Implementing structured team debriefing using a Black Box in the operating room: surveying team satisfaction.

BACKGROUND: Surgical safety may be improved using a medical data recorder (MDR) for the purpose of postoperative team debriefing. It provides the team in the operating room (OR) with the opportunity to look back upon their joint performance objectively to discuss and learn from suboptimal situations or possible adverse events. The aim of this study was to investigate the satisfaction of the OR team using an MDR, the OR Black Box®, in the OR as a tool providing output for structured team debriefing. METHODS: In this longitudinal survey study, 35 gastro-intestinal laparoscopic operations were recorded using the OR Black Box® and the output was subsequently debriefed with the operating team. Prior to study, a privacy impact assessment was conducted to ensure alignment with applicable legal and regulatory requirements. A structured debrief model and an OR Back Box® performance report was developed. A standardized survey was used to measure participant's satisfaction with the team debriefing, the debrief model used and the performance report. Factor analysis was performed to assess the questionnaire's quality and identified contributing satisfaction factors. Multivariable analysis was performed to identify variables associated with participants' opinions. RESULTS: In total, 81 team members of various disciplines in the OR participated, comprising 35 laparoscopic procedures. Mean satisfaction with the OR Black Box® performance report and team debriefing was high for all 3 identified independent satisfaction factors. Of all participants, 98% recommend using the OR Black Box® and the outcome report in team debriefing. CONCLUSION: The use of an MDR in the OR for the purpose of team debriefing is considered to be both beneficial and important. Team debriefing using the OR Black Box® outcome report is highly recommended by 98% of team members participating.

Legal perspectives on black box recording devices in the operating environment.

BACKGROUND: A video and medical data recorder in the operating theatre is possible, but concerns over privacy, data use and litigation have limited widespread implementation. The literature on legal considerations and challenges to overcome, and guidelines related to use of data recording in the surgical environment, are presented in this narrative review. METHODS: A review of PubMed and Embase databases and Cochrane Library was undertaken. International jurisprudence on the topic was searched. Practice recommendations and legal perspectives were acquired based on experience with implementation and use of a video and medical data recorder in the operating theatre. RESULTS: After removing duplicates, 116 citations were retrieved and abstracts screened; 31 articles were assessed for eligibility and 20 papers were finally included. According to the European General Data Protection Regulation and US Health Insurance Portability and Accountability Act, researchers are required to make sure that personal data collected from patients and healthcare professionals are used fairly and lawfully, for limited and specifically stated purposes, in an adequate and relevant manner, kept safe and secure, and stored for no longer than is absolutely necessary. Data collected for the sole purpose of healthcare quality improvement are not required to be added to the patient's medical record. CONCLUSION: Transparency on the use and purpose of recorded data should be ensured to both staff and patients. The recorded video data do not need to be used as evidence in court if patient medical records are well maintained. Clear legislation on data responsibility is needed to use the medical recorder optimally for quality improvement initiatives.

ANTECEDENTES: Es posible instalar un sistema de video y grabación de datos médicos en el quirófano, pero su implementación se ha visto limitada por las dudas relativas a la privacidad, uso de datos y aspectos de litigio. Estas dudas deberían superarse, motivo por el que en este trabajo se proponen unas guías sobre el uso de sistemas de registro en el ambiente quirúrgico. MÉTODOS: Se realizó una revisión en las bases de datos Pubmed y Embase y de la Biblioteca Cochrane. Se buscó la jurisprudencia internacional sobre el tema. Se establecieron unas recomendaciones prácticas y de las perspectivas legales adquiridas a través de la experiencia de la implementación y el uso de sistemas de video y registro de datos médicos en el quirófano. RESULTADOS: Se obtuvieron 116 referencias, de las que una vez eliminadas las duplicadas (n = 5) y revisados los resumenes, 31 artículos cumplían los criterios de eligibilidad. En el estudio final se incluyeron 20 artículos. De acuerdo con la Ley Orgánica de Protección de Datos (General Data Protection Regulation, GDRP) y la Ley de Transferencia y Responsabilidad de Seguro Médico (Health Insurance Portability and Accountability Act, HIPAA), los investigadores deben asegurar que los datos personales recopilados pertenecientes a los pacientes y profesionales de la salud se utilicen de manera justa y legal, con fines definidos y bien establecidos, de manera adecuada y relevante, y mantenidos a resguardo y almacenados no más tiempo del estrictamente necesario. No es necesario que los datos recopilados con el único propósito de mejorar la calidad de la atención médica se agreguen a la historia clínica del paciente. CONCLUSIÓN: Se debe asegurar por parte del personal sanitario como del paciente, la transparencia tanto en la utilización como en el objetivo de los datos almacenados. Los datos registrados en video no es necesario que sean usados como evidencia en procesos judiciales si la historia clínica de los pacientes cumple los estandares establecidos. Se precisa una legislación clara sobre la responsabilidad de los datos para la utilización óptima de los registros médicos en las iniciativas de mejora de la calidad.

[Long-term goals for oral health]. / Lang leve de duurzame mondzorg.

The current, optimistic prognosis is that newborns will reach an average age of 100 years. This increased life-expectancy requires a renewed vision of long-term goals for oral health. The starting-point could be a prospective end-point with minimal oral function which should be reached, for example, in the last years of one's life. The consequence is that adequate oral healthcare for the elderly starts in childhood. Choices such as the extraction of premolars for orthodontic reasons and the dental re-restoration cycle have a great negative impact on reaching this goal. The average sustainability of dental restorations or prosthetic constructions is commonly much shorter than the life-expectancy of a patient. If oral treatment is necessary, it is recommended to give priority to maintaining a minimally functional dentition up to an advanced age, instead offocusing on short- or medium-term goals.

Pelvic floor dysfunction is not a risk factor for febrile urinary tract infection in adults.

OBJECTIVE: To determine whether pelvic floor dysfunction (PFD) might be a risk factor for or consequence of febrile urinary tract infection (UTI), as UTI in adults is a common infection in which an underlying urological abnormality is often considered, and as in children, PFD is also thought to have a pathophysiological role in adults with UTI. PATIENTS AND METHODS: A multicentre case-control study was conducted at 26 primary-care centres and at six Emergency Departments of regional hospitals. Cases were consecutive patients aged > or =18 years, who presented with febrile UTI. Controls were randomly selected subjects who visited their general practitioner for reasons other than UTI or fever. A validated pelvic floor questionnaire (the Pelvic Floor Inventories Leiden, PelFIs) was used to assess pelvic floor function. RESULTS: Between October 2006 and December 2007, 153 cases were included; of these, the completed questionnaires of 102 (response rate 67%) were compared to those of 100 of 110 (response rate 91%) controls. The median age of cases and controls was 65 and 58 years, respectively; 40% of cases and controls were men. The percentage of PelFIs outcomes consistent with PFD were comparable between cases and controls, at 21% vs 23%, respectively (odds ratio 0.9, 95% confidence interval, CI, 0.4-1.78). In the multivariate analysis, comorbidity (odds ratio 4.9, 95% CI 2.2-11.1) and a history of UTI (odds ratio 2.5, 95% CI 1.0-6.1) were independent significant risk factors for febrile UTI, whereas PFD was not (odds ratio 1.0, 0.5-2.2). Within the group of cases, PFD was not associated with bacteriuria during assessment of PelFIs (odds ratio 1.1, 95% CI 0.4-3.5) and inversely related to a history of UTI within the previous year (odds ratio 0.2, 0.1-0.9). CONCLUSIONS: PFD is common among adults but it does not seem to be a risk factor for febrile UTI.

Significance of serum CA125 and TPS antigen levels for determination of overall survival after three chemotherapy courses in ovarian cancer patients during long-term follow-up.

PURPOSE OF INVESTIGATION: To evaluate the prognostic significance for overall survival rate for the marker combination TPS and CA125 in ovarian cancer patients after three chemotherapy courses during long-term clinical follow-up. METHODS: The overall survival of 212 (out of 213) ovarian cancer patients (FIGO Stages I-IV) was analyzed in a prospective multicenter study during a 10-year clinical follow-up by univariate and multivariate analysis. RESULTS: In patients with ovarian cancer FIGO Stage I (34 patients) or FIGO Stage II (30 patients) disease, the univariate and multivariate analysis of the 10-year overall survival data showed that CA125 and TPS serum levels were not independent prognostic factors. In the FIGO Stage III group (112 patients), the 10-year overall survival was 15.2%; while in the FIGO Stage IV group (36 patients) a 10-year overall survival of 5.6% was seen. Here, the tumor markers CA125 and TPS levels were significant prognostic factors in both univariate and multivariate analysis (p < 0.0001). In a combined FIGO Stage III + FIGO Stage IV group (60 patients with optimal debulking surgery), multivariate analysis demonstrated that CA125 and TPS levels were independent prognostic factors. For patients in this combined FIGO Stage III + IV group having both markers below respective discrimination level, 35.3% survived for more than ten years, as opposed to patients having one marker above the discrimination level where the 10-year survival was reduced to 10% of the patients. For patients showing both markers above the respective discrimination level, none of the patients survived for the 10-year follow-up time. CONCLUSION: In FIGO III and IV ovarian cancer patients, only patients with CA 125 and TPS markers below the discrimination level after three chemotherapy courses indicated a favorable prognosis. Patients with an elevated level of CA 125 or TPS or both markers after three chemotherapy courses showed unfavorable prognosis.

Tumour markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines for clinical use.

The aim of this article is to present updated guidelines for the use of serum, tissue and faecal markers in colorectal cancer (CRC). Lack of specificity and sensitivity preclude the use of all existing serum markers for the early detection of CRC. For patients with stage II or stage III CRC who may be candidates for either liver resection or systemic treatment should recurrence develop, CEA should be measured every 2-3 months for at least 3 years after diagnosis. Insufficient evidence exists to recommend routine use of tissue factors such as thymidylate synthase, microsatellite instability (MSI), p53, K-ras and deleted in colon cancer (DCC) for either determining prognosis or predicting response to therapy in patients with CRC. Microsatellite instability, however, may be used as a pre-screen for patients with suspected hereditary non-polyposis colorectal cancer. Faecal occult blood testing but not faecal DNA markers may be used to screen asymptomatic subjects 50 years or older for early CRC.

Definite involuntary childlessness: associations between coping, social support and psychological distress.

BACKGROUND: Around 4% of all couples remain involuntarily childless. These people often experience insufficient social support, which further aggravates the distress symptoms such as physical health problems, anxiety, depression and complicated grief. This study investigates the association of coping style and the degree of satisfaction regarding social support from primary support groups with distress symptoms of involuntarily childless individuals. MATERIALS AND METHODS: Subjects in this cross-sectional study were people who wanted to have children with their partner but were unable to conceive and had acknowledged their involuntary childlessness. The sample consisted of 116 persons (response 88%) with an average age of 39 years (SD = 6.0), with 75% women. The sample group completed a questionnaire consisting of passive and active coping styles from the Utrecht Coping List (UCL), the discrepancy variant of the Social Support List (SSL-D), the short version of the Questionnaire on Experienced Health Complaints (VOEG-21), the Hospital Anxiety and Depression Scale (HADS) and the Inventory of Complicated Grief-Revised (ICG-R), adapted for this study. RESULTS: Women especially experienced more health complaints, more anxiety and depression symptoms and more complicated grief than the general population. Regression analysis shows that when controlled for sex and the duration of involuntary childlessness, the concepts passive coping style and dissatisfaction with social support were positively associated with health complaints, depression, anxiety and complicated grief. The concept active coping style was negatively associated with depression, anxiety and complicated grief. Explained variance of the different distress symptoms varied from 30 to 65%. A moderating association of perceived social support is only found between a passive coping style and health complaints. CONCLUSIONS: Psychosocial interventions should be continued after the childlessness has become definite. By teaching couples how to cope actively with their childlessness and how to ask for support, the negative consequences of their childlessness may be decreased.

TPS and CA 19-9 measurements in the follow-up of patients with pancreatic cancer and chronic pancreatitis.

The aim of this study was to assess the value of TPS and CA 19-9 in a long-term follow-up analysis of 11 patients with chronic pancreatitis (CP) and 15 patients with pancreatic cancer (PC). In all monitored patients with chronic pancreatitis the initial TPS level was below 200 U/L, whereas CA 19-9 was elevated in two of them. In one patient a dramatic increase in the TPS concentration (820 U/L) was measured at the last follow-up visit (after 8.6 months), which led to the detection of PC. In all patients with PC the preoperative TPS level exceeded 200 U/L, whereas CA 19-9 was elevated in only nine patients. After the Kausch-Whipple operation 11 patients showed no evidence of disease and in eight of these patients both TPS and CA 19-9 were within the reference range; however, in three patients liver metastases were detected after 8-24 months from the last tumor marker measurement. In four of the 15 patients both markers were elevated at the end of the follow-up period and distant metastases were clinically confirmed. Our results indicate that in patients with CP and PC undergoing long-term follow-up, TPS reflects the clinical status of patients more accurately than CA 19-9.

Vascular endothelial growth factor (VEGF) concentration in sera and tumor effusions from patients with ovarian carcinoma.

VEGF is an important angiogenic cytokine with a critical role in tumor angiogenesis. VEGF concentrations were measured using an ELISA assay, detecting VEGF165 isoform, in tumor cyst and/or ascitic fluids and in sera of 86 patients with malignant neoplasms and in 53 patients with benign ovarian neoplasms. VEGF levels were significantly elevated in the sera and cyst fluids of carcinoma patients compared with patients who had benign neoplasms. In carcinoma patients, statistically higher VEGF levels were detected in tumor effusions than in corresponding sera. The differences between VEGF values in sera and tumor effusions in relation to histological subtypes of ovarian carcinoma and FIGO stages were statistically insignificant. High VEGF levels in ascitic fluids appeared to be significantly associated with shorter disease-free survival and overall survival In multivariate analysis, besides FIGO stage and age of patients, only serum VEGF concentration was an independent prognostic factor for overall survival. The elevated VEGF levels in sera and tumor effusions of patients with FIGO stages I/II indicated that angiogenesis promoted by VEGF is a continuous process, independent of clinical advancement of the disease.

[Cantilever resin-bonded bridges with one adhesive surface. A review of the literature]. / Eénvleugelige adhesiefbruggen nader bekeken. Een literatuuronderzoek.

Conventional resin-bonded bridges are designed with adhesive surfaces on both sides of the dummy. As a consequence both abutment teeth are rigidly connected to each other. Loading of the abutment teeth or dummy will lead to wringing forces in the cement. Adhesive bridges with one adhesive surface are actually cantilever bridges. Theoretically this type of bridges will be less prone to wringing forces due to loading. However, long term research into the performance of cantilever resin-bonded bridges (RBBs) is hardly available. The results of research into the longevity of conventional RBBs differ remarkably between Europe, and the United States and Japan. These difference are discussed in this article. This article compares the fixed-fixed design RBBs with the cantilever RBBs. The differences are discussed based on eight articles, the earliest being published in 1991, which are dedicated, completely or partially, to the subject of cantilever adhesive bridges. One can conclude that in The Netherlands RBBs are wrongly considered to be unreliable. On the contrary, they appear to be reliable and predictable restorations provided their preparations meet the right standards. Although a number of authors conclude that cantilever RBBs are performing better than their fixed-fixed design counterparts in similar situations, further research is needed concerning the longevity of this type of adhesive bridges.

Clinical utility of biochemical markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines.

In recent years, numerous serum and cell/tissue-based markers have been described for colorectal cancer (CRC). The aim of this article was to provide guidelines for the routine clinical use of some of these markers. Lack of sensitivity and specificity preclude the use of any available serum markers such as carcinoembryonic antigen (CEA), CA 19-9, CA 242, CA 72-4, tissue polypeptide antigen (TPA) or tissue polypeptide-specific antigen (TPS) for the early detection of CRC. However, preoperative measurement of CEA is desirable as this may give independent prognostic information, help with surgical management and provide a baseline level for subsequent determinations. For patients with stage 2 (Dukes' B) and 3 (Dukes' C) disease who may be candidates for liver resection, CEA levels should be measured every 2-3 months for at least 3 years after diagnosis. For monitoring treatment of advanced disease, CEA should also be tested every 2-3 months. Insufficient evidence is presently available to recommend the routine use of other serum markers for monitoring purposes. Similarly, the new cell and tissue-based markers (e.g, ras, P53) cannot yet be recommended for routine clinical use.

Reference levels of the tumor markers carcinoembryonic antigen, the carbohydrate antigens 19-9 and 72-4, and cytokeratin fragment 19 using the Elecsys Relecsys 1010 analyzer in a normal population in Kuwait. The importance of the determination of local reference levels.

The tumor markers CEA, CA 19-9, CA 72-4 and CYFRA 21-1 were analyzed in a group of apparently healthy subjects (n=232) in Kuwait using the Elecsys Relecsys 1010 analyzer. The distribution of the tumour marker levels was analyzed separately in Kuwaitis (n=103), non-Kuwaitis (n=129), smokers (n=68), non-smokers (n=164), males (n=138) and females (n=94). The distribution of CEA was significantly different in Kuwaitis vs. non-Kuwaitis in the total population (p=0.033) and in non-smokers (p=0.049); in males vs. females in the total population (p<0.0001) and in non-smokers (p=0.0002); and in smokers vs. non-smokers in the total population (p<0.0001) using the non-parametric Mann-Whitney U test. None of the other tumour markers showed significant differences in the subgroups. The upper reference level was defined as the 95th percentile of the normal values in each group. A higher reference level of CEA was observed in smokers (vs. non-smokers) in the total population. Also higher reference levels of CEA were observed in males (vs. females) both in the total population and in non-smokers. In the total population the respective reference levels were: CEA: 4.4 microg/L, CA 19-9: 35 kU/L, CA 72.4: 2.4 kU/L, and CYFRA 21.1: 2.1 microg/L. These results were compared with data in the kit inserts and literature data. The impact of 95th percentiles in a local heterogeneous population is discussed.

Lateralisation and depth of the internal mammary chain determined by scintigraphy and by ultrasonography: a comparative study in 124 primary breast cancer patients.

In 124 primary breast cancer patients the maximum values of the lateralisation of the internal mammary chain (IMC) and their corresponding depths could be determined by scintigraphy and ultrasonography in 77% and 85% of the cases, respectively. With respect to the lateralisation it appeared that these values were uncorrelated between the two methods. With respect to depth correlation was found (correlation coefficient 0.34; P=0.001). We conclude that substantial differences are noted. Irradiation of the IMC based on computed tomography treatment planning might be a better alternative.

Minimally invasive surgery for solitary parathyroid adenomas in patients with primary hyperparathyroidism: role of US with supplemental CT.

PURPOSE: To determine the role of ultrasonography (US) with supplemental computed tomography (CT) in patients with primary hyperparathyroidism who undergo minimally invasive surgery instead of conventional neck exploration. MATERIALS AND METHODS: US and CT were performed in 61 consecutive patients with primary hyperparathyroidism (part 1) to identify and localize solitary adenomas for resection by means of minimally invasive surgery and to provide a surgical road map. In part 2, involving 33 consecutive patients, CT was performed only when no solitary adenoma was identified with US or for road map information. Minimally invasive surgery was considered successful when serum calcium levels normalized and remained stable. RESULTS: In part 1, 46 definite solitary adenomas were found with US and two additional ones with CT. Minimally invasive surgery was successful in 45 patients and failed once. In part 2, US helped identify 23 solitary adenomas, and CT helped to find one. Minimally invasive surgery was successful in 22 patients and failed in two. Combined results in 94 patients demonstrated successful minimally invasive surgery in 67 (71%), with 64 of them selected with US alone (95% CI: 61, 80). The sensitivity of US in the diagnosis of solitary adenoma was 78% (95% CI: 67%, 86%), with a positive predictive value of 96% (95% CI: 88%, 99%). CONCLUSION: US examination of patients with primary hyperparathyroidism allowed successful selection for minimally invasive surgery in more than two-thirds of the cases, with additional CT useful chiefly for surgical road mapping.

The acute effects of norharman on cocaine self-administration and sensorimotor function in male Wistar rats.

The purpose of the present study was to determine the acute effects of the beta-carboline norharman on cocaine dependence. Male Wistar rats were allowed to self-administer cocaine for 3 h for seven sessions. A single injection of norharman (0.2-20 mg/kg, i.p.) was given 30 min before the onset of the seventh session. It was shown that norharman decreased the cocaine intake in a U-shaped manner with the dose of 10 mg/kg having the most potent effect. These results indicate that several receptor mechanisms mediate the effects of norharman. In addition, 15 min following the administration of norharman on session 7, motor and sensory skill tests were performed. Six naïve animals were tested with the dose, which has the most pronounced effect on cocaine self-administration intake, in order to examine whether the observed effects were due to norharman or due to the combination of norharman and cocaine. It was observed that norharman in both the naïve and cocaine-exposed animals significantly increased the response time in the somato-sensory orienting test. However, only in the naïve animals a significant effect of norharman on the grasp reflex was observed.

Intrinsic genetic instability of normal human lymphocytes and its implication for loss of heterozygosity.

A combination of flow cytometry and microsatellite analysis was used to investigate loss of expression of HLA-A and/or HLA-B alleles and concurrent LOH at polymorphic chromosome 6 loci both in freshly isolated lymphocytes (in vivo mutations) and in lymphocytes cultured ex vivo. The fraction of in vivo mutants that showed LOH at 6p appeared to vary from 0%-49% for various donors. During culturing ex vivo, HLA-A(-) cells arose at a high rate and showed simultaneous loss of expression at the linked HLA-B locus. Up to 90% of the ex vivo arisen HLA-A2(-) cell population showed LOH of multiple 6p markers, and 50% had lost heterozygosity at 6q. This ex vivo spectrum resembles that found in HLA-A2 mutants obtained from lymphoblastoid cells. The HLA-A2 mutants present in vivo may reflect only a small fraction of the mutants that can be detected ex vivo. In normal lymphocytes, in vivo only mitotic recombination appears to be sustained, indicating the importance of this mechanism for tumor initiation in normal cells. Although mutations resulting in LOH at both chromosome 6 arms were shown to result in nonviable cells in normal lymphocytes, they have been shown to result in viable mutants in lymphoblastoid cells. We hypothesize that these types of mutations also occur in vivo but only survive in cells that already harbor a mutated genetic background. In light of the high rate at which these types of mutations occur, they may contribute to cancer progression.

Immunohistochemical profiles of 30 monoclonal antibodies against cytokeratins 8, 18 and 19. Second report of the TD5 workshop.

In the first report of the TD5 workshop (TD5-1), the epitope specificities of 30 different monoclonal antibodies against cytokeratins 8, 18 and 19 were determined. This second report presents the immunohistochemical profiles of these antibodies using human appendix and normal skin for evaluation. Each antibody was tested by one or two different laboratories recruited from the Dutch Working Group on Immunohistochemistry and Cytochemistry. Eight different laboratories participated. The histological specimens were pretreated by the participants in three different ways for immunohistochemistry: microwave antigen retrieval in citrate buffer, enzymatic digestion to restore epitope exposure, no specific treatment (untreated paraffin-embedded samples), and tested blindly without knowledge of cytokeratin or epitope specificity of the antibodies at three different concentrations of 50, 10 and 1 microg/ml. Most of the tested antibodies (29/30) were useful in at least one pretreatment method, with microwave antigen retrieval being the most sensitive approach. For some antibodies, very high backgrounds were observed. Furthermore, it can be concluded that 11 MAbs performed well using all three staining protocols, including untreated paraffin-embedded sections. Interestingly, all the antibodies with documented selected specificity towards cytokeratin 8 (i.e. 178, 191, 199, 202 and 206) are reactive with an immunodominant region corresponding to amino acids 340-365 on cytokeratin 8, which evidently is well-suited as target for immunohistochemical interactions. Similarly, three antibodies with the same capacity to react with untreated samples had specificity against cytokeratin 19 (i.e. 179, 197 and 204) in the corresponding region in this filament, i.e. amino acids 311-335, or the KS 19.1 epitope. None of the six antibodies against the other major cytokeratin 19 epitope (BM 19.21) were found useful for immunohistochemistry on untreated samples. The overall conclusions from the present investigation are that all cytokeratin-8-specific antibodies with defined epitope specificities were very useful. Only one of the major two epitopes on cytokeratin 19 seems to be available for efficient immunohistochemistry. Cytokeratin 18 exposes some epitopes outside the immunodominant region reactive with the antibodies 190, 203 and 205 which can be used for untreated samples. The implications of these findings are of significance both for diagnostic histopathology and for the biology of tumor marker epitope expression in tissues.

Prognostic significance of CA 125 and TPS levels after 3 chemotherapy courses in ovarian cancer patients.

OBJECTIVE: To evaluate the prognostic significance of and predictive value for survival of CA 125 and TPS levels after three chemotherapy courses in ovarian cancer patients. METHODS: We analyzed in a prospective multicenter study the 1- and 2-year overall survival (OS) in ovarian carcinoma patients. The prognostic significance of CA 125 and TPS levels above the discrimination value (25 kU/L and 100 U/L, respectively) was examined by univariate and multivariate analyses. RESULTS: Of the 213 cases included, 64 patients were staged as FIGO I + II and 149 patients were staged as FIGO III + IV. Tumor marker levels in stage I + II were not correlated with survival. However, stage III and IV patients with elevated levels of CA 125 or TPS after three chemotherapy courses had a worse 2-year OS (69% vs 26%, P < 0.0001 and 57% vs 20%, P < 0.0001, respectively) than patients with normal levels of the markers. In univariate analysis the result of operation (staging laparatomy and partial debulking) and advanced FIGO stage (IV) were also adverse prognostic factors. Independent factors predictive of low 2-year OS by multivariate analysis were staging laparotomy, TPS elevated, and CA 125 elevated. The only factors predictive of low 1-year OS were TPS elevated and staging laparotomy. CONCLUSIONS: Ovarian cancer patients with elevated CA 125 levels after three chemotherapy courses have a poor prognosis. However, the prognostic accuracy can be significantly increased by the parallel determination of serum TPS.

Molecular methods for the detection of mutations.

We report the results of a collaborative study aimed at developing reliable, direct assays for mutation in human cells. The project used common lymphoblastoid cell lines, both with and without mutagen treatment, as a shared resource to validate the development of new molecular methods for the detection of low-level mutations in the presence of a large excess of normal alleles. As the "gold standard, " hprt mutation frequencies were also measured on the same samples. The methods under development included i) the restriction site mutation (RSM) assay, in which mutations lead to the destruction of a restriction site; ii) minisatellite length-change mutation, in which mutations lead to alleles containing new numbers of tandem repeat units; iii) loss of heterozygosity for HLA epitopes, in which antibodies can be used to direct selection for mutant cells; iv) multiple fluorescence-based long linker arm nucleotides assay (mf-LLA) technology, for the detection of substitutional mutations; v) detection of alterations in the TP53 locus using a (CA) array as the target for the screening; and vi) PCR analysis of lymphocytes for the presence of the BCL2 t(14:18) translocation. The relative merits of these molecular methods are discussed, and a comparison made with more "traditional" methods.

Tissue polypeptide specific antigen (TPS), a marker for differentiation between pancreatic carcinoma and chronic pancreatitis. A comparative study with CA 19-9.

BACKGROUND: The value of serum tissue polypeptide specific antigen (TPS) as a complement to CA 19-9 in the detection of pancreatic carcinoma was determined prospectively. TPS and CA 19-9 levels obtained at the time of diagnosis in patients suspected of having chronic pancreatitis or pancreatic carcinoma were evaluated in receiver operating characteristic (ROC) curve analysis. METHODS: Serum TPS and CA 19-9 levels were measured by immunoassays in 122 subjects, 48 with pancreatic carcinoma and 74 with chronic pancreatitis. RESULTS: Elevated levels of CA 19-9 were detected preoperatively in 70% of pancreatic carcinoma patients and in 19% of chronic pancreatitis patients. Elevated levels of TPS were detected in 100% of patients with pancreatic carcinoma and in 22% of patients with chronic pancreatitis. The median levels of TPS and CA 19-9 for pancreatic carcinoma were significantly higher than those for chronic pancreatitis (P < 0.0001). Increasing the upper reference value of TPS allowed for better discrimination between chronic pancreatitis and pancreatic carcinoma. ROC curve analysis showed that the introduction of 200 U/L as a decision criterion for TPS did not reduce its sensitivity but significantly improved its specificity. At a specificity of 98% for TPS, discrimination between pancreatic carcinoma and chronic pancreatitis was found to be 97%. Increasing the upper reference level for CA 19-9 to attain a specificity of 98% decreased its sensitivity from 70% to 33%. CONCLUSIONS: At an elevated cut-off level for TPS (200 U/L), almost complete discrimination between pancreatic carcinoma and chronic pancreatitis was obtained. TPS will be more useful than CA 19-9 in the differential diagnosis of pancreatic carcinoma and chronic pancreatitis.