Can we improve the clinical risk score? The prognostic value of p53, Ki-67 and thymidylate synthase in patients undergoing radical resection of colorectal liver metastases

Objectives: The aim of this study was to assess whether biological markers can provide prognostic information additional to that supplied by the clinical risk score (CRS) in patients with colorectal liver metastases.Methods: A retrospective review of a prospectively maintained database was conducted. Patients selected for this study were treated between 1996 and 2011 with potentially curative liver surgery. Expressions of p53, Ki-67 and thymidylate synthase were assayed using immunohistochemical techniques on tissue microarrays.Results: A total of 98 (24%) of 406 patients met the inclusion criteria. The median follow-up was 103 months. Analysis revealed a correlation between p53 protein overexpression and high CRS (P = 0.058). Following multivariate analysis, only high CRS remained as an independent negative prognostic predictor of survival (P = 0.018), as well as an indicator of early recurrence of disease (P = 0.010). Of the biological markers investigated, only Ki-67 overexpression was identified as a positive predictor of survival on multivariate analysis (P = 0.038).Conclusions: Ki-67 overexpression was a positive predictor of survival. Only high CRS remained an independent negative prognostic predictor.     

Pulmonary microthrombi during left ventricular assist device implantation

Critically ill heart failure patients undergoing left ventricular assist device implantation have alterations in their coagulation profiles; as a result, hemorrhagic complications during the postoperative period are the most common and serious problems during device support of these patients. The use of aprotinin therapy is generally accepted for reducing bleeding after coronary artery bypass grafting procedures, heart transplantation, and insertion of a left ventricular assist device. We describe the case of a patient who had a suprasystemic increase in pulmonary artery pressure, caused by thromboembolic occlusion of the pulmonary arterioles after urgent implantation of a left ventricular assist device. The complications developed after the patient was weaned from cardiopulmonary bypass and heparinization was reversed with protamine. Although the thrombosis was successfully reversed with intraoperative administration of tissue plasminogen activator directly to the pulmonary artery, the patient died of massive hemorrhage 6 hours later. To our knowledge, the direct application of tissue plasminogen activator into the pulmonary artery in such a catastrophic situation has not been used elsewhere.     

Acute presentation of a solid pseudopapillary tumor of the pancreas

We report a case of acute presentation of a solid pseudopapillary tumor of the pancreas in a young boy who had suffered a blunt abdominal trauma. Urgently performed CT examination and repeated ultrasound revealed a subhepatic mass, which gradually increased in size, but the imaging features were not specific enough to permit a precise diagnosis. Because signs of peritoneal irritation and increased circulatory instability gradually developed within the hours of observation, the decision was made to perform an urgent exploratory laparotomy. The exploration revealed a hematoperitoneum and a large hematoma-like subhepatic bleeding mass. Further exploration showed that this mass was a tumor arising from the head of the pancreas, which had ruptured on the surface. A curative pancreatoduodenectomy was performed. Pathohistological examination of the resected specimen revealed a solid pseudopapillary tumor of the pancreas, an extremely rare tumor predominantly occurring in adolescent girls and in young adult women. It has a favorable prognosis if resected radically. The boy in our report is feeling well 36 months after the operation.     

Do C1q or IgM nephropathies predict disease severity in children with minimal change nephrotic syndrome?

Background

It has been suggested that C1q and immunoglobulin M (IgM) nephropathy are variants of minimal change nephrotic syndrome (MCNS). Many researchers believe that these two conditions signify a worse prognosis for children with MCNS in comparison with immunofluorescence (IF)-negative MCNS. The aim of our study was to determine the prognostic significance of C1q nephropathy and IgM nephropathy in children with MCNS.

Methods

Fifty-five children with MCNS who had been biopsied over the course of 24 years at our institution were retrospectively categorized into three groups on the basis of IF microscopy findings: IF-negative MCNS (29/55 patients), MCNS with IgM nephropathy (19/55 patients), and MCNS with C1q nephropathy (7/55 patients). Clinical characteristics at disease presentation, clinical course, and renal outcome were compared between groups during the median follow-up period of 16.9 years (minimum 1.0, maximum 31.1 years).

Results

No statistically significant differences in clinical characteristics at disease presentation, clinical course, and renal outcome were found. Children with IgM nephropathy, C1q nephropathy, and IF-negative MCNS were clinically indistinguishable.

Conclusions

We concluded that C1q or IgM nephropathy variants do not seem to signify a worse prognosis in children with MCNS in comparison with IF-negative MCNS.     

Mucosal immunotherapy of tuberculosis: is there a value in passive IgA?

Immunotherapeutic approaches, which have been considered for tuberculosis (TB), include immuno-potentiating or suppressing agents, cytokines, antibodies, DNA vaccines, non-pathogenic mycobacteria and mycobacterial extracts. While most or all of these potential agents showed at least some degree of promise in various experimental models, few progressed to clinical trials, yielding only moderately encouraging, though controversial results. Consequently, further research is required, as the need for an immunological agent, adjunct to chemotherapy, remains strongly justified. Its purpose is to shorten the currently protracted (6-9 months) drug treatment and thus increase compliance rates, which are most disappointing in areas with the highest disease prevalence. Using a mouse model of Mycobacterium tuberculosis (Mtb) infection, we recently reported, that an intranasally given monoclonal IgA antibody significantly reduced the bacterial load in the infected lungs, and that this protective effect of IgA could be further extended by co-inoculation with interferon gamma (IFNgamma). In this review, we describe the main features of IgA and its cellular receptors, the extent and possible mechanisms of passive vaccination with an IgA monoclonal antibody against the alpha-crystallin antigen of Mtb and discuss the potentials of this approach in the wider context of immunotherapy of TB.     

C1Q nephropathy in children

C1q nephropathy (C1qNP) is a peculiar form of glomerulonephritis characterized by mesangial immunoglobulin and complement deposits, predominantly C1q, with no evidence of systemic lupus erythematosus. We describe the incidence, manifestation, histopathologic findings, follow-up, treatment and outcome of C1qNP. Twelve C1qNP patients were identified among 131 children who had undergone renal biopsy, accounting for a 9.16% incidence of C1qNP. Light microscopy examination showed focal segmental glomerulosclerosis (FSGS) with or without diffuse mesangial proliferation (n=6), minimal change disease (MCD) (n=4) or focal glomerulonephritis (n=2). C1q deposits were found in all, while electron microscopy revealed visible deposits in nine cases. Eight children presented with nephrotic syndrome, while one had nephrotic proteinuria and renal insufficiency that progressed to end-stage renal failure. The remaining three patients presented with nonnephrotic proteinuria associated with microhematuria, hypertension or renal insufficiency. Only one nephrotic syndrome patient responded excellently to corticosteroids, while four became corticosteroid dependent, and three were corticosteroid resistant, showing a very poor response to other immunosuppressive therapy as well. Patients with non-nephrotic proteinuria demonstrated fixed laboratory findings. Most C1qNP patients had FSGS or MCD, the majority of them presenting with corticosteroid-dependent or corticosteroid-resistant nephrotic syndrome. The latter showed a very poor response to any immunosuppressive therapy and high risk for progressive renal insufficiency.     

Changes in muscle tissue oxygenation during stagnant ischemia in septic patients

Objective To determine changes in the rate of thenar muscles tissue deoxygenation during stagnant ischemia in patients with severe sepsis and septic shock.Design and setting Prospective observational study in the medical ICU of a general hospital.Patients and participants Consecutive patients admitted to ICU with septic shock (n=6), severe sepsis (n=6), localized infection (n=3), and healthy volunteers (n=15).Interventions Upper limb ischemia was induced by rapid automatic pneumatic cuff inflation around upper arm.Measurements and results Thenar muscle tissue oxygen saturation (StO₂) was measured continuously by near-infrared spectroscopy before and during upper limb ischemia. StO₂ before intervention was comparable in patients with septic shock, severe sepsis, or localized infection and healthy volunteers (89 [65, 92]% vs. 82 [72, 91]% vs. 87 [85, 92]% vs. 83 [79, 93]%, respectively; p>0.1). The rate of StO₂ decrease during stagnant ischemia after initial hemodynamic stabilization was slower in septic shock patients than in those with severe sepsis or localized infection and in controls (–7.0 [–3.6, –11.0] %/min vs. –10.4 [–7.8, –13.3] %/min vs. –19.5 [–12.3, –23.3] vs. –37.4 [–27.3, –56.2] %/min, respectively; p=0.041). At ICU discharge the rate of StO₂ decrease did not differ between the septic shock, severe sepsis, and localized infection groups (–17.0 [–9.3, –28.9] %/min vs. –19.9 [–13.3, –23.6] %/min vs. –23.1 [–20.7, –26.2] %/min, respectively), but remained slower than in controls (p<0.01). The rate of StO₂ decrease was correlated with Sequential Organ Failure Assessment (SOFA) score (r=0.739, p<0.001).Conclusions After hemodynamic stabilization thenar muscle tissue oxygen saturation during stagnant ischemia decreases slower in septic shock patients than in patients with severe sepsis or localized infection and in healthy volunteers. During ICU stay and improvement of sepsis the muscle tissue deoxygenation rate increases in survivors of both septic shock and severe sepsis and was correlated with SOFA score.