The association between quality care and outcomes for a real-world population of Australian patients diagnosed with pancreatic cancer.

BACKGROUND: This study: (i) assessed compliance with a consensus set of quality indicators (QIs) in pancreatic cancer (PC); and (ii) evaluated the association between compliance with these QIs and survival. METHODS: Four years of data were collected for patients diagnosed with PC. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). A multivariable analysis tested the relationship between significant patient and hospital characteristics, patient cluster effects within hospitals and survival. RESULTS: 1061 patients were eligible for this study. Significant association with improved survival were: (i) in the potentially resectable group having adjuvant chemotherapy administered following surgery or a reason documented (HR, 0.29; 95 CI, 0.19-0.46); (ii) in the locally advanced group included having chemotherapy ± chemoradiation, or a reason documented for not undergoing treatment (HR, 0.38; 95 CI, 0.25-0.58); and (iii) in the metastatic disease group included having documented performance status at presentation (HR, 0.65; 95 CI, 0.47-0.89), being seen by an oncologist in the absence of treatment (HR, 0.48; 95 CI, 0.31-0.77), and disease management discussed at a multidisciplinary team meeting (HR, 0.79; 95 CI, 0.64-0.96). CONCLUSION: Capture of a concise data set has enabled quality of care to be assessed.

Correlations between histopathological diagnosis of chemotherapy-induced hepatic injury, clinical features, and perioperative morbidity.

BACKGROUND: Chemotherapy has in some series been linked with increased morbidity after a hepatectomy. Hepatic injuries may result from the treatment with chemotherapy, but can also be secondary to co-morbid diseases. The aim of the present study was to draw correlations between clinical features, treatment with chemotherapy and injury phenotypes and assess the impact of each upon perioperative morbidity. PATIENTS AND METHODS: Retrospective samples (n= 232) were scored grading steatosis, steatohepatitis and sinusoidal injury (SI). Clinical data were retrieved from medical records. Correlations were drawn between injury, clinical features and perioperative morbidity. RESULTS: Injury rates were 18%, 4% and 19% for steatosis, steatohepatitis and SI, respectively. High-grade steatosis was more common in patients with diabetes [odds ratio (OR) = 3.33, P= 0.01] and patients with a higher weight (OR/kg = 1.04, P= 0.02). Steatohepatitis was increased with metabolic syndrome (OR = 5.88, P= 0.02). Chemotherapy overall demonstrated a trend towards an approximately doubled risk of high-grade steatosis and steatohepatitis although not affecting SI. However, pre-operative chemotherapy was associated with an increased SI (OR = 2.18, P= 0.05). Operative morbidity was not increased with chemotherapy, but was increased with steatosis (OR = 2.38, P= 0.02). CONCLUSIONS: Diabetes and higher weight significantly increased the risk of steatosis, whereas metabolic syndrome significantly increased risk of steatohepatitis. The presence of high-grade steatosis increases perioperative morbidity, not administration of chemotherapy per se.

mRNA gene expression correlates with histologically diagnosed chemotherapy-induced hepatic injury.

INTRODUCTION: Chemotherapy-induced hepatic injuries (CIHI) are an increasing problem facing hepatic surgeons. It may be possible to predict the risk of developing CIHI by analysis of genes involved in the metabolism of chemotherapeutics, previously established as associated with other forms of toxicity. METHODS: Quantitative reverse transcriptase-polymerase chain reaction methodology (q-RT-PCR) was employed to quantify mRNA expression of nucleotide excision repair genes ERCC1 and ERCC2, relevant in the neutralization of damage induced by oxaliplatin, and genes encoding enzymes relevant to 5-flurouracil metabolism, [thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD)] in 233 hepatic resection samples. mRNA expression was correlated with a histopathological injury scored via previously validated methods in relation to steatosis, steatohepatitis and sinusoidal obstruction syndrome. RESULTS: Low-level DPD mRNA expression was associated with steatosis [odds ratio (OR) = 3.95, 95% confidence interval (CI) = 1.53-10.19, P < 0.003], especially when stratified by just those patients exposed to chemotherapy (OR = 4.48, 95% CI = 1.31-15.30 P < 0.02). Low expression of ERCC2 was associated with sinusoidal injury (P < 0.001). There were no further associations between injury patterns and target genes investigated. CONCLUSIONS: Predisposition to the development of CIHI may be predictable based upon individual patient expression of genes encoding enzymes related to the metabolism of chemotherapeutics.

KRAS mutation is associated with lung metastasis in patients with curatively resected colorectal cancer.

PURPOSE: Oncogene mutations contribute to colorectal cancer development. We searched for differences in oncogene mutation profiles between colorectal cancer metastases from different sites and evaluated these as markers for site of relapse. EXPERIMENTAL DESIGN: One hundred colorectal cancer metastases were screened for mutations in 19 oncogenes, and further 61 metastases and 87 matched primary cancers were analyzed for genes with identified mutations. Mutation prevalence was compared between (a) metastases from liver (n = 65), lung (n = 50), and brain (n = 46), (b) metastases and matched primary cancers, and (c) metastases and an independent cohort of primary cancers (n = 604). Mutations differing between metastasis sites were evaluated as markers for site of relapse in 859 patients from the VICTOR trial. RESULTS: In colorectal cancer metastases, mutations were detected in 4 of 19 oncogenes: BRAF (3.1%), KRAS (48.4%), NRAS (6.2%), and PIK3CA (16.1%). KRAS mutation prevalence was significantly higher in lung (62.0%) and brain (56.5%) than in liver metastases (32.3%; P = 0.003). Mutation status was highly concordant between primary cancer and metastasis from the same individual. Compared with independent primary cancers, KRAS mutations were more common in lung and brain metastases (P < 0.005), but similar in liver metastases. Correspondingly, KRAS mutation was associated with lung relapse (HR = 2.1; 95% CI, 1.2 to 3.5, P = 0.007) but not liver relapse in patients from the VICTOR trial. CONCLUSIONS: KRAS mutation seems to be associated with metastasis in specific sites, lung and brain, in colorectal cancer patients. Our data highlight the potential of somatic mutations for informing surveillance strategies.

Laparoscopic hepatectomy is a safe procedure for cancer patients.

BACKGROUND: Utilizing laparoscopy for major surgeries such as hepatectomy is a relatively new concept. Initially, benign pathologies dominated indications for resection. Our experience in an Australian setting with primarily malignant diagnoses is described. METHODS: A review of patients' profiles, pathology, surgery and outcome was performed on 35 patients between December 2005 and August 2008. Data were collected and analysed retrospectively from medical records on a pre-designed datasheet. RESULTS: Commonest indication for resection was colorectal metastasis (54%), 71% of all resections were for malignancy. Average operating time was 2 h 31 min (range 30 min-7 h, 15 min). Major morbidity consisted of one bile leak, two subphrenic abscesses and one pulmonary embolus. There were no deaths. Conversion to open was required in 20% and two patients required intra-operative blood transfusions. Average length of stay overall was 6.1 days (range 1-27), but as low as 2 days for some left lateral sectionectomies. Cessation of parenteral analgesia, return to normal diet and full mobility were achieved on average at 2.4, 2.3 and 2.8 days. Significant post-operative liver dysfunction was seen in two patients, which returned to normal by discharge. One patient died of disease progression 4 months after surgery. There were two involved margins in 35 patients (6%). CONCLUSIONS: Laparoscopic hepatectomy is a developing and safe technique in a select group of patients including those with malignancies, resulting in short hospital stays, rapid return to normal diet, full mobility and minimal morbidity with acceptable oncological parameters. This study is not comparative in nature, but provides evidence to support further investigation and establishment of this new technique for liver resection.

Gallbladder carcinoma as a long-term complication of cholecystojejunostomy.

INTRODUCTION: Development of gallbladder cancer following cholecystojejunostomy has not previously been described. METHODS: A case of a patient who developed gallbladder cancer 22 years following cholecystojejunostomy is presented, and a literature review of known complications of cholecysto-enteric anastomosis was performed. DISCUSSION: Cholangitis is the commonest reported complication, known to predispose the biliary epithelium to malignant change, but has not been described until now as being carcinogenic for the gallbladder. Gallbladder carcinoma may be a rare long-term complication of cholecystojejunostomy.

A review of the surgical strategies for the management of gallbladder carcinoma based on T stage and growth type of the tumour.

AIMS: Surgery for gallbladder carcinoma is a technically challenging exercise. The extent of resection varies based on a number of factors, and controversy exists regarding what constitutes an acceptable resection. A review of current recommendations and practice was undertaken. METHODS: A comprehensive literature review was performed, searching Medline for articles published since 2000, using the MeSH heading of 'gallbladder cancer' and 'surgery'. Abstracts were reviewed and articles retrieved if the main focus of the article centred on the surgical management of gallbladder carcinoma. OBSERVATIONS: The extent of hepatic resection and lymph node dissection required varies in particular with T stage. Growth pattern and anatomical location of the tumour within the gallbladder also influence surgical management. CONCLUSIONS: Discrepancy exists between the Eastern and Western literature in terms of what constitutes an acceptable limit of resection, and these issues are discussed.

Lower gastrointestinal haemorrhage and superselective angiographic embolization.

BACKGROUND: Little information is available in the surgical literature regarding the use of superselective embolization for bleeding with its origin distal to the ligament of Treitz. The outcome of this treatment remains, to some extent, an unknown. The present paper evaluates the Alfred Hospital's experience using superselective transcatheter embolization in the treatment of acute lower gastrointestinal haemorrhage. METHODS: An uncontrolled case series analysis was undertaken of all 15 patients who underwent arterial embolization for lower gastrointestinal bleeding, defined as distal to the ligament of Treitz, from July 1998 to January 2003 at the Alfred Hospital, Victoria. RESULTS: Transcatheter embolization achieved satisfactory haemostasis in 14 out of 15 patients (93%). Eight patients had rebleeding within 24 h of the initial procedure (53.3%). Two groups of patients emerged: 10 patients who had active bleeding identified on angiography (67%) and five patients whose angiograms failed to find an active bleeding site (33%). Ten per cent of patients with active bleeding observed on angiogram developed bowel ischaemia and 20% died from ischaemia or continued bleeding. Patients without active bleeding identified at the time of angiogram had a proven ischaemia rate of 60% and a 60% mortality rate from continued bleeding or intestinal ischaemia. CONCLUSION: High-risk patients, with active bleeding identified on angiography, can be successfully treated by superselective angiographic embolization and this appears to be an acceptable alternative to emergency resection. If active bleeding is not identified angiographically embolization is not recommended.