P-OGC97 Development and piloting of surgical quality assurance methods for randomised controlled trials (RCTs): an example from a trial comparing laparoscopically assisted oesophagectomy vs. open oesophagectomy

Background RCTs in surgery are frequently criticised because the standard to which operations are performed (quality assurance - QA) is not considered during study design and delivery, risking performance bias. Lack of clarity about surgical QA may also influence the successful implementation of RCT results into routine practice, because it is unclear how procedures were undertaken. We developed QA measures for an RCT comparing laparoscopically assisted and open oesophagectomy (LAO and OO). Methods Five QA categories were developed during the pilot and applied to the main trial, using data from patients receiving their randomized allocation in each group: i) entry criteria for centres; ii) entry criteria for surgeons; surgical protocols for key components of LAO and OO with mandated, prohibited and flexible components, monitored using iii) case report forms (CRFs) to record protocol adherence; and iv) intra-operative photographs to demonstrate protocol adherence (using the visible anatomical structures to determine if the component had been fully completed); and v) lymph node count and length of oesophagus. Results 8 centres and 39 surgeons participated and met entry criteria. 145 (LAO) and 149 (OO) patients underwent their randomized surgical procedure. Key procedural components were reported as complete in CRFs at similar rates in both groups, with >70% undergoing mandated components. However, adherence assessed using photographs was consistently lower than the CRFs. For example, left gastric artery lymphadenectomies were reported as complete in > 98% CRFs (LAO and OO) whereas photographs found this to be complete in 42% (OO) and 54% (LAO). Median nodal count was similar in both groups (145 LAO=24.7, SD = 10.6 and 149 OO = 26.4, SD = 10.2) as was length of resected oesophagus. Conclusions Assessing surgical QA in a multi-centre trial is logistically challenging but feasible. Whilst video data from laparoscopic cases could be collected and assessed, it was not possible with open surgery. Understanding adherence to the study protocol using photographs in addition to CRFs was important because of marked differences between what surgeons reported had been undertaken and images of what had been achieved. It is recommended that surgical trials include QA processes to understand protocol adherence and examine performance bias between groups.

The Influence of Lymph Node Count on Oncological Outcome of Radical Cystectomy in Chemotherapy Pre-Treated and Chemotherapy-Naïve Patients with Muscle Invasive Bladder Cancer

Radical cystectomy (RC) with pelvic lymph node dissection (PLND) remains the mainstay of treatment for muscle-invasive bladder cancer (MIBC). The extent of PLND and number of removed lymph nodes (LNs) have been associated with improved staging and survival outcomes in several series of RC patients. Neoadjuvant chemotherapy (NAC) has become standard of care for cisplatin-eligible patients qualified to RC, yet few studies on PLND stratified cases according to the receipt of NAC. We aimed to address this issue and reevaluate the prognostic value of PLND nodal yields in series of patients who underwent RC on the verge of the NAC era. This single-center, retrospective, clinical follow-up study enrolled 439 consecutive patients, out of whom 83 received NAC. We analyzed survival outcome of RC according to the number of removed nodes between NAC and non-NAC subgroups. We found PLND thresholds of 10 and 15 LNs prognostically meaningful in our study cohort, and this association was particularly pronounced in the non-NAC subgroup. Higher numbers of LNs provided a 25% reduction in risk of all-cause mortality and correspondingly correlated with up to a 14% increase in 3-year overall survival. The receipt of NAC diminished the benefit of adequate PLND, as the number of retrieved LNs was not associated with survival in the NAC-RC cohort. Given the limitations of our study, additional research is needed to verify these findings.

The prognostic value of lymph node ratio in comparison to positive lymph node count in penile squamous cell carcinoma

Purpose Penile cancer is a rare male neoplasm with a wide variation in its global incidence. In this study, the prognostic value of lymph node ratio (LNR) was compared to that of positive lymph node count (PLNC) in penile squamous cell carcinoma. Methods A total of 249 patients with penile squamous cell carcinoma were enrolled from The Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. The X-tile program was used to calculate the optimal cut-off values of LNR and PLNC that discriminate survival. We used the χ2 or the Fisher exact probability test to assess the association between clinical-pathological characteristics and LNR or PLNC. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors for survival. Spearman correlation analysis was used to determine the correlation between LNR and PLNC. Results We found that patients with high LNR tended to have advanced N stage, the 7th AJCC stage, and higher pathological grade, while patients with high PLNC had advanced N stage and the 7th AJCC stage. Univariate Cox regression analysis revealed that the N stage, M stage, the 7th AJCC stage, lymph-vascular invasion, LNR, and PLNC were significantly associated with prognosis. Multivariate Cox regression analysis demonstrated that LNR rather than PLNC was an independent prognostic factor for cancer-specific survival. Subgroup analysis of node-positive patients showed that LNR was associated with CSS, while PLNC was not. Conclusion LNR was a better predictor for long-term prognosis than PLNC in patients with penile squamous cell carcinoma.

Central vascular ligation and mesentery based abdominal surgery

In the nineteenth century the idea of a correct surgical approach in oncologic surgery moved towards a good lymphadenectomy. In colon cancer the segment is removed with adjacent mesentery, in gastric cancer or pancreatic cancer a good oncologic resection is obtained with adequate lymphadenectomy. Many guidelines propose a minimal lymph node count that the surgeon must obtain. Therefore, it is essential to understand the adequate extent of lymphadenectomy to be performed in cancer surgery. In this review of the current literature, the focus is on “central vascular ligation”, understood as radical lymphadenectomy in upper and lower gastrointestinal cancer, the evolution of this approach during the years and the improvement of laparoscopic techniques. For what concerns laparoscopic surgery, the main goal is to minimize post-operative trauma introducing the “less is more” concept whilst preserving attention for oncological outcomes. This review will demonstrate the importance of a scientifically based standardization of oncologic gastrointestinal surgery, especially in relation to the expansion of minimally invasive surgery and underlines the importance to further investigate through new randomized trials the role of extended lymphadenectomy in the new era of a multimodal approach, and most importantly, an era where minimally invasive techniques and the idea of “less is more” are becoming the standard thought for the surgical approach.

Optimal examined lymph node count in node-negative colon cancer should be determined

Background: We aimed to investigate the association between optimal examined lymph node (ELNs) and overall survival to determine the optimal cutoff point. Methods: Cox models and locally weighted scatterplot smoothing were used to fit hazard ratios and explore an optimal cutoff point based on the Chow test. Results: Overall survival increased significantly with the corresponding increase in the number of ELNs after adjusting for covariates. In Chow's test, the optimal cutoff point for node-negative colon cancer was 15, which was validated in both cohorts after controlling for confounders (Surveillance, Epidemiology, and End Results database: hazard ratio: 0.701, p < 0.001; single-center: HR: 0.563, p = 0.031). Conclusions: We conservatively suggest that the optimal number of ELNs for prognostic stratification is 15 in node-negative colon cancer.

Impact of Examined Lymph Node Count and Lymph Node Density on Overall Survival of Penile Cancer

BackgroundFew studies have explored the optimal examined lymph node count and lymph node density cutoff values that could be used to predict the survival of patients with penile cancer. We further clarify the prognostic value of lymph node density and examined lymph node count in penile cancer.MethodsThe Surveillance, Epidemiology, and End Results (SEER) database was explored to recruit penile cancer patients from 2010 to 2015. A retrospective analysis of penile cancer patients’ data from the First Affiliated Hospital of Anhui Medical University was performed for verification (2006–2016). The cutoff values of examined lymph node count and lymph node density were performed according to the ROC curve. Kaplan-Meier survival analysis was used to compare survival differences among different groups. Univariate and multivariate Cox proportional hazard regression analyses were used to determine the significant variables. On the basis of Cox proportional hazards regression model, a nomogram was established and validated by calibration plot diagrams and concordance index (C-index).ResultsA total of 528 patients in the Surveillance, Epidemiology, and End Results cohort and 156 patients in the Chinese cohort were included in this study. Using the ROC curve, we found that the recommended cutoff values of ELN and LND were 13 and 9.3%, respectively (P &lt;0.001). Kaplan–Meier curves suggested the significant differences of overall survival among different examined lymph nodes and lymph node density. Multivariate analysis indicated ELN and LND were independent prognostic factor for OS of penile cancer patients. Nomogram showed the contribution of ELN and LND to predicting OS was large. The C-index at 3-, and 5-year were 0.744 for overall survival (95% CI 0.711–0.777).ConclusionsThe more lymph nodes examined, the lower the density of lymph nodes, and the higher the long-term survival rate of penile cancer. We recommended 13 examined lymph nodes and lymph node density &gt;9.3% as the cutoff value for evaluating the prognosis of penile cancer patients.

The Adequacy of Pelvic Lymphadenectomy During Radical Cystectomy for Carcinoma Urinary Bladder: A Narrative Review of Literature

An adequate pelvic lymph node dissection (PLND) is an essential part of radical cystectomy for muscle invasive bladder cancer. However, the definition of what constitutes an adequate PLND is often shrouded in controversy. Various authors have defined different anatomic templates of PLND based on levels of pelvic lymph nodes. Some have suggested other surrogate markers of the adequacy of PLND, namely lymph node count and lymph node density. While individual studies have shown the efficacy and reliability of some of the above markers, none of them have been recommended forthright due to the absence of robust prospective data. The use of non-standardized nomenclature while referring to the above variables has made this matter more complex. Most of older data seems to favor use of extended template of PLND over the standard template. On the other hand, one recent randomized controlled trial (RCT) did not show any benefit of one template over the other in terms of survival benefit, but the study design allowed for a large margin of bias. Therefore, we conducted a systematic search of literature using EMBASE, Medline, and PubMed using PRISMA-P checklist for articles in English Language published over last 20 years. Out of 132 relevant articles, 47 articles were included in the final review. We have reviewed existing literature and guidelines and have attempted to provide a few suggestions toward a uniform nomenclature for the various anatomical descriptions and the extent of PLND done while doing a radical cystectomy. The results of another large RCT (SWOG S1011) are awaited and until we have a definitive evidence, we should adhere to these suggestions as much as possible and deal with each patient on a case to case basis.

A nomogram for predicting feasibility of laparoscopic anterior resection with trans-rectal specimen extraction (NOSES) in patients with upper rectal cancer

Background Laparoscopic anterior resection with trans-rectal specimen extraction (NOSES) has been demonstrated as a safe and effective technique in appropriate patients with upper rectal cancer (RC). However, improper selection of RC candidates for NOSES may lead to potential surgical and oncological unsafety as well as complications such as bacteria contamination and anastomotic leak. Unfortunately, no tools are available for evaluating the risk and excluding improper cases before surgery. This study aims to estimate its clinical relevancy and to investigate independent clinical-pathological predictors for identifying candidates for NOSES in patients with upper RC and to develop a validated scoring nomogram to facilitate clinical decision making. Methods The study was performed at Shanghai East hospital, a tertiary medical center and teaching hospital. 111 eligible patients with upper RC who underwent elective laparoscopic anterior resection between February and October of 2017 were included in the final analysis. Univariate and multivariate analyses were performed to compare characteristics between the two surgical techniques. Odds ratios (OR) were determined by logistic regression analyses to identify and quantify the clinical relevancy and ability of predictors for identifying NOSES candidate. The nomogram was constructed and characterized by c-index, calibration, bootstrapping validation, ROC curve analysis, and decision curve analysis. Results Upper RC patients with successful NOSES tended to be featured with female gender, negative preoperative CEA/CA19-9, decreased mesorectum length (MRL), ratio of diameter (ROD) and ratio of area (ROA) values, while no significant statistical correlations were observed with age, body mass index (BMI), tumor location, and tumor-related biological characteristics (ie., vascular invasion, lymph node count, TNM stages). Furthermore, the two techniques exhibited comparably low incidence of perioperative complications and achieved similar functional results under the standard procedures. The nomogram incorporating three independent preoperative predictors including gender, CEA status and ROD showed a high c-index of 0.814 and considerable reliability, accuracy and clinical net benefit. Conclusions NOSES for patients with upper RC is multifactorial; while it is a safe and efficient technique if used properly. The nomogram is useful for patient evaluation in the future.

Audit of Lymph Node Sampling in Colorectal Carcinoma Resections-implication for Prognosis and Management

Aims: To review lymph node yield in colorectal carcinoma (CRC) resections and its associated factors in a Nigerian Teaching Hospital practice. Study design: This was a retrospective cross-sectional study. Place and duration of study: Department of Pathology, University College Hospital Ibadan Nigeria and colectomies from January 2014 to December 2018 were reviewed. Methodology: Surgical Pathology reports of CRC resections at the University College Hospital Ibadan over 5 years (2014-2018) were reviewed. Colectomy lengths, tumour location (colon/rectum), tumour size, comment on presence of lymph node (yes/no), lymph node count, presence of attached mesentery (yes/no), histological subtype, tumour grade, presence of tumour-positive node and count, and pT stage were documented. Fisher’s Exact test was employed to test the effects of these variables on presence of lymph node and tumour-positive node at histology using SPSS 20. Significance level was set at P < .05. Results: Of 66 histology reports retrieved, 62 (93.9%) had comments on search for lymph nodes and attached mesentery was documented in 25 (37.9%). The median colectomy length and tumour size were 25cm (6cm-152cm) and 6.75cm (3-30cm) respectively. Lymph nodes were present in 52 (78.8%) specimens; 28 (53.8%) of these had tumour-positive lymph nodes. Adenocarcinoma NOS was the commonest histological subtype 53 (80.3%), mucinous carcinoma 12 (18.2%) and signet ring carcinoma 1 (1.5%). Eighteen, 9 and 1of adenocarcinoma NOS, mucinous carcinoma, and signet ring carcinoma respectively had tumour-positive lymph nodes. Finding of lymph node was significantly associated with comment on search for lymph node (p < .01) while finding tumour-positive nodes was associated with histological subtype, presence of mesentery, late tumour stage and lymph node count ≥ 12 (p < .05). Conclusion: If lymph nodes were present, more than likely there will be metastatic involvement. To increase Lymph node yield in CRC resections, submission of mesentery and search for lymph nodes is indicated. When nodes are absent, a mention is required for practice audit. It is imperative to include both clinical and grossing notes for lymph nodes to certify and guide precise staging of the cancer.