Cancer survivors' experiences of discharge from hospital follow-up.

Discharge from hospital follow-up is a key time point in the cancer journey. With recommendations for earlier discharge of cancer survivors, attention to the discharge process is likely to become increasingly important. This study explored cancer survivors' experiences of discharge from hospital follow-up. Survivors of breast, colorectal and prostate cancer (n= 1275), 5-16 years post diagnosis were approached to take part in a questionnaire survey. The questionnaire included questions about discharge status, provision of time/information prior to discharge, feelings at discharge and satisfaction with how discharge was managed. Completed questionnaires were returned by 659 survivors (51.7%). Approximately one-third of respondents were not discharged from follow-up 5-16 years post diagnosis. Of those discharged, a substantial minority reported insufficient time (27.9%), information (24.5-45.0%) or adverse emotions (30.9%) at the time of discharge. However, 90.6% of respondents reported satisfaction with how discharge from hospital follow-up was managed. Despite high levels of satisfaction, discharge of cancer survivors from hospital follow-up could be improved with the provision of additional time, information and support. Better structuring of the final hospital appointment or a review appointment in primary care at this time could help to ensure that discharge from hospital follow-up is managed optimally for cancer survivors.

Primary care endorsement letter and a patient leaflet to improve participation in colorectal cancer screening: results of a factorial randomised trial.

BACKGROUND: The trial aimed to investigate whether a general practitioner's (GP) letter encouraging participation and a more explicit leaflet explaining how to complete faecal occult blood test (FOBT) included with the England Bowel Cancer Screening Programme invitation materials would improve uptake. METHODS: A randomised controlled 2 × 2 factorial trial was conducted in the south of England. Overall, 1288 patients registered with 20 GPs invited for screening in October 2009 participated in the trial. Participants were randomised to either a GP's endorsement letter and/or an enhanced information leaflet with their FOBT kit. The primary outcome was verified with return of the test kit within 20 weeks. RESULTS: Both the GP's endorsement letter and the enhanced procedural leaflet, each increased participation by ∼6% - the GP's letter by 5.8% (95% CI: 4.1-7.8%) and the leaflet by 6.0% (95% CI: 4.3-8.1%). On the basis of the intention-to-treat analysis, the random effects logistic regression model confirmed that there was no important interaction between the two interventions, and estimated an adjusted rate ratio of 1.11 (P=0.038) for the GP's letter and 1.12 (P=0.029) for the leaflet. In the absence of an interaction, an additive effect for receiving both the GP's letter and leaflet (11.8%, 95% CI: 8.5-16%) was confirmed. The per-protocol analysis indicated that the insertion of an electronic GP's signature on the endorsement letter was associated with increased participation (P=0.039). CONCLUSION: Including both an endorsement letter from each patient's GP and a more explicit procedural leaflet could increase participation in the English Bowel Cancer Screening Programme by ∼10%, a relative improvement of 20% on current performance.

Impact of dermoscopy and short-term sequential digital dermoscopy imaging for the management of pigmented lesions in primary care: a sequential intervention trial.

BACKGROUND: Studies have shown the benign to malignant ratio of excised pigmented skin lesions is suboptimal in primary care. OBJECTIVES: To assess the impact of dermoscopy and short-term sequential digital dermoscopy imaging (SDDI) on the management of suspicious pigmented skin lesions by primary care physicians. METHODS: A total of 63 primary care physicians were trained in the use of dermoscopy and SDDI (interventions) and then recruited pigmented lesions requiring biopsy or referral in routine care by naked eye examination. They were then given a dermatoscope and the option of a SDDI instrument, and change of diagnosis and management was assessed. RESULTS: Following the use of the interventions on 374 lesions a total of 163 lesions (43.6%) were excised or referred, representing a reduction of 56.4%. Of the 323 lesions confirmed to be benign, 118 (36.5%) were excised or referred, leading to a reduction of 63.5% (P < 0.0005) in those requiring excision or referral. The baseline naked eye examination benign to melanoma ratio was 9.5 : 1 which decreased to 3.5 : 1 after the diagnostic interventions (P < 0.0005). Of the 42 malignant lesions included in the study (34 melanoma, six pigmented basal cell carcinoma and two Bowen disease) only one in situ melanoma was incorrectly managed (patient to return if changes occur) resulting in the correct management of 97.6% and 97.1% of malignant pigmented lesions and melanoma, respectively. CONCLUSIONS: In a primary care setting the combination of dermoscopy and short-term SDDI reduces the excision or referral of benign pigmented lesions by more than half while nearly doubling the sensitivity for the diagnosis of melanoma.

Current and potential providers of blood pressure self-screening: a mixed methods study in Oxfordshire.

OBJECTIVES: To (1) establish the extent of opportunities for members of the public to check their own blood pressure (BP) outside of healthcare consultations (BP self-screening), (2) investigate the reasons for and against hosting such a service and (3) ascertain how BP self-screening data are used in primary care. DESIGN: A mixed methods, cross-sectional study. SETTING: Primary care and community locations in Oxfordshire, UK. PARTICIPANTS: 325 sites were surveyed to identify where and in what form BP self-screening services were available. 23 semistructured interviews were then completed with current and potential hosts of BP self-screening services. RESULTS: 18/82 (22%) general practices offered BP self-screening and 68/110 (62%) pharmacies offered professional-led BP screening. There was no evidence of permanent BP self-screening activities in other community settings.Healthcare professionals, managers, community workers and leaders were interviewed. Those in primary care generally felt that practice-based BP self-screening was a beneficial activity that increased the attainment of performance targets although there was variation in its perceived usefulness for patient care. The pharmacists interviewed provided BP checking as a service to the community but were unable to develop self-screening services without a clear business plan. Among potential hosts, barriers to providing a BP self-screening service included a perceived lack of healthcare commissioner and public demand, and a weak-if any-link to their core objectives as an organisation. CONCLUSIONS: BP self-screening currently occurs in a minority of general practices. Any future development of community BP self-screening programmes will require (1) public promotion and (2) careful consideration of how best to support-and reward-the community hosts who currently perceive little if any benefit.

Mechanisms of apoptosis in T cells from patients with renal cell carcinoma.

Tumors may escape immune recognition and destruction through the induction of apoptosis in activated T lymphocytes. Results from several laboratories suggest that FasL (L/CD95L) expression in tumors may be responsible for this process. In this study of patients with renal cell carcinoma (RCC), we provide evidence for two mechanisms of T-cell apoptosis. One mechanism involves the induction of apoptosis via FasL expression in tumor cells. This is supported by several observations, including the fact that tumor cells in situ as well as cultured cell lines expressed FasL mRNA and protein by a variety of techniques. The FasL in RCC is functional because in coculture experiments, FasL+ tumors induced apoptosis in Fas-sensitive Jurkat T cells and in activated peripheral blood T cells but not in resting peripheral blood T cells. Most importantly, antibody to FasL partially blocked apoptosis of the activated T cells. Moreover, Fas was expressed by T cells derived from the peripheral blood (53% median) and tumor (44.3% median) of RCC patients. Finally, in situ staining for DNA breaks demonstrated apoptosis in a subset of T cells infiltrating renal tumors. These studies also identified a second mechanism of apoptosis in RCC patient peripheral T cells. Whereas these cells did not display DNA breaks when freshly isolated or after culture for 24 h in medium, peripheral blood T cells from RCC patients underwent activation-induced cell death after stimulation with either phorbol 12-myristate 13-acetate/ionomycin or anti-CD3/CD28 antibodies. Apoptosis mediated by exposure to FasL in tumor cells or through T-cell activation may contribute to the failure of RCC patients to develop an effective T-cell-mediated antitumor response.

Are autoimmune thyroid dysfunction and depression related?

The objective of this study was to examine the relationship between autoimmune thyroid disease and depression in perimenopausal women. Thyroid function [TSH, free T4, and thyroid peroxidase antibodies (TPO-Ab)] and depression (using the Edinburgh Depression Scale) were assessed cross-sectionally together with other determinants of depression. The subjects were 583 randomly selected perimenopausal women (aged 47-54 yr) from a community cohort of 6846 women. The main outcome measures were the occurrence of thyroid dysfunction (abnormal free T4 and/or TSH or elevated levels of TPO-Ab) and the concomitant presence of depression according to the Edinburgh Depression Scale. Neither biochemical thyroid dysfunction nor menopausal status was related to depression. Apart from several psycho-social determinants (the occurrence of a major life event, a previous episode of depression, or financial problems), an elevated level of TPO-Ab (> or = 100 U/mL) was significantly associated with depression (odds ratio, 3.0, 95% confidence interval, 1.3-6.8). We conclude that women with elevated TPO-Ab levels are especially vulnerable to depression, whereas postmenopausal status does not increase the risk of depression.

Endothelial cell expression of the intercellular adhesion molecule-1 (ICAM-1) in the central nervous system of guinea pigs during acute and chronic relapsing experimental allergic encephalomyelitis.

This study investigated the expression of intercellular adhesion molecule-1 (ICAM-1; CD54) by cells of the central nervous system (CNS) during acute experimental allergic encephalomyelitis (EAE) and chronic relapsing EAE (CREAE). In the CNS of normal guinea pigs, only a few endothelial cells expressed detectable levels of ICAM-1, whereas during the active phases of the disease ICAM-1 was present on cells of the perivascular infiltrate and the endothelia of both lesion- and non-lesion-associated blood vessels. In addition, cultured cerebrovascular endothelia maintained in 'standard' culture medium did not express ICAM-1, but they could be induced to express this antigen on incubation in a lymphocyte-conditioned medium. These findings suggest that the induction of ICAM-1 on CNS endothelia may be important in antigen presentation or in promoting lymphocyte extravasation across the blood-brain barrier in inflammatory disorders of the CNS.

Behavioral responsiveness in preterm infants with intraventricular hemorrhage.

Preterm infants with varying degrees of intraventricular hemorrhage (none, n = 21; grade I to II, n = 22; grade II to IV, n = 24) and a group of full-term infants (n = 21) were compared with regard to behavioral responsiveness and parental reports of the infant's temperament. Behavioral responsiveness was assessed during the presentation of 15 visual, auditory, and tactile stimuli at 3 months of age (corrected age for preterm infants). Summary scores for positive and negative responsiveness, as well as sociability, soothability, and overall activity levels, were derived from behavioral observations by coders who were unaware of the infant's characteristics. The Bates Infant Characteristic Questionnaire was completed by the main care giver and scored on four summary variables: fussy-difficult, unadaptable, dull, and unpredictable. Preterm infants, regardless of the presence or severity of intraventricular hemorrhage, showed less positive responses and less overall activity in response to stimulation. Infants with grade I to II intraventricular hemorrhage were less sociable and more difficult to soothe than full-term control infants. Individual differences in positive, negative, sociability, and soothability were related to the questionnaire scores of fussy-difficult and unadaptability. Both prematurity and degree of intraventricular hemorrhage affect behavioral responsiveness and these individual differences are related to parental reports of the infant's temperament.

Prediction of local recurrence of ductal carcinoma in situ of the breast using five histological classifications: a comparative study with long follow-up.

The increased detection of ductal carcinoma in situ (DCIS) by mammographic screening and the more widespread use of breast-conserving surgery have led to a search for histological features associated with the risk of recurrence. In a case control study of 141 patients with long follow-up, we compared the ability of five morphological classifications to predict recurrence after local excision. A significant correlation was not found between recurrence and growth pattern when a traditional classification based on architecture was used nor with necrosis when a scheme based principally on this feature was employed. A correlation was, however, found between recurrence and "differentiation" as defined by nuclear features and cell polarization in a classification recently formulated by the European Pathologists Working Group (EPWG), but this failed to reach statistical significance at the 5% level. A stronger and statistically significant correlation was found between nuclear grade as defined by the EPWG and recurrence when cell polarization was disregarded, using the classification currently employed by the UK National Health Service and European Commission-funded Breast Screening Programmes. This was attributable to a small number of recurring cases being downgraded as a consequence of exhibiting polarized cells. A significant correlation between histology and recurrence was also observed using the Van Nuys classification, which is based on nuclear grade and necrosis. Whether the tumor recurred as in situ or invasive carcinoma was unrelated to histological classification, as was the time course over which it occurred. These findings strongly support the use of nuclear grade to identify cases of DCIS at high risk of recurrence after local excision, but further work is necessary to determine whether nuclear grade or necrosis is more appropriate to subdivide the non-high-grade cases.

Biochemical features of intrahepatic cholestasis.

PIP: A pattern of results is reported which was found to be common among patients who had intrahepatic cholestasis (IHC) which was rarely found in patients with other hepatic conditions. The pattern was recognized from over 1000 cases suspected of hepatobiliary disease. 29 were diagnosed with IHC, and excluding 4, 25 revealed the following etiological pattern: chlorpromazine (12 patients); pregnancy and oral contraceptive use (8); and other (5). As opposed to patients with acute and chronic hepatic disease, IHC sufferers had relatively normal values for immunoglobulins and antibody titers. A disproportionate elevation of serum bilirubin vis-a-vis serum enzymatic activities separated potential IHC cases into intra- and extrahepatic cholestasis. The following factorial evaluations were useful in distinguishing hepatic disease states: 1) when the sum of the activities of serum alkaline phosphatase, 5'-nucleotidase, aspartate and alanine amiotransferases, and isocitrate dehydrogenase was divided by the serum bilirubin concentration, there was good resolution of the distinction between patients with IHC and those with primary biliary cirrhosis, early and late viral hepatitis, cholelithiasis, and pancreatic and bile duct cancers. 2) Resolution was also achieved when the numerator included alkaline phosphatase, 5'-nucleotidase, and aspartate aminotransferase, but not when alkaline phosphatase alone, or alkaline phosphatase combined with 5'-nucleotidase, was used. The essential lesion in IHC is an excretory defect.^ieng

Serum enzyme tests in diseases of the liver and biliary tree.

Eight serum enzyme tests were performed over a three-year period in 1,147 cases of patients with suspected hepatobiliary disease, of whom 580 had identifiable primary disease of the liver or biliary system. Individually, aminotransferase assays did not provide good discrimination among the various categories of hepatobiliary disease, but when expressed as a ratio a useful degree of discrimination was obtained. Isocitrate dehydrogenase, guanase and glutamate dehydrogenase alone were poor discriminants of the various disease categories studied; combination of the latter enzyme with the aminotransferases in various ratios did not achieve worthwhile improvement. Adenosine deaminase was normal in most patients with extrahepatic obstruction and abnormal in most patients with parenchymal hepatic disease, and is potentially a useful test additional to the aminotransferases in routine diagnosis. 5'-Nucleotidase was more sensitive and specific than alkaline phosphatase in diagnosing hepatobiliary disorders. Abnormalities of all these enzymes were encountered in patients who did not have hepatobiliary disease, most frequently among subjects with cancer, diabetes mellitus, and diseases of the respiratory and cardiovascular systems.

Tubular metaplasia in Bowman's capsule.

Proximal tubular type metaplasia of the epithelium of Bowman's capsule is described in a fit young adult male. This form of metaplasia is unlike those previously described and could cause initial confusion if encountered in a percutaneous renal biopsy.

The structure of the breast in mucoviscidosis.

The histological appearances of the breast in a patient with mucoviscidosis are those of complete lobular agenesis. Ducts and ductules are well developed, and there is abundant fibrous tissue giving the breast a normal contour. The appearances are contrasted with those of gynaecomastia, and the aetiology is discussed.

Alpha1 antitrypsin deficiency and liver disease in childhood: genetic, immunochemical, histological, and ultrastructural diagnosis.

alpha(1) Antitrypsin deficiency is a significant factor in the pathogenesis of neonatal cholestasis and progressive juvenile cirrhosis. The diagnosis may be suggested by the liver biopsy appearances and confirmed by immunochemical analysis of the serum. Genetic counselling of affected families is of importance, as medical treatment is ineffective at the present time.

Diagnostic value of liver function tests and Entamoeba histolytica antibody studies in East Africans.

Liver function tests and Entamoeba histolytica (E.H.) antibody titres have been studied in a variety of tropical and liver diseases. Patients with hepatic amoebiasis had a raised E.H. antibody titre and tended to have a low pseudocholinesterase activity. In two cases of amoebic liver abscess, which were treated by aspiration and emetine, there was a remarkable drop in the E.H. antibody titre. In a number of other hepatic and tropical conditions the E.H. antibody titre was not significantly raised and the liver function tests were typical of the various conditions studied.

Should continent diversion be performed in patients with locally advanced bladder cancer?

OBJECTIVES: To assess the effect of local, regional, and distant recurrence on pouch function in patients with locally advanced bladder cancer treated by cystectomy and continent diversion. METHODS: A review of 64 consecutive patients undergoing orthotopic (n = 40) or continent cutaneous (n = 24) urinary diversion was performed; 25 patients (39.1%) had locally advanced cancers as defined by deep muscle invasion, extension into perivesical fat, stromal invasion of the prostate, or node-positive disease. Patients were followed at 6-month intervals with physical examination, assessment of voiding function, and computed tomography (CT) scans. RESULTS: The pelvic recurrence rate was 4.7% in the overall group and 12% in patients with locally advanced disease. In the 39 patients with organ-confined tumors, 34 (87%) are alive without evidence of recurrence and have normal pouch function with a median follow-up of 27 months. Four patients in this group receiving systemic chemotherapy for clinical recurrences have retained normal pouch function until last follow-up or death. In the 25 patients with locally advanced tumors, 15 (60%) are alive without evidence of recurrence and have normal pouch function with a median follow-up of 15 months. Seven patients in this group received a median three cycles of adjuvant chemotherapy, and 4 patients received chemotherapy for clinically evident recurrences. Surgical recovery did not delay the onset of adjuvant therapy in any patient, nor did problems specifically related to the presence of a continent pouch delay any cycle of chemotherapy in those patients treated for recurrent disease in either group. Only 1 patient (1.5%) experienced treatment-related toxicity related to the presence of a continent diversion. CONCLUSIONS: This experience suggests that the use of orthotopic or continent cutaneous diversions after cystectomy in patients with locally advanced bladder cancer is safe, does not interfere with the delivery of subsequent therapy, and allows most patients to anticipate normal pouch function even in the presence of recurrent disease.

Serum alpha fetoprotein kinetics in hepatocellular carcinoma. A case for cessation of therapy.

As chemotherapy with adriamycin is accompanied by toxic side effects, early recognition of ineffective treatment is important. Marker kinetics, apparent half-life (AFL) and doubling time (DT), showed that in five patients with advanced hepatocellular carcinoma, adriamycin was ineffective. Failure of the chemotherapeutic regimen was apparent by the third course of treatment.

Ureteropelvic junction obstruction in children. Unique considerations for open operative intervention.

The treatment of UPJ obstruction in children should be approached in a fashion that recognizes the differences between children and adults. Radiographic definition of the urinary tract is different in children than in adults because of the size of the child and technical difficulties with instrumentation. Retrograde pyelography, in general, is not necessary in children, although this decision must be individualized. The surgical incision should be chosen based on the size of the child and the unique considerations of individual renal anatomy and pathology, as well as the surgeon's experience. In children, tubeless surgery may be performed with excellent results, however, diversion with nephrostomies and stents may be necessary in selected cases. With attention to technical details and the unique considerations in children, the results of repair of the UPJ should be excellent and reproducible.

Amniotic fluid acetylcholinesterase isoenzyme patterns in the diagnosis of neural tube defects.

Acetylcholinesterase isoenzyme patterns were determined in amniotic fluid from 140 normal pregnancies and from 68 pregnancies with various fetal abnormalities. A fast acetylcholinesterase isoenzyme was detected in all cases of neural tube defect, exomphalos and intrauterine death. The fast isoenzyme was not seen in any of the normal pregnancies. Blood-contaminated amniotic fluids with false positive elevation of alphafetoprotein gave a single isoenzyme band. The qualitative demonstration of a fast acetylcholinesterase isoenzyme in amniotic fluid provides a useful adjunct to the alphafetoprotein assay in the prenatal diagnosis of neural tube defects.

A diagnostic triad for portal cirrhosis.

Abnormal serum aminotransferase activities with dominance of aspartate aminotransferase over alanine aminotransferase activity, and elevated serum adenosine deaminase activity and immunoglobulin. A concentration, were commonly encountered among patients with portal cirrhosis. The full triad was present in 31 of 49 cases (63%). As isolated abnormalities, these features were not uncommon in patients with other diseases of the liver and biliary tree, but the full triad was found only in 11 of 163 such cases (6.8%). The presence of this triad in a patient with unexplained hepatomegaly is indicative of portal cirrhosis.