Timothy G. John

Evaluation of long-term survival after hepatic resection for metastatic colorectal cancer: a multifactorial model of 929 patients.

Objective:To identify risk factors associated with cancer-specific survival and develop a predictive model for patients undergoing primary hepatic resection for metastatic colorectal cancer. Background:No published studies investigated collectively the inter-relation of factors related to patient cancer-specific survival after hepatectomy for metastatic colorectal cancer. Methods:Clinical, pathologic, and complete follow-up data were prospectively collected from 929 consecutive patients undergoing primary (n = 925) or repeat hepatic resection (n = 80) for colorectal liver metastases at a tertiary referral center from 1987 to 2005. Parametric survival analysis was used to identify predictors of cancer-specific survival and develop a predictive model. The model was validated using measures of discrimination and calibration. Results:Postoperative mortality and morbidity were 1.5% and 25.9%, respectively. 5-year and 10-year cancer-specific survival were 36% and 23%. On multivariate analysis, 7 risk factors were found to be independent predictors of poor survival: number of hepatic metastases >3, node positive primary, poorly differentiated primary, extrahepatic disease, tumor diameter ≥5 cm, carcinoembyonic antigen level >60 ng/mL, and positive resection margin. The first 6 of these criteria were used in a preoperative scoring system and the last 6 in the postoperative setting. Patients with the worst postoperative prognostic criteria had an expected median cancer-specific survival of 0.7 years and a 5-year cancer-specific survival of 2%. Conversely, patients with the best prognostic postoperative criteria had an expected median cancer-specific survival of 7.4 years and a 5-year cancer-specific survival of 64%. When tested both predictive models fitted the data well with no significant differences between observed and predicted outcomes (P > 0.05). Conclusion:Resection of liver metastases provides good long-term cancer-specific survival benefit, which can be quantified pre- or postoperatively using the criteria described. The “Basingstoke Predictive Index” may be used for risk-stratifying patients who may benefit from intensive surveillance and selection for adjuvant therapy and trials.

Repeat hepatic resection for recurrent colorectal liver metastases is associated with favourable long-term survival†

The management of patients with recurrent colorectal liver metastases (RCLM) remains controversial. This study aimed to determine whether repeat liver resection for RCLM could be performed with acceptable morbidity, mortality and long‐term survival.

Quantification of risk of a positive (R1) resection margin following hepatic resection for metastatic colorectal cancer: An aid to clinical decision-making

BACKGROUND AND AIMS Margin involvement following liver resection for colorectal cancer is associated with early disease recurrence and shorter long-term survival. This study aimed to develop a predictive index for quantifying the likelihood of a positive resection margin (R1) for patients undergoing hepatic resection for metastatic colorectal cancer. METHODS Clinical, pathological and complete follow-up data were prospectively collected from 1005 consecutive liver resections performed in 929 patients for colorectal liver metastases with curative intent at a single centre between 1987 and 2005. Ninety-four resections in 81 patients with extra-hepatic disease were excluded, leaving 911 resections (844 primary and 67 repeat) in 848 patients for analysis. Multivariate logistic regression was used to identify independent predictors of margin involvement and from the beta-coefficients generated, develop a predictive model that was validated using measures of discrimination and calibration. RESULTS There were 80 (8.8%) R1 resections, with a 5-year cancer-specific survival for R0 and R1 hepatic resections of 39.7% and 17.8%, respectively; p<0.001. On multivariate analysis, five risk factors were found to be independent predictors of an R1 resection: non-anatomical resection vs. anatomical resection (odds ratio (OR)=4.3, p=0.001), >3 hepatic metastases involving >50% of the liver vs. <3 metastases (OR=4.0, p<0.001); bilobar vs. unilobar disease (OR=2.9, p<0.001); repeat vs. primary hepatic resection (OR=3.1, p=0.006); abnormal vs. normal pre-operative liver function tests (OR=1.6, p=0.044). These five factors were used to develop a predictive model, which when tested, fitted the data well, with an area under the receiver operating characteristic curve of 78.1% (S.E.=2.7%). CONCLUSIONS This study describes an accurate model for quantifying the risk of a positive margin following hepatic resection for liver metastases. It may be used pre-operatively by multi-disciplinary teams to identify patients who may benefit from neoadjuvant therapy prior to liver surgery, thus minimizing the risk of a positive resection margin.

Open liver resection for colorectal metastases: better short- and long-term outcomes in patients potentially suitable for laparoscopic liver resection

BACKGROUND There is no prospective randomized data comparing laparoscopic to open hepatectomy. This study compared short- and long-term outcomes in patients undergoing hepatectomy for colorectal metastases (CRM), who were suitable for either laparoscopic or open surgery. METHODS Data were prospectively collected from consecutive patients undergoing hepatic resection of CRM at a single centre (1987-2007). Patients who were suitable for laparoscopic resection (Group 1) were compared with patients whose tumour characteristics would best be considered for open resection (Group 2). RESULTS Out of 1152 hepatectomies, 266 (23.1%) were deemed suitable for a laparoscopic approach. The median (IQR) number of metastases was greater in Group 2 [2(1-20) vs. 1(1-10), P < 0.001], as was the mean (SD) tumour size [5.3(3.6) cm vs. 3.3(1.2) cm, P < 0.001]. The median (IQR) operation time [210 (70) min vs. 240 (90) min, P < 0.001] and blood loss [270 (265) ml vs. 355 (320) ml, P < 0.001] were less in Group 1. There was no difference in length of stay, morbidity or mortality. Patients in Group 2 had a higher R1 resection rate (14.9%) compared with Group 1 (4.5%, P < 0.001) and lower 5-year survival (37.8% vs. 44.2%, P= 0.005). DISCUSSION Current criteria for laparoscopic hepatectomy selects patients who have more straight-forward surgery, with less risk of an involved resection margin and better long-term survival, compared with patients unsuited to a laparoscopic approach. Clearly defined criteria for laparoscopic hepatectomy are essential to allow meaningful analysis of outcomes and the results of unrandomized series of laparoscopic hepatectomies must be interpreted with caution.

The impact of pre-operative serum creatinine on short-term outcomes after liver resection.

BACKGROUND The aim of the present study was to determine whether raised pre-operative serum creatinine increased the risk of renal failure after liver resection. METHOD Data were studied from 1535 consecutive liver resections. Outcomes in patients with pre-operative creatinine </=124 micromol/l (Group 1) were compared with those with pre-operative creatinine >/=125 micromol/l (Group 2). RESULTS The median age of the 1446 (94.3%) patients resected in Group 1 was 62 years compared with 67 years in the 88 (5.7%) patients in Group 2 (P < 0.0001). Similarly this latter group had double the number of patients who were American Society of Anesthesiologists (ASA) III or IV (34.1% vs. 15.2%, P= 0.00004). Overall, the incidence of post-operative renal failure requiring haemofiltration was low (0.9%) but significantly more in Group 2 patients (5.7% vs. 0.6, P= 0.0007). In addition, patients in Group 2 were more likely to suffer acute kidney injury post-operatively (18.2% vs. 4.3%, P < 0.0001). Patients with acute kidney injury had significantly higher blood loss. Although there was no difference in mortality, patients in Group 2 had higher post-operative morbidity (37.5%) than Group 1 (21.7%, P= 0.0006), with the incidence of cardiorespiratory complications being higher in Group 2 (25.9% vs. 8.9%, P= 0.0025). CONCLUSIONS After liver resection, renal failure is rare but patients with an elevated creatinine pre-operatively are at an increased risk of both renal and non-renal complications.

Laparoscopic staging in selected patients with colorectal liver metastases as a prelude to liver resection

BACKGROUND Careful selection of patients with colorectal liver metastases for liver resection should minimize the risk of unnecessary laparotomy due to unresectable disease. The impact of staging laparoscopy with laparoscopic ultrasonography (LapUS) on clinical decision making in selected patients with potentially resectable colorectal liver metastases was evaluated. PATIENTS AND METHODS Staging laparoscopy with or without LapUS was performed in 77 of 415 consecutive patients (19%) with colorectal liver metastases deemed potentially resectable following liver-specific CT and/or MRI scanning. Retrospective analysis of prospectively collected data compared clinical outcomes with those in whom laparoscopy had been deferred in favour of laparotomy. RESULTS Staging laparoscopy was successful in 76 of 77 patients (99%). Adverse events occurred in three patients (4%): bowel injury n=2; late port site metastasis, n=1. Laparoscopic staging identified factors precluding curative resection in 16 patients (21%), thus averting unnecessary laparotomy. Of the 57 patients (74%) staged laparoscopically who underwent surgical exploration, 7 patients (12%) were unresectable and liver resection was achieved in 50 (88%). DISCUSSION Laparoscopic staging remains useful in detecting occult intra- and extra-hepatic tumour in selected patients with potentially operable colorectal liver metastases.

Patient-Reported Outcomes After Hepatic Resection of Colorectal Cancer Metastases

PURPOSE Hepatic resection of colorectal carcinoma (CRC) liver metastases is increasing, but evidence for the impact of surgery on patient-reported outcomes (PROs) is limited. This study aimed to describe comprehensively the impact of liver surgery for CRC hepatic metastases on PROs. PATIENTS AND METHODS Consecutive patients selected for hepatic resection completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and Quality of Life Questionnaire-Liver Metastases C21 before and 3, 6, and 12 months after surgery. For functional scales, mean scores with 95% CIs were calculated at each time point, with differences in scores of at least 10 points considered clinically significant. Responses to symptom scales and items were categorized as minimal or severe. Proportions and 95% CIs for each symptom category were calculated. RESULTS Hepatic surgery was planned in 241 patients but abandoned in nine because of unresectable disease. There were two postoperative deaths, 58 complications (25.2%), and 32 patients (14.9%) with disease recurrence. Questionnaire compliance was excellent (> 95% at all time points). After surgery, most functional aspects of health decreased, and the proportions of patients with severe symptoms increased; role function deteriorated significantly, and 30% of patients reported severe activity/vigor problems. Functional scales recovered by 6 months and were maintained at 1 year. Postoperative symptoms returned to baseline levels at 12 months, but 32.1% of patients reported severe problems with sexual dysfunction and 11.9% with abdominal pain. CONCLUSION These findings provide new evidence regarding outcomes of liver resection for CRC metastases. It is recommended that patients be reassured that surgery has a minimal and short-lived detrimental impact on health.

Propensity score-matched outcomes analysis of the liver-first approach for synchronous colorectal liver metastases.

Liver resection before primary cancer resection is a novel strategy advocated for selected patients with synchronous colorectal liver metastases (sCRLM). This study measured outcomes in patients with sCRLM following a liver‐first or classical approach, and used a validated propensity score.

Postoperative pain control using continuous i.m. bupivacaine infusion plus patient-controlled analgesia compared with epidural analgesia after major hepatectomy

OBJECTIVES There is debate concerning the best mode of delivery of analgesia following liver resection, with continuous i.m. infusion of bupivacaine (CIB) plus patient-controlled i.v. analgesia (PCA) suggested as an alternative to continuous epidural analgesia (CEA). This study compares these two modalities. METHODS A total of 498 patients undergoing major hepatectomy between July 2004 and July 2011 were included. Group 1 received CIB + PCA (n = 429) and Group 2 received CEA (n = 69). Groups were analysed on baseline patient and surgical characteristics. Primary endpoints were pain severity scores and total opioid consumption. Secondary endpoints were pain management failures, need for rescue medication, postoperative (opioid-related) morbidity and hospital length of stay (LoS). RESULTS In both groups pain was well controlled and >70% of patients had no or minimal pain on PoDs 1 and 2. The numbers of patients experiencing severe pain were similar in both groups: PoD 1 at rest: 0.3% in Group 1 and 0% in Group 2 (P = 1.000); PoD 1 on movement: 8% in Group 1 and 2% in Group 2 (P = 0.338); PoD 2 at rest: 0% in Group 1 and 2% in Group 2 (P = 0.126), and PoD 2 on movement: 5% in Group 1 and 5% in Group 2 (P = 1.000). Although the CIB + PCA group required more opioid rescue medication on PoD 0 (53% versus 22%; P < 0.001), they used less opioids on PoDs 0-3 (P ≤ 0.001), had lower morbidity (26% versus 39%; P = 0.018), and a shorter LoS (7 days versus 8 days; P = 0.005). CONCLUSIONS The combination of CIB + PCA provides pain control similar to that provided by CEA, but facilitates lower opioid consumption after major hepatectomy. It has the potential to replace epidural analgesia, thereby avoiding the occurrence of rare but serious complications.

Predictive Models in Colorectal Liver Metastases – Can We Personalize Treatment and Outcome?

Background/Aims: Hepatic resection for colorectal liver metastases offers patients the best chance of long-term survival. Survival rates after resection range from 25 to 60%. Predictive models may risk-stratify patients and allow improved selection for surgery or other therapies. This review aims to achieve consensus regarding the predictors of survival after hepatic resection for colorectal metastases and evaluate current predictive models of outcome. Methods: A comprehensive literature review of published studies with more than 500 patients describing models for predicting long-term survival in patients undergoing hepatic resection for colorectal metastases. Results: Five large predictive models have been published to date. The three predictive models developed from the largest series agree over the key independent predictors of poor long-term outcome for patients undergoing liver resection for colorectal metastases. All five models have individual shortcomings, and whilst three have been internally validated, two have been externally validated with conflicting results. The Basingstoke Predictive Index appears to be accurate and internally validated. Conclusions: There is need within the international surgical oncology community for consensus regarding a predictive model to be universally adopted for risk-stratifying patients who may benefit from intensive surveillance and selection for adjuvant therapy and clinical trials.