Comparing Genomic Landscapes of Oral and Cutaneous Squamous Cell Carcinoma of the Head and Neck: Quest for Novel Diagnostic Markers.

Squamous cell carcinoma is the most common head and neck malignancy arising from the oral mucosa and the skin. The histologic and immunohistochemical features of oral squamous cell carcinoma (OSCC) and head and neck cutaneous squamous cell carcinoma (HNcSCC) are similar, making it difficult to identify the primary site in cases of metastases. With the advent of immunotherapy, reliable distinction of OSCC and HNcSCC at metastatic sites has important treatment and prognostic implications. Here, we investigate and compare the genomic landscape of OSCC and HNcSCC to identify diagnostically useful biomarkers. Whole-genome sequencing data from 57 OSCC and 41 HNcSCC patients were obtained for tumor and matched normal samples. Tumor mutation burden (TMB), Catalogue of Somatic Mutations in Cancer (COSMIC) mutational signatures, frequent chromosomal alterations, somatic single nucleotide, and copy number variations were analyzed. The median TMB of 3.75 in primary OSCC was significantly lower (P < .001) than that of 147.51 mutations/Mb in primary HNcSCC. The COSMIC mutation signatures were significantly different (P < .001) between OSCC and HNcSCC. OSCC showed COSMIC single-base substitution (SBS) mutation signature 1 and AID/APOBEC activity-associated signature 2 and/or 13. All except 1 HNcSCC from hair-bearing scalp showed UV damage-associated COSMIC SBS mutation signature 7. Both OSCC and HNcSCC demonstrated a predominance of tumor suppressor gene mutations, predominantly TP53. The most frequently mutated oncogenes were PIK3CA and MUC4 in OSCC and HNcSCC, respectively. The metastases of OSCC and HNcSCC demonstrated TMB and COSMIC SBS mutation signatures similar to their primary counterparts. The combination of high TMB and UV signature in a metastatic keratinizing squamous cell carcinoma suggests HNcSCC as the primary site and may also facilitate decisions regarding immunotherapy. HNcSCC and OSCC show distinct genomic profiles despite histologic and immunohistochemical similarities. Their genomic characteristics may underlie differences in behavior and guide treatment decisions in recurrent and metastatic settings.

Patients' and healthcare professionals' views on a pre- and post-operative rehabilitation programme (SOLACE) for lung cancer: A qualitative study.

AIMS AND OBJECTIVES: To explore patients' and healthcare professionals' views and experiences of a pre- and post-operative rehabilitation intervention (SOLACE), for patients undergoing surgery for early-stage lung cancer. BACKGROUND: Considerable post-operative complications can occur after surgery. A specialist lung cancer service (SOLACE) was developed to optimise health and fitness levels prior to and following lung cancer resections, as well as reducing morbidity and mortality, and improving the physical and psychological well-being of patients. DESIGN: The design was an exploratory, descriptive qualitative interview study. METHODS: Seventeen lung cancer patients and eight healthcare professionals were recruited from a large teaching hospital in South England. Data were collected through semi-structured telephone and face-to-face interviews. Transcribed interview data were analysed thematically. The COREQ checklist was used to report on the study process. RESULTS: The SOLACE service was positively perceived by patients and healthcare professionals. Patients valued the provision of tailored support/advice and peer support and reported benefits to their health and well-being. Barriers to patient uptake of the classes included time constraints, motivation and access for patients who lived at a distance. CONCLUSIONS: There is benefit in providing a personalised approach through a pre- and post-operative rehabilitation service for lung cancer patients. Virtual support may address equality of access to service for those who live at a distance from the hospital. RELEVANCE TO CLINICAL PRACTICE: Introduction of a pre- and post-operative rehabilitation service provided by specialist peri-operative rehabilitation nurses and practitioners can yield positive outcomes for patients undergoing surgical treatment of early-stage lung cancer. Engagement of key healthcare professionals, consideration of virtual follow-up services and making patients aware of services could maximise patient uptake. Further consideration is needed of the best way to promote patient self-management and long-term continuation of patient rehabilitation in the community.

Multicentre review of readmission rates within 30 days of discharge following lung cancer surgery.

Postoperative complications following curative lung cancer surgery are well recognised, but there is limited data on 30-day readmission rates. The UK Thoracic Surgery Group conducted a multicentre review over a 3-month period to assess readmission rates. Overall readmission among the 268 patients who had undergone primary lung cancer surgery was 30 (11%); 14/30 of readmissions occurred within 7 days of discharge, with 13/30 patients readmitted to a hospital that had not performed the surgery. The causes of readmission were mainly pulmonary related (16/30). Readmission was associated with being discharged with a pleural drain 11/30 (P<0.01), having two or more postoperative complications 11/30 (P<0.01) and a patient's readiness for discharge 9/30 (P=0.001). There was a trend toward an association with smoking 13/30 (P=0.18). The authors suggest that a greater focus on patients presenting with characteristics associated with readmission, and incorporating a patient's readiness for discharge, may reduce readmission, although more studies are needed.

A prospective study of one-year clinical outcomes utilizing a composite three-dimensional device with a tissue-separating layer for repair of primary ventral and small incisional hernia.

Primary ventral and even small incisional hernias have historically been repaired by primary closure; however, data proves that use of mesh can significantly reduce hernia recurrence. Here we report clinical outcomes at one year using the International Hernia Mesh Registry following the use of a three-dimensional tissue-separating mesh device (Proceed Ventral Patch™, Ethicon, Somerville, NJ). This ongoing prospective multi-center registry collects preoperative, perioperative, and postoperative outcome data including adverse events at 1, 6, 12, and 24 months. Patient-reported outcomes are collected including a hernia-specific questionnaire. A total of 234 patients (72.1% male, 27.9% female) from 13 sites in the United States and Europe were enrolled. Mean age and BMI were 52.2 (SD 15.0) and 29.2 kg/m² (SD 5.2), respectively. Hernia types: umbilical 67.1%, epigastric 11.5%, small incisional including trocar 21.3%. Preoperatively 46.9% and 38.3% of patients reported symptomatic pain and movement scores, respectively. At 1 year, these were significantly reduced to 8.9% and 5.0%, respectively (p < 0.001). At 12 months hernia recurrence was 3.0% (95% CI, 1.2% to 6.1%), seroma (2.1%), infection (2.1%) with other events being less than 1%. These results indicate repair using this device led to significant improvement in pain and movement limitations and were associated with low complication and recurrence rates.

Quality of Life Impacts Following Surgery for Advanced Head and Neck Cancer.

Background: Understanding the impact of surgery on patients will enable clinicians to provide evidence-based perioperative management. This study aimed to investigate the quality of life (QoL) impacts following head and neck surgery for advanced stage head and neck cancer. Methods: Head and neck cancer survivors were invited to complete five validated questionnaires to investigate QoL. Associations between QoL and patient variables were analyzed. Variables included age, time since operation, length of surgery, length of stay, Comorbidity Index, estimated 10-year survival, sex, flap type, treatment and cancer type. Outcome measures were also compared to normative outcomes. Results: The majority of participants (N = 27; 55% male; mean (standard deviation) age: 62.6 (13.8) years; mean time since operation: 801 days) had a squamous cell carcinoma (88.9%) and free flap repair (100%). Time since operation was significantly (P < 0.05) associated with higher rates of depression (r = -0.533), psychological needs (r = -0.0415) and physical/daily living needs (r = -0.527). Length of surgery and length of stay were significantly associated with depression (r = 0.442; r = 0.435) and length of stay was significantly associated with speaking difficulties (r = -0.456). There was a significant association between work and education scores with age (r = 0.471), length of surgery (r = 0.424), Comorbidity Index (r = 0.456) and estimated 10-year survival (r = -0.523). Conclusions: Age, time since operation, length of surgery, length of stay, Comorbidity Index and estimated 10-year survival were the outcomes associated with QoL. Patient-reported outcome measures and psychological support could be included in the standard care pathway for head and neck cancer patients to ensure holistic management of their condition.

Should all patients receive extended thromboprophylaxis after resection of primary lung cancer?

OBJECTIVE: The optimal duration of thromboprophylaxis in patients undergoing resection of primary lung cancer is not known. We investigated the incidence of pulmonary emboli and venous thromboembolism in patients undergoing early-stage lung cancer resection and the impact of change from short duration to extended thromboprophylaxis. METHODS: We reviewed the outcomes of consecutive patients who underwent resection of early-stage primary lung cancer following a change in protocol from inpatient-only to extended thromboprophylaxis to 28 days. Propensity-score matching of control (routine inpatient pharmacologic thromboprophylaxis) and treatment group (extended pharmacologic thromboprophylaxis) was performed. Adjustment for covariates based on the Caprini risk assessment model was undertaken. Thromboembolic outcomes were compared between the 2 groups. RESULTS: Seven hundred fifty consecutive patients underwent resection of primary lung cancer at Oxford University Hospitals NHS Foundation Trust between January 2013 and December 2018. Six hundred patients were included for analysis and propensity-score matching resulted in 253 matched pairs. Extended prophylaxis was associated with a significant reduction in pulmonary emboli (10 of 253 patients [4%] vs 1 of 253 patients [0.4%], P = .01). One patient (0.4%) developed a bleeding complication within the treatment cohort. Multivariable logistic regression model demonstrated that extended thromboprophylaxis was independently associated with a reduction in postoperative pulmonary emboli. CONCLUSIONS: Patients undergoing lung cancer resection surgery are at moderate-to-high risk of postoperative thromboembolic disease. Extended dalteparin for 28 days is safe and is associated with reduced incidence of pulmonary embolus in patients undergoing resection of early-stage primary lung cancer.

Cancer Progression Gene Expression Profiling Identifies the Urokinase Plasminogen Activator Receptor as a Biomarker of Metastasis in Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinoma (cSCC) of the head and neck region is the second most prevalent skin cancer, with metastases to regional lymph nodes occurring in 2%-5% of cases. To further our understanding of the molecular events characterizing cSCC invasion and metastasis, we conducted targeted cancer progression gene expression and pathway analysis in non-metastasizing (PRI-) and metastasizing primary (PRI+) cSCC tumors of the head and neck region, cognate lymph node metastases (MET), and matched sun-exposed skin (SES). The highest differentially expressed genes in metastatic (MET and PRI+) versus non-metastatic tumors (PRI-) and SES included PLAU, PLAUR, MMP1, MMP10, MMP13, ITGA5, VEGFA, and various inflammatory cytokine genes. Pathway enrichment analyses implicated these genes in cellular pathways and functions promoting matrix remodeling, cell survival and migration, and epithelial to mesenchymal transition, which were all significantly activated in metastatic compared to non-metastatic tumors (PRI-) and SES. We validated the overexpression of urokinase plasminogen activator receptor (uPAR, encoded by PLAUR) in an extended patient cohort by demonstrating higher uPAR staining intensity in metastasizing tumors. As pathway analyses identified epidermal growth factor (EGF) as a potential upstream regulator of PLAUR, the effect of EGF on uPAR expression levels and cell motility was functionally validated in human metastatic cSCC cells. In conclusion, we propose that uPAR is an important driver of metastasis in cSCC and represents a potential therapeutic target in this disease.

Whole genome analysis reveals the genomic complexity in metastatic cutaneous squamous cell carcinoma.

Metastatic cutaneous squamous cell carcinoma (CSCC) is a highly morbid disease requiring radical surgery and adjuvant therapy, which is associated with a poor prognosis. Yet, compared to other advanced malignancies, relatively little is known of the genomic landscape of metastatic CSCC. We have previously reported the mutational signatures and mutational patterns of CCCTC-binding factor (CTCF) regions in metastatic CSCC. However, many other genomic components (indel signatures, non-coding drivers, and structural variants) of metastatic CSCC have not been reported. To this end, we performed whole genome sequencing on lymph node metastases and blood DNA from 25 CSCC patients with regional metastases of the head and neck. We designed a multifaceted computational analysis at the whole genome level to provide a more comprehensive perspective of the genomic landscape of metastatic CSCC. In the non-coding genome, 3' untranslated region (3'UTR) regions of EVC (48% of specimens), PPP1R1A (48% of specimens), and ABCA4 (20% of specimens) along with the tumor-suppressing long non-coding RNA (lncRNA) LINC01003 (64% of specimens) were significantly functionally altered (Q-value < 0.05) and represent potential non-coding biomarkers of CSCC. Recurrent copy number loss in the tumor suppressor gene PTPRD was observed. Gene amplification was much less frequent, and few genes were recurrently amplified. Single nucleotide variants driver analyses from three tools confirmed TP53 and CDKN2A as recurrently mutated genes but also identified C9 as a potential novel driver in this disease. Furthermore, indel signature analysis highlighted the dominance of ID signature 13 (ID13) followed by ID8 and ID9. ID9 has previously been shown to have no association with skin melanoma, unlike ID13 and ID8, suggesting a novel pattern of indel variation in metastatic CSCC. The enrichment analysis of various genetically altered candidates shows enrichment of "TGF-beta regulation of extracellular matrix" and "cell cycle G1 to S check points." These enriched terms are associated with genetic instability, cell proliferation, and migration as mechanisms of genomic drivers of metastatic CSCC.

The Impact of Coercive Control on Use of Specific Sexual Coercion Tactics.

There is substantial evidence that women experience unwanted sex under nonviolent duress from partners. This study examined the relationship between coercive control and sexual coercion in heterosexual couples. Among a sample of 136 men arrested for domestic violence, extent of coercive control was used to predict the likelihood of using eight specific sexual coercion tactics. Findings indicated that coercive control predicted significantly greater likelihood of using covert tactics, but not physically violent or overtly aggressive tactics. The tactics that demonstrated the strongest relationship with coercive control seem indicative of a toxic relational environment that may subtly erode victim autonomy and sense of self over time. Implications discuss how use of more covert and insidious tactics maintain invisibility, isolation, blame, and perceived complicitness of victims in clinical, legal, and social settings.

Optimal resection rate for lung cancer in the UK: how high should we go?

BACKGROUND: The optimal resection rate for institutions managing early-stage primary lung cancer is not known. Whether the prognosis of patients who do not proceed to operation is determined by their comorbidities for which they were deemed at prohibitively high-operative risk, or disease progression, is uncertain. We investigated the outcomes of patients with early-stage lung cancer who were considered for surgical management. METHODS: We reviewed the outcomes of consecutive patients who were considered for resection of early-stage primary lung cancer at Oxford University Hospitals National Health Service Foundation Trust between 2012 and 2017. RESULTS: Between 29 November 2012 and 31 March 2017, 467 consecutive patients underwent resection with curative intent for primary lung cancer (operative group), while 81 patients were deemed resectable but either inoperable or did not wish to proceed to operation (non-operative group). Reason for not proceeding to resection was cardiovascular in 16 patients (19.8%), respiratory in 21 (25.9%), cardiorespiratory in 11 (13.6%), performance status in 8 (9.9%) and patient choice in 25 (30.9%) patients. Sixty-six patients (81.5%) received an alternative radical treatment. Median follow-up was 169 weeks (IQR 119-246 weeks) in the operative group and 118 weeks (IQR 74-167 weeks) in the non-operative group. Median survival of patients with early-stage lung cancer who did not proceed to operation was 2.5 years; median survival of patients undergoing lung cancer resection was undefined (p<0.0001). Lung cancer was documented as directly or indirectly leading to or contributing to death in 40 patients (76.9%). In 11 patients, the cause of death was due to comorbidities (21.2%). CONCLUSIONS: Patients turned down for operation in a high-resection rate UK unit have limited survival due to lung cancer progression. We conclude that 'optimal' resection rates may not have been reached in the UK even in high-resection rate centres.

Computed tomography follow-up identifies radically treatable new primaries after resection for lung cancer.

OBJECTIVES: The optimal imaging programme for the follow-up of patients who have undergone resection of primary lung cancer is yet to be determined. We investigated the incidence and patterns of new and recurrent malignancy after resection for early-stage lung cancer in patients enrolled into a computed tomography (CT) follow-up programme. METHODS: We reviewed the outcomes of consecutive patients who underwent CT follow-up after resection of early-stage primary lung cancer at the Oxford University Hospitals NHS Foundation Trust, between 2013 and 2017. RESULTS: Four hundred and sixty-six consecutive patients underwent resection of primary lung cancer between 1 January 2013 and 31 March 2017. Three hundred and thirty-one patients (71.0%) were enrolled in CT follow-up. The median follow-up was 98 weeks (range 26-262). Sixty patients (18.2%) were diagnosed with programme-detected malignancy. Recurrence was diagnosed in 36 patients (10.9%), new primary lung cancer in 16 patients (4.8%) and non-lung primary tumours in 8 patients (2.4%). A routine CT scan identified the majority of new primary lung cancers (84.2%) and those with disease recurrence (85.7%). The majority of programme-detected malignancies were radically treatable (55%). The median survival of programme-detected cancers was 92.4 versus 23.0 weeks for patients with clinically detected tumours (P < 0.0001). Utilizing the CT scout image as a surrogate for chest X-ray, the sensitivity of this modality was 16.95% (8.44-28.97%) and specificity was 89.83% (79.17-96.18%). Negative likelihood ratio was 0.92 (0.8-1.07). CONCLUSIONS: CT follow-up of surgically treated primary lung cancer patients identifies malignancy at a stage where radical treatment is possible in the majority of patients. Chest X-ray follow-up may not be of benefit following lung cancer resection.

Relevance of a specialised nurse in thoracic surgery.

This review of the development of a specialist nursing service within a thoracic surgery centre looks at the implementation of a specialist nursing role. An analysis of the needs of the service allowed identification of areas where specialist nursing input could have a positive impact on the patient pathway: (I) a nurse-led clinic for review of patients who require early review after discharge, in particular those discharged home with chest drains, was developed; (II) improvements to the patient pathway such as day of surgery admission were introduced along with a reduction in the number of patients who require admission to intensive care after surgery; (III) the specialist nurse leads on the introduction of new technology such as electronic chest drains. The specialist nurse works in the follow-up clinic, seeing patients autonomously, with a particular emphasis on patients under long-term follow-up after thoracic surgery. A telephone clinic has been introduced for patients on long-term CT follow-up. These are well received by patients; (IV) specialist nurses also work on in-patient wards, providing specialist input to the patient pathway, and can also take on work traditionally undertaken by junior medical staff. To be successful the specialist nursing role needs to be supported by the multidisciplinary team (MDT). These roles are developed to meet the needs of each unit and can have a very positive impact on the patient pathway.

Evaluation of Pacific obstetric and gynaecological ultrasound scanning capabilities, personnel, equipment and workloads.

AIMS: There are no published data on the coverage, training or experience of ultrasound services in the Pacific. This study aimed to obtain information on the knowledge, experience and training of ultrasound operators and scanning equipment and workloads in the Pacific region. METHODS: Participants for the survey were recruited by post, via the Pacific Society of Reproductive Health (PSRH) website and at the PSRH conference. Questions obtained information on ultrasound scanning capabilities, personnel, equipment and workloads in the Pacific region RESULTS: 30 respondents from 17 hospitals in 11 countries provided completed questionnaires. Close to 50% of the responses were from Fiji. The majority of respondents were sonographers or obstetricians. Lack of transvaginal probes (7/17) in some facilities limit accuracy of early pregnancy scanning. 17/17 respondents felt an advanced course would be the preferred type of course. CONCLUSION: There is a sound basic level of ultrasound being performed in the Pacific region. A multimodal training programme, incorporating a practical hands-on course based in New Zealand, combined with CD/published materials appears to be the best method of developing more advanced skills in order to optimise antenatal care in the region.

The use of ultrasound measurement of fetal lung length to predict neonatal respiratory outcome after prolonged premature rupture of the membranes.

OBJECTIVE: The purpose of this study was to investigate the use of fetal lung length estimation by ultrasound in the prediction of adverse neonatal respiratory outcome after prolonged preterm rupture of the membranes. METHODS: From the hospital database of all cases of spontaneous membrane rupture /=7 days after membrane rupture needed to be available and the last lung length prior to delivery was used to predict adverse respiratory outcome. Complete neonatal follow-up was available on all babies. Neonatal outcome measures included survival, bronchopulmonary dysplasia defined as an oxygen requirement at 36 weeks' gestation, and neonatal respiratory death in non-survivors. Two groups, good and poor outcomes, were defined. A comparison of the last lung length before delivery (corrected for gestation) between the good and poor outcome groups was made to determine whether lung length could predict neonatal outcome. RESULTS: There were 43 live births. All had received antenatal corticosteroids as part of the management of prematurity. There were no differences in maternal age, ethnicity, parity and the incidence of antepartum haemorrhage between the good and poor outcome groups. Parameters significantly associated with good outcome included gestation at membrane rupture, large pool of amniotic fluid and gestation at delivery. The last fetal lung length did not predict adverse neonatal respiratory outcome. In the 28 babies where membrane rupture was >/=21 days the findings were the same. CONCLUSION: Fetal lung length determined by antenatal ultrasound does not predict adverse neonatal respiratory outcome and the prediction of pulmonary hypoplasia in live borns after prolonged preterm rupture of the membranes remains an elusive goal.