Neoangiogenesis and sinusoidal "capillarization" in dysplastic nodules of the liver.

The blood supply of hepatocellular carcinoma (HCC) is primarily arterial. Recent studies reported differences of vascular, especially arterial, supply among low- and high-grade dysplastic nodules and HCC. We assessed arterialization using monoclonal antibody specific for smooth muscle actin as well as simultaneous changes in sinusoidal capillarization in cirrhotic nodules, dysplastic nodules, and HCC. We immunohistochemically stained 56 cirrhotic nodules, 20 low-grade dysplastic nodules, 27 high-grade dysplastic nodules, and 20 HCCs for alpha smooth muscle actin (to identify unpaired arteries (i.e., arteries not accompanied by bile ducts) and CD34 (indicating sinusoidal capillarization). Distribution and number of unpaired arteries and distribution of sinusoidal capillarization were graded semiquantitatively. Unpaired arteries were rare in cirrhotic nodules, significantly more common in dysplastic nodules of both types (p < 0.00001), and most common in HCC. Sinusoidal capillarization was least common in cirrhotic nodules, significantly more common in dysplastic nodules (p < 0.0035), and most common in HCC. No topographic relationship between unpaired arteries and sinusoidal capillarization was identified. These findings showed that (1) distributions of sinusoidal capillarization and unpaired arteries in dysplastic nodules are intermediate between those in cirrhotic nodules and HCC, supporting dysplastic nodules as premalignant lesions; (2) unpaired arteries are histologically useful for distinguishing dysplastic nodules from large cirrhotic nodules; and (3) areas of sinusoidal capillarization within dysplastic nodules are unrelated to location of arterialization.

Use of livers with microvesicular fat safely expands the donor pool.

BACKGROUND: The safety of transplanting livers with moderate to severe microvesicular steatosis is unknown. Livers that appear fatty are often abandoned at the donor hospital. We have recently used frozen-section biopsy to distinguish between microvesicular and macrovesicular steatosis. We present here our single-center experience with transplantation of 40 allografts with moderate or severe microvesicular steatosis. METHODS: We reviewed our data on 426 transplants and identified 40 cases in which the donor liver contained at least 30% microvesicular steatosis. Early graft function, patient and graft survival, and donor risk factors for steatosis were examined, and results in this cohort were compared with results in all other patients who received liver transplants at our center during the same time period. We also analyzed the reliability of donor frozen-section biopsies in quantitating microsteatosis. Persistence of steatosis was assessed on the basis of 1-year follow-up biopsies. RESULTS: The incidence of primary nonfunction and poor early graft function was 5% and 10%, respectively. One-year patient and graft survival rates were 80% and 72.5%, respectively. Donor obesity and traumatic death were commonly identified risk factors for microvesicular steatosis. Frozen-section biopsy was reliable for pretransplant decision-making about the use of potential grafts, and the steatosis had disappeared from the graft at 1 year in the majority of cases. CONCLUSIONS: Livers with even severe microvesicular steatosis can be reliably used for transplantation without the fear of high rates of primary nonfunction. There was a significant incidence of poor early graft function, but this did not affect outcome. Microsteatosis is usually associated with some underlying risk factor in the donor and is reversible, as demonstrated by follow-up biopsies after transplant.

Hepatic stellate cell activation in dysplastic nodules: evidence for an alternate hypothesis concerning human hepatocarcinogenesis.

We have previously suggested that dysplastic nodules (also referred to as "adenomatous hyperplasia" or "macroregenerative nodules"), likely precursors of hepatocellular carcinoma (HCC), develop as an infiltrating clonal expansion, in advance of or parallel to cirrhosis. As part of this hypothesis, to explain aspects of their gross and microscopic appearance, we suggested that dysplastic nodules are resistant to the scarring process affecting the rest of the liver. We sought to test this hypothesis by examining the distribution of activated hepatic stellate cells (HSCs), the hallmark of hepatic scarring, in cirrhotic nodules, dysplastic nodules and HCC. We immunohistochemically stained 56 cirrhotic nodules, 20 low grade dysplastic nodules, 27 high grade dysplastic nodules, and 20 HCCs with monoclonal antibodies against alpha-smooth muscle actin to identify activated HSCs. Distribution and number of HSCs were graded semiquantitatively (0 to 4+). In our results, HSCs were significantly less widespread in dysplastic nodules than in cirrhotic nodules or in HCCs (both: p < 0.00001). HSCs were also more prominent in the periphery of dysplastic nodules than in the center, though still fewer in number than in cirrhotic nodules. In conclusion, the low number of activated HSCs in dysplastic nodules, compared to both cirrhotic nodules and HCC, supports our hypothesis concerning dysplastic nodule development: that they arise as clonal expansions of neoplastic hepatocytes in advance of, or parallel to, the development of cirrhosis.

Effects of octreotide on healing of intestinal anastomosis following small bowel obstruction in rats.

PURPOSE: Octreotide is an analog of somatostatin, with the same biologic effects but a longer half-life than somatostatin. The purpose of this experimental study was to search the effects of octreotide on the healing of bowel anastomosis and to observe the anatomic and physiologic changes in the obstructed bowel. METHODS: Two groups of ten male Wistar albino rats (average weight, 250 grams) were used in this study. One group was the octreotide group, and the other was the control group. In both groups, the basal diameters of jejunum were measured before ligation of the bowel 20 cm from the duodenum. Octreotide was administered subcutaneously (7 micrograms/kg/day, in two equal doses) in the first group, and the same volume of saline was used in the control group. Diameters of the obstructed segments were measured, and sodium and potassium levels, obtained from the luminal fluid of the obstructed bowel, were recorded 48 hours following the first operation. Dilated segments were resected, and end-to-end intestinal anastomoses were performed. In rats sacrificed on the fourth and seventh days following the second operation, bursting pressures of the anastomotic and hydroxyproline levels in tissue samples taken from the anastomosis were measured. RESULTS: The diameter of the obstructed bowel increased significantly in the control group (P < 0.05). Sodium and potassium losses were significantly less in the octreotide group (P < 0.001 for sodium; P < 0.01 for potassium). In histopathologic examination, ischemic changes were more evident in the control group (P < 0.05). Anastomotic bursting pressure differences were not significant on the fourth postoperative day (P > 0.05), but differences were significant on the seventh postoperative day (P < 0.05). Anastomotic tissue hydroxproline synthesis on the fourth and seventh postoperative days of the octreotide and control groups did not show significant difference (P > 0.05). CONCLUSION: In this experimental model, it appears that octreotide attenuates the ischemic changes and electrolyte losses in the obstructed bowel.