Prevention and treatment of cancer-associated thrombosis in France: A national survey among vascular disease and supportive care specialists.

BACKGROUND/AIM: Long-term use of low-molecular-weight heparins (LMWH) for the treatment of cancer-associated thrombosis (CAT) has been well-established. Conversely, the use of thromboprophylaxis in patients with cancer remains controversial in the absence of homogeneous guidelines. Our aim was to assess the awareness of treatment guidelines and the management of patients with CAT in daily clinical practice. METHODS: A national survey based on an open questionnaire developed by a panel of health professionals including specialists in vascular medicine, oncology, supportive care and pharmacy, was proposed on line to 2104 specialists experts in the management of CAT with the objective to collect at least 400 answers. Clinical practice assessment included the treatment of lung adenocarcinoma-associated thrombosis, the use of thromboprophylaxis and factors influencing the management of patients with CAT. RESULTS: A total of 401 questionnaires were completed by specialists of vascular medicine (68%), oncology (12%) and other (20%). LMWH was the preferred option for over 90% of the participants for the treatment of recent overt proximal pulmonary embolism or deep-vein thrombosis. Up to 70% of the participants considered treatment duration for 6 months and more than 12 months in case of active malignancy. Patient management in the setting of incidental VTE and thromboprophylaxis were heterogeneous in the absence of clear guidance while VTE risk scores would be used by only 14% of participants. CONCLUSION: Patients with CAT are properly managed based on clear and consistent guidelines. Patient care is heterogeneous regarding treatment duration beyond 6 months and thromboprophylaxis while VTE risk scores are misused. Identification of referent health care professionals for CAT management and more clear guidelines are required.

[What haemostatic technique should we use for opportunistic salpingectomy during benign laparoscopic hysterectomy?] / Quelle technique d'hémostase faut-il utiliser lors des salpingectomies prophylactiques ?

OBJECTIVE: To compare ovarian function before and after laparoscopic hysterectomy with bilateral salpingectomy for benign lesions with two different systems of haemostasis. METHODS: In this prospective randomized study comparing two types of energy used for coagulation in bilateral salpingectomy (group A: bipolar electric energy, versus group B: ultrasonic advanced energy [Harmonic®]), forty consecutive non-menopausal patients undergoing laparoscopic hysterectomy for benign lesions were included. Values of anti-Müllerian hormone (AMH), LH and FSH, antral follicle count (AFC) and ovarian vascularization on bilateral Doppler ultrasound, quality of life (questionnaire) were assessed preoperatively and at 1 and 3 months postoperatively. RESULTS: Preliminary analysis showed shorter salpingectomy operating time (P<0.0001) and less bleeding (P<0.005) in group B. In group A, there was no statistical difference except a decrease in AFC at 1 and 3 months on the right ovary (P=0.04). In group B, AMH levels were significantly lower postoperatively at 3 months and LH levels were increased at 3 months (respectively P=0.02 et P=0.04). There was no statistical difference in the ultrasonographic data. Quality of life did not significantly differ in both groups. CONCLUSION: Preliminary findings showed reduced AMH levels at 3months postoperatively in ultrasonic energy group whereas there was no significative menopausal symptoms. It seems important to continue this study in order to know the real effects of both energy systems on the ovarian function.

Low-molecular-weight heparins for cancer-associated thrombosis: Adherence to clinical practice guidelines and patient perception in TROPIQUE, a 409-patient prospective observational study.

PURPOSE: Data on long-term treatment with low-molecular-weight heparins (LMWH) in cancer patients treated for venous thromboembolism are scarce. Study objectives were to document the long-term clinical use of LMWH and patient perception in this setting. METHODS: Adult cancer patients receiving antineoplastic treatment or palliative care and LMWH for cancer associated venous thromboembolism (CAT) were eligible to participate in this prospective observational study. Main outcome was adherence to clinical practice guidelines based on recommended LMWH treatment doses for at least 3months in the absence of severe renal insufficiency. Patients' perception of the treatment was assessed in an ancillary study using the Perception Anticoagulant Treatment Questionnaire (PACT-Q). RESULTS: Among 409 included cancer patients aged 65±12.1years, overall adherence to practice guidelines as defined in the protocol was 55.3% (226 patients). However, 98.0% of patients received a prescription for 3months or more and mean LMWH treatment duration for VTE was 6.27±0.15months which meets guidelines recommendations. Main patients' expectations scored on a 1-5 scale were blood clots prevention (mean 3.94±0.75), symptom relief (mean 3.98±1.04) and ease of use (mean 4.22±0.9). LMWH treatment appeared convenient (global score 79.7±17.1 on a 0 to 100 scale) and 69.1% of patients were satisfied or very satisfied. CONCLUSION: Despite incomplete strict adherence to guidelines, treatment duration with LMWH was adequate showing substantial progress in the management of CAT patients. Patients expectations were high while treatment was perceived convenient with a high degree of satisfaction.

[Septic shock with multiple organ failure after returning from Southeast Asia]. / Choc septique avec défaillance multiviscérale au retour d'Asie du Sud-Est.

For a patient recently returned from a tropical country in intensive care, the leading hypothesis for a fever leading to multiple organ failure is evidently malaria. Nonetheless, many other causes are possible and should be considered: parasites, viruses, and bacteria. A multidisciplinary discussion between specialists in emergency medicine, radiology, pathology, and infectious diseases is essential to start appropriate treatment as quickly as possible without impairing the patient's prognosis.

[Imported malaria at Desgenettes Military Hospital in Lyon, France: a retrospective study of 115 cases from 2006 to 2008]. / Le paludisme d'importation à l'hôpital d'instruction des armées Desgenettes de Lyon en 2006-2008 : étude rétrospective de 115 cas.

PURPOSE: The purpose of this report is to describe the clinical, epidemiologic, and parasitological features and therapeutic modalities associated with cases of imported malaria managed at the Desgenettes Military Hospital in Lyon, France. MATERIAL AND METHODS: Review of the files of all patients treated for imported malaria in the emergency and travel medicine departments of the Desgenettes Military Hospital from January 1, 2006, through December 31, 2008. RESULTS: The study included 115 patients (13 of them French armed forces personnel). Most cases (75.6%) were due to falciparum malaria. Only 28.7% of patients had taken proper malaria prophylaxis. Severe symptoms were seen in none of the ambulatory care patients versus 22.7% of the hospitalized patients. Quinine treatment was used for 67% of ambulatory care patients and 89.4% of those hospitalized. CONCLUSIONS: The epidemiologic features observed in the patients described here are similar to those reported by the French national reference center for imported and autochthonous malaria. The frequent use of quinine for ambulatory treatment was not consistent with current guidelines recommending first-line treatment with atovaquone-proguanil or artemether-lumefantrine.

[Pulmonary hypertension and femoral neck fracture: interest of continuous spinal anaesthesia]. / Hypertension pulmonaire et fracture du col fémoral : intérêt de la rachianesthésie continue.

Anaesthetic management of patients with pulmonary hypertension is challenging and alternatives to general anaesthesia are encouraged. We report anaesthetic management of two patients with pulmonary hypertension admitted for femoral neck fracture. In order to reduce the risk of right-sided heart failure and systemic hypotension, it was decided to operate the patients under continuous spinal anaesthesia. Anaesthesia was induced with excellent hemodynamic tolerance. Quality and extension of the block was correct and allowed surgery. No postoperative complication was observed. These cases suggest that continuous spinal anaesthesia may be considered for the management of patients with pulmonary hypertension undergoing femoral neck fracture surgery.

Sexual and urinary dysfunction after proctectomy for rectal cancer.

Sexual and urinary dysfunction occur frequently after rectal surgery. Total mesorectal excision (TME) is currently the optimal technique for resection of rectal cancer, providing superior carcinological and functional outcomes. Age, pre-operative radiation therapy, abdominoperineal resection, and surgery which fails to respect the "sacred planes" of TME are the four major risk factors for post-operative sexual and urinary sequelae. In the era of TME, postoperative sexual dysfunction ranges from 10-35%, depending on the scores used to assess it, while urinary sequelae have decreased to less than 5%. The place of laparoscopic surgery remains to be defined, particularly with respect to these complications. It is essential to inform the patient pre-operatively about the possibility of such disorders not only for patient informed consent but also to help with correct post-operative management of the problem. Management is multifaceted, and includes psychological, pharmacological, and sometimes surgical therapy.

Dual roles of Drosophila p53 in cell death and cell differentiation.

The mammalian p53 family consists of p53, p63 and p73. Whereas p53 accounts for tumor suppression through cell-cycle arrest and apoptosis, the functions of p63 and p73 are more diverse and also include control of cell differentiation. The Drosophila genome contains only one p53 homolog, Dp53. Previous work has established that Drosophila p53 (Dp53) induces apoptosis, but not cell-cycle arrest. In this study, using the developing eye as a model, we show that Dp53-induced apoptosis is primarily dependent on the pro-apoptotic gene, head involution defective (hid), but not reaper (rpr), and occurs through the canonical apoptosis pathway. Importantly, similar to p63 and p73, expression of Dp53 also inhibits cellular differentiation of photoreceptor neurons and cone cells in the eye independently of its apoptotic function. Intriguingly, expression of the human cell-cycle inhibitor p21 or its Drosophila homolog dacapo (dap) can suppress both Dp53-induced cell death and differentiation defects in Drosophila eyes. These findings provide new insights into the pathways activated by Dp53 and reveal that Dp53 incorporates functions of multiple p53 family members.

Ectopic hyperprolactinaemia in a woman with a mesocolic perivascular epithelioid cell tumor ("PEComa").

Ectopic prolactin secretion remains exceptional and originates mainly from malignant tumors. We report the case of a 47-year-old woman who presented amenorrhea leading to unravel important hyperprolactinaemia (269 ng/mL) with no hypothalamo-pituitary mass on magnetic resonance imaging (MRI). Pelvic imaging revealed the presence of a large pelvic mass that originated from the mesocolon. After complete surgical extraction, histological examination was in favour of a "perivascular epithelioid cell tumor" (PEComa). Prolactin levels normalized after surgical extraction and remained normal after a 3-year follow-up, totally free of tumour recurrence and/or metastasis. This suggests that hyperprolactinaemia was most likely related to the PEComa, despite negative reactions with antiprolactin antibodies at immunohistochemistry. Alternatively to a direct prolactin secretion by the tumor, one could hypothesize that the tumour secreted a prolactin stimulating factor or a dopamine antagonist that could not be identified. In conclusion, in face of an important hyperprolactinaemia without any hypothalamic-pituitary mass, it remains important to search for an ectopic prolactin production, such as a PEComa.

Peptic ulcer of the gastric tube after esophagectomy for cancer: clinical implications.

The use of the stomach as an esophageal substitute has become a well-established treatment procedure after esophagectomy for cancer. During the procedure, a bilateral truncal vagotomy is performed, which should prevent the occurrence of acid-related diseases in the gastric tube and in the remaining esophagus. We report the case of a man who presented a plugged perforated peptic ulcer that subsequently decompensated following endoscopic examination 1 year after a transthoracic esophagectomy with neoadjuvant chemo-radiation for a middle third squamous cell carcinoma. Resection of the ulcer and suture with a pleural patch was performed. There was no evidence of recurrent malignancy at time of surgery. The pathophysiology of gastric tube ulcer is multifactorial. Long-term treatment with an anti-secretory proton pump inhibitor may decrease esophageal complications of duodeno-gastric-esophageal reflux and could prevent the recurrence of gastric tube ulcers.

Impact of preoperative radiochemotherapy on postoperative course and survival in patients with locally advanced squamous cell oesophageal carcinoma.

BACKGROUND: The aim of this study was to determine the effect of neoadjuvant radiochemotherapy (RCT) on postoperative complications and survival after surgery for locally advanced oesophageal squamous cell carcinoma. METHODS: Postoperative course and survival were compared in 144 patients who had neoadjuvant RCT and 80 control patients who had surgery alone for locally advanced oesophageal squamous cell carcinoma (radiological stage T3, N0 or N1, M0). RESULTS: The two groups were comparable in terms of American Society of Anesthesiologists grade, age, sex, weight loss, tumour location, presence of lymph node metastasis and surgical approach. Postoperative mortality rates were 6.3 and 9 per cent (P=0.481), with morbidity rates of 40.3 and 41 percent (P=0.887) in the RCT and control group respectively. Complete resection (R0) rates were 74.3 and 48 percent respectively (P<0.001). Significant downstaging was observed in the RCT group (P<0.001), with 16.0 percent of patients having a complete pathological response. Median survival was 29 versus 15 months, and the 5-year survival rate 37 versus 17 percent (P=0.002) in RCT and control groups respectively. CONCLUSION: Neoadjuvant RCT significantly enhanced R0 resection and survival rates in patients with stage T3 oesophageal squamous cell carcinoma, with no increase in postoperative mortality and morbidity rates.

[Paragangliomas: clinical and secretory profile. Result of 39 cases]. / Paragangliomes: profil clinique et sécrétoire. A propos de 39 cas.

THIS RETROSPECTIVE STUDY AIMS: To define a clinical and secretory profile of paragangliomas extra-adrenal chromaffin tumors. METHODS: From 1971 throughout 2002, 39 paragangliomas have been observed in 38 patients (22 male, 16 female, average age 41,2 years). RESULTS: Four were located above the diaphragm, 35 were sub-phrenic (6 of the organ of Zuckerkandl), 32 secreted catecholamines, 23 were hypertensive (with only one without hypersecretion of catecholamines). Among 29 (131)I-metaiodobenzylguanidine scans (MIBG) reviewed, 20 tumors took up the radiopharmaceutical. The treatment was surgical in 35 cases with addition of external radiotherapy and MIBG in one case each; two patients died before any treatment. Two patients with persistent disease after surgery were successfully treated by surgery or MIBG. Histologically, 20 were malignant and 17 were seemingly benign. All exclusive dopamine secreting paragangliomas were malignant. Six patients relapsed two of which for a tumor initially classified as benign. The treatment of recurrences was surgical, by MIBG or by external radiotherapy. Nine patients had a family history of chromaffin tumor(s). The genetic survey made in five of these nine patients was positive in all cases.

[Patients surviving 5 years after curative oesophagectomy for oesophageal cancer]. / Patients vivants à 5 ans après oesophagectomie curative pour cancer.

AIM OF THE STUDY: To analyse the clinical and pathological parameters of 5-year survival patients after curative oesophageal resection for cancer and to identify factors predictive of long-term survival. METHODS: The data of 370 patients who underwent oesophagectomy with curative intent from January 1982 for oesophageal squamous cell carcinoma (n = 320) or adenocarcinoma (n = 50) were reviewed. After excluding postoperative deaths (n = 20), these patients were surviving (S group, n = 113) or dead (NS group, n = 237) with a 60-month follow-up. Uni- and multivariate analysis allowed comparison between the two groups. RESULTS: Postoperative mortality and morbidity rates were 4.0% and 37.6%, respectively. Parameters related to 5-year survival were: absence of preoperative malnutrition or dysphagia, transhiatal resection, no reoperation, limited tumour, histological response to neoadjuvant treatment, absence of lymph node capsular invasion, number of invaded lymph nodes < or = 4, invaded lymph node ratio < or = 0.1, absence of tumour recurrence or metachronous primary cancer. On multivariate analysis, factors predictive of 5-year survival were: absence of preoperative dysphagia (P < 0.001), stage 0-I-IIA tumour (P<0.001) and absence of metachronous cancer (P = 0.016). CONCLUSION: Complete surgical resection allows 5-year survival. Factors predictive of long-term survival assessed in preoperative evaluation, dysphagia and tumour stage, should be useful to select patients for neoadjuvant treatment.

Adenocarcinoma in a gastric tube after esophagectomy for esophageal carcinoma.

The development of an adenocarcinoma in a reconstructed tube after subtotal esophagectomy for esophagus squamous cell carcinoma (ESCC) is uncommon and has been reported in articles from the Japanese medical community. We report three cases of patients who had this clinical presentation. We suggest an approach to postoperative management of ESCC to identify early tumors in gastric tubes and to allow endoscopic or surgical curative treatment.

[Acute peritonitis: a rare presentation of chylous ascites]. / Péritonite aiguë: un mode de révélation rare d'ascite chyleuse.

Chylous ascites is a rare case of peritonitis. We report here a case arising in a 21-year-old lady.

[Coagulation activation with intraportal islets of Langerhans transplantation in swine]. / Activation de la coagulation par la greffe intraportale d'îlots de Langerhans chez le porc.

STUDY AIM: Intraportal islet allograft appears to be one of the promising treatments for type I diabetes. However, many limiting factors persist. An activation of the coagulation cascade upon contact with islets, has been reported recently in vitro and could play a crucial role in a non specific inflammatory reaction and favour the specific immune reaction. The aim of this experimental study was to confirm in vivo this activation of the coagulation cascade. MATERIAL AND METHODS: An allogenic islets preparation or a material control (inert microbeads) was injected intraportally, in Large White pigs (n = 26), associated with or without an anticoagulant treatment (heparin). Systemic markers of haemostasis were measured in pigs for 72 hours following injection of the studied material. RESULTS: The thrombin-antithrombin complex increased and platelet count decreased in groups receiving preparation of islets, both indicators of an activation of the coagulation cascade. This activation was proportional to the injected volume and was partially attenuated by heparin. No activation was observed in pigs receiving the material control. CONCLUSION: The activation of the coagulation cascade and the non specific inflammatory reaction could be one of the obstacles to the success of the islet allografts. The use of anticoagulant and anti-inflammatory molecules could potentially allow an improvement of the present results of islet allograft.

[Decompensation of lower limb arteritis after bone and joint surgery]. / Décompensation d'une artérite après chirurgie osseuse et articulaire.

PURPOSE OF THE STUDY: Decompensation of lower limb arteritis after bone and joint surgery is an unusual finding compared with the large number of procedures performed in both emergency and controlled settings. There is however a functional and limb-threatening risk that must not be overlooked. MATERIAL AND METHODS: We report a series of 9 patients followed in our department over the last 3 years. Emergency surgery had been required in 6 patients after trauma and 3 had undergone a planned orthopedic procedure. All the patients had at least one vascular risk factor, and 7 of them had a cardiovascular history. The inaugural sign was a trophic disorder due to a grade IV decompensated arteritis in 8 patients, including 2 with nonunion. Delay to treatment ranged from 1 to 3 months. Acute embolic ischemia required emergency care in 1 patient. RESULTS: A revascularization procedure was performed on 6 limbs and was successful in 3. There were also 6 amputations, three initially, 1 after septic shock and 2 because revascularization was impossible. Three of the amputations were required after failed revascularization. Prosthesis wearing and walking was possible in only two amputated patients. Overall rate of successful salvage was 33% (3 successful revascularizations among 9 limbs). One of the nonunions healed after revascularization; the limb was amputated for the other one. One patient died from septicemia. DISCUSSION: Our series further illustrates the severity of decompensated arteritis after bone and joint surgery, emphasizing the importance of searching for cardiovascular risk factors and functional signs suggestive of a vascular disorder. Arterial duplex Doppler and if necessary arteriography of the lower limbs should be obtained in case of doubt. Two different situations can be distinguished depending on the predictable vascular risk and the localization of the planned bone reconstruction. If the patient has an asymptomatic proximal arteritis and bone and joint surgery is planned above the knee, a revascularization procedure would not appear necessary prior to bone surgery. In other cases, it may be more advisable to treat the arteritis before attempting bone surgery. For trauma victims, the osteosynthesis technique depends greatly on knowledge of the vascular risk.