CAnceR IN PreGnancy (CARING) - a retrospective study of cancer diagnosed during pregnancy in the United Kingdom.

BACKGROUND: The incidence of cancer diagnosed during pregnancy is increasing. Data relating to investigation and management, as well as maternal and foetal outcomes is lacking in a United Kingdom (UK) population. METHODS: In this retrospective study we report data from 119 patients diagnosed with cancer during pregnancy from 14 cancer centres in the UK across a five-year period (2016-2020). RESULTS: Median age at diagnosis was 33 years, with breast, skin and haematological the most common primary sites. The majority of cases were new diagnoses (109 patients, 91.6%). Most patients were treated with radical intent (96 patients, 80.7%), however, gastrointestinal cancers were associated with a high rate of palliative intent treatment (63.6%). Intervention was commenced during pregnancy in 68 (57.1%) patients; 44 (37%) had surgery and 31 (26.1%) received chemotherapy. Live births occurred in 98 (81.7%) of the cases, with 54 (55.1%) of these delivered by caesarean section. Maternal mortality during the study period was 20.2%. CONCLUSIONS: This is the first pan-tumour report of diagnosis, management and outcomes of cancer diagnosed during pregnancy in the UK. Our findings demonstrate proof of concept that data collection is feasible and highlight the need for further research in this cohort of patients.

A thematic literature review of innovative strategies to prepare nursing students for aged-care.

BACKGROUND: The exponential rise in people living longer but requiring residential care is adding pressure to already overstretched aged care nurses. Consequently, a person-centred care culture in residential care remains aspirational, rather than a reality. For nursing students in Australia and elsewhere, clinical placements in aged care facilities are under-utilised due to negative perceptions about the likelihood for learning. Creative strategies to engage students to safely challenge ageist thinking and to inspire enthusiasm for learning in this context are needed. OBJECTIVES: The purpose of this thematic review of the literature is to better understand challenges related to learning in aged care settings and identify innovative strategies to enhance nursing student learning experiences in residential aged care placements. REVIEW METHODS: A literature review was undertaken in 2019 using CINAHL, PUBMED, Elsevier, Medline, ProQuest and Google Scholar. The search was limited to papers that were peer reviewed, in English, and published between 2001 and the date of review (mid-2019) in order to situate the review in the new millennium. RESULTS: 47 articles and books were included in the review that introduce solutions and innovative strategies that could be used to improve students' attitudes to learning in aged care and from older people. The literature review was categorized into three main themes, including: barriers to working with older people; the need for pedagogical change to foster empathy; and innovative strategies to address barriers. CONCLUSION: These themes are useful to consider in designing engaging learning and teaching for nursing students to be effective in working in aged care.

Second toe proximal phalanx interposition bone graft to correct a failed Keller's arthroplasty. A new technique.

We present a case report of a novel salvage technique for a failed Keller's arthroplasty using nonvascularised phalanx transfer from the second toe to the hallux on the same foot. The technique restores length, function and relieves pain.

Hypofractionated Concomitant Chemoradiation in Inoperable Locally Advanced Non-small Cell Lung Cancer: A Report on 100 Patients and a Systematic Review.

AIMS: Concomitant chemoradiation is the standard of care in patients with inoperable non-small cell lung cancer. The purpose of this study was to analyse the survival outcome and toxicity data of using hypofractionated chemoradiation. MATERIALS AND METHODS: One hundred patients were treated from June 2011 to November 2016. Treatment consisted of 55 Gy in 20 daily fractions concurrently with split-dose cisplatin vinorelbine chemotherapy over 4 weeks followed by two cycles of cisplatin vinorelbine only. Survival was estimated using Kaplan-Meier and Cox regression was carried out for known prognostic factors. A systematic search of literature was conducted using Medline, Embase and Cochrane databases and relevant references included. RESULTS: In total, 97% of patients completed radiotherapy and 73% of patients completed all four cycles of chemotherapy. One patient died of a cardiac event during consolidative chemotherapy. There were two cases of grade 4 toxicities (one sepsis, one renal impairment). Grade 3 toxicities included nausea/vomiting (17%), oesophagitis (15%), infection with neutropenia (12%) and pneumonitis (4%). Clinical benefit was seen in 86%. Two-year progression-free survival and overall survival rates were 49% and 58%, respectively. The median progression-free survival and overall survival were 23.4 and 43.4 months, respectively. The only significant prognostic factor was the number of chemotherapy cycles received (P = 0.02). The systematic review identified 13 relevant studies; a variety of regimens were assessed with variable reporting of outcomes and toxicity but with overall an improvement in survival over time. CONCLUSION: Our experience compared with the original phase II trial showed improved treatment completion rates and survival with acceptable morbidity. With appropriate patient selection this regimen is an effective treatment option for locally advanced non-small cell lung cancer. This study helps to benchmark efficacy and toxicity rates while considering the addition of new agents to hypofractionated concurrent chemoradiotherapy. The agreement of a standard regimen for assessment in future trials would be beneficial.

Interferon-gamma response to the treatment of active pulmonary and extra-pulmonary tuberculosis.

BACKGROUND: Interferon-gamma (IFN-γ) release assays (IGRAs) are used to diagnose tuberculosis (TB) but not to measure treatment response. OBJECTIVE: To measure IFN-γ response to active anti-tuberculosis treatment. DESIGN: Patients from the Henan Provincial Chest Hospital, Henan, China, with TB symptoms and/or signs were enrolled into this prospective, observational cohort study and followed for 6 months of treatment, with blood and sputum samples collected at 0, 2, 4, 6, 8, 16 and 24 weeks. The QuantiFERON® TB-Gold assay was run on collected blood samples. Participants received a follow-up telephone call at 24 months to determine relapse status. RESULTS: Of the 152 TB patients enrolled, 135 were eligible for this analysis: 118 pulmonary (PTB) and 17 extra-pulmonary TB (EPTB) patients. IFN-γ levels declined significantly over time among all patients (P = 0.002), with this decline driven by PTB patients (P = 0.001), largely during the initial 8 weeks of treatment (P = 0.019). IFN-γ levels did not change among EPTB patients over time or against baseline culture or drug resistance status. CONCLUSION: After 6 months of effective anti-tuberculosis treatment, IFN-γ levels decreased significantly in PTB patients, largely over the initial 8 weeks of treatment. IFN-γ concentrations may offer some value for monitoring anti-tuberculosis treatment response among PTB patients.

Myogenic transcription factors regulate pro-metastatic miR-182.

Approximately 30% of patients with soft-tissue sarcoma die from pulmonary metastases. The mechanisms that drive sarcoma metastasis are not well understood. Recently, we identified miR-182 as a driver of sarcoma metastasis in a primary mouse model of soft-tissue sarcoma. We also observed elevated miR-182 in a subset of primary human sarcomas that metastasized to the lungs. Here, we show that myogenic differentiation factors regulate miR-182 levels to contribute to metastasis in mouse models. We find that MyoD directly binds the miR-182 promoter to increase miR-182 expression. Furthermore, mechanistic studies revealed that Pax7 can promote sarcoma metastasis in vivo through MyoD-dependent regulation of pro-metastatic miR-182. Taken together, these results suggest that sarcoma metastasis can be partially controlled through Pax7/MyoD-dependent activation of miR-182 and provide insight into the role that myogenic transcription factors have in sarcoma progression.

A 35-year experience with the post-sophomore fellowship in pathology: analysis of its effectiveness as a recruitment resource.

Recent reports have indicated a shortage of pathologists coming out of training programs over the next few years. This is due, in part, to a decrease in the number of medical students entering pathology and an overall decline in the popularity of the field as a specialty choice. Medical students electing to spend a year in a post-sophomore fellowship in pathology would be expected to enter the field at a higher than average rate. In this study, the specialty choices of 140 former student fellows were analyzed. The students included in the study were enrolled in a year-long University of California, Los Angeles post-sophomore fellowship in pathology between 1953 and 1988. Twenty-seven of the 140 students (19.3%) ultimately chose pathology as a career. This represents a 9- to 10-fold increase over the average percentage of medical students entering pathology through the match (less than 2%) for any given year. Of all students from the University of California, Los Angeles who entered pathology, 75% did not elect to spend a year in fellowship. Eighty percent of the former fellows chose some other field, medicine and surgery being the most popular choices.

Disseminated coccidioidomycosis detected by percutaneous liver biopsy in a liver transplant recipient.

The authors report the first case, to their knowledge, of disseminated coccidioidomycosis occurring in a liver transplant recipient. The case is also interesting in that the diagnosis of disseminated coccidioidomycosis was made fortuitously, only after finding the characteristic endosporulating spherules on a percutaneous liver biopsy. In addition, the authors reviewed the literature on post-transplant infection with particular emphasis on fungal pathogens. All studies concurred that Candida species was the most prevalent infecting fungal organism when both localized and disseminated forms of infection are included. Aspergillus was the second most common offender, and disseminated infection was associated with a very grave prognosis for the transplant recipient. Rare infections with Mucor and Cryptococcus neoformans are described in the literature.

Fine-needle aspiration of gastrointestinal stromal tumors.

Gastrointestinal stromal tumors are a group of neoplasms encompassing leiomyoma, leiomyosarcoma, and an epithelioid variant of leiomyosarcoma, as well as lesions expressing neural differentiation. These neoplasms are rare and account for 1% of all gastrointestinal tumors. With increasing frequency, fine-needle aspiration (FNA) has been used to diagnose intra-abdominal neoplasms before institution of definitive treatment. We encountered four patients with gastrointestinal stromal tumors diagnosed by FNA who ultimately underwent surgical excision of their tumors. The age of the patients ranged from 57 to 88 years. Smears from the aspirates were cellular and consisted of numerous small spindle cells distributed as cohesive fragments and individual cells. The dispersed cell population appeared largely as stripped nuclei. Several nuclei had perinuclear or paranuclear vacuoles, similar to the "halos" seen in sections. Cytologic evidence of malignancy (pleomorphism, nuclear irregularity, mitoses) were not identified in smears. Corresponding histologic sections demonstrated varying degrees of malignancy ranging from benign or low grade to frankly sarcomatous gastrointestinal stromal tumors. We conclude that the diagnosis of gastrointestinal stromal tumors can be made with a certain degree of confidence by using FNA findings. However, predictions about potential aggressiveness are best reserved for gross and histologic examination of the resected specimen.

Prevalence of non-A,non-B hepatitis/hepatitis C virus antibody in human immunoglobulins.

Human intravenous immunoglobulins prepared by the cold ethanol fractionation technique of Cohn are considered safe with respect to infectivity. However, there have been several instances of transmission of both hepatitis B and non-A,non-B hepatitis viruses after administration of intravenous immunoglobulins. To determine the prevalence of hepatitis C virus antibody in intravenous immunoglobulins and protein preparations, 30 commercially available products were tested. Using the Abbott enzyme immunoassay for hepatitis C virus antibody, 27 of 30 (90%) immunoglobulins tested positive. The Ortho immunoassay showed that 28 of 30 (93%) were positive, with one discordant result between the Ortho and Abbott assays. An antigen-blocking or neutralization test (Abbott) confirmed the results of the Ortho assay. Bovine, sheep, goat, and horse sera also were tested before and after isolation of animal immunoglobulins. All results on the animal sera were negative, indicating that the fractionation process did not produce false-positive results. The high prevalence rate of hepatitis C virus antibody in intravenous immunoglobulins has important implications for follow-up of recipients, selection of serum donors, and implementation of anti-hepatitis C virus testing.

Prospective correlation of cervicovaginal cytologic and histologic specimens.

An effective, prospective, computer-guided method of correlation is reported. The mechanism for identification of cases, comparison of diagnoses, and reconciliation of discrepancies are explained. The results are similar to prior, retrospective, correlation studies. The benefits specific to this unique prospective approach include optimal capture of cases for correlation, minimization of errors before diagnoses are released to clinicians and patients, and internal standardization of diagnostic criteria. Three thousand four hundred and four consecutive paired cervicovaginal cytologies and biopsies were accessioned at the Pathology Department of Duke University Medical Center over a 43-month period. Of these, 481 paired cases (14%) had discordant diagnoses, defined as differing more than one degree of dysplasia or as dysplasia or carcinoma identified by only one modality. Additional evaluation reconciled the diagnostic differences in 35 cases. Eighteen initial diagnostic differences arose from cytologic screening errors, 16 from interpretive errors by staff pathologists, and one from superficial initial histologic sections. The remaining 446 discordances were attributed to sampling differences. The cytologic smear contained the diagnostic lesion in 40% of the cases and the biopsy the remainder, emphasizing the utility of pairing these sampling techniques in patients at risk for dysplasia.

Calcifying fibrous pseudotumor of pleura. A report of three cases of a newly described entity involving the pleura.

A newly recognized distinctive fibrous soft tissue lesion called "calcifying fibrous pseudotumor" (CFPT) was recently described in the soft tissues of the extremities, trunk, scrotum, groin, neck, or axilla. To date, CFPT has not been described in the pleura. The authors reviewed the clinical, radiologic, and pathologic features of three cases. A 23-year old woman and 34-year old man who presented with chest pain, and a 28-year old woman without chest symptoms were found to have a pleural mass on chest radiographs. Computed tomography (CT) scans of each patient revealed pleural-based nodular masses with central areas of increased attenuation due to calcifications. Each lesions consisted of circumscribed, but unencapsulated masses of hyalinized collagenous fibrotic tissue interspersed with lymphoplasmacytic infiltrates and calcifications, many of which had psammomatous features. The lesions were limited to the pleura and did not involve the underlying lung parenchyma. Electron microscopy in one case showed fibroblasts scattered in dense collagenous tissue. Calcifying fibrous pseudotumor is distinct from other pleural lesions such as fibrous tumor of pleura, calcified granulomas, calcified pleural plaques, and chronic fibrous pleuritis as well as intrapulmonary lesions such as hyalinizing granuloma, inflammatory pseudotumor, and amyloid. As in the soft tissues, local excision appears adequate therapy for CFPT of the pleura. If these lesions behave in a similar fashion to CFPT of soft tissues, one might expect a low frequency of local recurrence.

Do proficiency test results correlate with the work performance of screeners who screen Papanicolaou smears?

We rescreened Papanicolaou smear slides from 40,245 women, which had been examined by 81 cytology screeners, scored the screeners' work performance, and compared these scores with the results of the screeners' performance on glass slide and computer-based proficiency tests. All diagnoses (i.e., from the proficiency tests, the original slides, and the rescreened slides) were classified in the 4 diagnostic categories specified in the Clinical Laboratory Improvement Amendments. The rescreening scores were standardized to account for different distributions of abnormalities in the proficiency tests and rescreened slides. We compared a standardized score with the proficiency test scores. Of the cases, 91% were categorized as normal, benign, or reactive changes when rescreened, and 98% of these agreed with the original diagnosis. Sixteen percent of low-grade and 15% of high-grade intraepithelial lesions were classified as normal. The rank correlation between the rescreening scores and both proficiency tests was 0.24 using a scoring scheme for cytotechnologists. The correlation between the rescreening and proficiency testing scores indicates that performance on a 10-slide test gives some indication of the true performance of screeners. The computer-based test shows promise as an alternative to the glass slide test but needs further development and validation.

Glomus jugulare tumor metastatic to the sacrum after high-dose radiation therapy: case report.

A 47-year-old woman with left ear pain and hearing loss was diagnosed with a glomus jugulare tumor for which she received radiation therapy as the primary treatment. Over a period of 20 years, she developed temporal bone necrosis, brain stem calcifications, local tumor recurrence, and eventually metastases to her lungs and sacrum. This case underscores the often indolent nature of glomus jugulare tumors, the late sequelae of radiation therapy for benign intracranial tumors, and the potential of these tumors to metastasize. This patient's history suggests that aggressive surgical resection should be considered early for such tumors, particularly because radiation treatment does not ablate the tumor. This is only the second reported case of a glomus jugulare tumor metastatic to the sacrum.

Osteogenic sarcoma of the head and neck. The UCLA experience.

Eighteen cases of osteogenic sarcoma of the head and neck were treated at our institution between 1955 and 1987. The patients' ages ranged from 5 to 73 years, with a median age of 28 years. The sex distribution was equal. Follow-up ranged from 1 to 276 months, with a median of 79 months. The primary site of the tumor was the mandible in nine cases, maxilla and paranasal sinuses in six, skull in two, and orbit in one. Six of 18 patients were free of disease with greater than 5 years of follow-up. Four of the six received combined surgery, radiation therapy, and chemotherapy as their primary treatment. Of the five patients treated with surgery alone, four suffered recurrences, one of whom was salvaged with further surgery and chemotherapy. Five patients were treated initially without surgery. They received radiation therapy with or without chemotherapy; all five developed local recurrence. We conclude that osteogenic sarcoma of the head and neck is an aggressive tumor, prone to both local and distant failure. Based on our series and from published experience involving the extremities, osteogenic sarcoma of the head and neck should be managed with multimodality therapy.

Midline nasal destruction in cocaine abusers.

Idiopathic midline destructive disease (IMDD) is a diagnosis of exclusion in patients who manifest midline nasal necrosis with no specific etiology such as infection, tumor, or Wegener's granulomatosis. Recently, a group of cocaine abusers has been identified that manifests a syndrome that mimics IMDD, but is less fulminant in its course. To better define the natural history of this syndrome, we reviewed the medical records, radiographs, and pathologic material from five such patients treated at the University of California, Los Angeles. Other causes of midline nasal destruction were excluded in each patient on the basis of histopathology, cultures, and laboratory tests. Biopsy material, available in four patients, demonstrated inflammation and necrosis without vasculitis. Treatment was conservative in four of the five patients, using antibiotics, local care, debridement, and cessation of cocaine use. During the follow-up period, progressive disease developed in one of the five patients, requiring radiation and steroid therapy. We conclude that the treatment of midline nasal destruction in cocaine abusers should initially be conservative, once other etiologies have been systematically excluded.

Fine-needle aspiration cytology of adenoid (acantholytic) squamous-cell carcinoma.

Adenoid squamous-cell carcinoma (ASCCa) is an uncommon cancer which occurs most frequently in the skin of the head and neck region of elderly, sun-exposed individuals. Histologically, ASCCa is characterized by gland-like, "adenoid" cell groups with a central, detached acantholytic cellular component and an intact peripheral rim of cells. The cytological features of five fine-needle aspiration cytology (FNAC) samples from four patients with primary or metastatic ASCCa are presented. These were assessed for features which would allow distinction of this variant from conventional squamous carcinoma. The adenoid component was represented in FNAC by intact, sometimes three-dimensional cell groups simulating glandular structures. Also present were cells in short chains of two or three in single cell files and scattered, individual dyskeratotic cells. Individual cells had rounded, accentuated borders, cytoplasmic keratinization, and often pyknotic nuclei, representing acantholytic cells from the adenoid "lumens." Features of malignancy, including cellular atypia and increased mitotic rate, were present allowing for distinction between ASCCa and benign acantholytic processes such as pemphigus.

Cytologically low grade malignancies: an important interpretative pitfall responsible for false negative diagnoses in fine-needle aspiration of the breast.

Failure to diagnose breast carcinoma by fine-needle aspiration (FNA) is a major obstacle to expanded use of that technique. While the majority of false negative diagnoses are due to inadequate sampling and insufficient specimens, a significant minority of false negative cases result from inaccurate interpretation of adequate material. Low grade carcinomas including lobular, tubular, low grade adenosquamous, and papillary carcinomas appear to account for many of these diagnostic errors. Careful attention to nuclear detail, monomorphism of cell population and the presence of neoplastic cells with retained cytoplasm should allow the recognition of the majority of these neoplasms as malignant by cytologic examination.