In a world in which charitable activities are increasingly crossing national borders, the Australian Government has had to reconsider its regulation of cross-border charity. Recent developments have ...resulted in a number of proposed regulatory reforms and a new tax ruling directly impacting Australian charities operating overseas. This article evaluates the government's existing and proposed measures to regulate Australian cross-border charity in a changing global landscape. In doing so, it examines whether the promised reforms will enable the government to fulfil its policy goals of reducing the administrative complexity for Australian charities operating overseas and safeguarding their charitable assets, while ensuring that public trust and confidence in these charities is preserved.
53 mutations are highly prevalent in head and neck squamous cell carcinoma (HNSCC) and associated with increased resistance to conventional treatment primarily consisting of chemotherapy and ...radiation. Restoration of wild-type p53 function in
53-mutant cancer cells represents an attractive therapeutic approach and has been explored in recent years. In this study, the efficacy of a putative p53 reactivator called COTI-2 was evaluated in HNSCC cell lines with different
53 status.
Clonogenic survival assays and an orthotopic mouse model of oral cancer were used to examine
and
sensitivity of HNSCC cell lines with either wild-type, null, or mutant
53 to COTI-2 alone, and in combination with cisplatin and/or radiation. Western blotting, cell cycle, live-cell imaging, RNA sequencing, reverse-phase protein array, chromatin immunoprecipitation, and apoptosis analyses were performed to dissect molecular mechanisms.
COTI-2 decreased clonogenic survival of HNSCC cells and potentiated response to cisplatin and/or radiation
and
irrespective of
53 status. Mechanistically, COTI-2 normalized wild-type p53 target gene expression and restored DNA-binding properties to the p53-mutant protein in HNSCC. In addition, COTI-2 induced DNA damage and replication stress responses leading to apoptosis and/or senescence. Furthermore, COTI-2 lead to activation of AMPK and inhibition of the mTOR pathways
in HNSCC cells.
COTI-2 inhibits tumor growth
and
in HNSCC likely through p53-dependent and p53-independent mechanisms. Combination of COTI-2 with cisplatin or radiation may be highly relevant in treating patients with HNSCC harboring
53 mutations.
Syphilis is an infectious disease caused by the spirochete Treponema pallidum. Rates have been rising in the US and globally. Known as the “Great Imitator,” syphilis can involve head and neck ...subsites, and often can masquerade as possible carcinoma of the head and neck. Here, we present three distinct cases of syphilis presenting as suspected head and neck malignancy involving the oropharynx, larynx and oral cavity. All cases were diagnosed on surgical pathologic examination of diseased tissues and treated. It is important for practicing otolaryngologists to understand head and neck manifestations of syphilis to facilitate proper diagnosis and treatment. Laryngoscope, 134:236–239, 2024
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
An ageing population combined with decades of economic growth has correlated with a rise in inheritance disputes. While many of these disputes involve wills, non-probate instruments known as ‘will ...substitutes’ that operate during the donor’s lifetime but also transfer specific assets upon death are playing a significant role.To date,the academic literature has not adequately addressed how undue influence claims against will substitutes have been, or should be, resolved. Our case survey reveals two distinct doctrinal approaches taken by the English courts to resolve these claims. The first approach treats will substitutes as estate-planning instruments on par with wills; the second focuses on the lifetime operations of will substitutes.We argue that the first ‘testamentary’ approach is preferred to the second ‘lifetime’ approach. The testamentary approach not only better promotes testamentary intent and respects relational norms, it also decreases the risk of discrimination and paternalism against elderly people.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Background
Patients with locoregionally advanced oral cavity squamous cell carcinoma (OCSCC) have a poor survival outcome. Treatment involves extensive surgery, adjuvant radiation, or chemoradiation ...and results in high morbidity. In this study, the authors' objective was to evaluate their experience with induction chemotherapy (IC) in the treatment of locoregionally advanced OCSCC.
Methods
A retrospective review of the medical records of all patients with locoregionally advanced (stage III and IV) OCSCC who received IC followed by definitive local therapy was conducted. Outcomes included response to IC and survival.
Results
In total, 120 patients were included in the study. The overall stage was stage IV in 79.2% of patients. After 2 cycles of IC, 76 patients (63.3%) achieved at least a partial response, including 13 who had a complete response. Stable disease was observed in 30 patients (25%), and 14 patients (11.7%) had progressive disease. Among responders, 16 patients received definitive chemoradiation or radiation therapy, and 60 underwent surgical resection, of whom 15 had less extensive surgery than was originally planned. Overall, organ preservation was achieved in 40.8% of patients who had a favorable response to IC. The 5‐year overall and disease‐specific survival rates were 51.4% and 66.9%, respectively. Patients who had at least a partial response had better 5‐year overall survival (60.1%) and disease‐specific survival (78.5%) compared with nonresponders (33.8% and 46.4%, respectively).
Conclusions
The results demonstrate a response rate to IC in patients with advanced OCSCC similar to what has been observed in patients with cancer in other head and neck subsites. Patients who achieved at least a partial response to IC had a more favorable outcome, with ensuing organ preservation. Further studies are warranted.
In this study, patients with advanced oral cavity squamous cell carcinoma demonstrate a response rate to induction chemotherapy similar to that observed in patients with cancer in other head and neck subsites. Those who achieve at least a partial response to induction chemotherapy have a more favorable outcome, with ensuing organ preservation, and further studies are warranted.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Although the majority of patients with HPV(+) oropharyngeal cancers have a favorable prognosis, there are some patients with tumors that are resistant to aggressive chemoradiotherapy with unusual ...patterns of locoregional and systemic recurrences. Therefore, more effective therapies are needed. In this study, we investigated the chemosensitizing efficacy of the selective Wee-1 kinase inhibitor, AZD-1775, in HPV(+) head and neck squamous cell carcinoma (HNSCC).
Clonogenic survival assays and an orthotopic mouse model of HPV(+) oral cancer were used to examine the in vitro and in vivo sensitivity of HPV(+) HNSCC cell lines to AZD-1775 in combination with cisplatin, respectively. Cell-cycle analysis, DNA damage (γH2AX), homologous recombination (HR), and apoptosis were examined to dissect molecular mechanisms.
We found that AZD-1775 displays single-agent activity and enhances the response of HPV(+) HNSCC cells to cisplatin both in vitro and in vivo. The sensitivity of the HPV(+) HNSCC cells to AZD-1775 alone or in combination with cisplatin was associated with G2 checkpoint abrogation, persistent DNA damage, and apoptosis induction. This finding of AZD-1775 increasing the sensitivity of HPV(+) HNSCC cells to cisplatin through apoptosis was not seen previously in the HPV(-) HNSCC cancer cells and is accompanied by a decreased expression of the antiapoptotic proteins, MCl-1and XIAP, which appear to be cleaved following AZD-1775 treatment.
AZD-1775 selectively sensitizes HPV(+) HNSCC cells and orthotopic oral xenografts to cisplatin through apoptosis and support the clinical investigation of AZD-1775 in combination with cisplatin particularly in patients with advanced and recurrent metastatic HPV(+) HNSCC tumors.
Lymph node metastases from oral cavity cancers are seen frequently, and there is still inconsistency, and occasional controversies, regarding the surgical management of the neck in patients with oral ...cancer. This review is intended to offer a surgically focused discussion of the current recommendations regarding management of the neck, focusing on the indications and extent of dissection required in patients with oral cavity squamous cell carcinoma while balancing surgical risk and oncologic outcome.
The surgical management of the neck for oral cavity cancer has been robustly studied, as evidenced by substantial existing literature surrounding the topic. Prior published investigations have provided a sound foundation on which data-driven treatment algorithms can generally be recommended.
Existing literature suggests that patients with oral cavity cancer should be fully staged preoperatively, and most patients should receive a neck dissection even when clinically N0. Quality standards supported by the literature include separation of each level during specimen handling and lymph node yield of 18 or more nodes. Sentinel lymph node biopsy can be considered in select tumors and within a well-trained multidisciplinary team.
Primary fit tracheoesophageal puncture (TEP) is widely preferred for individuals who have not undergone prior radiation. However, there is no consensus on the relative utility of primary-fit TEP in ...the setting of salvage laryngectomy.
A retrospective, single-center review was conducted of individuals undergoing laryngectomy with primary fit TEP between 2012 and 2018. Multivariable analysis was conducted to compare short-term and long-term complications, as well as speech and swallowing outcomes, of those who underwent primary versus salvage laryngectomy.
In this study, 134 patients underwent total laryngectomy with primary fit TEP. Aside from a higher rate of peristomal dehiscence (13.1% vs. 1.4%) found in the salvage group, there was no difference in incidence of all other complications, including pharyngocutaneous fistula formation. The groups had comparable speech and swallow outcomes.
Primary fit TEP is a safe and effective surgical choice for individuals undergoing salvage laryngectomy who desire a voice prosthesis.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Disparate clinical outcomes for pharyngeal squamous cell carcinoma (PSCC) of the oropharynx (OPSCC) and hypopharynx (HPSCC) have been observed in Black compared with White patients. Higher tobacco ...and alcohol use has been associated with decreased survival in Black patients with PSCC. Higher human papilloma virus (HPV) infection rates, associated with specific subsites of the oropharynx, are linked to improved overall survival (OS). Using an institutional cohort of Black and White patients with PSCC, we performed a retrospective analysis using multiple disease endpoints including local control (LC), local–regional control (LRC), freedom from distant metastases (DMFS), OS, cause-specific survival (CSS), and recorded tobacco and alcohol use. 1419 patients Black (
n
= 111) and White (
n
= 1,308) treated for PSCC from 1973 to 2013 were evaluated. PSCC 5- and 10-year LC, LRC, and DMFS and CSS rates were lower for Blacks. Notably, Black patients with OPSCC had higher stage cancers, higher percentage of soft palate tumors, and lower percentage of base of tongue cancers, were more likely to receive radiotherapy, and had higher tobacco and alcohol use. OS was significantly lower in Black patients at both anatomic sites, with the greatest difference observed for OPSCC. Multivariate analysis showed race and tobacco independently predicted DMFS, OS, and CSS; however, tobacco use had a greater impact on DMFS (HR 2.5,
p
= 0.021) than race (HR 1.9,
p
= 0.027). Overall, we propose that the higher burden of tobacco use along with a lower rate of tumors arising from traditional HPV-related subsites were important contributors to disparate disease outcomes seen in our Black patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
To direct interventions, the Florida counties with the greatest risk of current and future human papillomavirus‒associated cancers were identified by estimating county-level (1) percentages of ...adolescents aged 13–17 years who initiated (≥1 dose) and were up to date (2–3 doses) for the human papillomavirus vaccine and (2) human papillomavirus‒associated cancer incidence rates.
Records were obtained for human papillomavirus vaccinations from the Florida immunization registry (2006–2019), incident cancer cases from the Florida registry (2013–2017), and annual population counts from the Florida Department of Health (2006–2019). In 2020, annual county-level human papillomavirus vaccine initiation, human papillomavirus vaccine up-to-date, and age-adjusted human papillomavirus‒associated cancer incidence rates were estimated.
Among adolescents aged 13–17 years, average 2018–2019 county-specific human papillomavirus vaccine initiation ranged from 38% to 100% for females and from 34% to 96% for males. Up-to-date estimates ranged from 20% to 72% for females and from 24% to 77% for males. The majority (78%) of counties with initiation and up-to-date estimates within the lowest tercile were located in Northern Florida. County-specific 2013–2017 annualized, adjusted human papillomavirus‒associated cancer incidence rates ranged from 0 to 29.8 per 100,000 among females and from 5.4 to 24.1 per 100,000 among males. Counties within the highest tercile for human papillomavirus‒associated cancers were primarily (90% for females and 77% for males) located in Northern Florida.
Human papillomavirus‒associated cancer risk varies widely across Florida counties, with particularly high risk within Northern Florida. Targeting interventions toward counties with low vaccination and high cancer rates may reduce human papillomavirus‒associated cancers.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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