Quality assessment of surgery for colorectal cancer: Where do we stand?

Quality assurance in surgery has been one of the most important topics of debate among colorectal surgeons in the past decade. It has produced new surgical standards that led in part to the impressive oncological outcomes we see in many units today. Total mesorectal excision, complete mesocolic excision (CME), and the Japanese D3 lymphadenectomy are now benchmark techniques embraced by many surgeons and widely recommended by surgical societies. However, there are still ongoing discrepancies in outcomes largely based on surgeon performance. This is one of the main reasons why many countries have shifted colorectal cancer surgery only to high volume centers. Defining markers of surgical quality is thus a perquisite to ensure that standards and oncological outcomes are met at an institutional level. With the evolution of CME surgery, various quality markers have been described, mostly based on measurements on the surgical specimen and lymph node yield, while others have proposed radiological markers (i.e. arterial stumps) measured on postoperative scans as part of the routine cancer follow-up. There is no ideal marker; however, taken together and assembled into a new score or set of criteria may become a future point of reference for reporting outcomes of colorectal cancer surgery in research studies and defining subspecialization requirements both at an individual and hospital level.

Splenectomy Does Not Increase Early Morbidity in Patients Undergoing Total Gastrectomy: A Case-Control Study with Propensity Score Analysis.

AIM: In gastric cancer (GC), D2 lymph node dissection is, alongside negative-margins gastrectomy, of paramount importance. There is a debate between Western and Eastern scientific communities concerning the risk-benefit balance with respect to splenectomy, as Western countries are inclined to perform spleen-preserving gastrectomy due to an increased risk for postoperative complications. In Eastern countries (such as Japan) this is not the case. Our study aimed to determine whether or not spleen-sacrificing total gastrectomy for GC was associated with a higher rate of early postoperative morbidity or mortality. METHOD: We performed a retrospective case-control study in which we included patients who underwent total gastrectomy with D2 lymphadenectomy for GC (stages I-III) with curative intent, in a single high-volume tertiary oncologic centre. We divided the cases into two groups: spleenpreserving (SP) and spleen-sacrificing (SS) and evaluated the early complications rate following surgery. Afterwards, we performed propensity score matching (PSM) and analysis of the two groups. Results: We included 74 patients, 29 in the SS group and 45 in the SP group. Fifteen cases (20.2%) developed early postoperative complications and the complication rate was 53% (n=8) in the SS group and 46% (n=7) in the SP group. The overall 30-day mortality rate was 2.7%. Conclusions: Splenectomy is not associated with increased early morbidity following total gastrectomy with D2 lymphadenectomy if performed by an experienced surgeon.

Predictive and Prognostic Role of Neutrophil to Lymphocyte Ratio in Rectal Cancer: A Case Control Study with Propensity Score Analysis.

Background: Neutrophil to lymphocyte ratio (NLR) is promoted as a marker reflecting the antitumoral inflammatory response. Herein, we aim to assess whether NLR at the time of diagnosis can predict response to neoadjuvant therapy and long-term survival in a matched cohort of rectal cancer patients. Methods: This is a case control study on rectal cancer patients who underwent standard oncological treatment and had NLR sampled at each stage. ROC curve was used to establish the cut off value of NLR at diagnosis. Two groups (high and low NLR) were compared. Kaplan Meier overall and disease-free survival (DFS) analysis was done comparatively between two groups of patients: low and high NLR. Pearson and Log Rank tests were used to establish statistical significance. Propensity score matching (PSM) was performed, and all variables were compared again on the matched subgroups. Results: One hundred patients were included and 54 were compared again after PSM. NLR at diagnosis did not correlate with tumor regression grade (p=0.77). High NLR at diagnosis (NLR 2.58) was not found to be significantly associated with worse overall survival (p=0.096) or DFS (p=0.128). Similar results were achieved after PSM, except when stage III subgroups were compared, where higher NLR was associated with worse DFS (p=0.04), while results for OS were borderline (p=0.05). Conclusions: Overall, a pretherapeutic high NLR ( 2.58) was not found to predict survival or response do neoadjuvant therapy in patients with rectal cancer. However, a higher NLR may be associated with worse outcomes in advanced colorectal cancer.

Age, blood tests and comorbidities and AIMS65 risk scores outperform Glasgow-Blatchford and pre-endoscopic Rockall score in patients with upper gastrointestinal bleeding.

BACKGROUND: Upper gastrointestinal (GI) bleeding is a life-threatening condition with high mortality rates. AIM: To compare the performance of pre-endoscopic risk scores in predicting the following primary outcomes: In-hospital mortality, intervention (endoscopic or surgical) and length of admission (≥ 7 d). METHODS: We performed a retrospective analysis of 363 patients presenting with upper GI bleeding from December 2020 to January 2021. We calculated and compared the area under the receiver operating characteristics curves (AUROCs) of Glasgow-Blatchford score (GBS), pre-endoscopic Rockall score (PERS), albumin, international normalized ratio, altered mental status, systolic blood pressure, age older than 65 (AIMS65) and age, blood tests and comorbidities (ABC), including their optimal cut-off in variceal and non-variceal upper GI bleeding cohorts. We subsequently analyzed through a logistic binary regression model, if addition of lactate increased the score performance. RESULTS: All scores had discriminative ability in predicting in-hospital mortality irrespective of study group. AIMS65 score had the best performance in the variceal bleeding group (AUROC = 0.772; P < 0.001), and ABC score (AUROC = 0.775; P < 0.001) in the non-variceal bleeding group. However, ABC score, at a cut-off value of 5.5, was the best predictor (AUROC = 0.770, P = 0.001) of in-hospital mortality in both populations. PERS score was a good predictor for endoscopic treatment (AUC = 0.604; P = 0.046) in the variceal population, while GBS score, (AUROC = 0.722; P = 0.024), outperformed the other scores in predicting surgical intervention. Addition of lactate to AIMS65 score, increases by 5-fold the probability of in-hospital mortality (P < 0.05) and by 12-fold if added to GBS score (P < 0.003). No score proved to be a good predictor for length of admission. CONCLUSION: ABC score is the most accurate in predicting in-hospital mortality in both mixed and non-variceal bleeding population. PERS and GBS should be used to determine need for endoscopic and surgical intervention, respectively. Lactate can be used as an additional tool to risk scores for predicting in-hospital mortality.

Laparoscopic versus open resection of primary colorectal cancers and synchronous liver metastasis: a systematic review and meta-analysis.

PURPOSE: Combined resection of primary colorectal cancer and associated liver metastases is increasingly common. This study compares peri-operative and oncological outcomes according to surgical approach. METHODS: The study was registered with PROSPERO. A systematic search was performed for all comparative studies describing outcomes in patients that underwent laparoscopic versus open simultaneous resection of colorectal primary tumours and liver metastases. Data was extracted and analysed using a random effects model via Rev Man 5.3 RESULTS: Twenty studies were included with a total of 2168 patients. A laparoscopic approach was performed in 620 patients and an open approach in 872. There was no difference in the groups for BMI (mean difference: 0.04, 95% CI: 0.63-0.70, p = 0.91), number of difficult liver segments (mean difference: 0.64, 95% CI:0.33-1.23, p = 0.18) or major liver resections (mean difference: 0.96, 95% CI: 0.69-1.35, p = 0.83). There were fewer liver lesions per operation in the laparoscopic group (mean difference 0.46, 95% CI: 0.13-0.79, p = 0.007). Laparoscopic surgery was associated with shorter length of stay (p < 0.00001) and less overall postoperative complications (p = 0.0002). There were similar R0 resection rates (p = 0.15) but less disease recurrence in the laparoscopic group (mean difference: 0.57, 95% CI:0.44-0.75, p < 0.0001). CONCLUSION: Synchronous laparoscopic resection of primary colorectal cancers and liver metastases is a feasible approach in selected patients and does not demonstrate inferior peri-operative or oncological outcomes.

Targeted Cancer Therapy via pH-Functionalized Nanoparticles: A Scoping Review of Methods and Outcomes.

(1) Background: In recent years, several studies have described various and heterogenous methods to sensitize nanoparticles (NPs) to pH changes; therefore, in this current scoping review, we aimed to map current protocols for pH functionalization of NPs and analyze the outcomes of drug-loaded pH-functionalized NPs (pH-NPs) when delivered in vivo in tumoral tissue. (2) Methods: A systematic search of the PubMed database was performed for all published studies relating to in vivo models of anti-tumor drug delivery via pH-responsive NPs. Data on the type of NPs, the pH sensitization method, the in vivo model, the tumor cell line, the type and name of drug for targeted therapy, the type of in vivo imaging, and the method of delivery and outcomes were extracted in a separate database. (3) Results: One hundred and twenty eligible manuscripts were included. Interestingly, 45.8% of studies (n = 55) used polymers to construct nanoparticles, while others used other types, i.e., mesoporous silica (n = 15), metal (n = 8), lipids (n = 12), etc. The mean acidic pH value used in the current literature is 5.7. When exposed to in vitro acidic environment, without exception, pH-NPs released drugs inversely proportional to the pH value. pH-NPs showed an increase in tumor regression compared to controls, suggesting better targeted drug release. (4) Conclusions: pH-NPs were shown to improve drug delivery and enhance antitumoral effects in various experimental malignant cell lines.

Postoperative Quality Assessment Score Can Select Patients with High Risk for Locoregional Recurrence in Colon Cancer.

BACKGROUND: Monitoring surgical quality has been shown to reduce locoregional recurrence (LRR). We previously showed that the arterial stump length (ASL) after complete mesocolic excision (CME) is a reproducible quality instrument and correlates with the lymph-node (LN) yield. We hypothesized that generating an LRR prediction score by integrating the ASL would predict the risk of LRR after suboptimal surgery. METHODS: 502 patients with curative resections for stage I-III colon cancer were divided in two groups (CME vs. non-CME) and compared in terms of surgical data, ASL-derived parameters, pathological parameters, LRR and LRR-free survival. A prediction score was generated to stratify patients at high risk for LRR. RESULTS: The ASL showed significantly higher values (50.77 mm ± 28.5 mm) with LRR vs. (45.59 mm ± 28.1 mm) without LRR (p < 0.001). Kaplan-Meier survival analysis showed a significant increase in LRR-free survival at 5.58 years when CME was performed (Group A: 81%), in contrast to non-CME surgery (Group B: 67.2%). CONCLUSIONS: The prediction score placed 76.6% of patients with LRR in the high-risk category, with a strong predictive value. Patients with long vascular stumps and positive nodes could benefit from second surgery to complete the mesocolic excision.

Impact of Quilting Sutures on Surgical Outcomes After Mastectomy: A Systematic Review and Meta-Analysis.

BACKGROUND: Seroma after mastectomy and/or axillary lymph node dissection (ALND) is among the most common issue surgeons have to face in the early postoperative management of breast cancer. Using quilting sutures (QS) to aid in tissue approximation and decrease dead space is proposed as a simple technique to reduce seroma rate. We aimed to perform a systematic review, and analyse, in a meta-analytical model, the role of QS in improving wound outcomes and decrease volume, duration of drainage, and length of stay in hospital. METHODS: The study was registered with PROSPERO. A systematic search of the PubMed, EMBASE, and SCOPUS databases was performed for all comparative studies examining surgical outcomes in patients who underwent QS versus conventional closure (CC) after mastectomy ± ALND. RESULTS: Twenty-one studies with a total of 3473 patients (1736 in the study group and 1737 in the control group) were included based on the selection criteria. The study group showed significantly lower rates of seroma (p < 0.00001), total volume of drainage (p < 0.0001), days to drain removal (p < 0.00001), and length of stay (p < 0.00001) compared with the control group, while wound complication rates (surgical site infection, flap necrosis, hematoma, skin dimpling) were comparable between the two groups. CONCLUSIONS: QS are a reliable intraoperative technique that decrease seroma formation, volume of postoperative drainage, duration of drainage and length of hospital stay, and should be considered in mastectomies with or without ALND.

Post-operative computed tomography scan - reliable tool for quality assessment of complete mesocolic excision.

BACKGROUND: Quality control in colon cancer surgery is an ongoing debate ever since standardization proved to be highly efficient in improving survival in rectal cancer. Complete mesocolic excision (CME) is widely acclaimed as the new gold-standard in colon cancer resections, thus it is imperative to establish quality criteria of CME in order to make it easily understood and verified by surgeons worldwide. One simple and reproducible tool could be the measurement of arterial stumps postoperatively and a straightforward way to test its reliability is to test it in a comparative study between CME and non-CME surgery. AIM: To validate arterial stump measurement as a surgical quality tool by comparing CME with conventional radical colectomies. METHODS: This was a retrospective study, carried out on a prospective database. We collected data from two groups of patients, divided according to standard CME with D2 central vascular ligation (group A) and non-standardized surgery (group B). The two groups were compared with regard to the arterial stump length after right- and left-sided colectomies for colon cancer. The actual stump lengths of the ileocolic artery (ICA) and inferior mesenteric artery (IMA) were compared with their theoretical best D2 position of predicted ligation levels (D2PLLs) for calculating the potential for improvement. Measurements on follow-up computed tomography scans were carried out by three observers. Pathological data were recorded (specimen length, lymph node yield) and correlated with stump length. RESULTS: We analysed 58 colectomies. The stump lengths (mean ± SD) in group A were 16.97 ± 4.77 mm for ICA and 31.70 ± 15.71 mm for IMA, whereas group B had 49.93 ± 20.29 mm for ICA and 67.24 ± 28.71 mm for IMA. Shorter lengths were obtained in group A, by a mean difference of 35.66 mm (χ 2 = 27.38, P < 0.001), which was significant for all types of colectomies. Except for a 5.85 ± 4.71 mm difference for right colectomies, all the ligations from group A significantly reached their potential height (0.26 ± 12.18 mm from D2PLL; χ 2 = 0.005, P = 0.944). Apart from three left colectomies, group B failed to reach D2PLL, by a mean difference of 32.14 ± 26.15 mm (χ 2 = 21.77, P < 0.001). The calculated improvement potentials were significantly shorter in group A than in group B, by a mean of 31.88 mm (χ 2 = 22.13, P < 0.001). The large spread of results in group B showed that there is significant variability (P = 0.004) when compared to standard surgery. Significant correlations were found between stump length, specimen length and number of lymph nodes (P = 0.018 and P = 0.008 respectively). No statistical difference was found between observers' measurements (P = 0.866). CONCLUSION: Arterial stump monitoring is a significant step in defining surgical quality, as longer stumps contain residual mesocolic tissue and correlate with major prognostic factors.