Cholesteatoma Severely Impacts the Integrity and Bone Material Quality of the Incus.

Cholesteatoma can lead to progressive destruction of the auditory ossicles along with conductive hearing loss but precise data on the microstructural, cellular, and compositional aspects of affected ossicles are not available. Here, we obtained incus specimens from patients who had cholesteatoma with conductive hearing loss. Incudes were evaluated by micro-computed tomography, histomorphometry on undecalcified sections, quantitative backscattered electron imaging, and nanoindentation. Results were compared with two control groups taken from patients with chronic otitis media as well as from skeletally intact donors at autopsy. The porosity of incus specimens was higher in cholesteatoma than in chronic otitis media, along with a higher osteoclast surface per bone surface. Histomorphometric assessment revealed higher osteoid levels and osteocyte numbers in cholesteatoma incudes. Incudes affected by cholesteatoma also showed lower matrix mineralization compared with specimens from healthy controls and chronic otitis media. Furthermore, the modulus-to-hardness ratio was higher in cholesteatoma specimens compared with controls. Taken together, we demonstrated increased porosity along with increased osteoclast indices, impaired matrix mineralization, and altered biomechanical properties as distinct features of the incus in cholesteatoma. Based on our findings, a possible impact of impaired bone quality on conductive hearing loss should be further explored.

Does Minimally Invasive Surgery Provide Better Clinical or Radiographic Outcomes Than Open Surgery in the Treatment of Hallux Valgus Deformity? A Systematic Review and Meta-analysis.

BACKGROUND: Hallux valgus is the most common foot deformity and affects 23% to 35% of the general population. More than 150 different techniques have been described for surgical correction. Recently, there has been increasing interest in the use of minimally invasive surgery to correct hallux valgus deformities. A variety of studies have been published with differing outcomes regarding minimally invasive surgery. However, most studies lack sufficient power and are small, making it difficult to draw adequate conclusions. A meta-analysis can therefore be helpful to evaluate and compare minimally invasive and open surgery. QUESTIONS/PURPOSES: We performed a systematic review and meta-analysis of randomized controlled trials and prospective controlled studies to answer the following question: Compared with open surgery, does minimally invasive surgery for hallux valgus result in (1) improved American Orthopaedic Foot and Ankle Society (AOFAS) scores and VAS scores for pain, (2) improved radiologic outcomes, (3) fewer complications, or (4) a shorter duration of surgery? METHODS: The systematic review and meta-analysis was conducted according to the guidelines of the Cochrane Handbook for Systematic Reviews of Intervention and the Preferred Reporting Items for Systematic Reviews and Meta-analyses. A search was performed in the PubMed, Embase, Scopus, CINAHL, and CENTRAL databases on May 3, 2022. Studies were eligible if they were randomized controlled or prospective controlled studies that compared minimally invasive surgery and open surgery to treat patients with hallux valgus. We defined minimally invasive surgery as surgery performed through the smallest incision required to perform the procedure accurately, with an incision length of approximately 2 cm at maximum. Open surgery, on the other hand, involves a larger incision and direct visualization of deeper structures. Seven studies (395 feet), consisting of six randomized controlled studies and one prospective comparative study, were included in the qualitative and quantitative data synthesis. There were no differences between the minimally invasive and open surgery groups regarding age, gender, or severity of hallux valgus deformity. Each included study was assessed for the risk of bias using the second version of the Cochrane tool for assessing the risk of bias in randomized trials or by using the Newcastle-Ottawa Scale for comparative studies. Most of the included studies had intermediate quality regarding the risk of bias. We excluded one study from our analysis because of its high risk of bias to avoid serious distortions in the meta-analysis. We performed a sensitivity analysis to confirm that our meta-analysis was robust by including only studies with a low risk of bias. The analyzed endpoints included the AOFAS score (range 0 to 100), where higher scores represent less pain and better function; the minimum clinically important difference on this scale was 29 points. In addition, the VAS score was analyzed, which is based on a pain rating scale (range 0 to 10), with higher scores representing greater pain. Radiologic outcomes included the hallux valgus angle, intermetatarsal angle, and distal metatarsal articular angle. Complications were qualitatively assessed and evaluated for differences. A random-effects model was used if substantial heterogeneity (I 2 > 50%) was found; otherwise, a fixed-effects model was used. RESULTS: We found no clinically important difference between minimally invasive and open surgery in terms of the AOFAS score (88 ± 7 versus 85 ± 8, respectively; mean difference 4 points [95% CI 1 to 6]; p < 0.01). There were no differences between the minimally invasive and open surgery groups in terms of VAS scores (0 ± 0 versus 0 ± 1, respectively; standardized mean difference 0 points [95% CI -1 to 0]; p = 0.08). There were no differences between the minimally invasive and open surgery groups in terms of the hallux valgus angle (12° ± 4° versus 12° ± 4°; mean difference 0 points [95% CI -2 to 2]; p = 0.76). Radiographic measurements of the intermetatarsal angle did not differ between the minimally invasive and open surgery groups (7° ± 2° versus 7° ± 2°; mean difference 0 points [95% CI -1 to 1]; p = 0.69). In addition, there were no differences between the minimally invasive and open surgery groups in terms of the distal metatarsal articular angle (7° ± 4° versus 8° ± 4°; mean difference -1 point [95% CI -4 to 2]; p = 0.28). The qualitative analysis revealed no difference in the frequency or severity of complications between the minimally invasive and the open surgery groups. The minimally invasive and open surgery groups did not differ in terms of the duration of surgery (28 ± 8 minutes versus 40 ± 10 minutes; mean difference -12 minutes [95% CI -25 to 1]; p = 0.06). CONCLUSION: This meta-analysis found that hallux valgus treated with minimally invasive surgery did not result in improved clinical or radiologic outcomes compared with open surgery. Methodologic shortcomings of the source studies in this meta-analysis likely inflated the apparent benefits of minimally invasive surgery, such that in reality it may be inferior to the traditional approach. Given the associated learning curves-during which patients may be harmed by surgeons who are gaining familiarity with a new technique-we are unable to recommend the minimally invasive approach over traditional approaches, in light of the absence of any clinically important benefits identified in this meta-analysis. Future research should ensure studies are methodologically robust using validated clinical and radiologic parameters, as well as patient-reported outcome measures, to assess the long-term outcomes of minimally invasive surgery.

FABP1 expression in human tumors: a tissue microarray study on 17,071 tumors.

Fatty acid-binding proteins (FABPs) play a pivotal role in the metabolism of fatty acids and are expressed in a tissue-specific manner. FABP1 is most abundantly expressed in the liver where it accounts for about 10% of the total cytosolic protein and is thought to have diagnostic utility. To comprehensively determine FABP1 expression in normal and neoplastic tissues, a tissue microarray containing 17,071 samples from 150 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. Among normal tissues, a strong FABP1 immunostaining was observed in hepatocytes, proximal tubuli of the kidney and epithelium of small intestine, appendix, and the colorectum. FABP1 positivity was found in 24 of 150 tumor categories, including 17 tumor categories with at least 1 strongly positive case. The highest FABP1 positivity rates were seen in colorectal adenomas (86%), in colorectal adenocarcinomas (71.1%), and in hepatocellular carcinomas (65.3%), followed by mucinous carcinoma of the ovary (34.6%), cholangiocarcinoma (21.6%), and various adenocarcinomas from the digestive tract (10-23%). Eleven additional entities had positivity rates between 0.2 and 6.5%. FABP1 staining was not seen in 169 primary adenocarcinomas of the lung. In colorectal cancer, reduced FABP1 expression was linked to poor-grade, right-sided tumor location, microsatellite instability (p < 0.0001 each), and absence of BRAF V600E mutations (p = 0.001), but unrelated to pT and pN status. FABP1 expression has considerably high tumor specificity. As FABP1 expression was virtually absent in adenocarcinomas of the lung, FABP1 immunohistochemistry might be particularly helpful to assist in the identification of metastatic colorectal or gastrointestinal adenocarcinoma to the lung.