Age-related changes in liver function are important because they may promote susceptibility to adverse drug reactions, neurotoxicity, atherosclerosis, and other important diseases in older people. Age-related changes in the rat hepatic sinusoidal endothelium, termed pseudocapillarization, have been described recently and these may contribute to hepatic impairment. The present study has examined surgical and post-mortem specimens with immunohistochemistry and transmission electron microscopy to determine whether pseudocapillarization also occurs in older humans. The age of the subject, independent of systemic disease or hepatic pathology in surgical and post-mortem samples of human liver, was associated with increased peri-sinusoidal expression of von Willebrand's factor, collagen I, collagen IV, and staining with Masson's trichrome. Electron microscopy revealed significant age-related thickening of the sinusoidal endothelium (young 165 +/- 17 nm, middle age 222 +/- 11 nm, older 289 +/- 9 nm, p < 0.001) with loss of fenestrations (young 7.7 +/- 0.7 per 10 micro m, middle age 3.6 +/- 0.5 per 10 micro m, older 1.5 +/- 0.4 per 10 micro m, p < 0.001), and age-related deposition of basal lamina and collagen. In conclusion, ageing in humans is associated with morphological changes in the sinusoidal endothelium and space of Disse which are presumptively related to the ageing process and potentially represent an important link between the ageing process and disease susceptibility.

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One hundred thirty-nine surgically treated patients with medullary carcinoma of the thyroid gland (MTC) were seen in our institution between January, 1926 and December, 1973. The incidence of this tumor among all thyroid cancers was 8%. Twenty-nine patients had the familial form of MTC; they were subclassified, on the basis of the phenotype, into a group of 15 patients with Sipple syndrome (or multiple endocrine neoplasia (MEN) Type 2A) and a group of 14 patients with mucosal-neuroma phenotype (or MEN type 2B). Better survivorship was seen in the younger patients, in those with bilateral tumors, in familial MTC, and in patients whose tumor was confined to the thyroid gland at the initial surgery. The incidence of tumor recurrence was 34%. However, in those with adequate surgical treatment, the recurrence was only 23%. The 5- and 10-year survivorships were 80% and 67%, respectively. The best chance of cure lies in early diagnosis through the use of immunoreactive calcitonin measurement in family members at risk, and an aggressive surgical attack on the primary tumor and any cervical metastases.

BackgroundThe management of unresectable or metastatic gastrointestinal stromal tumors (GISTs) has previously been difficult as they are resistant to conventional chemotherapy and radiation. The development of imatinib mesylate has made a major impact on the management of advanced GISTs. It is apparent that there are sanctuary sites such as the central nervous system where imatinib does not achieve adequate concentrations. We describe the case of a man with metastatic GIST who experienced multiple cerebral relapses of disease while systemic disease progression appeared to be controlled by imatinib.Case presentationA 47-year-old man presented in July 1999 with a jejunal GIST with multiple hepatic metastases. The jejunal primary was resected and after unsuccessful cytoreductive chemotherapy, the liver metastases were also resected in December 1999. The patient subsequently relapsed in August 2001 with symptomatic hepatic, subcutaneous gluteal, left choroidal and right ocular metastases all confirmed on CT and PET scanning. Biopsy confirmed recurrent GIST. MRI and lumbar puncture excluded central nervous system involvement. The patient was commenced on imatinib 400 mg bd in September 2001 through a clinical trial.The symptoms improved with objective PET and CT scan response until December 2002 when the patient developed a right-sided foot drop. MRI scan showed a left parasagittal tumor which was resected and confirmed histologically to be metastatic GIST. Imatinib was ceased pre-operatively due to the trial protocol but recommenced in February 2003 on a compassionate use program. The left parasagittal metastasis recurred and required subsequent re-excision in September 2003 and January 2004. Control of the systemic GIST was temporarily lost on reduction of the dose of imatinib (due to limited drug supply) but on increasing the dose back to 800 mg per day, systemic disease was stabilized for a period of time before generalised progression occurred.ConclusionThis case illustrates that the brain can be a sanctuary site to treatment of GISTs with imatinib. Maintaining dosing of imatinib in the face of isolated sites of disease progression is also important, as other metastatic sites may still be sensitive.

INTRODUCTIONThe aim of this study was to determine the efficacy and complications of postoperative endoscopic retrograde cholangiopancreatography (ERCP) in confirming and treating choledocholithiasis found at intraoperative cholangiography during laparoscopic cholecystectomy.METHODSPatients who had undergone ERCP following a cholecystectomy between 2008 and 2011 with an indication of intraoperative cholangiography findings consistent with choledocholithiasis were identified from a prospectively collected database of a single endoscopist. Deep biliary access rate, confirmation of choledocholithiasis, clearance rate of bile duct stones, delay between cholecystectomy and postoperative ERCP, and the complication rates following the procedure were analysed.RESULTSThe median age of the 41 patients (16 male, 25 female) was 42 years (range: 18–82 years). Sixteen surgeons performed the operations with a median delay of 6 days (range: 1–103 days) between cholecystectomy and postoperative ERCP. Common bile duct access was achieved in 100% of the patients, with ERCP taking a median time of 16 minutes (range: 6–40 minutes). Initial ERCP confirmed the presence of a stone in 30 patients (73%) and successful stone removal occurred in 28 of these 30 patients (93%) during the first ERCP and in the remaining 2 on a subsequent ERCP. Following ERCP, two patients (4.9%) experienced extended hospital stays for four and eight days owing to complications, including one patient (2.4%) with mild acute pancreatitis.CONCLUSIONSThis study demonstrates that postoperative ERCP is highly effective in both confirming and treating choledocholithiasis. However, there is a significant risk of short-term complications that must be taken into consideration when deciding management.

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