Drug Reaction with Eosinophilia and Systemic Symptoms and Agranulocytosis Presenting as Cervical Lymphadenopathy.

Objective: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare cause of cervical lymphadenopathy. It is a potentially life-threatening hypersensitivity reaction, commonly characterized by fever, rash, hematological abnormalities, and multi-organ involvement. Its association with agranulocytosis is even rarer, with fewer than 10 cases describing the coexistence of DRESS with agranulocytosis reported in the English literature. Case Summary: An otherwise well 40-year-old female presented with a sore throat and cervical lymphadenopathy, with investigations revealing DRESS and agranulocytosis secondary to carbamazepine. Conclusion: DRESS and agranulocytosis are serious, potentially life-threatening adverse drug reactions which can initially present as cervical lymphadenopathy. As carbamazepine is considered first-line therapy for certain chronic neuropathic conditions such as trigeminal neuralgia, clinicians should be aware of the varying clinical presentations of both conditions.

Neoadjuvant chemotherapy in locally advanced colon cancer: a systematic review and meta-analysis.

BACKGROUND: There is increasing evidence to support the use of neoadjuvant chemotherapy (NAC) in locally advanced colon cancer (LACC). However, its safety, efficacy and side effect profile is yet to be completely elucidated. This review aims to assess NAC regimens, duration, compare completion rates, intra-operative and post-operative complication profiles and oncological outcomes, in order to provide guidance for clinical practice and further research. METHODS: PubMed, EMBASE and MEDLINE were searched for a systematic review of the literature from 2000 to 2020. Eight eligible studies were included, with a total of 1213 patients, 752 (62%) of whom received NAC. Of the eight studies analysed, two were randomised controlled trials comparing neoadjuvant chemotherapy followed by oncological resection to upfront surgery and adjuvant chemotherapy, three were prospective single-arm phase II trials analysing neoadjuvant chemotherapy followed by surgery only, one was a retrospective study comparing neoadjuvant chemotherapy followed by surgery versus surgery first followed by adjuvant chemotherapy and the remaining two were single-arm retrospective studies of neoadjuvant chemotherapy followed by surgery. RESULTS: All cases of LACC were determined and staged by computed tomography; majority of the studies defined LACC as T3 with extramural depth of 5 mm or more, T4 and/or nodal positivity. NAC administered was either folinic acid, fluorouracil and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (XELOX) with the exception of one study which utilised 5-fluorouracil and mitomycin. Most studies had NAC completion rates of above 83% with two notable exceptions being Zhou et al. and The Colorectal Cancer Chemotherapy Study Group of Japan who both recorded a completion rate of 52%. Time to surgery from completion of NAC ranged on average from 16 to 31 days. The anastomotic leak rate in the NAC group ranged from 0 to 4.5%, with no cases of postoperative mortality. The R0 resection rate in the NAC group was 96.1%. Meta-analysis of both RCTs included in this study showed that neoadjuvant chemotherapy increased the likelihood of a negative resection margin T3/4 advanced colon cancer (pooled relative risk of 0.47 with a 95% confidence interval) with no increase in adverse consequence of anastomotic leak, wound infection or return to theatre. CONCLUSIONS: Our systematic review and meta-analysis show that NAC is safe with an acceptable side effect profile in the management of LACC. The current data supports an oncological benefit for tumour downstaging and increased in R0 resection rate.

Incidence and management of metabolic acidosis with sodium bicarbonate in the ICU: An international observational study.

BACKGROUND: Metabolic acidosis is a major complication of critical illness. However, its current epidemiology and its treatment with sodium bicarbonate given to correct metabolic acidosis in the ICU are poorly understood. METHOD: This was an international retrospective observational study in 18 ICUs in Australia, Japan, and Taiwan. Adult patients were consecutively screened, and those with early metabolic acidosis (pH < 7.3 and a Base Excess < -4 mEq/L, within 24-h of ICU admission) were included. Screening continued until 10 patients who received and 10 patients who did not receive sodium bicarbonate in the first 24 h (early bicarbonate therapy) were included at each site. The primary outcome was ICU mortality, and the association between sodium bicarbonate and the clinical outcomes were assessed using regression analysis with generalized linear mixed model. RESULTS: We screened 9437 patients. Of these, 1292 had early metabolic acidosis (14.0%). Early sodium bicarbonate was given to 18.0% (233/1292) of these patients. Dosing, physiological, and clinical outcome data were assessed in 360 patients. The median dose of sodium bicarbonate in the first 24 h was 110 mmol, which was not correlated with bodyweight or the severity of metabolic acidosis. Patients who received early sodium bicarbonate had higher APACHE III scores, lower pH, lower base excess, lower PaCO2, and a higher lactate and received higher doses of vasopressors. After adjusting for confounders, the early administration of sodium bicarbonate was associated with an adjusted odds ratio (aOR) of 0.85 (95% CI, 0.44 to 1.62) for ICU mortality. In patients with vasopressor dependency, early sodium bicarbonate was associated with higher mean arterial pressure at 6 h and an aOR of 0.52 (95% CI, 0.22 to 1.19) for ICU mortality. CONCLUSIONS: Early metabolic acidosis is common in critically ill patients. Early sodium bicarbonate is administered by clinicians to more severely ill patients but without correction for weight or acidosis severity. Bicarbonate therapy in acidotic vasopressor-dependent patients may be beneficial and warrants further investigation.

Risk of malignancy in incidental oropharyngeal lesions exhibiting fluorodeoxyglucose uptake which proceed to tissue biopsy.

BACKGROUND: Utilization of positron emission tomography/computed tomography (PET/CT) with fluorodeoxyglucose is increasing in use for a variety of indications, including surveillance of cancer patients. There is a paucity of evidence pertaining to the significance of incidental PET-avid oropharyngeal lesions. This study aims to examine the clinical and radiological features of these incidental oropharyngeal lesions in patients undergoing PET for indications other than head and neck cancer. METHODS: Retrospective cohort study of three Australian tertiary hospitals, from 2015 to 2021, on adult patients undergoing biopsy of incidental PET-avid oropharyngeal lesions. Primary outcome of interest was the incidence of malignancy. Patients with a previous history of, or undergoing investigations for, head and neck cancer were excluded. RESULTS: Thirty-one patients were included, wherein 21 patients had tonsillar uptake, and 13 patients had base of tongue uptake. Tonsillar disease was mostly asymmetrical (n = 15/21), bilateral (n = 11/21), and had median SUVmax 9.35 (n = 12, IQR 7.4-11.15). Base of tongue was mostly asymmetrical (n = 7/13, 54%), bilateral (n = 8/13, 62%), and had median SUVmax 8.2 (n = 10, IQR 6.9-12.65). Seven patients had malignancy confirmed on tissue biopsy: five biopsies confirmed the tissue diagnosis of suspected lymphoma, and two incidental findings of unexpected malignancies: one p16 positive tonsillar squamous cell carcinoma, and one metastatic breast cancer. CONCLUSION: In 31 patients undergoing tissue biopsy for incidental PET-avid oropharyngeal lesions, there were two unexpected malignancies. Our study results indicate that although unexpected malignancies are uncommon, a malignant diagnosis cannot be excluded from clinical features alone.

Molecular Factors in Carcinoma Ex Pleomorphic Adenoma: Systematic Review and Meta-Analysis.

OBJECTIVE: Carcinoma ex pleomorphic adenoma (CXPA) is a rare malignant salivary gland tumor. Although multiple reviews have been published on salivary gland malignancies, it has been a decade since the last dedicated systematic review pertaining to CXPA alone was published. This study examines molecular factors in CXPA diagnosis. DATA SOURCES: MEDLINE, CINAHL, Embase, Scopus, Web of Science (BIOSIS), Cochrane CENTRAL, Health Collection (Informit), OpenDOAR, and GreyNet International. REVIEW METHODS: Systematic review and meta-analysis from inception to October 31, 2022 for all English language studies pertaining to "carcinoma ex pleomorphic adenoma." Predicted incidence of each biomarker was calculated with meta-analysis. Comparison against pleomorphic adenoma (PA) and salivary duct carcinoma (SDC) when reported within the same study are performed. Risk of bias performed with JBI tool for prevalence studies. RESULTS: Of 19151 unique studies undergoing abstract screening, 55 studies (n = 1322 patients) underwent data analysis. Biomarkers with >3 studies were p53, HER2, AR, EGFR, PLAG1, ERBB, ER, PR, HMGA2, p16, p63, a-SMA, RAS, PTEN, PDL1, BRAF, PIK3CA, and c-kit. Highest incidence was seen in AR, EGFR, p16, and p53. Significant differences were demonstrated compared with PA and SDC. There was high heterogeneity and overall high risk of bias within studies. CONCLUSION: Molecular factors are an area of interest in the diagnosis of CXPA. Our study results support examining CXPA as a discrete cohort in future targeted therapy trials. Laryngoscope, 134:1042-1053, 2024.

Recent Levels of Evidence in Otolaryngology Journals.

OBJECTIVE: The development of evidence-based medicine has contributed to improved patient outcomes. This study aims to identify the trends in levels of evidence in otolaryngology journals over time, as represented by the 4 most widely circulated peer-reviewed otolaryngology journals. METHODS: A review of all articles from 2007, 2010, 2013, 2016, and 2019, in 4 major otolaryngology journals. Data points included journal source, year of publication, country of origin, first author sex, and subspecialty category within otolaryngology. Level of evidence was determined based on the study's primary research question and was graded on a scale of 1 (strongest) to 4 (weakest) based on the Oxford Centre of Evidence-based Medicine - Levels of Evidence guideline. Comparison of levels of evidence was performed using Kruskal-Wallis analysis of variance for ordinal data. RESULTS: About 4297 articles were identified over 12 years. The number of research articles remained consistent over the 12 years of this study. Clinical research increased from 78.6% to 85.1%. Female first authorship increased from 20.3% in 2007 to 31.0% in 2019. Of 3558 articles that constituted clinical research from 2007 to 2019, level 1 studies increased from 0.9% to 3.6%, with level 4 studies remaining stable at an overall rate of 60.3%. Randomized controlled trials remained stable at 4.6% of all studies. Systematic reviews increased from 3.2% to 8.4%. CONCLUSION: This article provides an update on the levels of evidence to allow for an honest self-assessment of otolaryngology as a scientific field.

Cost-minimisation analysis of polysomnography and pulse oximetry in a risk stratification protocol for paediatric adenotonsillectomy.

BACKGROUND: Severe obstructive sleep apnoea (OSA) is associated with increased risk of respiratory compromise in the post-operative period following adenotonsillectomy (AT). This study analyses the economic cost of polysomnography or overnight oximetry as part of pre-operative risk stratification in paediatric AT, supplementing previously published research demonstrating the efficacy of this protocol in predicting respiratory complications. METHODS: This cost-minimisation analysis examines costs associated with pre-operative overnight oximetry and polysomnography in triaging paediatric patients older than 2 years old, with no major comorbidities except for OSA, undergoing AT for OSA (n = 1801) to either a secondary or quaternary Australian hospital. Decision analysis modelling via probability trees were utilized to estimate pre- and peri-operative costs. A third hypothetical 'no investigation' model based upon conducting all AT at a secondary hospital was performed. Costs are derived from the financial year 2020-2021, censored at discharge. RESULTS: The total cost per patient of AT including pre-operative investigations of oximetry and polysomnography, and associated inpatient costs, were AUD4181.34 and 5013.99 respectively. This is more expensive compared to a hypothetical no-investigation model (AUD3958.98). CONCLUSION: Within the scope of this partial economic evaluation, this study finds a small additional cost for a model of care involving overnight oximetry as a pre-operative triage tool, balanced by the reduced cost of care in a lower acuity centre for low-risk patients and potential high cost of complications if all children are treated in a low acuity centre. This supports oximetry in peri-operative risk stratification for paediatric AT from a financial perspective.

Systematic review of prognostic factors in carcinoma ex pleomorphic adenoma.

OBJECTIVES: Carcinoma ex Pleomorphic Adenoma (CXPA) is a rare primary salivary gland malignancy, typically arising from a pre-existing pleomorphic adenoma. This systematic review examines prognostic factors affecting overall survival (OS) in major and minor salivary gland CXPA. MATERIALS AND METHODS: Systematic review of MEDLINE, Cochrane, Scopus, Web of Science, CINAHL, and Open Grey databases from inception to 31st March 2022 for all English-language literature pertaining to 'carcinoma ex pleomorphic adenoma'. All study types with greater than five patients with CXPA of the major and minor salivary glands were eligible for inclusion. RESULTS: Of 8143 studies, 39 studies (n = 5637 patients) meeting the inclusion criteria were included. Median OS at one, three, five, and ten years were 90.0 %, 72.0 %, 61.9 %, and 45.0 % respectively for all CXPA. Higher staging, T stage, nodal disease, grading, and invasion ≥ 1.5 mm had worse outcomes. Histological subtype, perineural invasion, and radiotherapy did not demonstrate a consistent trend. Three studies were evaluated to have high risk of bias, and was removed for sensitivity analysis. CONCLUSION: Survival outcomes worsen with time for all salivary gland CXPA. Further research on histopathological features and the utility of radiation therapy is required to guide patient selection for more aggressive treatment. REGISTRATION: CRD42021238544 (PROSPERO).

Surgeon-performed ultrasound changes surgical management in patients with thyroid cancer.

BACKGROUND: A comprehensive neck ultrasound (US) is essential in the operative planning of patients with thyroid disease. Recent literature has shown surgeon-performed US (SUS) can be more accurate than radiology-performed US for the purpose of surgical planning. Missed findings on radiology-performed ultrasound may lead to inadequate surgical management. METHODS: A retrospective cohort study of patients undergoing total thyroidectomy with lateral neck dissection for thyroid cancer, with both radiology-performed US and SUS performed by a Head and Neck surgeon. Ultrasound findings and adherence to American Thyroid Association (ATA) guidelines were compared, and changes in management based on SUS findings were identified. RESULTS: A total of 26 patients who underwent total thyroidectomy with lateral neck dissection met the inclusion criteria. Preconsultation US investigations fulfilled criteria as recommended by the American Thyroid Association (ATA) guidelines in 57.7%% of cases. The central and lateral neck compartments were assessed in 57.7% and 84.6% of preconsultation US investigations respectively. Central and lateral metastatic neck metastases were incorrectly reported or not reported in 78.6% and 42.3% of cases. The SUS findings prompted a change in surgical management in 65.4% of cases. CONCLUSION: SUS changed surgical management in two thirds (65.4%) of patients. Reliance on radiology-performed ultrasound alone may result in incorrect staging. Awareness of the additional benefits of SUS is important for surgeons treating patients with thyroid disease to prevent inadequate surgery being performed.

Systematic review and meta-analysis of cervical metastases in oral maxillary squamous cell carcinoma.

BACKGROUND: Management of the node-negative neck in oral maxillary squamous cell carcinoma (SCC), encompassing the hard palate and upper alveolar subsites of the oral cavity, is controversial, with no clear international consensus or recommendation regarding elective neck dissection in the absence of cervical metastases. AIM: To assess the occult metastatic rate in patients with clinically node negative oral maxillary SCC; both as an overall metastatic rate, and a comparison of patients managed with an elective neck dissection at index surgery, compared to excision of the primary with clinical observation of the neck. METHODS AND RESULTS: A systematic review was performed by two independent investigators for studies relating to oral maxillary SCC and analysed according to PRISMA criteria. Data were extracted from Pubmed, Ovid MEDLINE, EMBASE, and SCOPUS via relevant MeSH terms. Grey literature was searched through Google Scholar and OpenGrey. Five hundred and fifty-three articles were identified on the initial search, 483 unique articles underwent screening against eligibility criteria, and 29 studies were identified for final data extraction. Incidence of occult metastases in patients with clinically node negative oral maxillary SCC was identified either on primary elective neck dissection or on routine follow up. Meta-analyses were performed. Of 553 relevant articles identified on initial search, 29 were included for analysis. The pooled overall rate of occult metastases in patients initially presenting with clinically node-negative disease was 22.2%. There is a statistically significant effect of END on decreasing regional recurrence demonstrated in this study (RR 0.36, 95% CI 0.24, 0.59). CONCLUSION: The results of this systematic review and meta-analysis suggest elective neck dissection for patients presenting with hard palate or upper alveolar SCC, even in a clinically node negative neck.

Diagnostic Utility of Salivary Pepsin as Compared With 24-Hour Dual pH/Impedance Probe in Laryngopharyngeal Reflux.

OBJECTIVE: Laryngopharyngeal reflux (LPR) is defined as the retropulsion of gastric contents into the larynx, oropharynx, and/or nasopharynx. The 24-hour combined hypopharyngeal-esophageal multichannel intraluminal impedance with dual pH probe (24h-HEMII-pH) is currently the gold standard in LPR diagnosis; however, it is invasive, user dependent, and not always tolerated. This study assesses the diagnostic utility of salivary pepsin (Peptest) at different thresholds and during symptomatic periods as compared with the 24h-HEMII-pH probe in diagnosing LPR. STUDY DESIGN: Prospective cohort study. SETTING: Private laryngology clinic in Melbourne, Australia. SUBJECTS AND METHODS: Thirty-five patients with a clinical history and endoscopic findings of LPR were recruited and simultaneously evaluated for LPR via 24h-HEMII-pH probe and salivary pepsin analysis at 5 key time points over the same 24-hour period. RESULTS: Salivary pepsin was 76.9% sensitive and had a positive predictive value (PPV) of 87.0% at a threshold of 16 ng/mL when compared with the 24h-HEMII-pH probe. If the pathologic pepsin threshold was raised to 75 ng/mL, salivary pepsin had a sensitivity of 57.7%, a specificity of 75.0%, and a PPV of 93.8%. Symptomatic testing conferred a superior specificity at 16 ng/mL (66.7%) and 75 ng/mL (100.0%) and a superior PPV at 16 ng/mL (92.3%) and 75 ng/mL (100.0%). CONCLUSION: Salivary pepsin detection is a simpler, more cost-effective, and less traumatic universal first-line alternative to 24h-HEMII-pH probe in diagnosing LPR. Superior specificities conferring greater diagnostic value may be achieved with higher thresholds and symptomatic testing. If clinical suspicion remains high following negative salivary pepsin analysis, a 24h-HEMII-pH study could provide further diagnostic information.

Prostate cancer recurrence presenting as an isolated small bowel tumour.

Prostate cancer is the most commonly diagnosed cancer in males and third most common cause of cancer deaths in Australia. With improved survival rates and increasing reports of metastatic disease, we can expect to see more interesting and unusual presentations of recurrent disease. We present the case of a 66-year-old male with a prostate cancer recurrence to small bowel after curative treatment. We present this case to raise clinical suspicion in the medical fraternity regarding cancer recurrence; Even in the absence of biochemical markers or typical clinical signs and symptoms.