Invasive lobular carcinoma of the breast; clinicopathologic profile and response to neoadjuvant chemotherapy over a 15-year period.

INTRODUCTION: Invasive lobular carcinoma (ILC) accounts for 5-15% of invasive breast cancers. Typical ILC is oestrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) negative. Atypical biomarker profiles (ER- and HER2+, ER+ and HER2+ or triple negative) appear to differ from typical ILCs. This study compared subtypes of ILC in terms of clinical and pathological parameters, and response to neoadjuvant chemotherapy (NACT) according to biomarker profile. METHODS: All patients with ILC treated in a single centre from January 2005 to December 2020 were identified from a prospectively maintained database. Clinicopathologic and outcome data was collected and analysed according to tumour biomarker profile. RESULTS: A total of 582 patients with ILC were treated. Typical ILC was observed in 89.2% (n = 519) and atypical in 10.8% (n = 63). Atypical ILCs were of a higher grade (35% grade 3 vs 9.6% grade 3, p < 0.001). A larger proportion of atypical ILC received NACT (31.7% vs 6.9% p < 0.001). Atypical ILCs showed a greater response to NACT (mean RCB (Residual Cancer Burden Score) 2.46 vs mean RCB 3.41, p = 0.0365), and higher pathological complete response rates (15% vs 0% p = 0.017). Despite this, overall 5-year disease-free survival (DFS) was higher in patients with typical ILC (91% vs 83%, p = 0.001). CONCLUSIONS: Atypical ILCs have distinct characteristics. They are more frequently of a higher grade and demonstrate a superior response to NACT. Despite the latter, atypical ILCs have a worse 5-year DFS which should be taken into consideration in terms of prognostication and may assist patient selection for NACT.

Case of metastatic clear cell odontogenic carcinoma with response to chemoimmunotherapy.

Our patient initially presented with 6 months of left jaw pain and gingival bleeding, leading to the discovery of a radiolucent left maxillary mass on dental evaluation. A biopsy confirmed clear cell odontogenic carcinoma, and the patient was treated with definitive surgery and radiation for localised disease. Unfortunately, the patient was found to have pulmonary metastases 3 months after initial management and was subsequently treated with a combination of cytotoxic chemotherapy and immunotherapy with a partial response. To our knowledge, this is the first case demonstrating the successful use of chemoimmunotherapy in metastatic clear cell odontogenic carcinoma.

The Impact of a Pandemic on a Military Oral and Maxillofacial Pathology Biopsy Service.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) and the resulting societal reaction presented new challenges to the medical community by limiting patient access to care in 2020 and 2021. The Navy Postgraduate Dental School (NPDS) oral and maxillofacial pathology biopsy service is dependent on in-office physician or dentist appointments and patient biopsies. The purpose of this study was to understand the regulatory and societal impacts of COVID-19 restrictions on biopsy service submissions by assessing NPDS biopsy submission quantities and disease distribution. MATERIALS AND METHODS: All NPDS oral and maxillofacial pathology biopsy submissions from calendar years 2015 to 2016 and 2019 to 2021 were evaluated, and patient demographics and biopsy diagnoses were recorded in a biopsy registry. Data collected included age, sex, biopsy site, and diagnosis. Data from 2015, 2016, and 2019 were defined as pre-COVID and 2020 and 2021 as COVID. Biopsy reports for each year were organized in quarters. Diagnoses were categorized as malignant, pre-malignant, or benign. Categorical and continuous data were evaluated and presented as counts with percentages and means or medians with standard deviations, respectively. Significant differences in proportions or means were assessed using chi-square analysis or Student t-test, respectively. Cases were aggregated by quarter and year and assessed for temporal trends using linear regression analysis. RESULTS: The study evaluated 9,351 biopsy submission reports. The annual pre-COVID count mean (± standard deviation) and yearly counts for 2020 and 2021 were 2,063 ± 33.3, 1,421, and 1,742, respectively. The mean (± standard deviation) percentage of diagnoses classified as malignant from pre-COVID, 2020, and 2021 were 2.46 ± 0.005%, 3.59%, and 3.04%, respectively. Case counts and representation as a percentage of all biopsy diagnoses for Human Papillomavirus (HPV)-associated squamous cell carcinoma increased significantly during COVID compared to pre-COVID years (P < .05). CONCLUSIONS: Overall, preventative COVID-19 health measures and protocols resulted in a reduction in biopsy submission frequency, particularly during the second quarter (April to June) of 2020. However, case counts for malignant biopsies remained consistent between pre-COVID and COVID time intervals, suggesting that the identification and analysis of cases requiring follow-on care were unaffected by COVID-19 protocols.

A bridge to recovery: Acute amantadine prior to environmental enrichment after brain trauma augments cognitive benefit.

Environmental enrichment (EE) facilitates motor and cognitive recovery after traumatic brain injury (TBI). Historically, EE has been provided immediately and continuously after TBI, but this paradigm does not model the clinic where rehabilitation is typically not initiated until after critical care. Yet, treating TBI early may facilitate recovery. Hence, we sought to provide amantadine (AMT) as a bridge therapy before commencing EE. It was hypothesized that bridging EE with AMT would augment motor and cognitive benefits. Anesthetized adult male rats received a cortical impact (2.8 mm deformation at 4 m/s) or sham surgery and then were housed in standard (STD) conditions where they received intraperitoneal AMT (10 mg/kg or 20 mg/kg) or saline vehicle (VEH; 1 mL/kg) beginning 24 h after surgery and once daily during the 6-day bridge phase or once daily for 19 days for the non-bridge groups (i.e., continuously STD-housed) to compare the effects of acute AMT plus EE vs. chronic AMT alone. Abbreviated EE, which was presented to closer emulate clinical rehabilitation (e.g., 6 h/day), began on day 7 for the AMT bridge and chronic EE groups. Motor (beam-walking) and cognition (acquisition of spatial learning and memory) were assessed on days 7-11 and 14-19, respectively. Cortical lesion volume and hippocampal cell survival were quantified on day 21. EE, whether provided in combination with VEH or AMT, and AMT (20 mg/kg) + STD, benefitted motor and cognition vs. the STD-housed VEH and AMT (10 mg/kg) groups (p < 0.05). The AMT (20 mg/kg) + EE group performed better than the VEH + EE, AMT (10 mg/kg) + EE, and AMT (20 mg/kg) + STD groups in the acquisition of spatial learning (p < 0.05) but did not differ in motor function (p > 0.05). All groups receiving EE exhibited decreased cortical lesion volumes and increased CA3 neuron survival relative to the STD-housed groups (p < 0.05) but did not differ from one another (p > 0.05). The added cognitive benefit achieved by bridging EE with AMT (20 mg/kg) supports the hypothesis that the temporal separation of combinational therapies is more effective after TBI.

The dilemma of Pituri: a review and case report.

Smokeless tobacco is the term used to describe a range of products found worldwide which individuals use to extract nicotine, but without smoking. Ways of achieving this include chewing, sniffing and placing in areas of the body where tissues are sufficiently thin for absorption to take place such as the oral mucosa or postauricular skin. In Central Australia, Aboriginal groups across a wide area have chewed wild tobacco plants, commonly known as Pituri, for countless generations. As well as inducing a sense of well-being, the habit has strong cultural significance. While some smokeless tobacco products used outside Australia are known to have a detrimental effect on oral health, particularly malignant change, little is known about Pituri. To date, reports of adverse oral outcomes have been elusive. Most Pituri research seems to have focussed on obstetric issues, arguably unexpected as the tobacco seems to be in contact with the mouth for longer than any other body tissues. The following report describes a lesion on the anterior buccal mucosa resulting from prolonged Pituri use. The relevant literature is reviewed. A clinical and ethical management dilemma arises between respecting the associated cultural issues and ignoring an apparent pathological entity. © 2022 Australian Dental Association.

A Rare Case of Monomorphic T-Cell Posttransplant Lymphoproliferative Disorder Presenting as Primary Cutaneous Anaplastic Large Cell Lymphoma, ALK Negative.

ABSTRACT: Posttransplant lymphoproliferative disorders are a serious complication of hematopoietic and solid organ transplants secondary to iatrogenic immunosuppression. Most cases present as B-cell proliferations which are often Epstein-Barr virus positive; however, ∼10% of cases are T/NK cell and are less commonly associated with Epstein-Barr virus. Of these, cutaneous T/NK-cell lymphomas are exceedingly rare. We report a case of a 69-year-old male, liver transplant recipient who presented with a tender, bright red papule on the left arm during his annual skin cancer screening. Histopathologic evaluation revealed pleomorphic cells with enlarged nuclei, vesicular chromatin, and frequent mitotic figures, intercalating through the dermis. The tumor formed single strands and small cords without epidermal involvement. A patchy mild mixed inflammatory infiltrate was associated with the tumor. Tumor cells were CD2(+), CD4(+), CD30(+), CD3(-), CD20(-), ALK-1(-), and EBER(-). Molecular studies revealed a monoclonal T-cell receptor gamma gene rearrangement by polymerase chain reaction (PCR); ALK gene rearrangement was negative by fluorescence in situ hybridization (FISH). Taken together, the findings were consistent with an ALK-negative anaplastic large cell lymphoma involving skin, which, given the history of liver transplant, qualified as a monomorphic T-cell posttransplant lymphoproliferative disorder. Follow-up imaging studies showed no evidence of systemic disease, supporting an interpretation of primary cutaneous anaplastic large cell lymphoma.

Utility of Cone-Beam CT for Bronchial Artery Embolization and Chemoinfusion: A Single-Institution Retrospective Case Series.

PURPOSE: To describe the technique and document utility of adjunctive cone-beam CT (CBCT) in patients undergoing bronchial artery embolization (BAE) or chemoinfusion (BAC). MATERIALS AND METHODS: Between August 2010 and February 2021, 26 patients (62 bronchial arteries) were evaluated with CBCT in addition to the usual digital subtraction angiography (DSA) during BAE or BAC. 19 patients (43 arteries) underwent BAE for hemoptysis; 7 patients (19 arteries) had BAC for palliation of lung malignancy. Retrospective review of procedural reports and the archived DSA and CBCT images was assessed for (1) whether CBCT findings added unique diagnostic information prior to treatment of target arteries compared to DSA alone; and (2) whether these unique CBCT findings led to modification of embolization or chemoinfusion technique. RESULTS: In 61 of 62 (98%) interrogated bronchial arteries, CBCT provided additional unique diagnostic information over planar DSA, primarily cross-sectional assessment of the spinal canal for spinal arteries. In 46/62 (74%) of the bronchial arteries the unique information did not lead to a change in therapeutic technique. In 15 bronchial arteries (24%), the added information from CBCT led to change in embolization and/or chemoinfusion technique. Embolization of one small unrecognized spinal artery branch (1.6%), which was missed intra-procedurally but retrospectively seen on CBCT led to transient spinal cord ischemia. CONCLUSIONS: These results suggest that adjunctive use of CBCT technique may improve diagnostic confidence from information provided by DSA in nearly all cases of BAE and BAC leading to improved therapeutic targeting or change in technique of embolization or chemoinfusion.

Risk-Based Screening Tools to Optimise HIV Testing Services: a Systematic Review.

PURPOSE OF REVIEW: Effective ways to diagnose the remaining people living with HIV who do not know their status are a global priority. We reviewed the use of risk-based tools, a set of criteria to identify individuals who would not otherwise be tested (screen in) or excluded people from testing (screen out). RECENT FINDINGS: Recent studies suggest that there may be value in risk-based tools to improve testing efficiency (i.e. identifying those who need to be tested). However, there has not been any systematic reviews to synthesize these studies. We identified 18,238 citations, and 71 were included. The risk-based tools identified were most commonly from high-income (51%) and low HIV (<5%) prevalence countries (73%). The majority were for "screening in" (70%), with the highest performance tools related to identifying MSM with acute HIV. Screening in tools may be helpful in settings where it is not feasible or recommended to offer testing routinely. Caution is needed for screening out tools, where there is a trade-off between reducing costs of testing with missing cases of people living with HIV.

Real-world analysis of clinical and economic impact of 21-gene recurrence score (RS) testing in early-stage breast cancer (ESBC) in Ireland.

PURPOSE: Results from TAILOR-X suggest that up to 70% of hormone receptor-positive (HR+) node-negative (N0) ESBC patients (pts) may avoid chemotherapy (CT) with RS ≤ 25. We assess clinical and economic impacts of RS testing on treatment using real-world data. METHODS: From October 2011 to February 2019, a retrospective, cross-sectional observational study was conducted of HR+ N0 ESBC pts who had RS testing in Ireland. Pts were classified low risk (RS ≤ 25) and high risk (RS > 25). Clinical risk was calculated. Data were collected via electronic patient records. Cost data were supplied by the National Healthcare Pricing Regulatory Authority. RESULTS: 963 pts. Mean age is 56 years. Mean tumour size is 1.7 cm. 114 (11.8%), 635 (66%), 211 (22%), 3 (0.2%) pts had G1, G2, G3 and unknown G, respectively. 796 pts (82.8%) low RS, 159 (16.5%) high RS and 8 pts (0.7%) unknown RS. 263 pts (26%) were aged ≤ 50 at diagnosis; 117 (45%) had RS 0-15, 63 (24.5%) 16-20, 39 (15.3%) 21-25 and 40 (15.2%) RS 26-100. 4 pts (1.5%) had unknown RS. Post-RS testing, 602 pts (62.5%) had a change in CT decision; 593 changed to hormone therapy (HT) alone. In total, 262 pts received CT. Of pts receiving CT; 138 (53%) had RS > 25, 124 (47%) had RS ≤ 25. Of pts aged ≤ 50, 153 (58%) had high clinical risk, of whom 28 had RS 16-20. Assay use achieved a 62.5% change in treatment with 73% of pts avoiding CT. This resulted in savings of €4 million in treatment costs. Deducting assay costs, savings of €1.9 million were achieved. CONCLUSION: Over the 8 years of the study, a 62.5% reduction in CT use was achieved with savings of over €1,900,000.

Implications of Calcification in Peyronie's Disease, A Review of the Literature.

A common characteristic of Peyronie's Disease (PD) is plaque calcification, which is associated with decreased response to treatments and higher rates of surgical intervention. Despite its prevalence in the PD population, the literature on plaque calcification is limited. While the diagnosis of PD is mostly clinical, imaging modalities such as ultrasound can be used to identify plaque calcification. The proper identification of plaque calcification is crucial for guiding management and setting therapeutic expectations for patients with PD. Herein we discuss what is known about PD plaque calcification, including epidemiology, etiology, diagnosis, and management.

Alternative metrics for assessing clinical benefit with immunotherapy in oncology.

Therapies for cancer have traditionally been assessed with metrics such as the response rate, hazard ratio, or median survival. Such metrics have value in measuring the outcomes of conventional therapies, but may not be the most appropriate for new therapies. Immuno-oncology therapies offer a new approach to treating cancer by stimulating patients' immune systems to fight cancer. The value of these novel therapies has so far been assessed with traditional metrics, but the different ways in which immuno-oncology therapies work can mean the full value is not captured. Immuno-oncology therapies can produce longer survival times but this effect can be delayed or even preceded by an apparent phase of progression, which median survival or response rates may not reflect. This paper discusses a range of traditional and alternative metrics and their benefits or disadvantages in measuring the effects of immuno-oncology therapies, using examples of several novel drugs as case studies.

The approach to an isolated close anterior margin in breast conserving surgery.

INTRODUCTION: Although close radial margins after breast-conserving surgery routinely undergo re-excision, appropriate management of patients with close anterior margins remains a topic of controversy. An increasing body of literature suggests that re-excision of close anterior margins yields low rates of residual malignancy and may only be necessary in selected patients. The aim of this study was to examine the management of close anterior margins after breast conserving surgery in a single institution and to analyse the rate of residual disease in re-excised anterior margins. METHODS: All patients having breast conserving surgery at St Vincent's University Hospital from January 2008 to December 2012 were reviewed retrospectively. Data collected included patient demographics, tumour characteristics, margin positivity, re-excision rates and definitive histology of the re-excision specimens. A close margin was defined as les than 2 mm. RESULTS: A total of 930 patients were included with an average age of 65 years (range 29-94 years). Of these, 121 (13%) had a close anterior margin. Further re-excison of the anterior margin was carried out in 37 patients (30.6%) and a further 16 (13.2%) proceeded to mastectomy. Residual disease was found in 18.5% (7/36) of those who underwent re-excision and 7/16 (43.75%) of those who underwent mastectomy. Overall, 11.57% (14/121) of patients with close anterior margins were subsequently found to have residual disease. CONCLUSION: The low yield of residual disease in re-excised anterior margins specimens supports the concept that routine re-excision of close anterior margins is not necessary. Further research is required to definitively assess its influence on the risk of local recurrence.

Ergonomics in the Development and Prevention of Musculoskeletal Injury in Interventional Radiologists.

Interventional radiology is a constantly evolving specialty overlapping with multiple other specialties, including cardiology, vascular surgery, orthopedic surgery, urology, and minimally invasive surgery. Unique ergonomic considerations for interventional radiology include utilization of intraoperative viewing monitors and personal radiation protection equipment. Work-related injuries are common in interventional radiologists,1 often leading to pain while performing procedures or during time away from work. This review article aims to identify the ergonomic challenges related to interventional radiology and provide background, guidelines, and specific recommendations for prevention of musculoskeletal injury.

Prognostic impact of macrometastasis linear size in sentinel node biopsy for breast carcinoma.

AIM: The aim of the present study was to evaluate the risk of axillary non-sentinel lymph-node metastases (ALN) in breast cancer patients presenting macrometastasis (Mac-m) in the sentinel lymph node (SN). MATERIALS AND METHODS: A retrospective series of 1464 breast cancers from patients who underwent ALN dissection following the diagnosis of Mac-m in the sentinel node (SN) was studied. In all the cases the MAC-m linear size was evaluated and correlated with presence or absence of non-SN ALN metastases. RESULTS: Non-SN metastases were detected in 644∖1464 cases (43.98%). The risk of further axillary metastases ranged from 20.2% (37/183) in cases with Mac-m between 2 and 2.9 mm, to 65.3% (262/401) in cases with Mac-m measuring > 10 mm. The risk of non-SN ALN metastases showed a 3% increase, parallel to each mm increment in SN metastasis size. The data evaluated with the receiver operating characteristic (ROC) curve showed that the Mac-m could be subdivided according to a new cut-off of 7 mm. pT1 tumours, with Mac-m < 7 mm had a risk of non-SN ALN metastases of <30%. Furthermore 109/127 of these (85.8%) had 3 or less non-SN ALN -metastases. CONCLUSIONS: The present data give a detailed description on the risk of non-SN ALN involvement, that may be useful in the evaluation of breast cancer patients. It is suggested that a Mac-m size of <7 mm is related to a low residual axillary disease burden in breast cancer patients with small (pT1) tumours.

Impact of receptor phenotype on nodal burden in patients with breast cancer who have undergone neoadjuvant chemotherapy.

BACKGROUND: Optimal evaluation and management of the axilla following neoadjuvant chemotherapy (NAC) in patients with node-positive breast cancer remains controversial. The aim of this study was to examine the impact of receptor phenotype in patients with nodal metastases who undergo NAC to see whether this approach can identify those who may be suitable for conservative axillary management. METHODS: Between 2009 and 2014, all patients with breast cancer and biopsy-proven nodal disease who received NAC were identified from prospectively developed databases. Details of patients who had axillary lymph node dissection (ALND) following NAC were recorded and rates of pathological complete response (pCR) were evaluated for receptor phenotype. RESULTS: Some 284 patients with primary breast cancer and nodal metastases underwent NAC and subsequent ALND, including two with bilateral disease. The most common receptor phenotype was luminal A (154 of 286 tumours, 53·8 per cent), with lesser proportions accounted for by the luminal B-Her2 type (64, 22·4 per cent), Her2-overexpressing (38, 13·3 per cent) and basal-like, triple-negative (30, 10·5 per cent) subtypes. Overall pCR rates in the breast and axilla were 19·9 per cent (54 of 271 tumours) and 37·4 per cent (105 of 281) respectively. Axillary pCR rates were highest in the Her2-overexpressing group (27 of 35, 77 per cent) and lowest in the luminal A group (35 of 153, 22·9 per cent) (P < 0·001). Nodal burden (median number of positive nodes excised) was lower in the Her2-overexpressing group compared with the luminal A group (0 versus 3; P < 0·001). CONCLUSION: Her2 positivity was associated with increased rates of axillary pCR and reduced nodal burden following NAC.

Radiation Protection for the Fluoroscopy Operator and Staff.

OBJECTIVE: The purposes of this article are to review available data regarding the range of protection devices and garments with a focus on eye protection and to summarize techniques for reducing scatter radiation exposure. CONCLUSION: Fluoroscopy operators and staff can greatly reduce their radiation exposure by wearing properly fitted protective garments, positioning protective devices to block scatter radiation, and adhering to good radiation practices. By understanding the essentials of radiation physics, protective equipment, and the features of each imaging system, operators and staff can capitalize on opportunities for radiation protection while minimizing ergonomic strain. Practicing and promoting a culture of radiation safety can help fluoroscopy operators and staff enjoy long, productive careers helping patients.

A Positive Node on Ultrasound-Guided Fine Needle Aspiration Predicts Higher Nodal Burden Than a Positive Sentinel Lymph Node Biopsy in Breast Carcinoma.

INTRODUCTION: Axillary status remains an important prognostic indicator in breast cancer. Certain patients with a positive sentinel node (SLNB) may not benefit from axillary clearance (AC). Uncertainty remains if this approach could be applied to patients diagnosed with axillary metastases on ultrasound-guided fine needle aspiration cytology (USFNAC). The aim of this study was to compare nodal burden in patients with positive USFNAC and a positive SLNB. METHODS: A retrospective study was performed involving all BC patients between 2007 and 2014 who had either pre-operative USFNAC or a SLNB. Patient/tumour characteristics and nodal burden were examined in all patients proceeding to AC. RESULTS: 974 patients were eligible for analysis. 439 patients (45 %) had positive USFNAC and 535 (55 %) had a positive SLNB. USFNAC-positive patients were more likely to undergo mastectomy (Chi-square test; p < 0.001), have extra-nodal extension (p < 0.001), be oestrogen receptor negative (p < 0.001) and be HER2 positive (p < 0.001). The median total number of lymph nodes (LNs) excised during AC was higher in the USFNAC group (Mann-Whitney test; 23 vs. 21; p < 0.001). The median total number of involved LNs was 3 (range 1-47) in FNAC-positive patients versus 1 (range 1-37) in SLNB-positive patients (p < 0.001). The median number of involved LNs in level 1 was 3 in FNAC-positive patients versus 1 in SLNB-positive patients (p < 0.001). Within the SLN-positive group, 49 % of the patients had only one involved LN, 28 % had two nodes involved and 23 % had ≥3. In comparison, within the FNAC-positive group only 13 % of the patients had one involved LN, 12 % had two nodes involved and 74 % had ≥3. CONCLUSION: Patients with positive USFNAC have more aggressive clinico-pathological characteristics and higher nodal burden compared to SLNB-positive patients. Currently, the authors advocate that patients not receiving neoadjuvant chemotherapy, with a positive USFNAC, should proceed directly to an axillary ALND.

Role of bone scan in addition to CT in patients with breast cancer selected for systemic staging.

BACKGROUND: The majority of women with breast cancer present with localized disease. The optimal strategy for identifying patients with metastatic disease at diagnosis remains unclear. The aim of this study was to evaluate the additional diagnostic yield from isotope bone scanning when added to CT staging of the thorax, abdomen and pelvis (CT-TAP) in patients with newly diagnosed breast cancer. METHODS: All patients diagnosed with breast cancer who underwent staging CT-TAP and bone scan between 2011 and 2013 were identified from a prospective database of a tertiary referral breast cancer centre that provides a symptomatic and population-based screening breast service. Criteria for staging included: biopsy-proven axillary nodal metastases; planned neoadjuvant chemotherapy or mastectomy; locally advanced or inflammatory breast cancer and symptoms suggestive of metastases. RESULTS: A total of 631 patients underwent staging by CT-TAP and bone scan. Of these, 69 patients (10·9 per cent) had distant metastasis at presentation, with disease confined to a single organ in 49 patients (71 per cent) and 20 (29 per cent) having metastatic deposits in multiple organs. Bone metastasis was the most common site; 39 of 49 patients had bone metastasis alone and 12 had a single isolated metastatic deposit. All but two of these were to the axial skeleton. No preoperative histological factors identified a cohort of patients at risk of metastatic disease. Omission of the bone scan in systemic staging would have resulted in a false-negative rate of 0·8 per cent. CONCLUSION: For patients diagnosed with breast cancer, CT-TAP is a satisfactory stand-alone investigation for systemic staging.