatment in an animal model. STUDY DESIGN: This was a randomized controlled study using rats. METHODS: Twenty-four Sprague-Dawley rats were randomized to BL or KTP laser treatment. Laser was delivered in non-overlapping pulses to normal rat vocal folds. Larynges in each group were harvested at three time points: post-operative day 1, 30, and 90. Three animals served as negative controls. The excised whole larynges were sectioned transversely and stained with hematoxylin/eosin and trichrome. Presence of subepithelial inflammation and protein deposition/fibrosis indicative of scarring were scored semi-quantitatively (from grade 1-3) by two pathologists blinded to treatment groups. RESULTS: Between-group comparison showed that both laser treatments resulted in significantly elevated subepithelial protein deposition/fibrosis 90 days after treatment compared to negative controls (BL: 2 ± 0; KTP: 2.67 ± 0.29; control: 1.17 ± 0.29; P < .05). However, the degree of protein deposition/fibrosis was significantly higher in the KTP group compared to the BL group (P = .016). Within-group comparison showed that the KTP group showed evidence of fibrosis as early as 30 days after treatment, which was not observed in the BL group. CONCLUSIONS: The current study suggests that the degree of scarring is significantly less after BL laser treatment compared to KTP in normal rat vocal fold tissue. LEVEL OF EVIDENCE: NA Laryngoscope, 131:853-858, 2021.

Pure tissue repairs: a timely and critical revival.

"The majority of hernias can be satisfactorily repaired by using the tissues at hand. The use of mesh prosthesis should be restricted to those few hernias in which tension or lack of good fascial structures prevents a secure primary repair. This group includes large direct inguinal hernias and incisional hernias in which the defect is too large to close primarily without undue tension. Most recurrent hernias, because of this factor are best repaired with mesh prosthesis". These words, penned in 1960 by Francis Usher have reconfirmed what had been a mantra of the Shouldice Hospital (Usher in 81:847-854, 1960). The Shouldice Hospital has specialized in the treatment of abdominal wall hernias since 1945. It has, since its beginning, insisted on the fact that a thorough knowledge of anatomy coupled with large volumes of surgical cases would lead to unparalleled expertise. It was Cicero who taught us that "Practice, not intelligence or dexterity, will win the day"! Since the seminal contribution of Bassini (1844-1924), there have been no less than 80 procedures imitating his inguinal herniorrhaphy and much more since the introduction of mesh and mesh devices (Iason in Hernia. The Blakiston Company, Philadelphia, pp 475-604, 1940). All have failed to some extent and it appears that the common denominator for these failures was the inability to understand the importance of entering the preperitoneal space. Only Shouldice and McVay (Lotheissen, Narath) realized the shortcoming and have continued to thrive as a successful procedure. Entering the preperitoneal space eliminates any temptation to plicate the posterior inguinal wall, a layer normally deficient in direct inguinal hernias, but it also allows the identification of muscle layers rectus, transversus and internal oblique muscles which will go to reconstruct the posterior inguinal wall, without tension as reported by Schumpelick (Junge in 7(1):17-20, 2003).

A Pathology of Mesh and Time: Dysejaculation, Sexual Pain, and Orchialgia Resulting From Polypropylene Mesh Erosion Into the Spermatic Cord.

OBJECTIVE: The ubiquitous use of polypropylene mesh in hernia surgery has spawned a new clinical syndrome: chronic post-herniorrhaphy neuralgia. A subset of that clinical picture is dysejaculation, sexual pain, and orchialgia. We propose to identify the processes that lead to that pain. SUMMARY OF BACKGROUND DATA: Specimens of vas adherent to polypropylene mesh, explanted in an attempt to control severe, life-changing inguinodynia are extremely difficult to obtain. This scarcity may be due to ingrained attitudes in our society about removal of vas and/or testicles for whatever reason. Attempts at preserving such damaged structures may paradoxically contribute to the chronicity and severity of such pain. METHODS: The medical files of patients who had mesh specimens explanted because of severe chronic post-herniorrhaphy pain were reviewed to identify cases with recorded evidence, at the time of surgery, of involvement of spermatic cord/vas deferens with mesh. These criteria were met in 13 cases and the specimens were analyzed histologically. RESULTS: The vas deferens was resected in 83% (5 of 6) of the patients with a history of sexual pain and/or dysejaculation (vs 14% of those without a history of sexual pain, P = 0.03). Histology demonstrated unequivocal mesh invasion of the spermatic cord, where the initial damage occurred to nerves (autonomic, somatic), then to the smooth muscle of the vas while the lumen remained patent. In 50% (3 of 6), the vas and other cord structures appeared to be completely invaded by the mesh and replaced by scar tissue. CONCLUSIONS: Irreversible damage of the nerves and vas musculature due to mesh migration is one of the mechanisms for sexual pain and dysejaculation. Attempts at all cost to preserve elements of the spermatic cord may not be justified in cases of severe pain, especially sexual pain (and/or dysejaculation) and intraoperative finding of cord involvement by the mesh. Vasectomy with mesh removal may well be indicated and be considered not a radical procedure but a conservative measure given the severity of the pain!

Mapping genomic and transcriptomic alterations spatially in epithelial cells adjacent to human breast carcinoma.

Almost all genomic studies of breast cancer have focused on well-established tumours because it is technically challenging to study the earliest mutational events occurring in human breast epithelial cells. To address this we created a unique dataset of epithelial samples ductoscopically obtained from ducts leading to breast carcinomas and matched samples from ducts on the opposite side of the nipple. Here, we demonstrate that perturbations in mRNA abundance, with increasing proximity to tumour, cannot be explained by copy number aberrations. Rather, we find a possibility of field cancerization surrounding the primary tumour by constructing a classifier that evaluates where epithelial samples were obtained relative to a tumour (cross-validated micro-averaged AUC = 0.74). We implement a spectral co-clustering algorithm to define biclusters. Relating to over-represented bicluster pathways, we further validate two genes with tissue microarrays and in vitro experiments. We highlight evidence suggesting that bicluster perturbation occurs early in tumour development.

A feasibility study of photoacoustic imaging of ex vivo endoscopic mucosal resection tissues from Barrett's esophagus patients.

BACKGROUND AND STUDY AIMS: Accurate endoscopic detection of dysplasia in patients with Barrett's esophagus (BE) remains a major clinical challenge. The current standard is to take multiple biopsies under endoscopic image guidance, but this leaves the majority of the tissue unsampled, leading to significant risk of missing dysplasia. Furthermore, determining whether there is submucosal invasion is essential for proper staging. Hence, there is a clinical need for a rapid in vivo wide-field imaging method to identify dysplasia in BE, with the capability of imaging beyond the mucosal layer. We conducted an ex vivo feasibility study using photoacoustic imaging (PAI) in patients undergoing endoscopic mucosal resection (EMR) for known dysplasia. The objective was to characterize the esophageal microvascular pattern, with the long-term goal of performing in vivo endoscopic PAI for dysplasia detection and therapeutic guidance. MATERIALS AND METHODS:  EMR tissues were mounted luminal side up. The tissues were scanned over a field of view of 14 mm (width) by 15 mm (depth) at 680, 750, and 850 nm (40 MHz acoustic central frequency). Ultrasound and photoacoustic images were simultaneously acquired. Tissues were then sliced and fixed in formalin for histopathology with hematoxylin and eosin staining. A total of 13 EMR specimens from eight patients were included in the analysis, which consisted of co-registration of the photoacoustic images with corresponding pathologist-classified histological images. We conducted mean difference test of the total hemoglobin distribution between tissue classes. RESULTS: Dysplastic and nondysplastic BE can be distinguished from squamous tissue in 84 % of region-of-interest comparisons (42/50). However, the ability of intrinsic PAI to distinguish dysplasia from NDBE, which is the clinically important challenge, was only about 33 % (10/30). CONCLUSION: We demonstrated the technical feasibility of this approach. Based on our ex vivo data, changes in total hemoglobin content from intrinsic PAI (i. e. without exogenous contrast) can differentiate BE from squamous esophageal mucosa. However, most likely intrinsic PAI is unable to differentiate dysplastic from nondysplastic BE with adequate sensitivity for clinical translation.

33 W continuous output power semiconductor disk laser emitting at 1275 nm.

We demonstrate a semiconductor disk laser emitting at 1275nm, employing a wafer fused AlInGaAs/InP-AlAs/GaAs gain mirror. A built-in Au-reflector was used to reflect the pump light not absorbed in a single pass through the gain chip active region. The laser exhibited an output power of 33 W for a pump spot with a diameter of 0.86 mm, an output coupler of 2.5%, and a heat-sink temperature of -5°C. When the temperature of the heat-sink was increased to 15 °C, the maximum output power reached a value of ~24 W. The study reveals that the wafer fused gain mirrors have a high optical quality and good uniformity enabling scaling of the maximum emitted power with the diameter of the pump spot, i.e. at least up to the 1 mm diameter.

Oxidation and degradation of polypropylene transvaginal mesh.

Polypropylene (PP) transvaginal mesh (TVM) repair for stress urinary incontinence (SUI) has shown promising short-term objective cure rates. However, life-altering complications have been associated with the placement of PP mesh for SUI repair. PP degradation as a result of the foreign body reaction (FBR) has been proposed as a contributing factor to mesh complications. We hypothesized that PP oxidizes under in vitro conditions simulating the FBR, resulting in degradation of the PP. Three PP mid-urethral slings from two commercial manufacturers were evaluated. Test specimens (n = 6) were incubated in oxidative medium for up to 5 weeks. Oxidation was assessed by Fourier Transform Infrared Spectroscopy (FTIR), and degradation was evaluated by scanning electron microscopy (SEM). FTIR spectra of the slings revealed evidence of carbonyl and hydroxyl peaks after 5 weeks of incubation time, providing evidence of oxidation of PP. SEM images at 5 weeks showed evidence of surface degradation, including pitting and flaking. Thus, oxidation and degradation of PP pelvic mesh were evidenced by chemical and physical changes under simulated in vivo conditions. To assess changes in PP surface chemistry in vivo, fibers were recovered from PP mesh explanted from a single patient without formalin fixation, untreated (n = 5) or scraped (n = 5) to remove tissue, and analyzed by X-ray photoelectron spectroscopy. Mechanical scraping removed adherent tissue, revealing an underlying layer of oxidized PP. These findings underscore the need for further research into the relative contribution of oxidative degradation to complications associated with PP-based TVM devices in larger cohorts of patients.

Degradation of polypropylene in vivo: A microscopic analysis of meshes explanted from patients.

Polypropylene meshes, originally introduced for hernia repair, are presently utilized in several anatomical sites. Several million are implanted annually worldwide. Depending on the device, up to 10% will be excised to treat complications. The excised meshes can provide material to study the complications, however, they have remained underutilized over the last decades and the mechanisms of complications continue to be incompletely understood. The fundamental question as to whether polypropylene degrades in vivo is still debated. We have examined 164 excised meshes using conventional microscopy to search for features of polypropylene degradation. Four specimens were also examined by transmission electron microscopy. The degraded material, detected by its ability to absorb dyes in the degradation nanopores, formed a continuous layer at the surface of the mesh fibers. It retained birefringence, inclusions of non-degraded polypropylene, and showed ability to meld with the non-degraded fiber core when heated by the surgical cautery. Several features indicated that the degradation layer formed in vivo: inflammatory cells trapped within fissures, melting caused by cautery of excision surgery, and gradual but progressive growth of the degradation layer while in the body. Cracking of the degraded material indicated a contribution to clinically important mesh stiffening and deformation. Chemical products of degradation need to be analyzed and studied for their role in the mesh-body interactions. The described methods can also be used to study degradation of other materials. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 237-248, 2017.

An Eustachian Tube Neuroendocrine Carcinoma: A Previously Undescribed Entity and Review of the Literature.

Primary sinonasal and middle ear neuroendocrine carcinomas are rare malignancies of the head and neck. Owing to the rarity of these tumors, the clinical behavior and optimal management of these tumors are not well defined. We present a case of an incidentally discovered sinonasal neuroendocrine carcinoma that was found to originate from the Eustachian tube, which has not previously been described in the literature. This patient was treated with primary surgical resection using a combination of transnasal and transaural approaches and achieved an incomplete resection. Follow-up imaging demonstrated continued tumor growth in the Eustachian tube as well as a new growth in the ipsilateral cerebellopontine angle and findings suspicious of perineural invasion. However, the tumor exhibited a benign growth pattern and despite continued growth the patient did not receive additional treatment and he remains asymptomatic 35 months following his original surgery.

Differentiation between Melanin-Laden Macrophages and Melanoma Cells in Vitreous Aspirates.

OBJECTIVE: The differential diagnosis between retinal detachment and melanoma metastatic to the vitreous can be challenging, both clinically and cytologically. We demonstrate the diagnostic features and pitfalls of the cytological assessment. STUDY DESIGN: A case of a metastatic melanoma to the vitreous is compared to a case of retinal detachment initially suspected as melanoma metastasis. Case 1 was a 54-year-old patient with a vague history of pigmented lesions 20 years previously and a current presentation of a visual defect. Case 2 was a 68-year-old patient with a history of melanoma and a presentation of floaters and flashing lights. RESULTS: The vitreous fluid of case 1 contained atypical, pigment-laden cells positive for HMB-45 and assessed as melanoma. On enucleation, a melanoma metastatic to the vitreous was diagnosed. The vitreous fluid of case 2 revealed atypical cells containing pigment granules. The cells were negative for melanocytic markers, while the granules stained positive for melanin. Macrophage marker CD163 was positive in all cells. The interpretation was one of macrophages reactive to the retinal detachment. CONCLUSION: Melanin-laden macrophages can mimic melanoma cells. This needs to be considered in the differential diagnosis. Additional stains can help the distinction.

750 nm 1.5 W frequency-doubled semiconductor disk laser with a 44 nm tuning range.

We demonstrate 1.5 W of output power at the wavelength of 750 nm by intracavity frequency doubling a wafer-fused semiconductor disk laser diode-pumped at 980 nm. An optical-to-optical efficiency of 8.3% was achieved using a bismuth borate crystal. The wavelength of the doubled emission could be tuned from 720 to 764 nm with an intracavity birefringent plate. The beam quality parameter M2 of the laser output was measured to be below 1.5 at all pump powers. The laser is a promising tool for biomedical applications that can take advantage of the large penetration depth of light in tissue in the 700-800 nm spectral range.

Safety considerations for synthetic sling surgery.

Implantation of a synthetic midurethral sling (SMUS) is the most commonly performed anti-incontinence operation in women worldwide. The effectiveness of the SMUS is comparable to that of the historical gold standards--autologous fascial slings and the Burch colposuspension. Much controversy, however, has evolved regarding the safety of this type of sling. Overall, the quality of the studies with respect to assessing risks of SMUS-associated complications is currently poor. The most common risks in patients with SMUS include urethral obstruction requiring surgery (2.3% of patients with SMUS), vaginal, bladder and/or urethral erosion requiring surgery (1.8%) and refractory chronic pain (4.1%); these data likely represent the minimum risks. In addition, the failure rate of SMUS implantation surgery is probably at least 5% in patients with stress urinary incontinence (SUI). Furthermore, at least one-third of patients undergoing sling excision surgery develop recurrent SUI. Considering the additional risks of refractory overactive bladder, fistulas and bowel perforations, among others, the overall risk of a negative outcome after SMUS implantation surgery is ≥15%.

High-power flip-chip semiconductor disk laser in the 1.3 µm wavelength band.

We present 6.1 W of output power from a flip-chip semiconductor disk laser (SDL) emitting in the 1.3 µm wavelength region. This is the first demonstration of a flip-chip SDL in this wavelength range with output powers that are comparable to those obtained with intracavity diamond heat spreaders. The flip-chip configuration circumvents the optical distortions and losses that the intracavity diamond heat spreaders can introduce into the laser cavity. This is essential for several key applications of SDLs.

High performance wafer-fused semiconductor disk lasers emitting in the 1300 nm waveband.

We report for the first time on the performance of 1300 nm waveband semiconductor disc lasers (SDLs) with wafer fused gain mirrors that implement intracavity diamond and flip-chip heat dissipation schemes based on the same gain material. With a new type of gain mirror structure, maximum output power values reach 7.1 W with intracavity diamond gain mirrors and 5.6 W with flip-chip gain mirrors, using a pump spot diameter of 300 µm, exhibiting a beam quality factor M(2)< 1.25 in the full operation range. These results confirm previously published theoretical modeling of these types of SDLs.

Transverse mode discrimination in long-wavelength wafer-fused vertical-cavity surface-emitting lasers by intra-cavity patterning.

Transverse mode discrimination is demonstrated in long-wavelength wafer-fused vertical-cavity surface-emitting lasers using ring-shaped air gap patterns at the fused interface between the cavity and the top distributed Bragg reflector. A significant number of devices with varying pattern dimensions was investigated by on-wafer mapping, allowing in particular the identification of a design that reproducibly increases the maximal single-mode emitted power by about 30 %. Numerical simulations support these observations and allow specifying optimized ring dimensions for which higher-order transverse modes are localized out of the optical aperture. These simulations predict further enhancement of the single-mode properties of the devices with negligible penalty on threshold current and emitted power.

Multilevel whole-genome analysis reveals candidate biomarkers in clear cell renal cell carcinoma.

Renal cell carcinoma (RCC) is the most common neoplasm of the kidney. We conducted an integrated analysis of copy number, gene expression (mRNA and miRNA), protein expression, and methylation changes in clear cell renal cell carcinoma (ccRCC). We used a stepwise approach to identify the most significant copy number aberrations (CNA) and identified regions of peak and broad copy number gain and loss, including peak gains (3q21, 5q32, 5q34-q35, 7p11, 7q21, 8q24, 11q13, and 12q14) and deletions (1p36, 2q34-q37, 3p25, 4q33-q35, 6q23-q27, and 9p21). These regions harbor novel tumor-related genes and miRNAs not previously reported in renal carcinoma. Integration of genome-wide expression data and gene set enrichment analysis revealed 75 gene sets significantly altered in tumors with CNAs compared with tumors without aberration. We also identified genes located in peak CNAs with concordant methylation changes (hypomethylated in copy number gains such as STC2 and CCND1 and hypermethylated in deletions such as CLCNKB, VHL, and CDKN2A/2B). For other genes, such as CA9, expression represents the net outcome of opposing forces (deletion and hypomethylation) that also significantly influences patient survival. We also validated the prognostic value of miRNA let-7i in RCCs. miR-138, located in chromosome 3p deletion, was also found to have suppressive effects on tumor proliferation and migration abilities. Our findings provide a significant advance in the delineation of the ccRCC genome by better defining the impact of CNAs in conjunction with methylation changes on the expression of cancer-related genes, miRNAs, and proteins and their influence on patient survival.