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Papers by John Karani

Liver International, 2009

Regression of hepatic adenomata after cessation of selective oestrogen receptor modulator A 75-ye... more Regression of hepatic adenomata after cessation of selective oestrogen receptor modulator A 75-year-old lady underwent left hepatectomy in 1985 for giant cell adenoma. Annual surveillance magnetic resonance imaging of small residual adenomata in the right lobe was performed. In 2007, a sudden dramatic increase in size was seen (see Fig. 1). She had been prescribed raloxifene, an oral selective oestrogen receptor modulator (SERM) to prevent osteoporosis. On cessation of this medication, the adenomata receded (see Fig. 2). Selective oestrogen receptor modulators have paradoxical oestrogenic and anti-oestrogenic effects in various tissues. They act as oestrogen receptor agonists on bone, increasing the bone mineral density in post-menopausal women (1). In breast tissue, an oestrogen antagonistic effect reduces the relative risk of breast cancer in post-menopausal women (2), but no associated increase in endometrial proliferation or uterine cancer has been reported (3). Human liver contains oestrogen receptors (4), and regression of hepatocellular adenomas after withdrawal of contraceptive agents has been widely reported. An association between SERMs and hepatic adenomas has not been reported previously.

Journal of Clinical Oncology, 2016

e15617Background: Hepatocellular carcinoma (HCC) is sixth most common cancer worldwide. Prognosis... more e15617Background: Hepatocellular carcinoma (HCC) is sixth most common cancer worldwide. Prognosis following trans arterial (chemo) embolization (TAE/TACE) for HCC remains unclear. The hepatoma arte...

Nature, May 1, 2018

Liver transplantation is a highly successful treatment, but is severely limited by the shortage i... more Liver transplantation is a highly successful treatment, but is severely limited by the shortage in donor organs. However, many potential donor organs cannot be used; this is because sub-optimal livers do not tolerate conventional cold storage and there is no reliable way to assess organ viability preoperatively. Normothermic machine perfusion maintains the liver in a physiological state, avoids cooling and allows recovery and functional testing. Here we show that, in a randomized trial with 220 liver transplantations, compared to conventional static cold storage, normothermic preservation is associated with a 50% lower level of graft injury, measured by hepatocellular enzyme release, despite a 50% lower rate of organ discard and a 54% longer mean preservation time. There was no significant difference in bile duct complications, graft survival or survival of the patient. If translated to clinical practice, these results would have a major impact on liver transplant outcomes and waiti...

Oxford medical case reports, 2017

Intrahepatic bleeding secondary to rupture of hepatic microaneurysms is an uncommon clinical enti... more Intrahepatic bleeding secondary to rupture of hepatic microaneurysms is an uncommon clinical entity more frequently associated with polyarteritis nodosa (PAN) or rarely with other vasculitis or autoimmune disease. Hepatic vasculitis is reported in chronic hepatitis C virus (HCV) infection and an association between hepatitis C and PAN is described. The current report presents the case of a middle-aged female patient with a medical history remarkable for HCV infection who underwent a percutaneous liver biopsy, which was complicated by severe intrahepatic and perihepatic haemorrhage. Computed tomography angiography revealed innumerous microaneurysms. She underwent transcatheter angiography and coil embolization of a peripheral branch of the right hepatic artery which controlled the bleeding. Subsequently, she was empirically treated with a course of Prednisolone. Follow-up imaging showed a good response to treatment.

Journal of Hepatology, 2017

Journal of pediatric gastroenterology and nutrition, 2017

Primary Budd-Chiari syndrome is a rare cause of liver disease in children in the western world. H... more Primary Budd-Chiari syndrome is a rare cause of liver disease in children in the western world. Here we present a retrospective review of children with Primary Budd-Chiari syndrome presenting from January 2001 to November 2015 to our hospital. Seven children were identified. Their presentation was mostly chronic. All had predisposing factors for thrombosis and were started on anticoagulation. Radiological interventions (2 transjugular intrahepatic portosystemic shunts and 1 hepatic vein stenting), liver transplant and mesocaval shunt were done in 3, 2, and 1 patients, respectively; 1 child underwent bone marrow transplantation following transjugular intrahepatic portosystemic shunts and 1 child was managed only medically. After liver transplantation, one child died 3 years later as a result of subarachnoid haemorrhage, whereas others remain well at a median follow-up of 6 years. Despite high morbidity, the disease can have a good long-term outcome with a multidisciplinary approach.

Hepatobiliary & pancreatic diseases international : HBPD INT, 2010

Pancreatitis is associated with arterial complications in 4%-10% of patients, with untreated mort... more Pancreatitis is associated with arterial complications in 4%-10% of patients, with untreated mortality approaching 90%. Timely intervention at a specialist center can reduce the mortality to 15%. We present a single institution experience of selective embolization as first line management of bleeding pseudoaneurysms in pancreatitis. Sixteen patients with pancreatitis and visceral artery pseudoaneurysms were identified from searches of the records of interventional angiography from January 2000 to June 2007. True visceral artery aneurysms and pseudoaneurysms arising as a result of post-operative pancreatic or biliary leak were excluded from the study. In 50% of the patients, bleeding complicated the initial presentation of pancreatitis. Alcohol was the offending agent in 10 patients, gallstones in 3, trauma, drug-induced and idiopathic pancreatitis in one each. All 16 patients had a contrast CT scan and 15 underwent coeliac axis angiography. The pseudoaneurysms ranging from 0.9 to 9....

Transplantation, 1998

Variant arterial anatomy must be recognized and appropriately managed during split liver transpla... more Variant arterial anatomy must be recognized and appropriately managed during split liver transplantation to ensure complete vascular supply to both grafts. We describe an accessory posterior right hepatic artery, arising from the left and passing behind the portal vein bifurcation. Thirty-seven consecutive livers were examined during ex vivo liver-splitting procedures. An abnormal right accessory artery arising from the left hepatic artery was identified high in the porta hepatis. The anatomical variant is described and illustrated by methylene blue injection and arteriography. The anomaly was encountered in 2 of 37 split liver procedures. The two right lobes with the abnormal artery were discarded. Care should be taken during dissection behind the portal vein bifurcation to exclude an accessory segmental right hepatic artery. If present, the liver may not be suitable for splitting without compromising the right lobe, unless the left hepatic artery can be divided distal to the origin of the accessory vessel.

The Tohoku Journal of Experimental Medicine, 1997

Journal of Pediatric Surgery, 2006

Background: Management of bile leaks after blunt abdominal trauma remains controversial. Conventi... more Background: Management of bile leaks after blunt abdominal trauma remains controversial. Conventionally, open surgery has been considered necessary, but new modalities of treatment, including endoscopic biliary stenting and laparoscopy, offer a minimally invasive alternative. Materials and Methods: A retrospective review of all cases of blunt liver trauma in children treated at our institution between May 2002 and October 2004 was performed looking for possible biliary injury. Results: Five children (3 boys), median age 13 years (range, 10-15 years), were referred to our institution at a median time of 4 days (1-15 days) after the initial trauma. Mechanism of injury was motor vehicle accident (n = 3), fall from a motorbike/Quad bike (n = 2), and a scooter handlebar injury (n = 1). Two, who were hemodynamically unstable, required laparotomy within 24 hours, although their subsequent management was minimally invasive. Endoscopic retrograde cholangiopancreatography, performed at a median time of 15 days (2-28 days), demonstrated an intrahepatic biliary leak in all 5 patients. Biliary stenting was performed in each case, with 2 also having a sphincterotomy. One subsequently developed a bile duct stricture that was managed by endoscopic dilatation. Four required additional percutaneous external drainage of intraabdominal collections. Two underwent laparoscopy to facilitate peritoneal lavage and rule out bowel injuries. No child required open surgery to treat the bile leak. Median hospital stay was 43 days (range, 15-58 days). Conclusions: A minimally invasive, multidisciplinary approach to traumatic bile leaks, as an alternative to open surgery, is practical and safe. It requires flexibility, particularly if the diagnosis has been delayed, and may still involve a prolonged hospital stay.

Journal of Pediatric Surgery, 2007

Background: The management of children with main pancreatic duct injuries is controversial. We re... more Background: The management of children with main pancreatic duct injuries is controversial. We report a series of patients with pancreatic trauma who were treated using minimally invasive techniques. Methods: Retrospective review of children with pancreatic trauma treated at a UK tertiary referral institution between 1999 and 2004. Results: Fifteen children (11 boys) were admitted with pancreatic trauma. Twelve (80%) were less than 50th centile for body weight. Contrast-enhanced computed tomography (CT) scans were used to define organ injury, supplemented by magnetic resonance cholangiopancreatography (MRCP) in 7. Twelve (80%) underwent diagnostic endoscopic retrograde cholangiopancreatography (ERCP) with a median time after injury of 11 (range, 6-29) days. The degree of pancreatic injury was defined by ERCP and CT/ MRCP as grade II (n = 2), grade III (n = 4), grade IV (n = 9) (American Association for the Surgery of Trauma grades). Nine children had a transductal pancreatic stent inserted endoscopically. Computed tomography/ultrasound-guided drainage was performed in 4 children for acute fluid collections. Two children later underwent endoscopic cyst-gastrostomy, one of whom later required conversion to an open cyst-gastrostomy. Conclusion: Body habitus may predispose to pancreatic duct trauma. Contrast-enhanced CT scan (and MRCP) should dictate the need for ERCP. Transductal pancreatic stenting allows internal drainage of peripancreatic collections and may reestablish duct continuity, although a proportion still requires percutaneous or endoscopic cyst-gastrostomy drainage. Open surgery for pancreatic trauma should now be an exception.

The Journal of Immunology, 2004

α-Fetoprotein (AFP) is a tumor-associated Ag, and its serum level is elevated in patients with he... more α-Fetoprotein (AFP) is a tumor-associated Ag, and its serum level is elevated in patients with hepatocellular carcinoma (HCC). In vitro, AFP induces functional impairment of dendritic cells (DCs). This was demonstrated by the down-regulation of CD40 and CD86 molecules and the impairment of allostimulatory function. Also, AFP was found to induce significant apoptosis of DCs, and AFP-treated DCs produced low levels of IL-12 and TNF-α, a cytokine pattern that could hamper an efficient antitumor immune response. Ex vivo, APCs of patients with HCC and high levels of AFP produced lower levels of TNF-α than that of healthy individuals. In conclusion, these results illustrate that AFP induces dysfunction and apoptosis of APCs, thereby offering a mechanism by which HCC escapes immunological control.

Journal of Hepatology, 2001

ObjectiveTo investigate clinical features and to establish optimal management in children with pr... more ObjectiveTo investigate clinical features and to establish optimal management in children with primary immunodeficiency (PID) and liver disease.

Journal of Hepatology, 1993

We evaluated the contribution of flush and selective hepatic angiography in defining the extent a... more We evaluated the contribution of flush and selective hepatic angiography in defining the extent and pattern of major vessel and microvascular arterial lesions and their significance in graft survival. The 50 consecutive patients investigated comprised three clinical groups: Group A (n = 18) were patients with severe graft dysfunction within the first seven days post-transplantation. In this group six of 18 angiograms demonstrated intrahepatic attenuation of the arterial tree suggestive of acute cellular rejection and four of these grafts were lost, compared to a 78% graft survival in the non-arteriopathic group. Group B (n = 16) comprised patients with clinically suspected hepatic arterial thrombosis or stenosis, these diagnoses were confirmed in all patients compared to only 10 positive findings with doppler ultrasonography. Graft survival was only 10% in those patients with artery thrombosis as compared to 100% in those with arterial anastomotic stenoses. Group C patients (n = 16) had histologically confirmed chronic allograft rejection and in ten of them (65%) evidence of arteriopathy was demonstrated despite histological evidence of arteriopathy being present in only 19% of patients. All patients in this group with arteriopathic changes lost their grafts with the exception of one successfully treated with FK506. In two other patients reversibility of chronic rejection was observed, neither of whom had evidence of an arteriopathy.

Journal of Hepatology, 1991

European Journal of Pediatrics, 2005

We report a case of a 6-year-old girl of Afro-Caribbean origin, known to have sickle cell disease... more We report a case of a 6-year-old girl of Afro-Caribbean origin, known to have sickle cell disease (SCD), with recurrent history of jaundice and abdominal pain. She was extensively investigated, including endoscopic retrograde cholangiopancreatography (ERCP), which revealed diffuse cholangiopathy of both extrahepatic and intrahepatic bile ducts. A pigtail stent was placed and balloon dilatation was performed for stricture of the extrahepatic duct. Since then, she remains well and asymptomatic. We suggest that cholangiopathy is the consequence of sickling in the end arteries of the biliary arterial tree.