Anatomical variations of the internal iliac veins in the presacral area: Clinical implications during sacral colpopepxy or extended pelvic lymphadenectomy

The purpose of this study was to classify anatomical variations of the internal iliac vein (IIV) in relation to robotic or laparoscopic extended lymphadenectomy. Between March 2011 and July 2012, 60 consecutive patients underwent robotic or laparoscopic extended lymphadenectomy. We retrospectively reviewed surgical video clips and analyzed the pattern of the IIVs in the presacral area. IIV variations were classified into seven types: Type A, normal (n = 39, 65.0%); Type A with a dilated middle sacral vein (n = 5, 8.3%); Type B, left IIV connecting centrally to the left external iliac vein (n = 5, 8.3%); Type C, a separated trunk of the left IIV draining into the left central common iliac vein (CIV; n = 1, 1.7%); Type D, a separated trunk of the right IIV draining into the left central CIV (n = 8, 13.3%); Type E, a separated trunk of the right IIV draining into the right central CIV (n = 0, 0%); and Type F, separated trunks of the bilateral IIV connecting with each other before draining into the left central CIV (n = 2, 3.3%). The prevalence of IIV anomalies was 26.7%; the incidence of separated IIV trunks was 18.3%. To prevent life‐threatening IIV injury during extended lymphadenectomy or sacral colpopexy, the anatomical variations of the IIVs should be known exactly. Clin. Anat. 28:661–664, 2015. © 2014 Wiley Periodicals, Inc.     

The use of budesonide in the treatment of autoimmune hepatitis in Canada.

BACKGROUND: Autoimmune hepatitis (AIH) is a chronic inflammatory disease that is successfully treated with prednisone and/or azathioprine immunosuppressive therapy in 70% to 80% of patients. The remaining patients are intolerant or refractory to these standard medications. Budesonide, a synthetic glucocorticoid, undergoes a high degree of first-pass metabolism, reducing its systemic bioavailability, and has a 15-fold greater affinity for the glucocorticoid receptor than prednisolone. Budesonide may be a potentially useful systemic steroid-sparing immunosuppressive agent in the treatment of AIH. OBJECTIVE: To review the Canadian experience using budesonide to treat AIH. METHODS: Patients with AIH currently or previously treated with budesonide were identified through the Canadian Association for the Study of the Liver membership. Data were collected regarding their clinical and treatment history. RESULTS: A total of nine patients were identified. All patients were female, with an average age of 39 years (range 12 to 66 years). The indications for budesonide were adverse side effects of prednisone in two patients, noncompliance with prednisone and azathioprine in one patient and intolerance to azathioprine resulting in prednisone dependence in the remaining six patients. Patients were treated in doses ranging from 9 mg daily to 3 mg every other day for 24 weeks to eight years. Seven of nine patients had a complete response, defined as sustained normalization of the aminotransferase levels. The remaining two patients were classified as nonresponders (less than a 50% reduction in pretreatment aminotransferase levels). CONCLUSIONS: In Canada, budesonide has been successfully used in seven of nine patients with autoimmune hepatitis who were either intolerant to prednisone and azathioprine or prednisone-dependent. No adverse effects were reported with budesonide. Budesonide is potentially a valuable treatment option for AIH patients refractory or intolerant to standard therapy, and is deserving of further study.     

Efficacy of commercial condoms in the prevention of hepatitis B virus infection

Tips of synthetic and natural condoms were filled with serum samples containing either hepatitis B virus, herpes simplex virus, or cytomegalovirus, then fit over an 8-in. mechanical vibrator and inserted vibrating into sterile bath solutions for 30 min. Phosphorus 32-labeled hepatitis B and cytomegalovirus molecular probes and viral culture techniques for herpes simplex and cytomegalovirus were used to determine whether leakage of virus had occurred into the surrounding bath solutions. Natural condoms allowed leakage of hepatitis B virus but not herpes simplex virus or cytomegalovirus, whereas synthetic condoms prevented leakage of all viruses. These results suggest that natural condoms might not be effective in preventing sexually transmitted hepatitis B virus infection.     

Human immunodeficiency virus infection in patients with leukemia

Eighteen human immunodeficiency virus (HIV)-seropositive patients were found among 211 previously treated adult patients with a variety of leukemias who had been multiply transfused before April 1985. Patients known to be homosexual or intravenous drug users were excluded from this study. The spouse of one HIV-seropositive patient became HIV infected and subsequently developed the acquired immune deficiency syndrome. Patients with leukemia who were multiply transfused before the availability of screening of blood products for HIV antibody should be counseled regarding their individual risks of HIV infection and the risk to sexual contacts.     

Effects of daily,light and moderate-heavy ethanol exposure on extent of hepatic injury and recovery following toxin-induced acute hepatitis in rats

Daily, light ethanol consumption enhances hepatic regeneration following 70% partial hepatectomy in rats. Whether such consumption has a beneficial effect on the outcome following toxin-induced acute hepatitis has yet to be determined. One hundred ten adult male Spragne-Dawlay rats (200–250 g) were randomized to receive daily gavages with ethanol 1.0 g/kg (light ethanol group), 3.0 g/kg (moderate–heavy ethanol group), or an equal volume of tap water (controls). On day 30, a single injection of D-galactosamine hydrochloride (1.0 g/kg) (D-gal), a potent hepatotoxin that induces liver failure within 24–48 hr, was administered intraperitoneally. Gavages were discontinued and rats killed (N = 4–6/group) on days 1, 3, 5, 7, and 10 after D-gal. Serum AST, bilirubin, and liver histology served to document the extent of liver injury and [³H] thymidine incorporation into hepatic DNA: hepatic regenerative activity. Compared to controls, peak serum AST levels were significantly decreased in the light (–40%, P < 0.05) and increased in the moderate–heavy (+32%, P < 0.05) ethanol groups. Serum bilirubin levels approximately doubled in the light ethanol group while increasing sixfold in the moderate–heavy and control groups (P < 0.05). Histologic evidence of hepatic injury (graded 0–IV) was limited in the light ethanol group, intermediate in controls, and most extensive in the moderate–heavy ethanol group (P < 0.05). Despite less hepatic injury, hepatic regeneration was similar in the light ethanol group compared to controls and significantly impaired in the moderate–heavy ethanol group (P < 0.01). In conclusion, the results of this study indicate that daily, light ethanol administration attenuates hepatic injury, improves hepatic function, and enhances hepatic regeneration following toxin-induced hepatitis in rats.     

Pre-core mutant infections in the Canadian Inuit

BACKGROUND/AIMS: Previous cross-sectional data suggested that chronic hepatitis B viral (HBV) infections in the Canadian Inuit were inactive. The aim of this study was to confirm these findings and document the prevalence of the subsequently described "pre-core mutant" variant of HBV in this population. METHODS: We obtained sera from residents of five remote Canadian Inuit communities. Residents were selected if they were known to be hepatitis B surface antigen (HBsAg) positive or had a history of liver disease. HBV serology, HBV-DNA, and pre-core mutant testing were performed by commercially available assays, polymerase chain reaction (PCR) and direct sequencing of the viral genome, respectively. RESULTS: Sera were obtained from 176/266 (66%) of selected individuals. Thirty-eight (22%) were HBsAg positive and 16 (9.1%) anti-HBs positive. Of HBsAg positive carriers 25/38 (66%) were male as compared to 68/138 (49%) of the remaining individuals (p<0.05). Of 37 HBsAg positive carriers, none were HBeAg positive, 36 (97%) anti-HBe positive and one (3%) HBeAg and anti-HBe negative. Liver enzyme and function tests were normal in all cases. 30/37 (81%) HBsAg positive carriers were HBV-DNA positive and 26/30 (87%) were pre-core mutant positive. CONCLUSION: The majority of HBV infections in community-based Canadian Inuit are inactive and the prevalence of pre-core mutant infections is the highest reported to date.     

Immediate-Early Protooncogene Expression and Liver Function Following Various Extents of Partial Hepatectomy in the Rat

Immediate–early protooncogenes (IEP) are thought to play an important role in hepatocyte replication. Whether the extent of their expression correlates with the strength of the proliferative stimulus and subsequent regenerative activity has yet to be documented in vivo. Data are also lacking with respect to the level at which liver disease is associated with biochemical evidence of hepatic dysfunction. Thus, the objectives of this study were to determine whether a correlation exists between IEP gene mRNA expression and varying extents of partial hepatectomy (PHx) and to document the extent of resection required to result in increases in serum bilirubin levels. Eighty-nine adult, male Sprague-Dawley rats underwent either sham surgery or 20%, 35%, 55%, 70% or 90% PHx. Postoperatively, rats were killed (N = 3–6/group) at 15 and 30 mins and 8 and 24 hrs for c-fos, c-jun, and c-myc mRNA expression by northern blot analyses. Rats killed at 24 hrs also had hepatic regenerative activity documented by [³H]thymidine incorporation into hepatic DNA and serum bilirubin determinations. While c-fos mRNA expression at 15 mins and c-myc mRNA expression at 8 hrs after PHx did not correlate with the extent of PHx (r² = 0.478 and 0.018, respectively), a weak correlation existed between c-jun mRNA expression at 30 mins and the extent of PHx (r² = 0.662, P < 0.05). In terms of IEP mRNA expression and hepatic regenerative activity, a strong correlation existed between c-fos mRNA expression and [³H]thymidine incorporation (r² = 0.851, P < 0.01) but not c-jun or c-myc mRNA expression. Compared to sham operated controls, [³H]thymidine incorporation was 2.0×, 3.4×, 3.2×, 7.8×, and 2.2× increased following 20%, 35%, 55%, 70%, and 90% PHx, respectively. Serum bilirubin levels remained unchanged until 70% PHx, when they increased from baseline values of 0.54 ± 0.05 mg/dl to 1.02 ± 0.15 mg/dl (P < 0.05). A further increase occurred following 90% PHx (1.83 ± 0.30 mg/dl, P < 0.01). In conclusion these findings indicate that c-fos mRNA expression 15 mins after PHx correlates with hepatic regenerative activity but not the strength of the regenerative stimulus and that hepatic parenchymal loss of 55–70% must occur prior to the detection of elevated serum bilirubin levels. The results also indicate that relative to a 70% PHx, 90% PHx is associated with decreased rather than increased hepatic regenerative activity.     

Exogenous Adenosine 5′-triphosphate does not Improve Survival in Rats with Acute Liver Failure

Background Acute liver failure is associated with a marked depletion of intrahepatic adenosine 5′-triphosphate (ATP), a compound required for the maintenance of hepatic function and enhanced hepatic regeneration. Aim The aim of this study was to test the safety and efficacy of exogenous ATP at various doses in a rat model of acute liver failure. Methods Adult male Sprague-Dawley rates (n = 56) received an intraperitoneal dose (1.0 g/kg) of the potent hepatotoxin d-galactosamine (d-galN). Thereafter, rats were divided into groups that received saline (n = 18), low (n = 8), moderate (n = 18) or high (n = 12) doses of ATP for 7 days. Results There was an inverse correlation between ATP dose and survival such that rats treated with low dose ATP had the highest survival rate (50%) compared to moderate (39%) and high (17%) dose treated groups. However, survival in all treated groups was similar (P = 0.085) to that of controls (45%). Liver biochemistry, regenerative activity and ATP levels were similar in the highest survival group (low dose ATP) versus controls. Conclusion These findings suggest that exogenous ATP does not improve and indeed at high doses may impair survival in rats with acute liver failure. Further studies involving a wider range of ATP doses and different routes and frequency of ATP administration are required to determine whether exogenous ATP has therapeutic value in the treatment of acute liver failure.     

Hepatic 31P MRS in rat models of chronic liver disease: assessing the extent and progression of disease

BACKGROUND: Hepatic adenosine triphosphate (ATP) levels are an accurate reflection of functioning hepatic mass following surgical resections and acute liver injury. OBJECTIVE: To determine whether hepatic ATP levels can serve as a non-invasive means of documenting progression of chronic liver disease to cirrhosis. METHODS: In vivo phosphorus-31 magnetic resonance spectroscopy ((31)P MRS) was performed in three animal models of chronic liver disease. Sixty six adult Sprague- Dawley rats were subjected to either thioacetamide, carbon tetrachloride (CCl(4)), or common bile duct ligation (CBDL) to induce liver disease (n=35, 21, and 10, respectively). Serial MRS examinations, blood samples, and liver biopsies (when appropriate) were obtained throughout and/or on completion of the study. RESULTS: Over the course of the chronic liver disease, a progressive decrease in hepatic ATP levels was consistently observed in each model. The findings were most striking when end stage liver disease (cirrhosis) was established. The reduction in hepatic ATP levels correlated with significant changes in serum albumin concentrations (CCl(4) and CBDL models) and the extent of hepatocyte loss seen histologically (all models). CONCLUSION: The results of this study indicate that during progression of chronic liver disease to cirrhosis, there is a progressive reduction in hepatic ATP levels. In addition, changes in hepatic ATP levels correlate with changes in liver function and histology. Thus hepatic (31)P MRS provides a non-invasive means of documenting the severity and progression of parenchymal and cholestatic models of chronic liver disease in rats.     

Health-related quality-of-life in patients with newly diagnosed multiple myeloma in the FIRST trial: lenalidomide plus low-dose dexamethasone versus melphalan,prednisone, thalidomide

We compared the health-related quality-of-life of patients with newly diagnosed multiple myeloma aged over 65 years or transplant-ineligible in the pivotal, phase III FIRST trial. Patients received: i) continuous lenalidomide and low-dose dexamethasone until disease progression; ii) fixed cycles of lenalidomide and low-dose dexamethasone for 18 months; or iii) fixed cycles of melphalan, prednisone, thalidomide for 18 months. Data were collected using the validated questionnaires (QLQ-MY20, QLQ-C30, and EQ-5D). The analysis focused on the EQ-5D utility value and six domains pre-selected for their perceived clinical relevance. Lenalidomide and low-dose dexamethasone, and melphalan, prednisone, thalidomide improved patients’ health-related quality-of-life from baseline over the duration of the study across all pre-selected domains of the QLQ-C30 and EQ-5D. In the QLQ-MY20, lenalidomide and low-dose dexamethasone demonstrated a significantly greater reduction in the Disease Symptoms domain compared with melphalan, prednisone, thalidomide at Month 3, and significantly lower scores for QLQ-MY20 Side Effects of Treatment at all post-baseline assessments except Month 18. Linear mixed-model repeated-measures analyses confirmed the results observed in the cross-sectional analysis. Continuous lenalidomide and low-dose dexamethasone delays disease progression versus melphalan, prednisone, thalidomide and has been associated with a clinically meaningful improvement in health-related quality-of-life. These results further establish continuous lenalidomide and low-dose dexamethasone as a new standard of care for initial therapy of myeloma by demonstrating superior health-related quality-of-life during treatment, compared with melphalan, prednisone, thalidomide.