Current trends in craniofacial reconstruction.

Reconstruction of the head and neck continues to pose a variety of difficult functional and aesthetic challenges to the plastic surgeon. While the surgical treatment for midfacial and skull base tumours continues to advance, the three-dimensional reconstruction predicaments continue to increase in complexity. Reconstructive strategies of the head and neck require the restoration of intricate skeletal architecture and large volumes of both internal and external soft tissue envelopes that can withstand adjuvant therapies. Vascularized bone grafts in combination with microsurgical techniques is the current trend of most reconstruction and has replaced local and pedicle flaps as the preferred modality for large defects. This article will focus on concise areas of difficulty in craniofacial reconstruction, including mandibular, midfacial, scalp and base of skull reconstruction. As our goals now move from flap survival to refinement, more complex and innovative reconstructions are executed. The problems with each modality are examined, and the frontiers of head and neck reconstruction are explored. With the potential combination of virtual surgery and tissue engineered biotechnology, we may someday be able to expand our reconstructive capabilities beyond free tissue transfer.

Declining incidence of keratinocyte carcinoma in organ transplant recipients.

BACKGROUND: All organ transplant populations are predisposed to increased rates of keratinocyte carcinoma (KC). Since this increased risk was first appreciated, immunosuppressive regimens have changed and organ transplant recipients (OTRs) have been aggressively screened for KC. There is a perception that these measures have impacted on KC incidence but there is a paucity of population-based studies on post-transplant rates of basal cell carcinoma (BCC). OBJECTIVES: To identify trends in incidence rates for KC following solid organ transplantation over the past two decades. METHODS: This nationwide, population-based study included all solid OTRs transplanted between 1994 and 2014. Patient data were matched to national cancer registry data to determine the standardized incidence ratio (SIR) of KC in solid OTRs compared with the general population. RESULTS: In total 3580 solid OTRs were included. The total follow-up time was 28 407 person-years (median follow-up 7·11 years). The overall SIRs for squamous cell carcinoma (SCC) and BCC were 19·7 and 7·0, respectively. Our study documents a progressive fall in the SIRs for SCC and BCC from peak SIRs (95% confidence intervals) in 1994-1996 of 26·4 (21·5-32·4) and 9·1 (7·4-11·3) to 6·3 (2·3-16·7) and 3·2 (1·4-7·1) in 2012-2014, respectively. The ratio of SCC to BCC has remained at 3 to 1 over the last two decades. CONCLUSIONS: Our study is the first to demonstrate a significant reduction over the past two decades in the incidences of both SCC and BCC following solid organ transplantation. The SCC-to-BCC ratio was maintained, demonstrating that both are reducing equally. This trend coincided with temporal changes in immunosuppressive protocols and the introduction of skin cancer prevention programmes. What's already known about this topic? Prior studies have shown that the risk of cutaneous squamous cell carcinoma (SCC) has declined over recent decades following solid organ transplantation. It is not known whether the risk of basal cell carcinoma (BCC) has reduced in line with this. What does this study add? Our study documents a progressive fall in the risk of SCC and BCC following solid organ transplantation over the last two decades. The SCC-to-BCC ratio was maintained, demonstrating that both are reducing equally. The trends observed in our study coincided with temporal changes in immunosuppressive protocols and the introduction of cancer prevention programmes, suggesting that these factors have positively impacted on the risk of keratinocyte carcinoma in this cohort.

Use of the Portsmouth Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity ('P-POSSUM') to predict morbidity in patients undergoing surgery with reconstruction for temporal bone malignancy.

OBJECTIVE: The Portsmouth Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity ('P-POSSUM') is a two-part scoring system that includes a physiological assessment and a measure of operative severity. This study sought to determine whether risk estimates for this scoring system could be used in major head and neck reconstructive surgery. METHOD: A retrospective review was performed of patients undergoing resection for a temporal bone malignancy in a single head and neck centre in Dublin, Ireland, from 2002 to 2021. RESULTS: The mean ± standard deviation morbidity estimate calculated using the scoring system was 47.6 per cent ± 19.5 per cent. The actual rate of complications was 47 per cent. The optimal cut-off for the scoring system was calculated using the Youden index from the receiver operating characteristic curve, which was 40.5 per cent in this case. CONCLUSION: The study indicates that the Portsmouth Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity is a useful tool for predicting morbidity risk in patients undergoing head and neck resection with reconstruction for temporal bone malignancies.

Concurrent management of suppurative intracranial complications of sinusitis and acute otitis media in children.

OBJECTIVE: Intracranial complications of sinusitis and acute otitis media (AOM) are rare but life-threatening events. In children with suppurative intracranial complications, concurrent neurosurgical and otolaryngological (ORL) intervention has been recommended to optimize outcomes. The aim of this study was to investigate outcomes following concurrent neurosurgical and ORL intervention. METHODS: A retrospective cohort study of children undergoing neurosurgical intervention for intracranial complications of sinusitis or AOM in two neurosurgical centres in Ireland was conducted. RESULTS: 65 children were identified. Mean age was 11.9 years. The most prevalent symptoms were headache, pyrexia, altered level of consciousness, facial swelling, and vomiting. Subdural empyema (n = 24, 36.9%) and extradural abscess (n = 17, 26.2%) were the most common complications. 54 underwent same admission ORL intervention; 47 (87%) were performed concurrently or earlier. For rhinogenic infections, 35 (64.8%) underwent endoscopic sinus surgery (ESS), 13 (24.1%) underwent frontal sinus trephine, and 5 (9.3%) underwent maxillary sinus washout alone. For otogenic infections, 10 (90.9%) underwent mastoidectomy and 7 (63.6%) underwent tympanostomy tube placement. 19 (29.2%) had post-operative neurological deficits, of which 2 (3.1%) were permanent. Streptococcus intermedius was the most common pathogen (n = 30, 46.2%). Concurrent intervention reduced the prevalence of residual collection (p = 0.018) and the need for revision neurosurgical intervention (p = 0.039) for sinogenic complications. The same trends did not achieve statistical significance for the otogenic group. Mortality was 0%. CONCLUSION: Intracranial complications of sinusitis and AOM are best managed in a specialist centre with multidisciplinary input. Concurrent ORL and neurosurgical intervention reduces abscess recurrence and requirement for revision neurosurgery in sinogenic complications and should represent the standard of care. ESS is the ORL modality of choice in experienced hands.

Gender and immunosuppression impact on Merkel cell carcinoma diagnosis and prognosis. A population based cohort study.

Background: Merkel cell carcinoma (MCC), a rare cutaneous neuroendocrine endocrine tumour is increasing in incidence, and continues to carry a poor prognosis. Objectives: The objectives of this study were to examine all Irish cases of MCC from 1 January 1994 over 2 decades, focusing on gender and organ transplantation recipients (OTRs). Cases were identified from the National Cancer Registry of Ireland. Covariates of interest included age, body site, period of diagnosis, deprivation-status and history of non-melanoma skin cancer (NMSC). Results: In total 314 MCC cases were identified. A female predominance was noted (53.8%). Comparison between age-standardised rates between the earliest period (1994-1996) with the latest period (2012-2014) showed an increase of 105% in total. The trend in age-standardised incidence rates were noted to be increasing significantly (p = 0.0004). Average age at diagnosis was 77.6 years (male 75.1 years, female 79.7 years). Overall, the majority of MCC cases presented on the head and neck (n = 170, 54.1%). Differences in anatomical location of MCCs were noted between genders. Males were found to be more likely to have a history of previous NMSCs (males n = 73 [57.9%], females n = 53 [42.1%]). Thirty-one percentage of patients died from MCC, average survival was 3.5 years in those who died of this malignancy. Ten organ transplant recipients developed MCC. OTR who developed MCC were diagnosed at a younger average age of 65.1 years. Standardized incidence ratio for MCC in OTR was 59.96. A higher proportion of OTR died from MCC (70%), with a shorter median survival of 0.14 years. In competing risks regression, gender was not significantly associated with risk of dying, females having a non-significantly higher hazard of dying. Organ transplant recipients and patients from less deprived areas were at greater risk of dying from MCC. Conclusions: This population based study provides epidemiological, clinical and outcome data for MCC over a 20-year period.

Gene mutations with characteristic deletions in cord blood T lymphocytes associated with passive maternal exposure to tobacco smoke.

We have investigated the molecular effects of passive maternal cigarette exposure in a newborn population and consider the possible implications of the observed genetic changes in the development of neoplastic diseases in children. We present a distribution analysis of somatic mutational events in a reporter gene, HPRT, in cord blood T lymphocytes from newborns after transplacental exposure to cigarette smoke. Analysis of 30 HPRT mutant isolates from 12 newborn infants born to mothers with no evidence of environmental exposure to cigarette smoke and 37 HPRT mutant isolates from 12 infants born to mothers exposed to passive cigarette smoke showed a significant difference in the HPRT mutational spectrum in those exposed in utero to cigarette smoke. The most notable change was an increase in 'illegitimate' genomic deletions mediated by V(D)J recombinase, a recombination event associated with hematopoietic malignancies in early childhood. Recent epidemiological studies of maternal and paternal cigarette smoke exposure and childhood cancers may need to be re-interpreted, given these results.

Challenging the use of the lymphocyte to white cell count ratio in the diagnosis of infectious mononucleosis by analysis of a large cohort of Monospot test results.

OBJECTIVE: We investigated the hypothesis that a lymphocyte/white cell count ratio should be used as a diagnostic indicator of infectious mononucleosis. DESIGN: Retrospective study to compare lymphocyte counts and white blood cell counts, against the criterion standard, the mononucleosis spot test. SETTING: Department of Otolaryngology, Mater Misericordiae University Hospital, Dublin, Ireland. PARTICIPANTS: We reviewed 1000 patients who had Monospot assays, 500 positive and 500 negative. MAIN OUTCOME MEASURES: The lymphocyte counts and white blood cell ratio was calculated and compared with the monospot result to calculate the sensitivity and specificity at various ratios. RESULTS: The lymphocyte counts and white blood cell ratio was significantly different in the positive and negative monospot groups (P < 0.05). The mean lymphocyte counts and white blood cell ratio in the positive group was 0.49 and the mean lymphocyte to white cell count ratio in the monospot negative group was 0.29.A ratio of 0.35 had a specificity of 72% and a sensitivity of 84% for the detection of glandular fever. A higher ratio will give a greater specificity, but a lower sensitivity, and vice versa. CONCLUSIONS: The mean lymphocyte to white cell count ratio is not sufficient to diagnose or exclude infectious mononucleosis. Thus, this study does not confirm the conclusions of earlier studies.

Complete traumatic laryngo-tracheal separation.

Laryngotracheal separation injuries are rare and potentially fatal. Immediate respiratory signs may include dysphonia, aphonia, hemoptysis, subcutaneous emphysema and a sucking wound. Patients with this injury usually die at the site of the trauma. The absolute life saving intervention for patients with laryngotracheal injury is airway control via routine intubation or emergency tracheostomy. We present an extremely rare case of complete laryngotracheal separation in a teenager driving a quad bike in a 'clothes line' type injury with chicken wire. This case highlights the need for prompt airway evaluation, radiological imaging required, surgical management and long term injury sequelae.

The recurrent laryngeal nerve in thyroid surgery.

The recurrent laryngeal nerve (RLN) is an essential nerve for phonation and psychosocial interaction. Throughout the annals oflaryngological history, vocal cord paralysis has been a well recognised disorder. A rich heritage of scientific investigation and research has considered the complexity of vocal cord function, laryngoscopic presentation and surgical rehabilitation. Identification and preservation of the RLN is the major concern in thyroid surgery. Controversy exists regarding the correct pre- and postoperative management in vocal cord evaluation. We fully review this topic and challenge, in part, the recent Thyroid Clinical Guidelines as published by RCSI.

Lucja Frey--historical relevance and syndrome review.

BACKGROUND: This article documents an objective review ofthe neuro-anatomical, diagnostic and clinical implications of the auriculotemporal syndrome (Frey's syndrome). The incidence of Frey's syndrome after parotidectomy as cited in the literature varies. It may also be a sequela to a variety of inflammatory, infective and traumatic aetiologies. METHOD: An electronic search using the search engine Google, Medline and Pubmed was performed under 'Lucja Frey', 'Gustatory sweating', 'The auriculotemporal syndrome', 'Botulinum toxin'. Relevant papers were systematically reviewed from 1965 to present. CONCLUSIONS: This disorder is important for ENT surgeons and allied specialties. We present the main surgical and cosmetic therapeutic strategies in the literature. We also discuss the fascinating life of Lucja Frey. As one of the first female academic neurologists in Europe, her career and life were tragically altered by the events of World War II.

Prognostic markers in well differentiated papillary and follicular thyroid cancer (WDTC).

OBJECTIVES: WDTC (papillary and follicular thyroid cancer) make up around 90% of all thyroid tumours. Overall, the prognosis in patients with WDTC is excellent. However, there are small cohorts of patients who experience a more aggressive form of disease which is often associated with certain poor prognostic factors. Identifying these patients at an early stage is imperative for guiding treatment decisions. With recent developments in this area we plan to discuss the current evidence surrounding prognostic markers. METHODS: The literature regarding prognostic factors in WDTC was reviewed using an electronic database Medline - Pubmed. Using the MeSH search engine specific prognostic factors including age, size, grade, lymph node involvement, distant metastasis, extension/invasion, ethnic background, radioactive iodine avidity, and thyroglobulin level and their association with WDTC were evaluated. A broader search of prognostic markers in thyroid cancer was also carried out to avoid missing other pertinent markers. RESULTS: Multiple clinical and pathologic variables have been shown to be poor prognostic factors in WDTC with statistical significance. Extensive extrathyroidal extension and age may be the most important factors when predicting clinical outcomes in WDTC, although the age threshold may be increased from 45 to 55 years in due course. CONCLUSIONS: Management of WDTC has changed considerably over the last two years as reflected in evolving British and American Thyroid Guidelines. In all cases a combined multi-disciplinary approach, with consideration of the available guidelines and stratification systems should be utilised when planning an individualised treatment program to offer the best contemporary care to WDTC patients.

Hypoxanthine-guanine phosphoribosyltransferase deficiency: biochemical and molecular findings in six Argentine patients.

Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency is an inborn error of purine metabolism responsible for Lesch-Nyhan Disease (LND) and its partial phenotypes, HPRT-related hyperuricemia with neurologic dysfunction (HRND) and hyperuricemia alone. We report here the recognition of six Argentine patients, two with LND and four with HRND. All patients presented elevated excretion of uric acid, hypoxanthine, and xanthine and decreased HPRT enzyme activities <1 nmol/h/mg Hb. The molecular analysis demonstrated in the two LND patients a novel inherited transition mutation, c.203T >C (L68P), in one subject and a germline transition mutation, c.209G >A (G70E), in the other. In the HRND patients a novel transversion mutation, c.584 A >C (Y195S), was found in three related patients and an inherited transition mutation, c.143G >A (R48H), in the fourth subject.

High-risk cutaneous malignancies and immunosuppression: Challenges for the reconstructive surgeon in the renal transplant population.

Renal transplantation is the most frequently performed transplant procedure. Immunosuppressive therapies have dramatically increased survival rates in transplant recipients but are associated with an increased risk of skin cancers. Recent changes in immunosuppressive strategies have been adopted with the aim of reducing this challenging adverse effect. Despite these new strategies, cutaneous malignancies tend to be numerous, aggressive and associated with a higher risk of local and distant dissemination than in the non-transplant population. This represents a significant workload for transplant physicians, dermatologists, and head and neck and plastic surgeons. This review highlights key concepts in the pathogenesis of skin cancer in transplant patients, the impact current and evolving immunosuppressive strategies and regimens will have on the epidemiology, and the management of cutaneous malignancies in renal transplant patients, with particular focus on the implications for the plastic surgery community.

Aggressive medullary thyroid cancer, an analysis of the Irish National Cancer Registry.

BACKGROUND AND OBJECTIVES: Medullary thyroid cancer consists of a spectrum of disease that ranges from extremely indolent tumors to aggressive types associated with a high mortality rate. The objective of our study is to evaluate the prognostic factors and outcomes of patients diagnosed with MTC in a homogenous population, and to examine patients diagnosed with MTC for mutations in the RET proto-oncogene from the same period. METHODS: A retrospective analysis of the National Cancer Registry in Ireland was undertaken, between 1998 and 2007. The Kaplan-Meier method was used to determine overall survival and factors predictive of outcome were determined by univariate and multivariate analysis by cox regression using Stata 13 software. MAIN FINDINGS: Forty-three patients were diagnosed with medullary thyroid cancer, 55.8 % were female and 44.2 % were male. A median age of 52 was found. The overall median survival was 6.32 years and the 1- and 5-year overall survival was 88.37 and 62.79 %, respectively, with 10-year survival calculated at 48.63 %. On univariate analysis age, stage and surgical intervention were statistically significant indicators of prognosis. T stage and age remained statistically significant indicators of prognosis on multivariate analysis. Two patients with no history of MEN syndromes or family history of medullary thyroid cancer had RET proto-onocogene mutations. CONCLUSIONS: Our patient cohort was substantially older and presented at an advanced T status than what is commonly seen in the literature. This may account for poor survival outcomes and the very low pick-up of RET mutations in sporadic medullary thyroid cancer.

Serum mannose-binding lectin deficiency is associated with cryptosporidiosis in young Haitian children.

BACKGROUND: Mannose-binding lectin (MBL) is a component of the innate immune response and binds microbial surfaces through carbohydrate recognition domains. MBL deficiency may contribute to susceptibility to a variety of infectious diseases, particularly in young children. MBL binds to the Cryptosporidium sporozoite and may be important in resistance to cryptosporidiosis. METHODS: We studied the association of serum MBL levels and cryptosporidiosis in a case-control study of young Haitian children with cryptosporidiosis versus children who were control subjects. RESULTS: Ninety-nine children were enrolled, as follows: 49 children with cryptosporidiosis, 41 healthy controls, and 9 children with diarrhea from other causes. Case children were more malnourished than controls, and 49% had persistent or chronic diarrhea. At enrollment, mean serum MBL levels were markedly lower in children with cryptosporidiosis (P = .002), as was the number of children with an MBL deficiency of < or = 70 ng/mL (P = .005). In multivariate analysis, the association of cryptosporidiosis and MBL deficiency persisted (P = .002; adjusted odds ratio, 22.4), as did the association of cryptosporidiosis with general malnutrition. The subset of children with cryptosporidiosis and MBL deficiency were more likely to be male (P = .025). CONCLUSIONS: MBL may be an important component of innate immune protection against Cryptosporidium infection in young children. Additional studies are necessary to determine whether MBL intestinal losses, deficient epithelial expression, and/or genetic polymorphisms in the MBL gene contribute to MBL deficiency in cryptosporidiosis and other enteric infections in young children.

Gestational age and gender-specific in utero V(D)J recombinase-mediated deletions.

Recent studies have brought to the forefront the importance of somatic mutations during human fetal development and malignant transformation in children, specifically leukemia. Therefore, a better understanding of the frequency and mutational spectrum of spontaneous in utero mutations is essential for understanding the genetic mechanisms associated with pediatric malignancies. Previously we reported that the frequency of somatic mutations during the late stages of fetal development was dependent on both gestational age and gender. Here we present the hypoxanthine-guanine phosphoribosyltransferase (HPRT) reporter gene mutational spectra analysis for 60 T-cell mutant isolates from the umbilical cord blood of preterm newborns to gain insight into background mutational events during the late stages of fetal development. Logistic regression analyses showed a significant increase in HPRT deletions mediated by V(D)J recombinase in preterm newborns compared with full-term newborns (P = 0.009). A comparative analysis of deletion mutations also revealed that V(D)J recombinase-mediated HPRT deletions increased with decreasing gestational age (P = 0.012) and were significantly higher in females than males of the same developmental status (P = 0.031). Developmental and gender-specific differences in HPRT deletions mediated by V(D)J recombinase provide insight into the gender-specific differences seen in infant leukemia.

Mutagenicity of heterocyclic nitrogen mustards (ICR compounds) in cultured mammalian cells.

The mutagenicity of six heterocylic nitrogen mustards (ICR compounds) has been determined in a cultured mammalian cell system by use of resistance to the purine analog 6-thioguanine to select for mutation induction at the hypoxanthine-guanine phosphoribosyltransferase locus in Chinese hamster ovary cells. The six compounds tested are ICR 191, 170, 292, 372, 191-OH, and 170-OH. The first four contain a single 2-chloroethyl group (nitrogen half-mustard) on the side chain and are mutagenic, with the tertiary amine types (170 and 292) 3 to 5 times more mutagenic than the secondary amine types (191 and 372). The remaining two compounds (191-OH and 170-OH) are not mutagenic, indicating that the 2-chloroethyl group is needed for mutation induction.

Effect of folate deficiency on mutations at the hprt locus in Chinese hamster ovary cells exposed to monofunctional alkylating agents.

Multiplex PCR amplification of hprt exons from 113 Chinese hamster ovary cell clones selected for resistance to 6-thioguanine was performed to investigate the molecular basis for the synergistic mutagenic effects of nutritional folic acid deficiency and alkylating agents. In cells treated with ethyl methanesulfonate, intragenic deletions were detected in 9 of 46 (19.6%) clones derived from folate-deficient cells, but in none of 16 mutants grown in folate-replete medium. The number of deletions found in mutants generated by N-nitroso-N-ethylurea was low in both folate-deficient (1 of 25; 4%) and folate-replete (1 of 26; 3.8%) cells. Correction of folate deficiency may decrease the frequency of intragenic deletions caused by some alkylating agents.