Tarek Ezzat

Use of hepatocyte and stem cells for treatment of post‐resectional liver failure: are we there yet?

Post‐operative liver failure following extensive resections for liver tumours is a rare but significant complication. The only effective treatment is liver transplantation (LT); however, there is a debate about its use given the high mortality compared with the outcomes of LT for chronic liver diseases. Cell therapy has emerged as a possible alternative to LT especially as endogenous hepatocyte proliferation is likely inhibited in the setting of prior chemo/radiotherapy. Both hepatocyte and stem cell transplantations have shown promising results in the experimental setting; however, there are few reports on their clinical application. This review identifies the potential stem cell sources in the body, and highlights the triggering factors that lead to their mobilization and integration in liver regeneration following major liver resections.

Dynamic tracking of stem cells in an acute liver failure model

AIM To investigate a dual labeling technique, which would enable real-time monitoring of transplanted embryonic stem cell (ESC) kinetics, as well as long-term tracking. METHODS Liver damage was induced in C57/BL6 male mice (n = 40) by acetaminophen (APAP) 300 mg/kg administered intraperitoneally. Green fluorescence protein (GFP) positive C57/BL6 mouse ESCs were stained with the near-infrared fluorescent lipophilic tracer 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR) immediately before transplantation into the spleen. Each of the animals in the cell therapy group (n = 20) received 5 × 10(6) ESCs 4 h following treatment with APAP. The control group (n = 20) received the vehicle only. The distribution and dynamics of the cells were monitored in real-time with the IVIS Lumina-2 at 30 min post transplantation, then at 3, 12, 24, 48 and 72 h, and after one and 2 wk. Immunohistochemical examination of liver tissue was used to identify expression of GFP and albumin. Plasma alanine aminotransferase (ALT) was measured as an indication of liver damage. RESULTS DiR-stained ESCs were easily tracked with the IVIS using the indocyanine green filter due to its high background passband with minimal background autofluorescence. The transplanted cells were confined inside the spleen at 30 min post-transplantation, gradually moved into the splenic vein, and were detectable in parts of the liver at the 3 h time-point. Within 24 h of transplantation, homing of almost 90% of cells was confirmed in the liver. On day three, however, the DiR signal started to fade out, and ex vivo IVIS imaging of different organs allowed signal detection at time-points when the signal could not be detected by in vivo imaging, and confirmed that the highest photon emission was in the liver (P < 0.0001). At 2 wk, the DiRsignal was no longer detectable in vivo; however, immunohistochemistry analysis of constitutively-expressed GFP was used to provide an insight into the distribution of the cells. GFP +ve cells were detected in tissue sections resembling hepatocytes and were dispersed throughout the hepatic parenchyma, with the presence of a larger number of GFP +ve cells incorporated within the sinusoidal endothelial lining. Very faint albumin expression was detected in the transplanted GFP +ve cells at 72 h; however at 2 wk, few cells that were positive for GFP were also strongly positive for albumin. There was a significant improvement in serum levels of ALT, albumin and bilirubin in both groups at 2 wk when compared with the 72 h time-point. In the cell therapy group, serum ALT was significantly (P = 0.016) lower and albumin (P = 0.009) was significantly higher when compared with the control group at the 2 wk time-point; however there was no difference in mortality between the two groups. CONCLUSION Dual labeling is an easy to use and cheap method for longitudinal monitoring of distribution, survival and engraftment of transplanted cells, and could be used for cell therapy models.

The flavonoid monoHER prevents monocrotaline-induced hepatic sinusoidal injury in rats.

Sinusoidal obstruction syndrome (SOS) occurs in 50–70% of patients after oxaliplatin treatment for hepatic colorectal metastasis. SOS is associated with portal hypertension and is caused by oxidative damage to endothelial cells and matrix metalloproteinase (MMP) induction. We studied the effect of a flavonoid (monoHER) on SOS prevention.

Primary hyperparathyroidism with water clear cell content: the impact of histological diagnosis on clinical management and outcome

Water clear cell hyperplasia (WCCH) and water clear cell adenomas (WCCA) of the parathyroid glands are rare causes of primary hyperparathyroidism. We report in this series one case of WCCH and two cases of WCCA representing 0.3% of patients with primary hyperparathyroidism presenting to our institution. Increased parathyroid cellular water content was responsible for relatively larger parathyroid gland sizes. However, this was not associated with higher biochemical markers or more severe clinical presentations. Histological distinction between WCCH and WCCA is difficult but important since patients with WCCH who have had a parathyroidectomy via a unilateral neck exploration may carry an increased risk of future disease recurrence.

Hepato-biliary Cystadenoma with Intraductal Extension: Unusual Cause of Obstructive Jaundice.

Hepatobiliary cystadenoma with mesenchymal stroma was first described as a distinct histopathologic entity by Wheeler et al. [1]. These potentially malignant tumours, representing a small proportion of all cystic lesions of the liver and biliary tract, occur more commonly in women of child-bearing age [2, 3]. Complete surgical excision is the recommended treatment in view of their malignant potential [2]. Histologically, these tumours are defined by a columnar or cuboidal epithelium, an intermediary subepithelial layer of mesenchymal or fusiform cells (ovarian-like stroma) and an external layer formed by a fibroconjunctive sheath that separates it from adjacent hepatic parenchyma, making a pseudocapsule [3]. Two distinct types are recognized depending on the presence or absence of mesenchymal “ovarian-type” stroma [3]. We present an interesting case of a female patient admitted with painless obstructive jaundice. Imaging and endoscopic retrograde cholangio-pancreatography (ERCP) revealed the presence of an obstructing endobiliary lesion with extension into the liver. Histology confirmed the lesion to be a mucinous cystadenoma of the liver with ovarian type stroma.

Cystic lesions of the pancreas: current trends in approach and management

The more frequent deployment of cross-sectional imaging for various abdominal conditions has resulted in an increased detection of cystic pancreatic lesions, particularly cystic pancreatic neoplasms. Cystic pancreatic lesions may be neoplastic or non-neoplastic. They may appear radiologically similar and often present a diagnostic dilemma; they need to be diagnosed and differentiated with accuracy in order to offer optimum treatment. Some of the cystic neoplasms are potentially malignant and have a wide spectrum of histological variation from the frankly benign ‘adenomas’ to invasive adenocarcinomas .When identified, these cystic lesions need a systematic work up and a diagnostic algorithm should be followed to its logical conclusion. This article reviews these cystic lesions of the pancreas, neoplastic and pseudocysts, and aims to update readers with the current trends in their diagnosis and management.

Wandering hemi-spleen: Laparoscopic management of wandering spleen in a case of polysplenia

INTRODUCTION Several congenital anomalies of the spleen have been reported. The polysplenia is a rare anomaly in which the normal spleen is replaced with two or more smaller spleens. The wandering spleen is another anomaly resulting from the laxity of the splenic ligaments. The concomitance of both anomalies is very rare. PRESENTATION OF A CASE A 22-year old female patient presented with intermittent left hypochondrial pain for more than a year. After a thorough examination of the patient, she only had bilateral accessory nipples. Routine laboratory investigations were all normal. An abdominal ultrasound U/S scan was unremarkable except for a ptotic spleen. with a large splenule 5cm×3cm located near the fundus of the stomach. These findings were confirmed by a CT scan. A decision for a surgical intervention was then made, and the laparoscopic approach was chosen which revealed the condition. Laparoscopic removal of the wandering part was executed. The patient discharged on the first post-operative day. DISCUSSION The decision making in cases of wandering spleen is not always the same. The association of a wandering spleen with polysplenia is an asset to the surgical decision, along with the age of the patient. CONCLUSION The laparoscopic approach is an important tool in the diagnosis and management of wandering spleen. The diagnosis of polysplenic anomaly could provide a guidance for the surgical strategy in patients with wandering spleen.

MEN 2 syndrome masquerading as MEN 1

Patients with multiple endocrine neoplasia (MEN) type 2A develop medullary thyroid cancer, which is associated with poor prognosis in its metastatic stage. Hyperparathyroidism is a common finding in both MEN 1 and 2. We report a 68-year-old patient diagnosed clinically with MEN 1 based on the presence of hyperparathyroidism and pituitary Cushing’s disease with no supporting genetic evidence. The hyperparathyroidism was later found to be part of MEN 2A with underlying metastatic medullary thyroid cancer. We highlight the importance of genetic confirmation before a diagnosis of MEN 1 is made as other more serious pathologies might be overlooked.

Sinusoidal obstruction syndrome: Correct dosing of monocrotaline and the validity of the rat model

TAREK EZZAT, MD, PhD, DIPOK K. DHAR, MD, PhD, AND STEVEN W.M. OLDE DAMINK, MD, MSc, PhD* UCL Institute for Liver and Digestive Health, Department of HPB and Liver Transplantation Surgery, University College London Medical School, Royal Free Campus, London, UK Department of Surgery, University of Alexandria, Alexandria, Egypt Department of Surgery, Maastricht University Medical Centre, Nutrition and Toxicology Research Institute (NUTRIM), Maastricht, The Netherlands

Surgery of the Suprarenal Gland

The first anatomical report of the adrenal glands comes from Eustachius in 1563. The anatomical division in two zones, an outer cortex and an inner medulla, came in 1805 by Cuvier [1]. Other prominent scientists that have contributed to the understanding of the role and function of the adrenal glands are Thomas Addison who described the features of adrenal insufficiency, Harvey Cushing who in 1932 reported 11 patients with the characteristic features of the syndrome that today bears his name, and Conn who in 1955 described the syndrome resulting from excessive secretion of this mineralocorticoid [2].