The majority of cryptoglandular fistula-in-ano were treated by primary fistulotomy or staged fistulotomy with a loose seton. This was associated with a low recurrence rate and low rates of faecal incontinence. There was a low reliance on imaging techniques in this group. However, we would urge caution when dealing with fistula-in-ano related to Crohn's disease. In this group of patients, the fistulae tended to be more complex and require additional imaging and multiple procedures.

Abstract. Death-associated protein 1 (DAP1) is a member of the DAP family and has been implicated in the regulation of cell growth and death including that of cancer cells. However, the roles of DAP1 in clinical cancer and in the regulation of colorectal cancer cells are largely unknown. The present study investigated the expression profile of DAP1 in human colorectal cancer and the impact of DAP1 on apoptosis and the cellular response to 5-FU. Human colorectal cancer specimens (n=94) and human colorectal cancer cell lines HRT18 and HT115 were used. DAP1 transcript and protein were evaluated using quantitative transcript analysis and immunohistochemistry. DAP1-knockdown cells were generated using anti-DAP1 transgene. The results revealed that human colorectal cancer tissues had lower levels of DAP1 when compared with the normal tissues. The reduced levels were associated with higher Dukes' stage and lymph node metastasis. Patients with low DAP1 expression had a markedly reduced survival. Loss of DAP1 in colorectal cancer cells resulted in a gain in cellular migration and loss of their sensitivity of apoptosis to chemotherapeutic agent, 5-FU. DAP1 was found to be correlated with disease progression and long-term survival of the colorectal patients. DAP1 is also a pivotal regulator of the growth and apoptosis and cellular response to chemotherapy agents. IntroductionDAP1 is one of the members of the death-associated protein (DAP) family, first isolated as a gene involved in IFN-γ-induced apoptosis through a technical knockout strategy (TKO), i.e. random inactivation of genes with antisense cDNA libraries (1). The DAP family is comprised of DAP1, DAP2 (DAP kinase), DAP3, DAP4 and DAP5. DAP2 was found to be involved in apoptosis induced by IFN-γ, TNF-α and Fas (2-3). Serine/threonine kinase catalytic activity and the death domain contribute to the pro-apoptotic function. Based on the loss of DAP2 expression in certain types of cancers, it has been proposed as a candidate tumour-suppressor gene. While the clinical significance of other members of the DAP Family that also exhibit death-promoting functions remain largely unknown, there have been recent reports on the possible association between the DAP family and the clinical outcome of patients with malignant diseases, for example breast cancer (4).Induction of apoptosis is an important mechanism of chemotherapeutic agents in the treatment of cancer. Among the DAP family members, DAP3 was found to be a mitochondrial protein that has a specific amino acid sequence to recognise and anchor to mitochondria. Mitochondria play a key role in apoptosis including release of pro-apoptotic substances such as cytochrome c and AIF, production of reactive oxygen species (ROS) and reduction in ATP synthesis (5-8). All of these findings indicate that DAP may be involved in both the intrinsic and extrinsic apoptosis pathways. In addition, it was reported that DAP2 methylation is associated with a reduced response to chemotherapy and poor prognosis in gastric cancer (9).In the present...

The consensus process has provided guidance for the management of patients with PRC-bTME or RRC, taking into account global variations in surgical techniques and technology. It has further identified areas of research priority.

The local recurrence rates achieved with APR were not significantly different from those achieved with restorative operations. Tumours at the ano-rectal junction should not be dissected off the pelvic floor, but radically excised en bloc with the surrounding levator ani, as a cylinder, as originally described by Miles.

Between 5% and 10% of patients with rectal cancer present with locally advanced rectal cancer (LARC), and 10% of rectal cancers recur after surgery, of which half are limited to locoregional disease only (locally recurrent rectal cancer). Exenterative surgery offers the best long-term outcomes for patients with LARC and locally recurrent rectal cancer so long as a complete (R0) resection is achieved. Accurate preoperative multimodal staging is crucial in assessing the potential operability of advanced rectal tumors, and resectability may be enhanced with neoadjuvant therapies. Unfortunately, surgical options are limited when the tumor involves the lateral pelvic sidewall or high sacrum due to the technical challenges of achieving histological clearance, and must be balanced against the high morbidity associated with resection of the bony pelvis and significant lymphovascular structures. This group of patients is usually treated palliatively and subsequently survival is poor, which has led surgeons to seek innovative new solutions, as well as revisit previously discarded radical approaches. A small number of centers are pioneering new techniques for resection of beyond-total mesorectal excision tumors, including en bloc resections of the sciatic notch and composite resections of the first two sacral vertebrae. Despite limited experience, these new techniques offer the potential for radical treatment of previously inoperable tumors. This narrative review sets out the challenges facing the management of LARCs and discusses evolving management options.