Patient-Reported Bowel, Urinary, and Sexual Outcomes After Laparoscopic-Assisted Resection or Open Resection for Rectal Cancer: The Australasian Laparoscopic Cancer of the Rectum Randomized Clinical Trial (ALaCart).

OBJECTIVE: The aim of this study was to compare patient-reported urinary, bowel, and sexual functioning of ALaCaRT Trial participants randomized to open or laparoscopic surgery for rectal cancer. SUMMARY BACKGROUND DATA: The primary endpoint, noninferiority of laparoscopic surgical resection adequacy, was not established. METHODS: Participants completed QLQ-CR29 at baseline, 3, and 12 months post-surgery. Additionally, women completed Rosen's Female Sexual Functioning Index (FSFI). Men completed the International Index of Erectile Function (IIEF) and QLQ-PR25. We compared the proportions of participants in each group who experienced moderate/severe symptoms/dysfunction at each time-point and compared mean difference scores from baseline to 12 months between groups. All analyses were intention-to-treat. Sexual functioning analyses included only the participants who expressed sexual interest at baseline. RESULTS: Baseline PRO compliance of 475 randomized participants was 88%. At 12 months, a lower proportion of open surgery participants experienced moderate-severe fecal incontinence and sore skin, compared to Laparoscopic participants, and a lower proportion of men randomized to open surgery experienced moderate-severe urinary symptoms. There were no differences at 3 months for bowel or urinary symptoms. Sexual functioning among sexually interested participants was similar between groups at 3 and 12 months; however, a lower proportion of women reported moderate to severe sexual dissatisfaction at 3 months in the open as compared to the laparoscopic group, (Rebecca.mercieca@sydney.edu.au., 95% CI 0.03-0.39). DISCUSSION: Despite the slightly lower proportions of open surgery participants self-reporting moderate-severe symptoms for 3 of 16 urinary/bowel domains, and lack of differences in sexual domains, it remains difficult to recommend one surgical approach over another for rectal resection.

The use of a porcine model to teach advanced abdominal wall dissection techniques.

BACKGROUND: In the era of minimally invasive surgery, it is clear that a robust simulation model is required for the training of surgeons in advanced abdominal wall reconstruction. The purpose of this experimentation was to evaluate whether a porcine model could be used to teach advanced minimally invasive abdominal wall dissection techniques to novice surgeons. Secondary objectives included: time to completion, identification of various anatomical landmarks, to note the difference in porcine and human models and finally, the ability to dock a Da Vinci Xi robotic platform on the porcine model. METHODOLOGY: Two post-fellowship surgeons were given the task of performing an extended total extraperitoneal dissection (ETEP) on one female Landrace pig under the supervision of a surgeon experienced in robotic-assisted ventral hernia repair. This included insertion of ports, developing a retro-rectus plane, crossover from left to right rectus, bilateral transverse abdominus release, and sub-diaphragmatic dissection. A 5-mm vessel sealer was used to facilitate the dissection. The steps of the surgery were given to the trainees, and an experienced hernia surgeon guided the steps of dissection. The emphasis of the tasks was to develop the planes of extraperitoneal dissection to demonstrate that the porcine model could be considered for a viable and realistic model for training. RESULTS: The candidates were able to successfully complete the task and dock a Da Vinci Xi with the porcine model providing a realistic platform for training. CONCLUSION: The porcine model can be a considerable tool in the education of surgeons embarking on learning the art of minimally invasive abdominal wall reconstruction techniques. The advantage of live tissue dissection, similarity in anatomy and the relatively inexpensive availability of porcine models, makes it an unparalleled form of simulation-based training. We believe that this will have transitional capabilities to robotic ETEP education for complex hernia repair.

Sociocultural and Demographic Factors Predict Readmissions for General Surgery Patients.

INTRODUCTION: Readmission is a poor outcome for both patients and healthcare systems. The association of certain sociocultural and demographic characteristics with likelihood of readmission is uncertain in general surgical patients. METHOD: A multi-centre retrospective cohort study of consecutive unique individuals who survived to discharge during general surgical admissions was conducted. Sociocultural and demographic variables were evaluated alongside clinical parameters (considered both as raw values and their proportion of change in the 1-2 days prior to admission) for their association with 7 and 30 days readmission using logistic regression. RESULTS: There were 12,701 individuals included, with 304 (2.4%) individuals readmitted within 7 days, and 921 (7.3%) readmitted within 30 days. When incorporating absolute values of clinical parameters in the model, age was the only variable significantly associated with 7-day readmission, and primary language and presence of religion were the only variables significantly associated with 30-day readmission. When incorporating change in clinical parameters between the 1-2 days prior to discharge, primary language and religion were predictive of 30-day readmission. When controlling for changes in clinical parameters, only higher comorbidity burden (represented by higher Charlson comorbidity index score) was associated with increased likelihood of 30-day readmission. CONCLUSIONS: Sociocultural and demographic patient factors such as primary language, presence of religion, age, and comorbidity burden predict the likelihood of 7 and 30-day hospital readmission after general surgery. These findings support early implementation a postoperative care model that integrates all biopsychosocial domains across multiple disciplines of healthcare.

Depression after stoma surgery: a systematic review and meta-analysis.

BACKGROUND: Depression is the leading cause of global disability and can develop following the change in body image and functional capacity associated with stoma surgery. However, reported prevalence across the literature is unknown. Accordingly, we performed a systematic review and meta-analysis aiming to characterise depressive symptoms after stoma surgery and potential predictive factors. METHODS: PubMed/MEDLINE, Embase, CINAHL and Cochrane Library were searched from respective database inception to 6 March 2023 for studies reporting rates of depressive symptoms after stoma surgery. Risk of bias was assessed using the Downs and Black checklist for non-randomised studies of interventions (NRSIs), and Cochrane RoB2 tool for randomised controlled trials (RCTs). Meta-analysis incorporated meta-regressions and a random-effects model. REGISTRATION: PROSPERO, CRD42021262345. RESULTS: From 5,742 records, 68 studies were included. According to Downs and Black checklist, the 65 NRSIs were of low to moderate methodological quality. According to Cochrane RoB2, the three RCTs ranged from low risk of bias to some concerns of bias. Thirty-eight studies reported rates of depressive symptoms after stoma surgery as a proportion of the respective study populations, and from these, the median rate across all timepoints was 42.9% 42.9% (IQR: 24.2-58.9%). Pooled scores for respective validated depression measures (Hospital Anxiety and Depression Score (HADS), Beck Depression Inventory (BDI), and Patient Health Questionnaire-9 (PHQ-9)) across studies reporting those scores were below clinical thresholds for major depressive disorder according to severity criteria of the respective scores. In the three studies that used the HADS to compare non-stoma versus stoma surgical populations, depressive symptoms were 58% less frequent in non-stoma populations. Region (Asia-Pacific; Europe; Middle East/Africa; North America) was significantly associated with postoperative depressive symptoms (p = 0.002), whereas age (p = 0.592) and sex (p = 0.069) were not. CONCLUSIONS: Depressive symptoms occur in almost half of stoma surgery patients, which is higher than the general population, and many inflammatory bowel disease and colorectal cancer populations outlined in the literature. However, validated measures suggest this is mostly at a level of clinical severity below major depressive disorder. Stoma patient outcomes and postoperative psychosocial adjustment may be enhanced by increased psychological evaluation and care in the perioperative period.

Immunohistochemistry features and molecular pathology of appendiceal neoplasms.

Primary appendiceal neoplasms (ANs) comprise a heterogeneous group of tumors. The pathology and classification of ANs have been controversial, and thus, a new classification of these neoplasms was published in the World Health Organization (WHO) classification of tumors (5th edition, 2019). However, immunohistochemistry (IHC) features of epithelial ANs are not explained in this edition and the limited data on the molecular pathology of these tumors shows inconsistent findings in various studies. It would be useful to identify biomarkers appropriate for each subtype to better aid in treatment selection. Therefore, we reviewed the literature to investigate what is known of the molecular pathology and IHC features of the most frequently diagnosed pathological subtypes of epithelial ANs based on the recent classification. The inconsistencies in research findings regarding the IHC features and molecular pathology of ANs could be due to differences in the number of samples and their collection and preparation as well as to the lack of a universally accepted classification system for these neoplasms. However, the literature shows that epithelial ANs typically stain positive for MUC2, CK20, and CDX2 and that the expression of SATB2 protein could be used as a biomarker for appendix tumor origin. Low-grade appendiceal mucinous neoplasms tend to have mutations in KRAS and GNAS but are usually wild-type for BRAF, APC, and P53. Conversely, appendiceal adenocarcinomas are frequently found with mutations in KRAS, GNAS, P53, PIK3CA, and APC, and have significant nuclear expression of ß-catenin, loss of nuclear or nuclear and cytoplasmic expression of SMAD4, and loss of cytoplasmic membranous expression of E-cadherin. Goblet cell carcinomas (GCCs) typically stain positive for keratin and mucin markers and are frequently mutated in P53 and chromatin-modifier genes, but they tend to be wild-type for KRAS, GNAS, APC, and PIK3CA. The expression of CK7 and SATB2 proteins is usually negative in appendiceal neuroendocrine neoplasms and they lack the mutations in common cancer-associated genes including APC, BRAF, SMAD4, and PIK3C. The available data suggest that GCCs have distinct molecular and immunohistochemical features and that they have characteristics more in common with adenocarcinoma than classical neuroendocrine tumors. In addition, MSI does not seem to have a role in the pathogenesis of epithelial ANs because they are rarely detected in these tumors. Finally, hereditary predisposition may have a role in the development of ANs because heterozygous CTNNß1, NOTCH1, and NOTCH4 germline mutations have recently been identified in low and high grades ANs.

Clinical Evaluation of Intraoperative Near Misses in Laparoscopic Rectal Cancer Surgery.

OBJECTIVE: To investigate the frequency, nature, and severity of intraoperative adverse near miss events within advanced laparoscopic surgery and report any associated clinical impact. BACKGROUND: Despite implementation of surgical safety initiatives, the intraoperative period is poorly documented with evidence of underreporting. Near miss analyses are undertaken in high-risk industries but not in surgical practice. METHODS: Case video and data from 2 laparoscopic total mesorectal excision randomized controlled trials were analyzed (ALaCaRT ACTRN12609000663257, 2D3D ISRCTN59485808). Intraoperative adverse events were identified and categorized using the observational clinical human reliability analysis technique. The EAES classification was applied by 2 blinded assessors. EAES grade 1 events (nonconsequential error, no damage, or need for correction) were considered near misses. Associated clinical impact was assessed with early morbidity and histopathology outcomes. RESULTS: One hundred seventy-five cases contained 1113 error events. Six hundred ninety-eight (62.7%) were near misses (median 3, IQR 2-5, range 0-15) with excellent inter-rater and test-retest reliability (κ=0.86, 95% CI 0.83-0.89, P < 0.001 and κ=0.88, 95% CI 0.85-0.9, P < 0.001 respectively). Significantly more near misses were seen in patients who developed early complications (4 (3-6) vs. 3 (2-4), P < 0.001). Higher numbers of near misses were seen in patients with more numerous (P = 0.002) and more serious early complications (P = 0.003). Cases containing major intraoperative adverse events contained significantly more near misses (5 (3-7) vs. 3 (2-5), P < 0.001) with a major event observed for every 19.4 near misses. CONCLUSION: Intraoperative adverse events and near misses can be reliably and objectively captured in advanced laparoscopic surgery. Near misses are commonplace and closely associated with morbidity outcomes.

Middle Eastern women's attitudes and expectations towards vaginal natural orifice transluminal endoscopic surgery (vNOTES): a survey-based observational study.

BACKGROUND: Trans-vaginal natural orifice transluminal endoscopic surgery (vNOTES) is a recently popularised minimally invasive surgical procedure, aimed at minimising abdominal wall scars and improving pain and patient recovery times. Although vNOTES has been studied in the context of post-operative pain and cosmesis, women's acceptance of the technique has only been cursorily examined. In this survey-based observational study, we assessed the acceptability of this technique among a cohort of Middle Eastern women. MATERIALS AND METHODS: A cohort of 175 Middle Eastern women were surveyed using a 13-item questionnaire at a single gynaecology centre. The survey used was a translated version of a questionnaire from a previous study (1) and comprised open-response, five-point Likert Scale and agree-disagree items. RESULTS: Among 175 Middle Eastern women participated in this study most of them holding neutral view on abdominal and gynaecological procedures via vagina. 47% of participants were unsure regarding the effect of surgery via vagina on their sexual function. Although 61% of the participants showed no preference towards vNOTES over laparoscopic cholecystectomy, more than half of them indicated preference if vNOTES shown to be as effective and safe as laparoscopic cholecystectomy. The gender of the surgeon was shown to have no influence on the perspectives of the majority of participants to undergo vNOTES. CONCLUSIONS: vNOTES may hold value for women who have conservative upbringing and/or value cosmesis. This study provides information regarding Middle Eastern women's perspectives on vNOTES, which may be of considerable clinical use as the popularity of this surgical technique continues to increase.

High preoperative levels of circulating SFRP5 predict better prognosis in colorectal cancer patients.

The purpose of this research was to investigate the diagnostic and prognostic value of circulating SFRP5 (cSFRP5) in colorectal cancer (CRC). We evaluated preoperative cSFRP5 levels in CRC patients and controls (n = 208). We found significantly higher cSFRP5 levels in CRC patients compared with non-CRC controls (p < 0.001). Levels of cSFRP5 were significantly lower in CRC patients with either vascular invasion (p = 0.001) or liver metastasis (p = 0.016). High cSFRP5 levels were associated with longer disease-free survival in both univariate (p = 0.024) and multivariate (p = 0.015) analyses. Analysis of an independent tissue cohort from The Cancer Genome Atlas database revealed significantly lower SFRP5 RNA expression in CRC tumor tissue compared with adjacent normal mucosa (n = 590 vs 47; p < 0.0001). Our findings confirm the role of cSFRP5 as a physiologic tumor suppressor and demonstrate its potential diagnostic and prognostic value in CRC.

Suppression of type 2 diabetes mellitus-induced aortic ultrastructural alterations in rats by insulin: an association of vascular injury biomarkers.

Diabetes represents a major public health problem and an estimated 70% of people with diabetes die of cardiovascular complications. The protective effect of insulin treatment against ultrastructural damage to the tunica intima and tunica media of the aorta induced by type 2 diabetes mellitus (T2DM) has not been investigated before using transmission electron microscopy (TEM). Therefore, we induced T2DM in rats using high fat diet and streptozotocin (50 mg/kg) and administered insulin daily by i.v injection for 8 weeks to the treatment group. Whereas, the T2DM control group were left untreated for the duration of the experiment. A comparison was also made between the effect of insulin on aortic tissue and the blood level of biomarkers of vascular injury, inflammation, and oxidative stress. T2DM induced profound ultrastructural damage to the aortic endothelium and vascular smooth muscle cells, which were substantially protected with insulin. Furthermore, insulin returned blood sugar to a control level and significantly (p < .05) inhibited diabetic up-regulation of endothelial and leukocyte intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion protein 1 (VCAM-1), endothelial cell adhesion molecules, P-selectin and E-selectin, tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), and malondialdehyde (MDA). Furthermore, insulin augmented the blood level of the anti-oxidant enzyme superoxide dismutase (SOD). We conclude that in a rat model of T2DM, insulin treatment substantially reduces aortic injury secondary to T2DM for a period of 8 weeks, possibly due to the inhibition of hyperglycemia, vascular activation, inflammation, and oxidative stress.

Disease-free Survival and Local Recurrence After Laparoscopic-assisted Resection or Open Resection for Rectal Cancer: The Australasian Laparoscopic Cancer of the Rectum Randomized Clinical Trial.

OBJECTIVE: The aim of the study was to determine the efficacy of laparoscopic rectal resection (Lap) versus open laparotomy and rectal resection (Open) for rectal cancer on locoregional recurrence (LRR) and disease-free survival (DFS) at 2 years. SUMMARY BACKGROUND DATA: Although a Lap approach to colon cancer surgery may offer similar oncological outcomes to Open with potentially less morbidity, this remains to be clearly established for the treatment of rectal cancer. METHODS: A randomized, multicenter noninferiority phase 3 trial of 475 patients with T1 to T3 rectal adenocarcinoma <15 cm from anal verge, given Lap or Open and followed for a minimum 2 years to assess LRR, DFS, and overall survival (OS). RESULTS: Secondary endpoint analyses included 450 patients (95%) without metastases at baseline (mean age 64; 34% women) who received Lap (n = 225) or Open (n = 225). Median follow-up was 3.2 years (range: 0.1-5.4 yrs). LRR cumulative incidence at 2 years: Lap 5.4%; Open 3.1% [difference, 2.3%; 95% confidence interval (CI), -1.5% to 6.1%; hazard ratio (HR) 1.7; 95% CI, 0.74-3.9]. DFS at 2 years: Lap 80%; Open 82% (difference, 2.0%; 95% CI, -9.3% to 5.4%; HR for recurrence or death, 1.17; 95% CI, 0.81-1.68; P = 0.41). After adjustment for baseline factors HR = 1.07 (95% CI, 0.7-1.6). OS at 2 years: Lap 94%; Open 93% (difference 0.9%; 95% CI, -3.6% to 5.4%). CONCLUSIONS: Laparoscopic surgery for rectal cancer did not differ significantly from open surgery in effects on 2-year recurrence or DFS and OS. Confidence intervals included potentially clinically important differences favoring open resection, so that the combination of primary and secondary study endpoints may not support laparoscopic resection of rectal cancer as a routine standard of care and further follow-up is required.

The ALCCaS Trial: A Randomized Controlled Trial Comparing Quality of Life Following Laparoscopic Versus Open Colectomy for Colon Cancer.

BACKGROUND: This study reports the quality-of-life assessment of the ALCCaS trial. The ALCCaS trial compared laparoscopic and open resection for colon cancer. It reported equivalence of survival at 5 years. Quality of life was measured as a secondary outcome. OBJECTIVE: This study aimed to report on the quality of life data of the ALCCaS Trial. DESIGN: This study reports a randomized controlled trial comparing laparoscopic with open colonic resection. SETTINGS: The study was conducted in Australasia. PATIENTS: Patients with a single adenocarcinoma of the right, left, or sigmoid colon, presenting for elective treatment, were eligible for randomization. INTERVENTIONS: Open and laparoscopic colonic resections were performed. MAIN OUTCOME MEASURES: Patient symptoms and quality of life were measured using the Symptoms Distress Scale, the Quality of Life Index, and the Global Quality of Life Score preoperatively, and at 2 days, 2 weeks, and 2 months postoperatively. RESULTS: Of the 592 patients enrolled in ALCCaS, 425 completed at least 1 quality-of-life measure at 4 time points (71.8% of cohort). Those who received the laparoscopic intervention had better quality of life postoperatively in terms of the Symptoms Distress Scale (p < 0.01), Quality of Life Index (p < 0.01), and Global Quality of Life (p < 0.01). In intention-to-treat analyses, those assigned to laparoscopic surgery had a better quality of life postoperatively in terms of the Symptoms Distress Scale (p < 0.01) and Quality of Life Index (p < 0.01), whereas Global Quality of Life was not significant (p = 0.056). The subscales better for laparoscopic resection at all 3 postoperative time points were appetite, insomnia, pain, fatigue, bowel, daily living, and health (p < 0.05). LIMITATIONS: The primary limitation was the different response rates for the 3 quality-of-life measures. CONCLUSIONS: There was a short-term gain in quality of life maintained at 2 months postsurgery for those who received laparoscopic relative to open colonic resection. See Video Abstract at http://links.lww.com/DCR/A691.

Soluble HLA-G is a differential prognostic marker in sequential colorectal cancer disease stages.

The expression of HLA-G by tumour cells is an established mechanism to escape recognition and immune mediated destruction, allowing tumour survival, growth and metastasis. However, the prognostic value of soluble HLA-G (sHLA-G) remains unknown. Mucinous carcinoma (MC) is a distinct form of colorectal cancer (CRC) found in 10 to 15% of patients, which has long been associated with poor response to treatment. To investigate the prognostic value of plasma sHLA-G levels in CRC patients, preoperative plasma sHLA-G levels were determined by ELISA in CRC patients (n = 133). In addition, the local expression of HLA-G in tumour biopsies was assessed using tissue microarray analysis (n = 255). Within the high 33rd percentile of sHLA-G levels (265-890 U/mL; n = 44) we observed higher frequency of MC patients (p = 0.012; Chi-square), and higher sHLA-G levels in patients with vascular invasion (p = 0.035; two-tailed t-test). Moreover, MC patients had significantly higher sHLA-G levels compared to those with adenocarcinoma not otherwise specified (p = 0.036; two-tailed t-test). Surprisingly, while stage II patients showed negative correlation between sHLA-G levels and liver metastasis free survival (LMFS) (p = 0.041; R = -0.321), in stage III patients high sHLA-G levels were associated with significantly longer LMFS (p = 0.002), and sHLA-G levels displayed positive correlation with LMFS (p = 0.006; R = 0.409). High HLA-G expression in tumours was associated with poor cancer specific overall survival in stage II to III (p = 0.01), and with shorter LMFS in stage II patients (p = 0.004). Our findings reveal that sHLA-G levels are associated with distinct progression patterns in consecutive disease stages, indicating a potential value as surrogate marker in the differential prognosis of CRC.

Findings in young adults at colonoscopy from a hospital service database audit.

BACKGROUND: Colorectal cancer (CRC) diagnosed at <50 years is predominantly located in the distal colon and rectum. Little is known about which lesion subtypes may serve as CRC precursors in young adults. The aim of this work was to document the prevalence and histological subtype of lesions seen in patients aged <50 years, and any associated clinical features. METHODS: An audit of the colonoscopy database at The Queen Elizabeth Hospital in Adelaide, South Australia over a 12-month period was undertaken. Findings were recorded from both colonoscopy reports and corresponding histological examination of excised lesions. RESULTS: Data were extracted from colonoscopies in 2064 patients. Those aged <50 comprised 485 (24%) of the total. CRC precursor lesions (including sessile serrated adenoma/polyps (SSA/P), traditional serrated adenomas, tubular adenomas ≥10 mm or with high-grade dysplasia, and conventional adenomas with villous histology) were seen in 4.3% of patients aged <50 and 12.9% of patients aged ≥50 (P <0.001). Among colonoscopies yielding CRC precursor lesions in patients under 50 years, SSA/P occurred in 52% of procedures (11/21), compared with 27% (55/204) of procedures in patients aged 50 and older (P = 0.02). SSA/P were proximally located in (10/11) 90% of patients aged under 50, and 80% (43/54) of those aged 50 and older (P = 0.46). CONCLUSIONS: SSA/P were the most frequently observed CRC precursor lesions in patients aged <50. Most CRCs in this age group are known to arise in the distal colon and rectum suggesting that lesions other than SSA/P may serve as the precursor for the majority of early-onset CRC.

Adjuvant capecitabine plus bevacizumab versus capecitabine alone in patients with colorectal cancer (QUASAR 2): an open-label, randomised phase 3 trial.

BACKGROUND: Antiangiogenic agents have established efficacy in the treatment of metastatic colorectal cancer. We investigated whether bevacizumab could improve disease-free survival in the adjuvant setting after resection of the primary tumour. METHODS: For the open-label, randomised, controlled QUASAR 2 trial, which was done at 170 hospitals in seven countries, we recruited patients aged 18 years or older with WHO performance status scores of 0 or 1 who had undergone potentially curative surgery for histologically proven stage III or high-risk stage II colorectal cancer. Patients were randomly assigned (1:1) to receive eight 3-week cycles of oral capecitabine alone (1250 mg/m2 twice daily for 14 days followed by a break for 7 days) or the same regimen of oral capecitabine plus 16 cycles of 7·5 mg/kg bevacizumab by intravenous infusion over 90 min on day 1 of each cycle. Randomisation was done by a computer-generated schedule with use of minimisation with a random element stratified by age, disease stage, tumour site, and country. The study was open label and no-one was masked to treatment assignment. The primary endpoint was 3-year disease-free survival, assessed in the intention-to-treat population. Toxic effects were assessed in patients who received at least one dose of randomised treatment. This trial is registered with the ISRCTN registry, number ISRCTN45133151. FINDINGS: Between April 25, 2005, and Oct 12, 2010, 1952 eligible patients were enrolled, of whom 1941 had assessable data (968 in the capecitabine alone group and 973 in the capecitabine and bevacizumab group). Median follow-up was 4·92 years (IQR 4·00-5·16). Disease-free survival at 3 years did not differ between the groups (75·4%, 95% CI 72·5-78·0 in the capecitabine and bevacizumab group vs 78·4%, 75·7-80·9 in the capecitabine alone group; hazard ratio 1·06, 95% CI 0·89-1·25, p=0·54). The most common grade 3-4 adverse events were hand-foot syndrome (201 [21%] of 963 in the capecitabine alone group vs 257 [27%] of 959 in the capecitabine and bevacizumab group) and diarrhoea (102 [11%] vs 104 [11%]), and, with the addition of bevacizumab, expected increases were recorded in all-grade hypertension (320 [33%] vs 75 [8%]), proteinuria (197 [21%] vs 49 [5%]), and wound healing problems (30 [3%] vs 17 [2%]). 571 serious adverse events were reported (221 with capecitabine alone and 350 with capecitabine and bevacizumab). Most of these were gastrointestinal (n=245) or cardiovascular (n=169). 23 deaths within 6 months of randomisation were classified as being related to treatment, eight in the capecitabine alone group and 15 in the capecitabine and bevacizumab group. INTERPRETATION: The addition of bevacizumab to capecitabine in the adjuvant setting for colorectal cancer yielded no benefit in the treatment of an unselected population and should not be used. FUNDING: Roche.

Acquisition and retention of laparoscopic skills is different comparing conventional laparoscopic and single-incision laparoscopic surgery: a single-centre, prospective randomized study.

BACKGROUND: Training in laparoscopic surgery is important not only to acquire and improve skills but also avoid the loss of acquired abilities. The aim of this single-centre, prospective randomized study was to assess skill acquisition of different laparoscopic techniques and identify the point in time when acquired skills deteriorate and training is needed to maintain these skills. METHODS: Sixty surgical novices underwent laparoscopic surgery (LS) and single-incision laparoscopic surgery (SILS) baseline training (BT) performing two validated tasks (peg transfer, precision cutting). The novices were randomized into three groups and skills retention testing (RT) followed after 8 (group A), 10 (group B) or 12 (group C) weeks accordingly. Task performance was measured in time with time penalties for insufficient task completion. RESULTS: 92 % of the participants completed the BT and managed to complete the task in the required time frame of proficiency. Univariate and multivariate analyses revealed that SILS (P < 0.0001) and precision cutting (P < 0.0001) were significantly more difficult. Males performed significantly better than females (P < 0.005). For LS, a deterioration of skills (comparison of BT vs RT) was not identified; however, for SILS a significant deterioration of skills (adjustment of BT and RT values) was demonstrated for all groups (A-C) (P < 0.05). DISCUSSION: Our data reveal that complex laparoscopic tasks (cutting) and techniques (SILS) are more difficult to learn and acquired skills more difficult to maintain. Acquired LS skills were maintained for the whole observation period of 12 weeks but SILS skills had begun to deteriorate at 8 weeks. These data show that maintenance of LS and SILS skills is divergent and training curricula need to take these specifics into account.

Detection and Clinical Significance of Circulating Tumor Cells in Colorectal Cancer--20 Years of Progress.

Circulating tumor cells (CTC) may be defined as tumor- or metastasis-derived cells that are present in the bloodstream. The CTC pool in colorectal cancer (CRC) patients may include not only epithelial tumor cells, but also tumor cells undergoing epithelial-mesenchymal transition (EMT) and tumor stem cells. A significant number of patients diagnosed with early stage CRC subsequently relapse with recurrent or metastatic disease despite undergoing "curative" resection of their primary tumor. This suggests that an occult metastatic disease process was already underway, with viable tumor cells being shed from the primary tumor site, at least some of which have proliferative and metastatic potential and the ability to survive in the bloodstream. Such tumor cells are considered to be responsible for disease relapse in these patients. Their detection in peripheral blood at the time of diagnosis or after resection of the primary tumor may identify those early-stage patients who are at risk of developing recurrent or metastatic disease and who would benefit from adjuvant therapy. CTC may also be a useful adjunct to radiological assessment of tumor response to therapy. Over the last 20 years many approaches have been developed for the isolation and characterization of CTC. However, none of these methods can be considered the gold standard for detection of the entire pool of CTC. Recently our group has developed novel unbiased inertial microfluidics to enrich for CTC, followed by identification of CTC by imaging flow cytometry. Here, we provide a review of progress on CTC detection and clinical significance over the last 20 years.

Rising incidence of early-onset colorectal cancer in Australia over two decades: report and review.

The average age at diagnosis for colorectal cancer (CRC) in Australia is 69, and the age-specific incidence rises rapidly after age 50 years. The incidence has stabilized or is declining in older age groups in Australia during recent decades, possibly related to the increased uptake of screening and high-risk surveillance. In the same time frame, a rising incidence of CRC in younger adults has been well-documented in the United States. This rise in incidence in the young has not been reported from other countries that share long-term exposure to westernised urban lifestyles. Using data from the Australian Institute of Health and Welfare, we examined trends in national incidence rates for CRC under age 50 years and observed that rates in people under age 40 years have been rising for the last two decades. We further performed a review of the literature regarding CRC in young adults to outline the extent of current understanding, explore potential risk factors such as obesity, alcohol, and sedentary lifestyles, and to identify the questions remaining to be addressed. Although absolute numbers might not justify a population screening approach, the dispersal of young adults with CRC across the primary health-care system decreases probability of their recognition. Patient and physician awareness, aided by stool and emerging blood-screening tests and risk profiling tools, have the potential to aid in identification of those young adults who would most benefit from a colonoscopy through early detection of CRCs or by removal of advanced polyps.

Prospective randomized assessment of acquisition and retention of SILS skills after simulation training.

BACKGROUND: Skills in single-incision laparoscopic surgery (SILS) are difficult to acquire. Simulation training leads to skill acquisition but circumstances about skill deterioration are unclear. The aim of this study was to evaluate skill acquisition and retention after single-incision laparoscopic simulation training. METHODS: From October 2013 to January 2014, 30 surgically naive participants underwent a SILS training curriculum and completed two validated tasks (peg transfer, precision cutting) with subsequent testing to assess acquisition of skills (baseline testing, BT). The participants were randomized into two groups and skill retention testing (RT) was measured after 4 weeks (group A) or 12 weeks (group B). Task completion was measured in time with penalties for inaccurate performance. RESULTS: A SILS training curriculum was established. 90 % of the participants completed the training successfully and reached the required levels of proficiency. Comparison of BT and RT revealed significantly better RT performances for peg transfer and precision cutting in group A (P < 0.05). These effects were not seen for RT in group B. Evaluating the RT performance of both groups, group A showed a non-significant trend for improved peg transfer and precision cutting compared to group B. CONCLUSION: A proficiency-based training curriculum for acquisition of basic SILS skills was successfully established in our department. The results of this study indicate that acquired SILS skills are well retained for a short period without training (4 weeks) but a longer non-training period (12 weeks) resulted in a significant loss of acquired skills. For enhancement of surgical skills, specialised SILS training curricula could be developed for novices and inexperienced surgeons; however, continuous training is essential to maintain these acquired skills.

Effect of Laparoscopic-Assisted Resection vs Open Resection on Pathological Outcomes in Rectal Cancer: The ALaCaRT Randomized Clinical Trial.

IMPORTANCE: Laparoscopic procedures are generally thought to have better outcomes than open procedures. Because of anatomical constraints, laparoscopic rectal resection may not be better because of limitations in performing an adequate cancer resection. OBJECTIVE: To determine whether laparoscopic resection is noninferior to open rectal cancer resection for adequacy of cancer clearance. DESIGN, SETTING, AND PARTICIPANTS: Randomized, noninferiority, phase 3 trial (Australasian Laparoscopic Cancer of the Rectum; ALaCaRT) conducted between March 2010 and November 2014. Twenty-six accredited surgeons from 24 sites in Australia and New Zealand randomized 475 patients with T1-T3 rectal adenocarcinoma less than 15 cm from the anal verge. INTERVENTIONS: Open laparotomy and rectal resection (n = 237) or laparoscopic rectal resection (n = 238). MAIN OUTCOMES AND MEASURES: The primary end point was a composite of oncological factors indicating an adequate surgical resection, with a noninferiority boundary of Δ = -8%. Successful resection was defined as meeting all the following criteria: (1) complete total mesorectal excision, (2) a clear circumferential margin (≥1 mm), and (3) a clear distal resection margin (≥1 mm). Pathologists used standardized reporting and were blinded to the method of surgery. RESULTS: A successful resection was achieved in 194 patients (82%) in the laparoscopic surgery group and 208 patients (89%) in the open surgery group (risk difference of -7.0% [95% CI, -12.4% to ∞]; P = .38 for noninferiority). The circumferential resection margin was clear in 222 patients (93%) in the laparoscopic surgery group and in 228 patients (97%) in the open surgery group (risk difference of -3.7% [95% CI, -7.6% to 0.1%]; P = .06), the distal margin was clear in 236 patients (99%) in the laparoscopic surgery group and in 234 patients (99%) in the open surgery group (risk difference of -0.4% [95% CI, -1.8% to 1.0%]; P = .67), and total mesorectal excision was complete in 206 patients (87%) in the laparoscopic surgery group and 216 patients (92%) in the open surgery group (risk difference of -5.4% [95% CI, -10.9% to 0.2%]; P = .06). The conversion rate from laparoscopic to open surgery was 9%. CONCLUSIONS AND RELEVANCE: Among patients with T1-T3 rectal tumors, noninferiority of laparoscopic surgery compared with open surgery for successful resection was not established. Although the overall quality of surgery was high, these findings do not provide sufficient evidence for the routine use of laparoscopic surgery. Longer follow-up of recurrence and survival is currently being acquired. TRIAL REGISTRATION: anzctr.org Identifier: ACTRN12609000663257.