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1.
Oncoimmunology ; 7(5): e1424673, 2018.
Article in English | MEDLINE | ID: mdl-29721386

ABSTRACT

Despite successful introduction of NK-based cellular therapy in the treatment of myeloid leukemia, the potential use of NK alloreactivity in solid malignancies is still elusive. We performed a phase I clinical trial to assess the safety and efficacy of in situ delivery of allogeneic NK cells combined with cetuximab in liver metastasis of gastrointestinal origin. The conditioning chemotherapy was administrated before the allogeneic NK cells injection via hepatic artery. Three escalating doses were tested (3.106, 8.106 and 12.106 NK cells/kg) following by a high-dose interleukin-2 (IL-2). Cetuximab was administered intravenously every week for 7 weeks. Nine patients with liver metastases of colorectal or pancreatic cancers were included, three per dose level. Hepatic artery injection was successfully performed in all patients with no report of dose-limiting toxicity. Two patients had febrile aplasia requiring a short-term antibiotherapy. Grade 3/4 anemia and thrombopenia were also observed related to the chemotherapy. Objective clinical responses were documented in 3 patients and among them 2 occurred in patients injected with cell products harboring two KIR ligand mismatches and one in a patient with one KIR ligand mismatch. Immune monitoring revealed that most patients presented an increase but transient of IL-15 and IL-7 cytokines levels one week after chemotherapy. Furthermore, a high expansion of FoxP3+regulatory T cells and PD-1+ T cells was observed in all patients, related to IL-2 administration. Our results demonstrated that combining allogeneic NK cells transfer via intra-hepatic artery, cetuximab and a high-dose IL-2 is feasible, well tolerated and may result in clinical responses.

2.
Eur J Surg Oncol ; 43(1): 218-225, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27425578

ABSTRACT

BACKGROUND: Even though the perioperative chemotherapy improves the overall survival (OS) compared to surgery alone in patients with a resectable gastroesophageal adenocarcinoma (GEA), prognosis of these patients remains poor. Docetaxel (D), cisplatin (C), and 5-fluorouracil (F) regimen improves OS compared to CF among patients with advanced GEA. We evaluated the potential interest of a perioperative DCF regimen, compared to standard (S) regimens, in resectable GEA patients. METHODS: We identified 459 patients treated with preoperative DCF or S regimens. The primary endpoint was OS. Propensity scores were estimated with a logistic regression model in which all baseline covariates were included. We then used two methods to take PS into account and thus make DCF and S patients comparable. OS analyses were performed with Kaplan-Meier and Cox models in propensity score matched samples, and inverse probability of treatment weighted (IPTW) samples. RESULTS: In the propensity score matched sample, the p-value from the log rank test for OS was 0.0961, and the 3-year OS rate was 73% and 55% in DCF and S groups, respectively. The multivariate Cox regression underlined a Hazard Ratio of 0.55 (95% CI 0.27-1.13) for DCF patients compared to S patients. The results from IPTW analyses showed that DCF was significantly and independently associated with OS (HR = 0.52; 95% CI 0.40-0.69). CONCLUSIONS: In this retrospective multicenter, hypothesis-generating study, the propensity score analyses underlined encouraging results in favor of DCF compared to S regimens regarding OS. This promising result should be validated in a phase-3 trial.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Esophageal Neoplasms/drug therapy , Stomach Neoplasms/drug therapy , Adenocarcinoma/surgery , Adult , Aged , Cisplatin/administration & dosage , Combined Modality Therapy , Docetaxel , Esophageal Neoplasms/surgery , Female , Fluorouracil/administration & dosage , France , Humans , Male , Middle Aged , Propensity Score , Retrospective Studies , Stomach Neoplasms/surgery , Survival Analysis , Taxoids/administration & dosage , Treatment Outcome
3.
Ann Oncol ; 24(12): 3045-50, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24114858

ABSTRACT

BACKGROUND: Squamous cell carcinoma of the anal canal (SCCA) is a rare disease, mostly diagnosed at early stage. After concurrent chemoradiation (CRT) with mitomycin C and 5-fluorouracil (5FU), local or metastatic recurrences occur in >20% of the patients. After treatment failure, cisplatin (CDDP)-based chemotherapy is the standard option, but complete response (CR) is a rare event and the prognosis remains poor. PATIENTS AND METHODS: Eight consecutive patients with advanced recurrent SCCA after CRT were treated with DCF regimen (docetaxel 75 mg/m(2) day 1, CDDP 75 mg/m(2) day 1 and 5FU at 750 mg/m(2)/day for 5 days every 3 weeks). Tumour samples were analysed for human papillomavirus (HPV) genotyping, as well as p16 and p53 expression. RESULTS: After a median follow-up of 41 months, the overall survival rate at 12 months was 62.5% (95% CI 22.9-86.1 months). Four patients achieved a complete remission and remain relapse-free at the time of analysis with a progression-free survival of 19, 33, 43 and 88 months. Three of these patients underwent surgery for all involved metastatic sites. For all of them, pathological CR was confirmed. DCF regimen appeared feasible in these patients previously exposed to pelvic CRT, and no grade IV toxicity occurred. All patients in complete remission had HPV-16-positive SCCA, while HPV could only be detected among 50% of the non-responding patients. Of interest, immunohistochemical study revealed a p16(+)/p53(-) phenotype in these patients, while none of non-responders expressed p16. CONCLUSION: The high level of complete and long-lasting remission among SCCA patients treated with DCF regimen supports the assessment of this strategy in prospective cohorts.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Anus Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Neoplasms, Squamous Cell/drug therapy , Papillomavirus Infections/drug therapy , Adult , Aged , Anus Neoplasms/mortality , Anus Neoplasms/pathology , Anus Neoplasms/virology , Cisplatin/administration & dosage , Disease-Free Survival , Docetaxel , Female , Fluorouracil/administration & dosage , Human papillomavirus 16/genetics , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasms, Squamous Cell/mortality , Neoplasms, Squamous Cell/secondary , Neoplasms, Squamous Cell/virology , Papillomavirus Infections/mortality , Papillomavirus Infections/pathology , Papillomavirus Infections/virology , Prospective Studies , Retrospective Studies , Taxoids/administration & dosage , Treatment Outcome
4.
Perspect Med Educ ; 2(2): 95-98, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23670682

ABSTRACT

The registered screen resolution of e-learning study moments in MedicalEducation.nl was used in this research to investigate the readiness of students and medical professionals to study e-learning on a mobile device. Between January 2008 and September 2012 the use of e-learning on a mobile device by students has quintupled to 2.29 %, while medical professionals lag behind in this development. If the use of mobile devices for e-learning is better supported, a rapid further increase should be anticipated. Further research on the desire of both students and medical professionals to study e-learning on a mobile device should be conducted.

5.
Cardiovasc Intervent Radiol ; 35(4): 820-5, 2012 Aug.
Article in English | MEDLINE | ID: mdl-21901581

ABSTRACT

PURPOSE: To report the clinical efficiency and complications in patients treated with retrograde transvenous ethanol embolization of high-flow peripheral arteriovenous malformations (AVMs). Retrograde transvenous ethanol embolization of high-flow AVMs is a technique that can be used to treat AVMs with a dominant outflow vein whenever conventional interventional procedures have proved insufficient. METHODS: This is a retrospective study of the clinical effectiveness and complications of retrograde embolization in five patients who had previously undergone multiple arterial embolization procedures without clinical success. RESULTS: Clinical outcomes were good in all patients but were achieved at the cost of serious, although transient, complications in three patients. CONCLUSION: Retrograde transvenous ethanol embolization is a highly effective therapy for high-flow AVMs. However, because of the high complication rate, it should be reserved as a last resort, to be used after conventional treatment options have failed.


Subject(s)
Arteriovenous Malformations/therapy , Embolization, Therapeutic/methods , Peripheral Vascular Diseases/therapy , Adult , Aged , Aged, 80 and over , Child , Enbucrilate/therapeutic use , Ethanol/therapeutic use , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome
6.
Ann Surg ; 247(5): 877-84, 2008 May.
Article in English | MEDLINE | ID: mdl-18438127

ABSTRACT

OBJECTIVE: To evaluate a modified technique for carotid body tumor (CBT) resection. BACKGROUND: Resection of CBT can lead to substantial postoperative morbidity because of a rich vascularization and close connection to neurovascular structures. The impact of a modified surgical technique on postoperative outcome was evaluated and compared with a historical group and the literature. METHODS: Medical records of patients who underwent CBT surgery at Leiden University Medical Center between 1963 and 2005 were retrospectively reviewed. Before 1992, a standard approach was conducted. After 1992, most tumors were resected using an alternative technique, working in a craniocaudal fashion from skull base to carotid bifurcation. Data were reported as details of the pre, intra-, and postoperative periods. RESULTS: A total of 111 CBT resections (69 standard, 42 craniocaudal) were performed in 94 patients (44 male/50 female, mean age 41). The standard group consisted of 39 Shamblin I (56%), 22 II (32%), and 8 III (12%) tumors. The craniocaudally approached CBT included 12 Shamblin I (29%), 13 II (31%), and 17 III (40%) tumors. The mean blood loss was 901 mL (standard operations) versus 281 mL (craniocaudal approach, P < 0.0005). Persistent cranial nerve damage was encountered after 26 (23%) of 111 operations; 21 after the standard operations (30% within this group, including 3 preexistent nonresolved cranial nerve deficits); and 5 (12%, including 2 due to additional vagal body resections) after the craniocaudal operations (P = 0.025). CONCLUSIONS: The craniocaudal dissection technique of a CBT can be applied with little blood loss, thereby reducing the risk of postoperative morbidity.


Subject(s)
Carotid Body Tumor/surgery , Dissection/methods , Neurosurgical Procedures , Vascular Surgical Procedures , Adolescent , Adult , Aged , Blood Loss, Surgical/prevention & control , Carotid Body Tumor/blood supply , Carotid Body Tumor/pathology , Cohort Studies , Cranial Nerve Injuries/etiology , Cranial Nerve Injuries/prevention & control , Dissection/adverse effects , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome
8.
Geriatrics ; 61(12): 14-20, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17184138

ABSTRACT

Approximately 50% to 80% of persons diagnosed with Alzheimer's disease (AD) have some type of behavioral or psychiatric condition (eg, agitation, psychosis, and/or disinhibition). Agitation is defined in the context of restlessness, irritability, and resistiveness. Psychosis is recognized as a disturbance in the perception of objective reality. Disinhibition means a chronic loss of social restraint. In the case of AD, disinhibition can present as aggression, hyperactivity, and socially intrusive behavior. Such conditions can be burdensome for physicians and caregivers to manage. Consequences may include caregiver burnout or illness, patient abuse, and even institutionalization for the patient. Management of behavioral disturbances is no longer primarily handled by psychiatrists, but is now entering the realm of family practice and primary care. This article provides evaluation methods and treatment options for the aforementioned behavioral disturbances.


Subject(s)
Alzheimer Disease/psychology , Antipsychotic Agents/therapeutic use , Mental Disorders/drug therapy , Antidepressive Agents/therapeutic use , Cholinesterase Inhibitors/therapeutic use , Humans , Inhibition, Psychological , Mental Disorders/etiology , Psychomotor Agitation/drug therapy , Psychotic Disorders/drug therapy
9.
J Vasc Surg ; 43(4): 855-7, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16616252

ABSTRACT

Complete removal of an aortic endograft with suprarenal fixation is difficult. We report the use of a simple device to extract a Zenith endograft. This device is made by cutting off the tip of the cylinder of a 20-mL syringe and rounding off the edges. The main body of the graft is resheathed by advancing the cylinder cranially while keeping the graft in a stable position. This way, the graft collapses and the hooks are withdrawn without tearing the wall of the aorta. The supraceliac clamping time in our patient was less than 2 minutes. This technique offers a safe and fast solution to the potentially hazardous removal of an aortic endograft with suprarenal fixation.


Subject(s)
Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis/adverse effects , Device Removal/instrumentation , Renal Artery/surgery , Blood Vessel Prosthesis Implantation/methods , Device Removal/methods , Equipment Design , Equipment Safety , Humans , Sensitivity and Specificity
12.
J Vasc Surg ; 39(1): 260-2, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14718850

ABSTRACT

Patients with carotid body tumors referred to vascular surgeons usually undergo magnetic resonance imaging (MRI) as part of the workup. We present a case report of a 39-year-old woman with a presumed carotid body tumor, as was expected from clinical and MRI findings. At surgery, the ectopic thyroid tissue was suspected, and resection was performed. Histologic examination showed normal thyroid tissue with no sign of malignancy. Postoperative thyroid analysis showed a normally located, properly functioning thyroid gland. Ectopic thyroid glands are generally found in the midline, as a result of abnormal median migration. Their presence lateral to the midline with a proper functioning thyroid gland in its normal position is extremely rare. Although several submandibular thyroid glands have been reported, a close relation with the carotid arteries was described only once. When MRI scans of a presumed carotid body tumor show tumor characteristics that are not fully specific for a carotid body tumor, the possibility of ectopic thyroid tissue should be entertained, which can be the patient's only properly functioning thyroid tissue. In such cases, additional assessment, including thyroid tests, should be considered before surgery.


Subject(s)
Carotid Body Tumor/diagnosis , Choristoma/diagnosis , Thyroid Gland , Adult , Carotid Arteries/pathology , Diagnosis, Differential , Female , Humans , Magnetic Resonance Imaging
13.
J Vasc Surg ; 38(1): 116-22, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12844100

ABSTRACT

PURPOSE: We undertook this study to assess the outcome of spontaneous dissection of the renal artery and its branches surgically treated with extracorporeal reconstruction and autotransplantation. SUBJECTS: Between 1975 and 1996, 15 consecutive patients (19 kidneys) with spontaneous renal artery dissection underwent renal artery reconstruction. Fourteen patients had accelerated hypertension. Five patients had impaired renal function. In 14 patients the dissection was associated with fibrodysplasia, and in 1 patient it was related to arteriosclerosis. INTERVENTION: In 17 kidneys extracorporeal reconstruction and autotransplantation was used. The renal artery of 1 kidney was reconstructed in situ. One primary nephrectomy was performed. RESULTS: There were no operative deaths or major morbidity. All but 1 reconstruction was successful (94.4%). Results at follow-up (range, 1-8 years) were favorable in 14 patients; 79% had satisfactory blood pressure control, and all patients had normal renal function, including those with impaired renal function preoperatively. CONCLUSIONS: Extracorporeal reconstruction and autotransplantation can be effectively used in patients with spontaneous renal artery dissection located in or extending into the distal branches. Early recognition and appreciation of the clinical presentation of spontaneous renal artery dissection are important.


Subject(s)
Aortic Dissection/surgery , Renal Artery/surgery , Vascular Surgical Procedures/methods , Adult , Blood Pressure , Female , Humans , Male , Middle Aged , Nephrectomy , Renal Artery/transplantation , Retrospective Studies , Transplantation, Autologous , Treatment Outcome
14.
Stroke ; 33(3): 749-55, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11872899

ABSTRACT

BACKGROUND: Doppler ultrasound (duplex) tests are commonly applied after carotid endarterectomy to detect possible recurrent stenosis. The appropriate frequency and the benefits are unknown. We investigated the costs and effects of various follow-up strategies to determine the optimal strategy after carotid endarterectomy. METHODS: Using decision-analytic methods, a Monte Carlo Markov model was constructed. Probabilities and costs were obtained by systematic literature review. From empirical data regarding restenosis, a disease model was constructed to test the effect of various follow-up strategies using duplex testing and angiography. Main outcome measures were quality-adjusted life-years (QALYs), probability of stroke, and costs (for both the Dutch and the American situation). RESULTS: The average quality-adjusted life expectancy for a 66-year-old patient was 6.31 years for the symptom-guided strategy (with duplex scanning only being performed in case of symptoms of cerebral ischemia). The mean lifetime costs for this strategy were $5 600 for the US and 4 600 Euro for the Netherlands. The cumulative probability of stroke was 13%. Yearly routine duplex tests up to 5 years after operation resulted in similar QALYs and a similar probability of stroke, but higher costs ($7 300 for the US and 5 600 Euro for The Netherlands situation). No other strategy, including routine duplex surveillance, increased QALYs. When MR instead of conventional angiography was used as confirmatory test, no improvement was observed either. CONCLUSIONS: Routine duplex surveillance does not result in an increase in quality-adjusted life expectancy, but it does increase costs. After successful carotid endarterectomy, a symptom-guided follow-up is an appropriate approach.


Subject(s)
Decision Support Techniques , Endarterectomy, Carotid , Graft Occlusion, Vascular/diagnosis , Outcome Assessment, Health Care/economics , Ultrasonography, Doppler, Duplex/economics , Aged , Cost-Benefit Analysis , Endarterectomy, Carotid/adverse effects , Follow-Up Studies , Graft Occlusion, Vascular/etiology , Humans , Markov Chains , Monte Carlo Method , Quality-Adjusted Life Years , Stroke/etiology , Stroke/prevention & control
15.
Neuropsychobiology ; 13(1-2): 7-11, 1985.
Article in English | MEDLINE | ID: mdl-4033897

ABSTRACT

The authors found that adoptive fathers of children with aggressive conduct disorder less often had alcoholism and antisocial personality than the natural fathers of nonadopted children with the same disorder. This evidence suggests that social factors which are widely held to produce the disorder are not necessary causes.


Subject(s)
Aggression , Child Behavior Disorders/etiology , Mental Disorders/psychology , Adoption , Adult , Alcoholism/psychology , Antisocial Personality Disorder/psychology , Child , Family , Female , Humans , Male , Socioeconomic Factors
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