Outcomes of a Phase II Study of Intraperitoneal Paclitaxel plus Systemic Capecitabine and Oxaliplatin (XELOX) for Gastric Cancer with Peritoneal Metastases.

BACKGROUND: Adding intraperitoneal paclitaxel (IP-PTX) to paclitaxel/5-fluoropyrimidine has shown promising results in patients with gastric cancer peritoneal metastases (GCPM) but has not been studied with standard-of-care platinum/fluoropyrimidine combinations. Our goal to was evaluate IP-PTX with capecitabine/oxaliplatin (XELOX) in GCPM. METHODS: Forty-four patients with GCPM received IP PTX (40 mg/m2, Days 1, 8), oral capecitabine (1000 mg/m2 twice daily, Days 1-14) and intravenous oxaliplatin (100 mg/m2, Day 1) in 21-day cycles. Patients with synchronous GCPM underwent conversion surgery if they had good response after chemotherapy, conversion to negative cytology, no extraperitoneal metastasis, and no peritoneal disease during surgery. The primary endpoint was overall survival and secondary endpoints were progression-free survival and safety. Outcomes from the trial were compared against a matched cohort of 39 GCPM patients who received systemic chemotherapy (SC) comprising platinum/fluoropyrimidine. RESULTS: The median OS for the IP and SC groups was 14.6 and 10.6 months (hazard ratio [HR] 0.44; 95% confidence interval [CI], 0.26-0.74; p = 0.002). The median PFS for the IP and SC group was 9.5 and 4.4 months respectively (HR 0.39; 95% CI 0.25-0.66; p < 0.001). Patients in the SC group were younger (IP vs. SC, 61 vs. 56 years, p = 0.021) and had better performance status (ECOG 0, IP vs. SC, 47.7% vs. 76.9%, p = 0.007) compared with the IP cohort. In IP group, conversion surgery was performed in 36.1% (13/36) of patients, with a median OS of 24.2 (95% CI 13.1-35.3) months and 1-year OS of 84.6%. CONCLUSIONS: IP PTX with XELOX is a promising treatment option for GCPM patients. In patients with good response, conversion surgery was feasible with favourable outcomes.

Enhanced recovery program versus conventional care after colorectal surgery in the geriatric population: a systematic review and meta-analysis.

INTRODUCTION: Enhanced recovery after surgery (ERAS) programs for patients undergoing colorectal surgery has yielded promising results. However, there remains controversy regarding the application of ERAS protocols in an elderly population. The aim of this review is to compare the clinical outcomes between ERAS versus conventional peri-operative care (Non-ERAS) for colorectal surgery in patients aged ≥ 65 years old. METHODS: The PRISMA guidelines were adhered to. A comprehensive search was performed using Medline, Embase and the Cochrane Library electronic databases and relevant articles were identified. Indications for the colorectal resections included both benign and malignant diseases, while emergency surgeries were excluded. Primary outcomes include post-operative morbidity, length of stay and re-admission rates. Data analysis was performed using Revman 5.3. RESULTS: A total of six studies were included, which involved a total of 1174 patients. ERAS was associated with a lower incidence of post-operative morbidity compared to Non-ERAS (OR 0.38, 95% CI 0.25-0.59), p < 0.001). Similarly, ERAS was also associated with a significantly shorter hospital length of stay (MD - 2.49, 95% CI - 4.11 to 0.88, p = 0.002). Return of bowel function as measured by time to flatus was significantly faster in the ERAS group (MD - 20.01 95% CI - 36.23 to 3.79, p = 0.02), but post-operative ileus rates (OR 0.86, 95% CI 0.50-1.47, p = 0.58) were comparable. Re-admission, re-operation and post-operative mortality rates were also similar between both groups. CONCLUSION: The application of ERAS protocols in an elderly population provides the advantages of lower post-operative morbidity and shorter hospital length of stay. Future studies should aim to evaluate factors that can improve ERAS compliance rates in this group of patients.

Lymphocyte-White Cell Ratio Is a Novel Marker of Morbidity Following Colorectal Cancer Surgery.

BACKGROUND: A preoperative marker for morbidity in patients with colorectal cancer would help to risk stratify patients and allow for timely intervention to avert poor outcomes. We conducted this study to evaluate preoperative lymphocyte-white blood cell ratio (LWR) as a marker of postoperative morbidity. METHODS: A prospective cohort of patients who underwent elective surgery for colorectal cancer was reviewed. Three morbidity-related outcomes were described-overall morbidity, multiple morbidities, and severe morbidity, defined as Clavien-Dindo Class ≥3. Univariable and multivariable analyses of presurgical predictors of these three outcomes were performed. Preoperative variables included hemoglobin levels, neoadjuvant therapy, albumin levels, white blood cell count, lymphocyte count, LWR, neutrophil-lymphocyte ratio, and prognostic nutritional index. RESULTS: Of 177 patients, 31.6% (56/177) suffered at least one morbidity, 15.3% (27/177) had multiple morbidities, 7.9% (14/177) suffered severe morbidity. On multivariate analysis, only LWR <0.180 (odds ratio [OR] 2.53, 95% confidence interval [CI] 1.15-5.55) and neoadjuvant therapy (OR 2.49, 95% CI 1.16-5.24) were associated with overall morbidity. For multiple morbidities and severe morbidity, only LWR <0.180 was significantly associated on multivariate analysis with an OR of 2.92 (95% CI 1.19-7.13) and 4.62 (95% CI 1.45-14.73), respectively. CONCLUSIONS: LWR is a preoperative marker which can be conveniently applied using standard preoperative blood tests. LWR is an independent risk factor for overall morbidity, multiple morbidities, as well as severe morbidity when used with a cut-off of LWR<1.80.

A simple prediction score for prolonged length of stay following elective colorectal cancer surgery.

BACKGROUND: Current enhanced recovery after surgery (ERAS) protocols are designed for all patients without tailored programmes for at-risk groups. A risk score to determine elective colorectal cancer patients at risk for prolonged length of stay (LOS) would help to identify this group for preoperative intervention. METHODS: Multivariate analysis of demographic and preoperative variables was performed to identify independent risk factors for prolonged LOS, defined as 7 days or more. A stepwise variable selection approach using logistic regression was then used to build a risk prediction model. RESULTS: Among 172 patients in our population, 41.9% of patients had prolonged LOS. Five variables were included in our risk prediction model. These were age ≥ 65 years (OR 13.9 5.09-38.0; p < 0.0001), neoadjuvant therapy (OR 7.60 2.51-23.0; p < 0.0001), open approach (OR 3.96 1.68-15.9); p = 0.008), history of smoking (OR 5.18 1.68-15.9; p = 0.004) and white blood cell (WBC) count (OR 0.83/unit 0.69-0.99; p = 0.040). These variables were combined to produce a score, for which the area under the receiving operator curve was 0.82 (95% CI 0.76-0.88), and Hosmer-Lemeshow test showed a χ2 statistic of 9.14 and p = 0.519. Using 0.9 as a cut-off, the score has sensitivity of 81.9% and specificity of 65.0%. CONCLUSION: A simple, clinical score can be used to predict for prolonged LOS based on preoperative variables, allowing for intervention before surgery. Age, neoadjuvant therapy, smoking status, open approach and WBC count are independent risk factors for prolonged length of stay following elective colorectal cancer surgery. A risk score comprising the above independent variables was developed with area under the receiving operator curve of 0.82 (95% CI 0.76-0.88), and a Hosmer-Lemeshow test showing a χ2 statistic of 9.14 and p = 0.519.

Indocyanine green fluorescence angiography decreases the risk of colorectal anastomotic leakage: Systematic review and meta-analysis.

BACKGROUND: Anastomotic leakage after a colorectal resection results in devastating consequences for patients. Indocyanine green fluorescence angiography is a modality to visualize vascular perfusion at the anastomotic site and can help surgeons decide the viability of the anastomosis. We performed this systematic review and meta-analysis to evaluate the efficacy of indocyanine green fluorescence angiography in decreasing anastomotic leakage. METHODS: PubMed, Web of Science, Embase, and the Cochrane Library were searched to identify studies comparing the use of indocyanine green fluorescence angiography versus standard care on rates of anastomotic leakage. Data were pooled with the Mantel-Haenszel method and analyzed based on a random-effects model to estimate the pooled odds ratio and 95% confidence interval. The heterogeneity of studies was evaluated using I2 statistic. RESULTS: Twenty studies were included in this meta-analysis of 5,498 patients. The pooled estimate of the odds ratio was 0.46 (95% confidence interval 0.34-0.62; P < .00001) favoring indocyanine green fluorescence angiography. The overall anastomotic leak rate was 3.7% (n = 82) in the intervention group and 8.6% (n = 282) in the control group. Indocyanine green fluorescence angiography led to a change in the anastomotic site in 216 (9.7%) patients. Subgroup analyses of anastomotic leakage requiring intervention, patients requiring a low colorectal anastomosis, and prospective studies had a pooled estimate of odds ratio 0.55 (95% confidence interval 0.35-0.89), odds ratio 0.38 (95% confidence interval 0.27-0.54; P < .0001), and odds ratio 0.49 (95% confidence interval 0.30-0.81; P = .005) respectively. CONCLUSION: The use of indocyanine green fluorescence angiography is associated with a decrease in anastomotic leakage. This association is present in patients with severe anastomotic leakage requiring intervention as well as low colorectal anastomoses.

Age is an independent risk factor for increased morbidity in elective colorectal cancer surgery despite an ERAS protocol.

INTRODUCTION: Elderly patients with colorectal cancer are high-risk surgical candidates. ERAS protocols have been developed to mitigate against these risks. We performed this study to quantify the risks which elderly patients face and then to determine independent risk factors for short-term ERAS-specific outcomes. METHODS: An analysis of a prospectively collected audit database of all patients who underwent elective colorectal cancer resection within an ERAS framework from January 2018 to December 2018 was performed. Elderly was defined in our study as age ≥ 65 years. RESULTS: There were 172 elective colorectal cancer resections performed. Ninety-seven (56.4%) were elderly. Elderly patients were at increased risk of developing post-operative complications (33.0% vs 16.0%, p = 0.011), longer time to diet (3.4 vs 2.2 days, p = 0.001), and longer hospital stay (10.9 vs 6.7 days, p = 0.007). Independent risk factors were determined for the abovementioned three outcomes. Elderly status was the only risk factor for increased complications (OR 2.61 95% CI (1.05-6.51), p = 0.040). For delayed time to soft diet, male gender (OR 6.67(1.92-20.0), p = 0.002), open approach (OR 9.06(2.26-36.30), p = 0.002), and increased operative time (OR 1.01(1.00-1.01) p = 0.014) were risk factors. Finally, elderly age (OR 5.53(1.82-16.84), p = 0.003), leucocyte count (OR 1.39(0.76-2.57), p = 0.038), open approach (OR 5.26(1.41-19.62), p = 0.013), operative time (OR 1.01(1.00-1.01), p = 0.021), and Clavien-Dindo classification (OR 7.97(1.27-49.88), p = 0.027) were risk factors for prolonged length of stay. CONCLUSION: Elderly patients are intrinsically at risk for increased complications, longer time to soft diet and longer hospital stay. ERAS protocols may need to be specifically tailored for elderly patients.

Exploring UK medical school differences: the MedDifs study of selection, teaching, student and F1 perceptions, postgraduate outcomes and fitness to practise.

BACKGROUND: Medical schools differ, particularly in their teaching, but it is unclear whether such differences matter, although influential claims are often made. The Medical School Differences (MedDifs) study brings together a wide range of measures of UK medical schools, including postgraduate performance, fitness to practise issues, specialty choice, preparedness, satisfaction, teaching styles, entry criteria and institutional factors. METHOD: Aggregated data were collected for 50 measures across 29 UK medical schools. Data include institutional history (e.g. rate of production of hospital and GP specialists in the past), curricular influences (e.g. PBL schools, spend per student, staff-student ratio), selection measures (e.g. entry grades), teaching and assessment (e.g. traditional vs PBL, specialty teaching, self-regulated learning), student satisfaction, Foundation selection scores, Foundation satisfaction, postgraduate examination performance and fitness to practise (postgraduate progression, GMC sanctions). Six specialties (General Practice, Psychiatry, Anaesthetics, Obstetrics and Gynaecology, Internal Medicine, Surgery) were examined in more detail. RESULTS: Medical school differences are stable across time (median alpha = 0.835). The 50 measures were highly correlated, 395 (32.2%) of 1225 correlations being significant with p < 0.05, and 201 (16.4%) reached a Tukey-adjusted criterion of p < 0.0025. Problem-based learning (PBL) schools differ on many measures, including lower performance on postgraduate assessments. While these are in part explained by lower entry grades, a surprising finding is that schools such as PBL schools which reported greater student satisfaction with feedback also showed lower performance at postgraduate examinations. More medical school teaching of psychiatry, surgery and anaesthetics did not result in more specialist trainees. Schools that taught more general practice did have more graduates entering GP training, but those graduates performed less well in MRCGP examinations, the negative correlation resulting from numbers of GP trainees and exam outcomes being affected both by non-traditional teaching and by greater historical production of GPs. Postgraduate exam outcomes were also higher in schools with more self-regulated learning, but lower in larger medical schools. A path model for 29 measures found a complex causal nexus, most measures causing or being caused by other measures. Postgraduate exam performance was influenced by earlier attainment, at entry to Foundation and entry to medical school (the so-called academic backbone), and by self-regulated learning. Foundation measures of satisfaction, including preparedness, had no subsequent influence on outcomes. Fitness to practise issues were more frequent in schools producing more male graduates and more GPs. CONCLUSIONS: Medical schools differ in large numbers of ways that are causally interconnected. Differences between schools in postgraduate examination performance, training problems and GMC sanctions have important implications for the quality of patient care and patient safety.

The Analysis of Teaching of Medical Schools (AToMS) survey: an analysis of 47,258 timetabled teaching events in 25 UK medical schools relating to timing, duration, teaching formats, teaching content, and problem-based learning.

BACKGROUND: What subjects UK medical schools teach, what ways they teach subjects, and how much they teach those subjects is unclear. Whether teaching differences matter is a separate, important question. This study provides a detailed picture of timetabled undergraduate teaching activity at 25 UK medical schools, particularly in relation to problem-based learning (PBL). METHOD: The Analysis of Teaching of Medical Schools (AToMS) survey used detailed timetables provided by 25 schools with standard 5-year courses. Timetabled teaching events were coded in terms of course year, duration, teaching format, and teaching content. Ten schools used PBL. Teaching times from timetables were validated against two other studies that had assessed GP teaching and lecture, seminar, and tutorial times. RESULTS: A total of 47,258 timetabled teaching events in the academic year 2014/2015 were analysed, including SSCs (student-selected components) and elective studies. A typical UK medical student receives 3960 timetabled hours of teaching during their 5-year course. There was a clear difference between the initial 2 years which mostly contained basic medical science content and the later 3 years which mostly consisted of clinical teaching, although some clinical teaching occurs in the first 2 years. Medical schools differed in duration, format, and content of teaching. Two main factors underlay most of the variation between schools, Traditional vs PBL teaching and Structured vs Unstructured teaching. A curriculum map comparing medical schools was constructed using those factors. PBL schools differed on a number of measures, having more PBL teaching time, fewer lectures, more GP teaching, less surgery, less formal teaching of basic science, and more sessions with unspecified content. DISCUSSION: UK medical schools differ in both format and content of teaching. PBL and non-PBL schools clearly differ, albeit with substantial variation within groups, and overlap in the middle. The important question of whether differences in teaching matter in terms of outcomes is analysed in a companion study (MedDifs) which examines how teaching differences relate to university infrastructure, entry requirements, student perceptions, and outcomes in Foundation Programme and postgraduate training.