Radiation induced angiosarcoma of the breast: outcomes from a retrospective case series.

BACKGROUND: Radiation induced angiosarcoma (RIAS) of the breast is a rare and aggressive complication of radiotherapy. Due to the rarity of this disease, much of the evidence for its management is based on case reports or small retrospective series. We sought to describe the management and outcomes of RIAS in a large single-institution series. METHODS: All patients diagnosed with RIAS between January 2000 and January 2014 were identified from an institutional database. RESULTS: A total of 49 patients were identified. Median age at diagnosis was 72 years (range 51-93). Median time from completion of radiotherapy to diagnosis of RIAS was 7.5 years. Median tumour size at presentation was 5.0 cm (1.5-19.0). The majority of patients presented with localised disease (47, 95.9%). Of these, 35 (74.5%) were suitable for surgery and underwent surgery with curative intent. Twelve patients presented with localised irresectable disease. Of these, 7 received systemic chemotherapy, with a sufficient response to facilitate surgery in 3 patients. Following potentially curative surgery, 2-year local recurrence-free was 55.2%. Survival was significantly prolonged in patients presenting with resectable disease (2-year overall survival 71.1% vs 33.3%, p < 0.001). Tumour size >5 cm was prognostic of distant metastases-free survival and overall survival. CONCLUSION: RIAS are rare, aggressive soft-tissue lesions with limited treatment options and high-rates of both local and systemic relapse.

Long term results of treatment of breast cancer without axillary surgery - Predicting a SOUND approach?

BACKGROUND: Traditionally axillary surgery has been used to provide staging information and until recently was thought to improve loco-regional control. However, a more minimal approach to the axilla is now being adopted. The aim of this study was to assess long term outcomes of patients with 'low-risk' breast cancers who did not undergo any axillary surgery. 'Low-risk' criteria were: postmenopausal, <20 mm grade 1 or <15 mm grade 2, LVI-ve, ER +ve. METHODS: Women with invasive breast cancer that did not undergo any axillary surgery were identified. Patients were censored when an event or death occurred or at last follow-up at breast clinic or with their General Practitioner. RESULTS: Between 05/01/1995-20/11/2006, 194 patients (199 tumours) were operated upon without axillary surgery. Median follow-up was 10.4 years. 128 patients met low-risk criteria and 71 did not (patient choice = 42, medical fitness = 29). In the 'low risk' cohort there were two axillary recurrences, with a cumulative incidence of 0.8% and 1.9% at 5 and 10 years respectively. DDFS was 99.2% (94.1-99.9%), and 97% (90.0-99%) at 5 and 10 years respectively and DFS was 96.6% (91.1-98.7%) and 91.2% (82.6-95.6%). OS was 90.3% (95% CI: 83.6-94.4) and 75.5% (95% CI: 65.9-82.8) at 5 and 10 years respectively. CONCLUSION: Axillary recurrence and DDFS in this low-risk cohort is favourable. In the modern era of breast cancer management it is possible to define a group of women in whom axillary surgery can be omitted.

Glioblastoma adaptation traced through decline of an IDH1 clonal driver and macro-evolution of a double-minute chromosome.

BACKGROUND: Glioblastoma (GBM) is the most common malignant brain cancer occurring in adults, and is associated with dismal outcome and few therapeutic options. GBM has been shown to predominantly disrupt three core pathways through somatic aberrations, rendering it ideal for precision medicine approaches. METHODS: We describe a 35-year-old female patient with recurrent GBM following surgical removal of the primary tumour, adjuvant treatment with temozolomide and a 3-year disease-free period. Rapid whole-genome sequencing (WGS) of three separate tumour regions at recurrence was carried out and interpreted relative to WGS of two regions of the primary tumour. RESULTS: We found extensive mutational and copy-number heterogeneity within the primary tumour. We identified a TP53 mutation and two focal amplifications involving PDGFRA, KIT and CDK4, on chromosomes 4 and 12. A clonal IDH1 R132H mutation in the primary, a known GBM driver event, was detectable at only very low frequency in the recurrent tumour. After sub-clonal diversification, evidence was found for a whole-genome doubling event and a translocation between the amplified regions of PDGFRA, KIT and CDK4, encoded within a double-minute chromosome also incorporating miR26a-2. The WGS analysis uncovered progressive evolution of the double-minute chromosome converging on the KIT/PDGFRA/PI3K/mTOR axis, superseding the IDH1 mutation in dominance in a mutually exclusive manner at recurrence, consequently the patient was treated with imatinib. Despite rapid sequencing and cancer genome-guided therapy against amplified oncogenes, the disease progressed, and the patient died shortly after. CONCLUSION: This case sheds light on the dynamic evolution of a GBM tumour, defining the origins of the lethal sub-clone, the macro-evolutionary genomic events dominating the disease at recurrence and the loss of a clonal driver. Even in the era of rapid WGS analysis, cases such as this illustrate the significant hurdles for precision medicine success.

EMVI-positive stage II rectal cancer has similar clinical outcomes as stage III disease following pre-operative chemoradiotherapy.

BACKGROUND: Stage II rectal cancers comprise a heterogeneous group, and there is significant variability in practise with regards to adjuvant chemotherapy; the survival benefit of chemotherapy is perceived to be <4% in these patients. However, in recent years, the emergence of additional prognostic factors such as extramural venous invasion (EMVI) suggests that there may be sub-stratification of stage II tumours and, further, we may be under-estimating the benefit adjuvant chemotherapy provides in high-risk patients. This study examined the outcomes of patients with stage II and III rectal cancer to determine whether EMVI status influences disease-free survival (DFS). PATIENTS AND METHODS: An analysis of a prospectively maintained database was conducted of patients presenting with rectal cancer between 2006 and 2012. All patients underwent curative surgery and had no evidence of metastases at presentation. Clinicopathological factors were compared between stage II and III disease. The primary end point was 3-year DFS; univariate and multivariate analysis was carried out using Cox proportional hazards regression models; hazard ratios (HR) with 95% confidence intervals (CIs) were calculated. RESULTS: Four hundred and seventy-eight patients were included: 233 stage II; 245 stage III. The prevalence of EMVI was 34.9%; 57 stage II patients (24.5%) and 110 stage III patients (44.9%). On multivariate analysis, only EMVI status was a significant factor for DFS. The adjusted HR for EMVI either alone or in combination with nodal involvement was 2.08 (95% CI 1.10-2.95) and 2.74 (95% CI 1.66-4.52), respectively. CONCLUSION: EMVI is an independently poor prognostic factor for DFS for both stage II and stage III rectal cancer. These results demonstrate that there is risk-stratification within stage II tumours which affects prognosis. When discussing the use of adjuvant chemotherapy with patients that have EMVI-positive stage II tumours, these results provide evidence for a similarly increased risk of distant failure as stage III disease without venous invasion.

Whole-genome sequencing reveals complex mechanisms of intrinsic resistance to BRAF inhibition.

BACKGROUND: BRAF is mutated in ∼42% of human melanomas (COSMIC. http://www.sanger.ac.uk/genetics/CGP/cosmic/) and pharmacological BRAF inhibitors such as vemurafenib and dabrafenib achieve dramatic responses in patients whose tumours harbour BRAF(V600) mutations. Objective responses occur in ∼50% of patients and disease stabilisation in a further ∼30%, but ∼20% of patients present primary or innate resistance and do not respond. Here, we investigated the underlying cause of treatment failure in a patient with BRAF mutant melanoma who presented primary resistance. METHODS: We carried out whole-genome sequencing and single nucleotide polymorphism (SNP) array analysis of five metastatic tumours from the patient. We validated mechanisms of resistance in a cell line derived from the patient's tumour. RESULTS: We observed that the majority of the single-nucleotide variants identified were shared across all tumour sites, but also saw site-specific copy-number alterations in discrete cell populations at different sites. We found that two ubiquitous mutations mediated resistance to BRAF inhibition in these tumours. A mutation in GNAQ sustained mitogen-activated protein kinase (MAPK) signalling, whereas a mutation in PTEN activated the PI3 K/AKT pathway. Inhibition of both pathways synergised to block the growth of the cells. CONCLUSIONS: Our analyses show that the five metastases arose from a common progenitor and acquired additional alterations after disease dissemination. We demonstrate that a distinct combination of mutations mediated primary resistance to BRAF inhibition in this patient. These mutations were present in all five tumours and in a tumour sample taken before BRAF inhibitor treatment was administered. Inhibition of both pathways was required to block tumour cell growth, suggesting that combined targeting of these pathways could have been a valid therapeutic approach for this patient.

Adjuvant chemotherapy improves overall survival after TME surgery in mucinous carcinoma of the rectum.

INTRODUCTION: Mucinous tumours of the rectum are characterised by an abundance of extracellular mucin within the tumour complex. They are known to have a poor prognosis compared to non-mucinous adenocarcinomas. The effect of adjuvant chemotherapy on the survival outcomes of patients with mucinous cancer remains unclear. This study evaluated the 5-year overall survival of patients with mucinous rectal cancer following optimal TME surgery to determine whether adjuvant chemotherapy conferred a survival benefit. METHODS: An analysis of a prospectively-maintained database was conducted of patients presenting with mucinous rectal cancer between 2000 and 2010. Patients with mucinous tumours were identified from final pathology reports of the surgical resection specimens. The primary outcome was 5-year overall survival; univariate and multivariate analysis was performed using Cox proportional hazards regression models. RESULTS: A total of 191 patients were included for analysis with mean age of presentation 64.6 years (36-88 ± 11). On the fully adjusted multivariate model, EMVI status (HR 1.853, 95% CI 1.081-3.175) and not being given adjuvant chemotherapy (HR 2.888, 95% CI 1.801-4.633) were significant for disease recurrence. The 5-year overall survival for patients that had undergone adjuvant chemotherapy was 66.1% compared with 35.2% (Mantel Cox log-rank test - p < 0.0001). CONCLUSION: This study demonstrates that adjuvant chemotherapy is an independent factor for improvement in overall survival in patients with mucinous adenocarcinoma. Therefore, patients who have undergone TME surgery for mucinous carcinoma of the rectum should be offered adjuvant chemotherapy even in the absence of other high-risk features for poor outcomes.

Patupilone in patients with pretreated metastatic/locally recurrent colorectal cancer: results of the Phase II CINATRA trial.

BACKGROUND: Phase I trials of the microtubule stabilising agent patupilone showed encouraging tumour control and response rates in patients with metastatic colorectal cancer. METHODS: Patients with metastatic or locally recurrent colorectal cancer who had progressed following treatment with oxaliplatin, irinotecan and fluoropyrimidines were treated with patupilone (8 mg/m(2) IV every 3 weeks) in combination with dexamethasone or prednisolone. RESULTS: The trial was closed early after 29 patients had been enrolled due to concerns about toxicity. 20 patients (71.4 %) experienced at least one grade 3-5 toxicity, most commonly diarrhoea (14 patients), dehydration (7 patients) and lethargy (6 patients). The 12 week progression-free survival rate was 16.7 % (95 % CI 6.1 %-36.5 %) in the 24 patients with a 12 week scan available or who had died prior to the 12 week scan. No complete or partial responses were seen by 12 weeks. The median progression-free survival was 2.6 months (95 % CI 2.3-2.9) and median overall survival was 6.1 months (95 % CI 3.7-8.4). CONCLUSION: Patupilone given at a dose of 8 mg/m(2) IV over 20 min every 3 weeks was associated with high levels of toxicity and no significant evidence of efficacy in patients with pre-treated colorectal cancer.

Survival analysis after pancreatic resection for ampullary and pancreatic head carcinoma: an analysis of clinicopathological factors.

BACKGROUND AND OBJECTIVES: Surgery remains the only curative option for the treatment of pancreatic and ampullary carcinomas. To examine the survival differences between ampullary and pancreatic head carcinomas after pancreaticoduodenectomy. METHODS: A retrospective review of patients with ampullary or pancreatic head adenocarcinoma undergoing curative resection during a 6-year period prior to 2000. RESULTS: A total of 104 patients underwent pancreaticoduodenectomy for pancreatic head and ampullary carcinomas (n = 65 and n = 39, respectively). Histologically, pancreatic cancer was worse, with more lymph node involvement and more positive resection margins and vascular and perineural invasions than found in ampullary carcinoma. The median disease-free and overall survival rates were significantly better for ampullary cancer when compared with pancreatic cancer (17 vs. 9 months [P = 0.001] and 35 vs. 24 months [P = 0.006], respectively). The actuarial 5-year disease-free and overall survival rates were 4.4% and 10.5%, respectively, for pancreatic carcinoma and 27.9% and 31.8%, respectively, for ampullary carcinoma. Multivariate analysis showed that microscopic resection margin involvement (P = 0.02) and involvement of over three nodes (P < 0.001) were significant factors affecting the overall survival for pancreatic and ampullary carcinomas, respectively. CONCLUSIONS: In this study, patients with ampullary carcinoma have a better prognosis and survival than those with pancreatic carcinoma.

Kisspeptin-54 at high doses acutely induces testicular degeneration in adult male rats via central mechanisms.

BACKGROUND AND PURPOSE: The kisspeptins are critical regulators of reproduction and a therapeutic target for reproductive disease. Intracerebroventricular (i.c.v.) or peripheral injection of kisspeptin potently stimulates the hypothalamic-pituitary gonadal (HPG) axis via gonadotrophin-releasing hormone (GnRH). However, little is known regarding the effects of kisspeptin administration on testicular function. We investigated the mechanism(s) of kisspeptin-induced testicular degeneration in the rat. EXPERIMENTAL APPROACH: Kisspeptin-54 (50 nmol.day(-1)) was continuously administered subcutaneously (6 h to 3 days) to male Wistar rats and reproductive hormones and testicular histology analysed. We also investigated the effects of a single subcutaneous injection of 0.5, 5 or 50 nmol kisspeptin-54. In order to determine whether the testicular degeneration observed is peripherally or centrally mediated, we investigated effects of i.c.v. injections of 5 nmol kisspeptin-54 and pre-administered a GnRH-receptor antagonist (cetrorelix) to rats peripherally treated with kisspeptin-54. KEY RESULTS: Continuous subcutaneous administration of kisspeptin-54 caused testicular degeneration after only 12 h, when gonadotrophins were still markedly raised, suggesting that the degeneration is independent of the desensitization of the HPG axis to kisspeptin-54. Furthermore, a single subcutaneous injection of kisspeptin-54 caused dose-dependent testicular degeneration. Continuous kisspeptin-54 administration is thus not required to cause testicular degeneration. Pretreatment with cetrorelix blocked kisspeptin-induced testicular degeneration, and a single i.c.v. injection of kisspeptin-54 caused testicular degeneration, suggesting it is GnRH-mediated. CONCLUSIONS AND IMPLICATIONS: Kisspeptin-induced testicular degeneration appears to be centrally mediated, and result from acute hyper-stimulation of the HPG axis. Doses must be carefully considered if kisspeptin is to be used therapeutically.

High MMP-9 activity characterises pleural tuberculosis correlating with granuloma formation.

Tuberculosis (TB) pleural disease is complicated by extensive tissue destruction. Matrix metalloproteinase (MMP)-1 and -9 are implicated in immunopathology of pulmonary and central nervous system TB. There are few data on MMP activity in TB pleurisy. The present study investigated MMP-1, -2 and -9 and their specific inhibitors (tissue inhibitor of metalloproteinase (TIMP)-1 and -2) in tuberculous effusions, and correlated these with clinical and histopathological features. Clinical data, routine blood tests, and pleural fluid/biopsy material were obtained from 89 patients presenting with pleural effusions in a TB-endemic area. MMP-1, -2 and -9 were measured by zymography or western blot, and TIMP-1 and -2 by ELISA. Pleural biopsies were examined microscopically, cultured for acid-alcohol fast bacilli and immunostained for MMP-9. Tuberculous pleural effusions contained the highest concentrations of MMP-9 compared with malignant effusions or heart failure transudates. MMP-9 concentrations were highest in effusions from patients with granulomatous biopsies: median (interquartile range) 108 (61-218) pg x mL(-1) versus 43 (12-83) pg x mL(-1) in those with nongranulomatous pleural biopsies. MMP-1 and -2 were not upregulated in tuberculous pleural fluid. The ratio of MMP-9:TIMP-1 was significantly higher in TB effusions. Tuberculous pleurisy is characterised by a specific pattern of matrix metalloproteinase-9 upregulation, correlating with the presence of granulomas and suggesting a specific role for matrix metalloproteinase-9 in inflammatory responses in tuberculous pleural disease.

Fluorescence lifetime imaging distinguishes basal cell carcinoma from surrounding uninvolved skin.

BACKGROUND: Fluorescence lifetime imaging (FLIM) is a novel imaging technique that generates image contrast between different states of tissue due to differences in fluorescence decay rates. OBJECTIVES: To establish whether FLIM of skin autofluorescence can provide useful contrast between basal cell carcinomas (BCCs) and surrounding uninvolved skin. METHODS: Unstained excision biopsies of 25 BCCs were imaged en face with FLIM following excitation of autofluorescence with a 355 nm pulsed ultraviolet laser. RESULTS: Using FLIM we were able to distinguish areas of BCC from surrounding skin in an ex vivo study. Significant reductions in mean fluorescence lifetimes between areas of BCC and areas of surrounding uninvolved skin were demonstrated (P < 0.0001). These differences were apparent irrespective of the decay model used to calculate the fluorescence lifetimes (single vs. stretched exponential) or the long-pass filter through which the emitted autofluorescence was collected (375 vs. 455 nm). Conversely, there was no significant difference between the BCC and uninvolved areas of each sample when mean autofluorescence intensities were examined. Moreover, wide-field false-colour images of fluorescence lifetimes clearly discriminated areas of BCC from the surrounding uninvolved skin. CONCLUSIONS: We therefore believe that FLIM has a potential future clinical role in imaging BCCs for rapid and noninvasive tumour delineation and as an aid to determine adequate excision margins with best preservation of normal tissue.

Clinical and imaging experience with yttrium-90 microspheres in the management of unresectable liver tumours.

INTRODUCTION: Selective internal radiation therapy (SIRT) is emerging as a new therapeutic modality in recent years for management of non-resectable hepatic malignancies. Our experience in clinical application of this treatment is reported here. MATERIAL AND METHODS: From June 2004, patients whose liver tumours were no longer amenable for any conventional treatment with either chemotherapy or surgery were considered for yttrium-90 microspheres treatment after discussion at our multidisciplinary meeting. A pre-treatment planning was carried out with visceral angiography and technetium-99m macroaggregated albumin (MAA) for assessment of both tumour volume and extrahepatic shunting in addition to a baseline PET and CT scans, respectively. Two weeks later, a second visceral angiogram was performed to deliver the calculated dosage of microspheres into the arterial system supplying the tumour. Patients were then followed up with tumour markers, repeat PET and CT scans of abdomen at 6 weeks and 3 monthly thereafter. RESULT: Twenty-one patients (F=11, M=10; age range 40-75 years, mean=58 years) received yttrium-90 microspheres consisting of liver metastases from colorectal primary (n=10) and non-colorectal primaries (n=8), and primary liver tumours (n=3). One patient received 2 treatments. The mean administered activity of microspheres delivered was 1.9 GBq (range 1.2-2.5 GBq). Injection of microspheres had no immediate effect on either clinical haematology or liver function tests. At follow-up, 86% of patients showed decreased activity on PET scan at 6 weeks (p=0.01). The mean pre-treatment SUV was 12.2+/-3.7 and the mean post-treatment SUV was 9.3+/-3.7, indicating a significant improvement measured with PET activity. Only 13% showed a reduction in the size of tumour on CT scan. For patients with colorectal liver metastases, there was no significant reduction in CEA level (127+/-115 vs 75+/-72 micro/l, p=0.39). Complications were seen in 4 patients (19%) including radiation hepatitis (n=2), cholecystitis (n=1) and duodenal ulceration (n=1). All resolved without surgical intervention. Seven patients died at follow-up from progressive extrahepatic disease (33%). CONCLUSION: SIRT should be considered for patients with advanced liver cancer. It has a significant effect on liver disease in the absence of extrahepatic disease. PET imaging has an integral role in the assessment of patients treated with yttrium-90 SIR-Spheres.

A hyperspectral fluorescence lifetime probe for skin cancer diagnosis.

The autofluorescence of biological tissue can be exploited for the detection and diagnosis of disease but, to date, its complex nature and relatively weak signal levels have impeded its widespread application in biology and medicine. We present here a portable instrument designed for the in situ simultaneous measurement of autofluorescence emission spectra and temporal decay profiles, permitting the analysis of complex fluorescence signals. This hyperspectral fluorescence lifetime probe utilizes two ultrafast lasers operating at 355 and 440 nm that can excite autofluorescence from many different biomolecules present in skin tissue including keratin, collagen, nicotinamide adenine dinucleotide (phosphate), and flavins. The instrument incorporates an optical fiber probe to provide sample illumination and fluorescence collection over a millimeter-sized area. We present a description of the system, including spectral and temporal characterizations, and report the preliminary application of this instrument to a study of recently resected (<2 h) ex vivo skin lesions, illustrating its potential for skin cancer detection and diagnosis.

Management and prevention of adverse effects related to treatment of liver tumours with 90Y microspheres.

BACKGROUND AND AIM: Selective internal radiation therapy with 90Y microspheres (SIR spheres) is increasingly used in the treatment of extensive liver tumours. Careful selection and preparation of patients are necessary to avoid possible adverse effects. We aimed to evaluate the incidence and severity of adverse effects resulting from the administration of SIR spheres during therapy. MATERIALS AND METHODS: Between June 2004 and August 2006, 21 patients (11 women and 10 men; age range 40-75 years; mean, 58 years) with a wide range of extensive liver tumours were treated with SIR spheres. The mean administered dose was 1.87 GBq (range 1.2-2.5 GBq). During the follow-up period of 26 months, all adverse effects were monitored and classified according to the National Cancer Institute criteria. RESULTS: Four patients had adverse effects: one case of cholecystitis followed by fibrosis and portal hypertension, one case of peptic ulceration and two cases of radiation hepatitis. All cases responded to appropriate therapy. CONCLUSION: Proper selection of patients and accurate interpretation of pre-treatment investigations are vital for minimizing adverse effects following therapy with SIR spheres. In our experience, all adverse effects were moderate with no life-threatening consequences.

Optimal processing of bone marrow trephine biopsy: the Hammersmith Protocol.

Specimens of bone marrow trephine biopsy (BMT) are transported and fixed in acetic acid-zinc-formalin fixative, decalcified in 10% formic acid-5% formaldehyde and processed with other specimens to paraffin-wax embedding. Sections, 1-microm-thick, are cut by experienced histotechnologists and used for haematoxylin and eosin, Giemsa, reticulin silver and other histological stains. Further, all immunohistochemical procedures used in the laboratory, including double immunostaining, can be used on these sections with no or minimal modifications. About 10,000 BMT specimens have been analysed using this procedure since 1997 and diseases involving the bone marrow have been classified successfully. More recently, standardised polymerase chain reaction-based analysis and mRNA in situ hybridisation studies have been conducted. Excellent morphology with good antigen, DNA and RNA preservation is offered by the Hammersmith Protocol.

Intraepidermal animal-type melanoma.

Animal-type melanoma is a rare variant of melanoma in humans.1 Its name is derived from its histological appearance, which is similar to that described in melanomas occurring in white or gray horses.2 All tumors are dermally located, and characterized by a proliferation of deeply pigmented elongated or rounded cells, showing moderate atypia and a low mitotic rate. In some tumors, secondary infiltration of the epidermis has been noted. More than half of the patients are younger than 30 years, and prognosis seems to be much better than that expected for a superficial spreading or nodular melanoma of the same size. We report the first case of animal-type melanoma in situ.

A breastfeeding study in a rural population in South Australia.

INTRODUCTION: The benefits of breastfeeding for mothers and babies are well recognised; however, challenges to its establishment and maintenance exist in rural locations. METHOD: This study in a rural community aimed to: (1) collect rates of any breastfeeding at 6 weeks, 3 months and 6 months postpartum; and (2) seek women's postnatal breastfeeding needs and discern how they were met. Fifty-eight women, most of whom had planned to birth at one of two rural hospitals with fewer than 50 births a year were interviewed face-to-face or by telephone. Questions included whether they were still breastfeeding, reasons for stopping, and their breastfeeding support needs in hospital and after discharge on eight domains: establishment; attachment; engorgement; sore nipples; cracked nipples; ongoing support; supply and mastitis. RESULTS: The number breastfeeding at 3 months (55%) compared poorly with South Australia (62%) or nationally (63%). Midwives met most of the needs of the women in hospital while, at home, midwives and GPs remained the main sources of support. At home, small numbers contacted the Australian Breastfeeding Association, child and youth health service nurse; a midwife employed by a pharmacist and family members such as mothers and mothers-in-law for support. Overall, 25% of women who had an identified need did not seek help. Of those who did, 36% had the need met well and 28% poorly. After discharge, 52 (90%) would have welcomed a visit from a community midwife had it been available. In the regional town, facilities to breastfeed and change babies' nappies were rated poor or non-existent. CONCLUSION: Since this study, a part-time community midwife has been employed and a new project initiated that educates and assists older women volunteers to support and promote breastfeeding for isolated new mothers.

Toward the clinical application of time-domain fluorescence lifetime imaging.

High-speed (video-rate) fluorescence lifetime imaging (FLIM) through a flexible endoscope is reported based on gated optical image intensifier technology. The optimization and potential application of FLIM to tissue autofluorescence for clinical applications are discussed.

Optically sectioned fluorescence lifetime imaging using a Nipkow disk microscope and a tunable ultrafast continuum excitation source.

We demonstrate an optically sectioned fluorescence lifetime imaging microscope with a wide-field detector, using a convenient, continuously tunable (435-1150 nm) ultrafast source for fluorescence imaging applications that is derived from a visible supercontinuum generated in a microstructured fiber.