Clinical application of machine learning and computer vision to indocyanine green quantification for dynamic intraoperative tissue characterisation: how to do it.

INTRODUCTION: Indocyanine green (ICG) quantification and assessment by machine learning (ML) could discriminate tissue types through perfusion characterisation, including delineation of malignancy. Here, we detail the important challenges overcome before effective clinical validation of such capability in a prospective patient series of quantitative fluorescence angiograms regarding primary and secondary colorectal neoplasia. METHODS: ICG perfusion videos from 50 patients (37 with benign (13) and malignant (24) rectal tumours and 13 with colorectal liver metastases) of between 2- and 15-min duration following intravenously administered ICG were formally studied (clinicaltrials.gov: NCT04220242). Video quality with respect to interpretative ML reliability was studied observing practical, technical and technological aspects of fluorescence signal acquisition. Investigated parameters included ICG dosing and administration, distance-intensity fluorescent signal variation, tissue and camera movement (including real-time camera tracking) as well as sampling issues with user-selected digital tissue biopsy. Attenuating strategies for the identified problems were developed, applied and evaluated. ML methods to classify extracted data, including datasets with interrupted time-series lengths with inference simulated data were also evaluated. RESULTS: Definable, remediable challenges arose across both rectal and liver cohorts. Varying ICG dose by tissue type was identified as an important feature of real-time fluorescence quantification. Multi-region sampling within a lesion mitigated representation issues whilst distance-intensity relationships, as well as movement-instability issues, were demonstrated and ameliorated with post-processing techniques including normalisation and smoothing of extracted time-fluorescence curves. ML methods (automated feature extraction and classification) enabled ML algorithms glean excellent pathological categorisation results (AUC-ROC > 0.9, 37 rectal lesions) with imputation proving a robust method of compensation for interrupted time-series data with duration discrepancies. CONCLUSION: Purposeful clinical and data-processing protocols enable powerful pathological characterisation with existing clinical systems. Video analysis as shown can inform iterative and definitive clinical validation studies on how to close the translation gap between research applications and real-world, real-time clinical utility.

Surgical Management of Idiopathic Perianal Fistulas: A Systematic Review and Meta-Analysis.

BACKGROUND: Perianal fistula is a common colorectal condition with an incidence of 9 per 100,000. Many surgical treatments exist, all aiming to eliminate symptoms with minimal risk of recurrence and impact upon continence. Despite extensive evaluation of the therapeutic modalities, no clear consensus exists as to what is the gold standard approach. This systematic review aimed to examine all available evidence pertaining to the surgical management of perianal fistulas. Primary outcomes examined were recurrence and incontinence. SUMMARY: This study was conducted according to PRISMA guidelines. Primary outcomes were analyzed for each group and expressed as pooled odds ratio with confidence intervals of 95%. 687 studies were identified from which 28 relevant studies were included. There was no significant difference in rates of incontinence identified between various surgical approaches. Glues and plugs show higher recurrence rates. Newer treatments continue to emerge with promise but lack supporting evidence of benefit over conventional therapies. Key Messages: While we await more robust randomized data, we will continue to proceed cautiously trying to offset the benefits of fistula healing against the inherent risk of altered continence.

Preoperative C-reactive protein and other inflammatory markers as predictors of postoperative complications in patients with colorectal neoplasia.

BACKGROUND: Inflammatory markers are measured following colorectal surgery to detect postoperative complications. However, the association of these markers preoperatively with subsequent postoperative course has not yet been usefully studied. AIM: The aim of this study is to assess the ability of preoperative C-reactive protein (CRP) and other inflammatory marker measurements in the prediction of postoperative morbidity after elective colorectal surgery. METHODS: This is a retrospective study which catalogs 218 patients undergoing elective, potentially curative surgery for colorectal neoplasia. Preoperative laboratory results of the full blood count (FBC), C-reactive protein (CRP) and carcinoembryonic antigen (CEA) were recorded. Multivariable analysis was performed to examine preoperative variables against 30-day postoperative complications by type and grade (Clavien-Dindo (CD)), adjusting for age, sex, BMI, smoking status, medical history, open versus laparoscopic operation, and tumor characteristics. RESULTS: Elevated preoperative CRP (≥ 5 mg/L) was significantly predictive of all-cause mortality, with an OR of 17.0 (p < 0.001) and was the strongest factor to predict a CD morbidity grade ≥ 3 (OR 41.9, p < 0.001). Other factors predictive of CD morbidity grade ≥ 3 included smoking, elevated preoperative platelet count and elevated preoperative neutrophil-lymphocyte ratio (OR 15.6, 8.6, and 6.3 respectively, all p < 0.05). CRP values above 5.5 mg/L were indicative of all-cause morbidity (AUC = 0.871), and values above 17.5 mg/L predicted severe complications (AUC = 0.934). CONCLUSIONS: Elevated preoperative CRP predicts increased postoperative morbidity in this patient cohort. The results herein aid risk and resource stratification and encourage preoperative assessment of inflammatory propensity besides simple sepsis exclusion.

Systematic review and meta-analysis of factors which reduce the length of stay associated with elective laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy is a safe ambulatory procedure in appropriately selected patients; however, day case rates remain low. The objective of this systematic review and meta-analysis was to identify interventions which are effective in reducing the length of stay (LOS) or improving the day case rate for elective laparoscopic cholecystectomy. METHODS: Comparative English-language studies describing perioperative interventions applicable to elective laparoscopic cholecystectomy in adult patients and their impact on LOS or day case rate were included. RESULTS: Quantitative data were available for meta-analysis from 80 studies of 10,615 patients. There were an additional 17 studies included for systematic review. The included studies evaluated 14 peri-operative interventions. Implementation of a formal day case care pathway was associated with a significantly shorter LOS (MD = 24.9 h, 95% CI, 18.7-31.2, p < 0.001) and an improved day case rate (OR = 3.5; 95% CI, 1.5-8.1, p = 0.005). Use of non-steroidal anti-inflammatories, dexamethasone and prophylactic antibiotics were associated with smaller reductions in LOS. CONCLUSION: Care pathway implementation demonstrated a significant impact on LOS and day case rates. A limited effect was noted for smaller independent interventions. In order to achieve optimal day case targets, a greater understanding of the effective elements of a care pathway and local barriers to implementation is required.

The Impact of Sarcopenia and Low Muscle Attenuation on Overall Survival in Epithelial Ovarian Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: Sarcopenia is defined as a progressive loss of skeletal muscle mass, strength and physical performance. Myosteatosis is an increase of intra- and intermuscular fat and can be measured radiologically by muscle attenuation. The study aim was to perform a systematic review and meta-analysis on the prognostic potential of sarcopenia and low muscle attenuation in relation to 3-year survival rates (3YSR) and 5YSR in epithelial ovarian cancer (EOC). METHODS: A systematic literature search was conducted using the databases Ovid Medline, EMBASE, and Scopus, using PRISMA guidelines, from inception to 10th of May 2019. Studies evaluated the prognostic potential of sarcopenia and low muscle attenuation on 3YSR and 5YSR in EOC. Quality assessment of included studies was performed using the Methodological Index for Non-Randomised Studies criteria. RESULTS: A comprehensive search of databases resulted in the identification of 2194 studies, resulting in 1695 citations meeting the inclusion criteria. Six studies were included for systematic review. Sarcopenia was not significantly associated with improved 3YSR (OR 1.7, 95% CI 0.8-3.5, p = 0.15) or 5YSR (OR 1.8, 95% CI 1.0-3.2, p = 0.07) in meta-analysis. Normal muscle attenuation was associated with a favourable 3YSR (OR 3.0, 95% CI 2.0-4.5, p < 0.001) and 5YSR (OR 2.3, 95% CI 1.6-3.4, p < 0.001) compared to low muscle attenuation. CONCLUSION: Our meta-analysis indicated normal muscle attenuation was significantly associated with improved 3YSR and 5YSR in patients with EOC. Sarcopenia was not significantly associated with 3YSR or 5YSR in patients with EOC.

A meta-analysis of carbon dioxide versus room air insufflation on patient comfort and key performance indicators at colonoscopy.

BACKGROUND: Carbon dioxide (CO2) has been used as an alternative to air insufflation at endoscopy with good results; however, uptake of the technique has been poor, possibly due to perceived lack of outcome equivalency. This meta-analysis evaluates the effectiveness of CO2 versus air in reducing pain post-colonoscopy and furthermore examines other key performance indicators (KPIs) such as sedative use, procedure times and polyp detection rates. METHODS: This meta-analysis was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Pubmed, Pubmed Central, Embase and Cochrane Library were searched for randomized studies from 2004 to 2019, reporting outcomes for patients undergoing colonoscopy with air or CO2 insufflation, who reported pain on a numerical or visual analogue scale (VAS). Results were reported as mean differences (MD) or pooled odds ratios (OR) with 95% confidence intervals (95% CI). RESULTS: Of 3586 citations, 23 studies comprising 3217 patients were analysed. Patients undergoing colonoscopy with air insufflation had 30% higher intraprocedural pain scores than those receiving CO2 (VAS 3.4 versus 2.6, MD -0.7, 95% CI - 1.4-0.0, p = 0.05), with a sustained beneficial effect amongst those in the CO2 group at 30 min, 1-2-h and 6-h post procedure (MD - 0.8, - 0.6 and - 0.2, respectively, p < 0.001 for all), as well as less distension, bloating and flatulence (p < 0.01 for all). There were no differences between the two groups in KPIs such as the sedation required, procedure time, caecal intubation or polyp detection rates. CONCLUSIONS: CO2 insufflation improves patient comfort without compromising colonoscopic performance.

Prophylactic human papillomavirus vaccination to prevent recurrence of cervical intraepithelial neoplasia: a meta-analysis.

OBJECTIVE: The aim of this systematic review and meta-analysis was to review evidence supporting the use of prophylactic human papillomavirus (HPV) vaccines to influence the risk of recurrence of cervical intraepithelial neoplasia after surgical treatment. METHODS: A systematic literature search was performed for publications reporting risk of recurrence of cervical intraepithelial neoplasia after surgical treatment in patients receiving HPV vaccination (either in the prophylactic or adjuvant setting). Comprehensive searches of six electronic databases (MEDLINE, Embase, Web of Science, PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and references of identified studies) from their inceptions were performed (English language only), and hand search reference lists were performed. Two independent reviewers applied inclusion and exclusion criteria to select manuscripts, with differences discussed and agreed by consensus. The literature search was performed using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Results were reported as mean differences or pooled odds ratios (OR) with 95% confidence intervals (95% CI). RESULTS: A total of 5744 citations were reviewed; 5 studies comprising 2912 patients were selected for the analysis. There were 1338 patients in the vaccinated group and 1574 in the placebo or unvaccinated group. The incidence of histologically confirmed cervical intraepithelial neoplasia 2+ was reduced in the vaccinated compared to the unvaccinated group (OR 0.34, 95% CI 0.21-0.54, p=< 0.00001). The number needed to treat to prevent one recurrence was 27. Both pre-treatment vaccination (OR 0.40, 95% CI 0.21-0.78, p=0.007, number needed to treat - 37) and adjuvant vaccination (OR 0.28, 95% CI 0.14-0.56, p=0.0003, number needed to treat - 30) reduced recurrence rates. CONCLUSION: Prophylactic or adjuvant HPV vaccination reduces the risk of recurrent cervical intraepithelial neoplasia 2+. These data support further investigation of its role as an adjuvant to surgical treatment.

Fixation versus no fixation in laparoscopic totally extraperitoneal repair of primary inguinal hernia-a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: The necessity of mesh fixation in laparoscopic totally extraperitoneal (TEP) inguinal hernia repair remains controversial. We performed a systematic review and meta-analysis to compare the effectiveness of mesh fixation versus no fixation in laparoscopic TEP repair for primary inguinal hernia. MATERIALS AND METHODS: PubMed, EMBASE, and Cochrane databases were searched for relevant articles from January 1992 until May 2020. All trials that compared fixation versus no fixation in TEP repairs for inguinal herniae were included. Recurrent and femoral herniae were excluded from the current analysis. The primary outcome measure was recurrence while secondary outcomes included postoperative pain at 24 h, mean operative time, urinary retention, and seroma rates. Random effects models were used to calculate pooled effect size estimates. Sensitivity analyses were also carried out. RESULTS: Eight randomized controlled trials were included capturing 557 patients and 715 inguinal herniae. On random effects analysis, there were no significant differences between fixation and no fixation with respect to recurrence (RD 0.00, 95% CI = - 0.01 to 0.01, p = 1.00), operative time (MD 1.58 min, 95% CI = - 0.22 to 3.37, p = 0.09), seroma (OR = 0.70, 95% CI = 0.28 to 1.74, p = 0.44), or urinary retention (RD 0.09, 95% CI = - 0.18 to 0.36, p = 0.53). However, fixation was associated with more pain at 24 h (MD 0.93, 95% CI = 0.20 to 1.66, p = 0.01). CONCLUSIONS: Mesh fixation in laparoscopic TEP repair for primary inguinal herniae is associated with increased postoperative pain at 24 h but similar recurrence, seroma, and urinary retention. Therefore, it may be omitted.

Gender and Specialty Influences on Personal and Professional Life Among Trainees.

OBJECTIVE: This study aimed to determine the impact of surgical training on lifestyle and parenthood, and to assess for gender-based workplace issues. BACKGROUND: The effects of a surgical career on lifestyle are difficult to quantify and may vary between male and female doctors. A gender gap is present in the highest tiers of the profession, and reasons why women do not attain senior positions are complex but likely relate to factors beyond merit alone. METHODS: An anonymous Web-based survey was distributed to Irish surgical and nonsurgical trainees. They were asked questions regarding family planning, pregnancy outcomes, parenthood, and gender issues in the workplace, with results analyzed by sex and specialty. RESULTS: Four hundred sixty trainees responded with a response rate of 53.0%; almost two thirds were female. Female trainee surgeons were less likely to have children than their male counterparts (22.5% vs 40.0%, P = 0.0215). Pregnant surgical trainees were more likely to have adverse pregnancy events than the partners of their male contemporaries (65.0% vs 11.5%, P = 0.0002), or than their female nonsurgical colleagues (P = 0.0329). Women were more likely to feel that they had missed out on a job opportunity (P < 0.001) and that their fellowship choice was influenced by their gender (P < 0.001). CONCLUSIONS: The current study highlights some areas of difficulty encountered by female surgical trainees. Surmounting the barriers to progression for female surgeons, by addressing the perceived negative impacts of surgery on lifestyle, will likely encourage trainee retention of both genders.

A meta-analysis of morbidity and mortality in primary cytoreductive surgery compared to neoadjuvant chemotherapy in advanced ovarian malignancy.

Aim The aim of this meta-analysis is to review the morbidity and mortality associated with primary cytoreductive surgery (PCS) compared to neoadjuvant chemotherapy and interval cytoreductive surgery (NACT + ICS) for advanced ovarian cancer. METHODS: A literature search was performed for publications reporting morbidity and mortality in patients undergoing PCS compared to NACT + ICS. Databases searched were Cochrane, Medline, Pubmed, Pubmed Central, clinicaltrials.gov and Embase. Two independent reviewers applied inclusion and exclusion criteria to select included papers, with differences agreed by consensus. A total of 1341 citations were reviewed; 17 studies comprising 3759 patients were selected for the analysis. The literature search was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results were reported as mean differences or pooled odds ratios (OR) with 95% confidence intervals (95% CI). RESULTS: Patients in the PCS group were significantly more likely to have a Clavien-Dindo grade ≥ 3 morbidity with an overall rate of 21.2% compared to 8.8% (95%CI 1.9-4.0, p < 0.0001) and were more likely to die within 30 days of surgery (OR 6.1, 95% CI 2.1-17.6, p = 0.0008). Patients who underwent NACT + ICS had significantly shorter procedural times (MD -35 min, p = 0.01), lost less blood intraoperatively (MD-382 ml, p < 0.001) and had an average admission 5.0 days shorter (MD -5.0 days, 95% CI -8.1 to -1.9 days, p = 0.002) than those undergoing PCS. While NACT was associated with significantly increased optimal and complete cytoreduction rates (OR 1.9, 95% CI 1.3-2.9, p = 0.001, and OR 2.2, 95% CI 1.5-3.3, p = 0.0001 respectively), this did not confer any additional survival benefit (OR 1.0, p = 0.76). CONCLUSION: NACT is associated with less morbidity and mortality and improved complete cytoreduction compared to PCS, with no survival benefit. Hence NACT is an acceptable alternative in selected patients in particular with medical co-morbidities or a high tumour burden.

Meta-analysis of Histological Margin Positivity in the Prediction of Recurrence After Crohn's Resection.

BACKGROUND: Despite significant advances in the medical management of Crohn's disease, many patients will require intestinal resection during their lifetime. It is disappointing that many will also develop disease recurrence. OBJECTIVES: The current study utilizes meta-analytical techniques to determine the effect of positive histological margins at the time of index resection on disease recurrence. DATA SOURCES: Embase, Medline, PubMed, PubMed Central, and Cochrane databases were searched using a Boolean search algorithm for articles published up to August 2017. STUDY SELECTION: Meta-analysis was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. MAIN OUTCOME MEASURES: Databases were searched for studies reporting the outcomes for patients with Crohn's disease undergoing primary resection that correlated resection margin status with disease recurrence. Results were reported as pooled ORs with 95% CI. RESULTS: A total of 176 citations were reviewed; 18 studies comprising 1833 patients were ultimately included in the analysis, with a mean rate of histopathological margin positivity of 41.7 ± 17.4% and a pooled mean follow-up of 69 ± 39 months. Histopathological margin positivity was associated with a higher rate of overall recurrence (OR, 1.7; 95% CI, 1.3-2.1; p < 0.001), clinical recurrence (OR, 1.7; 95% CI, 1.0-2.8; p = 0.04), and anastomotic recurrence (OR, 1.6; 95% CI, 1.0-2.3; p = 0.03). In studies reporting plexitis specifically at the resection margin, there was an increase in recurrence (OR, 2.3; 95% CI, 1.1-4.9; p = 0.02). LIMITATIONS: The definitions of histological margin positivity and postoperative recurrence vary between the studies and follow-up durations vary. CONCLUSIONS: The presence of involved histological margins at the time of index resection in Crohn's disease is associated with recurrence, and plexitis shows promise as a marker of more aggressive disease. Further studies with homogeneity of histopathological and recurrence reporting are required.

Meta-analysis of outcomes of endoscopic ultrasound-guided gallbladder drainage versus percutaneous cholecystostomy for the management of acute cholecystitis.

BACKGROUND: Endoscopic ultrasound-guided gallbladder drainage is a novel method of treating acute cholecystitis in patients deemed too high risk for surgery. It involves endoscopic stent placement between the gallbladder and the alimentary tract to internally drain the infection and is an alternative to percutaneous cholecystostomy (PC). This meta-analysis assesses the clinical outcomes of high-risk patients undergoing endoscopic drainage with an acute cholecystoenterostomy (ACE) compared with PC in acute cholecystitis. METHODS: A literature search was performed using the preferred reporting items for systematic reviews and meta-analyses guidelines. Databases were searched for studies reporting outcomes of patients undergoing ACE or PC. Results were reported as mean differences or pooled odds ratios (OR) with 95% confidence intervals (95% CI). RESULTS: A total of 1593 citations were reviewed; five studies comprising 495 patients were ultimately selected for analysis. There were no differences in technical or clinical success rates between the two groups on pooled meta-analysis. ACE had significantly lower post-procedural pain scores (mean difference - 3.0, 95% CI - 2.3 to - 3.6, p < 0.001, on a 10-point pain scale). There were no statistically significant differences in procedure complications between groups. Re-intervention rates were significantly higher in the PC group (OR 4.3, 95% CI 2.0-9.3, p < 0.001). CONCLUSION: ACE is a promising alternative to PC in high-risk patients with acute cholecystitis, with equivalent success rates, improved pain scores and lower re-intervention rates, without the morbidities associated with external drainage.

The Twin Evils of Concomitant Rare Pathology with Variant Anatomy: Superior Mesenteric Artery Aneurysm and a Replaced Right Hepatic Artery.

Aneurysmal degeneration of the superior mesenteric artery (SMA) is a rare clinical finding, estimated to affect <1% of the general population in postmortem studies. Due to the rare prevalence of aneurysms affecting the SMA, there are no clear or definitive published consensus guidelines for its management at presentation, with both surgical and endovascular options described. An aberrant or replaced right hepatic artery (RRHA) is thought to affect 10-15% of the population. The prevalence of both conditions presenting concomitantly is unknown, but undoubtedly even rarer. We describe the successful management of a symptomatic SMA aneurysm with an RRHA emerging from the aneurysmal sac presenting to our vascular unit. This was repaired via an open surgical approach with SMA aneurysmectomy and interposition grafting using reversed vein with preservation of RHA liver perfusion via a novel reconstruction option. This case highlights the challenge that visceral aneurysms pose, especially when simple or orthodox reconstruction options are limited due to rare or unusual anatomy.

Using the diamond intermediate anastomosis in composite sequential bypass grafting for critical limb ischemia.

Composite sequential bypass grafting is an effective alternative in the treatment of peripheral vascular disease when autologous vein is limited. We describe a modified technique for composite sequential bypass grafting anastomosis using a combination of synthetic graft with native vein connected via a common intermediate anastomotic junction, which also benefits from having additional outflow at the native, noncontiguous arteriotomy in a diamond configuration. This technique was piloted on six patients to treat critical limb ischemia when no other revascularization options were deemed suitable. Limb salvage with resolution of symptoms was achieved in all six patients at the 6-month follow-up. The diamond anastomosis is a promising method to maximize limb salvage using a unique composite sequential bypass configuration when native vein is limited.

Mycotic Aneurysm of the Extracranial Internal Carotid Artery, Resect and Ligate or Reconstruct?

Mycotic aneurysmal disease of the extracranial carotid arteries (ECA) is a rare entity associated with a high morbidity, including rupture, hemorrhage, airway obstruction, and stroke. Surgical management is challenging due to difficult dissection through infected or inflamed tissue. This report highlights a case of ECA-aneurysm infection presenting with stroke and an occluded internal carotid artery, likely due to microbial arteritis on a background of osteomyelitis. Operative intervention was performed to definitively treat the infection and prevent the potential associated complications. In this case, the incident vessel was 100% occluded at presentation, allowing vessel ligation and resection without carotid complex reconstruction.

Multicenter Evaluation of Rectal cancer ReImaging pOst Neoadjuvant (MERRION) Therapy.

OBJECTIVE: The aim of this study was to evaluate the utility of reimaging rectal cancer post-CRT (chemoradiotherapy) with magnetic resonance (MR) imaging of the pelvis for local staging and computed tomography of thorax, abdomen, and pelvis (CT TAP) to identify distant metastases. BACKGROUND: The success of neoadjuvant CRT for locally advanced rectal cancer has changed an already complex management algorithm. There is no consensus whether patients should be restaged before surgery. METHODS: Data from 5 institutions with prospectively maintained databases including patients who received neoadjuvant CRT for locally advanced rectal cancer were acquired. Only patients who had been staged pre- and post-CRT with MR imaging and CT TAP were included. MR findings were correlated with histopathological stage using weighted κ (kappa) statistics to test agreement, where a κ value of less than 0.5 was deemed unacceptable. RESULTS: A total of 285 patients fulfilled the criteria for the study; 84% had American Joint Committee for Cancer stage 3 disease pre-CRT, and the remainder had stage 2 disease. Fourteen patients did not proceed to surgery post-CRT-2 were observed as "complete responders," and the remainder either had unresectable disease or were unfit for surgery. MR imaging could not predict T stage (κ = 0.212) or nodal involvement (κ = 0.336). Most pertinently, MR imaging was unable to detect a complete pathological response (κ = 0.021), nor could it discriminate T4 disease (κ = 0.445). CT TAP restaging altered management in 6.7% of patients, who had metastatic disease. CONCLUSIONS: MR reimaging using standard protocols is of limited value in determining surgical approaches; a better modality of local restaging is required.

Prognostic significance of tumor budding in rectal cancer biopsies before neoadjuvant therapy.

Tumor budding is an increasingly important prognostic feature for pathologists to recognize. The aim of this study was to correlate intra-tumoral budding in pre-treatment rectal cancer biopsies with pathological response to neoadjuvant chemoradiotherapy and with long-term outcome. Data from a prospectively maintained database were acquired from patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy. Pre-treatment rectal biopsies were retrospectively reviewed for evidence of intra-tumoral budding. Multivariate logistic regression was used to identify factors contributing to cancer-specific death, expressed as hazard ratios with 95% confidence intervals. Of the 185 patients with locally advanced rectal cancer, 89 patients met the eligibility criteria, of whom 18 (20%) exhibited budding in a pre-treatment tumor biopsy. Intra-tumoral budding predicted a poor pathological response to neoadjuvant chemoradiotherapy (higher ypT stage, P=0.032; lymph node involvement, P=0.018; lymphovascular invasion, P=0.004; and residual poorly differentiated tumors, P=0.005). No patient with intra-tumoral budding exhibited a tumor regression grade 1 or complete pathological response, providing a 100% specificity and positive predictive value for non-response to neoadjuvant chemoradiotherapy. Intra-tumoral budding was associated with a lower disease-free 5-year survival rate (33 vs 78%, P<0.001), cancer-specific 5-year survival rate (61 vs 87%, P=0.021) and predicted cancer-specific death (hazard ratio 3.51, 95% confidence interval 1.03-11.93, P=0.040). Intra-tumoral budding at diagnosis of rectal cancer identifies those who will poorly respond to neoadjuvant chemoradiotherapy and those with a poor prognosis.

The frequencies and clinical implications of mutations in 33 kinase-related genes in locally advanced rectal cancer: a pilot study.

BACKGROUND: Locally advanced rectal cancer (LARC: T3/4 and/or node-positive) is treated with preoperative/neoadjuvant chemoradiotherapy (CRT), but responses are not uniform. The phosphatidylinositol 3-kinase (PI3K), MAP kinase (MAPK), and related pathways are implicated in rectal cancer tumorigenesis. Here, we investigated the association between genetic mutations in these pathways and LARC clinical outcomes. METHODS: We genotyped 234 potentially clinically relevant nonsynonymous mutations in 33 PI3K and MAPK pathway-related genes, including PIK3CA, PIK3R1, AKT, STK11, KRAS, BRAF, MEK, CTNNB1, EGFR, MET, and NRAS, using the Sequenom platform. DNA samples were extracted from pretreatment LARC biopsy samples taken from 201 patients who were then treated with long-course neoadjuvant CRT followed by surgical resection. RESULTS: Sixty-two mutations were detected in 15 genes, with the highest frequencies occurring in KRAS (47 %), PIK3CA (14 %), STK11 (6.5 %), and CTNNB1 (6 %). Mutations were detected in BRAF, NRAS, AKT1, PIK3R1, EGFR, GNAS, MEK1, PDGFRA, ALK, and TNK2, but at frequencies of <5 %. As expected, a pathologic complete response (pCR) was associated with improved 5-year recurrence-free survival (RFS; hazard ratio, 0.074; 95 % CI 0.01-0.54; p = 0.001). Mutations in PI3K pathway-related genes (odds ratio, 5.146; 95 % CI 1.17-22.58; p = 0.030), but not MAPK pathway-related genes (p = 0.911), were associated with absence of pCR after neoadjuvant CRT. In contrast, in patients who did not achieve pCR, mutations in PI3K pathway-related genes were not associated with recurrence-free survival (p = 0.987). However, in these patients, codon 12 (G12D/G12 V/G12S) and 13 mutations in KRAS were associated with poor recurrence-free survival (hazard ratio, 1.579; 95 % confidence ratio, 1.00-2.48; p = 0.048). CONCLUSIONS: Mutations in kinase signaling pathways modulate treatment responsiveness and clinical outcomes in LARC and may constitute rational targets for novel therapies.

A virtual outpatient department provides a satisfactory patient experience following endoscopy.

PURPOSE: The purpose of this study was to investigate telephone follow-up of post-endoscopy patients as an alternative to attendance at the outpatient department. METHODS: Access to outpatient appointments is often a target for improvement in healthcare systems. Increased outpatient clinic capacity is not feasible without investment and extra manpower in an already constrained service. Outpatient attendance was audited at a busy colorectal surgical service. A subset of patients appropriate for follow-up in a "virtual outpatient department" (VOPD) were identified. A pilot study was designed and involved telephone follow-up of low-risk endoscopic procedures. Patient satisfaction was assessed using the Medical Interview Satisfaction Scale (MISS), which is a standardised survey of patient satisfaction with healthcare experiences. This was conducted via anonymous questionnaire at the end of the study. RESULTS: Of a total of 166 patients undergoing endoscopy in the time period, 79 were prospectively recruited to VOPD follow-up based on eligibility criteria. Overall, 67 (84.8 %) were successfully followed up by telephone consultation; nine patients (11.4 %) were contacted by mail. The remaining three patients (3.8 %) were brought back to the OPD. Patients recruited were more likely to be younger (55.82 ± 14.96 versus 60.78 ± 13.97 years, P = 0.029) and to have had normal examinations (49.4 versus 31.0 %, χ (2) = 5.070, P = 0.025). Nearly three quarters of patients responded to the questionnaire. The mean scores for all four aspects of the MISS were satisfactory, and overall patients were satisfied with the VOPD experience. CONCLUSION: VOPD is a target for improved healthcare provision, with improved efficiency and a high patient satisfaction rate.

Laparoscopic lavage for perforated diverticulitis: a population analysis.

BACKGROUND: Laparoscopic lavage has shown promising results in nonfeculent perforated diverticulitis. It is an appealing strategy; it avoids the complications associated with resection. However, there has been some reluctance to widespread uptake because of the scarcity of large-scale studies. OBJECTIVE: This study investigated national trends in management of perforated diverticulitis. DESIGN: This retrospective population study used an Irish national database to identify patients acutely admitted with diverticulitis, as defined by the International Classification of Diseases. Demographics, procedures, comorbidities, and outcomes were obtained for the years 1995 to 2008. SETTINGS: The study was conducted in Ireland. PATIENTS: Patients with International Classification of Diseases codes corresponding to diverticulitis who underwent operative intervention were included. MAIN OUTCOME MEASURES: The primary outcome was mortality, and secondary outcomes were length of stay and postoperative complications. RESULTS: Two thousand four hundred fifty-five patients underwent surgery for diverticulitis, of whom 427 underwent laparoscopic lavage. Patients selected for laparoscopic lavage had lower mortality (4.0% vs 10.4%, p < 0.001), complications (14.1% vs 25.0%, p < 0.001), and length of stay (10 days vs 20 days, p < 0.001) than those requiring laparotomy/resection. Patients older than 65 years were more likely to die (OR 4.1, p < 0.001), as were those with connective tissue disease (OR 7.3, p < 0.05) or chronic kidney disease (OR 8.0, p < 0.001). LIMITATIONS: This retrospective study is limited by the quality of data obtained and is subject to selection bias. Furthermore, the lack of disease stratification means it is not possible to identify the extent of peritonitis; feculent peritonitis has worse outcomes and is not likely to be included in the lavage group. CONCLUSIONS: The number of patients selected for laparoscopic lavage in perforated diverticulitis is increasing, and the outcomes in this study are comparable to other reports. Those patients in whom laparoscopic lavage alone was suitable had lower mortality and morbidity than those in whom resection was considered necessary.