Serum methylation levels of TAC1. SEPT9 and EYA4 as diagnostic markers for early colorectal cancers: a pilot study.

OBJECTIVE: To identify methylated genes in serum with diagnostic potentials for early colorectal cancer (CRC). METHODS: Serum methylation levels of up to 12 genes were measured in two sets of serum samples with the second set from 26 stage I CRC patients and 26 age/gender-matched controls. RESULTS: Serum methylation levels of TAC1, SEPT9, and EYA4 were significant discriminants between stage I CRC and healthy controls. Combination of TAC1 and SEPT9 rendered 73.1% sensitivity with 92.3% specificity. CONCLUSION: Serum methylation levels of TAC1. SEPT9 and EYA4 may be useful biomarkers for early detection of CRC though a validation study is necessary.

Stage IV colorectal cancers: an analysis of factors predicting outcome and survival in 728 cases.

INTRODUCTION: Stage IV colorectal cancer (CRC) is a heterogeneous disease with many treatment options. The optimum management algorithm is yet to be established. The aim of this study was to evaluate the prognostic factors of survival and to determine the operative benefit of resection of the primary tumour followed by chemotherapy. METHODS: Seven hundred twenty-eight consecutive patients who presented with stage IV CRC from 1999 to 2007 were identified. The demographics and clinicopathological characteristics of these patients were reviewed. Survival curves were constructed using the Kaplan-Meier method. Multivariate analysis assessed independent prognostic factors. RESULTS: In the surgical management of the primary, 79% (n = 572) were performed electively, 18% (n = 134) as an emergency procedure and 3% (n = 22) did not have any surgery. Twelve percent (n = 78) had a permanent stoma. Major morbidity was 4.3% (n = 31), and 30-day mortality was low at 6% (n = 46). Ten percent (n = 71) had a subsequent metasectomy. Patients who underwent curative resections tended to be female (p = 0.05), of a younger age group (age, ≤ 50; p = 0.005), as well as had better haemoglobin (p = 0.0001) and albumin levels (p = 0.0001). For the study cohort, the cancer-specific survival (CSS) at 1 year was 47.9% [95% confidence interval (CI), 44.2-51.6%], 3-year CSS was 10.8% (95% CI, 3.3-13.3%) and 5-year CSS was 7.0% (95% CI, 4.8-9.2%). CSS was significantly higher in patients that underwent colonic resection. In cases where resection of the primary was possible, multivariate analysis revealed that CEA value >40 ng/ml, low albumin levels ≤ 34 g/l, poorly differentiated tumours, advanced tumour stage (T3/T4), nodal disease (N1/N2) and presence of diffuse metastasis were all significant factors associated with poorer cancer-specific survival. CONCLUSION: This study has shown a good survival benefit in stage IV CRC when an aggressive policy of primary resection is adopted. Resection of metastases with curative intent should be performed whenever possible.

Endoscopic stenting and elective surgery versus emergency surgery for left-sided malignant colonic obstruction: a prospective randomized trial.

PURPOSE: This study aims to evaluate the role of colonic stenting as a bridge to surgery in acutely obstructed left-sided colon cancer. METHODS: Patients with acute left-sided malignant colonic obstruction with no evidence of peritonitis were recruited. After informed consent, patients were randomized to colonic stenting followed by elective surgery or immediate emergency surgery. Patients who had successful colonic stenting underwent elective surgery 1 to 2 weeks later, while the other group had emergency surgery. Patients in whom stenting was unsuccessful also underwent emergency surgery. RESULTS: Twenty patients were randomized to stenting and 19 to emergency surgery. Fourteen patients (70%) had successful stenting and underwent elective surgery at a median of 10 days later; the rest underwent emergency surgery. Technical stent failure occurred in five patients (25%). One patient failed to decompress after successful stent deployment. All patients underwent definitive colonic resection with primary anastomosis. Two of 20 patients in the stenting group required defunctioning stomas compared to 6 of 19 in emergency surgery group, p = 0.127. Overall complication rate was 35% versus 58% (p = 0.152) and mortality was 0% versus 16% (p = 0.106) in the stenting group and emergency surgery group, respectively. Postoperatively, the stenting group was discharged from hospital earlier (median of 6 versus 8 days, p = 0.028) than the emergency surgery group. CONCLUSION: Colonic stenting followed by interval elective surgery may be safer, with a trend towards lower morbidity and mortality when compared with the current practice of emergency surgery for left-sided malignant colonic obstruction.

Evaluation of laparoscopic versus open colorectal surgery in elderly patients more than 70 years old: an evaluation of 727 patients.

BACKGROUND: With longer life expectancy, surgeons can expect to operate on older patients. Laparoscopic colorectal (LC) surgery has been demonstrated to be superior to open surgery. Controversy persists, however, regarding benefits of LC in the elderly due to increase in operative time. The aim of our study was to compare short-term outcomes of LC versus open colorectal (OC) surgery in elderly patients. MATERIALS AND METHODS: Patients ≥70 years old that underwent elective LC between 2005 and 2008 were compared with controls who underwent OC. Data was extracted from a prospectively collected database. RESULTS: Seven hundred and twenty-seven patients underwent colorectal resection in this study period (LC n = 225, OC n = 502). The laparoscopic arm was characterised by shorter incisions (LC 6.0 cm vs. OC 12.0 cm, p < 0.001) but longer operating times (LC 125 min vs. OC 85 min, p < 0.001). Median use of narcotics and length of stay were significantly shorter in the laparoscopic group (LC 2 days vs. OC 3 days, p < 0.001 and LC 6 days vs. OC 7 days, p < 0.001, respectively). There was no significant difference in median recovery of bowel function (LC 4 days vs. OC 4 days, p = 0.14) and post-operative morbidity (p = 0.725). Thirty-day mortality was significantly lower in the laparoscopic arm (LC 1.3% vs. OC 4.6%, p = 0.03) CONCLUSION: This is the largest series from a single institution comparing LC and OC in elderly patients. In our series, LC in elderly patients was safe and not associated with a higher morbidity. LC was also associated with less narcotic use and shorter length of stay.

Results of 7302 stapled haemorrhoidectomy operations in a single centre: a seven-year review and follow-up questionnaire survey.

BACKGROUND: This study aims to evaluate the results of all 7302 stapled haemorrhoidectomy operations performed in a single centre. METHOD: A retrospective review of all 7302 patients who underwent stapled haemorrhoidectomy at our department over seven years was conducted. The hospital database was reviewed for subsequent readmissions and re-operations. A questionnaire survey was also sent out to all the patients. RESULTS: A total of 302 patients (4.1%) were admitted with post-operative bleeding and 281 stopped with conservative measures. Twenty one required surgical haemostasis. A total of 301 patients (4.1%) were admitted for an inability to void and 191 (2.6%) had true acute retention of urine, requiring catheterization. There were 124 patients (1.7%) admitted for pain, but all resolved with oral analgesia subsequently. Anal stricture requiring surgery occurred in only 86 patients (1.2%). Serious complications such as staple line dehiscence or anorectal sepsis occurred in seven patients. There were a total of 14 recurrences requiring readmission over this seven-year period, of which 12 were treated successfully with a second haemorrhoidectomy. A total of 1834 patients returned their questionnaire surveys and 95% of the patients reported complete resolution or improvement of their symptoms. Only 27 patients reported subsequent severe bleeding requiring medical attention. CONCLUSION: Stapled haemorrhoidectomy is safe, and most patients are satisfied with the long-term outcome.

Laparoscopic resection for colorectal polyps: a single institution experience.

BACKGROUND: Endoscopic polypectomy, although routinely used for the treatment of colorectal polyps, may be limited by polyp size, location and histology. Laparoscopic resection for malignant polyps and polyps not amenable to endoscopic removal has the advantage of adequate disease clearance as well as the short-term benefits of laparoscopic surgery. This study evaluates the outcomes of such an approach. METHODS: Patients who had laparoscopic resection for colorectal polyps between January 2005 and July 2008 were identified from a prospective database. Polyps that were malignant, large, difficult to snare or incompletely excised, were included. Demographics, perioperative details and histopathology were analysed. RESULTS: Seventy-eight patients (44 male) with a median age of 62.5 years (range 24-86) were studied. The majority (79%) were laparoscopic anterior resections for sigmoid or rectal polyps. Median operating time was 125 min (range, 65-225). Eight cases (10.3%) were converted to open mainly due to adhesions. There was no post-operative mortality. Perioperative complications occurred in seven patients (8.9%). Median hospital stay was 6 days (range 4-78). Median polyp size was 20 mm (range, 5-75). There were 44 benign polyps (55.7%); majority were tubulovillous adenomas (n= 22), and tubular adenomas (n= 10). Thirty-five patients (44.3%) had invasive cancer, with T1 (n= 27) and T2 (n= 2) tumours. Three of these patients (8.6%) had lymph node metastases. Median number of lymph nodes sampled was six (range 0-23). CONCLUSION: Laparoscopic resection is safe and effective for colorectal polyps not amenable to colonoscopic removal, and is especially important for adequate clearance in the case of malignant polyps.

Evaluation of current devices in single-incision laparoscopic colorectal surgery: a preliminary experience in 32 consecutive cases.

BACKGROUND: Single-incision laparoscopic colorectal surgery (SILS) suggests a promising alternative to conventional laparoscopic surgery. In this report we describe our initial experience with SILS for both right hemicolectomies and anterior resections. METHODS: Between June 2009 and May 2010, SILS was performed for 32 consecutive cases with benign and malignant pathology. Demographic data, intraoperative parameters, postoperative data, and pathologic data were assessed. RESULTS: Twenty-one SILS right hemicolectomies, ten ARs, and one abdominal perineal resection (APR) were performed. For SILS right hemicolectomies, one case required full "conversion" to a laparoscopic procedure. The median operating time was 85 min (range 45-150 min) and the median wound length was 5.0 cm (range 3.0-10.0 cm). Median number of lymph nodes extracted in malignant cases was 17(range 10-30) and the overall median length of stay was 6 days (range 5-11). For left-sided lesions, ten cases of ARs (7 high ARs, 2 low ARs, 1 ultralow AR) and one APR were performed. Three cases were completed successfully via the SILS procedure, four cases required one additional port, and four cases required full "conversion" to a laparoscopic procedure. The median operating time was 120 min (range 65-235 min) and the median wound length was 5.0 cm (range 3.0-7.0 cm). Overall median length of stay was also 6 days (range 5-21). There was one case of anastomotic leak and one case of postoperative bleeding. CONCLUSION: In our experience, SILS for right hemicolectomies is safe and effective with reproducible oncologic results. SILS AR, however, requires greater modifications in current devices and techniques. SILS AR can be performed for both malignant and benign diseases but additional ports may be necessary for the safe completion of the procedure.

Redefining conversion in laparoscopic colectomy and its influence on outcomes: analysis of 418 cases from a single institution.

BACKGROUND: The reported rates of conversion in laparoscopic colectomy are varied. The incidence of conversion is not, however, well defined. The aim of the present study is to redefine conversion and to analyze differences in outcome. METHODS: Treatment parameters of a total of 418 consecutive patients who underwent laparoscopic colonic resection from 2005 to 2007 were analyzed. Treatment was classified as laparoscopic colonic resection, laparoscopy-assisted colonic resection (lap-assisted), and laparoscopic conversion. RESULTS: There were significant differences in median operating time between laparoscopic colonic resection, lap-assisted, and laparoscopic conversion (125 min, 160 min, and 140 min; p = 0.0001); median hospital length of stay was significantly different (laparoscopic, 5.0 days, versus lap-assisted, 6.0 days, versus laparoscopic conversion, 6.5 days; p = 0.0001); and median incision length was also noted to vary significantly (laparoscopic, 5.0 cm, lap-assisted, 8.0 cm, and conversion, 12.0 cm; p = 0.00001). Multivariate analysis reveals that older age (Odds Ratio [OR] = 1.07, 95% Confidence Interval [CI] = 1.02-1.12), higher Body Mass Index ([BMI], OR = 1.15, 95% CI = 1.03-1.29), and pT stage were significant factors affecting conversion. Disease-free survival for cancers was not influenced by conversion (p = 0.653). The overall complication rate was 16.7% and was significantly increased in lap-assisted cases and in conversion cases (26% versus 13%; p = 0.003). CONCLUSIONS: A consistent definition for conversion in laparoscopic colonic resection is required. Our proposed definitions may provide a solution. The definition of lap-assisted as a separate entity serves as a bridge between laparoscopy and full conversion. Risk factors of age, BMI, and advanced tumor stage are conversion predictors and are associated with increased hospital stay and postoperative morbidity.

Single site laparoscopic right hemicolectomy: an oncological feasible option.

INTRODUCTION: We present the first 7 cases of single site right hemicolectomy in Asia using the new Single Site Laparoscopy (SSL) access system from Ethicon Endo-surgery. METHODS: Right hemicolectomy was performed using the new Single Site Laparoscopy (SSL) access system. Patient demographics, operative time, histology and post operative recovery and complications were collected and analysed. RESULTS: The median operative time was 90 mins (range 60 - 150 mins) and a median wound size of 2.5 cm (range 2 to 4.5 cm). The median number of lymph nodes harvested was 24 (range 20 to 34 lymph nodes). The median length of proximal margin was 70 mm (range 30 to 145 mm) and that of distal margin was 50 mm (35 to 120 mm). All patients had a median hospital stay of 7 days (range 5 to 11) and there were no significant perioperative complications except for 1 patient who had a minor myocardial event. CONCLUSION: Right hemicolectomy using SSL access system is feasible and safe for oncologic surgery.

Critical analysis of mucin and signet ring cell as prognostic factors in an Asian population of 2,764 sporadic colorectal cancers.

INTRODUCTION: Conflicting data on the clinicopathological characteristics as well as prognosis and survival of signet ring cell (SRC) and mucinous adenocarcinomas (MA) of the colorectum persist. METHODS: Consecutive patients (2,764) with sporadic colorectal cancer from 1999 to 2005 were evaluated. The clinicopathological characteristics of these patients were reviewed. Univariate analysis was performed, and survival curves were constructed using the Kaplan-Meier method. Multivariate analysis assessed independent prognostic factors. RESULTS: The incidence of MA and SRC is 6% and 1.1%, respectively. MA and SRC tend to occur in patients aged

Stapled anastomosis for anterior resection is safe even after previous stapled haemorrhoidectomy--a report of five cases.

INTRODUCTION: Stapled haemorrhoidectomy has become popular for the treatment of symptomatic bleeding or prolapsing piles. There are concerns about the safety of another stapled low colorectal anastomosis after rectal resection if a patient who has had previous stapled haemorrhoidectomy subsequently develops colorectal neoplasia requiring an anterior resection. METHODS: A retrospective review of patients who underwent stapled haemorrhoidectomy and subsequently had anterior resection from 1999 to 2008 was performed. RESULTS: Five patients (all male) were found to have distal sigmoid or rectal tumours on surveillance colonoscopy after stapled haemorrhoidectomy. Median age was 65 years (range 58-71). All underwent anterior resection with stapled end-to-end colorectal anastomosis at median of 29 months (range 18-60 months) after the initial stapled haemorrhoidectomy. Median anastomotic height was 12 cm (range 1-12 cm). A defunctioning ileostomy was created for three out of five patients. All the colorectal anastomoses healed uneventfully. CONCLUSIONS: Stapled colorectal anastomosis may be safely performed after previous stapled haemorrhoidectomy.

Prospective randomised study to evaluate the use of DERMABOND ProPen (2-octylcyanoacrylate) in the closure of abdominal wounds versus closure with skin staples in patients undergoing elective colectomy.

BACKGROUND: Topical 2-octylcyanoacrylate tissue (OCA) adhesive has been used as an alternative to close wounds with a comparable cosmetic outcome. The use of 2-OCA in the closure of abdominal laparotomy wounds has not been thoroughly evaluated. Our aim was to compare 2-OCA with conventional skin stapling devices in colorectal surgery. METHODS: A prospective randomised study was conducted in which 74 consecutive patients above the age of 21 undergoing open elective colectomies for benign or malignant indications were allocated to skin closure with 2-OCA or skin staples. Cosmetic outcome as assessed with the Hollander Cosmesis Scale with a single assessor, complication rates, and patient satisfaction were recorded at discharge (4-10POD) 2 weeks after discharge and then at 3 months. RESULTS: Of the 74 patients, 38 were randomised to skin staples and 36 to 2-OCA. There was no significant difference in cosmetic outcomes between the two groups as assessed with a visual analogue scale or the Hollander Cosmesis Scale but showed a trend to better cosmetic outcomes in the 2-OCA group. Patient satisfaction scores were higher but did not reach statistical significance. The time taken to close a wound with 2-OCA was significantly longer than with skin staples. There was no statistical difference in rates of wound infection. CONCLUSION: 2-OCA is a safe and effective means of skin closure in patients undergoing elective colectomies with a good and at least equivalent outcome to traditional methods of closure.

A 'metastasis-prone' signature for early-stage mismatch-repair proficient sporadic colorectal cancer patients and its implications for possible therapeutics.

Metastasis is the major cause of cancer mortality. We aimed to find a metastasis-prone signature for early stage mismatch-repair proficient sporadic colorectal cancer (CRC) patients for better prognosis and informed use of adjuvant chemotherapy. The genome-wide expression profiles of 82 age-, ethnicity- and tissue-matched patients and healthy controls were analyzed using the Affymetrix U133 Plus 2 array. Metastasis-negative patients have 5 years or more of follow-up. A 10 x 10 two-level nested cross-validation design was used with several families of classification models to identify the optimal predictor for metastasis. The best classification model yielded a 54 gene-set (74 probe sets) with an estimated prediction accuracy of 71%. The specificity, sensitivity, negative and positive predictive values of the signature are 0.88, 0.58, 0.84 and 0.65, respectively, indicating that the gene-set can improve prognosis for early stage sporadic CRC patients. These 54 genes, including node molecules YWHAB, MAP3K5, LMNA, APP, GNAQ, F3, NFATC2, and TGM2, integrate multiple bio-functions in various compartments into an intricate molecular network, suggesting that cell-wide perturbations are involved in metastasis transformation. Further, querying the ;Connectivity Map' with a subset (70%) of these genes shows that Gly-His-Lys and securinine could reverse the differential expressions of these genes significantly, suggesting that they have combinatorial therapeutic effect on the metastasis-prone patients. These two perturbagens promote wound-healing, extracellular matrix remodeling and macrophage activation thus highlighting the importance of these pathways in metastasis suppression for early-stage CRC.

Peutz-Jeghers syndrome: data from the Singapore Polyposis Registry and a shifting paradigm in management.

INTRODUCTION: Peutz-Jeghers Syndrome (PJS) is an uncommon autosomal dominant hamartomatous polyposis syndrome. Morbidity arises from polyp-related complications and increased risks of malignancy. We report on PJS patients registered in the Singapore Polyposis Registry, identified principal causes of morbidity and appraised current management strategies. A followup protocol based on recent literature has been proposed. MATERIALS AND METHODS: A search of a prospectively collected database in the Singapore Polyposis Registry was made. Only patients who fulfilled the diagnostic criteria of PJS were included. The clinical records were retrieved for review. Information on affected family members was obtained from the Registry's pedigree records. RESULTS: Seven unrelated patients fulfilled the criteria of having PJS. Principal causes of morbidity include recurrent bouts of abdominal colic, episodes of intestinal obstruction, gastrointestinal bleeding and the need for repeated laparotomies. Six out of 7 patients had initial presentation with acute intestinal obstruction requiring emergency laparotomy. Management was mostly problem-oriented and marked inter-surgeon variation with regard to cancer screening and genetic counselling was observed. CONCLUSION: Patients with PJS suffer gastrointestinal complications from polyposis and are at increased risks for developing cancers. A move towards surveillance and planned comprehensive care may reduce the morbidity of the condition. A protocol driven approach conducted in the setting of a Polyposis Registry is ideally suited to facilitate such care.

Metabolic profiling in colorectal cancer reveals signature metabolic shifts during tumorigenesis.

Colorectal cancer (CRC) arises as the consequence of progressive changes from normal epithelial cells through polyp to tumor, and thus is an useful model for studying metabolic shift. In the present study, we studied the metabolomic profiles using high analyte specific gas chromatography/mass spectrometry (GC/MS) and liquid chromatography tandem mass spectrometry (LC/MS/MS) to attain a systems-level view of the shift in metabolism in cells progressing along the path to CRC. Colonic tissues including tumor, polyps and adjacent matched normal mucosa from 26 patients with sporadic CRC from freshly isolated resections were used for this study. The metabolic profiles were obtained using GC/MS and LC/MS/MS. Our data suggest there was a distinct profile change of a wide range of metabolites from mucosa to tumor tissues. Various amino acids and lipids in the polyps and tumors were elevated, suggesting higher energy needs for increased cellular proliferation. In contrast, significant depletion of glucose and inositol in polyps revealed that glycolysis may be critical in early tumorigenesis. In addition, the accumulation of hypoxanthine and xanthine, and the decrease of uric acid concentration, suggest that the purine biosynthesis pathway could have been substituted by the salvage pathway in CRC. Further, there was a step-wise reduction of deoxycholic acid concentration from mucosa to tumors. It appears that to gain a growth advantage, cancer cells may adopt alternate metabolic pathways in tumorigenesis and this flexibility allows them to adapt and thrive in harsh environment.