Smell-related quality of life changes after total laryngectomy: a multi-centre study.

PURPOSE: A total laryngectomy creates an alternate airway for gas exchange that bypasses the upper aerodigestive tract. The subsequent reduction in nasal airflow, and therefore, reduction in deposition of particles to the olfactory neuroepithelium leads to hyposmia or anosmia. The aim of this study was to assess the quality of life impairment conferred by anosmia following laryngectomy and identify any specific patient-related risk factors that are associated with poorer outcomes. METHODS: Consecutive patients with a total laryngectomy presenting for review at three tertiary head and neck services (in Australia, the United Kingdom and India) over a 12-month period were recruited. Patient demographic and clinical data were collected, and each subject completed the validated assessment of self-reported olfactory functioning and olfaction-related quality of life questionnaire (ASOF). Dichotomous comparisons were performed using the student's unpaired t-test for continuous variables (SRP), a chi-squared test for categorical variables, and a Kendall's tau-b for ordinal variables (SOC) to assess for a correlation with poorer questionnaire scores. RESULTS: A total of 66 laryngectomees (13.4% female; age 65.7 ± 8.6 years) were included in the study. The mean SRP score of the cohort was found to be 15.6 ± 7.4, while the mean ORQ score was noted to be 16.4 ± 8.1. No other specific risk factors associated with poorer quality of life were identified. CONCLUSION: A significant quality of life detriment from hyposmia is conferred following laryngectomy. Further research to assess treatment options and the patient population that would best benefit from these interventions is required.

Endoscopic or external approach revision surgery for pharyngeal pouch following primary endoscopic stapling: which is the favoured approach?

This study aimed to assess outcomes of revision endoscopic stapling and external excision of pharyngeal pouch. A 5-year prospective study was performed on all patients requiring revision pouch surgery following primary endoscopic stapling. Data were collected retrospectively. Eighteen patients underwent revision pouch surgery. In seven patients, pouch size was down-graded from 3 to 2, and these were stapled endoscopically. Two leaks resulted. Eleven patients with grade 1 or 3 pouches underwent external excision of pouch, with no post-operative complications. As per results external excision of pouch is safe for grade 1 and 3 pouches. It avoids risking redundant mucosa and recurrence of symptoms which can complicate stapling and enables a myotomy to be performed to reduce cricopharyngeal hypertonicity. The highest predictable success is with grade 2 pouches, whose size is amenable to adequate endoscopic stapling. However, the "staple over staple" effect of revision stapling leads to unpredictable fibrosis, which can contribute to risk of perforation.

Swallowing outcomes following division of pseudo-epiglottis resulting from vertical pharyngeal closure in laryngectomy.

BACKGROUND: Vertical closure of the pharynx after laryngectomy can result in an outpouch of the anterior wall of the neopharynx below the tongue base, called a pseudo-diverticulum. The prolapsed mucosa that separates the rest of the neopharynx from the pseudo-diverticulum is termed a pseudo-epiglottis. METHODS: Prospective study of patients with pseudo-epiglottis. M. D. Anderson Dysphagia Inventory (MDADI) scores were used to assess swallowing outcomes pre- and post-pseudo-epiglottis division, including minimally clinically important difference (MCID) assessment. RESULTS: Of 16 patients with a pseudo-epiglottis, 12 had dysphagia (75%). Symptomatic patients had significantly worse global MDADI and subscale scores. After division, the mean composite MDADI increased from 48.3 to 64.7 (p = 0.035), including a high MCID (16.4) with a similar improvement in the global question rating findings (31.1 vs. 60, p = 0.021). The MCID was significant for all MDADI subscales. CONCLUSIONS: Pseudo-epiglottis formation is associated with significantly worse global and subscale MDADI scores. A clinically- and statistically-significant improvement in the MDADI scores was found following surgical division.

Isolated vocal cord palsy secondary to a paraoesophageal hiatus hernia: a rare variant of Ortner's syndrome.

Dysphonia is a common presenting symptom to the outpatient ear, nose and throat team and the need to have a systematic approach to its investigation and management is imperative. Red flag features combined with clinical examination including flexible nasoendoscopy will help to identify laryngeal causes of dysphonia. Vocal cord palsy can have both laryngeal and extralaryngeal aetiologies including Ortner's syndrome. We present a case where a woman in her 70s was referred with persistent hoarseness, found to have an isolated vocal cord palsy with CT scan revealing a very large hiatus hernia producing mass effect at the aortopulmonary window with no other pathology identified. To our knowledge, this is the second case in the literature of a hiatus hernia causing a vocal cord palsy. This case underpins the need for prompt assessment by flexible laryngoscopy, and consideration of extralaryngeal causes of vocal cord palsy during a dysphonia assessment.

Antimalarial bromotyrosine derivatives from the Australian marine sponge Hyattella sp.

A drug discovery program aimed at identifying new antimalarial leads from a prefractionated natural product library has resulted in the identification of a new bromotyrosine alkaloid, psammaplysin G (1), along with the previously isolated compound, psammaplysin F (2). When tested against two different strains of the parasite Plasmodium falciparum (Dd2 and 3D7), 2 displayed IC(50) values of 1.4 and 0.87 microM, respectively, while 1 showed 98% inhibition at 40 microM against the chloroquine-resistant (Dd2) strain of P. falciparum.

Antimalarial benzylisoquinoline alkaloid from the rainforest tree Doryphora sassafras.

Mass-directed isolation of the CH(2)Cl(2)/MeOH extract of Doryphora sassafras resulted in the purification of a new benzylisoquinoline alkaloid, 1-(4-hydroxybenzyl)-6,7-methylenedioxy-2-methylisoquinolinium trifluoroacetate (1), and the known aporphine alkaloid (S)-isocorydine (2). The structures of 1 and 2 were determined by 1D and 2D NMR and MS data analyses. The compounds were isolated during a drug discovery program aimed at identifying new antimalarial leads from a prefractionated natural product library. When tested against two different strains of the parasite Plasmodium falciparum (3D7 and Dd2), 1 displayed IC(50) values of 3.0 and 4.4 microM, respectively. Compound 1 was tested for cytotoxicity toward a human embryonic kidney cell line (HEK293) and displayed no activity at 120 microM.

Clavatadines C-E, guanidine alkaloids from the Australian sponge Suberea clavata.

Three new marine alkaloids, clavatadines C-E (1-3), together with the three known compounds aerophobin 1 (4), purealdin L (5), and aplysinamisine II (6) were isolated from extracts of the sponge Suberea clavata by bioassay-guided fractionation using a serine protease factor XIa assay. Their structures were determined by 1D and 2D NMR spectroscopy. Compounds 1-6 exhibited weak inhibition of factor XIa.

Cystic schwannoma of the cervical plexus masquerading as a type II second branchial cleft cyst.

This case illustrates the rare occurrence of a cystic schwannoma of the neck, presenting clinically and ultrasonographically as a type II second branchial cleft cyst. Histology demonstrated that it was in fact a rare cystic schwannoma, most likely arising from the cervical plexus. This is the first documented case of a cystic schwannoma of the neck being mistaken for a type II second branchial cleft cyst based on clinical and ultrasound findings alone. It suggests that more sophisticated radiological investigations, such as magnetic resonance imaging, may enable accurate diagnosis of a cystic schwannoma of the neck pre-operatively.

Buccal space tumours.

OBJECTIVE: To review the available literature as it pertains to the buccal space with a specific focus on the pathologies encountered within this space. Clinical presentation, investigations, and surgical approaches to the region are also reviewed. METHODS: A systematic review of the available literature was performed on buccal space tumours from 1980 to 2017. Data was extracted on clinical presentation, investigations and surgical approaches to the buccal space. The pathologies encountered in the buccal space were reviewed and presented. RESULTS: Forty-nine unique articles were reviewed, with a total 217 patients. The age of the patients ranged from 0 to 83 with a mean age of 45.8. A total of 51 pathologies were reported. The majority of these were vascular and salivary gland pathologies. The majority of salivary gland neoplasms were malignant. However a wide variety of benign and malignant soft tissue tumours were also reported to occur in this region. CONCLUSIONS: The buccal space is a small and complex region with a variety of pathologies occurring within it. This review clarifies the differential diagnosis of a mass which presents in this area and the pathologies which occur within it.

Clavatadine A, a natural product with selective recognition and irreversible inhibition of factor XIa.

Bioassay-guided fractionation of a CH2Cl2/MeOH extract of the sponge Suberea clavata using the serine protease factor XIa to detect antithrombotic activity led to the isolation of the new marine natural products, clavatadines A and B. Clavatadines A and B inhibited factor XIa with IC50's of 1.3 and 27 microM, respectively. A crystal structure of protein-inhibitor (clavatadine A) complex was obtained and revealed interesting selective binding and irreversible inhibition of factor XIa. The cocrystal structure provides guidance for the design and synthesis of future factor XIa inhibitors as antithrombotic agents.

Benign papilloma on core biopsy requires surgical excision.

BACKGROUND: When a papillary lesion is identified on core biopsy of an impalpable breast lesion, standard practice involves excisional biopsy. Recent literature has questioned the need for surgical excision in patients with benign core biopsy and radiological concordance. Our aim was to assess whether surgical excision is required by targeting this concordant group in a large screen-detected population. METHODS: A retrospective review of a prospectively collected database of all benign papillary core biopsies between February 1995 and September 2007 at North Western Breast Screen and Monash Breast Screen in Melbourne, Australia was performed. All patients had surgical excision, enabling correlation between core and final excisional biopsy results on all lesions. All histology reports were reviewed and the radiology was reassessed. RESULTS: During a 14-year period, 5783 core biopsies were performed from 633,163 screening mammograms. Eighty patients (0.01%) had benign papilloma on core biopsy, no patients had atypia on core biopsy, and all patients had benign radiological features. Of the 80 patients, 15 patients were found to have ductal carcinoma in situ (8) or invasive ductal carcinoma (7) on final pathology, yielding a 19% malignant rate. CONCLUSION: Core biopsy showing benign papillary lesion, even where radiology is also suggestive of a benign process, cannot exclude malignancy, and therefore surgical excision is required.

Predictors of surgical margin status in breast-conserving surgery within a breast screening program.

BACKGROUND: Breast-conserving surgery (BCS) requires clear surgical margins to minimize local recurrence. We sought to identify groups of patients at higher risk of involved margins who might benefit from preoperative counselling and/or more generous excision at the first operation. METHODS: We reviewed demographic, clinical, radiological and pathological records of all women diagnosed with ductal carcinoma in situ (DCIS) or invasive cancer (IC) through a population-based breast screening program in Melbourne, Australia between 1994 and 2005. RESULTS: A total of 2,160 women were diagnosed with DCIS or IC. We excluded 199 who had mastectomy (TM) as initial procedure or had missing data. Three hundred and thirteen had a diagnostic biopsy. Of 1,648 women who had BCS after a preoperative diagnosis of DCIS or IC, 13.5% had involved margins, 16.6% had close (1 mm) margins. Of the patients, 281/1,648 (17.1%) underwent re-excision, of whom 93 (33.1%) had residual disease identified. Mammographic microcalcifications (P < 0.0001), absence of a mammographic mass (P = 0.002), presence of DCIS (P < 0.0001), high tumour grade (P < 0.0001), large size (P < 0.0001), multifocal disease (P < 0.0001) and lobular histology (P = 0.005) were associated with involved margins. Microcalcifications (odds ratio [OR] 1.97), large size (OR 4.22) and multifocal disease (OR 2.85) were independently associated with involved margins. Residual disease was associated with involved margins (P < 0.0001), presence of DCIS (P = 0.05) and large tumour size (P = 0.01). CONCLUSION: After BCS, patients with mammographic microcalcifications, larger tumour size and multifocal tumours are more likely to have involved margins. Patients with involved margins, large tumour size and/or a DCIS component are more likely to have residual disease on re-excision.

Small-molecule inhibitors of the cancer target, isoprenylcysteine carboxyl methyltransferase, from Hovea parvicalyx.

Isoprenylcysteine carboxyl methyltransferase (Icmt) is enzyme target in anticancer drug discovery. An Icmt natural product high-throughput screening campaign was conducted and a hit extract from the roots of Hovea parvicalyx was identified. 2'-Methoxy-3'-prenyl-licodione and 2'-methoxy-3',3''-diprenyl-licodione, two prenylated beta-hydroxychalcone compounds, together with the known flavanone (S)-glabrol, were isolated and identified as bioactive constituents. Their structures were determined largely by 1D and 2D NMR spectroscopy.

Lysianadioic acid, a carboxypeptidase B inhibitor from Lysiana subfalcata.

A new natural product, lysianadioic acid, was isolated from the plant Lysiana subfalcata as a carboxypeptidase B (CPB) inhibitor. It is a potent inhibitor of CPB with an IC(50) of 0.36 microM. This is the first known example of a small molecule CPB inhibitor isolated from plant origin. Its structure was determined by NMR spectroscopy.

Aplysamine 6, an alkaloidal inhibitor of Isoprenylcysteine carboxyl methyltransferase from the sponge Pseudoceratina sp.

The anticancer target isoprenylcysteine carboxyl methyltransferase (Icmt) was the focus of a natural product high-throughput screening campaign. The Australian marine sponge Pseudoceratina sp. yielded aplysamine 6, a new bromotyrosine derivative with an alpha,beta-unsaturated amide linkage, as the bioactive constituent. Its structure was determined by 1D and 2D NMR spectroscopy.

Retropharyngeal abscess after chemotherapy.

Chemotherapy increases susceptibility to infection due to the effect on cell-mediated and humoral immunity. Retropharyngeal abscess is a serious head and neck infection that rapidly progresses from toxicity, whether the patient is neutropenic or not. The risk should be carefully assessed with any chemotherapeutic agent, especially docetaxel.

Spermatinamine, the first natural product inhibitor of isoprenylcysteine carboxyl methyltransferase, a new cancer target.

Isoprenylcysteine methyltransferase (Icmt) catalyzes the carboxyl methylation of oncogenic proteins in the final step of a series of post-translational modifications. The inhibition of Icmt provides an attractive and novel anticancer target. A natural product high-throughput screening campaign was conducted to discover inhibitors of Icmt. The Australian marine sponge, Pseudoceratina sp., yielded spermatinamine, a novel alkaloid with a bromotyrosyl-spermine-bromotyrosyl sequence, as the bioactive constituent. Its structure was determined by 1D and 2D NMR spectroscopy. Spermatinamine is the first natural product inhibitor of Icmt.

Reliance on hormone receptor assays of surgical specimens may compromise outcome in patients with breast cancer.

PURPOSE: To assess the concordance of breast cancer immunohistochemical receptor assays on core biopsy and surgical specimens. PATIENTS AND METHODS: We identified 100 patients whose core biopsy and definitive surgical specimens were processed in our hospital. New sections, with core and surgical specimens on the same slides, were stained for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) immunohistochemistry (IHC). Two pathologists assessed the sections independently. Raw scores and clinically significant groupings were compared. RESULTS: Concordance for ER, PR, overall hormone receptor (HR), and HER-2 status was seen in 86%, 83%, 90%, and 80% of patients, respectively. The core was positive, while the surgical specimen was negative in 13%, 11%, 9%, and 1% of patients, respectively. Using a log-linear model, differences in ER, PR, and HER-2 staining were all in the direction of stronger staining in the cores, and were statistically significant. Nine percent (95% CI, 4.2% to 16.4%) of women in this group would have had endocrine therapy inappropriately withheld if management decisions were based on surgical specimen results alone. CONCLUSION: ER and PR assays on core biopsy specimens are more reliable than assays on surgical specimens. Receptor IHC should be performed on core biopsy specimens to avoid patients with HR positive cancers not receiving appropriate hormonal therapy and being overtreated with systemic chemotherapy. Biopsy should be considered in patients with "receptor negative" cancer and recurrent disease.