Has the survival of patients with glioblastoma changed over the years?

BACKGROUND: Over the last decade, the approach to the management of brain tumours and the understanding of glioblastoma tumour biology has advanced and a number of therapeutic interventions have evolved, some of which have shown statistically significant effects on overall survival (OS) and progression-free survival in glioblastoma. The aim of this study is to compare survival in glioblastoma patients over a 10-year period (1999-2000 and 2009-2010). METHODS: A retrospective cohort study was performed. Identification of all histologically confirmed glioblastoma in a single centre in years 1999, 2000, 2009 and 2010, and production of survival analysis comparing 1999-2000 and 2009-2010 were achieved. RESULTS: A total of 317 patients were included in the analysis (133 in year 1999-2000, and 184 in year 2009-2010). Cox regression analysis showed that the survival was significantly longer in patients in years 2009-2010 than those in 1999-2000 at P<0.001 with HR=0.56, confidence interval (CI) (0.45-0.71). The 1- and 3-year survival rates were 20.7% and 4.4%, respectively, for patients in 1999-2000, improving to 40.0% and 10.3%, respectively, for patients in 2009-2010. The comparisons between the two groups in survival at 1, 2 and 3 years are all statistically significant at P<0.001, respectively. The median OS was 0.36 and 0.74 in 1999-2000 and 2009-2010 groups, respectively. CONCLUSIONS: Over this period, OS from glioblastoma has increased significantly in our unit. We believe this is due to the institution of evidence-based surgical and oncological strategies practised in a multidisciplinary setting.

Thyroid lobectomy for low-risk thyroid cancers.

BACKGROUND: The 2016 American Thyroid Association (ATA) guidelines proposed thyroid lobectomy for low-risk differentiated thyroid cancer (DTC); however, this approach is yet to be widely adopted. The aim of the study was to review our practice over three years following the publication of these guidelines identifying patients who underwent lobectomy-only for low-risk DTC in two regional units in the same multidisciplinary team (MDT). METHOD: A retrospective review of patients who were operated between January 2016 and December 2018 was carried out. RESULTS: In total, 288 patients undergoing thyroid surgery were included. The preoperative distribution of cytology was: Thy 1 or 2 in 46, THY3a in 57, THY3f in 154, THY4 in 18 and THY5 in 13 patients. Median size of nodules was 26mm (range 1-70mm). DTC was diagnosed in 95 patients (33%). Overall, 39% (n = 37) of patients underwent completion thyroidectomy according to ATA recommendations on size or adverse histological features. The only variable associated with likelihood of completion was tumour size (p < 0.05, OR 1.14). Ten patients were discharged following surgery with no further follow-up as they had T1a/b well-differentiated DTC with no high-risk histological features. CONCLUSION: Lobectomy-only appears to be the current surgical practice in two-thirds of patients presenting to our regional units with differentiated thyroid carcinoma. In the context of the current drive to reduce the extent of treatment for low-risk thyroid cancer, there is a need for a more homogeneous approach to these patients and for protocols for long-term follow-up after lobectomy-only.

System resilience and neighbourhood action on social determinants of health inequalities: an English Case Study.

AIMS: This article seeks to make the case for a new approach to understanding and nurturing resilience as a foundation for effective place-based co-produced local action on social and health inequalities. METHODS: A narrative review of literature on community resilience from a public health perspective was conducted and a new concept of neighbourhood system resilience was developed. This then shaped the development of a practical programme of action research implemented in nine socio-economically disadvantaged neighbourhoods in North West England between 2014 and 2019. This Neighbourhood Resilience Programme (NRP) was evaluated using a mixed-method design comprising: (1) a longitudinal household survey, conducted in each of the Neighbourhoods For Learning (NFLs) and in nine comparator areas in two waves (2015/2016 and 2018/2019) and completed in each phase by approximately 3000 households; (2) reflexive journals kept by the academic team; and (3) semi-structured interviews on perceptions about the impacts of the programme with 41 participants in 2019. RESULTS: A difference-in-difference analysis of household survey data showed a statistically significant increase of 7.5% (95% confidence interval (CI), 1.6 to 13.5) in the percentage of residents reporting that they felt able to influence local decision-making in the NFLs relative to the residents in comparator areas, but no effect attributable to the NRP in other evaluative measures. The analysis of participant interviews identified beneficial impacts of the NRP in five resilience domains: social connectivity, cultural coherence, local decision-making, economic activity, and the local environment. CONCLUSION: Our findings support the need for a shift away from interventions that seek solely to enhance the resilience of lay communities to interventions that recognise resilience as a whole systems phenomenon. Systemic approaches to resilience can provide the underpinning foundation for effective co-produced local action on social and health inequalities, but they require intensive relational work by all participating system players.

Post-thyroidectomy tracheomalacia: minimal risk despite significant tracheal compression.

BACKGROUND: Tracheomalacia is a feared complication of goitre surgery, but considered rare in the Western World. This study aimed to estimate the risk of tracheomalacia in a contemporary series of patients with goitres causing significant tracheal compression. METHODS: A retrospective review was conducted of thyroidectomies performed in a UK tertiary referral centre over a 30 month period. Anaesthetic, operative, radiological, and pathological data were obtained from medical notes and hospital software systems. RESULTS: Of 334 patients who underwent thyroid surgery, preoperative CT scan was performed in 101 (30%). Tracheal compression was reported in 62 patients (19%) with minimum tracheal diameter ranging from 2 to 15 mm (mean 7.6 mm) due to multinodular goitre (n=50), malignancy (n=10), or thyroiditis (n=2). Critical compression <5 mm was observed in 18 patients (6%) and 35 patients had compression to 6-10 mm. Awake fibreoptic intubation was performed in eight patients (six of those with tracheas <5 mm) and asleep fibreoptic intubation was performed in one. Standard intubation was performed otherwise. All patients were recovered on a general surgical ward. None required tracheostomy or tracheal stenting. The incidence of tracheomalacia was 0 (95% confidence interval 0.0-4.8%). Mean length of stay was 2.4 days in those with tracheas <5 mm and 2.0 days in those >5 mm. CONCLUSIONS: We found no evidence of tracheomalacia in high-risk patients with significant tracheal compression. This supports prior work on retrosternal goitres suggesting that the risk of tracheomalacia is minimal in modern thyroid surgery. For risk management, however, we would still advocate that such patients be managed in units with multispeciality support.

18Fluorocholine PET/CT scanning with arterial phase-enhanced CT is useful for persistent/recurrent primary hyperparathyroidism: first UK case series results.

INTRODUCTION: Redo parathyroidectomy for persistent/recurrent primary hyperparathyroidism is associated with a higher risk of complications and should be planned only with convincing localisation. We assessed whether 18fluorocholine positron emission tomography/computed tomography could identify parathyroid adenoma(s) in patients with persistent/recurrent primary hyperparathyroidism and negative conventional scans. MATERIALS AND METHODS: A departmental database was used to identify patients with failed localisation attempts (sestamibi single photon emission computed tomography/computed tomography and/or computed tomography/magnetic resonance imaging and/or selective parathyroid hormone sampling) after previous unsuccessful surgery for primary hyperparathyroidism. 18Fluorocholine positron emission tomography was performed in all patients and redo surgery offered to those with positive findings. RESULTS: 18Fluorocholine positron emission tomography incorporating arterial and portal phase enhanced computed tomography was performed in 12 patients with persistent/recurrent primary hyperparathyroidism (four men and eight women). Seven patients (58%) were cured after excision of adenomas located in ectopic positions (n = 3) or in anatomical position (n = 4). Five patients (42%) had persistent hypercalcaemia and repeat 18fluorocholine scan confirmed that the area highlighted on preoperative scans was excised. The arterial phase enhancement of the computed tomography was significantly different between cured and not-cured patients (P = 0.007). All seven cured patients had either a strong or weak enhancing pattern on computed tomography. Standardised uptake value at 60 minutes in patients with successful surgery (range 2.7-15.7, median 4.05) was higher than in patients with failed surgery (range 1.8-5.8, median 3.2) but was not statistically significant (P = 0.300). DISCUSSION: 18fluorocholine scanning can identify elusive parathyroid adenomas, including those that are ectopic, and is useful in the management of patients with persistent/recurrent primary hyperparathyroidism when first-line scans are negative. The grading of the arterial phase of computed tomography can help to differentiate between true adenomas and false positive targets (lymph nodes).

Selective axillary node sampling and radiotherapy to the axilla in the management of breast cancer.

AIMS: Axillary treatment for patients with early-stage breast cancer can be associated with considerable morbidity. Techniques, such as axillary node sampling (ANS) and, more recently, sentinel node biopsy, in combination with radiotherapy have the potential to reduce toxicity. A retrospective review of axillary treatment in patients with early-stage breast cancer treated at our institution between 1997 and 2003 was carried out to assess the outcome and morbidity of ANS in combination with radiotherapy. MATERIALS AND METHODS: The treatment policy was to carry out four-node, Edinburgh-style ANS except in those cases with either palpably enlarged nodes or cytological confirmation of involvement or with clinically obvious node involvement at surgery when level 2 axillary node clearance (ANC) was carried out. Patients with involved nodes after ANS received postoperative axillary radiotherapy. RESULTS: In total, 381 patients were included, 331 received ANS and 50 received ANC. The median follow-up was 6.5 years and overall survival at 5 years was 84%. Pathologically involved nodes were found in 152/331 (50%) ANS patients and 43/50 (86%) ANC patients. The rate of local recurrence (breast or chest wall) at 5 years was 4% (95% confidence interval 1-17%) in the ANC group and 2% (95% confidence interval 1-4%) in the ANS group. The nodal recurrence rate of those undergoing ANS was 3% (11/331) compared with 6% (3/50) for those treated by ANC. The rate of clinically significant lymphoedema at 5 years was significantly higher (P=0.01) in the ANC arm: 18% (95% confidence interval 9-32%) compared with 5% (95% confidence interval 3-8%) in those treated by ANS. Thirty-one cases received additional supraclavicular fossa irradiation because of the involvement of more than four nodes on ANS, which may not have been available with sentinel node biopsy and has implications for current practice. CONCLUSIONS: Selective ANS with the removal of a minimum of four nodes guides optimal locoregional treatment with good local control rates, low overall morbidity and may obviate the need for a second surgical procedure.

Deaf patient-provider communication and lung cancer screening: Health Information National Trends survey in American Sign Language (HINTS-ASL).

OBJECTIVE: To assess whether mode of communication and patient centered communication (PCC) with physicians were associated with the likelihood of deaf smokers inquiring about lung cancer screening. METHODS: An accessible health survey including questions about PCC, modes of communication, smoking status and lung cancer screening was administered in American Sign Language (HINTS-ASL) to a nationwide sample of deaf adults from February to August 2017. Of 703 deaf adults who answered the lung screening question, 188 were 55-80 years old. RESULTS: The odds ratio of asking about a lung cancer screening test was higher for people with lung disease or used ASL (directly or through an interpreter) to communicate with their physicians. PCC was not associated with asking about a lung cancer screening test. CONCLUSION: Current or former smokers who are deaf and use ASL are at greater risk for poorer health outcomes if they do not have accessible communication with their physicians. PRACTICE IMPLICATIONS: Optimal language access through interpreters or directly in ASL is critical when discussing smoking cessation or lung cancer screening tests. Counseling and shared decision-making will help improve high-risk deaf patients' understanding and decision-making about lung cancer screening.

Binding of aberrant glycoproteins recognizable by Helix pomatia agglutinin in adrenal cancers.

BACKGROUND: Aberrant glycosylation is a hallmark of cancer cells and plays an important role in oncogenesis and cancer progression including metastasis. This study aimed to assess alteration in cellular glycosylation, detected by lectin Helix pomatia agglutinin (HPA) binding, in adrenal cancers and to determine whether such altered glycosylation has prognostic significance. METHODS: HPA binding lectin histochemistry was performed on archival paraffin wax-embedded specimens of adrenocortical cancers excised from patients attending two tertiary referral centres. Benign tumours were used as controls. Demographic, histological and survival data were collected and compared between patients with HPA-positive and HPA-negative tumours. RESULTS: Thirty-two patients were treated for adrenal cancer between 2000 and 2016; their median age was 49 (range 23-79) years. Fifteen patients had functioning tumours (14 adrenal Cushing's tumours and 1 Conn's tumour). Mean(s.d.) tumour size was 127·71(49·70) mm. None of 10 control tumours expressed HPA-binding glycoproteins. Invasion was associated with HPA-binding glycoproteins (P = 0·018). Local recurrence or metastatic disease did not significantly differ between HPA-positive and HPA-negative adrenocortical cancers. Overall survival was significantly longer in patients with HPA-negative tumours (median survival not reached versus 22 months in patients with HPA-positive tumours; P = 0·002). CONCLUSION: Altered cellular glycosylation detected by lectin HPA is associated with poor survival in patients with adrenocortical cancer.

Bilateral adrenalectomy: a review of 10 years' experience.

INTRODUCTION The 2012 British Association of Endocrine and Thyroid Surgeons audit report showed that only 86 of 1359 patients who underwent adrenalectomy had a bilateral operation; thus the experience with this procedure remains limited. METHODS Retrospective review of patients undergoing bilateral adrenalectomy in a tertiary referral centre. RESULTS Between November 2005 and January 2016, bilateral adrenalectomy was performed in 23 patients (6 male, 17 female, age 43 ± 4 years) diagnosed with Cushing's disease (n = 13), hereditary phaeochromocytomas (n = 6), adrenocortical cancer (n = 2), colorectal metastatic disease (n = 1) and adrenocortical adenomas (n = 1). A laparoscopic transperitoneal approach was used in 17 patients, with one conversion to open. Three patients had open adrenalectomies for adrenocortical cancer and for simultaneous phaeochromocytomas and pancreatic neuroendocrine tumours in a patient with Von Hippel-Lindau syndrome. Three patients with Cushing's had a bilateral retroperitoneoscopic operation. The mean operating time was 195 ± 16 minutes for laparoscopic operations (n = 16), 243 ± 44 minutes for open adrenalectomies (n = 4) and 151 ± 12 minutes for retroperitoneal operations. It was significantly shorter for Cushing's disease than for phaeochromocytomas (162 ± 8 vs. 257 ± 39 minutes, P < 0.01). Median length of hospital stay was 5 days. Postoperative complications (Clavien-Dindo classification) included one chest infection (level 2), one postoperative haemorrhage and two chest drains for pneumothorax (level 3), two postoperative cardiac arrests (level 4) and one late cancer death from complications related to uncontrolled hypercortisolism (level 5). DISCUSSION Synchronous bilateral adrenalectomy remains an infrequent operation. The laparoscopic approach is feasible in the majority of patients. It is likely that the retroperitoneoscopic adrenalectomy will become the standard approach for bilateral operations.

Complications in methotrexate treatment of psoriasis with particular reference to liver fibrosis.

All patients taking methotrexate for treatment of psoriasis over the past 5 yr have been reviewed. Thirty-eight patients have had pretreatment liver biopsies and at least 1 repeat liver biopsy. Of the 38, nine (24%) have developed significant liver fibrosis or cirrhosis, and have stopped treatment. The high incidence of fibrosis is attributed to synergism between methotrexate and other hepatotoxic factors, particularly alcohol, the use of a baseline biopsy to identify subsequent changes, and the early detection of fibrosis by sensitive histological techniques.

Malignant haemangioendothelioma involving the liver.

The features of four cases of malignant haemangioendothelioma involving the liver and other organs are described. Two cases were associated with a microangiopathic haemolytic anaemia. The nature of the tumours and possible pathogenesis for the anaemias are discussed.

Spindle-cell tumours and hypoglycaemia.

The light microscopy and clinical features of two patients with extrapancreatic tumours and hypoglycaemic episodes are described-together with the electron microscopy findings in one patient. The primary tumour of one patient arose within the skull and later metastasized to the liver, while the other patient had a locally recurrent intrathoracic tumour. Neither the intracranial origin nor the ultrastructural features support the concept of a mesothelial origin for these tumours, and they should be referred to as spindle-cell tumours associated with hypoglycaemia. There are ultrastructural similarities between these neoplasms and those of the pancreatic beta cells.

Alpha-1-antitrypsin in human macrophages.

Preliminary studies have suggested that alpha-1-antitrypsin (A1AT) is a useful immunohistochemical marker of histiocytes (monocytes/macrophages) and malignant tumours derived from them. To confirm the reliability of this marker a wide variety of benign and malignant lymphoreticular cells and tissues have been stained by the immunoperoxidase technique for A1AT and positive staining was found to be confined to histiocytes. Immunodiffusion, isotope labelling, and isoelectric focusing studies performed on cell lysates confirmed that the positive staining shown by monocytes and malignant histiocytes is due to the presence of A1AT identical with serum A1AT and that this material is synthesised by these cells rather than taken up from their environment. Positive immunoperoxidase staining for A1AT is thus a reliable marker of lymphoreticular neoplasms of true histiocytic origin.

Strategies for reaching Asian Americans with health information.

INTRODUCTION: Cultural, linguistic, and economic barriers place many Asian Americans in jeopardy of missing opportunities for disease prevention, early diagnosis, prompt treatment, and participation in clinical trials. One way to learn how to address these barriers is through the development of a demonstration health education and prevention program focused on an indicator disease such as cancer. METHODS: In 1994, the University of California, San Diego (UCSD) Cancer Center began a highly focused cancer education program. Staffing was done with a variety of bicultural and bilingual undergraduates recruited from local colleges and trained to work as community health educators. Asian grocery stores were selected as optimal educational sites. Adaptation of sheltered English teaching techniques and hands-on teaching aids helped to overcome language and educational barriers. The educational intervention was evaluated using unobtrusive measures. RESULTS: With the volunteers' help, culturally sensitive means to disseminate information on cancer were evaluated. A variety of approaches evolved that effectively bridged many communication barriers. Fear of cancer itself, belief that thinking about cancer could provoke the onset of the disease, and financial barriers to care proved to be just as formidable barriers to cancer education in this ethnic group as they are in others. Using student volunteers and donated store space, this educational program was conducted with minimal expense. CONCLUSION: Reaching this population with the help of ethnically and linguistically compatible students was effective, but the barriers they faced when trying to connect with their potential audience were still considerable. Rigorous evaluation of the strategies used in this intervention is warranted.

Telephone counseling for smoking cessation: effects of single-session and multiple-session interventions.

Smokers (N = 3,030) were randomized to receive 1 of 3 interventions: (a) a self-help quit kit, (b) a quit kit plus 1 telephone counseling session, or (c) a quit kit plus up to 6 telephone counseling sessions, scheduled according to relapse probability. Both counseling groups achieved significantly higher abstinence rates than the self-help group. The rates for having quit for at least 12 months by intention to treat were 5.4% for self-help, 7.5% for single counseling, and 9.9% for multiple counseling. The 12-month continuous abstinence rates for those who made a quit attempt were 14.7% for self-help, 19.8% for single counseling, and 26.7% for multiple counseling. A dose-response relation was observed, as multiple sessions produced significantly higher abstinence rates than a single session. The first week after quitting seems to be the critical period for intervention.

Review of surgical management of aldosterone secreting tumours of the adrenal cortex.

AIMS: To evaluate the investigation and surgical management of primary hyperaldosteronism. Retrospective case note analysis of thirty-three patients who underwent adrenalectomy for primary hyperaldosteronism between 1982 and 2001 and a current relevant literature review. METHODS: The records of twelve male and twenty-one female patients, age range 18 to 81 (mean 48 years) were reviewed. Eleven operations were performed by an open approach and twenty-two laparoscopically. Preoperative investigations included computed tomography (CT), magnetic resonance imaging (MRI), selective venous sampling and seleno-cholesterol isotope scanning, along with biochemical and hormonal assays. Twenty-six benign adenomas, three nodular hyperplastic lesions, one primary adrenal hyperplasia and three functional carcinomas were excised. Mean follow up was 12 months. RESULTS: Patients had a mean blood pressure of 185/107 mmHg for 6.2 years mean duration. The mean severity of hypokalaemia was 2.7 mmol/l. Sensitivity of CT scanning was 85%, and of MRI 86%. Fifty percent of seleno-cholesterol scans were accurate. Mean operating time was 158 min for laparoscopic adrenalectomy whilst open surgery took 129 min (p=0.2, NS). Two cases commenced laparoscopically required open access for control of primary haemorrhage whilst one other bleed was managed via the operating ports. Mean postoperative stay was significantly shorter for the laparoscopic group (3 days compared with 7.9 days, p<0.0001). Thirty day mortality was zero. There were three infective complications in the open group (two chest, one wound) with no postoperative complications in the laparoscopic group. All patients were cured of hypokalaemia, whilst 62% cure of hypertension was achieved. Of those patients whose blood pressure was improved preoperatively by spironolactone 78% were cured by adrenalectomy. Adrenalectomy led to an overall reduction in the mean number of anti-hypertensive medications (2.3 drugs preoperative to 0.6 postoperative, p<0.0001). Of those not cured, 58% had improved blood pressure control requiring less medication on average (1.6 drugs compared with 2.6 drugs, p=0.08). Mean age of patients not cured by surgery was 55 years, whilst those cured was 44 years (p=0.03). CONCLUSIONS: Primary hyperaldosteronism is a rare but important cause of hypertension. Selective venous sampling is a useful tool where investigations are inconclusive and fail to lateralise secretion. Patients with primary hyperaldosteronism enjoy lower complication rates and earlier discharge with the advent of laparoscopic surgery. Most patients will be cured of their hypertension and all of hypokalaemia. Laparoscopic adrenalectomy is now the accepted method of surgery for benign hyperaldosteronism. Those with bilateral disease due to idiopathic hyperaldosteronism (IHA) are not candidates for surgery and should be treated medically.

Invasive cervical cancer in Southampton and South West Hampshire: effect of introducing a comprehensive screening programme.

A study of invasive cervical cancer in Southampton and South West Hampshire is reported, covering three consecutive three year periods during which the screening coverage increased from an estimated 60% to a recorded 87% of eligible women aged 20-64. From the first to the third periods of the study in that age group registrations of fully invasive squamous cell carcinoma (stage lb and above) fell from 64 to 30 (53%), which was largely counteracted by an increase in microinvasive squamous cell carcinoma (linear trend: P<0.0001). In the same age group registrations of adenocarcinoma rose slightly, which resulted from an increase in the number diagnosed at a depth of invasion of less than 3 mm. There were no significant changes in the numbers of stage III and IV cancers or among cancers in women aged 65 and over. A strong inverse association was found between stage of both histological types of cancer and their likelihood of being screen detected rather than symptomatic: 91% of screen detected cancers were diagnosed at stage I compared with 38% of symptomatic cancers. There was a slight downward trend in the incidence of cancer per 100,000 total female population across the three periods of the study with a significant trend towards low stage disease, which is likely to reduce mortality in years to come. The trend towards screen detected cancers and cancers of less than 3 mm depth of invasion is presented as a positive outcome to be expected in early rounds of increasing the screening coverage.