Long-term results of a double perfusion schedule using high dose hyperthermia and melphalan sequentially in extensive melanoma of the lower limb

The aim of this study was to assess the results of an isolated limb perfusion (ILP) schedule with high dose hyperthermia (42-43 degrees C) and melphalan, applied sequentially in patients with advanced melanoma of the limbs. Seventeen patients with extensive recurrent or bulky melanoma of a limb were treated with hyperthermic femoral ILP (42-43 degrees C) without drugs followed by normothermic (37-38 degrees C) ILP with melphalan. Eleven patients (65%) had a complete response. Three patients (27%) had limb recurrences after 5, 6 and 18 months, respectively. The 5 year limb recurrence-free interval for patients with a complete response was 63%. Limb toxicity was mild; pressure-related blistering and transient sensory disturbances occurred after the hyperthermic ILP, and 88% of the patients had a grade II reaction (mild erythema and oedema) after the second ILP. This sequential ILP schedule resulted in a high complete response rate and a low limb-recurrence rate in patients with extensive, recurrent melanoma of the limbs at the cost of only mild toxicity. This regimen could be an alternative to ILP with tumour necrosis factor-alpha and melphalan.     

Management of hypertension

Presently, many drugs are available for the treatment of patients with high blood pressure. Although there are several theoretical arguments favouring one particular type of drug over the other, prospective clinical trials have failed to show major differences between drug classes in terms of overall prognosis. A possible exception in this regard may be the development of diabetes mellitus which seems to occur less frequently with ACE inhibitors, AT1 receptor blockers and calcium entry blockers than with diuretics. The choice of the antihypertensive drug regimen should take certain patient characteristics into account, notably comorbid conditions. However, despite theoretical considerations concerning initial therapy many patients will end up using two or more medications.     

The effect of warfarin on the pharmacokinetics and pharmacodynamics of napsagatran in healthy male volunteers

OBJECTIVE: The effect of oral warfarin on the pharmacokinetics and pharmacodynamics of the synthetic direct thrombin inhibitor napsagatran was investigated. METHODS: In an open, randomised, two-way crossover study, 12 healthy male volunteers were infused napsagatran (80 micrograms/min) for 48 h. Each subject was administered 25 mg warfarin (Coumadin) at the start of the infusion in either the first or second treatment period. Sampling was performed regularly over the treatment period and 24 h thereafter for measurement of plasma levels of napsagatran, activated partial thromboplastin time (APTT) and prothrombin time (PT). RESULTS: The pharmacokinetic parameters of napsagatran were not significantly influenced by co-administration of warfarin. Napsagatran administration was followed by increases in APTT and PT. Co-administration of warfarin increased the AUEC (area under the effect curve) calculated for the period 0-48 h (corrected for baseline) for APTT by 45% (95% CI: 28-65%) and for PT by 438% (95% CI: 272-678%) compared to the treatment with napsagatran alone. CONCLUSION: Warfarin has no effect on the pharmacokinetics of napsagatran, but has a marked influence on the pharmacodynamic parameters (APTT, PT) of napsagatran. In clinical practice, this interaction between the two compounds should be taken into account. The PT cannot be used to monitor the effect of oral anticoagulants during the switch from this group of direct thrombin inhibitors to full oral anticoagulant therapy.     

Lymphatic Drainage Patterns from the Treated Breast

Introduction

Lymphatic drainage patterns from the breast have been described in the past. Drainage may change after treatment of a breast or axilla, and this may have implications for lymphatic mapping. The aim of this study was to determine the lymphatic drainage patterns in breast cancer patients with a previously treated ipsilateral breast.

Methods

Between January 1999 and November 2008, 115 sentinel node procedures were performed in breast cancer patients who had undergone treatment of the ipsilateral breast in the past. Lymphatic drainage patterns were analyzed based on preoperative lymphoscintigraphy and sentinel lymph node biopsy. Patients were divided into subgroups according to their previous treatment.

Results

Sentinel nodes were found in 84% of the patients: in 81 patients (70%) in the axilla, 43 patients (37%) had drainage to more than one site, and in 18 patients (16%) no drainage was detected. The percentage of drainage outside the axilla was higher than in a series of untreated breast cancer patients from our institution (51% versus 33%, P = 0.01). The 16% nonidentification rate was also higher than the 3.1% in patients without previous treatment (P = 0.003). Four patients (3.5%) had lymphatic drainage to the contralateral axilla. Twelve patients (10%) had involved sentinel nodes; these were harvested from the contralateral axilla in two of them. No lymph node recurrences were observed during a median follow-up time of 39 months.

Conclusion

Lymphatic mapping yields a lymph node in 84% of breast cancer patients who have undergone previous treatment of the breast. Nonidentification and extra-axillary nodes are more frequently encountered than in patients without treatment of the breast in the past. The finding of involved nodes suggests that sentinel node biopsy improves staging. Long-term follow-up will determine the sensitivity of the procedure in this specific situation.     

Network therapy: decreased secondary opioid use during buprenorphine maintenance

Network therapy (NT) employs family members and/or friends to support compliance with an addiction treatment carried out in office practice. This study was designed to ascertain whether NT is a useful psychosocial adjunct, relative to a control treatment, for achieving diminished illicit heroin use for patients on buprenorphine maintenance. Patients agreeing to randomization to either NT (N = 33) or medication management (MM, N = 33) were inducted onto short-term buprenorphine maintenance and then tapered to zero dose. NT resulted in significantly more urine toxicologies negative for opioids than MM (65% vs. 45%) and more NT than MM patients (50% vs. 23%) experienced a positive outcome relative to secondary heroin use by the end of treatment. The use of NT in office practice may therefore improve the effectiveness of eliminating secondary heroin use during buprenorphine maintenance. It may also be useful in enhancing compliance with an addiction treatment regimen in other contexts.