Neutropenic acute acalculous cholecystitis (AAC) in a 12-year-old boy with T-acute lymphoblastic leukemia successfully managed with conservative treatment.

Acute acalculous cholecystitis (AAC) is an inflammation of the gallbladder without the presence of gallstones. In children with malignancies or chemotherapy-induced neutropenia, AAC is very rare. Clinical diagnosis of AAC remains difficult in this patient population but an early recognition followed by an appropriate intervention may confer a benefit. Only three pediatric patients with underlying hematological malignancies whose clinical treatment course was complicated by the development of AAC have been described. We describe a neutropenic pediatric patient who developed AAC following chemotherapy for acute T-cell acute lymphoblastic leukemia (T-ALL), which was successfully managed with conservative treatment. ABBREVIATIONS: AAC: Acute acalculous cholecystitis; T-ALL: T-cell acute lymphoblastic leukemia; TPN: Total parenteral nutrition.

Obstructive uropathy and vesicovaginal fistula secondary to a retained sex toy in the vagina.

INTRODUCTION: Vaginal foreign bodies (FBs) are a rare cause of vesicovaginal, rectovaginal, or urethrovaginal fistulae. AIM: The aim of this study was to describe a rare case of vesicovaginal fistula (VVF) and obstructive uropathy and to review the literature. METHODS: A case is presented. A comprehensive review of the literature was performed (1948-2013). RESULTS: A 38-year-old woman presenting with sepsis, obstructive uropathy, and severe emaciation was found to have a sex toy retained in her vagina for 10 years. This had caused a VVF and bilateral hydroureteronephrosis. Bilateral nephrostomies were inserted and she underwent cystoscopy and examination under anesthesia (EUA) with retrieval of FB. A left ureteric stricture was demonstrated. Transabdominal VVF repair with omental flap and left ureteric re-implantation was performed. The VVF recurred, which was successfully re-repaired transvaginally. Seventy-six full text articles were reviewed. There were no previously published cases of VVF following vaginal sex toy insertion. There are four cases of obstructive uropathy secondary to a vaginal FB in the literature: three pessaries and one plastic cap. There are 44 cases of VVF secondary to FB: 22 plastic caps (typically from aerosol bottles, inserted for masturbation or contraception) and 5 pessaries. At least nine were in girls aged ≤18 years. Average presentation is 15 months (range 2 months to 35 years) after FB insertion. Most cases were managed with surgical repair; predominantly transvaginal. CONCLUSIONS: This case describes an extremely rare but potentially life-threatening case of obstructive uropathy caused by a chronically retained sex toy, and adds to the list of potentially rare causes of a VVF and obstructive uropathy. We advocate urinary diversion, staged removal of FB, upper urinary tract imaging, and EUA with VVF repair and/or ureteric reimplantation if required. Transvaginal is the preferred access for FB-associated VVF repair without concomitant ureteric reimplantation.

Synthesis, processing and solid state excipient interactions of cucurbit[6]uril and its formulation into tablets for oral drug delivery.

The synthesis, processing, and solid state excipient interactions of cucurbit[6]uril (CB[6]) and its formulation into oral tablets has been examined using a range of physical chemistry techniques. Rapid precipitation from HCl by the addition of water yields microcrystalline CB[6] with smaller and more consistent particle size (30-165 µm) compared with the sieved CB[6] (50-540 µm) produced from large crystals grown by slow evaporation from HCl. The microcrystalline particles also contain fewer water molecules in the crystal compared with the sieved particles: 10 and 16% respectively. Microcrystalline CB[6] can be formulated into tablets suitable for oral delivery with a CB[6] content of 1-50% w/w, with the other excipients including lactose, talc, Avicel, magnesium stearate and Ac-Di-Sol. In the solid state microcrystalline CB[6] does not interact significantly with the talc, Ac-Di-Sol or Avicel, but significant interactions are observed when mixed or ground with either magnesium stearate or lactose, resulting in the lowering of the melting points of both excipients. This work represents the first study of the physical processing and solid state chemistry of CB[n]s for pharmaceutical formulation and represents an important development step in the use of CB[n]s as drug delivery vehicles.

The status of platinum anticancer drugs in the clinic and in clinical trials.

Since its approval in 1979 cisplatin has become an important component in chemotherapy regimes for the treatment of ovarian, testicular, lung and bladder cancers, as well as lymphomas, myelomas and melanoma. Unfortunately its continued use is greatly limited by severe dose limiting side effects and intrinsic or acquired drug resistance. Over the last 30 years, 23 other platinum-based drugs have entered clinical trials with only two (carboplatin and oxaliplatin) of these gaining international marketing approval, and another three (nedaplatin, lobaplatin and heptaplatin) gaining approval in individual nations. During this time there have been more failures than successes with the development of 14 drugs being halted during clinical trials. Currently there are four drugs in the various phases of clinical trial (satraplatin, picoplatin, Lipoplatin and ProLindac). No new small molecule platinum drug has entered clinical trials since 1999 which is representative of a shift in focus away from drug design and towards drug delivery in the last decade. In this perspective article we update the status of platinum anticancer drugs currently approved for use, those undergoing clinical trials and those discontinued during clinical trials, and discuss the results in the context of where we believe the field will develop over the next decade.

Population screening for lung cancer using computed tomography, is there evidence of clinical effectiveness? A systematic review of the literature.

Lung cancer is the leading cause of death among all cancer types in the UK, killing approximately 34 000 people per year. By the time symptoms develop, the tumour is often at an advanced stage and the prognosis is bleak. Treatment at a less advanced stage of disease by surgical resection has been shown to substantially reduce mortality. Screening would be attractive if it could detect presymptomatic lung cancer at a stage when surgical intervention is feasible but has been the subject of scientific debate for the past three decades. The aim of this review was to examine the current evidence on the clinical effectiveness of screening for lung cancer using computed tomography. A systematic literature review searching 15 electronic databases and Internet resources from 1994 until December 2004/January 2005 was carried out. Information was summarised narratively. A total of 12 studies of computed tomography screening for lung cancer were identified including two RCTs and 10 studies of screening without comparator groups. The two RCTs were of short duration (1 year). None examined the effect of screening on mortality compared with no screening. The proportion of people with abnormal computed tomography findings varied widely between studies (5-51%). The prevalence of lung cancer detected was between 0.4% and 3.2% (number needed to screen to detect one lung cancer = 31 to 249). Incidence rates of lung cancer were lower (0.1-1%). Among the detected tumours, a high proportion were stage I or resectable tumours, 100% in some studies. Currently, there is insufficient evidence that computed tomography screening is clinically effective in reducing mortality from lung cancer.