Head and Neck Merkel Cell Carcinoma: A 12-Year Single Institutional Experience.

Background: Merkel cell carcinoma (MCC) is an aggressive malignancy of presumed neuroendocrine origin. Most case series of MCC are limited by low case numbers and are not specific to head and neck tumours. The purpose of this study was to provide a focused review of head and neck MCC diagnosis and management in a single Irish institution. Methods: Patient's demographics, tumour characteristics, pathological diagnosis, surgical treatment, adjuvant treatment, subsequent management and clinical course were collected. Estimates of progression-free MCC survival rates were calculated by the Kaplan-Meier statistical model. A Pearson product-moment correlation coefficient examined the association between surgical margins and disease-free follow-up. Results: In total, 11 patients were treated for head and neck MCC with a mean age of 79.6 years (range = 69-91 years). The mean average follow-up duration of patients was 18.3 months. Of the cohort, 18% (n=2) had a sentinel node biopsy (SLNB). A selective neck dissection was subsequently performed in 18% (n=2). In total, 72% (n=8) of patients received adjuvant radiotherapy. Median disease-specific survival was 15 months for the SLNB group and 17 months for the non-SLNB group, not statistically significant (p=0.23). There was no significant association between surgical margins and disease-free follow (p=0.65). Conclusions: Our case series adds to a limited body of evidence of head and neck MCC. Surgery remains the treatment priority in localized disease, with an increasing role of SLNB for accurate prognostication and staging. Early management of stage I disease results in moderate long-term disease-free survivability.

Referral of patients to plastic surgeons following self-harm: Opportunities for suicide prevention.

Self-harm is a common source of referral to plastic and hand surgery services. Appropriate management of these patients is complex and includes the need for close liaison with mental health services. Self-harm is the single biggest risk factor for completed suicide, thereby increasing the risk by a factor of 66.1 This study aimed to analyse the clinical pathway and demographics of patients referred to plastic surgeons following self-harm. This 6-year retrospective series included patients referred to plastic surgeons following self-harm within the Galway University Hospital group. Patients were identified through the Hospital inpatient enquiry system, cross-referenced with data from the National Suicide Research Foundation. Data collected included demographics, psychiatric history, details of self-harm injury, admission pathway and operative intervention. Forty-nine patients were referred to plastic surgery services during the study period, accounting for 61 individual presentations. The male-to-female ratio was 26 (53%) to 23 (47%). Mean age was 40 years (range 21-95 years). Alcohol or illicit substance use was recorded in 17 of 61 (28%) presentations. Mortality from suicide occurred in 4 patients (8%). Mental health assessment was not carried out in 9 presentations (15%). Documentation of need for close or one-to-one observation was made in 11 cases (20%) and was not referred to in 43 cases (83%) following mental health assessment. This study demonstrates significant diversity in the management of this vulnerable patient group and may inform development of referral pathways to improve the safety of transfer, surgical admission and discharge of patients following self-harm, in consultation with mental health services.

Analysis of sentinel node positivity in primary cutaneous melanoma: an 8-year single institution experience.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is a standard method for determining the pathologic status of the regional lymph nodes. AIMS: The aim of our study was to determine the incidence and clinicopathologic factors predictive of SLN positivity, and to evaluate the prognostic importance of SLNB in patients with cutaneous melanoma. METHODS: We performed a retrospective analysis of a prospectively maintained database of all patients who underwent SLNB for primary melanoma at our institution from 2005 to 2012. Statistical analysis was performed using χ 2 and Fischer exact test. RESULTS: In total, 318 patients underwent SLNB, of which 65 were for thin melanoma (≤1 mm). There were 36 positive SLNB, 278 negative SLNB and in four cases the SLN was not located. The incidence rate for SLNB was 11.3% overall and 1.5% in thin melanomas alone. Statistical analysis identified Breslow thickness >1 mm (P = 0.006), Clark level ≥ IV (P = 0.004) and age <75 years (P = 0.035) as the strongest predictors of SLN positivity. Our overall false negativity rate was 20% (9/45) with one case of false-negative SLNB in thin melanomas. CONCLUSION: Breslow thickness of the primary tumour remains the strongest predictor of SLN positivity. Our findings point to a possible limited role for SLNB in thin melanoma due to its low positivity rate, associated false-negative rate and related morbidity.

The Irish contribution to the plastic surgery literature: 21 years of publications.

INTRODUCTION: The Republic of Ireland has always had an influence on medicine and has produced many renowned doctors who have helped shape its history. Furthermore, many clinical articles that have originated from Ireland have changed clinical practice throughout the world. The Irish have also had an impact on the plastic surgery literature yet it has never specifically been analyzed before. The purpose of this study was to identify and analyze all papers that have originated from the plastic surgery units in the Republic of Ireland in the medical literature over the past 21 years. METHODOLOGY: Twenty-four well-known plastic surgery, hand surgery and burns journals were selected for this study. By utilizing Scopus, the largest abstract and citation database of peer-reviewed literature, we analyzed each of our chosen 24 journals looking for Irish publications. Each paper was examined for article type, authorship, year of publication, institution of origin and level of evidence. RESULTS: Papers from the Republic of Ireland were published in 20 of the 24 journals over the past 21 years. A total of 245 articles from Ireland were published in the plastic surgery, hand surgery and burns literature over the 21-year period. Of these, 111 were original articles and 73 were case reports. The institution that published the most papers over the past 21 years was University Hospital Galway (66 publications) followed by Cork University Hospital with 54 papers. The journal with the most Irish articles was the Journal of Plastic, Reconstructive and Aesthetic Surgery with 56 papers. 2014 was the year with the most publications (28 papers). Authorship numbers also increased over time as the average number of authors in 1994 was 3.5, whereas it was 5.54 in 2014. DISCUSSION: The number of publications per year continues to increase along with authorship numbers. This mirrors the trend in other specialties. Publications are now no longer required for selection on to a higher surgical training scheme. There is now a fear that the academic output of trainees will decrease as a consequence. To prevent this, each unit must actively support and encourage research activity with their trainees.

A review of sentinel lymph node biopsy for thin melanoma.

INTRODUCTION: Although there is a lack of established survival benefit of sentinel lymph node biopsy (SLNB), this technique has been increasingly applied in the staging of patients with thin (≤1.00 mm) melanoma (T1Nx), without clear supportive evidence. METHODS: We review the guidelines and available literature on the indications and rationale for performing SLNB in thin melanoma. RESULTS: As a consequence of the paucity of evidence of SLNB in thin melanoma, there is considerable variability in the guidelines. It is difficult to define clinicopathologic factors that reliably predict the presence of nodal metastasis. SLNB does not yet inform management in thin melanoma to improve survival outcome. CONCLUSION: Based on available evidence, high risk patients with melanomas between 0.75 and 1.00 mm may be appropriate candidates to be considered for SLN biopsy after discussing the likelihood of finding evidence of nodal progression, the risks of sentinel node biopsy, and the lack of proven survival benefit from any form of surgical nodal staging.

Microsurgical replantation of an ear with no venous repair.

Replantation of an avulsed ear was completely successful with only arterial repair (to the superficial temporal artery) and the use of medicinal leeches.

Pancreatic islet transplantation using vascularised chambers containing nerve growth factor ameliorates hyperglycaemia in diabetic mice.

Intraportal islet transplantation has shown initial promise for the treatment of type 1 diabetes. However, the portal vein site is associated with complications such as thrombosis and hepatic steatosis, leading to transplant failure. The aims of this study were to (1) test the feasibility of an alternative islet transplantation method that utilises a FDA-approved gelatin sponge as a novel islet carrier and (2) assess if exogenous addition of nerve growth factor (NGF) has any additional beneficial effects on graft performance in diabetic mice. Mice were rendered diabetic by a single intraperitoneal injection of streptozotocin. Five hundred syngeneic islets were seeded onto a Gelitaspon((R)) disc in the presence or absence of NGF, and placed into a silicone chamber surrounding the femoral neurovascular pedicle. Islet function was assessed by weekly monitoring of blood glucose levels and an intraperitoneal glucose tolerance test performed at the end of the study. Chambers were harvested for further histological analysis. Four of five mice transplanted with islets seeded onto Gelitaspon with NGF showed a significant reduction in blood glucose levels by 4 weeks after transplantation, and demonstrated a response similar to non-diabetic mice when tested with an intraperitoneal glucose tolerance test. Chamber tissue from this group contained islets with insulin-producing beta cells adjacent to the vascular pedicle. Islets seeded onto Gelitaspon with NGF and sited on femoral vessels using a tissue-engineering chamber offer an alternative method for islet transplantation in diabetic mice. This may have potential as a method for clinical islet transplantation.

An assessment of skin preparation in upper limb surgery.

Postoperative wound infections remain a major source of upper limb morbidity. The effectiveness of peri-operative human upper limb preparation was determined using a clear fluid antiseptic and an iodine-based solution over 60 and 90 seconds. Less area was missed using iodine over both times and increasing clear solution preparation time from 60 to 90 seconds improved coverage. Surgical experience had little outcome relevance and a 90-second preparation time with either solution was insufficient, with fingers being the sites most commonly missed.

An anatomical study of the gracilis muscle and its application in groin wounds.

The management of groin wounds is a common and challenging problem encountered in surgical practice. The purpose of this study is to examine the anatomic basis of the gracilis muscle with relation to this problem. Twelve cadaveric lower limbs were studied to examine both the extramuscular and intramuscular vasculature of the gracilis muscle. These underwent dissection and in 3 cases radiologic examination. The mean entry point of the dominant arterial pedicle was 9.4 cm, with mean length and width of the muscle recorded as 38.4 cm and 6.2 cm, respectively. Each gracilis muscle was then mobilized between the adductor longus and adductor magnus muscles on its dominant pedicle and transposed into the femoral triangle. In each case, the gracilis muscle mobilized easily on its dominant pedicle to adequately cover the groin. The gracilis muscle is a reliable muscle flap with a consistent blood supply, which can be transposed easily into the groin, based on its dominant pedicle, and offers adequate coverage of the femoral vessels.

Parsonage-Turner syndrome-case report and literature review.

Parsonage-Turner syndrome is the term used to describe a neuritis involving the brachial plexus. It may present with symptoms of an isolated peripheral nerve lesion, although the pathology is thought to lie more proximally. A case describing an isolated anterior interosseus nerve palsy due to an acute brachial neuritis is presented where the electromyographic findings confirmed the diagnosis, but also demonstrated the coexistence of a dual pathology in the form of a cervical radiculopathy. The literature is reviewed regarding etiology, treatment, and prognosis.

Ruptured abdominal aortic aneurysm in a 12-month-old boy.

A rare case of abdominal aortic aneurysm in a 12-month-old boy is reported. The clinical presentation was one of acute catastrophic rupture. The morphologic and histologic findings suggested an idiopathic etiology.

Inhibition of platelet thrombosis using an activated protein C-loaded stent: in vitro and in vivo results.

In high-risk and complicated coronary intervention, the risk of acute closure is unpredictable. Thrombus and platelet deposition at the intervention site may also have further effects on subsequent restenosis. In vivo infusion of activated protein C has previously been shown to achieve potent anticoagulation without any haemostatic side effects. We now evaluated the in vitro and in vivo efficacy of polymer-coated coronary stents loaded with purified rabbit Activated Protein C (APC). By measuring 125I-fibrinogen/fibrin deposition APC-loaded stent-wires were antithrombotic compared to albumin-loaded, inhibited-APC-loaded, plain polymer-coated and stainless steel stent-wires. In a balloon injury rabbit iliac artery model, APC-loaded stents did not occlude (0/14) compared to plain stents (9/15) and BSA-loaded stents (2/4). Relative 111In-labelled platelet deposition showed a similarly significant degree of inhibition. In conclusion, APC-loading could render stents significantly less thrombotic. Whether an effective antithrombogenic stent like this effectively reduces restenosis rates warrants further evaluation.

Human Mu-class glutathione S-transferases present in liver, skeletal muscle and testicular tissue.

The major human Mu-class glutathione S-transferases (GST) have been purified to allow comparisons of their catalytic, physicochemical and immunochemical properties. GST isoenzymes, purified from hepatic, testicular and skeletal muscle tissue were found to comprise three distinct subunits (M1, M2 and M3) which may combine to form both homodimeric and heterodimeric proteins. Two distinct subunits, M1a and M1b, which represent allelic charge variants have been isolated but no polymorphic forms encoded at the GST M2 and M3 loci have been observed. Three GST isoenzymes (M1a-1a, M1a-1b and M1b-1b) have been purified from a single liver specimen. In addition, GST M1a-2, M1b-2, M2-2 and M2-3 have been isolated from muscle, whilst the M3-3 homodimer has been purified from human testis. The homodimeric enzymes GST M1a-1a, M1b-1b, M2-2 and M3-3 have pI values of 6.1, 5.5, 5.3 and 5.0, whilst SDS-PAGE indicated that M1a, M1b, M2 and M3 have molecular masses of 26.7, 26.6, 26.0 and 26.3 kDa, respectively. The M1, M2 and M3 subunits isolated from either liver, skeletal muscle or testis, are catalytically distinct. Both M1-type subunits (M1a and M1b) possess a high activity for trans-4-phenyl-3-buten-2-one, whereas, the skeletal muscle subunit M2 has a high activity towards 1,2-dichloro-4-nitrobenzene. By contrast, the testicular GST subunit M3 has no detectable activity towards either of these substrates. However, all three Mu-class subunits are active towards the compounds 4-hydroxynonenal and 4-hydroxydecinal, possible endogenous substrates which are produced by lipid peroxidation. The human Mu-class subunits can be distinguished immunochemically; antisera raised against the testicular GST M3-3 showed no reactivity towards either the M1 or M2 subunits. The M3 subunit has a blocked N-terminus but automated amino-acid sequencing of a CNBr-derived peptide allowed 14 residues of the M3 subunit to be identified. These data indicated that testicular GST M3-3 is likely to correspond to the brain/testis Mu-class GST cDNA described by Campbell et al. (Campbell E., Takahashi Y., Abramovitz M., Peretz M., & Listowsky I. (1990) J. Biol. Chem. 265, 9188-9193).

Characterization of a human class-Theta glutathione S-transferase with activity towards 1-menaphthyl sulphate.

A purification scheme is described for a glutathione S-transferase (GST) from human liver that catalyses the conjugation of 1-menaphthyl sulphate (MS) with GSH; the method devised results in an approx. 500-fold increase in specific activity towards MS. The human enzyme which metabolizes MS is a homodimer comprising subunits of M(r) 25,100, and immunochemical experiments have shown it to be a member of the class-Theta GSTs. Automated Edman degradation of this enzyme has confirmed that it is a Theta-class GST bu the amino acid sequence obtained differs from that of GST theta described previously [Meyer, Coles, Pemble, Gilmore, Fraser & Ketterer (1991) Biochem. J. 274, 409-414]. We have therefore designated the enzyme that catalyses the conjugation of MS with GSH GST T2-2* (in the absence of complete amino acid sequence data, the T1 and T2 subunits are provisionally designated T1* and T2*); the evidence which indicates that GST theta (which should possibly now be called GST T1-1*) and GST T2-2* represent distinct isoenzymes is discussed.

Variation in the expression of Mu-class glutathione S-transferase isoenzymes from human skeletal muscle. Evidence for the existence of heterodimers.

The cytosolic glutathione S-transferases (GST) from human skeletal muscle were purified by a combination of affinity chromatography and anion-exchange chromatography followed by either chromatofocusing or hydroxyapatite chromatography. Pi-class and Mu-class GST, but not Alpha-class GST, were isolated from muscle. In addition to a Pi-class GST subunit, which exists as a homodimer, this tissue also contains a total of three distinct neutral-type Mu-class GST subunits, which hybridize to form homodimers or heterodimers. The neutral-type subunits are referred to as N1-N3 and are defined by the decreasing isoelectric points of the homodimers; GST N1N1, N2N2 and N3N3 have estimated pI values of 6.1, 5.3 and less than 5.0 respectively. SDS/PAGE showed that N1, N2 and N3 have Mr values of 26,700, 26,000 and 26,300 respectively. The N1, N2 and N3 subunits are catalytically distinct, with N1 possessing a high activity for trans-4-phenylbut-3-en-2-one and N2 having high activity with 1,2-dichloro-4-nitrobenzene. In skeletal muscle the expression of the N1 subunit, but not of N2 and N3 subunits, was found to differ from specimen to specimen. The N1 subunit was absent from about 50% of samples examined, and the purification results from two different specimens are presented to illustrate this inter-individual variation. Skeletal muscle from one individual (M1), which did not express N1, contained only GST N2N2, N2N3 and pi, whereas the second sample examined (M2) contained GST N1N2, N2N2 and N2N3 as well as GST pi. N-Terminal amino acid sequence analysis supported the electrophoretic evidence that the N2 subunit in GST N1N2, N2N2 and N2N3 represents the same polypeptide. The peptides obtained from CNBr digests of N2 were subjected separately to automated amino acid sequencing, and the results indicate that N2 is distinct but closely related to the protein encoded by the human Mu-class cDNA clone GTH4 [DeJong, Chang, Whang-Peng, Knutsen & Tu (1988) Nucleic Acids Res. 16, 8541-8554]. GST N2N2 is probably identical with GST 4 [Board, Suzuki & Shaw (1988) Biochim. Biophys. Acta 953, 214-217], as over the 24 N-terminal residues of GST 4 there is complete identity between the two enzymes. Our data suggest that the GST 1 and GST 4 loci are part of the same multi-gene family.