In a previous article we reported that mutations favoring cancer at adulthood seemed to improve fertility and limit miscarriages. Because spontaneous abortion may result from anomalies in embryo, we questioned if an increased frequency of congenital malformation could be evidenced among cancer-prone families. Oncogenetics database (≈193 000 members) of the comprehensive cancer center Jean Perrin was crossed with regional registry of congenital malformations (≈10 000). Among children born between 1986 and 2011, 176 children with malformation matched in both databases. In breast/ovaries cancer-prone families, the risk for malformations was multiplied by 2.4 [1.2-4.5] in case of a BRCA1 mutation. Frequencies of malformation in BRCA2 and MMR mutated families were similar to families without a cancer syndrome. In comparison to malformations concerning a unique anatomical system, multimalformations were significantly more frequent in case of BRCA or MMR mutations: compared to families without cancer syndrome, the risk of multimalformations was multiplied by 4.1 [0.8-21.7] for cancer-prone families but with no known deleterious mutation, by 6.9 [1.2-38.6] in families with a known mutation but an unknown parental mutational status and by 10.4 [2.3-46.0] when one parent carried the familial mutation. No association with the type of anatomical system was found, nor with multiple births. These results suggest that BRCA and MMR genes play an important role in human embryogenesis and that if their function is lowered because of heterozygote mutations, congenital malformations are either more likely (BRCA1 mutations) and/or more susceptible to concern several anatomical systems. 相似文献
In the phase II/III KEYNOTE-010 study (ClinicalTrials.gov, NCT01905657), pembrolizumab significantly prolonged overall survival over docetaxel in patients with previously treated, programmed death ligand 1–expressing (tumor proportion score ≥ 1%), advanced NSCLC. Health-related quality of life (HRQoL) results are reported here.
Methods
Patients were randomized 1:1:1 to pembrolizumab 2 or 10 mg/kg every 3 weeks or docetaxel 75 mg/m2 every 3 weeks. HRQoL was assessed using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLC) Core 30 (C30), EORTC QLQ–Lung Cancer 13 (LC13), and EuroQoL-5D. Key analyses included mean baseline-to-week-12 change in global health status (GHS)/quality of life (QoL) score, functioning and symptom domains, and time to deterioration in a QLQ-LC13 composite endpoint of cough, dyspnea, and chest pain.
Results
Patient reported outcomes compliance was high across all three instruments. Pembrolizumab was associated with better QLQ-C30 GHS/QoL scores from baseline to 12 weeks than docetaxel, regardless of pembrolizumab dose or tumor proportion score status (not significant). Compared with docetaxel, fewer pembrolizumab-treated patients had “deteriorated” status and more had “improved” status in GHS/QoL. Nominally significant improvement was reported in many EORTC symptom domains with pembrolizumab, and nominally significant worsening was reported with docetaxel. Significant prolongation in true time to deterioration for the QLQ-LC13 composite endpoint emerged for pembrolizumab 10 mg/kg compared to docetaxel (nominal two-sided p = 0.03), but not for the 2-mg/kg dose.
Conclusions
These findings suggest that HRQoL and symptoms are maintained or improved to a greater degree with pembrolizumab than with docetaxel in this NSCLC patient population. 相似文献
Background: Tight perioperative control of blood glucose improves the outcome of diabetic patients undergoing cardiac surgery. Because stress response and cardiopulmonary bypass can induce profound hyperglycemia, intraoperative glycemic control may become difficult. The authors undertook a prospective cohort study to determine whether poor intraoperative glycemic control is associated with increased intrahospital morbidity.
Methods: Two hundred consecutive diabetic patients undergoing on-pump heart surgery were enrolled. A standard insulin protocol based on subcutaneous intermediary insulin was given the morning of the surgery. Intravenous insulin therapy was initiated intraoperatively from blood glucose concentrations of 180 mg/dl or greater and titrated according to a predefined protocol. Poor intraoperative glycemic control was defined as four consecutive blood glucose concentrations greater than 200 mg/dl without any decrease in despite insulin therapy. Postoperative blood glucose concentrations were maintained below 140 mg/dl by using aggressive insulin therapy. The main endpoints were severe cardiovascular, respiratory, infectious, neurologic, and renal in-hospital morbidity.
Results: Insulin therapy was required intraoperatively in 36% of patients, and poor intraoperative glycemic control was observed in 18% of patients. Poor intraoperative glycemic control was significantly more frequent in patients with severe postoperative morbidity (37% vs. 10%; P < 0.001). The adjusted odds ratio for severe postoperative morbidity among patients with a poor intraoperative glycemic control as compared with patients without was 7.2 (95% confidence interval, 2.7-19.0). 相似文献
We report our initial experience with aortic valve replacement using robotic assistance. All procedures were performed with peripheral cardiopulmonary bypass, transthoracic aortic cross-clamp, and antegrade cold crystalloid cardioplegia. One or two ports and a 5-cm intercostal incision in the right chest were used for access. All patients had aortic valve replacement performed robotically. Between February and September 2004, five patients underwent robotic aortic valve replacement. The mean age was 59 years (range 35-82 years). There were no incisional conversions, death, stokes, or reoperations for bleeding. Overall mean study times were as follows: procedure, 231.2 min (range 180-315 min); cardiopulmonary bypass, 121.5 min (range 83-173 min), and cross-clamp, 98.2 min (range 67-140 min). One patient developed postoperative pneumonia. Aortic valve replacement can be successfully performed with the da Vinci robotic system. 相似文献
OBJECTIVE: To assess the therapeutic effect of the extent of lymph node dissection performed in patients with a stage pI non-small-cell lung cancer (NSCLC). METHODS: We analysed data on 465 patients with stage I NSCLC who were treated with surgical resection and some form of lymph node sampling. The median number of lymph node sampled was 10 and the median number of ipsilateral mediastinal lymph node stations sampled was two. We chose to define a procedure that harvested 10 or more lymph nodes and sampled two or more ipsilateral mediastinal stations as a lymphadenectomy, by contrast with sampling when one or both criteria were not satisfied. The effect of the surgical techniques: lymph node sampling (LS; n=207) vs. lymphadenectomy (LA; n=258) on 30-day mortality and overall survival were investigated. RESULTS: A total of 6244 lymph nodes was examined, including 4306 mediastinal lymph nodes. The mean (+/-SD) numbers of removed lymph nodes were 7+/-6.1 per patient following LS vs.18.6+/-9.3 following LA (P=0.001). An average mean of 1+/-0.90 mediastinal lymph node station per patient was sampled following LS vs. 2.7+/-0.8 following LA (P<10(-6)). Overall 30-day mortality rates were 2.4 and 3.1%, respectively. LA was disclosed as a favourable prognosticator at multivariate analysis (Hazard Risk: 1.43; 95% Confidence Interval: 1.00-2.04; P=0.048), together with younger patient age, absence of blood vessels invasion, and smaller tumour size. CONCLUSIONS: Importance of lymph node dissection affects patients outcome, while it does not enhance the operative mortality. A minimum of 10 lymph nodes assessed, and two mediastinal stations sampled are suggested as possible pragmatic markers of the quality of lymphadenectomy. 相似文献
OBJECTIVE: Dilation of aortic annulus, sinuses of Valsalva, and sinotubular junction (STJ) diameters are the characteristic lesions of aortic root aneurysm. The remodeling technique reduces STJ diameter and creates three neosinuses of Valsalva. Alternatively, the reimplantation technique reduces both annulus and STJ diameters to the detriment of aortic root dynamics. Although the remodeling technique is recognized as the most physiological valve-sparing procedure, aortic annulus dilation may jeopardize its results. A standardized approach that combines an external subvalvular aortic prosthetic ring annuloplasty with the remodeling technique is suggested. METHODS: Eighty-three patients underwent an elective aortic root remodeling procedure, either isolated (group 1, n=34) or combined with an external subvalvular aortic prosthetic ring annuloplasty (group 2, n=49). Preoperative aortic regurgitation was 1.59+/-1.1 (group 1) and 1.97+/-1.3 (group 2) (NS). The aortic annulus was more dilated in group 2 than in group 1 (27+/-2.77 mm vs 26.4+/-2.3 mm, p<0.01). Residual aortic regurgitation > or =grade II was the conversion criteria for aortic valve replacement. RESULTS: Operative mortality was 3.6% (n=3). Intraoperative conversion for valve replacement was 32.7% in group 1 (n=11) versus 4.2% in group 2 (n=2) (p<0.001). In group 1, preoperative annulus diameter was larger for converted than for valve-spared patients (27.6+/-1.7 mm vs 25.2+/-1.5 mm, p<0.02). In group 2, implanted aortic ring significantly reduced annulus diameter (20.6+/-1.8 mm) without significant aortic valve gradient (8.3+/-3 mmHg). Follow-up was 17.2+/-13.4 months (group 1) and 10.41+/-7.95 months (group 2). Reoperation for recurrent aortic regurgitation was 13% in group 1 (n=3) versus 4.2% in group 2 (n=2). Echocardiographic follow-up found residual aortic regurgitation < or =grade I in 17 patients in group 1 (90%) versus 43 patients in group 2 (95.5%) and of grade II in two patients in group 1 (10%) and two patients in group 2 (4.5%). CONCLUSION: The addition of external aortic prosthetic ring annuloplasty improves the remodeling technique's operative reproducibility and short-term results. Therefore, its use as a systematical adjunct to the remodeling procedure is suggested. However, further long-term evaluation comparing this valve-sparing procedure to composite graft replacement should define the best surgical strategy for aortic root aneurysm. 相似文献
In a prospective study of the effect of postoperative radiation therapy for the prevention of reproliferation of membranes and recurrent proliferative vitreoretinopathy (PVR) two similar groups of patients with retinal detachment and PVR grade D1 to D3 in one eye were compared. Half the eyes (30) received a total dose of 3000 cGy after surgery; the other half remained untreated. After a followup of 6 months and 14 months or more (maximum 36 months) the anatomical and functional results of each group were compared. After 6 months in the unirradiated group 57% (17/30) remained attached and 43% (13/30) had detached again. In the irradiated group 63% (19/30) were attached and 37% (11/30) had detached. However, there was no statistically significant difference between the two groups (P=0.479, Fisher's Exact Test). After 14 months the number of cured and uncured eyes remained the same in the unirradiated group, while in four of the eyes in the irradiated group a later onset of reproliferation and detachment occurred (after 7, 8, 12 and 14 months, respectively). A final cure rate of 57% (17/30) was achieved in the unirradiated group and a 50% (15/30) cure rate in the irradiated group. Thus the failure rate was 43% (13/30) in the unirradiated group and 50% (15/30) in the irradiated group (P=0.473, Fisher's Exact Test). No side effects from the radiation were observed in any case and no radiation retinopathy occurred during an observation period of up to 3 years. The visual acuity of the cured treated and cured untreated eyes was similar in the two groups. From these results we conclude that immediate radiation treatment does not improve the long-term results and does not reduce the number of reoperations. In a considerable number of treated eyes the onset of reproliferation was delayed from 7 to 14 months, whereas in the untreated group reproliferation was always observed during the first 6 months. A combination of various antiproliferative and antiinflammatory therapies are needed to suppress recurrent PVR after succesful vitreoretinal surgery and to minimize the side effects of these treatments.Presented in part at the XVIIth Meeting of the Club Jules Gonin, 1–6 September 1990, Lausanne 相似文献
Twenty-two premature neonates underwent surgical haemoclip closure of patent ductus arteriosus in a neonatal intensive care unit (NICU). Surgery was performed in the NICU in order to prevent hypothermia and interruption of care, and to avoid accidental vascular access removal and extubation. The results suggest that morbidity can be limited by performing the surgery in an NICU, and by switching from conventional to high-frequency mechanical ventilation in case of severe respiratory failure. 相似文献
Following the experience of the German authors, the treatment of choroidal melanoma with ruthenium 106 disk was introduced in Lyon. Between 1983 and 1988, 127 patients were treated. Results are analysed on a group of 84 patients followed 18 months and more. In 72 cases a reduction of thickness was noted. It was complete in 33 cases. Enucleation was performed in 10 patients due to no response or regrowth. In 3 cases the tumor was sterilized. Five patients died of metastases, and 73 are alive, 3 of them with liver metastases. An afterloading iridium template disk was used in 8 patients. 4 of them with a tumor thickness between 6.5 and 8 mm had a good response. Edema of the fovea was observed in 21% of cases, while cataracts were very unusual with Ru 106. An enucleation was performed in 6 patients because of a complication. A useful vision may be preserved in 60% of cases. The scleral tolerance dose is close to 1,500 Gy. These results are in agreement with those of the literature and are considered to be satisfactory for tumors not exceeding 5 to 6 mm in thickness. If the tumor is located close to the fovea or the papilla, and/or if the thickness is 8 mm or more, proton beam could be a good alternative. 相似文献