Humeral metastasis as the only recurrence of a 5-year resected gastrointestinal stromal tumor: a case report.

INTRODUCTION: Gastrointestinal stromal tumors represent the most frequently encountered primary mesenchymal tumors. Whereas the liver and the peritoneum are known to be the preferential metastasis sites, no therapeutic standard has yet been established for the management of bone metastases because of their very low incidence. We report a unique example of a single humerus metastasis of a jejunal gastrointestinal stromal tumor. CASE PRESENTATION: We report the case of a 72-year-old European woman whose jejunal gastrointestinal stromal tumor was resected in 2013 and treated during the following 3 years with imatinib (400 mg daily). In 2018, she developed a single humeral bone lesion that was identified as a gastrointestinal stromal tumor metastasis. After 7 months of imatinib intake, reconstructive surgery was performed. Pathologists confirmed the satisfactory histological regression and assessed the complete tumor resection. The patient is still on imatinib maintenance therapy, with no recurrence reported so far. She fully recovered the upper limb function after following an appropriate rehabilitation program. DISCUSSION: Current literature and published case reports indicate that bones are one of the rarest locations of gastrointestinal stromal tumor metastasis (about 1%), with occurrence mainly in the spine. Patients initially diagnosed with gastrointestinal stromal tumor of the small intestine and stomach are more likely to suffer from bone metastasis, compared with other gastrointestinal stromal tumor locations. The median overall survival rate is higher for patients with isolated bone metastasis compared with those having liver metastasis. Metastasis occurs on average 4 years after the primary, but it may take up to 20 years, emphasizing the need for long-term clinical and radiological monitoring. Although specific guidelines for such cases have not yet been established, we suggest that a multimodal concerted approach involving surgery or radiotherapy associated with tyrosine kinase inhibitor intake should be considered. CONCLUSION: Bones are one of the rarest locations of gastrointestinal stromal tumor metastasis. A multidisciplinary collaboration was set up to allow conservative surgery of our patient after several months of imatinib treatment. A year and a half later, the patient is still in complete remission. This specific case supports the concept of an intermediate stage between local and oligometastatic disease that should be managed with a curative aim, as much as possible.

[Knowledge of hypertension among hypertensive patients in general practice, and its relation to achieving therapeutic goals: The Co-HACT study, French West Indies]. / Niveau de connaissance de leur pathologie des patients hypertendus suivis en médecine générale et sa relation avec l'obtention des objectifs thérapeutiques. Étude Co-HACT, DOM-TOM.

OBJECTIVES: Appraisal of the agreement between patients' reports and general practitionners' declaration in a French Caribbean population and relationship with blood pressure normalization. METHODS: One hundred French Caribbean practitioners participated in this observational survey: each of them included five essential hypertensives treated for more than three months. BP was considered to be normalized if inferior to 140/90 mmHg. We considered that there is a total agreement between patient and GP declaration when SBP and DBP did not differ by more than 5 mmHg and when the eight risk factors or co-morbidity were identical. Identification of independent factors of BP normalization and awareness was performed using logistic regression. RESULTS: Five hundred and nine hypertensives (57% women) were recruited. Sixty-nine percent (n = 328) were less than 65 years, 75% (n = 341) had an educational level less than high school. The normalisation rate was 39% (n = 185) within the whole population. 63.4% had a high cardiovascular risk. BP normalization appeared to be closely associated to BP awareness. CONCLUSIONS: In this observational survey, in a French Caribbean hypertensive population, two third had a high cardiovascular risk. The normalization rate was 39%. This BP normalization appeared to be closely associated to BP awareness.

RAD, a new immunosuppressive macrolide in murine corneal transplantation.

BACKGROUND: RAD is a novel macrolide immunosuppressant with effects on growth factor signalling. We investigated the potency of RAD in inhibiting allograft rejection in the rat model of orthotopic allogeneic penetrating keratoplasty. METHODS: Fifty-four allogeneic orthotopic penetrating keratoplasties were performed using Fisher rats as donors and Lewis rats as recipients. The animals were divided into five groups: syngeneic control, allogeneic control, RAD 1.5 mg/kg bw per day, RAD 2.5 mg/kg bw per day, cyclosporin A (CSA) 10 mg/kg bw per day. Medication started on the day of operation and continued daily for the duration of 18 days. Each animal was examined by slit-lamp microscopy every 3rd day. For immunohistological evaluation rats were killed on day 14. Immunohistology was performed using monoclonal mouse anti-rat antibodies against CD4, CD8, CD25, CD45 and CD54. RESULTS: The average transplant survival time in the allogeneic combination was 12.3 days (+/- 0.3). Therapy with RAD 1.5 mg/kg and 2.5 mg/kg led to a statistically significant prolongation of transplant survival to 32.3 days (+/- 11.3, P<0.05) and 37.7 days (+/- 12.5), respectively. This efficacy was similar to that of CSA 10 mg/kg (39.7 +/- 12.5 days). There was a statistically significant reduction in the number of CD4+, CD8+ as well as CD45+ cells in both the RAD- and the CSA-treated animals compared with the allogeneic control. CONCLUSIONS: The results show that oral immunosuppression with RAD significantly prolongs corneal allograft survival. Further investigation of RAD in preclinical and clinical high-risk keratoplasty is warranted.

Coadministration of the new macrolide immunosuppressant RAD and mycophenolate mofetil in experimental corneal transplantation.

INTRODUCTION: The effect of RAD, a new macrolide immunosuppressant, was examined as mono- and combination therapy with mycophenolate mofetil (MMF) in prevention of acute allograft rejection in murine corneal transplantation. METHODS: Both drugs were administered orally for 18 days beginning at the day of transplantation. The inbred strains Fisher and Lewis were used as donors and recipients, respectively. Five groups were involved: syngeneic control, allogeneic control, 2.5 mg/kg RAD, 40 mg/kg MMF, and double drug therapy with 1.5 mg/kg RAD and 20 mg/kg MMF. RESULTS: The median transplant survival time in the allogeneic combination was 12 (+/-0.3) days. Monotherapy with 2.5 mg/kg RAD and 40 mg/kg MMF led to a statistically significant prolongation of transplant survival to 25.5 (+/-12.5, P=0.0001) days and 19.5 (+/-13.9, P=0.0053) days, respectively. Combination therapy was superior to both monotherapies (100+/-15.8 days, P=0.03). There was a significant reduction in the number of CD4+, CD8+, as well as CD45RA+ cells in the RAD- and double drug-treated animals when compared with the allogeneic control. This significant reduction in graft-infiltrating lymphocytes has not been found in the MMF monotherapy. CONCLUSIONS: The unique finding of this first study on the combination of RAD and MMF in murine corneal transplantation is that double drug therapy produces a highly synergistic effect in prevention of acute allograft rejection without a higher incidence of complications related to drug toxicity or overimmunosuppression.

Effect of mycophenolate mofetil, cyclosporin A, and both in combination in a murine corneal graft rejection model.

AIMS: To compare the effectiveness of mycophenolate mofetil (MMF), cyclosporin A (CSA), and both in combination, in preventing rejection following corneal transplantations. METHODS: Rats of the inbred strains Brown Norway and Lewis were used as donors and recipients respectively. MMF was administered orally in both monotherapy and combination therapy for 14 days in a dosage of 40 mg/kg body weight, and CSA was administered, likewise for 14 days, in an intramuscular dosage of 10 mg/kg body weight. The transplants were examined every third day by slit lamp microscopy. Every transplant was subjected to histological or immunohistological evaluation. RESULTS: The average transplant survival rate in the allogenic strain combination was 7.9 days (SEM 1.1). Monotherapy with MMF led to a statistically significant prolongation of transplant survival to 11.6 days (SEM 0.9, p < 0.05). Monotherapy with CSA delayed transplant rejection statistically significantly longer than MMF (21 days, 0.0, p < 0.05). The combination therapy with CSA and MMF was statistically significantly superior to the monotherapy with MMF (22.3 days, 0.5, p < 0.05). The combination therapy prolonged transplant survival compared with the CSA monotherapy, albeit not to a statistically significant extent. CONCLUSIONS: In this study we were able to prove the immunosuppressive effect of oral MMF on acute rejection following corneal transplantation. Double drug therapy with CSA and MMF conferred a marginal benefit without a higher incidence of complications related to drug toxicity or overimmunosuppression.

Beyond blood pressure measurements: monitoring of the appearance time of Korotkoff sounds.

We have recently proposed a new method to evaluate the physical properties of arteries based on measurement of the QKD interval together with blood pressure and heart rate with an ambulatory blood pressure monitoring device. This interval is the time between the onset of the depolarization (QRS) on the electrocardiogram (Q) and detection of the last Korotkoff (K) sound at the level of brachial artery during cuff deflation, corresponding to diastolic blood pressure (D). The QKD interval is the sum of the pre-ejection period and of the pulse transmission time from the aortic valves and the microphone. Thus, it is linked to the pulse wave velocity on an arterial segment which includes the ascending aorta and a portion of the subclavian and brachial arteries. From each 24 h monitoring, the average 24 h QKD, the slope of variation of QKD against blood pressure and a normalized QKD (QKD100-60) for systolic blood pressure of 100 mmHg and heart rate of 60 beats/min are calculated. Stiffer arteries as observed with ageing or hypertension are characterized by the reduction of these three parameters. The reproducibility of this method is good. In a pilot study of elderly hypertensive patients we have shown that QKD 100-60 has a strong and independent predictive value for future cardiovascular events. Therefore, this method may add significant information to ambulatory blood pressure monitoring.

[Spontaneous ecchymosis disclosing acquired factor VIII inhibitor]. / Ecchymoses spontanées révélatrices d'un inhibiteur acquis du facteur VIII.

An 81-year old woman suddenly developed extensive ecchymosis. A factor VIII:c inhibitor was detected. She received porcine factor VIII, corticosteroids, intravenous immunoglobulins and cyclophosphamide. Normalization of factor VIII level was achieved in 1 month. The patient died, 3 months later, of congestive heart failure. Spontaneous development of factor VIII inhibitors is an extremely rare event which usually occurs in dramatic bleeding. Many associated diseases have been reported. Patients with serious bleeding should be given porcine factor VIII. Immunosuppressive therapy consists of corticosteroids, cyclophosphamide and intravenous immunoglobulins.