Synthesis, in silico and in vitro anti-cancer studies of phosphorylated derivatives of didanosine targeting MDA-MB-231 breast cancer cell lines.

A series of new phosphorylated derivatives of didanosine were designed, synthesized and evaluated their anticancer effects on human breast cancer cells. Their binding affinities were evaluated against aromatase enzyme and the molecular docking studies demonstrated that 9a, 9h and 9i exhibited high binding interactions than the parent molecule (ddI) and other derivatives; evaluated the aromatase enzyme inhibition. The cell viability, cell proliferation, lactate dehydrogenase showed potential anti-proliferative in dose dependent manner, these results were well correlated with hoesch stain and DNA fragmentation on MDA-MB-231 breast cancer cell lines. Cytotoxicity results disclosed that tryptophan amino acid ester substituted derivative 9i showed potential cell death against MDA-MB-231 cancer cell lines. Furthermore, compound 9i has great potential significance for further investigations (in vivo).

Perceived changes in symptoms and quality-of-life amongst patients with dizziness: A single-centre experience in Malaysia.

INTRODUCTION: Dizziness is a common complaint by patients, yet it always presents as a diagnostic challenge to the attending clinician. An accurate diagnosis is essential to correctly administer the precise treatment regime, alleviate the symptoms, and improve the quality-of-life of patients who present with dizziness. A specialised vestibular clinic with a holistic approach of meticulous history-taking, complete physical examination, a collection of audiovestibular test battery, and facilities for vestibular rehabilitation was set up to assist in the management of these patients. This study aims to investigate the effect of vestibular clinic intervention on the symptoms and qualityof- life of patients who were managed in the vestibular clinic. MATERIALS AND METHODS: A total of 64 new patients who were managed in the vestibular clinic were selected and the validated Malay - Vestibular Rehabilitation Benefit Questionnaire (My-VRBQ) was completed during the first and follow-up visits to measure the changes in symptoms and quality-of-life before and after receiving care at the vestibular clinic. RESULTS: Our study showed that there was a positive effect of vestibular clinic intervention on the symptoms and quality-of-life of patients who were managed by the vestibular clinic. Statistically significant improvements were seen in the total My-VRBQ scores, symptoms scores, and quality-of-life scores. The subscale scores of dizziness, anxiety, and motion-provoked dizziness also showed statistically significant improvement among the patients who received care at the vestibular clinic. CONCLUSION: This indicates that the vestibular clinic was an essential part of the work-up, diagnosis, and treatment of patients with dizziness; and a specialised vestibular clinic was able to bring about positive outcomes in the symptoms and quality-of-life of patients with balance disorders.

Ex vivo specimen MRI and pathology confirm a rectosigmoid mesenteric waist at the junction of the mesorectum and mesocolon.

AIM: Continuity of the mesentery has recently been established and may provide an anatomical basis for optimal colorectal resectional surgery. Preliminary data from operative specimen measurements suggest there is a tapering in the mesentery of the distal sigmoid. A mesenteric waist in this area may be a risk factor for local recurrence of colorectal cancer. This study aimed to investigate the anatomical characteristics of the mesentery at the colorectal junction. METHOD: In this cross-sectional study, 20 patients were recruited. After planned colorectal resection, the surgical specimens were scanned in a MRI system and subsequently dissected and photographed as per national pathology guidelines. Mesenteric surface area and linear measurements were compared between MRI and pathology to establish the presence and location of a mesenteric waist. RESULTS: Specimen analysis confirmed that a narrowing in the mesenteric surface area was consistently apparent at the rectosigmoid junction. Above the anterior peritoneal reflection, the surface area and posterior distance of the mesentery of the upper rectum initially decreased before increasing as the mesentery of the sigmoid colon. These anatomical properties created the appearance of a mesenteric 'waist' at the rectosigmoid junction. Using the anterior reflection as a reference landmark, the rectosigmoid waist occurred at a mean height of 23.6 and 21.7 mm on MRI and pathology, respectively. CONCLUSION: A rectosigmoid waist occurs at the junction of the mesorectum and mesocolon, and is a mesenteric landmark for the rectum that is present on both radiology and pathology.

A systematic review and meta-analysis comparing adverse events and functional outcomes of different pouch designs after restorative proctocolectomy.

AIM: There is no consensus as to which ileoanal pouch design provides better outcomes after restorative proctocolectomy. This study compares different pouch designs. METHOD: A systematic review of the literature was performed. A random effects meta-analytical model was used to compare adverse events and functional outcome. RESULTS: Thirty comparative studies comparing J, W, S and K pouch designs were included. No significant differences were identified between the different pouch designs with regard to anastomotic dehiscence, anastomotic stricture, pelvic sepsis, wound infection, pouch fistula, pouch ischaemia, perioperative haemorrhage, small bowel obstruction, pouchitis and sexual dysfunction. The W and K designs resulted in fewer cases of pouch failure compared with the J and S designs. J pouch construction resulted in a smaller maximum pouch volume compared with W and K pouches. Stool frequency per 24 h and during daytime was higher following a J pouch than W, S or K constructions. The J design resulted in increased faecal urgency and seepage during daytime compared with the K design. The use of protective pads during daytime and night-time was greater with a J pouch compared to S or K. The use of antidiarrhoeal medication was greater after a J reservoir than a W reservoir. Difficulty in pouch evacuation requiring intubation was higher with an S pouch than with W or J pouches. CONCLUSION: Despite its ease of construction and comparable complication rates, the J pouch is associated with higher pouch failure rates and worse function. Patient characteristics, technical factors and surgical expertise should be considered when choosing pouch design.

The effect of adjuvant chemotherapy on survival and recurrence after curative rectal cancer surgery in patients who are histologically node negative after neoadjuvant chemoradiotherapy.

AIM: The aim of this study was to evaluate whether adjuvant chemotherapy will affect recurrence rate or disease-free and overall survival in patients with rectal adenocarcinoma who were staged with MRI node-positive disease (mrN+) preoperatively. These patients underwent neoadjuvant chemoradiotherapy with curative rectal cancer surgery and their pathological staging was negative for nodal disease (ypN0). There is no consensus on the role of adjuvant chemotherapy in such patients. METHOD: Patients who received neoadjuvant chemoradiotherapy and underwent curative rectal cancer surgery for rectal adenocarcinoma staged as [mrTxN+M0] on MRI staging and who on pathological staging were found to be [ypTxN0M0] were retrospectively identified from January 2008 December 2012 from two tertiary referral centres (Royal Marsden Hospital, London and Saint-Andre Hospital, Bordeaux). RESULTS: One hundred and sixty-three patients were recruited and, after propensity matching at a ratio of 2:1, n = 80 patients were divided to receive adjuvant (n = 28) or no adjuvant treatment (n = 52). A comparison of adjuvant chemotherapy vs no adjuvant therapy showed that the mean overall survival was 2.67 vs 3.60 years (P = 0.42) and disease-free survival was 2.27 vs 3.32 years (P = 0.14). CONCLUSION: This study found no significant difference in survival or disease recurrence between patients who received adjuvant chemotherapy and patients who did not. There is no clear evidence to support or dismiss the use of adjuvant chemotherapy for patients who were node positive on preoperative MRI and node negative on histopathological staging. Further multicentre prospective randomized trials are needed to identify the appropriate treatment regime for this group of patients.

The selection process can improve the outcome in locally advanced and recurrent colorectal cancer: activity and results of a dedicated multidisciplinary colorectal cancer centre.

AIM: There is wide disparity in the care of patients with multivisceral involvement of rectal cancer. The results are presented of treatment of advanced and recurrent colorectal cancer from a centre where a dedicated multidisciplinary team (MDT) is central to the management. METHOD: All consecutive MDT referrals between 2010 and 2014 were examined. Analysis was undertaken of the referral pathway, site, selection process, management decision, R0 resection rate, mortality/morbidity/Clavien-Dindo (CD) classification of morbidity, length of stay (LOS) and improvement of quality of life. RESULTS: There were 954 referrals. These included locally advanced primary rectal cancer (LAPRC b-TME) (39.0%), rectal recurrence (RR) (22.0%), locally advanced primary colon cancer (LAPCC T3c/d-T4) (21.1%), colon cancer recurrence (CR) (12.4%), locally advanced primary anal cancer (LAPAC-failure of CRT/T3c/d-T4) (3.0%) and anal cancer recurrence (AR) (2.2%). Among these patients 271 operations were performed, 212 primary and 59 for recurrence. These included 16 sacrectomies, 134 total pelvic exenterations and 121 other multi-visceral exenterative procedures. An R0 resection (no microscopic margin involvement) was achieved in 94.4% and R1 (microscopic margin involvement) in 5.1%. In LAPRC b-TME the R0 rate was 96.1% and for RR it was 79%. The LOS varied from 13.3 to 19.9 days. RR operations had the highest morbidity (CD 1-2, 33.3%) and LAPRC operations had the highest rate of CD 3-4 complications (18.4%). Most (39.6%) of the referred patients were from other UK hospitals. CONCLUSION: Advanced colorectal cancer can be successfully treated in a dedicated referral centre, achieving R0 resection in over 90% with low morbidity and mortality. Implementation of a standardized referral pathway is encouraged.

Adjuvant chemotherapy may improve disease-free survival in patients with rectal cancer positive for MRI-detected extramural venous invasion following chemoradiation.

AIM: MRI-detected extramural venous invasion (mrEMVI) is a poor prognostic factor in rectal cancer. Preoperative chemoradiotherapy (CRT) can cause regression in the severity of EMVI and subsequently improve survival whereas mrEMVI persisting after CRT confers an increased risk of recurrence. The effect of adjuvant chemotherapy (AC) following CRT on survival in rectal cancer remains unclear. The aim of this study was to determine whether there is a survival advantage for AC given to patients with mrEMVI persisting after CRT. METHOD: A prospective analysis was conducted of consecutive patients with locally advanced rectal cancer between 2006 and 2013. All patients underwent CRT followed by surgery. AC was given to selected patients based on the presence of specific 'high-risk' features. Comparison was made between patients offered AC with observation alone. The primary outcome was 3-year disease-free survival (DFS). RESULTS: Of 631 patients, 227 (36.0%) demonstrated persistent mrEMVI following CRT. Patients were grouped on the basis of AC or observation and were matched for age, performance status and final histopathological staging. Three-year DFS in the AC group was 74.6% compared with 53.7% in the observation only group. AC had a survival benefit on multivariate analysis (hazard ratio 0.458; 95% CI: 0.271-0.775, P = 0.004). CONCLUSION: Patients with persistent mrEMVI following CRT who receive AC may have a decreased risk of recurrence and an improved 3-year DFS compared with patients not receiving AC, irrespective of age and performance status.

A systematic review of transabdominal levator division during abdominoperineal excision of the rectum (APER).

BACKGROUND: The aim of the present study was to evaluate the surgical technique, short-term oncological and perioperative outcomes for the transabdominal division of the levator ani muscles during abdominoperineal excision of the rectum (APER). METHODS: A systematic review was performed to identify studies reporting on transabdominal division of the levator ani during APER. A comprehensive literature search was performed using a combination of free-text terms and controlled vocabulary when applicable on the following databases: MEDLINE, EMBASE, Science Citation Index Expanded and Cochrane Central Register of Controlled Trials in the Cochrane Library. The search period was from January 1945 to December 2015. The following search headings were used: "transabdominal", "transpelvic", "abdominal" or "pelvic" combined with either "levator" or "extralevator" and with "abdominoperineal". RESULTS: Nine publications were identified reporting on 99 participants. The male/female distribution was 1.44:1, respectively, and the mean age was 56.6 (30-77) years. All tumours were less than 5 cm from the anal verge. The preoperative radiological staging was T2 in 18% of cases, T3 in 53.5% and T4 in 28.5%. Transabdominal division of the levators was performed laparoscopically in 55 cases, robotically in 34 and open in 10. The mean operating time was 255 (177-640) min. Mean intraoperative blood loss was 140 (92-500) ml. There were no conversions to open. Circumferential resection margins were positive in two cases, and there was one intraoperative perforation. Mean post-operative length of stay was 9.3 (3-67) days. Follow-up (from 0 to 31 months) revealed 19 perineal wound infections, 15 cases of sexual dysfunction and 7 cases of urinary retention. There was no mortality and 1 readmission. CONCLUSIONS: Transabdominal division of the levators during APER is feasible and reproducible, with acceptable perioperative and good early oncological outcomes. Further comparative studies are needed.

A novel interaction between the FLJ33534 locus and smoking in obesity: a genome-wide study of 14 131 Pakistani adults.

BACKGROUND: Obesity is a complex disease caused by the interplay of genetic and lifestyle factors, but identification of gene-lifestyle interactions in obesity has remained challenging. Few large-scale studies have reported use of genome-wide approaches to investigate gene-lifestyle interactions in obesity. METHODS: In the Pakistan Risk of Myocardial Infraction Study, a cross-sectional study based in Pakistan, we calculated body mass index (BMI) variance estimates (square of the residual of inverse-normal transformed BMI z-score) in 14 131 participants and conducted genome-wide heterogeneity of variance analyses (GWHVA) for this outcome. All analyses were adjusted for age, age(2), sex and genetic ancestry. RESULTS: The GWHVA analyses identified an intronic variant, rs140133294, in the FLJ33544 gene in association with BMI variance (P-value=3.1 × 10(-8)). In explicit tests of gene × lifestyle interaction, smoking was found to significantly modify the effect of rs140133294 on BMI (Pinteraction=0.0005), whereby the minor allele (T) was associated with lower BMI in current smokers, while positively associated with BMI in never smokers. Analyses of ENCODE data at the FLJ33534 locus revealed features indicative of open chromatin and high confidence DNA-binding motifs for several transcription factors, providing suggestive biological support for a mechanism of interaction. CONCLUSIONS: In summary, we have identified a novel interaction between smoking and variation at the FLJ33534 locus in relation to BMI in people from Pakistan.

Adoption and success rates of perineal procedures for fistula-in-ano: a systematic review.

AIM: Several sphincter-preserving techniques have been described with extremely encouraging initial reports. However, more recent studies have failed to confirm the positive early results. We evaluate the adoption and success rates of advancement flap procedures (AFP), fibrin glue sealant (FGS), anal collagen plug (ACP) and ligation of intersphincteric fistula tract (LIFT) procedures based on their evolution in time for the management of anal fistula. METHOD: A PubMed search from 1992 to 2015. An assessment of adoption, duration of study and success rate was undertaken. RESULTS: We found 133 studies (5604 patients): AFP (40 studies, 2333 patients), FGS (31 studies, 871 patients), LIFT (19 studies, 759 patients), ACP (43 studies, 1641 patients). Success rates ranged from 0% to 100%. Study duration was significantly associated with success rates in AFP (P = 0.01) and FGS (P = 0.02) but not in LIFT or ACP. The duration of use of individual procedures since first publication was associated with success rate only in AFP (P = 0.027). There were no statistically significant differences in success rates relative to the number of the patients included in each study. CONCLUSION: Success and adoption rates tend to decrease with time. Differences in patient selection, duration of follow-up, length of availability of the individual procedure and heterogeneity of treatment protocols contribute to the diverse results in the literature. Differences in success rates over time were evident, suggesting that both international trials and global best practice consensus are desirable. Further prospective randomized controlled trials with homogeneity and clear objective parameters would be needed to substantiate these findings.

A systematic review of transanal total mesorectal excision: is this the future of rectal cancer surgery?

AIM: The surgical technique used for transanal total mesorectal excision (TaTME) was reviewed including the oncological quality of resection and the peri-operative outcome. METHOD: A literature search of MEDLINE, Embase, Science Citation Index Expanded and Cochrane was performed in order to identify studies reporting on TaTME. RESULTS: Thirty-six studies (eight case reports, 24 case series and four comparative studies) were identified, reporting 510 patients who underwent TaTME. The mean age ranged from 43 to 80 years and the mean body mass index from 21.7 to 31.8 kg/m(2) . The mean distance of the tumour from the anal verge ranged from 4 to 9.7 cm. The mean operation time ranged from 143 to 450 min and mean operative blood loss from 22 to 225 ml. The ratio of hand-sewn coloanal to stapled anastomoses performed was 2:1. One death was reported and the peri-operative morbidity rate was 35%. The anastomotic leakage rate was 6.1% and the reoperation rate was 3.7%. The mean hospital stay ranged from 4.3 to 16.6 days. The mesorectal excision was described as complete in 88% cases, nearly complete in 6% and incomplete in 6%. The circumferential resection margin was negative in 95% of cases and the distal resection margin was negative in 99.7%. CONCLUSION: TaTME is a feasible and reproducible technique, with good quality of oncological resection. Standardization of the technique is required with formal training. Clear indications for this procedure need to be defined and its safety further assessed in future trials.

Distribution, species composition and relative abundances of sandflies in North Waziristan Agency, Pakistan.

This study was conducted to investigate the diversity of sandflies (Psychodidae: Phlebotominae) and the incidence of leishmaniasis in three villages of North Waziristan Agency, Pakistan. Sandflies were sampled monthly during 2012, at dusk and dawn, in selected indoor habitats including both bedrooms and animal sheds using a knock-down spray catch method. A total of 3687 sandflies were collected, including 1444 individuals in Drezanda, 1193 in Damdil and 1050 in Dattakhel. This study revealed 14 species of two genera, Phlebotomus (Phlebotomus sergenti, Phlebotomus papatasi, Phlebotomus caucasicus, Phlebotomus kazeruni, Phlebotomus alexandri and Phlebotomus salehi) and Sergentomyia (Sergentomyia dentate, Sergentomyia baghdadis, Sergentomyia babu, Sergentomyia theodori, Sergentomyia sumbarica, Sergentomyia dreyfussitur kestanica, Sergentomyia hogsoni pawlowskyi and Sergentomyia fallax afghanica) (both: Diptera: Psychodidae). Phlebotomus sergenti was the most abundant species (42.1%), followed by S. dentata (17.7%) and S. baghdadis (17.4%). The number of males collected represented about twice that of female flies, and the maximum number was collected in July, followed by August. The determination of the species composition of sandfly populations, seasonal variations, relative abundances and estimations of infection in the vector population may provide information about the dynamics of leishmaniasis transmission that is useful in planning vector control activities.

Synovial haemangioma of the knee joint: an unusual cause of knee pain in a 14-month old girl.

We report a histologically proven case of synovial haemangioma of the knee in a 14-month old girl who presented to the emergency department with an acute 1-day history of refusing to weight-bear on the right leg and a preceding 3-week history of a right knee lump. Physical examination revealed a non-tender, soft lump over the lateral infrapatellar region. Radiographs revealed a poorly defined soft tissue density over the infrapatellar fat pad and a suprapatellar joint effusion. Ultrasound was used to confirm the presence of a vascular soft tissue mass compatible with a synovial haemangioma within the infrapatellar fat pad which showed both intra-articular and extra-articular extension. There was good correlation of the ultrasound findings with magnetic resonance imaging (MRI), highlighting the potential clinical utility of ultrasound as an alternative imaging modality in establishing the pre-operative diagnosis and extent of a synovial haemangioma about the knee joint.

Compression versus hand-sewn and stapled anastomosis in colorectal surgery: a systematic review and meta-analysis of randomized controlled trials.

Anastomotic leaks are a feared complication of colorectal resections and novel techniques that have the potential to decrease them are still sought. This study aimed to compare the anastomotic leak rates in patients undergoing compression anastomoses versus hand-sewn or stapled anastomoses. Randomized controlled trials (RCTs) comparing outcomes of compression versus conventional (hand-sewn and stapled) colorectal anastomosis were collected from MEDLINE, Embase and the Cochrane Library. The quality of the RCTs and the potential risk of bias were assessed. Pooled odds ratios (OR) were calculated for categorical outcomes and weighted mean differences for continuous data. Ten RCTs were included, comprising 1969 patients (752 sutured, 225 stapled, and 992 compression anastomoses). Most used the biofragmentable anastomotic ring. There was no significant difference between the two groups in terms of anastomotic leak rates (OR 0.80, 95 % confidence interval (CI) 0.47, 1.37; p = 0.42), stricture (OR 0.54: 95 % CI 0.18, 1.64; p = 0.28) or mortality (OR 0.70; 95 % CI 0.39, 1.26; p = 0.24). Compression anastomosis was associated with an earlier return of bowel function: 1.02 (95 % CI 1.37, 0.66) days earlier (p < 0.001) and a shorter postoperative stay; 1.13 (95 % CI 1.52, 0.74) days shorter (p < 0.001), but significant heterogeneity among studies was observed. There was an increased risk of postoperative bowel obstruction in the compression group (OR 1.87; 95 % CI 1.07, 3.26; p = 0.03). There was no significant difference in wound-related and general complications, or length of surgery. Compression devices do not appear to provide an advantage over conventional techniques in fashioning colorectal anastomoses and are associated with an increased risk of bowel obstruction.

Systematic review and network meta-analysis comparing clinical outcomes and effectiveness of surgical treatments for haemorrhoids.

BACKGROUND: The aim was to compare the clinical outcomes and effectiveness of surgical treatments for haemorrhoids. METHODS: Randomized clinical trials were identified by means of a systematic review. A Bayesian network meta-analysis was performed using the Markov chain Monte Carlo method in WinBUGS. RESULTS: Ninety-eight trials were included with 7827 participants and 11 surgical treatments for grade III and IV haemorrhoids. Open, closed and radiofrequency haemorrhoidectomies resulted in significantly more postoperative complications than transanal haemorrhoidal dearterialization (THD), LigaSure™ and Harmonic® haemorrhoidectomies. THD had significantly less postoperative bleeding than open and stapled procedures, and resulted in significantly fewer emergency reoperations than open, closed, stapled and LigaSure™ haemorrhoidectomies. Open and closed haemorrhoidectomies resulted in more pain on postoperative day 1 than stapled, THD, LigaSure™ and Harmonic® procedures. After stapled, LigaSure™ and Harmonic® haemorrhoidectomies patients resumed normal daily activities earlier than after open and closed procedures. THD provided the earliest time to first bowel movement. The stapled and THD groups had significantly higher haemorrhoid recurrence rates than the open, closed and LigaSure™ groups. Recurrence of haemorrhoidal symptoms was more common after stapled haemorrhoidectomy than after open and LigaSure™ operations. No significant difference was identified between treatments for anal stenosis, incontinence and perianal skin tags. CONCLUSION: Open and closed haemorrhoidectomies resulted in more postoperative complications and slower recovery, but fewer haemorrhoid recurrences. THD and stapled haemorrhoidectomies were associated with decreased postoperative pain and faster recovery, but higher recurrence rates. The advantages and disadvantages of each surgical treatment should be discussed with the patient before surgery to allow an informed decision to be made.

Palladium-catalyzed arylation of 2H-chromene: a new entry to pyrano[2,3-c]carbazoles.

Pyrano[2,3-c]carbazoles which are biologically valuable and synthetically challenging frameworks are synthesized in high yields over five steps from commercially available resorcinol. Palladium-catalyzed arylation remains a key step in this novel strategy. The versatility of this protocol has been demonstrated by the synthesis of naturally occurring alkaloid clauraila C and 7-methoxyglycomaurin. The anti-proliferative activity of these designed compounds (5a, 5f, and 5l) has been evaluated in a cancer cell line (MOLT-4). The molecular docking study revealed that this pyrano[2,3-c]carbazole class of molecules selectively occupies the colchicine binding site of the tubulin-polymer.

A systematic review of sacral nerve stimulation for low anterior resection syndrome.

AIM: The efficacy of sacral nerve stimulation (SNS) in low anterior resection syndrome (LARS) is largely undocumented. A review of the literature was carried out to study this question. METHOD: Pubmed, Medline and Cochrane databases were searched for relevant articles up to August 2014. Studies were included if they evaluated the use of SNS following rectal resection and assessed at least one of the following end-points: bowel function, quality of life and ano-neorectal physiology. No restrictions on language or study size were made. RESULTS: Seven papers were identified including one case report and six prospective case series. These included 43 patients with a median follow-up of 15 months. After peripheral nerve evaluation definitive implantation was carried out in 34 (79.1%) patients. Overall, 32 (94.1%) of the 34 patients experienced improvement of symptoms which, based on intention to treat, was 32/43 (74.4%). CONCLUSION: The review suggests that SNS for faecal incontinence in LARS has success rates comparable to its use for other forms of faecal incontinence.

Complete mesocolic excision in colorectal cancer: a systematic review.

AIM: Several studies have suggested an increased lymph node yield, reduced locoregional recurrence and increased disease-free survival after complete mesocolic excision (CME) for colorectal cancer. This review was undertaken to assess the use of CME for colon cancer by evaluating the technique and its clinical outcome. METHOD: A literature search of publications was performed using PubMed and Medline. Only studies published in English were included. Studies assessed for quality and data were extracted by two independent reviewers. End-points included number of lymph nodes per patient, quality of the plane of mesocolic excision, postoperative mortality and morbidity, 5-year locoregional recurrence and 5-year cancer-specific survival. RESULTS: There were 34 articles comprising 12 retrospective studies, nine prospective studies and 13 original articles including case series, observational studies and editorials. Of the prospective studies, four reported an increased lymph node harvest and a survival benefit. The others reported an improvement in the quality of the specimen as assessed by histopathological examination. Laparoscopic CME has the same oncological outcome as open surgery but completeness of excision during laparoscopy may be compromised for tumours in the transverse colon. CONCLUSION: Studies demonstrate that CME removes significantly more tissue around the tumour including maximal lymph node clearance. There is little information on serious adverse events after CME and a long-term survival benefit has not been proved.

Learning curve for the management of recurrent and locally advanced primary rectal cancer: a single team's experience.

AIM: The study aimed to define the learning curve required to gain satisfactory training to perform pelvic exenterative surgery for recurrent or locally advanced primary rectal cancer. METHOD: Consecutive patients undergoing exenterative pelvic surgery for recurrent and locally advanced primary rectal cancer, by one surgical team, between 2006 and 2011 were studied. They were divided into quartiles (Q1-Q4) according to the date of surgery. A risk-adjusted cumulative sum (RA-CUSUM) model was used to evaluate the learning curve. The chi-squared test with gamma ordinal was used to assess the change with time in the four quartiles. RESULTS: One hundred patients (70 males; median age 61 (25-85) years; 55 primary cancers) were included in the study. Thirty patients underwent abdominosacral resection. The number of patients who underwent plastic reconstruction (n = 53) increased from 12 in Q1 to 15 in Q4 (P = 0.781). The median operation time, intra-operative blood loss and hospital stay were 8 (3-17) h, 1.5 (0.1-17) l and 15 (9-82) days respectively. There was no significant change with time. Complete resection (R0) was achieved in 78 patients. Microscopic (R1) or macroscopic (R2) residual disease was present in 15 and seven patients respectively. The number of major complications was 20, and minor 30. RA-CUSUM analysis demonstrated an improvement in any complications after 14, in major after 12 and in minor after 25 operations. CONCLUSION: Pelvic exenterative surgery for recurrent or locally advanced primary rectal cancer is complex and requires a minimum of 14 cases for an expert colorectal surgeon to gain the desirable training and experience to improve morbidity.

Hand-sewn coloanal anastomosis for low rectal cancer: technique and long-term outcome.

AIM: This study compared the operative outcome and long-term survival of three types of hand-sewn coloanal anastomosis (CAA) for low rectal cancer. METHOD: Patients presenting with low rectal cancer at a single centre between 2006 and 2014 were classified into three types of hand-sewn CAA: type 1 (supra-anal tumours undergoing transabdominal division of the rectum with transanal mucosectomy); type 2 (juxta-anal tumours, undergoing partial intersphincteric resection); and type 3 (intra-anal tumours, undergoing near-total intersphincteric resection with transanal mesorectal excision). RESULTS: Seventy-one patients with low rectal cancer underwent CAA: 17 type 1; 39 type 2; and 15 type 3. The median age of patients was 61.6 years, with a male/female ratio of 2:1. Neoadjuvant therapy was given to 56 (79%) patients. R0 resection was achieved in 69 (97.2%) patients. Adverse events occurred in 25 (35.2%) of the 71 patients with a higher complication rate in type 1 vs type 2 vs type 3 (47.1% vs 38.5% vs 13.3%, respectively; P = 0.035). Anastomotic separation was identified in six (8.5%) patients and pelvic haematoma/seroma in five (7%); two (8.3%) female patients developed a recto-vaginal fistula. Ten (14.1%) patients were indefinitely diverted, with a trend towards higher long-term anastomotic failure in type 1 vs type 2 vs type 3 (17.6% vs 15.5% vs 6.7%). The type of anastomosis did not influence the overall or disease-free survival. CONCLUSION: CAA is a safe technique in which anorectal continuity can be preserved either as a primary restorative option in elective cases of low rectal cancer or as a salvage procedure following a failed stapled anastomosis with a less successful outcome in the latter. CAA has acceptable morbidity with good long-term survival in carefully selected patients.