BackgroundArtesunate is an antimalarial agent with broad anti-cancer activity in in vitro and animal experiments and case reports. Artesunate has not been studied in rigorous clinical trials for anticancer effects.AimTo determine the anticancer effect and tolerability of oral artesunate in colorectal cancer (CRC).MethodsThis was a single centre, randomised, double-blind, placebo-controlled trial. Patients planned for curative resection of biopsy confirmed single primary site CRC were randomised (n = 23) by computer-generated code supplied in opaque envelopes to receive preoperatively either 14 daily doses of oral artesunate (200 mg; n = 12) or placebo (n = 11). The primary outcome measure was the proportion of tumour cells undergoing apoptosis (significant if > 7% showed Tunel staining). Secondary immunohistochemical outcomes assessed these tumour markers: VEGF, EGFR, c-MYC, CD31, Ki67 and p53, and clinical responses.Findings20 patients (artesunate = 9, placebo = 11) completed the trial per protocol. Randomization groups were comparable clinically and for tumour characteristics. Apoptosis in > 7% of cells was seen in 67% and 55% of patients in artesunate and placebo groups, respectively. Using Bayesian analysis, the probabilities of an artesunate treatment effect reducing Ki67 and increasing CD31 expression were 0.89 and 0.79, respectively. During a median follow up of 42 months 1 patient in the artesunate and 6 patients in the placebo group developed recurrent CRC.InterpretationArtesunate has anti-proliferative properties in CRC and is generally well tolerated.

The frequency of CRC in young patients increased significantly. Vascular invasion is the single most important prognostic factor in young CRC. Along with vascular invasion, high proportion of T4 status in young patients increases the chances of recurrence and negates any survival advantage in young patients.

Background:Colorectal cancer (CRC) progression is associated with suppression of host cell-mediated immunity and local immune escape mechanisms. Our aim was to assess the immune function in terms of expression of TNF, IFNG and FOXP3 in CRC.Methods:Sixty patients with CRC and 15 matched controls were recruited. TaqMan quantitative PCR and methylation-specific PCR was performed for expression and DNA methylation analysis of TNF, IFNG and FOXP3. Survival analysis was performed over a median follow-up of 48 months.Results:TNF was suppressed in tumour and IFNG was suppressed in peripheral blood mononuclear cells (PBMCs) of patients with CRC. Tumours showed enhanced expression of FOXP3 and was significantly higher when tumour size was >38 mm (median tumour size; P=0.006, Mann–Whitney U-test). Peripheral blood mononuclear cell IFNG was suppressed in recurrent CRC (P=0.01). Methylated TNFpromoter (P=0.003) and TNFexon1 (P=0.001) were associated with significant suppression of TNF in tumours. Methylated FOXP3cpg was associated with significant suppression of FOXP3 in both PBMC (P=0.018) and tumours (P=0.010). Reduced PBMC FOXP3 expression was associated with significantly worse overall survival (HR=8.319, P=0.019).Conclusions:We have detected changes in the expression of immunomodulatory genes that could act as biomarkers for prognosis and future immunotherapeutic strategies.

Our experience shows that epidural analgesia is safe and effective in providing adequate pain relief following open liver surgery.

Although ectopic pancreas and intussusception are not unusual conditions, intussusception caused by ectopic pancreas is extremely rare. Its presence along with a ruptured congenital mesenteric vascular band raises the possibility of an anomaly of the vitelline vascular system. We report the case of a 26-year-old man presenting with acute abdominal pain, vomiting, and diarrhea. CT scan showed a large amount of free fluid in his abdomen and an ileo-ileal intussusception. At laparotomy he was found to have hemoperitoneum with a ruptured, actively bleeding congenital band attached to the ileal mesentery, which was ligated, with ileo-ileal intussusception that was resected. Histopathology showed ectopic pancreatic tissue as the lead point for the intussusception. It was likely to be a ruptured mesodiverticular band and along with other findings suggested a constellation of anomalies of the vitello-intestinal tract.

Metastatic tumours account for <1% of all breast malignancies, most originating in the contralateral breast. An 88-year-old woman presented with bilateral breast lumps 4 years after radical nephrectomy for a T2N0M0 renal cancer. Mammography showed a circumscribed 15 mm mass just below and medial to the left nipple without any micro-calcification. Ultrasound scan showed the presence of a solid vascular mass in the left breast; a guided core biopsy confirmed it as a metastatic renal cell carcinoma. Left simple mastectomy and excision of right breast lump was done. Histology of both lesions confirmed them as metastatic deposits. Bilateral breast metastasis from a renal cancer is very rare and this is the second reported case. This case illustrates the potential for rare sites of metastases and for the consideration of metastasis in the presence of previous renal cancer. Recognition as metastatic neoplasm is important to prevent unnecessary radical procedures.

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Introduction Colorectal cancer (CRC) progression is associated with suppression of host cell mediated immunity (CMI) and local immune escape mechanisms. A systemic suppression of CMI-associated cytokines, Tumour Necrosis Factor (TNF) and Interferon-γ (IFN-γ) has been demonstrated in patients with CRC. 1 FOXP3, a crucial regulatory protein for the development and function of regulatory T-cells could be an important cause of local immune escape mechanism in tumors. 2 The aim of the study was to assess immune function in terms of the expression of TNF, IFN-γ and FOXP3 and to identify potential targets for immunotherapy in CRC. Methods A total of 60 colorectal cancer (CRC) patients and 15 matched controls were recruited. Total RNA was isolated from the peripheral blood mononuclear cells (PBMC, separated from a venous blood sample), fresh frozen tumour tissue and normal mucosa. TaqMan quantitative PCR (qRT-PCR) was used to determine the relative fold change in the expression of TNF, IFNG, FOXP3 in the PBMC (compared to controls) and tumour (compared to normal mucosa), with GAPDH as internal control. Results TNF expression was suppressed in the tumour tissue (median fold change 0.48) compared to normal mucosa. IFN-γ was found to be suppressed in the PBMC (median 0.34) compared to healthy controls. There was a signifi cantly reduced expression of TNF (p = 0.048) and IFNG (p = 0.011) in Stage 4 CRC. There was a signifi cant suppression of IFNG in the recurrent CRC (p = 0.007), left CRC sided CRC (p = 0.027) and after neoadjuvant therapy (p = 0.021). The tumour tissue showed a higher expression of FOXP3 gene compared to normal mucosa (median 2.2). The expression of FOXP3 in tumour was significantly higher when the size of the tumour was more than 50 mm (p = 0.005). Late stage CRC (Stages 3 and 4) showed a signifi cantly high expression of FOXP3 compared to early stages of CRC (Stages 1 and 2) (p = 0.035). Conclusion The expression of TNF is suppressed and FOXP3 is enhanced in colorectal tumours and becomes more significant with tumour progression. Suppression of IFN-γ appears to be systemic and is signifi cantly suppressed in left sided CRC and recurrent CRC. Our study has identifi ed potential targets which may increase the chances of response to immunotherapy based on cytokines and T regulatory cell manipulation. Competing interests None.