Comparable Overall Survival in Patients with Hepatocellular Carcinoma Diagnosed within and outside a Surveillance Programme: The Potential Impact of Liver Cirrhosis.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death, and its incidence is rising. Mortality from HCC is predicted to increase by 140% by 2035. Surveillance of high-risk patients with cirrhosis or chronic liver disease may be one means of reducing HCC mortality, but the level of supporting evidence for international guidelines is low/moderate. This study explores the real-world experience of HCC surveillance at a tertiary referral centre. Electronic patient records for all new HCCs diagnosed between August 2012 and December 2021 were retrospectively reviewed. Patient and tumour characteristics were evaluated, including the co-existence of chronic liver disease, cancer treatment and survival, and categorised according to HCC diagnosis within or outside a surveillance programme. Patients with HCC who presented through surveillance had smaller tumours diagnosed at an earlier stage, but this did not translate into improved overall survival. All patients in surveillance had chronic liver disease, including 91% (n = 101) with cirrhosis, compared to 45% (n = 29) in the non-surveillance cohort. We propose that the immune dysfunction associated with cirrhosis predisposes patients to a more aggressive tumour biology than the largely non-cirrhotic population in the non-surveillance group.

Development and validation of a risk score to predict the overall survival following surgical resection of hepatocellular carcinoma in non-cirrhotic liver.

BACKGROUND: The aim of this study was to develop and validate a risk score to predict overall survival (OS) in patients undergoing surgical resection for hepatocellular carcinoma in non-cirrhotic liver (NC-HCC). METHODS: Patients who underwent resection for NC-HCC between 2004 and 2013 were identified from the SEER database. A derivation set of 75% of this cohort was used to develop a risk score. This was then internally validated on the remaining patients, and externally validated using a cohort of patients from The HPB Unit, Birmingham, UK. RESULTS: A total of 3897 patients were included from the SEER database, with a median post-diagnosis survival of 59 months. In the derivation set, multivariable analyses identified male sex, increasing tumour size, the presence of multiple tumours, bilobar tumours and major vascular invasion as adverse prognostic factors. A risk score generated from these factors was significantly predictive of OS, and was used to classify patients into low, medium and high-risk groups. These groups had a five-year OS of 69%, 51% and 19% in the internal, and 73%, 50% and 45% in the external validation sets. CONCLUSION: The proposed risk score is useful in the selection, pre-operative consenting and counselling of patients for surgery and to allow patients to make an informed decision regarding treatment.

Future liver remnant portal or hepatic vein reconstruction at stage I of ALPPS-How far can we push the boundaries?

Preservation of the future liver remnant (FLR) vascular integrity has always been considered crucial to achieving successful liver growths after major hepatectomies. Most surgeons appeared therefore reluctant to combine stage I of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) with vascular reconstructions. Here we describe a case series, where we combine parenchymal transection and venous in- or outflow reconstruction of the FLR at stage I of ALPPS. In addition, the cold flush of the FLR or delayed portal vein embolization is applied in selected cases.

Pancreas exocrine replacement therapy is associated with increased survival following pancreatoduodenectomy for periampullary malignancy.

BACKGROUND: Although many patients undergoing pancreatoduodenectomy (PD) for cancer have pancreatic exocrine insufficiency, pancreatic enzyme replacement therapy (PERT) is not routinely used, and effects upon post-operative survival are unclear. METHODS: This review of patients undergoing PD for periampullary malignancy sought to test for an association between PERT and overall survival, with post-hoc subgroup analysis performed after stratifying patients by the year of surgery, pancreatic duct width and tumour type. RESULTS: Some 202/469 (43.1%) patients received PERT. After accounting for pathological variables and chemotherapy, PERT use was found to be independently associated with improved survival on multivariable analysis [HR 0.72 (95% CI: 0.52-0.99), p = 0.044] and on propensity matched analysis (p = 0.009). The effect of PERT upon improved survival was predominantly observed amongst patients with a dilated pancreatic duct (≥3 mm). DISCUSSION: PERT use was independently associated with improved survival following PD for cancer. The validity of this observation is supported by an effect largely confined to those patients with a dilated pancreatic duct. The nutritional status of patients undergoing PD for cancer needs further investigation and the effects of PERT require verification in further clinical studies.

Comparing clinical presentations, treatments and outcomes of hepatocellular carcinoma due to hepatitis C and non-alcoholic fatty liver disease.

INTRODUCTION: Hepatocellular carcinoma (HCC) is increasing in incidence in the UK and globally. Liver cirrhosis is the common cause for developing HCC. The common reasons for liver cirrhosis are viral hepatitis C (HCV), viral hepatitis B and alcohol. However, HCC caused by non-alcoholic fatty liver disease (NAFLD)-cirrhosis is now increasingly as a result of rising worldwide obesity. AIM: : To compare the clinical presentation, treatment options and outcomes of HCC due to HCV and NAFLD patients. METHODS: Data were collected from two liver transplant centres in the UK (Birmingham and Newcastle upon Tyne) between 2000 and 2014. We compared 275 patients with HCV-related HCC against 212 patients with NAFLD- related HCC. RESULTS: Patients in the NAFLD group were found to be significantly older ( P < 0.001) and more likely to be Caucasian ( P < 0.001). They had lower rates of cirrhosis ( P < 0.001) than those in HCV-HCC group. The NAFLD group presented with significantly larger tumours ( P = 0.009), whilst HCV patients had a higher alpha fetoprotein ( P = 0.018). NAFLD patients were more commonly treated with TACE ( P = 0.005) than the HCV patients, whilst the HCV group were significantly more likely to be transplanted ( P < 0.001). In patients selected for liver transplantation, 5-year survival rates in NAFLD were not significantly different from HCV-HCC (44 and 56% respectively, P = 0.102). CONCLUSION: In this study, NAFLD patients presented with larger tumours that were less likely to be amenable to curative therapy, as compared with HCV patients. Despite this disadvantage, patients with NAFLD had similar overall survival compared to patients with HCV.

Role of neoadjuvant chemotherapy in resectable synchronous colorectal liver metastasis; An international multi-center data analysis using LiverMetSurvey.

BACKGROUND AND OBJECTIVES: The use of neo-adjuvant chemotherapy in resectable synchronous liver metastasis is ill defined. The aim of this study was to evaluate neo-adjuvant chemotherapy on outcomes following liver resection for synchronous CLM. METHODS: An analysis of a multi-centric cohort from the LiverMetSurvey International Registry, who had undergone curative resections for synchronous CLM was undertaken. Patients who received neo-adjuvant chemotherapy prior to liver surgery (group NAS; n = 693) were compared with those treated by surgery alone (group SG; n = 608). Baseline clinicopathological variables were compared. Predictors of overall (OS) and disease free survival (DFS) were subsequently identified. RESULTS: Clinicopathological comparison of the groups revealed a greater proportion of solitary metastasis in the SG compared to the NAS group (58.8% versus 38.4%; P < 0.001) therefore a separate analysis of solitary versus multi-centric analysis was performed. N-stage (> N1), number of metastasis (> 3), serum CEA (> 5 ng/ml) and no adjuvant chemotherapy independently predicted poorer OS, while N-stage (> N1), serum CEA (> 5 ng/ml) and no adjuvant chemotherapy independently predicted poorer DFS. Neo-adjuvant chemotherapy did not independently affect outcome. CONCLUSION: We present an analysis of a large multi-center series of the role of neo-adjuvant chemotherapy in resectable CLM and demonstrate no survival advantage in this setting.

Aetio-pathogenesis and the management of spontaneous liver bleeding in the West: a 16-year single-centre experience.

BACKGROUND: Spontaneous liver bleeding (SLB) is a rare but potentially fatal complication. In contrast to the East, various benign pathologies are the source of SLB in the West. An accurate diagnosis and a timely implementation of appropriate treatment are crucial in the management of these patients. The present study presents a large Western experience of SLB from a specialist liver centre. METHODS: A retrospective analysis of patients presented with SLB between January 1995 and January 2011. RESULTS: Sixty-seven patients had SLB, 44 (66%) were female and the median age at presentation was 47 years. Abrupt onset upper abdominal pain was the presenting symptom in 65 (97%) patients. The aetiology for SLB was hepatic adenoma in 27 (40%), hepatocellular carcinoma (HCC) in 17 (25%) and various other liver pathologies in the rest. Emergency treatment included a conservative approach in 42 (64%), DSA and embolization in 6 (9%), a laparotomy and packing in 6 (9%) and a liver resection in 11 (16%) patients. Eleven (16%) patients had further planned treatments. Seven (10%) died during the same admission but the mortality was highest in patients with HELLP syndrome. At a median follow-up of 54 months all patients with benign disease are alive. The 1-, 3- and 5-year survival of patients with HCC was 59%, 35% and 17%, respectively. CONCLUSION: SLB is a life-threatening complication of various underlying conditions and may represent their first manifestation. The management should include initial haemostasis followed by appropriate staging investigations to provide a definitive treatment for each individual patient.

Hepatic resection for non-colorectal, non-neuroendocrine, non-sarcoma metastasis: a single-centre experience.

BACKGROUND: The aim of the present study was to analyse the outcome after hepatic resection for non-colorectal, non-neuroendocrine, non-sarcomatous (NCNNNS) metastatic tumours and to identify the factors predicting survival. METHODS: All patients who underwent hepatic resection for NCNNNS metastatic tumours between September 1996 and June 2009 were included. Patients' demographics, clinical and histopathological parameters, overall survival and the factors predicting survival were analysed. RESULTS: In all, 65 patients underwent hepatic resection for metastasis. The most common site of a primary tumour was the kidney (24 patients). Fifteen patients had synchronous tumours. Fifty patients had major liver resections and 22 patients had bilobar disease. The median number of liver lesions resected was 1 and the median maximum diameter of the metastasis was 6 cm. A R0 resection was performed in 51 patients. The 1-, 3- and 5-year overall survival from the time of metastasectomy was 72.9%, 47.9% and 25.6%, respectively, with a median survival of 19 months. The presence of a tumour of greater than 6 cm (P= 0.048) and a positive resection margin (P= 0.04) were associated with poor survival. CONCLUSION: Hepatic resection for metastasis from NCNNNS tumours can offer acceptable long-term survival in selected patients. To offer a chance of a cure a R0 resection must be performed.

A reaudit of specialist-managed liver trauma after establishment of regional referral and management guidelines.

BACKGROUND: An earlier liver trauma audit (52 patients) noted that 50% were surgically managed at referring hospitals with a high morbidity and mortality, after which a regional referral and management algorithm was implemented in 2001. This study aims to reaudit specialist-managed liver trauma outcomes. METHODS: Prospective analysis of 99 patients (68 male) treated for liver injury (LI) between 2001 and 2008. Patient characteristics, management, and outcome results of these were compared with the results of previous audit. LI severity was determined by computed tomography, operative findings, and classified according to liver Organ Injury Scale. RESULTS: As implementation of guidelines, referrals increased from 5.2 patients/yr to 14.1 patients/yr, while LI profile was unchanged. Fewer patients were managed surgically with lower surgical intervention at referring hospitals (26 of 52 [50%] vs. 29 of 77 [38%]; p = 0.2). There has been a decrease in liver resection rates (14 of 26 [54%] vs. 3 of 37 [8%]; p = 0.0001]), overall mortality rate (12 of 52 [23%] vs. 11 of 99 [11%]; p = 0.059), and postoperative deaths. CONCLUSION: This reaudit confirms the role of nonoperative management of liver trauma. Early use of computed tomography scan with specialist discussion, selective use of perihepatic packing, and transfer to a specialist unit should be standard practice in the management of complex liver trauma.

Long-term outcome after sequential resections of liver and lung metastases from colorectal carcinoma.

BACKGROUND: Surgical resection of colorectal liver metastases (CLM) is an established form of treatment. Limited data exists on the value of sequential hepatic and pulmonary metastasectomy. We analysed patients who underwent sequential liver and lung resections for CLM. METHODS: A total of 910 patients who underwent liver resection for CLM between January 2000 and December 2007, were analysed to identify patients with resectable pulmonary metastases (n= 43; 4.7%). Patient demographics, overall survival and survival difference between synchronous and metachronous pulmonary metastasectomy groups were compared. In addition, outcomes in the 'liver and lung resection' group were compared with a matched group of 'liver resection only' patients (matched for age, primary disease stage, interval to liver resection and liver disease stage). RESULTS: Forty-three patients (median age 62, range 43-83 years, 22 males) underwent sequential liver and lung resection. A total of 36 patients underwent major hepatic resections, 18 patients had bilobar disease and the median number of liver lesions resected was 3 (range 1-5 lesions). Ten patients had synchronous liver and lung metastases. The median interval between liver and lung metastasectomy was 25 months (range 2-88 months). A total of two patients underwent major lobectomies, three patients had bilateral disease and the median number of lung lesions resected was one (range 1-3). The 1-, 3- and 5-year overall survival rates after first metastasectomy were 100%, 87.1% and 53.9%, respectively, with a median survival of 42 months. PATIENTS: Undergoing metachronous pulmonary metastasectomy had better 1-, 3- and 5-year survival rates than those with synchronous disease (100%, 88.9% and 60.9% vs. 100%, 75% and 0%, respectively; P= 0.02, log rank test). There was no significant survival difference between the 'liver and lung resection' and the 'liver resection only' groups. CONCLUSION: Sequential liver and lung resection for CLM is associated with good long-term survival in selected patients, except in those presenting with synchronous lung and liver metastases.