Improving the management of early colorectal cancers (eCRC) by using quantitative markers to predict lymph node involvement and thus the need for major resection of pT1 cancers

BackgroundSince implementing the NHS bowel cancer screening programme, the rate of early colorectal cancer (eCRC; pT1) has increased threefold to 17%, but how these lesions should be managed is currently unclear.AimTo improve risk stratification of eCRC by developing reproducible quantitative markers to build a multivariate model to predict lymph node metastasis (LNM).MethodsOur retrospective cohort of 207 symptomatic pT1 eCRC was assessed for quantitative markers. Associations between categorical data and LNM were performed using χ2 test and Fisher’s exact test. Multivariable modelling was performed using logistic regression. Youden’s rule gave the cut-point for LNM.ResultsAll significant parameters in the univariate analysis were included in a multivariate model; tumour stroma (95% CI 2.3 to 41.0; p=0.002), area of submucosal invasion (95% CI 2.1 to 284.6; p=0.011), poor tumour differentiation (95% CI 2.0 to 358.3; p=0.003) and lymphatic invasion (95% CI 1.3 to 192.6; p=0.028) were predictive of LNM. Youden’s rule gave a cut-off of p>5%, capturing 18/19 LNM (94.7%) cases and leading to a resection recommendation for 34% of cases. The model that only included quantitative factors were also significant, capturing 17/19 LNM cases (90%) and leading to resection rate of 35% of cases (72/206).ConclusionsIn this study, we were able to reduce the potential resection rate of pT1 with the multivariate qualitative and/or quantitative model to 34% or 35% while detecting 95% or 90% of all LNM cases, respectively. While these findings need to be validated, this model could lead to a reduction of the major resection rate in eCRC.

Efficacy of Laparoscopic Hepatectomy versus Open Surgery for Hepatocellular Carcinoma With Cirrhosis: A Meta-analysis of Case-Matched Studies

BackgroundThe role of laparoscopic hepatectomy (LH) in hepatocellular carcinoma (HCC) with cirrhosis remains controversial and needs to be further assessed. The present meta-analysis aimed to compare the surgical and oncological outcomes of LH with those of open hepatectomy (OH) for HCC with cirrhosis.MethodsThe PubMed, Embase, and Cochrane Library databases were searched for studies comparing LH and OH until Mar 2021. Weighted mean differences (WMDs), odds ratios (ORs), and hazard ratios (HRs) were calculated for continuous, dichotomous, and long-term variables, respectively, with 95% confidence intervals (CIs). Subgroup analysis was performed according to different resection types: major resection and minor resection. The meta-analysis was performed using the STATA 12.0.ResultsA total of 16 case-matched studies (784 patients in the LH group and 1,191 patients in the OH group.) were included in this meta-analysis. In terms of primary outcomes, LH was associated with decreased overall complication rate (OR 0.57; 95% CI 0.46 to 0.71; P <0.01), major complication rate (OR 0.52; 95% CI 0.33 to 0.82; P < 0.01), postoperative mortality (OR 0.27; 95% CI 0.11 to 0.66; P <0.01), 1-y overall survival (OS) rate (HR 0.48; 95% CI 0.31 to 0.73; P <0.01), 2-y OS (HR 0.61; 95% CI 0.45 to 0.83; P < 0.01), and 5-y OS (0.67; 95% CI 0.53 to 0.85; P < 0.01). With respect to secondary outcomes, blood loss (WMD −69.16; 95% CI −101.72 to −36.61; P < 0.01), length of hospitalization (LOH) (WMD −2.65; 95% CI −3.41 to −1.89; P < 0.01), minor complication rate (OR 0.70; 95% CI 0.53 to 0.94; P = 0.02), postoperative liver failure (OR 0.60; 95% CI 0.38 to 0.95; P = 0.03), and postoperative ascites (OR 0.44; 95% CI 0.28 to 0.72; P < 0.01) was lower in LH than in OH. No significant differences in operation time (P = 0.07), transfusion rate (P = 0.05), 1-, 2-, and 5-year DFS rate (1-year, P = 0.08; 2-year, P = 0.08; 5-year, P = 0.23) were noted between LH and OH. Subgroup analysis based on minor resection revealed that LH had similar favored outcomes in comparison with those in the overall pooled analysis. However, LH had a longer operation time than OH in the setting of major resection (P < 0.01).ConclusionLH is technically feasible and safe for selected HCC patients with cirrhosis. LH can achieve favored short-term and long-term oncological outcomes in minor liver resection. Laparoscopic major hepatectomy (LMH) seems to offer some advantages over the open approach; however concerns about surgical and oncological safety remain. More evidence on LMH is warranted before expanding its indication to patients with cirrhosis.

Biological impact of an enhanced recovery after surgery programme in liver surgery

Background The clinical and economic impacts of enhanced recovery after surgery (ERAS) programmes have been demonstrated extensively. Whether ERAS protocols also have a biological effect remains unclear. This study aimed to investigate the biological impact of an ERAS programme in patients undergoing liver surgery. Methods A retrospective analysis of patients undergoing liver surgery (2010–2018) was undertaken. Patients operated before and after ERAS implementation in 2013 were compared. Surrogate markers of surgical stress were monitored: white blood cell count (WBC), C-reactive protein (CRP) level, albumin concentration, and haematocrit. Their perioperative fluctuations were defined as Δvalues, calculated on postoperative day (POD) 0 for Δalbumin and Δhaematocrit and POD 2 for ΔWBC and ΔCRP. Results A total of 541 patients were included, with 223 and 318 patients in non-ERAS and ERAS groups respectively. Groups were comparable, except for higher rates of laparoscopy (24.8 versus 11.2 per cent; P < 0.001) and major resection (47.5 versus 38.1 per cent; P = 0.035) in the ERAS group. Patients in the ERAS group showed attenuated ΔWBC (2.00 versus 2.75 g/l; P = 0.013), ΔCRP (60 versus 101 mg/l; P <0.001) and Δalbumin (12 versus 16 g/l; P < 0.001) compared with those in the no-ERAS group. Subgroup analysis of open resection showed similar results. Multivariable analysis identified ERAS as the only independent factor associated with high ΔWBC (odds ratio (OR) 0.65, 95 per cent c.i. 0.43 to 0.98; P = 0.038), ΔCRP (OR 0.41, 0.23 to 0.73; P = 0.003) and Δalbumin (OR 0.40, 95 per cent c.i. 0.22 to 0.72; P = 0.002). Conclusion Compared with conventional management, implementation of ERAS was associated with an attenuated stress response in patients undergoing liver surgery.

A Pilot Study of Enhance Recovery after Surgery (ERAS) for Liver Resection

Background: Morbidity post hepatectomy still remain persistent throughout decades compared to other surgery. Modern approach have been introduced to improve safety and reduce morbidity whilst at the same time enhance patient recovery. Thus, enhanced recovery after surgery or fast track recovery program for liver resection was initiated. Objective: The aim of this study was to achieve discharge by postoperative day 3 for minor resection and day 5 for major resection. Design and Setting: This is a prospective study conducted in Hospital Universiti Kebangsaan Malaysia (HUKM) from September 2014 till April 2015. Material and Methods: All patients undergoing open liver resection were included in the study. They were then managed post operatively according to ERAS protocol that was drawn up based on previous studies. Patient’s demographics data, intra operative parameters, postoperative complications and adherence to postoperative recovery protocol were recorded. Results: Seventeen patients (7 major and 10 minor resection) were recruited. The mean length of hospital stay for minor resection was 5.9 and major resection was 9.6 .With regards to the targets, 4 out of 10 (40%)patients in minor resection group and 4 out 7 (57.1%) in the major group were discharged on time. 9 patients had postoperative complications with no mortality recorded. In terms of the ERAS protocol targets, the PCA morphine discontinuation target was achieved in 15 patients (88.3%) ,nasogastric tube removal (13 patients -76.5%) , urinary cathether removal (6 patients - 35.3%), abdominal drains removal (9 patients-52.9%) and resumption of full diet was achieved by 82.4% (14 patients). Conclusion: From these overall achievement, most of our targets have been met and this shows that our ERAS protocol is safe to be applied to patient undergoing hepatectomy. Limitations: Some patients had achieved their target but not discharged for unknown reason.

A simple and clinically applicable model to predict liver-related morbidity after hepatic resection for hepatocellular carcinoma

Background & aim Hepatic resection is a treatment option for patients with hepatocellular carcinoma (HCC). However, factors associated with candidacy for resection and predictive of liver-related morbidity after resection for HCC remain unclear. This study aimed to assess candidacy for liver resection in patients with HCC and to design a model predictive of liver-related morbidity after resection. Methods A retrospective analysis of 1,565 patients who underwent liver resection for HCC between January 2016 and December 2017 was performed. The primary outcome was liver-related morbidity, including post-hepatectomy biochemical dysfunction (PHBD), ascites, hepatic encephalopathy, rescue liver transplantation, and death from any cause within 90 days. PHBD was defined as international normalized ratio (INR) > 1.5 or hyperbilirubinemia (> 2.9 mg/dL) on postoperative day ≥ 5. Results The 1,565 patients included 1,258 (80.4%) males and 307 (19.6%) females with a mean age of 58.3 years. Of these patients, 646 (41.3%) and 919 (58.7%) patients underwent major and minor liver resection, respectively. Liver-related morbidity was observed in 133 (8.5%) patients, including 77 and 56 patients who underwent major and minor resection, respectively. A total of 83 (5.3%) patients developed PHBD. Multivariate analysis identified cut-off values of the platelet count, serum albumin concentration, and ICG R15 value for predicting liver-related morbidity after resection. A model predicting postoperative liver-related morbidity was developed, which included seven factors: male sex, age ≥ 55 years, ICG R15 value ≥ 15%, major resection, platelet count < 150,000/mm3, serum albumin concentration < 3.5 g/dL, and INR > 1.1. Conclusion Hepatic resection for HCC was safe with 90-day liver-related morbidity and mortality rates of 8.5% and 0.8%, respectively. The developed point-based scoring system with seven factors could allow the prediction of the risk of liver-related morbidity after resection for HCC.