Tumour M2-pyruvate kinase: a gastrointestinal cancer marker

BACKGROUND: Gastrointestinal cancer tumour markers are valuable in the detection of recurrence following resection or in monitoring response to chemotherapy. CEA, CA19-9, CA-50 and CA72-4 are currently available but are nonspecific and have a low sensitivity. 'Tumour M2-pyruvate kinase' was described by Eigenbrodt around 1985. In cancers the active tetrameric form of the M2 isoenzyme of pyruvate kinase converted to an inactive dimeric form by direct interaction with oncoproteins to channel glucose carbons into DNA synthesis. This review summarizes the current knowledge of this unique tumour marker with regard to its biochemistry, assay and potential use as a diagnostic and screening tool in gastrointestinal cancer. METHODS: A literature search was conducted for entries from 1980 to 2005 using PubMed and NeLH databases using tumour M2-pyruvate kinase, faecal tumour M2-pyruvate kinase, tumour metabolism, tumour markers and carcinoembryonic antigen as keywords. A total of 56 references relevant to tumour M2-pyruvate kinase were retrieved. Eighteen references were clinical studies involving plasma/faecal tumour M2-pyruvate kinase and gastrointestinal cancer. The remaining 38 references were clinical/nonclinical trials and reviews on tumour metabolism and plasma/faecal tumour M2-pyruvate kinase assay. Seven of the 18 clinical studies involved faecal M2-pyruvate kinase. Three of the 11 plasma tumour M2-pyruvate kinase studies were non-English language and were excluded. The sensitivity, specificity, positive predictive and negative predictive value for plasma/serum tumour M2-pyruvate kinase in the detection of gastrointestinal cancer was determined for each of the remaining eight studies. Data for gastrointestinal cancer M2-pyruvate kinase were compared with other gastrointestinal cancer markers. Data from three of the eight studies using a diagnostic cut-off value of 15 U/ml for ethylenediaminetetraacetic acid (EDTA) plasma tumour M2-pyruvate kinase were analysed together as a small meta-analysis. RESULTS: At a diagnostic cut-off value of 15 U/ml for tumour M2-pyruvate kinase in EDTA plasma the sensitivity, specificity, positive predictive and negative predictive value was 57.3, 89, 85.7 and 64.8%, respectively, for colorectal cancers, 62.1, 89, 88 and 64%, respectively, for gastric/oesophageal cancers and 72.5, 89, 58 and 94%, respectively, for pancreatic cancers. As a faecal marker for colorectal cancers, faecal tumour M2-pyruvate kinase has a sensitivity of 73-92% at a cut-off value of 4 U/ml as against 50% sensitivity for Guaiac faecal test. CONCLUSION: Circulating tumour M2-pyruvate kinase is more commonly elevated in oesophageal, gastric and colorectal cancer patients than conventional tumour markers. Faecal M2-pyruvate kinase is a sensitive marker of colorectal cancer. The clinical role of tumour M2-pyruvate kinase in gastrointestinal cancer management should be investigated in large-scale clinical trials.     

Mirizzi syndrome complicating an anomalous biliary tract: a novel cause of a hugely elevated CA19-9

A 71-year-old man presented with painful obstructive jaundice, weight loss and an elevated CA19-9 (>16,000 U/ml) (normal levels <39 U/ml). Imaging showed a hilar mass. After biliary stenting, the CA19-9 returned to normal. At surgery, biliary obstruction owing to a gallstone (Type II Mirizzi) was found to be complicating a congenital biliary tract anomaly. The obstructing stone was removed and the anomalous biliary tract reconstructed with a Roux-en-y loop, and the patient made an uneventful recovery and remained normal over a 2-year follow-up. A Type II Mirizzi with a biliary tract anomaly is an undocumented cause of an elevated CA19-9. The possibility of benign disease must be considered even with very high levels of the cancer marker CA19-9 or the opportunity for curative surgery may be missed.     

A history of the concept of atypical depression

The term atypical depression as a preferentially monoamine oxidase inhibitor (MAOI)-responsive state was first introduced by West and Dally in 1959. Further characterization of this syndrome and its responsiveness to antidepressants came to occupy the attention of many psychopharmacologists for the next 30 years. Different portrayals of atypical depression have emerged, for example, nonendogenous depression, phobic anxiety with secondary depression, vegetative reversal, rejection-sensitivity, and depression with severe chronic pain. Consistency across or within types has been unimpressive, and no coherent single type of depression can yet be said to be "atypical." In successfully demonstrating superiority of MAOI drugs to tricyclics, the Columbia (or DSM-IV) criteria have established their utility and become widely adopted, but other criteria have also passed this test. In this "post-MAOI" era, no novel compound or group of drugs has been clearly shown to have good efficacy in atypical depression, leaving the treatment of atypical depression as an unmet need.     

Accuracy of self-reported premorbid functioning in schizophrenia

BACKGROUND: Information on premorbid functioning is often based on patients recalling their past. Premorbid functioning is relevant as it is associated with treatment response and other outcomes. The extent to which memory impairments of persons with schizophrenia may bias such reporting has not been investigated. The purpose of the current study was to assess the extent to which persons with schizophrenia might exhibit biased reporting relative to controls. METHODS: Seventy males with schizophrenia or schizoaffective disorder and 51 males with no psychiatric symptoms participated in the study. Contemporaneous and retrospective reports from a behavioral functioning assessment conducted as part of the Israeli Draft Board were compared. This assessment routinely administered to all 17 years old males in the country assesses social functioning, individual autonomy, organizational ability, physical activity and functioning in structured environments. We compared the groups on the Draft Board behavioral measures at age 17 and at re-assessment. We also examined the relationship between symptom severity, neuropsychological performance and differences between age 17 and current behavioral assessment scores. RESULTS: In a repeated measures MANCOVA of the five measures there was no overall significant difference in accuracy of reporting between persons with schizophrenia and those without. Both groups showed a slight tendency to glorify their past. Consistency of reporting was not significantly correlated with neuropsychological performance or levels of psychotic symptoms. CONCLUSIONS: We found that when reporting on personal and social functioning during teen age years persons with schizophrenia report with the same level of consistency as persons without schizophrenia. This suggests that self-report of premorbid functioning of persons with schizophrenia can be trusted as being reasonably accurate.     

Clinical, histologic, and radiographic outcomes of distal femoral resurfacing with hypothermically stored osteoarticular allografts

BACKGROUND: Fresh osteoarticular allograft transplantation has a long history of clinical success. These grafts have typically been implanted less than 1 week from donor asystole. HYPOTHESIS: Osteoarticular allografts stored 4 to 6 weeks represent a viable alternative to treat full-thickness cartilage and osteochondral defects of the distal femur as measured by clinical, histologic, and magnetic resonance imaging (MRI) criteria. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Osteoarticular allografts were implanted after a mean graft storage time (at 4 degrees C) of 36 days (range, 28-43). Sixty-seven patients received massive hypothermically stored osteoarticular allografts. Ten knees in 8 of these patients underwent second-look arthroscopic evaluation and biopsy at a mean of 40 months (range, 23-60) after implantation. Clinical assessment was performed using multiple outcome measures and sequential MRI evaluations. Biopsy specimens were obtained from the graft as well as from native articular cartilage at the time of second-look arthroscopy for histologic analysis. RESULTS: The mean International Knee Documentation Committee scores were as follows: preoperative, 27 (range, 9-55); postoperative, 79 (range, 56-99); P = .002. The mean Lysholm scores were as follows: preoperative, 37 (range, 12-47); postoperative, 78 (range, 55-90); P = .002. The mean Short Form-36 physical scores were as follows: preoperative, 38 (range, 24-55); postoperative, 51 (range, 39-61); P = .002. The mean Tegner scores were as follows: preoperative, 4.3 (range, 1-9); postoperative, 5.3 (range, 4-7); P = .16. The mean International Cartilage Repair Society score at follow-up was 10 (nearly normal) (range, 7-11). The mean modified Outerbridge scores were as follows: preoperative, 4.3 (range, 3-5); postoperative, 0.6 (range, 0-1); P = .002. The mean graft and native cartilage cellular density and viability were not statistically different. CONCLUSIONS: Fresh-stored osteoarticular grafts for full-thickness articular surface defects of the distal femur appear to offer a viable biological method to restore knee function. Our study suggests that osteoarticular grafts stored in cell culture medium at 4 degrees C for 4 to 6 weeks provide successful short-term clinical outcomes.