Prognostic significance of microscopic and macroscopic extracapsular spread from metastatic tumor in the cervical lymph nodes

It has been established that the presence or absence of cervical node metastases in patients with head and neck squamous cell carcinoma (HNSCC) is a powerful prognostic indicator. This report reviews the evolution of thinking over the past 70 years with regard to the import and detection of cervical nodal metastases which exhibit spread of tumor beyond the confines of the original encompassing nodal capsule. In the process, this discussion touches upon clinical examination, gross and microscopic pathologic examination, and radiographic imaging studies. In particular, the distinction between gross nodal extracapsular spread of tumor and microscopic nodal extracapsular spread of tumor has been drawn in recent reports; this raises the possibility that identification of microscopic breaching of the node capsule by tumor might provide clinically significant information which is not provided by the gross observation of an intact lymph node capsule. While it remains to be seen whether microscopic extracapsular spread alone will prove to be an important prognostic factor, it is recommended that selective neck dissection continue to be offered even in those patients with clinically negative necks; further studies should aid in defining the import of microscopic extracapsular tumor spread in patients with positive cervical nodes.     

In vitro removal of therapeutic drugs with a novel adsorbent system

BACKGROUND/AIMS: Substances in the middle molecular weight range have been shown to play a significant pathogenetic role in as diverse disorders as end-stage renal disease and multiple organ failure. To overcome the limitations in the amount removed by hemofilters, new sorbents with a high biocompatibility are actively being developed. Furthermore, biocompatible sorbents by their nonspecific adsorptive behavior could have great impact on detoxification treatment in exogenous intoxications. We performed an in vitro evaluation of a newly developed highly biocompatible sorbent cartridge (Betasorb((R))), examining its adsorptive capacity concerning therapeutic drugs. METHODS: Uremic blood spiked with a range of therapeutic drugs was recirculated for 2 h in an in vitro hemoperfusion circuit containing a Betasorb device for hemoperfusion. The drug concentrations before and after the passage of the cartridge were measured, and the total amount removed was calculated. RESULTS: The sorbent showed effective removal of glycopeptide antibiotics, digoxin, theophylline, phenobarbital, phenytoin, carbamazepine, and valproic acid. Moderate removal could be demonstrated for tacrolimus and cyclosporine A; aminoglycosides were removed to a small extent only. CONCLUSION: Betasorb hemoperfusion shows a potent adsorptive capacity concerning therapeutic drugs (except aminoglycosides) and could be of major value in the treatment of intoxications. On the other hand, drug monitoring and possible adjustments are necessary during Betasorb hemoperfusion to maintain the therapeutic ranges of the drugs in blood.     

Continuous renal replacement therapy: opinions and evidence

Continuous arteriovenous haemofiltration (CAVH) is the first example of continuous renal replacement therapy (CRRT). CAVH was first applied for the treatment of diuretic unresponsive fluid overload. Subsequently, CRRT has undergone a remarkable growth, and it is now performed with pump technology (CVVH) and via double-lumen central venous catheters. In many intensive care units, especially in Australia and in Europe, CRRT has become the dominant, if not exclusive, form of artificial renal support. Continuous haemofiltration is now used beyond the original indications of blood purification, for the treatment of certain drug intoxications, for severe cardiac failure, for volume control during, after cardiopulmonary bypass, and to decrease the toxicity of chemotherapy. Furthermore, there is strong ongoing research into its role or that of derived techniques as possible adjuvant therapies during severe sepsis. Despite its large use, the current state of CRRT is surrounded by some controversies, and an effort should be made to give a dispassionate distillation of the literature for a final common definition of what is based on opinions and what carries sufficient evidence.     

Options for salvage after failed initial treatment of anterior vocal commissure squamous carcinoma

Persistence or recurrent cancer in the anterior commissure (AC) after primary radiotherapy may remain localized to its pretreatment anatomical site. If so, endoscopic CO₂ laser excision, in experienced hands, may achieve complete tumor excision and result in cure for many patients. Occasionally, second and third recurrences may be similarly salvaged by further endoscopic surgery. The use of the vertical hemilaryngectomy is an alternative treatment for similar localized lesions, with a higher first time surgical tumor eradication rate, but with a more protracted hospitalization and a less satisfactory voice and swallowing outcome. In both types of such surgical salvage, CT scanning must demonstrate no evidence of cartilage invasion or destruction. When there is evidence of minimal thyroid cartilage invasion, then the supracricoid partial laryngectomy is an alternative conservation option, and is likely to result in a cure, with the retention of a voicing larynx without a stoma. When the tumor has increased in size from the original pretreatment dimension and/or site, then imaging must be used to identify possible cartilage invasion, in which case the likelihood of tumor eradication by endoscopic or external vertical partial laryngectomy is highly unlikely. The indications for the routine use of total laryngectomy for the treatment of recurrent or persistent cancer involving the AC must be reviewed; there is current evidence that cure can be achieved by a less radical procedure. However, total laryngectomy may remain the only treatment option for advanced or aggressive first time recurrence, or in patients who develop subsequent recurrence following previous less aggressive surgery (endoscopic or external).     

Early and intensive continuous hemofiltration for severe renal failure after cardiac surgery

BACKGROUND: The aim of this study was to test whether early and intensive use of continuous venovenous hemofiltration (CVVH) achieved a better than predicted outcome in patients with severe acute renal failure undergoing cardiac operations, and whether a simple and yet accurate model could be developed to predict their outcome before starting CVVH. METHODS: Medical record analysis with collection of demographic, clinical, and outcome information was used. RESULTS: Sixty-five consecutive patients were treated with early and intensive CVVH (mean operation to CVVH time, 2.38 days; pump-controlled ultrafiltration rate, 2 L/h) after coronary artery bypass grafting (56.9%), single valve procedure (16.9%), or combined operations (26.2%). In 32.3% of patients, intraaortic balloon counterpulsation was required and 20% of patients were emergencies. Sustained hypotension despite inotropic and vasopressor support occurred in 40% of patients and prolonged mechanical ventilation in 58.5%. Using an outcome prediction score specific for acute renal failure, the predicted risk of death was 66%. Actual mortality was 40% (p = 0.003). Using multivariate logistic regression analysis and neural network analysis, patient outcome could be predicted with good levels of accuracy (receiver operating characteristic 0.89 and 0.9, respectively). CONCLUSIONS: Early and aggressive CVVH is associated with better than predicted survival in severe acute renal failure after cardiac operations. Using readily available clinical data, the outcome of such patients can be predicted before the implementation of CVVH.     

CD8+ cytotoxic T lymphocyte responses to lytic proteins of human herpes virus 8 in human immunodeficiency virus type 1-infected and -uninfected individuals

T cell immunity to lytic proteins of herpesviruses is important in host control of infection. We have characterized the cytotoxic T lymphocyte (CTL) response to 5 human herpesvirus 8 (HHV-8) homologues of lytic proteins in HHV-8-seropositive individuals. HLA class I-restricted, CD8(+) CTL responses to >/=1 HHV-8 lytic protein were detected in all 14 HHV-8-seropositive study subjects tested, with or without human immunodeficiency virus type 1 (HIV-1) infection, but not in any of 5 HHV-8-seronegative individuals. Seven of these study subjects with both HHV-8 and HIV-1 infection had greater anti-CTL reactivity to glycoprotein H (open-reading frame 22) than did the 7 study subjects infected only with HHV-8. Moreover, there was a strong, inverse correlation between HIV-1 load and glycoprotein H-specific CTL lysis in the study subjects infected with both viruses. CTL reactivity to HHV-8 lytic proteins may be involved in host control of HHV-8-related diseases, such as Kaposi's sarcoma.     

2-Methylbutyryl-coenzyme A dehydrogenase deficiency: a new inborn error of L-isoleucine metabolism

An 4-mo-old male was found to have an isolated increase in 2-methylbutyrylglycine (2-MBG) and 2-methylbutyrylcamitine (2-MBC) in physiologic fluids. In vitro oxidation studies in cultured fibroblasts using 13C- and 14C-labeled branched chain amino acids indicated an isolated block in 2-methylbutyryl-CoA dehydrogenase (2-MBCDase). Western blotting revealed absence of 2-MBCDase protein in fibroblast extracts; DNA sequencing identified a single 778 C>T substitution in the 2-MBCDase coding region (778 C>T), substituting phenylalanine for leucine at amino acid 222 (L222F) and absence of enzyme activity for the 2-MBCDase protein expressed in Escherichia coli. Prenatal diagnosis in a subsequent pregnancy suggested an affected female fetus, supporting an autosomal recessive mode of inheritance. These data confirm the first documented case of isolated 2-MBCDase deficiency in humans.