Incidence and prognostic value of respiratory events in acute leukemia.

Acute respiratory failure and infectious pneumonia are the major causes of death during induction chemotherapy of acute leukemia. However, the causes, incidence and prognostic value of all respiratory events (REs) occurring in this context have never been assessed prospectively. We recruited 65 consecutive patients with newly diagnosed acute leukemia into a 1-year prospective study (December 2000-November 2001) to evaluate the incidence and prognostic value of these events. REs were frequent: 38 were recorded in 30 patients. There was a significant relationship between REs and pre-existing respiratory disease and/or smoking. REs were caused by infection in 34% of cases, by an established cause other than infection in 42% and had an undetermined cause in 24%. Poor early outcome (death within 45 days of starting induction chemotherapy) in patients experiencing an RE was independently associated with a >25/min respiratory rate (P=0.003) and the nonachievement of complete remission (CR) (P<0.0001). Predictors of overall survival in the entire patient population were the absence of CR (P<0.0001), REs (P=0.02) and a > or =2 performance status (P=0.03). In conclusion, REs are frequent during induction chemotherapy of acute leukemia and represent an independent prognostic factor of poor outcome, regardless of their cause.     

Individual patient data meta-analyses in head and neck carcinoma: what have we learnt?]

Carcinoma of the upper aerodigestive tract (oral cavity, oropharynx, hypopharynx, nasopharynx, larynx) are frequent tumors for which surgery and/or radiotherapy are the main therapeutic agents. The main results of meta-analyses based on the collection of individual patients data are reported: 1) The meta-analysis on chemotherapy, regrouping data of nearly 11,000 patients issued from 63 randomized trials showed an absolute benefit of 4% at five years in overall survival, in favor of chemotherapy (P<0.0001). Most of the benefit was seen with concomitant radiochemotherapy, however with a relatively large heterogeneity in this subgroup of trials. An update of this meta-analysis was performed including 24 additional trials, which confirmed the magnitude of the benefit due to concomitant chemotherapy (8% at 5 years). 2) The meta-analysis on larynx preservation, using induction chemotherapy in larynx and hypopharynx carcinomas. No significant difference was seen between the control arm with total laryngectomy and the larynx preservation approach. 3) The meta-analysis on chemotherapy in nasopharynx carcinomas, from the data of 11 randomized trials including 2722 patients, and comparing the radiotherapy to radio-chemotherapy (1979-2001). The results showed an absolute benefit of 6% at five years in overall survival, in favor of chemotherapy (P<0.0001). Most of the benefit was seen with concomitant radiochemotherapy. 4) Finally, a meta-analysis on altered fractionated RT, compared to conventional RT in 15 randomized trials regrouping 6515 patients. The results showed a small but significant improvement in favor of altered fractionated RT for overall survival and local control with an absolute benefit at five years of 3 and 6%, respectively.     

Impact of EGFR expression on colorectal cancer patient prognosis and survival.

BACKGROUND: Epidermal growth factor receptor (EGFR) is overexpressed in many types of cancers, especially colorectal cancer (CRC), and seems to reflect more aggressive histological and clinical behaviors. The aim of this study was to evaluate EGFR immunohistochemical reactivity in CRC biopsies, and to analyze its relationship with various histological and clinical characteristics and survival. PATIENTS AND METHODS: A composite EGFR score, obtained by multiplying the grade (% positive cells) by the intensity of labeling (0-9) was used to define patients with low or high EGFR expression whose clinicopathological features were then compared. Univariate tests and multivariate Cox proportional hazards model were applied for data analysis. RESULTS: Tissue sections from 150 CRC patients with a median follow-up of 40 months were examined. Median patient age at diagnosis was 70 years (range 38-89 years). EGFR reactivity was positive for 143 patients (97%) and high for 118 (80%). According to multivariate analysis, EGFR overexpression was significantly associated with tumor stage, with a higher percentage of EGFR overexpression in T3 than T4 (P=0.003) and not with overall survival. CONCLUSIONS: EGFR was overexpressed in this CRC patient population and was significantly associated with TNM (tumor-node-metastasis) stage T3. In the context of a new therapeutic strategy using EGFR-targeted therapies, although EGFR remains a controversial prognostic factor, this expression-stage association may play a crucial role in a decision to initiate an adjuvant treatment.     

Cologne high-dose sequential chemotherapy in relapsed and refractory Hodgkin lymphoma: results of a large multicenter study of the German Hodgkin Lymphoma Study Group (GHSG).

BACKGROUND: We designed a dose- and time-intensified high-dose sequential chemotherapy regimen for patients with relapsed and refractory Hodgkin lymphoma (HD). PATIENTS AND METHODS: Eligibility criteria included age 18-65 years, histologically proven primary progressive (PD) or relapsed HD. Treatment consisted of two cycles DHAP (dexamethasone, high-dose cytarabine, cisplatinum); patients with chemosensitive disease received cyclophosphamide followed by peripheral blood stem cell harvest; methotrexate plus vincristine, etoposide and BEAM plus peripheral blood stem cell transplantation (PBSCT). RESULTS: A total of 102 patients (median age 34 years, range 18-64) were enrolled. The response rate was 80% (72% complete response, 8% partial response). With a median follow-up of 30 months (range 3-61 months), freedom from second failure (FF2F) and overall survival (OS) were 59% and 78% for all patients, respectively. FF2F and OS for patients with early relapse were 62% and 81%, for late relapse 65% and 81%; for PD 41% and 48%, and for multiple relapse 39% and 48%, respectively. In multivariate analysis response after DHAP (P <0.0001) and duration of first remission (PD and multiple relapse versus early and late relapse; P=0.0127) were prognostic factors for FF2F. Response after DHAP (P <0.0081), duration of first remission (P=0.0017) and anemia (P=0.019) were significant for OS. CONCLUSION: Based on the promising results of this study, a prospective randomized European intergroup study was started comparing this intensified regimen with two courses of DHAP followed by BEAM (HD-R2 protocol).     

Inhibitory purinergic P2 receptor characterisation in rat distal colon

The aim of this study was to characterise the P2 receptors involved in purinergic relaxant responses in rat distal colon circular muscle. Concentration-response curves for purinergic agonists were constructed on methacholine-precontracted circular muscle strips of rat distal colon in the absence and presence of the nerve blocker TTX and the ecto-nucleotidase inhibitor ARL67156. The effects of the P2 receptor antagonists RB2, PPADS, suramin, MRS2179 and NF279, the NO-synthase inhibitor L-NAME and the small conductance K(+) channel blocker apamin were investigated. The localisation of the different P2 receptors was examined immunocytochemically. Immunocytochemistry demonstrated the expression of P2Y(1), P2Y(6) and P2X(1) receptors on smooth muscle cells and P2Y(2), P2Y(12), P2X(2) and P2X(3) receptors in the myenteric plexus; almost a quarter of the P2Y(2)-immunopositive neurons co-expressed nNOS. The P2X-selective agonist alphabetameATP and the P2Y-selective agonist ADPbetaS were the most potent relaxants; their effects were abolished by apamin. The effect of ADPbetaS was antagonised by the P2Y(1)-selective antagonist MRS2179 pointing to interaction with the muscular P2Y(1)-receptors. The relaxant effect of alphabetameATP was partially reduced by TTX and concentration-dependently antagonised by PPADS, suramin, RB2 and the P2X(1)-selective antagonist NF279; this correlates with an interaction with neuronal P2X(3) and muscular P2X(1) receptors. UTP was the least potent agonist; its effect was markedly increased by ARL67156, nearly abolished by TTX and reduced by L-NAME. This points to interaction with the neuronal P2Y(2)-receptors inducing relaxation, at least partially, by NO release.     

Maternal morbidity after Thierry's spatulas and vacuum deliveries

OBJECTIVE: To compare maternal morbidity after Thierry's spatulas or vacuum-assisted deliveries. PATIENTS AND METHODS: Retrospective study, at the French hospital la Conception, in Marseilles. All successful instrumental deliveries between November 2003 and May 2005 were reviewed, that is to say 264. Univariate and multivariate analysis were performed comparing maternal morbidity in the two groups. The primary outcome measure was perineal trauma. Secondary outcomes were blood loss and duration of hospitalization. RESULTS: Among the 264 deliveries, there were 96 vacuum deliveries and 168 Thierry's spatulas extraction. Thierry's spatulas were use more often in nulliparous patient (<0.001). Patients in the group of Thierry's spatulas have a higher rate of epidural analgesia (p=0.05), a longer duration of first (p=0.002) and second stage of labor (p=0.03). There was no difference in incidence of sphincter tears between women who underwent Thierry's spatulas and those who underwent vacuum delivery with respective incidence of 4.2 and 3.2% (p=0.67). There was a significant difference in post-partum hemoglobin value with a higher blood loss in the group of Thierry's spatulas (<0.001). Mean duration of hospitalization was longer in the group with Thierry's spatulas (5.6 days) than in the group who underwent vacuum delivery (4.7 days) (p<0.001). DISCUSSION AND CONCLUSION: Incidence of third degree tears was similar between the vacuum and Thierry's spatulas group. Deliveries with vacuum are associated with less blood loss and a shorter hospitalization stay.     

Pelvic organ prolapse surgery in women aged more than 70 years: a literature review

OBJECTIVE: The purpose of the study was to report surgical techniques for pelvic organ prolapse and complications in women aged more than 70 years. PATIENTS AND METHODS: A Medline search was made for articles indexed between 2000 and 2006 and dealing with operative techniques for pelvic organ prolapse. Seven articles in English and French were included. RESULTS: Three hundred and ninety-four women were treated for pelvic organ prolapse. Transvaginal repairs were reported in 97% (384 women). Vaginal function was preserved in 57% (207 women) and vaginal obliteration techniques represented 40% (145 women) of all prolapse surgery. The death rate was 1% (four deaths). The blood transfusion rate was 12%. The mean complication rate was 3.8% with cardiovascular prevalence (seven pulmonary embolisms, two myocardial infarctions, two congestive heart failures, one prolonged angina, two transient arrhythmias, one cerebrovascular accident, one acute renal failure). The temporospatial disorientation rate was 4.6%. DISCUSSION AND CONCLUSION: Vaginal hysterectomy with colpo-perineorrhaphy and sacrospinous ligament fixation are alternative procedures instead of colpocleisis to treat pelvic organ prolapse in women aged more than 70 years. For all pelvic prolapse surgery, the overall perioperative morbidity and mortality rate in elderly women are acceptable. This surgery needs a good collaboration between anesthetist and surgeon team and vigilance during postoperative follow-up.     

Treatment of genital prolapse in young women: sacrohysteropexy or vaginal route?

Even if genital prolapse does particularly affect the elder woman, we often have to face a surgical demand with conservation of the uterus from a patient less than 50 years. Before making the decision of treating a non life-threatening symptom by a specific surgical technique, it is important to ask who should be operated and when. Then, the route of the surgery has to be chosen considering that the woman wants to preserve her fertility. In the past decade, some surgical acts, like the sacrohysteropexy, were known as having poorer results if the women got pregnant. Thus, if there was a persistent childbearing desire, more interventions allowing pregnancy (like the Manchester's or the Richardson's procedures) were preferred. Nowadays, the sacrohysteropexy is considered as the gold standard technique, but one question is coming out: could we substitute this traditional surgery by a vaginal repair with meshes? Despite the big diversity of the so-called "sacrohysteropexy", we think that it remains the first choice technique to cure a young woman. Vaginal meshes have too high a rate of morbidity (especially on sexual activity) to be considered as the best surgical treatment. But this question could probably find another answer in the future, when all the studies about the component of the meshes will be finished.     

Prospective evaluation of elective single-embryo transfer versus double-embryo transfer following in vitro fertilization: a two-year French hospital experience

OBJECTIVE: Multiple embryo transfer is responsible for a high rate of multiple pregnancies (ICSI), with subsequent risks of premature birth and perinatal death. This prospective non randomized study aimed to assess the ability of an elective single-embryo transfer (eSET) policy to reduce the twin pregnancy rate, compared to a double embryo transfer (DET) approach. PATIENTS AND METHODS: Between March 2005 and May 2006, 180 eligible women were proposed to benefit from an eSET transfer rather than a DET. Inclusion criteria were (i) age less than 37 years old; (ii) at least two good quality embryos available (three to five cells at day 2 or six to nine cells at day 3; less than 20% fragmentation and the absence of multinucleates blastomeres), after IVF or ICSI and (iii) no more than one previous failed treatment cycle. Outcome analysis included cycles with frozen-thawed embryo transfer (FET). RESULTS: According to patients' decision, 107 and 73 women had an eSET (59.4%) and a DET (40.6%) respectively. No differences were found between eSET and DET groups regarding demographics and biologicals parameters. The clinical pregnancy rate (PR) per transfer was 43.9% in eSET group and 57.5% in DET group (p=0.07). The twin pregnancy rates were 0 and 14.3%, in eSET and DET groups, respectively (p=0.007). The cumulative PR per patient, including the outcome of performed FET cycles, was 63.6% in eSET group and 61.6% in DET group. In this case, the cumulative twin pregnancy rates were 2.9 and 15.6% in eSET and DET groups, respectively (p=0.02). DISCUSSION AND CONCLUSION: Our data show that in a selected population of women, transferring one fresh embryo and then, if required, one or two frozen-thawed embryos significantly reduces the twin pregnancy rate without decreasing the overall pregnancy rate. This study supports the policy of eSET in this subgroup of patients.