In vitro interaction of posaconazole with calcineurin inhibitors and sirolimus against zygomycetes.

OBJECTIVES: Zygomycosis is an uncommon but devastating disease with few therapeutic options. Calcineurin inhibitors and sirolimus (mTOR inhibitor), commonly used in transplant patients as immunosuppressives, have antifungal activity. They are known to demonstrate synergy with triazoles against certain fungi, though limited data exist about their activity against zygomycetes. Our aim was to study the in vitro interaction of posaconazole with calcineurin inhibitors and sirolimus against zygomycetes. METHODS: Drug interactions were assessed with chequerboard dilution for posaconazole with calcineurin inhibitors and sirolimus according to the CLSI M38-A2 method for filamentous fungi. Twenty-eight clinical isolates were studied, including Rhizopus arrhizus, Rhizopus microsporus, Rhizomucor pusillus, Mucor sp., Cunninghamella bertholletiae, Myocladus corymbifera and Apophysomyces elegans. Combinations of posaconazole with tacrolimus, cyclosporin A or sirolimus were used. Experiments were performed in duplicate. Mean fractional inhibitory concentration indices were calculated. RESULTS: Posaconazole with calcineurin inhibitors demonstrated consistent synergy against C. bertholletiae, M. corymbifera and A. elegans, whereas synergy or no interaction was primarily observed against R. arrhizus, R. microsporus, R. pusillus and Mucor. Antagonism was seen with the combination of posaconazole and sirolimus. Strain variability was noted among the same species. CONCLUSIONS: The clinical significance of these findings is unclear, but further studies are warranted given the potential for concomitant use of these agents in transplant patients treated for zygomycosis.

Non-bacterial infections in allogeneic non-myeloablative stem cell transplant recipients.

Data on non-bacterial infections during allogeneic non-myeloablative hematopoietic stem cell transplantation (HSCT) are widely different. We evaluated data on 48 consecutive patients who received a conditioning regimen with fludarabine and cyclophosphamide (73%) or fludarabine and total body irradiation (27%) and then underwent allogeneic non-myeloablative HSCT. Cytomegalovirus (CMV) infection was common and occurred in 48% of patients; 3 patients developed CMV disease, and all survived. CMV reactivation was found to be common with both conditioning regimens in our patient population. Invasive aspergillosis occurred in 4 patients (8%) and 3 died. Other serious non-bacterial infections were uncommon. Review of the available literature on non-myeloablative HSCT suggests that the frequency and type of opportunistic infections vary considerably.

Sonographically guided mammotome excision of ducts in the diagnosis and management of single duct nipple discharge.

AIM: To describe our experience in the use of ultrasound guided mammotome in the diagnosis and management of single duct nipple discharge. METHODS: Patients for whom surgical excision of the single duct had been advised for single duct nipple discharge were offered ultrasound guided mammotome excision of the duct as an alternative to surgical excision. The procedure was performed in the breast clinic by a surgeon or a breast clinician who had interventional ultrasound skills. RESULTS: Seventy-seven patients had 81 procedures. Follow-up at a mean time of 16 months revealed resolution of the presenting problematic discharge in 95% of patients. Nipple discharge recurred in four patients. Two patients had microdochectomy and two had a repeat mammotome for recurrence of symptoms. Complications were mild and infrequent. CONCLUSION: Ultrasound guided mammotome excision is a new tool in the work up and management of single duct nipple discharge. It can be performed under local anaesthetic by a surgeon/breast clinician or radiologist with interventional ultrasound skills. It has the potential to replace surgical excision (microdochectomy) as a treatment for nipple discharge.

Preoperative mammotome biopsy of ducts beneath the nipple areola complex.

AIM: To evaluate the role of ultrasound guided mammotome biopsy of the ducts beneath the nipple areola complex (NAC), as a new technique in detecting the occult involvement of the NAC in breast cancer patients prior to nipple preserving subcutaneous mastectomy. METHOD: A prospective study where 33 women requesting nipple preserving mastectomy for invasive or in situ disease were offered the procedure to determine if leaving the nipple was safe. A 5 mm skin incision was made after infiltration with local anaesthetic and the 11G mammotome needle was positioned beneath the nipple under ultrasound guidance which was turned through 360 degrees as the biopsies were taken. The procedures were performed by trained non-radiologists. RESULTS: Thirty-three women had 36 procedures. Seven out of the 36 had a positive mammotome biopsy. Twenty-three patients had 26 NAC preserving mastectomies with immediate reconstruction. Three had bilateral procedures. Ten patients had NAC sacrificed. The histopathology of the mastectomy specimen correlated 100% with the mammotome biopsy. CONCLUSION: Preoperative ultrasound guided mammotome biopsy of the ducts beneath the NAC is a safe, reliable and accurate technique and is evolving as an oncologically safe procedure. The large mammotome needle can be visualized easily under high resolution, near field high frequency scanners and this increases the accuracy of the biopsy. It can replace the traditional frozen section and be used as an alternate. It can be performed safely by an appropriately trained non-radiologist (surgeon/breast clinician).

Recurrent abscess at site of laparoscopic cholecystectomy port due to spilled gallstones.

Spillage of gallstones is common during laparoscopic cholecystectomy and may lead to intra-abdominal abscesses and sinus formation. We describe two patients with recurrent abscess at the site of epigastric port due to presence of large spilled stone in the parietes following laparoscopic cholecystectomy. Removal of the stone led to resolution of symptoms.