Franklin Greif

Erythropoietin increases survival and attenuates fulminant hepatic failure injury induced by D-galactosamine/lipopolysaccharide in mice.

Background. Liver transplantation is the only therapy of proven benefit in fulminant hepatic failure (FHF). Lipopolysaccharide (LPS), d-galactosamine (GalN)-induced FHF is a well-established model of liver injury in mice. Erythropoietin has a powerful tissue-protective effect in animal models. The aim of this study was to investigate the effect and mechanism of recombinant human erythropoietin (rhEPO) administration in FHF mice. Methods. C57BL/6 (n=42) mice were studied in vivo in a fulminant model induced by GalN/LPS. rhEPO was administered 30 min after the induction of FHF. Serum liver enzymes and hepatic tumor necrosis factor (TNF)-&agr; and interleukin (IL)-1&bgr; levels were determined. Histologic analysis was performed, and apoptotic cells were identified by immunohistochemistry for caspase-3. Nuclear factor (NF)-&kgr;B and c-Jun-N-terminal kinase (JNK) activation were studied using Western blot analysis. Results. After the induction of FHF, all control mice died within 12 hr of GalN/LPS administration. However, 83% of mice that were administered rhEPO were alive 2 weeks later, and overall survival improved (Kaplan-Meier, P<0.001). The serum liver enzymes, hepatic TNF-&agr; and IL-1&bgr; levels, liver histologic injury, and apoptotic hepatocytes were significantly reduced in FHF mice that were administered rhEPO compared with untreated mice. A significant decrease in hepatic NF-&kgr;B and JNK activation was noted in FHF rhEPO-treated mice compared with FHF untreated mice. Conclusions. The administration of rhEPO brought about increased survival and attenuation of the hepatic injury. This was associated with decreased hepatic NF-&kgr;B and JNK activation and thus TNF-&agr; and IL-1&bgr; levels. These findings have important implications for the potential use of rhEPO in FHF.

Dual effect of erythropoietin on liver protection and regeneration after subtotal hepatectomy in rats

The only currently offered curative option for many patients with primary or secondary liver tumors is the resection of hepatic tumors. The aim of this study was to evaluate the role of recombinant human erythropoietin (rhEPO) in liver protection and regeneration after subtotal hepatectomy in rats. Rats undergoing 70% hepatectomy received an intraperitoneal injection of saline (control) or rhEPO (4 U/g) 30 minutes prior to resection. Liver function was assessed by the measurement of the international normalized ratio (INR) levels, and hepatic injury was assessed by serum alanine aminotransferase and aspartate aminotransferase levels. Hepatic apoptosis was assessed by intrahepatic caspase‐3 activity and morphological criteria. The regeneration capacity of remnant livers was assessed over 7 days with the regenerated liver/body weight ratio, immunohistochemistry markers of cell proliferation (Ki‐67) and angiogenesis (von Willebrand factor), and phosphorylated extracellular signal‐regulated kinase signaling. Two and 4 days after subtotal hepatectomy, the regenerated liver/body weight ratio was significantly higher in animals treated with rhEPO versus the control group (P < 0.005). Serum liver enzymes and INR levels on days 2 and 4 post‐hepatectomy were significantly lower in animals pretreated with rhEPO in comparison with the control group (P < 0.005). No statistically significant difference was noted in intrahepatic hepatic caspase‐3 activity, immunohistochemistry for caspase‐3, or a terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick‐end labeling assay between the hepatectomized groups. In the rhEPO‐pretreated group, the mitotic index, Ki‐67 and von Willebrand factor expression, and extracellular signal‐regulated kinase activity were significantly higher on day 2 post‐hepatectomy (P < 0.05) in comparison with the control group. In conclusion, rhEPO treatment may offer a unique beneficial dual‐function strategy for hepatic protection and regeneration immediately after subtotal hepatectomy in rats. Liver Transpl, 2010.

Acid ingestion: another cause of disseminated intravascular coagulopathy

This report presents a case of disseminated intravascular coagulopathy developing within 2 h after ingestion of 96% (glacial) acetic acid in an attempted suicide. Although bleeding from the GI tract is found commonly in acid injury, this case illustrates that it may also be an early manifestation of disseminated intravascular coagulopathy.

Mutations at Vicinity of Catalytic Sites of Hepatitis C Virus NS3 Serine Protease Gene Isolated from Hepatocellular Carcinoma Tissue

The mechanism of hepatitis C virus (HCV) -induced hepatotocellular carcinoma (HCC) is still unknown, but in vitro studies clearly suggest that HCV proteins exert a direct effect on liver carcinogenesis. HCV NS3 serine protease is known to play a key role in the life cycle of the virus and may interact with the host cellular regulatory proteins. The aim of the present study was to conduct a genetic analysis of the HCV NS3 gene coding for the serine protease isolated from serum, tumor, and nontumor tissue of HCC patients. RNA was extracted and HCV cDNA was amplified by nested reverse transcriptase–polymerase chain reaction (RT-PCR). Sequence comparison yielded unique changes at the vicinity of the catalytic sites of the NS3 clones isolated only from HCC tissue. These changes included the insertion of a “large” and charged amino acid, substitution of a polar with a hydrophobic amino acid, and substitution of a charged with a polar amino acid. Those changes affect the electrostatic charge around the active site, and thus the activity and substrate specificity of the serine protease. This is the first study to define significant amino acid changes at the catalytic domain of the NS3 serine protease gene isolated from HCC tissue.

Burkitt's lymphoma protruding through the anus

A four-year-old boy had a cecoanal intussusception prolapsing through the anus. A 4×4 cm cecal tumor served as the leading point of the intussusception. Laparotomy and histology revealed that the tumor was a solitary Burkitts lymphoma of the cecum. Isolated Burkitts lymphoma, as presented here, is rare, and such a combination has never been reported. Intussuception prolapsing through the anus and Burkitts lymphoma are discussed, as well as a possible reason for the rarity of the condition.

Breast Cancer and Sarcoidosis: Case Series and Review of the Literature.

Background: Sarcoidosis is a chronic inflammatory disease of unknown etiology, which can involve different organs and systems. Accordingly, sarcoidosis can mimic breast cancer, making the differential diagnosis very difficult. Case Report: 5 patients with a diagnosis of both sarcoidosis and breast cancer followed by the Rabin Medical Center between January 1993 and June 2012 were enrolled in this study. Additionally, a comprehensive literature review which identified 104 patients diagnosed with breast cancer and sarcoidosis was carried out. In both populations reviewed, the average age at diagnosis of sarcoidosis and breast cancer was 57 years. Among the 66 patients with both sarcoidosis and breast cancer, sarcoidosis preceded breast cancer in 31 cases, followed it in 23 cases, and appeared concurrently in 10 cases. Conclusion: Based on our clinical cases and literature review, a histological study is recommended over imaging if sarcoidosis or breast cancer may be present. Furthermore, breast cancer is rarely associated with sarcoidosis or sarcoidosis-like reaction.

Intraoperative ultrasound in colorectal surgery.

To assess the accuracy of intraoperative ultrasound (IOUS) as a localizing technique for colorectal resections, and its impact on surgical management.

Operative Treatment of Hepatic Hydatid Cysts: A Single Center Experience in Israel, a Nonendemic Country

Background. Hydatid cyst disease is a zoonosis caused by Echinococcus genera. The disease is endemic to certain rural areas in the world. Operative treatment is the main component in curing hydatid cysts of the liver. Objective. Describing the unique characteristics of the hydatid cyst patients in Israel, a nonendemic country. Methods. Data was collected form 29 patients treated operatively in Rabin Medical Center from 1994 to 2007. Results. The study included 18 females and 11 males with an average age of 54.9 years. Fifty-two% of the patients immigrated as children from Arab countries to Israel, 21% were Arab-Israelis leaving in the north and center of Israel, and 24% immigrated from the former Communist Bloc. Pericystectomy was performed in 20/29, and cyst unroofing was performed in 9/29. Hydatid cysts average size was 10.7 cm, and the cysts were located in the right or left or involved both lobes in 62%, 28%, and 10% of the lesions, respectively. Postoperative mortality occurred in one case, and severe morbidity occurred in 4 patients. Conclusions. Hydatid cyst disease in Israel is uncommon and is mostly seen in distinct 3 demographic groups. Despite the relatively low patient volume, good results in terms of morbidity, mortality, and recurrence were achieved.

Should Echogenic Material in the Urinary Bladder Noticed on FAST Preclude Urinary Catheter Insertion in a Trauma Patient Until Further Evaluation

Background:Serious urethral and bladder injuries are most often associated with severe blunt trauma. The most common diagnostic tool used to assess lower urinary tract injuries is a retrograde urethrogram. However, the decision to place a Foley catheter is often made on clinical grounds during initial stabilization phase of a trauma victim. If there is a clinical suspicion of a urethral injury, a Foley catheter should not be introduced until further evaluation is made. Focused abdominal sonography for trauma (FAST) is a major tool for primary evaluation of trauma victims. Treating trauma patients, we encountered an unusual “pick up”, namely, blood clots in the urinary bladder in two patients.Case Report:We report on two cases of severely traumatized patients on which FAST examination detected an echogenic material in the bladder. This correlated with severe injuries to the urethra and urinary bladder. Moreover, ignorance of this finding in a patient without obvious clinical signs of urethral injury (Patient 1) led to a Foley catheter insertion, and as a consequence, a complex jatrogenic injury to the urethra. On the basis of this study, we hypothesize that the presence of an echogenic material on FAST examination should be considered blood until proven otherwise, and a urinary bladder catheter should not be passed, even in the absence of clinical signs of urethral injury. Since urogenital trauma is rare, this concept should be validated in the prospective study in a high-volume trauma center.