Preferred and actual place of death in haematological malignancy.

OBJECTIVES: Home is considered the preferred place of death for many, but patients with haematological malignancies (leukaemias, lymphomas and myeloma) die in hospital more often than those with other cancers and the reasons for this are not wholly understood. We examined preferred and actual place of death among people with these diseases. METHODS: The study is embedded within an established population-based cohort of patients with haematological malignancies. All patients diagnosed at two of the largest hospitals in the study area between May 2005 and April 2008 with acute myeloid leukaemia, diffuse large B-cell lymphoma or myeloma, who died before May 2010 were included. Data were obtained from medical records and routine linkage to national death records. RESULTS: 323 deceased patients were included. A total of 142 (44%) had discussed their preferred place of death; 45.8% wanted to die at home, 28.2% in hospital, 16.9% in a hospice, 5.6% in a nursing home and 3.5% were undecided; 63.4% of these died in their preferred place. Compared to patients with evidence of a discussion, those without were twice as likely to have died within a month of diagnosis (14.8% vs 29.8%). Overall, 240 patients died in hospital; those without a discussion were significantly more likely to die in hospital than those who had (p≤0.0001). Of those dying in hospital, 90% and 75.8% received haematology clinical input in the 30 and 7 days before death, respectively, and 40.8% died in haematology areas. CONCLUSIONS: Many patients discussed their preferred place of death, but a substantial proportion did not and hospital deaths were common in this latter group. There is scope to improve practice, particularly among those dying soon after diagnosis. We found evidence that some people opted to die in hospital; the extent to which this compares with other cancers is of interest.

Variations in specialist palliative care referrals: findings from a population-based patient cohort of acute myeloid leukaemia, diffuse large B-cell lymphoma and myeloma.

OBJECTIVE: To develop and implement a methodology for capturing complete haematological malignancy pathway data and use it to identify variations in specialist palliative care (SPC) referrals. METHODS: In our established UK population-based patient cohort, 323 patients were diagnosed with acute myeloid leukaemia, diffuse large B-cell lymphoma or myeloma between May 2005 and April 2008, and died before April 2010. A day-by-day calendar approach was devised to collect pathway data, including SPC referrals, to supplement routinely collected information on clinical presentation, diagnosis, treatment, response, and date and place of death. RESULTS: 155 (47.9%) of the 323 patients had at least one SPC referral. The likelihood of referral increased with survival (OR 6.58, 95% CIs 3.32 to 13.03 for patients surviving ≥1 year compared to ≤1 month from diagnosis), and varied with diagnosis (OR 1.96, CIs 1.15 to 3.35 for myeloma compared to acute myeloid leukaemia). Compared to patients dying in hospital, those who died at home or in a hospice were also more likely to have had an SPC referral (OR 3.07, CIs 1.59 to 5.93 and 4.74, CIs 1.51 to 14.81, respectively). No associations were found for age and sex. CONCLUSIONS: Our novel approach efficiently captured pathway data and SPC referrals, revealing evidence of greater integration between haematology and SPC services than previously reported. The likelihood of referral was much higher among those dying outside hospital, and variations in practice were observed by diagnosis, emphasising the importance of examining diseases individually.

Determinants of survival in patients with chronic myeloid leukaemia treated in the new era of oral therapy: findings from a UK population-based patient cohort.

OBJECTIVES: To examine contemporary survival patterns in the general population of patients diagnosed with chronic myeloid leukaemia (CML), and to identify patient groups with less than optimal outcomes. DESIGN: Prospective population-based cohort. SETTING: The UK's Haematological Malignancy Research Network (catchment population 3.6 million, with >2000 new haematological malignancies diagnosed annually). PARTICIPANTS: All patients newly diagnosed with CML, from September 2004 to August 2011 and followed up to 31 March 2013. MAIN OUTCOME MEASURE: Incidence and survival. RESULTS: With a median diagnostic age of 59 years, the CML age standardised (European) incidence was 0.9/100 000 (95% CIs 0.8 to 0.9), 5-year overall survival was 78.9% (72.3 to 84.0) and 5-year relative survival 88.6% (81.0 to 93.3). The efficacy of treatment across all ages was clearly demonstrated; the relative survival curves for those under 60 and over 60 years being closely aligned. Survival findings were similar for men and women, but varied with deprivation; the age and sex adjusted HR being 3.43 (1.89 to 6.22) for deprivation categories 4-5 (less affluent) versus 1-3 (more affluent). None of these differences were attributable to the biological features of the disease. CONCLUSIONS: When therapy is freely provided, population-based survival for CML is similar to that reported in clinical trials, and age loses its prognostic significance. However, although most of the patients with CML now experience close to normal lifespans, those living in more deprived areas tend to have poorer outcomes, despite receiving the same clinical care. A significant improvement in overall population outcomes could be achieved if these socioeconomic differences, which may reflect the treatment compliance, could be eliminated.

Slowly fading super-luminous supernovae that are not pair-instability explosions.

Super-luminous supernovae that radiate more than 10(44) ergs per second at their peak luminosity have recently been discovered in faint galaxies at redshifts of 0.1-4. Some evolve slowly, resembling models of 'pair-instability' supernovae. Such models involve stars with original masses 140-260 times that of the Sun that now have carbon-oxygen cores of 65-130 solar masses. In these stars, the photons that prevent gravitational collapse are converted to electron-positron pairs, causing rapid contraction and thermonuclear explosions. Many solar masses of (56)Ni are synthesized; this isotope decays to (56)Fe via (56)Co, powering bright light curves. Such massive progenitors are expected to have formed from metal-poor gas in the early Universe. Recently, supernova 2007bi in a galaxy at redshift 0.127 (about 12 billion years after the Big Bang) with a metallicity one-third that of the Sun was observed to look like a fading pair-instability supernova. Here we report observations of two slow-to-fade super-luminous supernovae that show relatively fast rise times and blue colours, which are incompatible with pair-instability models. Their late-time light-curve and spectral similarities to supernova 2007bi call the nature of that event into question. Our early spectra closely resemble typical fast-declining super-luminous supernovae, which are not powered by radioactivity. Modelling our observations with 10-16 solar masses of magnetar-energized ejecta demonstrates the possibility of a common explosion mechanism. The lack of unambiguous nearby pair-instability events suggests that their local rate of occurrence is less than 6 × 10(-6) times that of the core-collapse rate.

An outburst from a massive star 40 days before a supernova explosion.

Some observations suggest that very massive stars experience extreme mass-loss episodes shortly before they explode as supernovae, as do several models. Establishing a causal connection between these mass-loss episodes and the final explosion would provide a novel way to study pre-supernova massive-star evolution. Here we report observations of a mass-loss event detected 40 days before the explosion of the type IIn supernova SN 2010mc (also known as PTF 10tel). Our photometric and spectroscopic data suggest that this event is a result of an energetic outburst, radiating at least 6 × 10(47) erg of energy and releasing about 10(-2) solar masses of material at typical velocities of 2,000 km s(-1). The temporal proximity of the mass-loss outburst and the supernova explosion implies a causal connection between them. Moreover, we find that the outburst luminosity and velocity are consistent with the predictions of the wave-driven pulsation model, and disfavour alternative suggestions.

PTF 11kx: a type Ia supernova with a symbiotic nova progenitor.

There is a consensus that type Ia supernovae (SNe Ia) arise from the thermonuclear explosion of white dwarf stars that accrete matter from a binary companion. However, direct observation of SN Ia progenitors is lacking, and the precise nature of the binary companion remains uncertain. A temporal series of high-resolution optical spectra of the SN Ia PTF 11kx reveals a complex circumstellar environment that provides an unprecedentedly detailed view of the progenitor system. Multiple shells of circumstellar material are detected, and the SN ejecta are seen to interact with circumstellar material starting 59 days after the explosion. These features are best described by a symbiotic nova progenitor, similar to RS Ophiuchi.

Light echoes reveal an unexpectedly cool η Carinae during its nineteenth-century Great Eruption.

η Carinae is one of the most massive binary stars in the Milky Way. It became the second-brightest star in our sky during its mid-nineteenth-century 'Great Eruption', but then faded from view (with only naked-eye estimates of brightness). Its eruption is unique in that it exceeded the Eddington luminosity limit for ten years. Because it is only 2.3 kiloparsecs away, spatially resolved studies of the nebula have constrained the ejected mass and velocity, indicating that during its nineteenth-century eruption, η Car ejected more than ten solar masses in an event that released ten per cent of the energy of a typical core-collapse supernova, without destroying the star. Here we report observations of light echoes of η Carinae from the 1838-1858 Great Eruption. Spectra of these light echoes show only absorption lines, which are blueshifted by -210 km s(-1), in good agreement with predicted expansion speeds. The light-echo spectra correlate best with those of G2-to-G5 supergiants, which have effective temperatures of around 5,000 kelvin. In contrast to the class of extragalactic outbursts assumed to be analogues of the Great Eruption of η Carinae, the effective temperature of its outburst is significantly lower than that allowed by standard opaque wind models. This indicates that other physical mechanisms such as an energetic blast wave may have triggered and influenced the eruption.

Hydrogen-poor superluminous stellar explosions.

Supernovae are stellar explosions driven by gravitational or thermonuclear energy that is observed as electromagnetic radiation emitted over weeks or more. In all known supernovae, this radiation comes from internal energy deposited in the outflowing ejecta by one or more of the following processes: radioactive decay of freshly synthesized elements (typically (56)Ni), the explosion shock in the envelope of a supergiant star, and interaction between the debris and slowly moving, hydrogen-rich circumstellar material. Here we report observations of a class of luminous supernovae whose properties cannot be explained by any of these processes. The class includes four new supernovae that we have discovered and two previously unexplained events (SN 2005ap and SCP 06F6) that we can now identify as members of the same class. These supernovae are all about ten times brighter than most type Ia supernova, do not show any trace of hydrogen, emit significant ultraviolet flux for extended periods of time and have late-time decay rates that are inconsistent with radioactivity. Our data require that the observed radiation be emitted by hydrogen-free material distributed over a large radius (∼10(15) centimetres) and expanding at high speeds (>10(4) kilometres per second). These long-lived, ultraviolet-luminous events can be observed out to redshifts z > 4.

Help-seeking behaviour in patients with lymphoma.

Reducing cancer mortality is a priority for the UK Government and emphasis has been placed on introducing targets to ensure prompt diagnosis. Help seeking is the first step on the pathway to diagnosis and should occur promptly; however, patients with lymphoma take longer to seek help for symptoms than those with many other cancers. Despite this, the help seeking behaviour of these patients has not been investigated. This qualitative study examined the beliefs and actions about help seeking among 32 patients, aged 65 and over and newly diagnosed with lymphoma in West Yorkshire during 2000. Patients reported an extremely wide range of symptoms which were not always interpreted as serious or potentially caused by cancer. This, in association with a clear lack of knowledge about lymphoma, often led to help seeking being deferred. The range and characteristics of symptoms can largely be explained in terms of variations in the type, site and size of the lymphoma. The UK Government targets focus on the time after help seeking, yet for lymphoma it is also crucial to reduce the time taken to seek help. More education about the potential symptoms of this disease is needed among the general public.

Referral pathways and diagnosis: UK government actions fail to recognize complexity of lymphoma.

To gain survival advantages potentially associated with prompt diagnosis, the UK government introduced identical waiting-time targets for all cancers, and guidelines to ensure that general practitioners make appropriate hospital referrals. For lymphoma, the evidence guiding these actions is limited. This study examined referral pathways in patients with lymphoma and variations in time to diagnosis by discipline of first referral. A case series study was conducted including all patients aged over 25 years, newly diagnosed with lymphoma in the UK county of West Yorkshire, during 2000. Data were extracted from primary care and hospital records of 189 patients. Referral pathways were described, and the number of days between first referral and diagnosis calculated. A distinct referral pathway did not exist; patients were initially referred to many disciplines. Surgical referrals predominated, and only 12% of patients were sent directly to haematology. Time to diagnosis varied by discipline and was shorter for patients sent to haematology than for most other common disciplines. UK government actions to ensure the prompt diagnosis of patients with lymphoma are not evidence-based. The complexity of the referral pathway in patients with lymphoma, which affects time to diagnosis, has been underestimated. Further government actions should be evidence-based, ensuring prompt diagnosis of lymphoma from whatever discipline patients originate.

Lymphoma: variations in time to diagnosis and treatment.

This study examines illness trajectories of patients with lymphoma and assesses whether UK government targets to reduce waiting time for diagnosis and treatment are achievable and appropriate. One hundred and ninety-four patients, residents in West Yorkshire, aged more than 25 years and newly diagnosed with lymphoma during 2000 were included. Data collected from interviews, primary care and hospital records were used to examine time between critical events on the illness trajectory and characteristics of patients not meeting proposed targets. Forty-two per cent of patients did not receive a hospital appointment within 2 weeks of general practitioner referral, 26% were not treated within 1 month of diagnosis and 64% were not treated within 2 months of referral. Target achievement differed by diagnostic group, and trends were seen by age and deprivation. The interval from onset of symptoms to treatment averaged more than 1 year and approximately half of this occurred before first medical contact. Results suggest that significant improvements are needed to achieve targets. Although existing targets particularly address referral and treatment intervals, these were the shortest intervals on the trajectory. Generalized targets may be inappropriate and unachievable for lymphoma as they do not consider individual disease characteristics or allow for variations in the urgency with which treatment is needed.

Endoscopic resection of benign tumors of the papilla of vater.

Most benign papillary tumors are adenomas which can potentially undergo the adenoma-carcinoma-sequence making complete removal mandatory for curative therapy. Endoscopic resection (papillectomy) of these lesions is being increasingly performed as a less traumatic alternative to surgery. Available data shows endoscopic papillectomy to be effective and safe in experienced hands with usually little morbidity and virtually no mortality. Success rates are around 80 % for lesions without intraductal involvement. Selected cases of limited distal intraductal involvement accessible after sphincterotomy may also be managed curatively by endoscopic resection. Endoscopic snare resection of entire lesions should be primarily regarded as a diagnostic procedure. It allows for an accurate histological diagnosis based on examination of the entire specimen rather than forceps biopsies and thus a reliable assessment of the need for surgical therapy. Subsequent surgery in operable patients is not precluded by previous endoscopic resection. Surgery is indicated in case of incomplete removal and if malignancy is present. The curative role of endoscopic papillectomy for early invasive carcinoma needs to be established. Histological features and individual risk for surgery are factors to be considered. Inoperable patients may still benefit from palliative endoscopic stenting. After endoscopic papillectomy has been completed, regular follow-up examinations including biopsies are warranted because of the risk of local recurrence. For benign looking papillary tumors, endoscopic papillectomy serves as a diagnostic tool and should be considered as first line procedure regardless of age. The following article details the approach to patients with benign papillary tumor and the technique of endoscopic papillectomy.

Endoscopic management of tumors of the major duodenal papilla: Refined techniques to improve outcome and avoid complications.

BACKGROUND: Adenomas of the major duodenal papilla have malignant potential and are traditionally treated by pancreaticoduodenectomy. This is a report of our experience with endoscopic management and a description of techniques for decreasing complications and enhancing efficacy. METHODS: Forty-one patients were referred for endoscopic management of papillary tumors. If there was no duct invasion and the appearance suggested a benign lesion, biductal sphincterotomy with pancreatic duct stent placement was performed. If the lesion could be elevated by injection of an epinephrine solution, piecemeal resection was performed. The base of the lesion was thermally ablated as needed. Resection/ablation together with stent removal was performed 1 month later. RESULTS: Nine patients (22%) had lesions other than papillary adenoma or cancer. Malignant appearance, ductal stricturing, or extension into the ducts was found in 16 of 41 patients (39%) in whom biopsy specimens alone were obtained. Three patients with adenomas (7%) did not undergo endoscopic resection (because of extremely large lesions and/or comorbid illnesses). Thirteen patients with adenomas (32%) had endoscopic resection; 12 (92%) were lesion-free after 32 ERCPs (mean 2.7). Endoscopic management was unsuccessful in 1 patient (8%). Pancreatitis developed in 1 patient. CONCLUSIONS: Endoscopically treatable papillary neoplasms can be identified on the basis of endoscopic, radiographic, and biopsy features. Preresection sphincterotomy, stent placement, elevation by epinephrine injection, and piecemeal resection may reduce complications and permit more aggressive treatment.

Infected pancreatic pseudocysts with colonic fistula formation successfully managed by endoscopic drainage alone: report of two cases.

Fistulization of pancreatic pseudocysts into surrounding viscera is a well-known phenomenon and usually requires surgical management. We report two cases of pancreatic pseudocysts that developed spontaneous fistulas to the colon with resulting fever and abdominal pain. The patients were managed nonoperatively with a combination of endoscopic drainage and antibiotics, and their pseudocysts and fistulas resolved. The patients have remained symptom-free for a mean of 14 months of follow-up.

Endoscopic treatment of pancreatic duct stones using a 10F pancreatoscope and electrohydraulic lithotripsy.

BACKGROUND: Endoscopic therapy with adjunctive extracorporeal shock wave lithotripsy fails to provide clearance of pancreatic duct stones in up to 25% of symptomatic patients. Direct contact lithotripsy may provide an additional option for removal of refractory stones. We report our initial experience using a prototype 10F "baby" endoscope to administer electrohydraulic lithotripsy. METHODS: Five patients failing extracorporeal shock wave lithotripsy and one patient with recurrent pancreatic duct stones after surgery were selected to undergo endoscopic electrohydraulic lithotripsy. After pancreatic sphincterotomy and balloon dilation (8 or 10 mm), the 10F endoscope was introduced and electrohydraulic lithotripsy was used to fragment stones under direct visualization. RESULTS: Six patients underwent 9 intraductal electrohydraulic lithotripsy procedures. Complete or partial pancreatic duct clearance was accomplished in all but one. No complications from the lithotripsy procedure were noted. The 5 patients with partial or complete duct clearance experienced complete relief of abdominal pain of at least 6 months' duration following their final procedure. CONCLUSION: Electrohydraulic lithotripsy within the pancreatic duct provides an adjunctive endoscopic option for treatment of patients with symptomatic pancreatic duct stones. Our initial experience suggests that electrohydraulic lithotripsy therapy can successfully fragment stones refractory to conventional endoscopic stone extraction methods or extracorporeal shock wave lithotripsy. Further experience is necessary to establish the risks of electrohydraulic lithotripsy within the pancreatic duct.

Pancreatic stones: treat or ignore?

Painful, chronic pancreatitis is of complex etiology, but increasing clinical experience suggests that removal of pancreatic duct stones in many cases significantly improves patients' symptoms. The development and refinement of therapeutic endoscopic retrograde choledochopancreatography have permitted improved access to the pancreatic duct, which makes the development of new techniques of stone fragmentation and fragment removal a much more successful nonsurgical intervention. A major step forward has been the understanding of the safety and efficacy of pancreatic sphincterotomy, which is necessary for the removal of these difficult stones. The recognition that extracorporeal shock wave lithotripsy can be delivered safely with good efficacy has revolutionized the nonsurgical management of pancreatic duct stones. Nevertheless, advanced and sophisticated therapeutic endoscopy is necessary to achieve clearance of the duct, which can generally be accomplished in the majority of selected patients. State-of-the-art treatments are described, and some new approaches using pancreatoscopy and electrohydrolic lithotripsy are discussed. Newly recognized long term complications are reviewed. Finally, it must be recognized that chronic pancreatitis is an ongoing disease that does not have a simple treatment or cure, and frequently represents a process of remissions and relapses requiring interventions and problem solving.

Endoscopically placed Gianturco endoprosthesis in the treatment of malignant and benign biliary obstruction.

Since the introduction of the Z-stent by Cesare Gianturco in 1985, the prominent role of endoscopically placed transpapillary endoprostheses as the treatment of choice to relieve malignant biliary obstruction has stimulated much interest and research in the evolution of his initial design. This article reviews the efficacy and limitation of prior Z-stent models in their attempt to relieve malignant and benign biliary obstructions and previews improvements in the design currently being evaluated in a large, multicenter trial.

Dilated common channel syndrome: endoscopic diagnosis, treatment, and relationship to choledochocele formation.

BACKGROUND: Choledochoceles (type III biliary cysts) are cystic dilations of the terminal common bile duct or common pancreatobiliary channel. Although no size criteria have been defined, it is generally assumed these must be large. However, we describe patients who do not meet the perceived size criteria for choledochoceles, but who nonetheless have a dilated common pancreatobiliary channel. METHODS: We reviewed the presenting symptoms, endoscopic and radiographic findings, and response to endoscopic therapy of patients meeting our criteria for the dilated common channel syndrome. RESULTS: Of 2847 patients undergoing ERCP, 100 (3.5%) had the dilated common channel syndrome. Common presenting symptoms and signs included abdominal pain in 97%, abnormal liver function test(s) in 66%, and a history of acute or recurrent pancreatitis in 46%. A bulge was visible above the papilla in 88%, with a dilated common bile duct in 54% and a dilated pancreatic duct in 28%. After endoscopic unroofing of the common channel, 77% had complete and long-lasting resolution of symptoms, 18% had partial or transient improvement, and 5% had no change. CONCLUSIONS: Although classic choledochoceles are rare, a lesser degree of dilation of the common channel is more frequent than generally appreciated. We postulate that this finding represents an "incomplete," acquired form of choledochocele, possibly caused by underlying papillary stenosis. Whatever the etiology and appropriate term, the presence of a dilated common channel predicts a high rate of clinical response to endoscopic therapy.