Expectations of outcomes in patients with colorectal cancer.

BACKGROUND: Understanding patients' expectations of their treatment is critical to ensure appropriate treatment decisions, and to explore how expectations influence coping, quality of life and well-being. This study aimed to examine these issues related to treatment in patients with colorectal cancer. METHODS: A literature search from January 1946 to September 2016 was performed to identify available data regarding patients' expectations of outcomes following colorectal cancer treatment. A narrative synthesis of the evidence was planned. RESULTS: Of 4337 items initially identified, 20 articles were included in the review. In studies presenting data on overall and short-term survival, patients considerably overestimated prognosis. Patients also had unrealistic expectations of the negative aspects of chemotherapy and stomas. There was marked discordance between patients' and clinicians' expectations regarding chemotherapy, end-of-life care, bowel function and psychosocial outcomes. Level of education was the most consistent factor influencing the accuracy of patients' expectations. CONCLUSION: Patients with colorectal cancer frequently have unrealistic expectations of treatment. Marked disparities exist between patients' and clinicians' expectations of outcomes.

Clinical outcomes of left hepatic trisectionectomy for hepatobiliary malignancy.

BACKGROUND: Left hepatic trisectionectomy (LHT) is a challenging major anatomical hepatectomy with a high complication rate and a worldwide experience that remains limited. The aim of this study was to describe changes in surgical practice over time, to analyse the outcomes of patients undergoing LHT for hepatobiliary malignancy, and to identify factors associated with morbidity and mortality. METHODS: A cohort study was undertaken of patients who underwent LHT at a single tertiary hepatobiliary referral centre between January 1993 and March 2013. Univariable and multivariable analysis was used to identify factors associated with short- and long-term outcomes following LHT. RESULT: Some 113 patients underwent LHT for colorectal liver metastasis (57), hilar cholangiocarcinoma (22), intrahepatic cholangiocarcinoma (12) and hepatocellular carcinoma (11); 11 patients had various other indications. Overall morbidity and 90-day mortality rates were 46.0 and 9.7 per cent respectively. Overall 1- and 3-year survival rates were 71.3 and 44.4 per cent respectively. Total hepatic vascular exclusion and intraoperative blood transfusion were independent predictors of postoperative morbidity, whereas blood transfusion was the only factor predictive of in-hospital mortality. Time period analysis revealed a decreasing trend in blood transfusion, duration of hospital stay, and postoperative morbidity and mortality in the last 5 years. CONCLUSION: Morbidity, mortality and long-term survival after LHT support its use in selected patients with a significant tumour burden.

Cost-utility analysis of operative versus non-operative treatment for colorectal liver metastases.

BACKGROUND: Surgical resection of colorectal liver metastases (CRLMs) is the standard of care when possible, although this strategy has not been compared with non-operative interventions in controlled trials. Although survival outcomes are clear, the cost-effectiveness of surgery is not. This study aimed to estimate the cost-effectiveness of resection for CRLMs compared with non-operative treatment (palliative care including chemotherapy). METHODS: Operative and non-operative cohorts were identified from a prospectively maintained database. Patients in the operative cohort had a minimum of 10 years of follow-up. A model-based cost-utility analysis was conducted to quantify the mean cost and quality-adjusted life-years (QALYs) over a lifetime time horizon. The analysis was conducted from a healthcare provider perspective (UK National Health Service) in a secondary care (hospital) setting. RESULTS: Median survival was 41 and 21 months in the operative and non-operative cohorts respectively (P < 0·001). The operative strategy dominated non-operative treatments, being less costly (€22,200 versus €32,800) and more effective (4·017 versus 1·111 QALYs gained). The results of extensive sensitivity analysis showed that the operative strategy dominated non-operative treatment in every scenario. CONCLUSION: Operative treatment of CRLMs yields greater survival than non-operative treatment, and is both more effective and less costly.

Management of gallbladder dyskinesia: patient outcomes following positive 99mtechnetium (Tc)-labelled hepatic iminodiacetic acid (HIDA) scintigraphy with cholecystokinin (CCK) provocation and laparoscopic cholecystectomy.

AIMS: To evaluate clinical outcomes in patients with typical biliary pain, normal ultrasonic findings, and a positive (99m)technetium (Tc)-labelled hepatic iminodiacetic acid analogue (HIDA) scintigraphy with cholecystokinin (CCK) provocation indicating gallbladder dyskinesia, as per Rome III criteria, undergoing laparoscopic cholecystectomy (LC). METHODS AND MATERIALS: Consecutive patients undergoing LC for gallbladder dyskinesia were identified retrospectively. They were followed up by telephone interview and review of the electronic case records to assess symptom resolution. RESULTS: One hundred consecutive patients (median age 44; 80% female) with abnormal gallbladder ejection fraction (GB-EF <35%) were followed up for a median of 12 months (range 2-80 months). Following LC, 84% reported symptomatic improvement and 52% had no residual pain. Twelve percent had persisting preoperative-type pain of either unchanged or worsening severity. Neither pathological features of chronic cholecystitis (87% of 92 incidences when histology available) nor reproduction of pain on CCK injection were significantly predictive of symptom outcome or pain relief post-LC. CONCLUSION: In one of the largest outcome series of gallbladder dyskinesia patients in the UK with a positive provocation HIDA scintigraphy examination and LC, the present study shows that the test is a useful functional diagnostic tool in the management of patients with typical biliary pain and normal ultrasound, with favourable outcomes following surgery.

Controlled infection with a therapeutic virus defines the activation kinetics of human natural killer cells in vivo.

Human natural killer (NK) cells play an important role in anti-viral immunity. However, studying their activation kinetics during infection is highly problematic. A clinical trial of a therapeutic virus provided an opportunity to study human NK cell activation in vivo in a controlled manner. Ten colorectal cancer patients with liver metastases received between one and five doses of oncolytic reovirus prior to surgical resection of their tumour. NK cell surface expression of the interferon-inducible molecules CD69 and tetherin peaked 24-48 h post-infection, coincident with a peak of interferon-induced gene expression. The interferon response and NK cell activation were transient, declining by 96 h post-infection. Furthermore, neither NK cell activation nor the interferon response were sustained in patients undergoing multiple rounds of virus treatment. These results show that reovirus modulates human NK cell activity in vivo and suggest that this may contribute to any therapeutic effect of this oncolytic virus. Detection of a single, transient peak of activation, despite multiple treatment rounds, has implications for the design of reovirus-based therapy. Furthermore, our results suggest the existence of a post-infection refractory period when the interferon response and NK cell activation are blunted. This refractory period has been observed previously in animal models and may underlie the enhanced susceptibility to secondary infections that is seen following viral infection.

Outcome after liver resection in patients presenting with simultaneous hepatopulmonary colorectal metastases.

BACKGROUND: The most common sites of metastasis from colorectal cancer (CRC) are hepatic and pulmonary; they can present simultaneously (hepatic and pulmonary metastases) or sequentially (hepatic then pulmonary metastases, or vice versa). Simultaneous disease may be aggressive, and thus may be approached with caution by the clinician. The aim of this study was to determine the outcomes following hepatic and pulmonary resection for simultaneously presenting metastatic CRC. METHODS: A retrospective review was undertaken of a prospectively maintained database to identify patients presenting with simultaneous hepatopulmonary disease who underwent hepatic resection. Patients' electronic records were used to identify clinicopathological variables. The log rank test was used to determine survival, and χ(2) analysis to determine predictors of failure of intended treatment. RESULTS: Fifty-nine patients were identified and underwent hepatic resection; median survival was 45·4 months and the 5-year survival rate 38 per cent. Twenty-two patients (37 per cent) did not have the intended pulmonary intervention owing to progression or recurrence of disease. Thirty-seven patients who progressed to hepatopulmonary resection had a median survival of 54·2 months (5-year survival rate 43 per cent). Those who had hepatic resection alone had a median survival of 24·0 months (5-year survival rate 30 per cent). Failure to progress to pulmonary resection was predicted by heavy nodal burden of primary colorectal disease and bilobar hepatic metastases. Redo pulmonary surgery following pulmonary recurrence did not confer a survival benefit. CONCLUSION: Selected patients with simultaneous hepatopulmonary CRC metastases should be considered for attempted curative resection, but some patients may not receive the intended treatment owing to progression of pulmonary disease after hepatic resection.

Performance of prognostic scores in predicting long-term outcome following resection of colorectal liver metastases.

BACKGROUND: Ten-year survival appears to define cure following resection of colorectal liver metastases (CRLMs). Various scores exist to predict outcome at 5 years. This study applied several scores to a patient cohort with 10 years of actual follow-up to assess their performance beyond 5 years. METHODS: The study included consecutive patients who underwent liver resection at a single institution between 1992 and 2001. The ability of eight prognostic scoring systems to predict disease-free (DFS) and disease-specific (DSS) survival was analysed using the C-statistic. RESULTS: Among 286 patients, the 1-, 3-, 5- and 10-year actual DSS rates were 86.6, 58.3, 39.5 and 24.5 per cent respectively. Seventy patients underwent 105 further resections for recurrent disease, of which 84.8 per cent were within 5 years of follow-up. Analysis of C-statistics showed only one score--the Rees postoperative index--to be a significant predictor of DFS and DSS at all time points. The remaining scores performed less well, and regularly showed no significant improvement in predictive accuracy over what would be expected by chance alone. No score yielded a C-statistic in excess of 0.8 at any time point. CONCLUSION: Although available risk scores can predict DFS and DSS, none does so with sufficient discriminatory accuracy to identify all episodes of recurrent disease. A non-negligible proportion of patients develop recurrent disease beyond 5 years of follow-up and so surveillance beyond this point may be advantageous.

Viral warfare! Front-line defence and arming the immune system against cancer using oncolytic vaccinia and other viruses.

BACKGROUND: Despite mankind's many achievements, we are yet to find a cure for cancer. We are now approaching a new era which recognises the promise of harnessing the immune system for anti-cancer therapy. Pathogens have been implicated for decades as potential anti-cancer agents, but implementation into clinical therapy has been plagued with significant drawbacks. Newer 'designer' agents have addressed some of these concerns, in particular, a new breed of oncolytic virus: JX-594, a genetically engineered pox virus, is showing promise. OBJECTIVE: To review the current literature on the use of oncolytic viruses in the treatment of cancer; both by direct oncolysis and stimulation of the immune system. The review will provide a background and historical progression for the surgeon on tumour immunology, and the interplay between oncolytic viruses, immune cells, inflammation on tumourigenesis. METHODS: A literature review was performed using the Medline database. CONCLUSIONS: Viral therapeutics hold promise as a novel treatment modality for the treatment of disseminated malignancy. It provides a multi-pronged attack against tumour burden; direct tumour cell lysis, exposure of tumour-associated antigens (TAA), induction of immune danger signals, and recognition by immune effector cells.

Nodular regenerative hyperplasia (NRH) complicating oxaliplatin chemotherapy in patients undergoing resection of colorectal liver metastases.

INTRODUCTION: Sinusoidal obstructive syndrome (SOS) is well associated with the use oxaliplatin-based chemotherapy, and represents a spectrum of hepatotoxicity, with nodular regenerative hyperplasia (NRH) representing the most significant degree of injury. The aim of this study was to determine the prevalence of NRH in patients undergoing resection of colorectal liver metastases (CRLM) and to determine its impact on outcome. METHODS: From January 2000 to December 2010, some 978 first primary liver resections were performed for CRLM. A prospectively maintained database was analysed to identify all patients with evidence of NRH in the non-tumour portion of their histopathology specimens. Clinical data of these patients was reviewed and outcomes assessed. RESULTS: Five patients exhibited NRH (four males, one female) with a median age of 69 years (range: 35-74). Three patients presented with synchronous hepatic metastases, and two with metachronous lesions. All received at least 6 cycles of oxaliplatin as either adjuvant or neo-adjuvant chemotherapy. Only one patient developed a post-operative complication namely transient hepatic failure that required a 4-day stay in the intensive care unit. The median hospital stay was 6 days (range: 6-14 days). There were no 90-day mortalities. One patient is alive and disease free at 55 months, the remaining 4 died of recurrent disease between 37 and 70 months following diagnosis of their primary tumours. CONCLUSIONS: NRH is not an uncommon finding amongst patients with SOS with all patients having received oxaliplatin-based chemotherapy. Data on outcome would suggest no increased morbidity and mortality associated with the presence of NRH.

Variation in referral practice for patients with colorectal cancer liver metastases.

BACKGROUND: Half of patients with colorectal cancer develop liver metastases. There remains great variability between hospitals in rates of liver resection for colorectal cancer liver metastases (CLM). This study aimed to determine how many patients with potentially resectable CLM are not seen by specialist liver surgeons. METHODS: Patients presenting with new CLM in a cancer network consisting of a tertiary centre and seven attached hospitals were studied prospectively over 12 months. Data were collected retrospectively for patients who did not have a complete data set. Outcomes for patients referred to the liver tertiary centre were collated. The radiology of tumours deemed inoperable by the local colorectal specialist teams was reviewed by specialist liver surgeons and radiologists. RESULTS: In total, 631 patients with CLM were assessed. Prospective data were complete for 241 patients, and 64 (26.6 per cent) of these were referred to the specialist liver team for consideration of resection. No decision was documented for 16 patients (6.6 per cent). Of those not referred, 30 (18.6 per cent) were deemed unfit or refused and 131 (81.4 per cent) were thought inoperable. Referral rates varied between hospitals (13-43.6 per cent). Of 131 patients deemed fit but inoperable by the colorectal specialist teams, 38 (29.0 per cent) were deemed operable and 20 (15.3 per cent) had equivocal imaging when assessed retrospectively by liver specialists. In total, 142 of the 631 patients were referred to liver specialists for consideration of treatments, and 107 (75.4 per cent) treated with curative intent. CONCLUSION: A considerable number of patients with potentially resectable CLM are not assessed by specialist liver teams. Improved referral rates could greatly improve resection rates for CLM, which may improve outcomes for patients with colorectal cancer.

Fatty liver disease as a predictor of local recurrence following resection of colorectal liver metastases.

BACKGROUND: Obesity and tissue adiposity constitute a risk factor for several cancers. Whether tissue adiposity increases the risk of cancer recurrence after curative resection is not clear. The present study analysed the influence of hepatic steatosis on recurrence following resection of colorectal liver metastases. METHODS: A prospective cohort of patients who had primary resection of colorectal liver metastases in two major hepatobiliary units between 1987 and 2010 was studied. Hepatic steatosis was assessed in non-cancerous resected liver tissue. Patients were divided into two groups based on the presence of hepatic steatosis. The association between hepatic steatosis and local recurrence was analysed, adjusting for relevant patient, pathological and surgical factors using Cox regression and propensity score case-match analysis. RESULTS: A total of 2715 patients were included. The cumulative local (liver) disease-free survival rate was significantly better in the group without steatosis (hazard ratio (HR) 1·32, 95 per cent confidence interval 1·16 to 1·51; P < 0·001). On multivariable analysis, hepatic steatosis was an independent risk factor for local liver recurrence (HR 1·28, 1·11 to 1·47; P = 0·005). After one-to-one matching of cases (steatotic, 902) with controls (non-steatotic, 902), local (liver) disease-free survival remained significantly better in the group without steatosis (HR 1·27, 1·09 to 1·48; P = 0·002). Patients with steatosis had a greater risk of developing postoperative liver failure (P = 0·001). CONCLUSION: Hepatic steatosis was an independent predictor of local hepatic recurrence following resection with curative intent of colorectal liver metastases.

Biliary and portal vein strictures following treatment of Hodgkin's lymphoma.

Treatment of abdominal lymphoma can be associated with bowel stricture or perforation. Rarely, the common bile duct or portal vein can be involved. This is the first case of stricture formation of both the portal vein and common bile duct in a patient following successful treatment of lymphoma. The development of extensive hilar varices rendered surgical management high risk. A staged approach to treatment was used. First, a percutaneous portal vein stent was placed, resulting in resolution of the hilar varices. This was followed by a surgical hepaticojejunostomy, performed without complication. Gastrointestinal complications are rare following treatment of lymphoma but may affect a variety of sites. The safe and effective treatment of this case highlights the benefit of a multidisciplinary approach to complex medical and surgical problems.

Repeat hepatic resection for colorectal liver metastases.

BACKGROUND: Some 75-80 per cent of patients undergoing liver resection for colorectal liver metastases develop intrahepatic recurrence. A significant number of these can be considered for repeat liver surgery. This study examined the outcomes of repeat liver resection for the treatment of recurrent colorectal metastases confined to the liver. METHODS: Patients who underwent repeat liver resection in a single tertiary referral hepatobiliary centre were identified from a database. Clinicopathological variables were analysed to assess factors predictive of survival. RESULTS: A total of 195 patients underwent repeat resection between 1993 and 2010. Median age was 63 years, and the median interval between first and repeat resection was 13·8 months. Thirty-three patients (16·9 per cent) underwent completion hemihepatectomy or extended hemihepatectomy and the remainder had non-anatomical or segmental resection. The 30-day mortality rate was 1·5 per cent, and the overall 30-day morbidity rate was 20·0 per cent. Overall 1-, 3- and 5-year survival rates were 91·2, 44·3 and 29·4 per cent respectively. Tumour size 5 cm or greater was the only independent predictor of overall survival (relative risk 1·71, 95 per cent confidence interval 1·08 to 2·70; P = 0·021). Neoadjuvant chemotherapy before resection, perioperative blood transfusion, bilobar disease, R1 resection margin and multiple metastases were among factors that did not significantly influence survival. CONCLUSION: Repeat hepatic resection remains the only curative option for patients presenting with recurrent colorectal liver metastases.

Omega-3 polyunsaturated fatty acids for the treatment and prevention of colorectal cancer.

Omega (ω)-3 polyunsaturated fatty acids (PUFAs) are naturally occurring substances that are well tolerated and have been used extensively for the prevention of cardiovascular disease. More recently, ω-3 PUFAs have been recognised to have anticancer activity. There is also evidence suggesting improved efficacy and/or tolerability of conventional cancer chemotherapy when administered with ω-3 PUFAs. The purpose of this review is to (i) describe the mechanisms by which ω-3 PUFAs are thought to have antineoplastic activity, (ii) review published preclinical and clinical studies that support anti-colorectal cancer activity and (iii) summarise current clinical trials investigating the potential therapeutic role(s) of ω-3 PUFAs at different stages of colorectal carcinogenesis, from adenoma (polyp) prevention to treatment of established malignant disease and prevention of cancer recurrence.

Epidural analgesia and liver resection: postoperative coagulation disorders and epidural catheter removal.

BACKGROUND: The aim of this study was to quantify the duration and severity of postoperative coagulopathy in order to establish the optimal time for epidural catheter removal. METHODS: In a 2-year retrospective study, 140 consecutive patients underwent major liver resection. RESULTS: Epidural catheters were present in 123 patients (87.9%). Resections were: 33 (26.8%) right hepatectomy (with or without left metastasectomy), 9 (7.3%) left hemihepatectomy (with or without right metastasectomy), 37 (30.1%) trisectionectomy (extended hemihepatectomy) and 44 (35.8%) non-anatomical metastasectomy. Surgery was quantified by segments resected (4 [range: 1-7]). Vascular inflow occlusion was used in 65.6%. Ischaemic time was 26.5 min (range: 0-104 min). Platelet count fell postoperatively and was lowest on day 2 (205±72 10(9) L(-1)). There was a significant increase in prothrombin time, activated partial thromboplastin time and International Normalised Ratio (INR) postoperatively, peaking on day 2 (21.5±5.6 s, 37.9±5.8 s and 1.9±0.5, respectively). Changes persisted beyond day 6. Epidural catheters were removed on day 5 (1-11), with a protocol criterion of INR <1.2. Actual INR on day 5 was 1.49±0.36. CONCLUSION: Despite this, no epidural or spinal haematoma was recorded.

The impact of postoperative infection on long-term outcomes in liver transplantation.

INTRODUCTION: Postoperative infection (POI) prolongs inpatient stay, delays return to normal activity, and may be detrimental to long-term survival after cancer resections. This study sought to identify the impact of postoperative infection on liver transplantation outcomes. METHODS: We analyzed our prospective database of 910 adult patients who underwent liver transplantation between 2000 and 2010 in a single UK center. POI was defined as pyrexia plus positive cultures from blood, sputum, urine, wound, or ascitic fluid. Patient demographic features and perioperative variables were analyzed for their effects on POI. The impacts of POI on overall survival (OS) and graft survival were analyzed using Kaplan-Meier curves with log-rank tests for significance, before entry into a multivariate regression analysis. We analyzed the effects of POI on the length of hospital stay (LOS) and the incidence of acute rejection episodes and readmissions within 1 year as secondary outcomes. RESULTS: Patients who developed a postoperative chest or wound infection showed poorer OS at a mean of 7.0 versus 8.8 years (P = .009) and 7.0 versus 8.8 years (P = .003), respectively. Infection in blood, ascitic fluid, or urine showed no significant impact on survival. LOS was significantly increased among patients with a wound (median 21 vs 17 days, P = .011), a sputum (median 24 vs 17 days, P < .001), or a blood infection (median 32 vs 17 days, P < .001). Higher rates of intraoperative blood transfusion were observed among subjects who developed a chest or a wound infection. There was no difference in other variables between those who did versus did not develop an infection. Upon multivariate analysis, wound infection was the strongest independent predictor of OS (P = .007). CONCLUSION: We demonstrated that wound or chest infections were associated with poorer OS. More aggressive prophylactic and/or therapeutic interventions targeting specific sites of infection may represent a simple and cost-effective measure to reduce hospital stay and improve OS.

Outcomes of intensive surveillance after resection of hepatic colorectal metastases.

BACKGROUND: The impact of computed tomography (CT)-based follow-up for the detection of resectable disease recurrence following surgery for colorectal liver metastases (CRLM) was evaluated. METHODS: Some 705 patients undergoing resection of CRLM between January 1993 and March 2007 were included. Surveillance comprised 3-monthly CT (thorax, abdomen and pelvis) in the first 2 years after surgery, 6 monthly for 3 years and annually from years 6 to 10. Survival differences following recurrence between patients managed surgically and palliatively were determined, and the cost was calculated. RESULTS: Five-year disease-free and overall survival rates were 28.3 and 32.3 per cent respectively. Of 402 patients who developed recurrence within 2 years, 88 were treated with liver resection alone and 36 with lung and/or liver resection. Their 5-year overall survival rates were 31 and 30 per cent respectively, compared with 3.9 per cent in 278 patients managed palliatively (P < 0.001). For each 3-month interval during the first year of follow-up, patients with recurrence treated surgically had better overall survival than those treated palliatively. The cost of surveillance that identified 124 patients amenable to further resection was 12,338 pounds per operated recurrence. Assuming that patients with recurrence gained 5 years' survival, the mean survival gain was 4.28 years per resection and the cost per life-year gained was 2883 pounds. CONCLUSION: Intensive 3-monthly CT surveillance after liver resection for CRLM detects recurrence that is amenable to further resection in a considerable number of patients. These patients have significantly better survival with a reasonable cost per life-year gained.