Minimally invasive and endoscopic versus open necrosectomy for necrotising pancreatitis: a pooled analysis of individual data for 1980 patients.

OBJECTIVE: Minimally invasive surgical necrosectomy and endoscopic necrosectomy, compared with open necrosectomy, might improve outcomes in necrotising pancreatitis, especially in critically ill patients. Evidence from large comparative studies is lacking. DESIGN: We combined original and newly collected data from 15 published and unpublished patient cohorts (51 hospitals; 8 countries) on pancreatic necrosectomy for necrotising pancreatitis. Death rates were compared in patients undergoing open necrosectomy versus minimally invasive surgical or endoscopic necrosectomy. To adjust for confounding and to study effect modification by clinical severity, we performed two types of analyses: logistic multivariable regression and propensity score matching with stratification according to predicted risk of death at baseline (low: <5%; intermediate: ≥5% to <15%; high: ≥15% to <35%; and very high: ≥35%). RESULTS: Among 1980 patients with necrotising pancreatitis, 1167 underwent open necrosectomy and 813 underwent minimally invasive surgical (n=467) or endoscopic (n=346) necrosectomy. There was a lower risk of death for minimally invasive surgical necrosectomy (OR, 0.53; 95% CI 0.34 to 0.84; p=0.006) and endoscopic necrosectomy (OR, 0.20; 95% CI 0.06 to 0.63; p=0.006). After propensity score matching with risk stratification, minimally invasive surgical necrosectomy remained associated with a lower risk of death than open necrosectomy in the very high-risk group (42/111 vs 59/111; risk ratio, 0.70; 95% CI 0.52 to 0.95; p=0.02). Endoscopic necrosectomy was associated with a lower risk of death than open necrosectomy in the high-risk group (3/40 vs 12/40; risk ratio, 0.27; 95% CI 0.08 to 0.88; p=0.03) and in the very high-risk group (12/57 vs 28/57; risk ratio, 0.43; 95% CI 0.24 to 0.77; p=0.005). CONCLUSION: In high-risk patients with necrotising pancreatitis, minimally invasive surgical and endoscopic necrosectomy are associated with reduced death rates compared with open necrosectomy.

Hepatocellular cancer: the impact of obesity, type 2 diabetes and a multidisciplinary team.

BACKGROUND & AIMS: Hepatocellular cancer (HCC) commonly complicates chronic liver disease and increases in incidence have been reported despite falling prevalences of viral hepatitis. METHODS: Following the introduction of centralised specialist teams to manage patients with cancer in England, we characterised the demographics of patients with HCC referred to the Newcastle-upon-Tyne Hospitals NHS Foundation Trust between 2000 and 2010. Regional HCC mortality data was from Public Health England. RESULTS: HCC related mortality in the region rose 1.8 fold in 10 years, from 2.0 to 3.7 per 100,000. 632 cases were reviewed centrally, with 2-3 fold increases in referrals of patients with associated hepatitis C, alcoholic liver disease or no chronic liver disease and a >10 fold increase in HCC associated with non-alcoholic fatty liver disease (NAFLD). By 2010 NAFLD accounted for 41/118 (34.8%) cases. Irrespective of associated etiologies, metabolic risk factors were present in 78/118 (66.1%) cases in 2010, associated with regional increases in obesity and diabetes. Median overall survival was just 10.7 months. Although patients with NAFLD associated HCC were older (71.3 yr vs. 67.1 yr; p<0.001) and their cancers less often detected by surveillance, their survival was similar to other etiologies. This was attributed to significantly higher incidental presentation (38.2%) and lower prevalence of cirrhosis (77.2%). CONCLUSIONS: HCC related mortality is increasing, with typical patients being elderly with metabolic risk factors. The prognosis for most of the cases is poor, but older patients with co-morbidities can do well, managed, within a specialist multidisciplinary team if their cancer is detected pre-symptomatically.

Biomarker in Hepatocellular Carcinoma.

Liver cancer is one of the most prevalent types of cancer and a major contributor to the socioeconomic burden worldwide. The pathogenesis of hepatocellular carcinoma (HCC) is contributed by various etiological factors like virus infection, excessive alcohol consumption, exposure to toxins, or metabolic disorders. Majority of patients are diagnosed with late-stage HCC, which restricts its management to only palliative care. HCC, if diagnosed early, increases the survival and quality of life. Currently available biomarker (alpha-fetoproteins) have several limitations, that impede the early diagnosis and staging of cancer. This warrants the continous search in pursuit of a novel biomarker. Several research works in diverse areas have contributed to the identification of various novel biomarkers that have shown multifaceted application in early disease diagnosis, which further aid in targeted and effective therapy that can prevent cancer progression. This improves the overall health status of the patient along with significant reduction in caretaker's burden. With the aid of novel technologies, several biomarkers have been investigated and validated in mutliple preliminary research works. Therefore in this review, we have outlined various novel biomarkers that showed promising outcomes in their trials and we have highlighted the developing areas that act as game changers in cancer diagnosis and management.

Liver Transplantation for Nonresectable Colorectal Liver Metastases (CRLM).

Transplantation represents the most radical locoregional therapy through removal of the liver, associated vasculature and locoregional lymph nodes, and replacing it with an allograft. Recent evidence has demonstrated that transplantation for unresectable CRLM is feasible with acceptable post-transplant outcomes in a highly selected cohort of patients. Controversy exists regarding whether transplantation is an appropriate treatment for such patients, due to concerns regarding disease recurrence in the transplanted graft in an immunosuppressed recipient along with utilising a donor liver which are in short supply. Expanding the indications for liver transplantation may also limit access for other patients with end-stage liver disease having ethical implications due to the effect of increasing the waiting list. In this review, we summarise the current evidence for liver transplantation in patients with nonresectable CRLM and highlight unresolved controversies and future directions for this type of treatment.

Exosomes in chronic liver disease.

Chronic liver disease (CLD) is the major cause of mortality and morbidity, particularly in developing countries. Although there has been a significant advancement in the identification and treatment of liver diseases over time, clinical results are not satisfactory in advanced liver disease. Thus, it is crucial to develop certain technology for early detection, and curative therapies and to investigate the molecular mechanisms behind CLD's pathogenesis. The study of exosomes in CLD is a rapidly developing field. They are structurally membrane-derived nano vesicles released by various cells. In CLD, exosomes released from injured hepatic cells affect intercellular communication, creating a microenvironment conducive to the illness's development. They also carry liver cell-specific proteins and miRNAs, which can be used as diagnostic biomarkers and treatment targets for various liver diseases. End-stage liver disease can only be treated by a liver transplant, however, the low availability of compatible organs, high expenses of treatment, and surgical complications significantly lower patient survival rates. Early diagnosis and therapeutic intervention of CLD positively affect the likelihood of curative treatment and high patient survival rates. Considering the possibility that exosomes could be employed as tools for disease diagnostics and clinical intervention, The current study briefly summarizes the roles of exosomes and their cargo in diagnosing and treating liver diseases.

A New Variant of an Old Itch: Novel Missense Variant in ABCB4 Presenting with Intractable Pruritus.

We report a novel homozygous missense variant in ABCB4 gene in a Yemeni child born to consanguineous parents, with a significant family history of liver disease-related deaths, resulting in a progressive familial intrahepatic cholestasis (PFIC) type 3 phenotype requiring liver transplantation for intractable pruritus.

Pancreaticobronchial fistula: a complication of acute pancreatitis.

CONTEXT: Pancreaticobronchial fistula is a rare complication of severe pancreatitis. Various diagnostic methods have been described previously. CASE REPORT: The presentation, diagnostic methods, management and 5-year follow-up of a 40-year-old woman with severe gallstone induced pancreatitis complicated by a pancreaticobronchial fistula were reviewed. Diagnosis was made on the endotracheal intubation when amylase rich-fluid was drained via the tube and confirmed by CT scanning. Successful management was achieved by an open pancreatic necrosectomy, during which air bubbles were seen emerging from the pancreatic collection which supported the diagnosis of the fistula. Five-year follow-up did not reveal any complications. CONCLUSIONS: Pancreaticobronchial fistulas have the potential to cause severe respiratory complications and mortality. Awareness of this condition is important in the treatment of complicated cases of pancreatitis.

The Use of a 3D Printing Model in Planning a Donor Hepatectomy for Living Donor Liver Transplantation: First in India.

INTRODUCTION: Three-dimensional (3D) anatomical relationships between the hepatic veins and portal structures can serve as a guide to plan resections in donor hepatectomy during living donor liver transplantation. We present the first case report from India on the use of a 3D printed liver model, as an assist to living donor liver transplantation. METHODS: A 3D model of the donor liver with hepatic venous structures printed within it was prepared using image acquisition data. The model was used for a simulated cut preoperatively, to mimic the donor hepatectomy based on the venous structures seen through the transparent material used for making the liver model. The volume of the graft measured by volume displacement in the actual surgery was compared with the volume of the model after the simulated cut. RESULTS: The calculated volume of the graft was 359 ml as per the preoperative simulation, and the observed weight/volume was 380 gm/310 ml. CONCLUSION: Three-dimensional printing of liver models using imaging data can help predict the actual size of the graft after donor hepatectomy, in patients undergoing living donor liver transplantation.

Successful management of necrotizing pancreatitis by percutaneous necrosectomy after orthotopic liver transplant for paracetamol induced acute liver failure: a case report.

OBJECTIVES: Acute pancreatitis, which can develop after any whole-organ transplant, is often associated with immunosuppression. Pancreatitis that complicates a liver transplant can be a significant problem that results in a high mortality rate. MATERIALS AND METHODS: We describe the successful use of minimally invasive techniques to treat severe acute pancreatitis. To our knowledge, this is the first reported case in which major laparotomy was precluded by the use of percutaneous necrosectomy to manage necrotizing pancreatitis in a liver transplant recipient. We also briefly review the published literature on severe acute pancreatitis in liver transplant recipients. RESULTS: Our patient, who had a Model for End- Stage Liver Disease score of 39 when transplanted and an Acute Physiology and Chronic Health Evaluation II score of 19 when infected necrosis in his pancreas was diagnosed, recovered completely after 92 days of hospitalization. He underwent 2 percutaneous drainage procedures and 3 percutaneous necrosectomies to treat his pancreatic complication. A review of the literature revealed that severe acute pancreatitis significantly increases morbidity and mortality in liver transplant recipients. Unlike necrotizing pancreatitis, which develops outside the context of liver transplant where there is a distinct shift towards minimally invasive procedures, infected necrosis associated with fulminant liver failure or a liver transplant is usually treated with open necrosectomy. CONCLUSIONS: Severe acute pancreatitis in liver transplant recipients should be managed exactly as it is in patients who have not received a liver transplant. Anatomically guided minimally invasive necrosectomy appears to be beneficial, especially when patients are critically unwell, as they are following a liver transplant.

Hepatic arterial communicating arcades-Case series and review of literature.

This case series describes the hepatic arterial communicating arcades and their importance in the endovascular management of hepatic artery pseudoaneurysm, pediatric post liver transplant lobar arterial occlusion, and lobar arterial stenosis due to gall bladder carcinoma. We describe new types of arterial communicating arcades which have not been described earlier.

Diaphragmatic herniation following donor hepatectomy for living donor liver transplantation: a serious complication not given due recognition.

A clear appreciation of benefits and risks associated with living donor hepatectomy is important to facilitate counselling for the donor, family, and recipient in preparation for living donor liver transplant (LDLT). We report a life-threatening complication occurring in one of our live liver donors at 12 weeks following hemi-liver donation. We experienced five donor complications among our first 50 LDLT: Clavien Grade 1, n=1; Clavien grade 2, n=3; and Clavien grade 3B, n=1. The one with Clavien grade 3B had a life-threatening diaphragmatic hernia occurring 12 weeks following hepatectomy. This was promptly recognized and emergency surgery was performed. The donor is well at 1-year follow-up. Here we provide a review of reported instances of diaphragmatic hernia following donor hepatectomy with an attempt to elucidate the pathophysiology behind such occurrence. Life-threatening donor risk needs to be balanced with recipient benefit and risk on a tripartite basis during the counselling process for LDLT. With increasing use of LDLT, we need to be aware of such life-threatening complication. Preventive measures in this regard and counselling for such complication should be incorporated into routine work-up for potential live liver donor.

Cyclooxygenase-2 polymorphisms and pancreatic cancer susceptibility.

OBJECTIVES: DNA sequence variants in the cyclooxygenase-2 (COX-2) gene may lead to altered COX-2 production and/or activity, resulting in interindividual differences in susceptibility to pancreatic cancer. To test this hypothesis, we investigated the relationship between polymorphisms in the COX-2 gene and the risk of pancreatic cancer in a European population. METHODS: The COX-2 genotypes for 7 single-nucleotide polymorphisms (rs2745557, rs5277, rs2066826, rs4648261, rs4648262, rs2206593, and rs5275) were determined in 162 pancreatic cancer patients and 170 control subjects without cancer who were matched for age and sex. Data analysis was by conditional logistic regression analysis, adjusting for age, sex, and smoking. RESULTS: Two haplotypes (GGAGGGT and GCGGGGT for rs2745557, rs5277, rs2066826, rs4648261, rs4648262, rs2206593, rs5275, respectively) were more frequent among the patients compared with control subjects (P < 0.024), although no individually statistically significant associations for the 7 single-nucleotide polymorphisms studied were detected. CONCLUSIONS: Our findings suggest the individual polymorphisms we studied in the COX-2 gene are not associated with risk of pancreatic cancer. However, the finding of a modest association with 2 haplotypes might be consistent with a small effect, which could be also seen at the genotype level had more samples been available.

The role of tobacco-derived carcinogens in pancreas cancer.

The extremely poor outcome from pancreas cancer is well known. However, its aetiology less well appreciated, and the molecular mechanisms underlying this are poorly understood. Tobacco usage is one of the strongest risk factors for this disease, and this is a completely avoidable hazard. In addition, there are well described hereditary diseases which predispose, and familial pancreas cancer. We have sought here to summarise the role of tobacco-derived carcinogens and the mode of their tumorigenic action on the pancreas. There is compelling evidence from animal and human studies (laboratory including cell line studies and epidemiologic) that tobacco derived carcinogens cause pancreas cancer. However, the manner in which they do so is not entirely apparent. There is also compelling evidence that synergism with genetic and other life-style factors-like diet obesity-results in a multifactorial causation of the disease. Ascertaining the role of tobacco carcinogens in the development of this cancer and their interaction with other risk factors will enable novel therapeutic and preventative strategies to improve outcome from this appalling malignancy.

Quality of life and functional outcome at 3, 6 and 12 months after acute necrotising pancreatitis.

PURPOSE: To prospectively determine the quality of life and functional outcome at 3, 6 and 12 months following acute necrotising pancreatitis. METHODS: Thirty-one consecutive patients with acute necrotising pancreatitis requiring intensive care in our hospital were identified. Survivors were assessed at 3, 6 and 12 months following hospital discharge by an investigator blinded to their previous treatment. Health-related quality of life was assessed by the Short Form 36 (SF-36) questionnaire and functional outcome by the six minute walk test. RESULTS: Twenty-one patients (68%) survived to leave hospital. The median score for the physical function domain increased from 32 at 3 months to 38 and 12 months (P = 0.013), but remained lower than the score in the normal population of 88 (P < 0.001). The median physical component summary score increased from 33 at 3 months to 40 at 12 months (P = 0.030), but remained lower than the score in the normal population of 50 (P = 0.009). Between 3 and 12 months the median distance walked in 6-min increased from 358 to 424 m (P = 0.021), but remained lower than the predicted distance of 503 m (P = 0.014). CONCLUSIONS: In the first year after acute necrotising pancreatitis patients showed improvement in their physical components of quality of life and in their physical function, but their outcome at 12 months was still poor compared to the general population. This patient group in particular may benefit from a structured rehabilitation programme continuing after hospital discharge.

Granular cell tumor as an unusual cause of obstruction at the hepatic hilum: report of a case.

A diagnosis of malignancy is reasonably assumed when a lesion is found at the hilum or bile ducts in a patient with jaundice who has never undergone biliary surgery. Although benign tumors occasionally develop in this location, preoperative recognition is difficult and most are treated as malignant lesions. We illustrate this clinical scenario in this case report of a granular cell tumor (GCT) that developed at the biliary bifurcation, necessitating right hemi-hepatectomy with extrahepatic biliary tree excision. We describe the clinical presentation, imaging findings, treatment, and histological findings of this tumor. Although rare, a GCT can develop at the hilum and mimic a malignant lesion such as cholangiocarcinoma (CC) radiologically. To our knowledge, this is the fourth report of a GCT at the hilum of the liver. However, the possibility of this tumor should be considered in the differential diagnosis of a lesion in this location.