Surgical treatment for Zenker’s diverticulum: comparison between diverticulectomy and diverticulopexy

Background

The ideal surgical technique for symptomatic Zenker’s diverticulum has not been identified yet. Endoscopic treatment, although frequently performed, has not replaced the open cricopharyngeal myotomy, which is still deemed the standard therapy by many dedicated physicians. The management of the diverticular sac after myotomy is still a matter of debate. The aim of this study is to compare the results of diverticulectomy and diverticulopexy after cricopharyngeal myotomy, in homogeneous groups of patients.

Methods

Thirty-seven patients were treated for Zenker’s diverticulum at the same university medical school, but in two different units, with open cricopharyngeal myotomy, associated with diverticulectomy in 17 patients and with diverticulopexy in the remaining. No clinical criteria influenced the different choice of treatment of the diverticular pouch, but only the surgeon’s preference. Clinical data, diverticulum size, postoperative course, and complications were analyzed. Patients were followed up for median duration of 37 months (range 12–113 months) through contrast swallow study and clinical evaluation, aided by a specifically conceived questionnaire. Records were analyzed by Mann–Whitney–Wilcoxon test and Fisher’s exact test.

Results

Homogeneous comparative values for sex, age, diverticulum size, and symptoms were found in the two groups. Statistical analysis indicated that diverticulopexy, as compared with diverticulectomy, allowed reduced postoperative complications and slightly improved long-term swallowing.

Conclusions

Diverticulopexy is feasible also in large Zenker’s diverticula and can achieve equivalent or even better results than diverticulectomy with a smoother postoperative course.

     

Molecular findings and clinical data in a cohort of 150 patients with anophthalmia/microphthalmia

Anophthalmia and microphthalmia (AM) are the most severe malformations of the eye, corresponding respectively to reduced size or absent ocular globe. Wide genetic heterogeneity has been reported and different genes have been demonstrated to be causative of syndromic and non‐syndromic forms of AM. We screened seven AM genes [GDF6 (growth differentiation factor 6), FOXE3 (forkhead box E3), OTX2 (orthodenticle protein homolog 2), PAX6 (paired box 6), RAX (retina and anterior neural fold homeobox), SOX2 (SRY sex determining region Y‐box 2), and VSX2 (visual system homeobox 2 gene)] in a cohort of 150 patients with isolated or syndromic AM. The causative genetic defect was identified in 21% of the patients (32/150). Point mutations were identified by direct sequencing of these genes in 25 patients (13 in SOX2, 4 in RAX, 3 in OTX2, 2 in FOXE3, 1 in VSX2, 1 in PAX6, and 1 in GDF6). In addition eight gene deletions (five SOX2, two OTX2 and one RAX) were identified using a semi‐quantitative multiplex polymerase chain reaction (PCR) [quantitative multiplex PCR amplification of short fluorescent fragments (QMPSF)]. The causative genetic defect was identified in 21% of the patients. This result contributes to our knowledge of the molecular basis of AM, and will facilitate accurate genetic counselling.     

Distribution of exogenous [125I]-3-iodothyronamine in mouse in vivo: relationship with trace amine-associated receptors

3-Iodothyronamine (T1AM) is a novel chemical messenger, structurally related to thyroid hormone, able to interact with G protein-coupled receptors known as trace amine-associated receptors (TAARs). Little is known about the physiological role of T1AM. In this prospective, we synthesized [125I]-T1AM and explored its distribution in mouse after injecting in the tail vein at a physiological concentration (0.3?nM). The expression of the nine TAAR subtypes was evaluated by quantitative real-time PCR. [125I]-T1AM was taken up by each organ. A significant increase in tissue vs blood concentration occurred in gallbladder, stomach, intestine, liver, and kidney. Tissue radioactivity decreased exponentially over time, consistent with biliary and urinary excretion, and after 24?h, 75% of the residual radioactivity was detected in liver, muscle, and adipose tissue. TAARs were expressed only at trace amounts in most of the tissues, the exceptions being TAAR1 in stomach and testis and TAAR8 in intestine, spleen, and testis. Thus, while T1AM has a systemic distribution, TAARs are only expressed in certain tissues suggesting that other high-affinity molecular targets besides TAARs exist.     

Assessment of the sensitivity of detecting drug-induced QTc changes using subject-specific rate correction

Aims

To quantify the sensitivity of QT heart-rate correction methods for detecting drug-induced QTc changes in thorough QT studies.

Methods

Twenty-four-hour Holter ECGs were analyzed in 66 normal subjects during placebo and moxifloxacin delivery (single oral dose). QT and RR time series were extracted. Three QTc computation methods were used: (1) Fridericia's formula, (2) Fridericia's formula with hysteresis reduction, and (3) a subject-specific approach with transfer function-based hysteresis reduction and three-parameter non-linear fitting of the QT–RR relation. QTc distributions after placebo and moxifloxacin delivery were compared in sliding time windows using receiver operating characteristic (ROC) curves. The area under the ROC curve (AUC) served as a measure to quantify the ability of each method to detect moxifloxacin-induced QTc prolongation.

Results

Moxifloxacin prolonged the QTc by 10.6 ± 6.6 ms at peak effect. The AUC was significantly larger after hysteresis reduction (0.87 ± 0.13 vs. 0.82 ± 0.12, p < 0.01) at peak effect, indicating a better discriminating capability. Subject-specific correction further increased the AUC to 0.91 ± 0.11 (p < 0.01 vs. Fridericia with hysteresis reduction). The performance of the subject-specific approach was the consequence of a substantially lower intra-subject QTc standard deviation (5.7 ± 1.1 ms vs. 8.8 ± 1.2 ms for Fridericia).

Conclusion

The ROC curve provides a tool for quantitative comparison of QT heart rate correction methods in the context of detecting drug-induced QTc prolongation. Results support a broader use of subject-specific QT correction.     

Liquid crystal self-assembly of random-sequence DNA oligomers

In biological systems and nanoscale assemblies, the self-association of DNA is typically studied and applied in the context of the evolved or directed design of base sequences that give complementary pairing, duplex formation, and specific structural motifs. Here we consider the collective behavior of DNA solutions in the distinctly different regime where DNA base sequences are chosen at random or with varying degrees of randomness. We show that in solutions of completely random sequences, corresponding to a remarkably large number of different molecules, e.g., approximately 10(12) for random 20-mers, complementary still emerges and, for a narrow range of oligomer lengths, produces a subtle hierarchical sequence of structured self-assembly and organization into liquid crystal (LC) phases. This ordering follows from the kinetic arrest of oligomer association into long-lived partially paired double helices, followed by reversible association of these pairs into linear aggregates that in turn condense into LC domains.     

Platform switching and matrix metalloproteinase-8 levels in peri-implant sulcular fluid

Objectives: The concept of platform switching has been introduced to implant therapy, however long‐term data are sparse. The aim of this study was to biochemically investigate the inflammatory response mediated by MMP‐8 to platform switching after 3 years of loading, in order to understand the long‐term effect of implant/abutment mismatching on peri‐implant health. Methods: A total of 70 implants had been inserted in the posterior maxilla in 26 patients and were randomly assigned to one of the four treatment regimens (implant diameter 3.8 [control group], 4.3 [Test group 1, T₁], 4.8 [Test group 2, T₂] and 5.5 mm [Test group 3, T₃]). All implants were restored using a 3.8 mm abutment. In the test groups, this restoration resulted in a mismatching of 0.25–0.85 mm of implant–abutment diameters. Results: Thirty‐six months after prosthetic rehabilitation, peri‐implant sulcular fluid samples were taken from two aspects of all implants and from periodontally healthy adjacent teeth. Samples were processed in a conventional ELISA using monoclonal antibodies recognizing the active entity of MMP‐8. In the test groups, MMP‐8 mean values were 2.76 ng for T₁ (SD: 2.91), 3.30 ng for T₂ (SD: 1.94) and 3.18 ng for T₃ (SD: 2.46). For the control group, MMP‐8 mean value was 3.6 ng (SD: 2.23), whereas 3.38 ng (SD: 2.2) was recorded at the adjacent teeth. There were no statistically significant differences in MMP‐8 values between the groups (P=0.113, Kruskal–Wallis). Conclusions: The presence of an implant/abutment mismatching specific for this prosthetic concept is compatible with long‐term peri‐implant health as demonstrated by analysis of a sensitive biomarker of the peri‐implant inflammatory response.