Patients' experiences of a suppoRted self-manAGeMent pAThway In breast Cancer (PRAGMATIC): quality of life and service use results.

PURPOSE: To describe trends and explore factors associated with quality of life (QoL) and psychological morbidity and assess breast cancer (BC) health service use over a 12-month period for patients joining the supported self-management (SSM)/patient-initiated follow-up (PIFU) pathway. METHODS: Participants completed questionnaires at baseline, 3, 6, 9 and 12 months that measured QoL (FACT-B, EQ 5D-5L), self-efficacy (GSE), psychological morbidity (GHQ-12), roles and responsibilities (PRRS) and service use (cost diary). RESULTS: 99/110 patients completed all timepoints; 32% (35/110) had received chemotherapy. The chemotherapy group had poorer QoL; FACT-B total score mean differences were 8.53 (95% CI: 3.42 to 13.64), 5.38 (95% CI: 0.17 to 10.58) and 8.00 (95% CI: 2.76 to 13.24) at 6, 9 and 12 months, respectively. The odds of psychological morbidity (GHQ12 >4) were 5.5-fold greater for those treated with chemotherapy. Financial and caring burdens (PRRS) were worse for this group (mean difference in change at 9 months 3.25 (95% CI: 0.42 to 6.07)). GSE and GHQ-12 scores impacted FACT-B total scores, indicating QoL decline for those with high baseline psychological morbidity. Chemotherapy patients or those with high psychological morbidity or were unable to carry out normal activities had the highest service costs. Over the 12 months, 68.2% participants phoned/emailed breast care nurses, and 53.3% visited a hospital breast clinician. CONCLUSION: The data suggest that chemotherapy patients and/or those with heightened psychological morbidity might benefit from closer monitoring and/or supportive interventions whilst on the SSM/PIFU pathway. Reduced access due to COVID-19 could have affected service use.

Global abnormalities in lymphatic function following systemic therapy in patients with breast cancer.

BACKGROUND: Breast cancer-related lymphoedema (BCRL) is a result of interaction between several pathophysiological processes, and is not simply a 'stopcock' effect resulting from removal of axillary lymph nodes. The aim of this study was to test the hypothesis that there is a constitutional 'global' lymphatic dysfunction in patients who develop BCRL. METHODS: Lower-limb lymphoscintigraphy was performed in 30 women who had undergone axillary lymph node dissection at least 3 years previously, of whom 15 had BCRL and 15 did not. No patient had any clinical abnormality of the lower limb. The control group comprised 24 women with no history of cancer or lower-limb lymphoedema. (99m) Tc-Nanocoll was injected subcutaneously into the first webspace of each foot, followed by whole-body imaging. Scans were reported as abnormal if there was delay in lymph transport or rerouting through skin or deep system. Quantification was expressed as the percentage injected activity accumulating in ilioinguinal nodes. RESULTS: Mean(s.d.) ilioinguinal nodal accumulation at 150 min was significantly lower in women with BCRL than in those without (2·7(2·5) versus 5·9(4·8) per cent respectively; P = 0·006). Abnormal findings on lower-limb lymphoscintigraphy were observed in 17 of the 30 patients: ten of the 15 women who had BCRL and seven of the 15 who did not. None of the 24 control subjects had abnormal scan findings. CONCLUSION: Women with BCRL had reduced lower-limb lymph drainage, supporting the hypothesis of a predisposition to BCRL. A surprisingly high proportion of patients with breast cancer also demonstrated lymphatic dysfunction, despite clinically normal lower limbs. Possible explanations could be a systemic effect of breast cancer or its treatment, or an unidentified association between breast cancer and lymphatic dysfunction. REGISTRATION NUMBER: ISRCTN84866416 ( http://www.isrctn.com).

[Primary prophylaxis of venous thromboembolism in ambulatory cancer patients treated with antineoplastic agents]. / Prophylaxie primaire de la maladie thromboembolique veineuse chez les patients cancéreux ambulatoires traités par les antinéoplasiques.

Apart from myeloma, primary prophylaxis of venous thromboembolism (VTE) in ambulatory cancer patients treated with chemotherapy is underused, despite its proven benefit for pancreatic cancer and to a lesser extent for lung cancer. This prophylaxis has been showed to be effective for myeloma, pancreas but in absolute numbers these cancers lead to a few venous thromboembolic events. Up to date, VTE risk scores cannot be used as a discriminatory criterion to select a high-risk population that could really benefit from this prevention. VTE depends in part on oncogenic mutations of tumor cells that result in an imbalance between activation and inhibition pathways that are involved in venous thrombus formation. So, stratification of risk of VTE in cancer patients could be considered from a clinical and molecular point of view and result in a tailored prophylaxis. This "personalized medicine" that is currently used for the anti-tumor treatment of many cancers and hematological malignancies, could lead to a more effective prophylaxis of VTE in cancer patients.

[Venous thromboembolism associated with long-term use of central venous catheters in cancer patients]. / Thromboses sur cathéter central chez le patient cancéreux.

OBJECTIVES: Increased incidence of cancers and the development of totally implanted venous access devices that contain their own port to deliver chemotherapy will lead to a greater than before numbers of central venous catheter related thrombosis (CVCT). Medical consequences include catheter dysfunction and pulmonary embolism. Compared with lower extremity deep venous thrombosis (DVT) (3 d) and with non CVC associated thrombosis (5 d), CVCT is associated with an increased duration of hospitalisation (9 d). CVCT oftentimes leads to the need to replace such ports at an average cost of 4500 euros. CURRENT KNOWLEDGE AND KEY POINTS: Vessel injury caused by the procedure of CVC insertion is the most important risk factor for development of CVCT. This event could cause the formation of a fresh thrombus, which is reversible in the large majority of patients. The incidence of CVC-related DVT assessed by venography has been reported to vary from 30 to 60% but catheter-related DVT in adult patients is symptomatic in only 5% of cases. The majority of patients with CVC-related DVT is asymptomatic or has non-specific symptoms: arm or neck swelling or pain, distal paresthesias, headache, congestion of subcutaneous collateral veins. In the case of clinical suspicion of CVC-related DVT, compressive ultrasonography (US), especially with Doppler and color imaging, currently is first used to confirm the diagnosis. The main criteria of color-Doppler US are visualization of mural thrombi or incompressibility of the veins. Consequently, contrast venography is reserved for clinical trials and difficult diagnostic situations. There is no consensus on the optimal management of patients with CVC-related DVT. Treatment of CVC-related VTE requires a 5- to 7-day course of adjusted-dose unfractionated heparin or LMWH followed by oral anticoagulants. Long-term LMWH that has been shown to be more effective than oral anticoagulant in cancer patients with lower limb DVT could be used in these patients. The optimal duration of oral anticoagulation treatment for CVC-related DVT is unknown, but patients with active cancer should be treated for at least 6 months or indefinitely. FUTURE PROSPECTS AND PROJECTS: The efficacy and safety of pharmacologic prophylaxis for CVC related thrombosis is not established. Additional studies performed in high risk populations are needed to define if LMWH or oral anticoagulation is indicated in this clinical setting.

[Recurrent unexplained lipothymia: do not forget the capillary leak syndrome]. / Lipothymie récidivante inexpliquée: penser au syndrome d'hyperperméabilité capillaire idiopathique.

INTRODUCTION: Systemic capillary leak syndrome (SCLS) is a rare disorder characterized by recurrent spontaneous episodes of hypovolaemic shock due to marked plasma shifts from the intravascular to the extravascular space. It presents as the characteristic triad of hypotension, haemoconcentration and hypoalbuminemia. CASE REPORT: We describe a patient with SCLS with recurrent lipothymia who presented first with delayed oedema that was thought to be due to orlistat treatment. On the second episode the patient was seen with a pulmonary hypertension when plasma came back into vessels. On the third time the characteristic triad led to the diagnosis of SCLS. DISCUSSION: SCLS should be considered in the differential diagnosis of recurrent hypovolemic shock without identifiable cause. Nevertheless, symptoms may be restricted to sole lipothymia or transient oedema or delayed hypoalbuminemia rendering the diagnosis difficult.

Increased expression of fibroblast growth factor 8 in human breast cancer.

Fibroblast growth factor 8 (FGF8) is an important developmental protein which is oncogenic and able to cooperate with wnt-1 to produce mouse mammary carcinoma. The level of expression of FGF8 mRNA was measured in 68 breast cancers and 24 non-malignant breast tissues. Elevated levels of FGF8 mRNA were found in malignant compared to non-malignant breast tissues with significantly more malignant tissues expressing FGF8 (P=0.019) at significantly higher levels (P=0.031). In situ hybridization of breast cancer tissues and analysis of purified populations of normal epithelial cells and breast cancer cell lines showed that malignant epithelial cells expressed FGF8 mRNA at high levels compared to non-malignant epithelial and myoepithelial cells and fibroblasts. Although two of the receptors which FGF8 binds to (FGFR2-IIIc, FGFR3-IIIc) are not expressed in breast cancer cells, an autocrine activation loop is possible since expression of fibroblast growth factor receptor (FGFR) 4 and FGFR1 are retained in malignant epithelial cells. This is the first member of the FGF family to have increased expression in breast cancer and a potential autocrine role in its progression.

A constitutional predisposition to breast cancer-related lymphoedema and effect of axillary lymph node surgery on forearm muscle lymph flow.

AIM: The aims of this prospective study were (a) to examine the relationship between pre-operative muscle lymph flow and the predisposition to BCRL in women treated by axillary nodal surgery for breast cancer; and (b) to test the 'stopcock' hypothesis that axillary lymph node surgery impairs forearm lymph flow in the short term. METHODS: (99m)Tc-nanocoll was injected intramuscularly into both forearms of women undergoing surgery for breast cancer. Lymphatic clearance rate constant, k, representing lymph flow per unit interstitial fluid volume, was measured as the fractional disappearance rate of radioactivity from the depot site by gamma camera imaging. Axillary lymph node activity was calculated as percentage injected activity. BCRL was assessed by clinical examination and upper limb perometry. RESULTS: Of 38 pre-operative women, 33 attended at 8 ± 6 weeks post-operatively and 31 at 58 ± 9 weeks post-operatively. Seven patients (18%) developed BCRL. Prior to surgery the BCRL-destined patients had a higher mean k (0.0962 ± 0.034%/min) than non-BCRL patients (0.0830 ± 0.019%/min) (p = 0.10, unpaired t test). Post-operative k values were not significantly different from pre-operative, in either the ipsilateral (operated) or contralateral limb. Also, post-operative k values did not differ significantly between both upper limbs. Furthermore, there was no significant difference between pre- and post-operative axillary activity. CONCLUSION: Patients who develop BCRL have high lymph flow pre-surgery, which may predispose them to lymphatic overload and failure. Axillary lymph node surgery has no early, measurable effect on forearm muscle lymph flow despite surgical disruption of routes of lymph drainage.

[Gemcitabine-induced thrombotic microangiopathy]. / Microangiopathie thrombotique due à la gemcitabine.

INTRODUCTION: Thrombotic microangiopathy (TMA) regroups the hemolytic and uremic syndrome (HUS) and thrombocytopenic thrombotic purpura (TTP). The TMA associated with cancer can be secondary to cancer, hence similar to TTP, or to chemotherapy, creating an HUS. Gemcitabine, used in the treatment of pulmonary, pancreatic and urothelial carcinomas, is generally well tolerated, but has recently been implied in the occurrence of TMA. OBSERVATION: In a patient treated for a metastatic urothelial carcinoma, HUS developed after 8 cues of gemcitabine used alone. After symptomatic treatment and withdrawal of gemcitabine, the hematological abnormalities disappeared and renal function returned to preceding values. DISCUSSION: The incidence of TMA is of around 5 to 6% of metastatic carcinomas. Gemcitabine-induced TMA are of recent occurrence and some twelve cases have been reported. Their occurrence is delayed with regard to the initiation of gemcitabine. They lead to HUS with good prognosis since, on withdrawal of gemcitabine the renal abnormalities regress. Search for TMA should therefore be proposed after more than 10 cycles of treatment with gemcitabine.

[Intestinal pneumatosis. Right colon cystic form with linear aspect on scan]. / Pneumatose intestinale. Forme kystique colique droite d'aspect linéaire au scanner.

INTRODUCTION: Digestive pneumatosis corresponds to the presence of air in a wall of digestive tract. It is common to oppose primary cystic-type pneumatosis, involving the left colon, with linear-type pneumatosis that may affect the whole of the digestive tract. OBSERVATION: In a 41 year-old man presenting with Sharp's syndrome, abdominal pain occurred revealing an isolated right colon pneumatosis. Although abdominal tomodensitometry showed a strictly linear pneumatosis, colposcopy revealed voluminous cysts. CONCLUSION: With this case report, the limits of tomodensitometry in distinguishing linear from cystic forms are apparent. The importance of avoiding surgery is underlined. Our patient presented with a pneumo-peritonitis only requiring medical treatment since this disease generally regresses spontaneously.

[Spontaneous portal vein thrombosis associated with acute cytomegalovirus infection in an immunocompetent patient]. / Thrombose porte spontanée associée à une infection aiguë à cytomégalovirus chez une patiente immunocompétente.

BACKGROUND: Portal vein thrombosis (PVT) generally results from a local cause (hepatocellular and pancreatic carcinoma). Spontaneous PVT related to a general cause is less common. We report here a case of spontaneous PVT associated with acute cytomegalovirus (CMV) infection in an immunocompetent patient. CASE REPORT: A 31-year-old white female was admitted with fever and lymph node enlargement. The patient was a heavy smoker and was taking oral contraception. Blood tests revealed an inflammatory syndrome. Liver enzymes were elevated (2N) and platelet count was 118 G/l. Abdominal ultrasonography disclosed partial portal thrombosis. Computed tomography did not show any evidence of a hepatic or pancreatic mass. Protein S, protein C, and anti-thrombin III levels were normal. No antiphospholipid antibodies, no mutation for factors II and V and no abnormality suggestive of paroxysmal nocturnal hemoglobinuria at flow cytometry could be demonstrated. Acute CMV infection was diagnosis with positive viremia (PCR). The patient was given anticoagulation treatment and has done well with no relapse. CONCLUSION: Cytomegalovirus, by damaging endothelial cells, is thought to trigger a cascade of events leading to deep vein thrombosis. CMV infection does not appear to act alone on endothelial cells but rather behaves as an associated factor.

ß2-adrenergic receptors protect axons during energetic stress but do not influence basal glio-axonal lactate shuttling in mouse white matter.

In vitro studies have demonstrated that ß2-adrenergic receptor activation stimulates glycogen degradation in astrocytes, generating lactate as a potential energy source for neurons. Using in vivo microdialysis in mouse cerebellar white matter we demonstrate continuous axonal lactate uptake and glial-axonal metabolic coupling of glutamate/lactate exchange. However, this physiological lactate production was not influenced by activation (clenbuterol) or blocking (ICI 118551) of ß2-adrenergic receptors. In two-photon imaging experiments on ex vivo mouse corpus callosum subjected to aglycemia, ß2-adrenergic activation rescued axons, whereas inhibition of axonal lactate uptake by α-cyano-4-hydroxycinnamic acid (4-CIN) was associated with severe axonal loss. Our results suggest that axonal protective effects of glial ß2-adrenergic receptor activation are not mediated by enhanced lactate production.

A pilot study to examine the experiences and attitudes of women with breast cancer towards one versus two-step axillary surgery.

PURPOSE: To elicit the views, experiences and preferences of women with clinically node negative breast cancer towards intra-operative sentinel lymph node biopsy (SLNB) analysis. METHODS: Focus groups with 14 women with breast cancer from two UK centres; one group had undergone the standard practice of waiting two weeks for results of their axillary surgery, the other had experienced the intra-operative SLNB analysis. RESULTS: Women generally were unaware about their lymph nodes, what their function is and how they are removed. Preference was indicated for intra-operative sentinel lymph node biopsy (SLNB) analysis provided clear descriptions were given about the risk of experiencing false negative and false positive results. DISCUSSION: Adopting an intra-operative analysis technique of axillary nodes was viewed as an excellent option by women from both centres. The immediacy of knowing the results was seen as a great advantage for their physical and psychological well being and more cost effective.

[Venous thromboembolism associated with long-term use of central venous catheters in cancer patients]. / Thromboses sur cathéter central chez le patient cancéreux.

Increased incidence of cancers and the development of totally implanted venous access devices that contain their own port to deliver chemotherapy will lead to a greater than before numbers of central venous catheter-related thrombosis (CVCT). Medical consequences include catheter dysfunction and pulmonary embolism. Vessel injury caused by the procedure of CVC insertion is the most important risk factor for development of CVCT. This event could cause the formation of a fresh thrombus, which is reversible in the large majority of patients. In some cases, thrombus formation is not related to catheter insertion. The incidence of CVC-related DVT assessed by venography has been reported to vary from 30 to 60% but catheter-related DVT in adult patients is symptomatic in only 5% of cases. The majority of patients with CVC-related DVT is asymptomatic or has nonspecific symptoms: arm or neck swelling or pain, distal paresthesias, headache, congestion of subcutaneous collateral veins. In the case of clinical suspicion of CVC-related deep venous thrombosis (DVT), compressive ultrasonography (US), especially with doppler and color imaging, currently is first used to confirm the diagnosis. Consequently, contrast venography is reserved for clinical trials and difficult diagnostic situations. There is no consensus on the optimal management of patients with CVC-related DVT. Treatment of CVC-related VTE requires a five- to seven-day course of adjusted-dose unfractionated heparin or low molecular weight heparin (LMWH) followed by oral anticoagulants. Long-term LMWH that has been shown to be more effective than oral anticoagulant in cancer patients with lower limb DVT, could be used in these patients. The efficacy and safety of pharmacologic prophylaxis for CVC related thrombosis is not established and the last recommendations suggest that clinicians not routinely use prophylaxis to try to prevent thrombosis related to long-term indwelling CVCs in cancer patients. Additional studies performed in high risk populations with appropriate dosage and timing will help to define which patients could benefit from prophylaxis.

Proliferation patterns of latent Pneumocystis carinii in rat organs during progressive stages of immunosuppression.

Pneumocystis carinii is known to proliferate mainly in the lung of an immunocompromised host. In AIDS and other immune disorders sporadic extrapulmonary presence of this organism has been documented. Occasionally, P. carinii does not appear to infect the lung. These observations have been based on the detection of P. carinii by conventional staining techniques. We have sought to determine the extent of these infections by the polymerase chain reaction (PCR) in a rat model. Harlan Sprague-Dawley rats weighing between 110 and 130 g were immunosuppressed with dexamethasone (1.2 mg/l) in drinking water. During progressive stages of immunosuppression 2 rats were sacrificed at 2, 3, 4 and 5 wk, and the lung, liver, kidney, spleen and bone marrow were taken. Sonicated crude extracts of the tissues were used as template DNA for the amplification of the dihydrofolate reductase (DHFR) gene of P. carinii. All the PCR products were analyzed by Southern hybridization with radiolabelled DHFR DNA. These analyses revealed a general trend of P. carinii proliferation first in bone marrow at 2 wk, followed by liver at 3 wk, and lung at 5 wk on immunosuppression. Kidney and spleen infections were infrequent. Although P. carinii appears to proliferate in the lung at later stages of immunosuppression, the degree of proliferation is several-fold greater than in extrapulmonary organs. The extrapulmonary proliferation of P. carinii, however small, may possibly suppress hematopoietic stem cell differentiation in bone marrow, and may also contribute to the pathology present in various organs.

Detection of Pneumocystis carinii in a rat model of infection by polymerase chain reaction.

The polymerase chain reaction (PCR) was employed to detect Pneumocystis carinii in organs of infected rats. Using a pair of oligonucleotides designed to the dihydrofolate reductase (DHFR) gene of rat P. carinii, specific amplification of an expected 415 bp region of P. carinii DHFR DNA of this organism was achieved, while no amplification occurred with the human, Candida albicans, and Mycobacterium avium and tuberculosis DNAs. Using rat P. carinii isolated from in vitro cultures and infected lung homogenates, the minimum detection level by PCR on an ethidium bromide gel was about 200 organisms and by Southern analysis with radiolabelled DHFR probe the detection level improved to 20 organisms. This level of sensitivity is sufficient to detect P. carinii specific band on the gel in infected rat lung and other organs. This PCR technique is potentially useful for detecting P. carinii in bronchoalveolar lavage (BAL) fluids of AIDS patients and for quantifying the organisms in tissues and in in vitro cultures where a high background with conventional stains makes it harder to determine the number of organisms.

[Treatment of thrombotic microangiopathies]. / Traitement des microangiopathies thrombotiques.

Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome appear as the same expression of thrombotic microangiopathy (TMA), which is a single pathological entity affecting small blood vessels leading to hemolytic anemia, circulatory changes with renal (hemolytic uremic syndrome, HUS) or nervous (thrombotic thrombocytopenic purpura, TTP) involvement. Because of his low incidence, prospective randomized clinical trials are difficult to conduct and apart from plasma exchanges (PE) which appear superior to plasma infusions (PI), other therapeutic recommendations are based on retrospective studies or on anecdotal reports with limited number of patients. In the absence of appropriate therapy, mortality rate was initially above 90% in adults with TTP. Plasma infusions and plasma exchanges have dramatically improved prognosis of the disease, since more than 80% of patients respond to therapy with a survival greater than 80 to 90%. Analysis of data of medical literature shows that plasma exchanges can cure 82% of TMA with 15% of refractory TMA and a mortality rate of 14%. In two randomized trials, PE are more effective than PI with a response rate benefit of 25% and an overall survival increase of 15%. Although severe thrombocytopenia is frequently observed, it is important to avoid platelet transfusions. Platelets infusions induce deleterious effects since they add to the severity and the extend of microvascular thrombi formation. Use of glucocorticoids, heparin, antiplatelet therapy, intravenous immunoglobulin and vincristine are associated with variable results and no controlled study supports their use. Splenectomy is still under discussion but could be of interest in case of relapsing thrombotic microangiopathies as an attempt to reduce the rate of TMA recurrence.