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!

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.

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.

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.

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.

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.

Microvascular density as an independent predictor of clinical outcome in renal cell carcinoma: an automated image analysis study.

Tumor microvascular density (MVD) has been shown to correlate with the aggressiveness of several cancers. With the introduction of targeted anti-angiogenic therapy, assessment of MVD has the potential not only as a prognostic but also as a therapeutic marker. The significance of tumor vascularity in clear cell renal cell carcinoma (ccRCC) has been debated, with studies showing contradictory results. Previous studies were limited by manual quantification of MVD within a small area of tumor. Since then, the validity of this method has been questioned. To avoid the inaccuracies of manual quantification, we employed a computerized image analysis, which allowed assessment of large areas of tumor and adjacent normal tissue. The latter was used as an internal reference for normalization. MVD and vascular endothelial growth factor (VEGF) were assessed in 57 cases of ccRCC. Sections were immunostained for CD34 and VEGF. Areas of ccRCC and normal kidney medulla were analyzed within scanned images using software that counted CD34-positive vessels and measured the intensity of VEGF staining. We obtained unadjusted values from tumoral areas and calculated adjusted values as tumor/normal ratios. Unadjusted MVD had no association with clinical outcome. However, similarly to tumor stage, higher adjusted MVD was associated with shorter disease-free survival (log-rank P=0.037, Cox P=0.02). This was significant in univariate and multivariate analyses. MVD did not correlate with tumor stage, pointing to its independent prognostic value. As expected due to the known molecular abnormalities in ccRCC, most tumors showed higher VEGF expression than normal tissue. Higher adjusted VEGF was associated with high tumor grade (P=0.049). The finding of increased MVD as an independent marker of tumor aggressiveness may prove useful in the development of new tests for prognostic and therapeutic guidance. Digital techniques can provide more accurate assessment of immunomarkers and may reveal less obvious associations.

8 mW fundamental mode output of wafer-fused VCSELs emitting in the 1550-nm band.

We report record-high fundamental mode output power of 8 mW at 0 °C and 1.5 mW at 100°C achieved with wafer-fused InAlGaAs-InP/AlGaAs-GaAs 1550 nm VCSELs incorporating a re-grown tunnel junction and un-doped AlGaAs/GaAs distributed Bragg reflectors. A broad wavelength tuning range of 15 nm by current variation and wavelength setting in a spectral range of 40 nm on the same VCSEL wafer are demonstrated as well. This performance positions wafer-fused VCSELs as prime candidates for many applications in low power consumption, "green" photonics.

Intra-cavity patterning for mode control in 1.3 µm coupled VCSEL arrays.

We report coupled VCSEL arrays, emitting at 1.3 µm wavelength, in which both the optical gain/loss and refractive index distributions were defined on different vertical layers. The arrays were electrically pumped through a patterned tunnel junction, whereas the array pixels were realized by intra-cavity patterning using sub-wavelength air gaps. Stable oscillations in coupled modes were evidenced for 2x2 array structures, from threshold current up to thermal roll-over, using spectrally resolved field pattern analysis.

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.

Genomic alterations in primary breast cancers compared with their sentinel and more distal lymph node metastases: an aCGH study.

Metastatic potential of breast cancer may be associated with specific genomic alterations and the earliest metastases are likely to be found in the sentinel lymph nodes (SLN). Using array comparative genomic hybridization (aCGH), we compared the genomes of primary breast invasive duct carcinomas (IDCs), their sentinel and more distal lymph node metastases, and IDCs without nodal metastasis. Thirty-three samples from 22 patients with IDC were subjected to aCGH: 8 IDC samples from patients without lymph node metastasis, 11 IDCs associated with SLN metastases out of which 7 had paired samples of metastases, and 14 samples of lymph node metastases out of which 8 were sentinel-distal pairs from 4 patients. aCGH data were analyzed by correlation of genomic profiles, cluster analysis, segmentation, and peak identification. Quantitative real-time PCR was used for data validation. We observed high genomic similarity between primary tumors and their nodal metastases as well as between metastases to the sentinel and distal lymph nodes. Several recurrent alterations were detected preferentially in IDC associated with SLN metastases compared to IDCs without metastasis. Amplification within the 17q24.1-24.2(59.96-62.76 Mb) region was associated with presence of sentinel or distal lymph node metastases; larger tumor size and higher histological grade. In our samples, there were genomic events associated with metastatic progression, which could be detected in both primary tumors and LN metastases. Gain on 17q24.1-24.2 is a candidate region for further testing as a predictor of nodal metastasis.

1.3 microm-wavelength phase-locked VCSEL arrays incorporating patterned tunnel junction.

We report the fabrication and the performance of phase-locked VCSEL arrays emitting near 1310 nm wavelength. The arrays were fabricated using double wafer fusion by patterning a tunnel junction layer, which serves to define the individual single mode array elements. Phase-locking in both one-dimensional and two-dimensional array configurations was confirmed by means of far field and spectral measurements as well as theoretical modeling. CW output powers of more than 12 mW were achieved.

Genomic differences between pure ductal carcinoma in situ of the breast and that associated with invasive disease: a calibrated aCGH study.

PURPOSE: In the quest for new targets, genomes of ductal carcinoma in situ (DCIS) and infiltrating duct carcinoma (IDC) have been compared previously; however, genomic alterations associated with cancer progression were difficult to identify. We hypothesized that significant events can be detected by comparing lesions with a broader range of behavior: from pure DCIS to IDC associated with lymph node metastasis. EXPERIMENTAL DESIGN: Array comparative genomic hybridization, calibrated by self-self hybridization tests, was used to study 6 cases of pure DCIS and 17 cases of DCIS paired with IDC where 8 tumors had spread to the local lymph nodes. RESULTS: Pure DCIS exhibited a marginally higher degree of genomic complexity than DCIS and IDC components of invasive tumors. The latter two showed similarity between tumors and between components of the same tumor with several regions detected preferentially compared with pure DCIS. IDC associated with lymph node metastases showed similarity of genomic profiles as a group. Gain on 17q22-24.2 was associated with higher histologic grade, large IDC size, lymphatic/vascular invasion, and lymph node metastasis (P < 0.05). CONCLUSIONS: Our findings suggest that DCIS and IDC are associated with specific genomic events. DCIS associated with IDC is genomically similar to the invasive component and therefore may represent either a clone with high invasive potential or invasive cancer spreading through the ducts. Specifically, gain on 17q22-24.2 is a candidate region for further testing as a predictor of invasion when detected in DCIS and predictor of nodal metastasis when detected in DCIS or IDC.

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).

Abelson interactor protein-1 positively regulates breast cancer cell proliferation, migration, and invasion.

Abelson interactor protein-1 (ABI-1) is an adaptor protein involved in actin reorganization and lamellipodia formation. It forms a macromolecular complex containing Hspc300/WASP family verprolin-homologous proteins 2/ABI-1/nucleosome assembly protein 1/PIR121 or Abl/ABI-1/WASP family verprolin-homologous proteins 2 in response to Rho family-dependent stimuli. Due to its role in cell mobility, we hypothesized that ABI-1 has a role in invasion and metastasis. In the present study, we found that weakly invasive breast cancer cell lines (MCF-7, T47D, MDA-MB-468, SKBR3, and CAMA1) express lower levels of ABI-1 compared with highly invasive breast cancer cell lines (MDA-MB-231, MDA-MB-157, BT549, and Hs578T), which exhibit high ABI-1 levels. Using RNA interference, ABI-1 was stably down-regulated in MDA-MB-231, which resulted in decreased cell proliferation and anchorage-dependent colony formation and abrogation of lamellipodia formation on fibronectin. Down-regulation of ABI-1 decreased invasiveness and migration ability and decreased adhesion on collagen IV and actin polymerization in MDA-MB-231 cells. Additionally, compared with control parental cells, ABI-1 small interfering RNA-transfected cells showed decreased levels of phospho-PDK1, phospho-Raf, phospho-AKT, total AKT, and AKT1. These data suggest that ABI-1 plays an important role in the spread of breast cancer and that this role may be mediated via the phosphatidylinositol 3-kinase pathway.

Quantitative detection of circulating epithelial cells by Q-RT-PCR.

INTRODUCTION: It has been shown that the quantity of circulating tumor cells (CTCs) in breast cancer patients is an independent predictor of survival and treatment response. Real time quantitative reverse transcriptase PCR (Q-RT-PCR) is a sensitive technique for detection of CTCs. Our aim was to investigate whether the technique can be used also to quantitate these CTCs. METHODS: We tested cytokeratin 19 (CK19), maspin, mammaglobin, GAPDH and RPL19 genes for their level of expression and linearity of amplification in serial dilutions of RNA extracted from the MDA-MB-231, UACC-812, T47D and HS578T breast cancer cell lines. To simulate CTCs, serial dilutions of cultured T47D and HS578T cells were added to peripheral blood from healthy volunteers. The samples were subjected to enrichment, RNA extraction and Q-RT-PCR. RESULTS: CK19 was reliably expressed in all four cell lines with a linear relationship between the quantity of added cells and the amount of CK19 RNA. The lower limit of reliable detection was 5 cells per sample, which corresponds to a concentration of 0.7 cell/ml in 7.5 ml of blood or would translate to a lower CTC concentration in a larger volume of blood. CONCLUSION: This technique may prove useful for high throughput comparative quantification of CTCs in individual patients during treatment and subsequent follow up for research and clinical management purposes.