Systematic Review of the Management of Local Kidney Cancer Relapse.

CONTEXT: Management of locally recurrent renal cancer is complex. OBJECTIVE: In this systematic review we analyse the available literature on the management of local renal cancer recurrence. EVIDENCE ACQUISITION: A systematic search (PubMed, Web of Science, CINAHL, Clinical Trials, and Scopus) of English literature from 2000 to 2017 was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. EVIDENCE SYNTHESIS: The search identified 1838 articles. Of those, 36 were included in the evidence synthesis. The majority of the studies identified were retrospective and not controlled. Local recurrence after thermal ablation (TA) may be managed with repeat TA. Alternatively, salvage nephrectomy is possible. However, a higher rate of complications should be expected than after primary nephrectomy. Salvage nephrectomy and TA represent treatment options for local recurrence after partial nephrectomy. Local retroperitoneal recurrence after radical nephrectomy is ideally treated with surgical resection, for which minimally invasive approaches might be applicable to select patients. For large recurrences, addition of intraoperative radiation may improve local control. Local tumour destruction appears to be more beneficial than systemic therapy alone for local recurrences. CONCLUSIONS: Management of local renal cancer relapse varies according to the clinical course and prior treatments. The available data are mainly limited to noncontrolled retrospective series. After nephron-sparing treatment, TA represents an effective treatment with low morbidity. For local recurrence after radical nephrectomy, the low-level evidence available suggests superiority of surgical excision relative to systemic therapy or best supportive care. As a consequence, surgery should be prioritised when feasible and applicable. PATIENT SUMMARY: In renal cell cancer, the occurrence and management of local recurrence depend on the initial treatment. This cancer is a disease with a highly variable clinical course. After initial organ-sparing treatment, thermal ablation offers good cancer control and low rates of complications. For recurrence after radical nephrectomy, surgical excision seems to provide the best long-term cancer control and it is superior to medical therapy alone.

General scope of 1,4-diastereoselective additions to a 2(3H)-quinazolinone: practical preparation of HIV therapeutics.

The practical and highly diastereoselective syntheses of CF(3)-substituted dihydroquinazolinones via 1,4-additions of nucleophiles to chiral auxiliary substituted 2(3H)-quinazolinones is described. This methodology is applied to the syntheses of the NNRTIs (nonnucleoside reverse transcriptase inhibitors) DPC 961 (1) and DPC 083 (2), which are useful for the treatment of HIV (human immunodeficiency virus). The synthesis of DPC 961 (1) requires three steps, proceeds in >55% overall yield from the keto-aniline 9, and gives synthetic access to DPC 083 (2). In addition, the scope of the new diastereoselective 1,4-addition chemistry is investigated. The first preparation of DPC 961 (1) described in this paper is a derivatization fractional crystallization protocol.