Recurrence of pseudomyxoma peritonei after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Background: Pseudomyxoma peritonei (PMP) is a rare clinical condition characterized by mucinous ascites, typically related to appendiceal or ovarian tumours. Current standard treatment involves cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), but recurrences occur in 20-30 per cent of patients. The aim of this study was to define the timing and patterns of recurrence to provide a basis for modifying follow-up of these patients. Methods: This observational study examined a prospectively developed multicentre national database (RENAPE working group) to identify patients with recurrence after optimal CRS and HIPEC for PMP. Postoperative complications, long-term outcomes and potential prognostic factors were evaluated. Results: Of 1411 patients with proven PMP, 948 were identified who had undergone curative CRS and HIPEC. Among these patients, 229 first recurrences (24·2 per cent) were identified: 196 (20·7 per cent) occurred within the first 5 years (early recurrence) and 30 (3·2 per cent) occurred between 5 and 10 years. Three patients developed a first recurrence more than 10 years after the original treatment. The mean(s.d.) time to first recurrence was 2·36(2·21) years. Preoperative chemotherapy and high-grade pathology were significant factors for early recurrence. Overall survival for the entire group was 77·9 and 63·1 per cent at 5 and 10 years respectively. The principal site of recurrence was the peritoneum. Conclusion: Recurrence of PMP was rare after 5 years and exceptional after 10 years.

Cytoreductive surgery and HIPEC improve survival compared to palliative chemotherapy for biliary carcinoma with peritoneal metastasis: A multi-institutional cohort from PSOGI and BIG RENAPE groups.

BACKGROUND: Peritoneal metastasis from biliary carcinoma (PMC) is associated with poor prognosis when treated with chemotherapy. OBJECTIVE: To evaluate the impact on survival of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), and compare with conventional palliative chemotherapy for patients with PMC. MATERIAL AND METHODS: A prospective multicenter international database was retrospectively searched to identify all patients with PMC treated with a potentially curative CRS/HIPEC (CRS/HIPEC group). The overall survival (OS) was compared to patients with PMC treated with palliative chemotherapy (systemic chemotherapy group). Survival was analyzed using Kaplan-Meier method and compared with Log-Rank test. RESULTS: Between 1995 and 2015, 34 patients were included in the surgical group, and compared to 21 in the systemic chemotherapy group. In the surgical group, median peritoneal cancer index was 9 (range 3-26), macroscopically complete resection was obtained for 25 patients (73%). There was more gallbladder localization in the surgical group compared to the chemotherapy group (35% vs. 18%, p = 0.001). Median OS was 21.4 and 9.3 months for surgical and chemotherapy group, respectively (p=0.007). Three-year overall survival was 30% and 10% for surgical and chemotherapy group, respectively. CONCLUSION: Treatment with CRS and HIPEC for biliary carcinoma with peritoneal metastasis is feasible and may provide survival benefit when compared to palliative chemotherapy.

Model-based drug development in oncology: what's next?

Model-based estimates of tumor growth inhibition (TGI) metrics have the potential to enhance learning in early (phase II) clinical studies. They can be used as end points and biomarkers to predict treatment effect on clinical outcome measures-e.g., overall survival (OS)-and support phase II study design, end-of-phase II decisions, and phase III planning and execution. Efforts should be made to assess models in simulating independent studies with treatments of varying mechanisms of action.

Adherence to monthly and weekly oral bisphosphonates in women with osteoporosis.

UNLABELLED: This primary care database survey evaluated whether osteoporotic women treated with bisphosphonates were more adherent to monthly than to weekly treatment. Both compliance (medication possession ratio [MPR]) and persistence (time to discontinuation) were superior in the monthly ibandronate treatment group. Better control of fracture risk may thus be achieved using monthly treatment regimens. INTRODUCTION: Treatment adherence in osteoporosis is poor. The objective of this study was to evaluate whether monthly bisphosphonate treatment provided superior adherence than weekly treatment. METHODS: We analysed medical claims from a national prescription database (Thales). All women aged >45 years receiving a first prescription of monthly ibandronate or weekly bisphosphonates in 2007 were included. Treatment adherence was monitored from initial prescription until January 2008. Compliance was measured by the MPR and persistence by the time from treatment initiation to discontinuation. Multivariate analysis was used to identify variables independently associated with adherence. RESULTS: Twelve-month persistence rates were 47.5% for monthly ibandronate and 30.4% for weekly bisphosphonates. Compliance was significantly higher in the monthly cohort (MPR = 84.5%) than in the weekly cohort (MPR = 79.4%). After adjustment for potential confounding variables, women with monthly regimens were 37% less likely to be non-persistent (HR = 0.63 [0.56-0.72]) and presented a 5% higher mean MPR (84.5% versus 79.3%, p < 0.001) than women with weekly regimens. Other major factors associated with improved adherence were previous densitometry and calcium or vitamin D supplementation (p < 0.01). CONCLUSIONS: Adherence to bisphosphonates may be superior for monthly treatment than for weekly treatment and may thus provide improved fracture protection.

[Recombinant activated factor VII as a life-saving therapy for severe postpartum haemorrhage unresponsive to conservative traditional management]. / Intérêt du facteur VII activé recombinant dans l'hémorragie de la délivrance sévère réfractaire à la prise en charge conservatrice conventionnelle.

Postpartum haemorrhage remains the main cause of maternal morbidity and mortality. Treatment aims at maintaining hemodynamic circulation and preventing shock by stopping blood loss both medically and surgically. We report two cases of major postpartum haemorrhage due to uterine atony. Patients developed haemorrhagic shock and severe coagulation disorders (nadir values of PTT were <10% and fibrinogen was <0.1 g/l). Well-codified medical (ocytocin, sulprostone) and surgical management (ligation of both hypogastic arteries in the two cases completed by staged uterine ligation in one case) failed to stop bleeding. Recently, several case reports described successful use of recombinant activated factor VII (rFVIIa) in scheduled surgery, trauma and major postpartum haemorrhage. Thus, after transfusion of more than one blood mass and failure of surgical haemostasis to stop bleeding, rFVIIa (60 microg/kg) was given. A single iv bolus injection stopped ongoing diffuse haemorrhage in the two cases. No further transfusion was required afterwards in both patients. RFVIIa might thus be a strong complementary agent in the management of major postpartum haemorrhage. Optimal dose, timing and safety characteristics of rVIIa administration remain to be determined. One patient developed four weeks later thrombosis of both ovarian veins, a complication that can be related to either rFVIIa or to the staged uterine ligations performed during surgery.

Comparison between conventional axillary block and a new approach at the midhumeral level.

We undertook this prospective, randomized study to compare the success rate, time spent performing the blocks, onset time of surgical anesthesia, presence of complete motor blockade, and lidocaine plasma concentrations between conventional axillary block and a new approach at the midhumeral level. Both techniques were performed using a peripheral nerve stimulator. Two nerves were located at the axillary crease, whereas four nerves were located at the midhumeral level. Sixty patients undergoing upper limb surgery were assigned to one of the two techniques. The sensory block was evaluated before surgery for all of the distributions of the four major nerves of the upper extremity. A subset of patients had lidocaine plasma concentrations determined. Times to perform the blocks, mean maximum plasma lidocaine concentration, and time to peak concentration were not different between groups. The success rate of the block, as well as the incidence of complete motor blockade, was greater with the midhumeral approach compared with the axillary approach. However, the onset time to complete anesthesia of the upper extremity was shorter in the axillary approach. For brachial plexus anesthesia, we conclude that the midhumeral approach provided a greater success rate than the traditional axillary approach.

[Autotransfusion during caesarean section with blood containing p salbutamol without adverse effects]. / Autotransfusion en cours de césarienne de sang contenant du salbutamol sans effets indésirables.

We report the case of a patient presenting with a placenta praevia and who donated autologous blood while she had beta 2-agonist tocolysis. As the restitution of blood containing salbutamol at therapeutic concentration may induce uterine atony and cardiovascular symptoms, we monitored maternal clinical signs and plasma concentrations of salbutamol when autologous blood was retransfused after the end of Caesarean section. The maternal plasma beta 2-agonist levels during tocolysis were in agreement with the usual therapeutic concentrations. The beta 2-agonist infusion was discontinued 30 minutes before the subarachnoid blockade and the blood concentration measured at the time of skin incision was below the therapeutic threshold. The retransfusion of autologous blood neither raised the salbutamol concentration above the therapeutic threshold value, nor induced any clinical symptoms. After Caesarean section the retransfusion of autologous blood containing therapeutic concentration of salbutamol seems to be innocuous.