Evaluation of absorbable and permanent mesh fixation devices: adhesion formation and mechanical strength

Purpose  

Laparoscopic ventral hernia repair is commonly performed with mesh prostheses; however, there is no standard for fixation devices used to secure mesh to the abdominal wall. This study is a functional comparison of novel, screw-type absorbable and permanent fixation devices with a traditional titanium fixation device.     

Decellularized biologic muscle-fascia abdominal wall scaffold graft

BackgroundComplex abdominal wall reconstruction using biologic mesh can lead to increased recurrence rates, nonincorporation, and high perioperative costs. We developed a novel decellularization method and applied it to porcine muscle fascia to mirror target-tissue architecture. The aims of this study were to analyze mechanical strength and tissue-graft incorporation.MethodsAfter serial decellularization, muscle-fascia mesh was created and tested for mechanical strength and DNA content. The muscle-fascia mesh was implanted subcutaneously in rats (n = 4/group) and the cohorts killed 1 to 4 weeks later. Explants were examined histologically or immunohistochemically.ResultsMechanical testing demonstrated equivalent strength compared with a commercially available biological mesh (AlloDerm), with mechanical strength attributable to the fascia component. Grafts were successfully implanted with no observable adverse events. Gross necroscopy revealed excellent subdermal scaffold engraftment. Microscopic evaluation identified progressive collagen deposition within the graft, neoangiogenesis, and presence of CD34 positive cells, in the absence of discernable graft rejection.ConclusionThis study confirms a decellularization process can successfully create a DNA-free composite abdominal wall (muscle-fascia) scaffold that can be implanted intraspecies without rejection. Expanding this approach may allow exploitation of the angiogenic capacities of decellularized muscle, concomitant with the inherent strength of decellularized fascia, to perform preclinical analyses of graft strength in animal models in vivo.     

Invasive biliary mucinous cystic neoplasm: a review

Objectives

Biliary mucinous cystic neoplasms (BMCNs) are recently redefined rare liver tumours in which insufficient recognition frequently leads to an incorrect initial or delayed diagnosis. A concise review of the subtle, sometimes non-specific, clinical, serologic and radiographic features will allow for a heightened awareness and more comprehensive understanding of these entities.

Methods

Literature relating to the presentation, diagnosis, treatment, pathology and outcomes of BMCNs and published prior to March 2012 was reviewed.

Results

Biliary mucinous cystic neoplasms most commonly occur in females (≥60%) in the fifth decade of life. Clinical symptoms, serologic markers and imaging modalities are unreliable for diagnosis of BMCNs, which leads to misdiagnosis in 55–100% of patients. Perioperative cyst aspiration is not recommended as invasive BMCNs can only be differentiated from non-invasive BMCNs by microscopic evaluation for the presence of ovarian-type stroma. Intraoperative biopsy and frozen section(s) are essential to differentiate BMCNs from other cystic liver lesions. The treatment of choice is complete excision and can result in excellent survival with initial correct diagnosis.

Conclusions

A low threshold for considering BMCN in the differential diagnosis of cystic liver lesions and increased attentiveness to its subtle diagnostic characteristics are imperative. The complete surgical resection of BMCNs and the use of appropriate nomenclature are necessary to improve outcomes and accurately define prognosis.     

Cytochrome P450-dependent metabolism of gefitinib

The in vitro metabolism of [¹⁴C]-gefitinib (1–3 µM) was investigated using human liver microsomes and a range of expressed human cytochrome P450 enzymes, with particular focus on the formation of O-desmethyl-gefitinib (M523595), the major metabolite observed in human plasma. High-performance liquid chromatography with ultraviolet light, radiochemical and mass spectral analysis, together with the availability of authentic standards, enabled quantification and structural identification of metabolites. On incubation with pooled human liver microsomes, [¹⁴C]-gefitinib underwent rapid and extensive metabolism to a number of metabolites, although M523595 was only a minor microsomal product. Formation of most metabolites was markedly decreased by ketoconazole, but M523595 production was inhibited only by quinidine. Gefitinib was metabolized extensively by expressed CYP3A4, producing a similar range of metabolites to liver microsomes, but M523595 was not formed. CYP1A2, 2C9 and 2C19 produced no measurable metabolism of gefitinib, while CYP3A5 produced a range of metabolites similar to CYP3A4, but to a much lower degree. In contrast, CYP2D6 catalysed rapid and extensive metabolism of gefitinib to M523595. While formation of M523595 was CYP2D6 mediated, the overall metabolism of gefitinib was dependent primarily on CYP3A4, and this was not obviously diminished in liver microsomes from CYP2D6 poor metabolizers.     

Treatment of spontaneously ruptured hepatocellular carcinoma: use of laparoscopic microwave ablation and washout

BackgroundRuptured, or bleeding, hepatocellular carcinoma (rHCC) is a relatively rare disease presentation associated with high acute mortality rates. This study sought to evaluate outcomes following laparoscopic microwave ablation (MWA) and washout in rHCC.MethodsA retrospective single-center review was performed to identify patients with rHCC (2008–2018). The treatment algorithm consisted of transarterial embolization (TAE) or trans-arterial chemoembolization (TACE) followed by laparoscopic MWA and washout.ResultsFifteen patients with rHCC were identified (n = 5 single lesion, n = 5 multifocal disease, n = 5 extrahepatic metastatic disease). Median tumor size was 83 mm (range 5–228 mm), and 10 of 15 underwent TAE or TACE followed by laparoscopic MWA/washout. One patient required additional treatment for bleeding after MWA with repeat TAE. Thirty-day mortality was 6/15. For those patients discharged (n = 9), additional treatments included chemotherapy (n = 5), TACE (n = 3), and/or partial lobectomy (n = 2). Median follow-up was 18.2 months and median survival was 431 days (range 103–832) (one-year survival n = 7; two-year survival n = 4; three-year survival n = 3). Six patients had post-operative imaging from which one patient demonstrated recurrence.ConclusionUsing laparoscopic MWA with washout may offer advantage in the treatment of ruptured HCC. It not only achieves hemostasis but also could have oncologic benefit by targeting local tumor and decreasing peritoneal carcinomatosis risk.     

In vitro metabolism of a triclyclic alkaloid (M445526) in human liver microsomes and hepatocytes

The in vitro metabolism of M445526 (ZD6126 phenol) was investigated by incubating [¹⁴C]-M445526 at a concentration of 10?µg?ml^?1 with human hepatic microsomes (4?mg?ml^?1) or human hepatocytes (2?×?10⁶ cells?ml^?1) for up to 180?min. Following incubation with microsomes and hepatocytes, up to 78% and 40% of [¹⁴C]-M445526 was metabolized after 180 and 120?min, respectively. High-performance liquid chromatography (HPLC) with radiochemical detection confirmed extensive metabolism of [¹⁴C]-M445526 by microsomes and hepatocytes. Mass spectrometry and ¹H-NMR spectroscopy enabled structural identification of up to eight metabolites. Human liver microsomes formed one major (O-desmethyl) and three minor (a further O-desmethyl and two different hydroxylated) phase I metabolites. Human hepatocytes produced one major metabolite, a sulphate conjugate of the major O-desmethyl metabolite formed by microsomes. Four minor metabolites were also formed, primarily by O-demethylation with subsequent glucuronidation. Taken collectively, [¹⁴C]-M445526 underwent extensive in vitro metabolism by human liver fractions. These data were confirmed by subsequent human in vivo studies.     

One plunge or two?--hand disinfection with alcohol gel.

OBJECTIVE: To compare health care workers' hand surface coverage using two different volumes of alcohol gel for hand disinfection. PARTICIPANTS: and methods. A total of 84 members of staff in our hospital were studied. Subjects were asked to disinfect their hands with alcohol gel containing a clear fluorescent substance. Performance was assessed by using UV light to identify areas which had been missed, and the total surface area missed was calculated. A total of 42 subjects received 3.5 ml of alcohol gel, and 42 age-, sex-, and job-matched subjects received 1.75 ml of alcohol gel. RESULTS: Significantly less area was missed when hand disinfecting with double the volume of alcohol gel; 1.23 versus 6.35% surface area was missed (P < 0.001). CONCLUSION: Doubling the volume of alcohol gel used for hand disinfection significantly improves the efficiency of coverage of the hands with alcohol gel. This may result in lower bacterial count on the hands and may reduce the spread of nosocomial infections including that of methicillin-resistant Staphylococcus aureus.     

The influence of 2,3-butanedione 2-monoxime (BDM) on the interaction between actin and myosin in solution and in skinned muscle fibres

Summary 2,3-butanedione 2-monoxime (BDM) inhibits muscle contraction and actomyosin ATPase both in fibres and in solution. It is potentially useful as a tool for exploring weak interactions between actin and myosin. We have examined the effect of BDM on several key steps of the myosin subfragment-1 and actomyosin subfragment-1 ATPase in solution. These studies show that BDM shifts the equilibrium between two actomyosin states towards a more weakly bound form when the acto.myosin complex has ADP alone or ADP and phosphate bound. We also confirm the findings of Herrmann and colleagues (1993, Biochemistry, 31, 12227–32) that the main effect of BDM on the myosin subfragment-1 ATPase is to slow the release of phosphate following ATP hydrolysis. Skinned fibre studies show that the effects of BDM and phosphate on the steady isometric tension of the fibres are additive. This is consistent with the interpretation that BDM is reducing fibre tension either by increasing phosphate binding or by a direct effect on the crossbridge. Tension transients induced by rapid pressure release were examined in single muscle fibres; they showed that BDM reduces the rate of tension generation following pressure release. This result suggest that BDM directly affects the force generating event in the crossbridge.Since we submitted this paper, Y. Zhao and M. Kawai have published evidence that BDM reduces the equilibrium constant of the power stroke step in rabbit psoas muscle fibres (Am. J. Physiol. 266, C437-47 (1994)). This is consistent with the main findings in our work.