Comparison of outcomes following surgical resection, percutaneous ablation or stereotactic body radiation therapy in early-stage, solitary and small (≤3 cm) treatment-naïve hepatocellular carcinoma.

INTRODUCTION: Stereotactic body radiation therapy (SBRT) is associated with high local control rates in hepatocellular carcinoma (HCC). This study reports the outcomes of SBRT compared to surgical resection (SR) and percutaneous ablation (PA) for treatment-naïve, solitary HCCs ≤3 cm. METHODS: This was a retrospective study of patients with BCLC stage 0/A HCC with a single ≤3 cm lesion, treated with curative intent between 2016 and 2020. SBRT was used for patients considered unsuitable for SR or PA. The co-primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints were treatment-related clinical toxicity rates and local control (LC) rates. RESULTS: There were 112 patients included in this study. SBRT was delivered in 36 patients (32.1%), 51 had PA (45.5%) and 25 underwent SR (22.3%). Median follow-up was 23 months (range, 3-60 months) from diagnosis. The 3-year PFS and OS were 67% and 69% following SBRT, 55% and 80% following PA, and 85% and 100% following SR, respectively. Patients in the SR cohort had significantly better 3-year PFS and OS compared to SBRT and PA groups (p = 0.03 and p = 0.04, respectively). There was no significant difference in PFS (p = 0.15) or OS (p = 0.23) between SBRT and PA treated patients. The 3-year LC rate for the entire cohort was 98%. CONCLUSIONS: In patients with treatment-naïve, early-stage solitary HCCs ≤3 cm, SBRT was associated with comparable PFS, OS and LC outcomes to PA. SBRT should be considered as a curative intent therapy to avoid treatment stage migration in this favourable prognostic cohort of patients.

Structured ternary fluids as nanocrystal incubators for enhanced crystallization control.

In crystallization from solution, a ubiquitous process in both industry and the natural world, nucleation is usually the rate-determining step, followed by faster crystal growth. Consequently, crystals typically exist in the nm-size range for such limited times that their investigation and manipulation is hindered. Here, we show that, owing to a degree of restricted diffusion, crystallization in structured ternary fluids (STFs) can proceed via higher nucleation rate and slower crystal growth pathways. This enables STFs to act as nanocrystal incubators, with the nanocrystals existing for extended times. We demonstrate that this generates enhanced crystallization control, with the three ambient pressure polymorphs of glycine, the α-, γ- and ß-forms, all crystallizing from the octanol/ethanol/water STF, despite the well-known difficulty in crystallizing the slow growing γ-form and the instability of the ß-form. The ability of STFs to produce notoriously hard to crystallize polymorphs should make them a versatile tool, ideal for polymorph discovery. This may enable a step change in the current, scatter-gun approach to polymorph screening. Furthermore, we show that aliquots of the nanocrystal-containing fluids can successfully seed metastable solutions. Hence, STFs may ultimately help provide a generic methodology for producing crystals and seed suspensions of any desired polymorph to supersede current targeted crystallization and seeding strategies.

Combined Heart-Lung-Liver Transplantation for Patients With Cystic Fibrosis: The Australian Experience.

BACKGROUND: Combined multivisceral transplantation has emerged as a therapeutic option for a select patient cohort; however, clinical decision-making remains complex and controversial. The aim of this study was to examine patient characteristics, operative complications, and long-term outcomes of all patients who have undergone combined heart-lung-liver transplantation (HLLTx) in Australia. METHODS: In this study, we performed a retrospective analysis of all adult patients who have undergone combined HLLTx in Australia to date. Recipient clinical characteristics, waitlist, and transplant outcomes are described. RESULTS: Eight adult patients have received HLLTx at a single Australian transplant center. Recipients of HLLTx have typically been young (median age, 30.1 years; range, 24-37), underweight (median body mass index, 19.8 kg/m2; range, 16.2-30.4) patients with cystic fibrosis (n = 8, 100%) with severe airflow obstruction (median forced expiratory volume in the first second of expiration, 24% predicted; range, 17%-48%) accompanied by liver cirrhosis confirmed on histopathology (n = 8, 100%). Despite relative preservation of synthetic function and low model for end-stage liver disease scores (median, 8; range, 6-17), all recipients had complications of portal hypertension prior to transplantation, with many patients having suffered life-threatening variceal hemorrhage. In this cohort, HLLTx was associated with overall posttransplant survival of 87.5% at 30 days, 71.4% at 1 year, and 42.9% at 5 years. Listing for combined HLLTx was associated with prolonged waitlist times relative to bilateral sequential single-lung transplantation (median 556 vs 56 days, respectively), however waitlist mortality and/or delisting was comparable between groups. CONCLUSIONS: Taken together, these findings highlight the opportunities and challenges facing combined (heart-) lung and liver transplantation in patients with multiorgan failure.

Efficacy and Toxicity of Stereotactic Body Radiotherapy for Early to Advanced Stage Hepatocellular Carcinoma - Initial Experience From an Australian Liver Cancer Service.

AIMS: Intrahepatic progression remains the predominant mode of cancer-related death in hepatocellular carcinoma (HCC) underscoring the need for effective local therapies. We report our initial experience with liver stereotactic body radiotherapy (SBRT) in the management of early to advanced stage HCC at an Australian tertiary liver cancer service. MATERIALS AND METHODS: Patients with liver-confined HCC unsuitable for surgical resection or thermal ablation treated with SBRT between October 2013 and December 2018 were retrospectively evaluated. The primary end point was freedom from local progression. Secondary end points were progression-free survival, disease-specific survival, overall survival and toxicity. RESULTS: Ninety-six patients were treated for 112 lesions (median size 3.8 cm, range 1.5-17 cm). The median follow-up was 13 months (range 3-65). Forty-six patients had received prior local therapies (median 1, range 1-5), 83 (86%) patients had cirrhosis with baseline Child-Pugh scores of A (88%) and B7-8 (12%). Fifty-nine (61%) patients had Barcelona Clinic Liver Cancer (BCLC) stage 0/A disease and 37 (39%) had stage B/C. Macrovascular invasion was present in 20 (21%). The median biologically effective dose (BED10) was 86 and 60 Gy for the BCLC 0/A and B/C cohorts, respectively. Freedom from local progression at 18 months was 94% for BCLC 0/A and 74% for BCLC B/C. Progression-free survival and overall survival at 12 months were 80 and 95% for BCLC 0/A and 40 and 71% for BCLC B/C, respectively. Five patients (7%) with cirrhosis and without disease progression had an increase in Child-Pugh score >1 within 3 months of SBRT, four of whom had intercurrent infections. Clinical toxicities grade ≥2 were reported in 20% of patients. CONCLUSION: SBRT is an effective ablative modality for early stage HCC with low rates of significant toxicity. Lower dose SBRT can provide durable local control for advanced stage HCC. However, out-of-field relapse remains common, providing a rationale to investigate SBRT in combination with other therapies.

Remifentanil patient-controlled intravenous analgesia during labour: a retrospective observational study of 10 years' experience.

BACKGROUND: Intravenous remifentanil patient-controlled analgesia (PCA) has been routinely available for labouring women in our unit since 2004, the regimen using a 40 µg bolus available two minutely on demand, continuous pulse oximetry and mandatory one-to-one care. We examined remifentanil use and compared, with the other analgesic options available in our unit, outcomes such as mode of delivery, Apgar scores, neonatal resuscitation and admission to the neonatal intensive care unit. METHODS: We retrospectively identified women who delivered in our unit between 2005 and 2014 and received remifentanil, diamorphine or epidural analgesia during labour. Data were drawn from the Northern Ireland Maternity System electronic database, which records birth details from all obstetric units in Northern Ireland. Additional data were identified from paper survey forms, completed by the midwife post delivery for all women who received remifentanil in our unit. Outcomes were compared between women who received remifentanil, diamorphine or an epidural technique for labour analgesia. RESULTS: Over the 10-year period, remifentanil was the most popular form of analgesia, being selected by 31.9% (8170/25617) women. Compared with women selecting diamorphine or epidural analgesia, those having remifentanil had similar rates of instrumental and operative delivery. Neonatal Apgar scores were also similar. Neonatal resuscitation or neonatal unit admission were not more likely in women choosing remifentanil PCA. CONCLUSION: We found remifentanil PCA to be neither less safe nor associated with poorer outcomes than other analgesic options offered in our unit, when used within our guidelines for more than a 10-year period.

Resonance-assisted stabilisation of hydrogen bonds probed by NMR spectroscopy and path integral molecular dynamics.

Path integral molecular dynamics and experimental NMR data are used to investigate resonance-assisted hydrogen bonds (RAHBs). When nuclear delocalisation is included in chemical shift calculations, the agreement with experiment is excellent, while static calculations show very poor performance. The results support the concept of RAHB, which has recently been questioned.

Beware frontotemporal dermoids - they may have intracranial extension: a case of a middle cranial fossa cyst.

Congenital orbitofacial dermoid cysts are epithelial lined structures of ectodermal origin that may be associated with sinus tracts and variable deep extension. Midline lesions may extend intracranially, while lateral lesions are thought never to do so. Consequently only midline lesions are usually imaged prior to surgery. We describe a lateral dermoid sinus communicating with an intracerebral dermoid cyst within the middle cranial fossa in a 3 year-old with recurrent periorbital cellulitis and intermittent discharge from a small pimple in the temporal region. This case demonstrates that some lateral "dermoids" need to be treated with more caution if there are unusual features such as dimpling, discharge of material or recurrent wider infection, and preoperative imaging should be carried out to exclude intracranial extension.

Multidisciplinary management of Blepharo-Cheilo-Dontic Syndrome and the role of overdenture in dental management.

AIM: Blepharo-Cheilo-Dontic (BCD) syndrome is a rare condition characterised by abnormalities of the eyelid, lip and teeth. A 12-year-old girl with BCD syndrome presented at the Dental Hospital following referral from the multi-disciplinary cleft lip and palate clinic. She had skeletal Class III relation, with left posterior cross bite, occlusal contacts on the second permanent molars with poor oral hygiene. The permanent units missing were 15, 14, 13, 12, 11, 21, 22, 25, in the upper arch and 35, 34, 32, 44 and 45 in the lower arch. This patient presented a complex aesthetic problem, which through multi- disciplinary care resulted in a satisfactory aesthetic outcome. In this case report we present the clinical management and the role of the overdenture in her dental management.

Cleft lip repair without suture removal.

The disadvantages of using non-absorbable sutures in cleft lip repair include a need for additional dressings, return to the ward for removal of the sutures under sedation or general anaesthetic and the problem of distressing the child and potentially disrupting the repair. Modern medical adhesives represent an alternative adjunctive technique for skin closure and their use was adopted by this unit in 2005. A few 'key' interrupted sutures of 7/0 Vicryl Rapide followed by layers of a cyanoacrylate adhesive, Dermabond, were used instead of more traditional methods. An audit of the results of cleft lip repairs from this period of change was conducted. Subjective and objective data were collected and are presented to justify the continued use of this technique in the Newcastle Cleft Lip and Palate Unit.

Oro-nasal fistula development and velopharyngeal insufficiency following primary cleft palate surgery--an audit of 148 children born between 1985 and 1997.

We present an audit of primary cleft palate surgery in our unit including rates of two important post-operative complications. Multidisciplinary audit clinics ran from March 1998 to April 2002 to follow up all local patients with a cleft lip or palate who had undergone primary palatal surgery in our unit. One hundred and forty eight patients were studied. Patient ages at follow-up ranged from 3 years and 10 months to 17 years and 4 months. Two surgeons performed the primary surgery. One hundred and twenty eight Wardill-Kilner and 20 Von Langenbeck repairs were performed. We found a 4.7% rate of oro-nasal fistula development requiring surgical closure, and a 26.4% rate of velopharyngeal insufficiency (VPI) requiring subsequent pharyngoplasty. We noted that the type of cleft involved affected the rate of VPI, 16% of patients with unilateral cleft lip and palate versus 29.2% of patients with a solitary cleft palate requiring secondary surgery. Outcome of surgery was determined by a 'Cleft Audit Protocol for Speech' (CAPS) speech therapy assessment at follow-up clinics. Only 14.9% of all patients assessed demonstrated any degree of hypernasality. Our results compare favourably with other recent studies including the Clinical Standards Advisory Group (CSAG) report into treatment of children with cleft lip and palate.

Follicular dendritic cell tumour in a 9-year-old child.

Follicular dendritic cell tumour (FDCT) or sarcoma is a rare tumour first described in 1986. Some 80 cases have been reported, the youngest being in teenagers. Our patient first presented at 9 years of age with a cervical mass that was removed and revealed an apparently benign, but florid reactive process. At age 14 the lump recurred and biopsy was diagnostic of FDCT. Radical block dissection showed disease to level III and 6 weeks of radiotherapy was followed by 6 months adjuvant chemotherapy. Three years after completing his final treatment he shows no signs of recurrent disease.

Factors influencing the development of wound infection following free-flap reconstruction for intra-oral cancer.

Wound infection following tissue transfer in head and neck oncology is common. Factors known to be associated with infective complications include blood transfusion, pre-operative radiotherapy, duration of surgery, duration of pre-operative stay and a history of smoking. The present study specifically examined 100 consecutive patients on a standard antibiotic protocol undergoing free flap reconstruction following resection of cancers of the oral cavity or oropharynx. Despite prophylactic antibiotics, 21 patients developed a head and neck wound infection. No statistically significant association was found between infective wound complications and a history of smoking, pre-operative radiotherapy or chemotherapy, length of pre-operative hospital stay, duration of surgery, or number of units of blood transfused. We conclude that, in this group of patients, wound infection is a common and difficult problem, but with no statistically significant association with any of the variables studied.

Transverse dephasing optimized solid-state NMR spectroscopy.

It is shown how coherence lifetimes in solid-state NMR experiments can be controlled. New decoupling schemes are introduced which actively optimize dephasing times, providing increases of up to a factor of 2 with respect to the best existing schemes. The new schemes are implemented in transverse-dephasing-optimized (TDOP) NMR experiments for the disorded solid cellulose, and for a microcrystalline protein, where sensitivity improvements of up to a factor of 5 are obtained.

Microvascular histopathology in head and neck oncology.

A histological study of both recipient and flap vessels was performed in 30 patients with head and neck cancer, and relevant preoperative risk factors were assessed. A total of 35 free flaps were transferred in 30 patients; 16 patients had preoperative radiotherapy, 13 were smokers, eight had hypertension and six had peripheral vascular disease. No significant venous pathology was found in either the flap or the neck veins. However, over two-thirds of the neck arteries and one-half of the flap arteries were found to have microscopic arterial pathology. The only pre-existing factor significantly influencing vessel pathology was hypertension (P=0.007). All flaps survived, although in two there was some loss of the skin paddle. This study reveals that the majority of patients undergoing microsurgery in the head and neck region have pre-existing arterial damage in both the flap and the recipient arteries, but this does not have a significant effect on the overall patency of the microvascular anastomoses.