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.

[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.

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).

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.

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.

[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.

[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.

Fibroblast growth factor 8 is expressed at higher levels in lactating human breast and in breast cancer.

Fibroblast growth factor 8 can transform NIH3T3 cells and its expression has been found to be associated with breast and prostate cancer. Following our finding that fibroblast growth factor 8 mRNA expression is increased in breast cancer, we have undertaken an immunohistochemistry study of fibroblast growth factor 8 expression in a series of human breast tissues and other normal tissues. Our findings confirm increased expression of fibroblast growth factor 8 in malignant breast tissue but also show significant fibroblast growth factor 8 expression in non-malignant breast epithelial cells. No significant difference in fibroblast growth factor 8 expression was found between different grades of ductal carcinoma, lobular carcinoma and ductal carcinoma in-situ or cancer of different oestrogen receptor, progesterone receptor or nodal status. The highest levels of fibroblast growth factor 8 expression were found in lactating breast tissues and fibroblast growth factor 8 was also detected in human milk. A survey of other normal tissues showed that fibroblast growth factor 8 is expressed in the proliferative cells of the dermis and epithelial cells in colon, ovary fallopian tube and uterus. Fibroblast growth factor 8 appears to be expressed in several organs in man and appears to have an importance in lactation.

Late results of selective axillary surgery based on contact cytology in women with operable breast cancer.

BACKGROUND: Interest in the possibility of intraoperative analysis of sentinel lymph nodes to select patients with operable breast cancer for immediate axillary clearance encouraged this review of a long-term experience of selective axillary surgery based on intraoperative contact cytology of conventionally sampled nodes. Survival was assessed as a potential marker for understaging. METHODS: Records of 437 patients who had surgery between 1991 and 1994 were reviewed to compare rates of axillary recurrence in patients who had contact cytology only with those who had contact cytology and axillary clearance. RESULTS: Axillary recurrence occurred in seven (3 per cent) of 219 patients who had negative contact cytology, three (4 per cent) of 75 patients who had positive contact cytology with axillary clearance and one (1 per cent) of 93 who had axillary clearance alone. In patients with positive contact cytology, 131 (78 per cent) of 168 positive nodes were in the sample specimen, which included all positive nodes on 19 occasions. Survival probability at 36, 72 and 96 months was 92, 87 and 84 per cent respectively for patients with negative contact cytology, and 85, 73 and 71 per cent for patients with positive cytology and axillary clearance. CONCLUSION: A selective approach to axillary surgery based on intraoperative contact cytology of sampled lymph nodes gave good long-term control of axillary disease.

Altered intracellular localization of fibroblast growth factor receptor 3 in human breast cancer.

Immunohistochemical staining of human breast tissues, using an antibody against fibroblast growth factor receptor 3 [FGFR-3], showed differences in cellular distribution. Both malignant and non-malignant epithelial cells contained FGFR-3 immunoreactivity, but myoepithelial cells and stroma were negative. The staining pattern in malignant epithelial cells was predominantly nuclear, whereas epithelial cells in normal breast tissue showed both cytoplasmic and nuclear elements. Reverse transcription-polymerase chain reaction (RT-PCR) revealed two isoforms of FGFR-3 corresponding to the FGFR-3-IIIb variant and a previously described exon-deleted nuclear form of FGFR-3, which were present in both malignant and non-malignant epithelial cells. The higher level of nuclear staining and loss of cytoplasmic staining seen in malignant epithelial cells did not correspond to an increase in expression of the exon-deleted form of FGFR-3, nor to any detectable activating point mutations. Since receptor activation can result in its movement to a perinuclear localization, an alternative explanation for the redistribution of FGFR-3-IIIb could be different degrees of activation by a ligand (FGF1 or FGF9). No FGF9 was detected by immunohistochemistry in breast tissues. FGF1, however, is present in the majority of breast cancers and a different tissue distribution of FGF1 was found in breast tissues, showing predominantly nuclear, or a mix of nuclear and cytoplasmic FGFR-3. The difference in FGFR-3 staining patterns may implicate this ligand-receptor pair in breast cancer.

Life-threatening eosinophilic pleuropericardial effusion related to vitamins B5 and H.

OBJECTIVE: To report a case of eosinophilic pleuropericarditis resulting from concomitant use of vitamins B5 and H. CASE SUMMARY: A 76-year-old white woman was admitted to the hospital because of chest pain and dyspnea related to pleurisy and a pericardial tamponade. This patient had no history of allergy and had been taking vitamins B5 and H for two months. Blood tests performed showed an inflammatory syndrome and a high eosinophil concentration (1200-1500 cells/mm3). Pleurocentesis and pericardiotomy yielded a sterile exudative fluid with an eosinophilic infiltrate. There were no nuclear antibodies and no rheumatic factor; screenings for viruses, parasites, bacteria, and malignant tumor were negative. A myelogram, biopsy of the iliac crest bone, and concentration of immunoglobulin E were also normal. After withdrawal of the vitamins, the patient recovered and the eosinophilia disappeared. DISCUSSION: Prolonged hypereosinophilia has marked predilection to damage specific organs, including the heart, but pleuropericardial effusion is uncommon. Drug-related pleuropericarditis usually occurs without an increased eosinophil count. Other drugs responsible for eosinophilic pleuropericarditis are cephalosporins, dantrolene, propylthiouracil, and nitrofurantoin. To our knowledge, this is the first case report of pleuropericarditis related to vitamins B5 and H. CONCLUSIONS: This case suggests that vitamins B5 and H may cause symptomatic, life-threatening, eosinophilic pleuropericarditis. Physicians prescribing these commonly used vitamins should be aware of this potential adverse reaction.

[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.