Circumferential resection margin positivity due to direct or indirect tumour involvement in rectal cancer - a call for better stratification.

BACKGROUND: A positive circumferential resection margin (CRM) after rectal cancer surgery, which can be the result of direct or indirect tumour involvement, has consistently been associated with increased local recurrence and poorer survival. However, little is known of the differential impact of the mode of tumour involvement on outcomes. METHODS: 1460 consecutive patients undergoing rectal cancer resection between 2003 and 2018 were retrospectively assessed. Histopathology reports for patients with a positive CRM were reviewed to determine cases of direct (R1-tumour) or indirect tumour involvement (R1-other). Disease-free survival (DFS) and overall survival (OS) were assessed by Kaplan-Meier analysis. The role of the mode of CRM positivity was examined by univariate and multivariate Cox proportional hazards models. RESULTS: Eighty-five patients had an R1 resection due to CRM involvement (5.8%). Of those, 69 were due to direct tumour involvement, while 16 were from indirect causes. Kaplan-Meier analysis revealed that R1-other was associated with increased OS (hazard ratio 0.40, log-rank P = 0.006) and DFS (P = 0.043). Multivariate regression confirmed that the mode of CRM positivity was an independent predictor of OS. More interestingly, the patterns of recurrence were different between the two groups, with R1-tumour leading to significantly more local recurrence (P = 0.04). CONCLUSIONS: Our data strongly suggests that direct tumour involvement of the CRM confers worse prognosis after rectal cancer surgery. Importantly, differences in the site and frequency of recurrences make a case for better stratification of patients with a positive CRM to guide treatment decisions.

Single Port Laparoscopic Surgery for Complex Crohn's Disease Is Safe with a Lower Conversion Rate.

PURPOSE: Single port laparoscopic surgery (SPLS) is a technique which is increasing in popularity. The benefit of SPLS in complex Crohn's disease (CD), which includes a significant cohort of young patients sometimes needing multiple operations, has not been comprehensively assessed. This study analyses our early experience with this technique. METHODS: Patients who underwent SPLS for CD were included. Data were collected prospectively from January 2013 to December 2015. Ileocolic resections, right hemicolectomy, small bowel stricturoplasties, and resections were included in the complex CD cohort. Primary and redo operations were analyzed separately. RESULTS: Forty-five patients were included in the study (39 ileocolic resections and 6 small bowel stricturoplasty/resections). Of the total, 27 were primary resections and 18 were redo resections. The median age was 41 years (range 14-72 years), and the median hospital stay was 8 days (range 3-28 days). The total complication rate was 35.5% most of which were Clavien-Dindo type 1 and 2. There was no difference in operating time, average blood loss, conversion rates, complication rate, and hospital stay, between those who had primary or redo surgery. CONCLUSIONS: SPLS can be performed safely in patients with complex CD even in redo surgery. There may be some technical advantages to the procedure in this group of patients.

Extended pelvic side wall excision for locally advanced rectal cancers.

Extended pelvic side wall excision is a useful technique for treatment of recurrent or advanced rectal cancer involving sciatic notch and does not compromise the dissection of major pelvic vessels and vascular control.

Does the outcome of colonic flexure cancers differ from the other colonic sites?

BACKGROUND: Anecdotally, colonic flexure cancers (FC) appear to have a poorer prognosis compared to other colonic cancers (OCC). The aim of this study was to determine the outcome of colonic flexure cancers compared to the cancers of the rest of the colon. METHODS: Patients with a diagnosis of colonic cancer over a 5-year period (2002-2006) were retrieved from a prospective database. Analysis was performed on flexure (hepatic/splenic) cancers versus remaining colon cancers. Overall, 1-, 3- and 5-year survival rates were calculated. All patients were followed up until death or end of study period (December 2008), with median follow-up of 32 months. Statistical analysis was performed using Kaplan-Meier with log rank statistic and Pearson chi-square test. RESULTS: Of 613 patients (54% males) with colonic cancers with median age 71 years, range (30-100), 67 (10.9%) were FC (35 hepatic/32 splenic) and 546 (89.1%) were arising from OCC. The curative resection rates were FC 73.2% (41 of 56) and OCC 83.4% (359 of 435) (p = 0.05). Post-operative mortality for FC and OCC was 10.7% (6 of 56) and 4.2% (18 of 434), respectively (p = 0.04). FC presented at a more advanced Dukes stage (p = 0.003). Recurrence rates were 9.8% (4 of 41) for FC and 20.9% (75 of 359) for OCC sites (p = 0.088). The overall mean survival was 48.8 and 58.2 m for FC and OCC, respectively (p = 0.158). Of 1-, 3- and 5-year survival, only 1-year survival was significantly different between the two groups (OCC (85%) vs FC (75%), p = 0.018). CONCLUSIONS: Nearly one in ten colonic cancers is located at a flexure. Despite FC presenting at an advanced stage, leading to a lower curative resection rate, no significant survival difference was noted compared to other colonic sites, beyond the first year.

Enhancing cytotoxic therapies for breast and prostate cancers with polyunsaturated fatty acids.

The role of omega-3 and omega-6 fatty acids has been extensively studied in most of the human malignancies including breast, colon, prostate, pancreas, and stomach cancers. In particular, the role of omega-3 and omega-6 fatty acids in carcinogenesis has been extensively investigated in epidemiological, laboratory cell culture studies and studies in vivo in animal. Findings from these studies suggest that omega-3 and omega-6 fatty acids are cytotoxic in different cancers and act synergistically with cytotoxic drugs. Although experimental evidence for the potential beneficial role of polyunsaturated fatty acids (PUFAs) in enhancing the effectiveness of various chemotherapeutic agents in animal models and in cell culture studies is increasing, there are only a few reports that have shown supportive evidence for linking these natural compounds with augmentation of anticancer chemotherapeutics in human trials. This review presents evidence for a commonality in the proposed molecular mechanisms of action elicited by various PUFAs believed to be responsible for their enhancement of the effectiveness of anticancer chemotherapy, specifically in breast and prostate cancers, and reviews laboratory and animal studies and few reported human clinical trials. It concludes that sufficient evidence is available to suggest that major clinical trials with these natural compounds as adjuncts to standard therapies should be undertaken as a priority.

Topical negative pressure in managing severe peritonitis: a positive contribution?

AIM: To assess the use of topical negative pressure (TNP) in the management of severe peritonitis. METHODS: This is a four-year prospective analysis from January 2005 to December 2008 of 20 patients requiring TNP following laparotomy for severe peritonitis. RESULTS: There were 11 males with an average age of (59.3 +/- 3.95) years. Nine had a perforated viscus, five had anastomotic leaks, three had iatrogenic bowel injury, and a further three had severe pelvic inflammatory disease. TNP and the VAC(R) Abdominal Dressing System were initially used. These were changed every two to three days. Abdominal closure was achieved in 15/20 patients within 4.53 +/- 1.64 d. One patient required relaparotomy due to residual sepsis. Two patients with severe faecal peritonitis due to perforated diverticular disease received primary anastomosis at second look laparotomy, as sepsis and their general condition improved. In the remaining 5/20 cases, the abdomen was left open due to bowel oedema and or abdominal wall oedema. Dressing was switched to TNP and VAC GranuFoam. Three of the five patients returned a few months later for abdominal wall reconstruction and restoration of intestinal continuity. Two patients developed intestinal fistulae. All 20 patients survived. CONCLUSION: The use of TNP is safe. Further studies are needed to assess its value in managing these difficult cases.

An unusual presentation of sclerosing mesenteritis as pneumoperitoneum: case report with a review of the literature.

Sclerosing mesenteritis is a rare condition that involves the small or large bowel mesentery. An unusual presentation of this condition, which led to difficult preoperative assessment and diagnosis, is described. This report is followed by a comprehensive review of the literature.

Gallstone ileus: surgical strategies and clinical outcome.

OBJECTIVE: Gallstone ileus is a rare cause of intestinal obstruction affecting mainly the elderly. This study aimed to analyze the surgical treatments and outcome of the disease. METHODS: We present a retrospective study of 13 patients diagnosed with gallstone ileus from January 2000 to December 2005 in our hospital and a review of the published literature. RESULTS: Three men and 10 women participated in the study, with a mean age of 74.3 (range: 63-85). The mean duration of symptoms was 6 days (range 2-14). A pre operative diagnosis was made in 10 patients. The mean delay in diagnosis was 3.5 days (range 1-10). Ten patients had an enterolithotomy (E) and three patients had a one-stage procedure comprising enterolithotomy, cholecystectomy and fistula repair (EC). There was no postoperative mortality in either group. The mean postoperative hospital stay for group E was 14 (range 6-31) days and for group EC was 19 (range: 5-28) days. Twelve patients were alive at the time of review. One patient from group E died of unrelated causes after three years. One patient in group E developed cholangitis but no surgical intervention was required on case note review over a mean postoperative period of 3.4 years. CONCLUSION: E alone is best suited in all elderly gallstone ileus patients with significant comorbidities. A one-stage procedure (EC) should be reserved for young, fit and low risk patients.

Docosahexaenoic acid enhances the efficacy of docetaxel in prostate cancer cells by modulation of apoptosis: the role of genes associated with the NF-kappaB pathway.

BACKGROUND: Evidence is growing for beneficial interactions between omega-3 fatty acids from fish and chemotherapy agents in certain human cancers. Evidence for similar effects in prostate cancer is lacking. We investigated the effects of docosahexaenoic acid (DHA-22:6n-3), a component of fish oil, on the cytotoxicity of docetaxel in prostate cancer cells. METHODS: Cell viability was studied using the MTT assay and apoptosis was evaluated by flow cytometry using PI, annexin V, and JC-1 staining. Cellular signaling mechanisms that might explain the observed pro-apoptotic effects were investigated using NF-kappaB pathway specific cDNA microarrays and RT-PCR validation. RESULTS: DHA enhanced the pro-apoptotic efficacy of docetaxel, synergistically, in hormone receptor positive and negative LNCaP, DU145 and PC3 cells, respectively. Cell cycle analysis showed an increase in G2M arrest and JC-1 staining showed a significant (P < 0.018) increase in apoptotic cells with combination treatments in LNCaP cells. Microarray and RTPCR showed decreased expression of FADD, AKT1, MAX, TRAF3, MAP2k4, TNFRSF11A, and RIPK1 in LNCaP cells. Similar results were obtained with DU145 cells; combinations were more effective than single treatments. Combination treatments suppressed NF-kappaB signaling that was induced by docetaxel alone; this is considered an anti-apoptotic response. CONCLUSION: DHA synergistically enhanced the cytotoxic effect of docetaxel in prostate cancer cells through increased apoptosis by suppression of genes involved in the NF-kappaB pathway. This highlights the possibility of developing such combination modalities for treatment of prostate cancer.