Circular RNA as a source of neoantigens for cancer vaccines.

BACKGROUND: The effectiveness of somatic neoantigen-based immunotherapy is often hindered by the limited number of mutations in tumors with low to moderate mutation burden. Focusing on microsatellite-stable colorectal cancer (CRC), this study investigates the potential of tumor-associated circular RNAs (circRNAs) as an alternative source of neoepitopes in CRC. METHODS: Tumor-associated circRNAs in CRC were identified using the MiOncoCirc database and ribo-depletion RNA sequencing of paired clinical normal and tumor samples. Candidate circRNA expression was validated by quantitative real-time PCR (RT-qPCR) using divergent primers. TransCirc database was used for translation prediction. Human leukocyte antigen binding affinity of open reading frames from potentially translatable circRNA was predicted using pVACtools. Strong binders from messenger RNA-encoded proteins were excluded using BlastP. The immunogenicity of the candidate antigens was functionally validated through stimulation of naïve CD8+ T cells against the predicted neoepitopes and subsequent analysis of the T cells through enzyme-linked immunospot (ELISpot) assay, intracellular cytokine staining (ICS) and granzyme B (GZMB) reporter. The cytotoxicity of T cells trained with antigen peptides was further tested using patient-derived organoids. RESULTS: We identified a neoepitope from circRAPGEF5 that is upregulated in CRC tumor samples from MiOncoCirc database, and two neoepitopes from circMYH9, which is upregulated across various tumor samples from our matched clinical samples. The translation potential of candidate peptides was supported by Clinical Proteomic Tumor Analysis Consortium database using PepQuery. The candidate peptides elicited antigen-specific T cells response and expansion, evidenced by various assays including ELISpot, ICS and GZMB reporter. Furthermore, T cells trained with circMYH9 peptides were able to specifically target and eliminate tumor-derived organoids but not match normal organoids. This observation underscores the potential of circRNAs as a source of immunogenic neoantigens. Lastly, circMYH9 was enriched in the liquid biopsies of patients with CRC, thus enabling a detection-to-vaccination treatment strategy for patients with CRC. CONCLUSIONS: Our findings underscore the feasibility of tumor-associated circRNAs as an alternative source of neoantigens for cancer vaccines targeting tumors with moderate mutation levels.

A functional personalised oncology approach against metastatic colorectal cancer in matched patient derived organoids.

Globally, colorectal cancer (CRC) is the third most frequently occurring cancer. Progression on to an advanced metastatic malignancy (metCRC) is often indicative of poor prognosis, as the 5-year survival rates of patients decline rapidly. Despite the availability of many systemic therapies for the management of metCRC, the long-term efficacies of these regimens are often hindered by the emergence of treatment resistance due to intratumoral and intertumoral heterogeneity. Furthermore, not all systemic therapies have associated biomarkers that can accurately predict patient responses. Hence, a functional personalised oncology (FPO) approach can enable the identification of patient-specific combinatorial vulnerabilities and synergistic combinations as effective treatment strategies. To this end, we established a panel of CRC patient-derived organoids (PDOs) as clinically relevant biological systems, of which three pairs of matched metCRC PDOs were derived from the primary sites (ptCRC) and metastatic lesions (mCRC). Histological and genomic characterisation of these PDOs demonstrated the preservation of histopathological and genetic features found in the parental tumours. Subsequent application of the phenotypic-analytical drug combination interrogation platform, Quadratic Phenotypic Optimisation Platform, in these pairs of PDOs identified patient-specific drug sensitivity profiles to epigenetic-based combination therapies. Most notably, matched PDOs from one patient exhibited differential sensitivity patterns to the rationally designed drug combinations despite being genetically similar. These findings collectively highlight the limitations of current genomic-driven precision medicine in guiding treatment strategies for metCRC patients. Instead, it suggests that epigenomic profiling and application of FPO could complement the identification of novel combinatorial vulnerabilities to target synchronous ptCRC and mCRC.

Preoperative Quality of Life and Mental Health Can Predict Postoperative Outcomes and Quality of Life after Colorectal Cancer Surgery.

Background and Objectives: It remains unclear which domains of preoperative health-related quality of life (HRQOL) and mental health are predictive of postoperative clinical and patient-reported outcomes in colorectal cancer (CRC) patients. Materials and Methods: A prospective cohort of 78 CRC patients undergoing elective curative surgery was recruited. The EORTC QLQ-C30 and HADS questionnaires were administered preoperatively and one month after surgery. Results: Preoperative cognitive functioning scores (95% CI 0.131-1.158, p = 0.015) and low anterior resection (95% CI 14.861-63.260, p = 0.002) independently predicted poorer 1-month postoperative global QOL. When postoperative complications were represented using the comprehensive complication index (CCI), poorer preoperative physical function scores were associated with higher CCI scores (B = -0.277, p = 0.014). Preoperative social function score (OR = 0.925, 95% CI 0.87 to 0.99; p = 0.019) was an independent predictor for 30-day readmission, while physical functioning score (OR = -0.620, 95% CI -1.073--0.167, p = 0.008) was inversely related to the length of hospitalization. The overall regressions for 1-month postoperative global QOL (R2: 0.546, F: 1.961, p = 0.023) and 30-day readmission (R2: 0.322, χ2: 13.129, p < 0.001) were statistically significant. Conclusions: Various QLQ-C30 domains were found to be predictive of postoperative outcomes, including complications, readmission, and length of hospitalization. Preoperative cognitive dysfunction and low AR were independent predictors of poorer postoperative global QOL. Future research should seek to examine the efficacy of targeting specific baseline QOL domains in improving clinical as well as patient-reported outcomes after CRC surgery.

Domain-specific p53 mutants activate EGFR by distinct mechanisms exposing tissue-independent therapeutic vulnerabilities.

Mis-sense mutations affecting TP53 promote carcinogenesis both by inactivating tumor suppression, and by conferring pro-carcinogenic activities. We report here that p53 DNA-binding domain (DBD) and transactivation domain (TAD) mis-sense mutants unexpectedly activate pro-carcinogenic epidermal growth factor receptor (EGFR) signaling via distinct, previously unrecognized molecular mechanisms. DBD- and TAD-specific TP53 mutants exhibited different cellular localization and induced distinct gene expression profiles. In multiple tissues, EGFR is stabilized by TAD and DBD mutants in the cytosolic and nuclear compartments respectively. TAD mutants promote EGFR-mediated signaling by enhancing EGFR interaction with AKT via DDX31 in the cytosol. Conversely, DBD mutants maintain EGFR activity in the nucleus, by blocking EGFR interaction with the phosphatase SHP1, triggering c-Myc and Cyclin D1 upregulation. Our findings suggest that p53 mutants carrying gain-of-function, mis-sense mutations affecting two different domains form new protein complexes that promote carcinogenesis by enhancing EGFR signaling via distinctive mechanisms, exposing clinically relevant therapeutic vulnerabilities.

Pan-cancer pervasive upregulation of 3' UTR splicing drives tumourigenesis.

Most mammalian genes generate messenger RNAs with variable untranslated regions (UTRs) that are important post-transcriptional regulators. In cancer, shortening at 3' UTR ends via alternative polyadenylation can activate oncogenes. However, internal 3' UTR splicing remains poorly understood as splicing studies have traditionally focused on protein-coding alterations. Here we systematically map the pan-cancer landscape of 3' UTR splicing and present this in SpUR ( http://www.cbrc.kaust.edu.sa/spur/home/ ). 3' UTR splicing is widespread, upregulated in cancers, correlated with poor prognosis and more prevalent in oncogenes. We show that antisense oligonucleotide-mediated inhibition of 3' UTR splicing efficiently reduces oncogene expression and impedes tumour progression. Notably, CTNNB1 3' UTR splicing is the most consistently dysregulated event across cancers. We validate its upregulation in hepatocellular carcinoma and colon adenocarcinoma, and show that the spliced 3' UTR variant is the predominant contributor to its oncogenic functions. Overall, our study highlights the importance of 3' UTR splicing in cancer and may launch new avenues for RNA-based anti-cancer therapeutics.

MiR-138 is a potent regulator of the heterogenous MYC transcript population in cancers.

3'UTR shortening in cancer has been shown to activate oncogenes, partly through the loss of microRNA-mediated repression. This suggests that many reported microRNA-oncogene target interactions may not be present in cancer cells. One of the most well-studied oncogenes is the transcription factor MYC, which is overexpressed in more than half of all cancers. MYC overexpression is not always accompanied by underlying genetic aberrations. In this study, we demonstrate that the MYC 3'UTR is shortened in colorectal cancer (CRC). Using unbiased computational and experimental approaches, we identify and validate microRNAs that target the MYC coding region. In particular, we show that miR-138 inhibits MYC expression and suppresses tumor growth of CRC and hepatocellular carcinoma (HCC) cell lines. Critically, the intravenous administration of miR-138 significantly impedes MYC-driven tumor growth in vivo. Taken together, our results highlight the previously uncharacterized shortening of the MYC 3'UTR in cancer, and identify miR-138 as a potent regulator of the heterogenous MYC transcript population.

Early surgery after bridge-to-surgery stenting for malignant bowel obstruction is associated with better oncological outcomes.

BACKGROUND: Placement of self-expanding metal stents has been increasingly adopted as a bridge to surgery in patients presenting with obstructed left-sided colorectal cancers. The optimal bridging time has yet to be widely established, hence this retrospective study aims to determine the optimal bridging time to elective surgery post endoluminal stenting. PATIENTS AND METHODS: All patients who underwent colorectal stenting for large bowel obstruction in a single, tertiary hospital in Singapore between January 2003 and December 2017 were retrospectively identified. Patients' baseline demographics, tumour characteristics, stent-related complications, intra-operative details, post-operative complications and oncological outcomes were analysed. RESULTS: Of the 53 patients who successfully underwent colonic stenting for malignant left sided obstruction, 33.96% of patients underwent surgery within two weeks of stent placement while 66.04% of patients underwent surgery after 2 weeks of stent placement. Univariate analysis between both groups did not demonstrate significant differences in postoperative complications and stoma formation. Significant differences were observed between both groups for stent complications (38.89% vs 8.57%, p = 0.022), on-table decompression (38.89% vs 2.86%, p = 0.001) and systemic recurrence (11.11% vs 40.00%, p = 0.030). Increased bridging interval to surgery (OR 13.16, CI 1.37-126.96, p = 0.026) was a significant risk factor for systemic recurrence on multivariate analysis. CONCLUSIONS: Patients undergoing definitive surgery within 2 weeks of colonic stenting may have better oncological outcomes without compromising on postoperative outcomes. Further prospective studies are required to compare outcomes between emergency surgery and different bridging intervals.

Kono-S anastomosis for Crohn's disease: a systemic review, meta-analysis, and meta-regression.

The Kono-S anastomosis was introduced in 2011 as an alternative anastomosis in Crohn's disease (CD) surgery. Since then, prevailing evidence of the favorable results of the Kono-S anastomosis has been published from around the world. We conducted this study to analyze the effectiveness of the Kono-S anastomosis, by searching Medline, Embase, CNKI, and google scholar. Binominal data were analyzed after Freeman-Tukey double-arcsine transformation. Comparative data were analyzed using the Mantel-Haenszel model for dichotomous outcomes and the mean difference for continuous outcomes. We identified 676 patients who underwent surgery with a Kono-S anastomosis. Surgical recurrence was pooled at an average of 0% (CI: 0.00-0.01) and a reduced mean Rutgeerts score of 1.375 (CI: 0.727-2.023) after Kono-S anastomosis. Endoscopic recurrence after sensitivity analysis was 5% (CI: 0.00-0.15). Complications were rare, with a 3% incidence of ileus (CI: 0.01-0.05), a 4% incidence of small bowel obstruction (CI: 0.01-0.10), a 1% incidence of an anastomotic leak incidence (CI: 0.00-0.03), and a 10% incidence of postoperative infection (CI: 0.03-0.20). Evidence from this meta-analysis favors the Kono-S anastomosis for CD patients, especially for ileocolic anastomosis. Thus, clinicians should consider the applicability of Kono-S anastomosis in respective institutions.

PIPAC-OX: A Phase I Study of Oxaliplatin-Based Pressurized Intraperitoneal Aerosol Chemotherapy in Patients with Peritoneal Metastases.

PURPOSE: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel laparoscopic, intraperitoneal chemotherapy delivery technique aiming to improve drug distribution and tissue penetration to treat peritoneal metastases. Thus far, PIPAC oxaliplatin is conducted at an arbitrary dose of 92 mg/m2. We conducted a phase I study to establish safety and tolerability. PATIENTS AND METHODS: We used a 3+3 dose-escalation design of PIPAC oxaliplatin for patients with peritoneal metastases from gastrointestinal tumors, after failure of at least first-line chemotherapy. Dose levels were planned at 45, 60, 90, and 120 mg/m2. RESULTS: This study included 16 patients with 24 PIPAC procedures (8 gastric; 5 colorectal; and 1 gallbladder, pancreas, and appendix cancer each). Median age and peritoneal cancer index (PCI) score were 62 years and 17, respectively. Two patients developed pancreatitis (grade 2 and 3) at 45 mg/m2, necessitating cohort expansion. Another patient developed grade 2 pancreatitis at 90 mg/m2. There were no other dose-limiting toxicities, and the highest-dose cohort (120 mg/m2) tolerated PIPAC well. Pharmacokinetic analyses demonstrated good linearity between dose and maximum concentration (r 2 = 0.95) and AUC (r 2 = 0.99). On the basis of RECIST, 62.5% and 50% had stable disease after one and two PIPAC procedures, respectively. A total of 8 patients underwent two PIPAC procedures, with improvement of median PCI and peritoneal regression grade score from 15 to 12 and 2.5 to 2.0, respectively. CONCLUSIONS: The recommended phase II dose is 120 mg/m2. Future studies should further delineate the efficacy and role of PIPAC oxaliplatin for peritoneal metastases.See related commentary by de Jong et al., p. 1830.

Study protocol: phase 1 dose escalating study of Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) with oxaliplatin in peritoneal metastasis.

BACKGROUND: Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) is a novel laparoscopic intraperitoneal chemotherapy technique, with advantages such as homogeneous distribution of aerosol and deeper tissue penetration. Thus far, PIPAC oxaliplatin has been administered at an arbitrary dose of 92 mg/m2. AIM: We aim to determine the dose-related safety profile and tolerability of PIPAC oxaliplatin using an evidence-based approach. The secondary aim is to evaluate clinic-pathologic response and the pharmacokinetic profile. METHODS: This is a phase I 3+3 dose escalation study for gastric and colorectal cancer with predominant peritoneal metastasis starting at a dose of 45 mg/m2. Safety is assessed according to Clavien-Dindo Classification and Common Terminology Criteria for Adverse Events (version 4.0). Clinico-pathologic response is assessed using the Peritoneal Regression Grading Score, Peritoneal Cancer Index, and Response Evaluation Criteria In Solid Tumour criteria (version 1.1). Pharmacokinetic analysis is performed using Inductively Coupled Plasma-Mass Spectrometry assay. This trial is registered on ClinicalTrials.gov (NCT03172416). CONCLUSIONS: This phase I study can provide the scientific basis to identify the optimal dose for PIPAC with oxaliplatin such that the benefits of this novel and promising intraperitoneal chemotherapy delivery technique can be maximized.

Predictors for outcomes after super-selective mesenteric embolization for lower gastrointestinal tract bleeding.

BACKGROUND: The optimal management of bleeding from the lower gastrointestinal tract (LGIB) remains controversial. We aim to evaluate the efficacy of mesenteric embolization for LGIB and to identify predictors for re-bleeding after the procedure. METHODS: We conducted a retrospective review of all patients who underwent mesenteric embolizations for LGIB in our institution over a 6-year period (from August 2007 to August 2013). Technical success was defined as the absence of contrast extravasation on post-embolization angiogram. Clinical success was defined as the absence of overt LGIB (clinical bleeding with >1 g/dL decrease in haemoglobin) within 30 days post-embolization. RESULTS: Mesenteric embolization was performed in 26 patients with LGIB. Technical success rate was 100%, with no occurrence of post-embolization ischaemia. Clinical success rate was 65.4%, with nine patients re-bleeding within 30 days post-embolization. Three underwent surgery, one underwent re-embolization and five were treated conservatively. Mortality rate was 19.3% (five patients), with two bleeding-associated mortalities. Site and aetiology of LGIB, platelet count and coagulation status prior to embolization, number of packed red blood cells and fresh frozen plasma transfusion were found to be predictors of clinical failure. After Bonferroni's correction (P < 0.005), platelet count of ≤140 × 10(9) /L prior to embolization was the only statistically significant factor associated with re-bleeding (odds ratio = 17.5, 95% confidence interval: 2.364-129.57; P = 0.004). CONCLUSION: Mesenteric embolization was found to be safe and effective in treating LGIB (100% technical success, no post-embolization ischaemia), with 65.4% of cases not requiring further intervention. Low platelet count prior to embolization appears to be associated with clinical failure.

Laparoscopic colorectal surgery is safe and benefits octogenarian patients with malignant disease: a matched case-control study comparing laparoscopic and open colorectal surgery.

PURPOSE: Increased physiological stress from laparoscopic surgery and the lower physiological reserves in the elderly are causes for concern. This study aims to compare the outcomes between laparoscopic and open colorectal surgery in octogenarians. METHODS: Octogenarians who underwent elective colorectal resections from 2000 to 2011 were reviewed. Patients who underwent laparoscopic surgery were matched for comorbidities, T-staging and type of resection performed to patients with open surgery. RESULTS: Each group had 36 patients. Both groups were comparable for median age (85 vs 83, p = 0.43), gender (21 vs 18 males, p = 0.64) and the American Society of Anaesthesiologists (ASA) score (p = 0.486). Both groups had comparable median maximal tumour dimensions (4.75 vs 4.25 cm, p = 0.38) and median number of lymph nodes harvested (15 vs 14, p = 0.94). The laparoscopic group had, however, a longer median operative time (167.5 vs 124.5 min, p < 0.001). Both groups had comparable median length of hospitalisation (8 vs 7, p = 0.83), number of complications with a grade of complication (GOC) of ≥3 (5 vs 7, p = 0.75) and 30-day mortality rates (8.3 vs 5.6%, p = 1.00). One-year survival rate for the open group was lower (75.0 vs 94.4%, p = 0.09). CONCLUSIONS: Despite a longer operating time, laparoscopic surgery had comparable short-term outcomes and might have a long-term survival benefit.

Snapshot in surgery: intraperitoneal encapsulated fat necrosis.

A 66-year-old man with rectal cancer was found to have an incidental ring-like lesion in the left rectovesical pouch. Histology revealed an encapsulated fat necrosis. Intraperitoneal encapsulated fat necroses are postulated to be a result of infarcted epiploic appendages resulting in a free-floating lesion.

Long-term outcome following advancement flaps for high anal fistulas in an Asian population: a single institution's experience.

BACKGROUND: The management of high anal fistula is often complicated and challenging. In spite of numerous new techniques, the advancement flap technique remained an integral procedure in its management. The purpose of this study was to determine the long-term outcome of advancement flap procedures for high anal fistulas. METHODS: A retrospective review of patients who have undergone an advancement flap procedure for high anal fistula of cryptoglandular origin from June 2003 to April 2012 was performed. Patients were contacted via telephone to evaluate their continence status using the Wexner score. RESULTS: Sixty-one patients with a median age of 48 (range, 19-74) years and a median follow-up of 6.5 (range, 1-59) months were evaluated. Fifty-three (86.9 %) patients had successful surgery while 8 (13.1 %) failed the procedure. Four of them underwent subsequent surgery. Of the 53 patients who had a successful procedure, 27 were successfully contacted for a telephone interview. Twenty-one (77.8 %) of them reported a Wexner score of '0'. Two (7.4 %) patients had a Wexner score of <4, another 2 had a score of '4' and '10', while the last 2 patients had a score of >10. CONCLUSION: Advancement flap procedure is effective in the management of high anal fistulas with an acceptable success rate. The majority of the patients experienced good anal continence.

Does the timing of an invasive mesenteric angiography following a positive CT mesenteric angiography make a difference?

BACKGROUND: Computed tomographic mesenteric angiography (CTMA) is integral in the management of patients with acute lower gastrointestinal tract bleeding (LGIB). An invasive mesenteric angiography (MA) with a view to embolize the site of bleeding is usually performed if active contrast extravasation was seen on the CTMA scans. However, the bleeding may have ceased by the time the invasive MA is performed. This study aims to identify predictors for active extravasation in invasive MA following a positive CTMA in patients with massive LGIB. METHODOLOGY: A single-center retrospective study of all patients who underwent an invasive MA following a positive CTMA for LGIB from August 2007 to October 2013 was performed. Comparison was performed between patients who had positive and negative invasive MA after a positive CTMA. RESULTS: Forty-eight invasive MA scans were performed in patients with LGIB following a positive CTMA scan. Twenty-three (47.9%) were due to diverticular disease while 20 (41.7%) bled from the small bowel. The median delay from a positive CTMA to invasive MA was 144 (32-587) min. Of the 48 invasive MA, 25 demonstrated active extravasation. Invasive MA scans that was performed within 90 min after a positive CTMA scan were 8.56 (95% CI 0.96-76.1, p = 0.05) times more likely to detect a positive extravasation. CONCLUSION: Invasive MA should be executed promptly after a positive CTMA to increase the probability of detecting the site of bleed to allow superselective embolization.

Endowrist versus wrist: a case-controlled study comparing robotic versus hand-assisted laparoscopic surgery for rectal cancer.

BACKGROUND: Laparoscopic total mesorectal excision (TME) remains a technically challenging procedure. This study aims to compare the surgical outcomes of the robotic-assisted laparoscopic (RAL) versus hand-assisted laparoscopic (HAL) techniques in performing TME for patients with rectal cancers. METHODS: A retrospective review of all patients who underwent RAL TME for rectal cancers was performed. These cases were matched for age, sex, and stage of malignancy with patients who underwent HAL TME. Data collected included age, sex, American Society of Anesthesiologists scores, comorbid conditions, types of surgical resections and operative times, perioperative complications, length of hospital stays, and histopathologic outcomes were analyzed. RESULTS: From August 2008 to August 2011, 19 patients, with a median age of 62 (range, 47 to 92) years underwent RAL TME. Eight (42.1%) patients received neoadjuvant chemoradiotherapy. The median docking and operative times were 10 (range, 3 to 34) and 390 (range, 289 to 771) minutes, respectively. There was 1 (5.3%) conversion to open surgery. The grade of mesorectal excision was histopathologically reported as complete in all 19 cases. Positive circumferential margin was reported in 1 (5.3%) patient.Comparing the 2 groups, more patients in the RAL group received neoadjuvant chemoradiotherapy (8 vs. 3; P=0.048). The operative times were longer in the RAL group (390 vs. 225 min; P<0.001). A higher proportion of patients in the HAL group required conversion to open surgery (5 vs. 1; P=0.180) and developed perioperative morbidities (3 vs. 7; P=0.269). The median length of hospitalization was comparable between both groups (RAL: 7 vs. HAL: 6 d; P=0.476).The procedural cost was significantly higher in the RAL group (US$12,460 vs. US$8560; P<0.001), whereas the nonprocedural cost remained comparable between the 2 groups (RAL: US$4470 vs. HAL: US$4500; P=0.729). CONCLUSIONS: RAL TME is associated with lower conversion and morbidity rates compared with HAL TME. The longer operating times and higher procedural costs are current limitations to its widespread adoption.

Routine histological sampling of doughnuts post oncologic anterior resection is not necessary.

BACKGROUND: A stapled end-to-end colo-rectal anastomosis is increasingly adopted following a proctectomy for various colorectal conditions. The ensuing doughnuts of colonic tissue created from the stapling device have been routinely sent for histological analysis. However, its efficacy remains debatable. This study aims to determine if there is a role in sending colonic doughnuts for histological examination following a stapled end-to-end colo-rectal anastomosis following proctectomy for colorectal cancers. METHODS: A retrospective review of all histological reports of the doughnuts from patients who underwent a proctectomy followed by a stapled end-to-end colo-rectal anastomosis for colorectal cancer in the National University Hospital, Singapore, from 2004-2010 was performed. RESULTS: A total of 336 patients who underwent a stapled end-to-end anastomosis following proctectomy for colorectal cancer from 2004-2010 had available histological reports. The specimen margins and colonic doughnuts were all negative for malignancy. Clinical decisions were not altered based on doughnut histology results. A total cost of USD$61,017.60 was incurred for the histological processing of these doughnuts. CONCLUSION: There appears to be no additional oncological or cost benefits in sending doughnuts after a stapled end-to-end colo-rectal anastomosis following proctectomy for colorectal cancers except in selected clinico-pathological conditions whereby the risk of a positive margin is deemed higher.

Laparoscopic resection for rectal cancer: what is the evidence?

Laparoscopic colectomy for colon cancer is a well-established procedure supported by several well-conducted large-scale randomised controlled trials. Patients could now be conferred the benefits of the minimally invasive approach while retaining comparable oncologic outcomes to the open approach. However, the benefits of laparoscopic proctectomy for rectal cancer remained controversial. While the laparoscopic approach is more technically demanding, results from randomised controlled trials regarding long term oncologic outcomes are only beginning to be reported. The impacts of bladder and sexual functions following proctectomy are considerable and are important contributing factors to the patients' quality of life in the long-term. These issues present a delicate dilemma to the surgeon in his choice of operative approach in tackling rectal cancer. This is compounded further by the rapid proliferation of various laparoscopic techniques including the hand assisted, robotic assisted, and single port laparoscopy. This review article aims to draw on the significant studies which have been conducted to highlight the short- and long-term outcomes and evidence for laparoscopic resection for rectal cancer.

Caecal pneumatosis is not an absolute contraindication for endoluminal stenting in patients with acute malignant large bowel obstruction.

BACKGROUND: The computed tomographic (CT) finding of caecal pneumatosis in patients with malignant large bowel obstruction has been associated with ischaemia and impending perforation. Emergency surgery is then usually performed without consideration of endoluminal stenting. The aim of our study was to correlate caecal viability to the CT finding of caecal pneumatosis in patients with acute malignant large bowel obstruction. METHODS: A retrospective review of the CT scans of all patients presenting with acute malignant large bowel obstruction was performed. Patients with CT evidence of caecal pneumatosis were identified and this was correlated with intraoperative and histopathological findings. RESULTS: There were 10 patients who had caecal pneumatosis on their CT scans between 2007 and 2010. Five underwent immediate surgery while the other five had emergency endoluminal stenting performed. One failed the stenting procedure and proceeded to emergency surgery. The other four were stented successfully and underwent interval surgery in an elective setting. In the six patients who underwent emergency surgery, four were found to have a viable caecum intra-operatively and underwent a segmental resection. The remaining two had an ischaemic caecum--one had curvilinear pneumatosis and the other had a predominantly bubbly pattern of pneumatosis on their CT scans. CONCLUSION: Caecal pneumatosis alone is not a reliable predictor of caecal viability in patients with acute malignant large bowel obstruction. Such a finding on CT scan should be correlated clinically before excluding the role of endoluminal stenting.