EQUSUM: Endometriosis QUality and grading instrument for SUrgical performance: proof of concept study for automatic digital registration and classification scoring for r-ASRM, EFI and Enzian.

STUDY QUESTION: Is electronic digital classification/staging of endometriosis by the EQUSUM application more accurate in calculating the scores/stages and is it easier to use compared to non-digital classification? SUMMARY ANSWER: We developed the first digital visual classification system in endometriosis (EQUSUM). This merges the three currently most frequently used separate endometriosis classification/scoring systems (i.e. revised American Society for Reproductive Medicine (rASRM), Enzian and Endometriosis Fertility Index (EFI)) to allow uniform and adequate classification and registration, which is easy to use. The EQUSUM showed significant improvement in correctly classifying/scoring endometriosis and is more user-friendly compared to non-digital classification. WHAT IS KNOWN ALREADY: Endometriosis classification is complex and until better classification systems are developed and validated, ideally all women with endometriosis undergoing surgery should have a correct rASRM score and stage, while women with deep endometriosis (DE) should have an Enzian classification and if there is a fertility wish, the EFI score should be calculated. STUDY DESIGN SIZE DURATION: A prospective endometriosis classification proof of concept study under experts in deep endometriosis was conducted. A comparison was made between currently used non-digital classification formats for endometriosis versus a newly developed digital classification application (EQUSUM). PARTICIPANTS/MATERIALS SETTING METHODS: A hypothetical operative endometriosis case was created and summarized in both non-digital and digital form. During European endometriosis expert meetings, 45 DE experts were randomly assigned to the classic group versus the digital group to provide a proper classification of this DE case. Each expert was asked to provide the rASRM score and stage, Enzian and EFI score. Twenty classic forms and 20 digital forms were analysed. Questions about the user-friendliness (system usability scale (SUS) and subjective mental effort questionnaire (SMEQ)) of both systems were collected. MAIN RESULTS AND THE ROLE OF CHANCE: The rASRM stage was scored completely correctly by 10% of the experts in the classic group compared to 75% in the EQUSUM group (P < 0. 01). The rASRM numerical score was calculated correctly by none of the experts in the classic group compared with 70% in the EQUSUM group (P < 0.01). The Enzian score was correct in 60% of the classic group compared to 90% in the EQUSUM group (P = 0.03). EFI scores were calculated correctly in 25% of the classic group versus 85% in the EQUSUM group (P < 0.01). Finally, the usability measured with the SUS was significantly better in the EQUSUM group compared to the classic group: 80.8 ± 11.4 and 61.3 ± 20.5 (P < 0.01). Also the mental effort measured with the SMEQ was significant lower in the EQUSUM group compared to the classic group: 52.1 ± 18.7 and 71.0 ± 29.1 (P = 0.04). Future research should further develop and confirm these initial findings by conducting similar studies with larger study groups, to limit the possible role of chance. LIMITATIONS REASONS FOR CAUTION: These first results are promising, however it is important to note that this is a preliminary result of experts in DE and needs further testing in daily practice with different types (complex and easy) of endometriosis cases and less experienced gynaecologists in endometriosis surgery. WIDER IMPLICATIONS OF THE FINDINGS: This is the first time that the rASRM, Enzian and EFI are combined in one web-based application to simplify correct and automatic endometriosis classification/scoring and surgical registration through infographics. Collection of standardized data with the EQUSUM could improve endometriosis reporting and increase the uniformity of scientific output. However, this requires a broad implementation. STUDY FUNDING/COMPETING INTERESTS: To launch the EQUSUM application, a one-time financial support was provided by Medtronic to cover the implementation cost. No competing interests were declared. TRIAL REGISTRATION NUMBER: N/A.

Intracorporeal knot tying in a box trainer: how proficient is in vitro evaluation in laparoscopic experts?

OBJECTIVE: To determine the applicability of motion analysis parameters of intracorporeal knot tying in box trainers in experts as predictors of surgical outcome. DESIGN: Consecutive series of 1534 advanced laparoscopic hysterectomies (Canadian Task Force classification II-2). INTERVENTION: Time, path length, and motion in depth of a standardized intracorporeal knot-tying task were compared with mean risk-adjusted primary clinical outcomes for each participant. RESULTS: Although a large variety in proficient knot tying and surgical skills factors was observed; after correction for patient mix in 50 expert surgeons, motion analysis of intracorporeal knot tying could not significantly determine surgical outcome skills in advanced laparoscopic surgery. CONCLUSION: Levels of proficiency in advanced laparoscopic surgery cannot be appropriately determined using motion analysis in box trainers. Therefore, box trainer assessments do not adequately differentiate proficient from suboptimal clinical performance.

Vaginal cuff dehiscence in laparoscopic hysterectomy: influence of various suturing methods of the vaginal vault.

Vaginal cuff dehiscence (VCD) is a severe adverse event and occurs more frequently after total laparoscopic hysterectomy (TLH) compared with abdominal and vaginal hysterectomy. The aim of this study is to compare the incidence of VCD after various suturing methods to close the vaginal vault. We conducted a retrospective cohort study. Patients who underwent TLH between January 2004 and May 2011 were enrolled. We compared the incidence of VCD after closure with transvaginal interrupted sutures versus laparoscopic interrupted sutures versus a laparoscopic single-layer running suture. The latter was either bidirectional barbed or a running vicryl suture with clips placed at each end commonly used in transanal endoscopic microsurgery. Three hundred thirty-one TLHs were included. In 75 (22.7 %), the vaginal vault was closed by transvaginal approach; in 90 (27.2 %), by laparoscopic interrupted sutures; and in 166 (50.2 %), by a laparoscopic running suture. Eight VCDs occurred: one (1.3 %) after transvaginal interrupted closure, three (3.3 %) after laparoscopic interrupted suturing and four (2.4 %) after a laparoscopic running suture was used (p = .707). With regard to the incidence of VCD, based on our data, neither a superiority of single-layer laparoscopic closure of the vaginal cuff with an unknotted running suture nor of the transvaginal and the laparoscopic interrupted suturing techniques could be demonstrated. We hypothesise that besides the suturing technique, other causes, such as the type and amount of coagulation used for colpotomy, may play a role in the increased risk of VCD after TLH.

Implementation of laparoscopic hysterectomy: maintenance of skills after a mentorship program.

BACKGROUND: To evaluate the implementation and maintenance of advanced laparoscopic skills after a structured mentorship program in laparoscopic hysterectomy (LH). METHODS: Cohort retrospective analysis of 104 successive LHs performed by two gynecologists during and after a mentorship program. LHs were compared for indication, patient characteristics and intraoperative characteristics. As a frame of reference, 94 LHs performed by the mentor were analyzed. RESULTS: With regard to indication, blood loss and adverse outcomes, both trainees performed LHs during their mentorship program comparable with the LHs performed by the mentor. The difference in mean operating time between trainees and mentor was not clinically significant. Both trainees progressed along a learning curve, while operating time remained statistically constant and comparable to that of the mentor. After completing the mentorship program, both gynecologists maintained their acquired skills as blood loss, adverse outcome rates and operating time were comparable with the results during their traineeship. CONCLUSION: A mentorship program is an effective and durable tool for implementing a new surgical procedure in a teaching hospital with respect to patient safety aspects, as indications, operating time and adverse outcome rates are comparable to those of the mentor in his own hospital during and after completing the mentorship program.

Implementation of advanced laparoscopic surgery in gynecology: national overview of trends.

STUDY OBJECTIVE: To estimate the implementation of laparoscopic surgery in operative gynecology. DESIGN: Observational multicenter study (Canadian Task Force classification II-2). SETTING: All hospitals in the Netherlands. SAMPLE: Nationwide annual statistics for 2002 and 2007. INTERVENTIONS: A national survey of the number of performed laparoscopic and conventional procedures was performed. Laparoscopy was categorized for complexity in level 1, 2, and 3 procedures. Outcomes were compared with results from 2002 to evaluate trends. MEASUREMENTS AND MAIN RESULTS: In 2002, 21 414 laparoscopic and 9325 conventional procedures were performed in 74 hospitals (response rate, 74%), and in 2007, 16 863 laparoscopic and 10 973 conventional procedures were performed in 80 hospitals (response rate, 80%). Compared with 2002, in 2007, level 1 procedures were performed significantly less often and level 2 and level 3 procedures were performed significantly more often. The mean number of performed laparoscopic procedures per hospital decreased from 289 to 211 procedures. Teaching hospitals performed more than twice as many therapeutic laparoscopic procedures as nonteaching hospitals do. Cystectomy, oophorectomy, and ectopic pregnancy surgery were preferably performed using the laparoscopic approach. Laparoscopic hysterectomy was performed significantly more often, accounting for 10% of all hysterectomies. Annually, 20% of hospitals in which laparoscopic hysterectomy was implemented performed 50% of all laparoscopic hysterectomies, and 50% of the hospitals performed 20% of laparoscopic hysterectomies. CONCLUSION: This study describes increasing implementation of therapeutic laparoscopic gynecologic surgery. Clinics increasingly opt to perform laparoscopic surgery rather than conventional surgery. However, implementation of advanced procedures such as laparoscopic hysterectomy seems to be hampered.

A novel approach to registration of adverse outcomes in obstetrics and gynaecology: a feasibility study.

OBJECTIVE: The central aim of this study was to assess the feasibility of the developed adverse outcome registration method. Furthermore, it was tested whether the information gathered through the registration system allowed for comparative analyses. DESIGN: Prospective observational multicentre study. SETTING: The obstetrics and gynaecology departments of three Dutch university and three general hospitals. Population Every consecutive admission to these departments during the 12-month study period. METHODS: All complications, during admission and up to 6 weeks after discharge, were registered using a standardised form. The complication type and origin were noted and the severity of the complications were graded. MAIN OUTCOME MEASURES: The differences in relative frequencies of complications between the participating university and general hospitals. RESULTS: A total of 10 470 admissions were observed at the obstetrics and gynaecology departments of the six hospitals combined. The standard complication registration form was completed for approximately 90% of these admissions. A total of 351 gynaecological (9.1%) and 960 obstetrical (14.5%) complications were reported. There was no significant difference in the percentage of complications between general hospitals and university hospitals. The severity of complications, however, varied significantly between the participating hospitals. CONCLUSIONS: A feasible framework for complication registration in the field of obstetrics and gynaecology has been developed. Before comparing frequencies of adverse events between hospitals, such outcome measures first need to be risk-adjusted to overcome the problem of patient variation and acuity between hospitals as a source of difference, leaving quality of care as a primary source of variation.

Effectiveness of temozolomide for primary glioblastoma multiforme in routine clinical practice.

Temozolomide has been used as a standard therapy for the treatment of newly diagnosed glioblastoma multiforme since 2005. To assess the effectiveness of temozolomide in routine clinical practice, we conducted an observational study at Maastricht University Medical Centre (MUMC). Data of patients receiving radiotherapy and temozolomide between January 2005 and January 2008 were retrieved from a clinical database (radiochemotherapy group), as were data of patients in a historical control group from the period before 2005 treated with radiotherapy only (radiotherapy group). The primary endpoint was overall survival. A total of 125 patients with GBM were selected to form the study cohort. Median survival benefit was 4 months: the median overall survival was 12 months (95% CI, 9.7-14.3) in the group with radiochemotherapy with temozolomide, versus 8 months (95% CI, 5.3-10.7) in the group with only radiotherapy. Progression-free survival was 7 months (95% CI, 5.5-8.5) in the radiochemotherapy group and 4 months (95% CI, 2.9-5.1) in the group with only radiotherapy. The two-year survival rate was 18% with radiochemotherapy with temozolomide against 4% with radiotherapy alone. Concomitant treatment with radiotherapy and temozolomide followed by adjuvant temozolomide resulted in grade III or IV haematological toxic effects in 9% of patients. The addition of temozolomide to radiotherapy in routine clinical practice for newly diagnosed glioblastoma resulted in a clinically meaningful survival benefit with minimal haematological toxicity, which confirms the experience of previous trials and justifies the continued use of temozolomide in routine clinical practice.

Twenty-first century laparoscopic hysterectomy: should we not leave the vaginal step out?

The objective of this study was to compare surgical outcomes for laparoscopically assisted vaginal hysterectomy (LAVH) with total laparoscopic hysterectomy (TLH) in three teaching hospitals in the Netherlands. This study is a multicenter cohort retrospective analysis of consecutive cases (Canadian Task Force classification II-2). One hundred and four women underwent a laparoscopic hysterectomy between March 1995 and March 2005 at one of three teaching hospitals. This included 37 women who underwent LAVH and 67 who underwent TLH. Blood loss, operating time, and intraoperative complications such as bladder or ureteric injury as well as conversion to an open procedure were recorded. In the TLH group, average age was statistically significant lower, as well as the mean parity, whereas estimated uterus size was statistically significant larger, compared to the LAVH group. Main indication in both groups was dysfunctional uterine bleeding. In the TLH group, mean blood loss (173 mL) was significant lower compared to the LAVH group (457 mL), whereas length of surgery, uterus weight, and complication rates were comparable between the two groups. The method of choice at the start of the study period was LAVH, and by the end of the study period, it had been superceded by TLH. LAVH should not be regarded as the novice's laparoscopic hysterectomy. Moreover, with regard blood loss, TLH shows advantages above LAVH. This might be due to the influence of the altered anatomy in the vaginal stage of the LAVH procedure. Therefore, when a vaginal hysterectomy is contraindicated, TLH is the procedure of choice. LAVH remains indicated in case of vaginal hysterectomy with accompanying adnexal surgery.

MR-imaging of the brain of neurologic asymptomatic patients with large cell or adenocarcinoma of the lung. Does it influence prognosis and treatment?

Magnetic resonance imaging (MRI) of the brain and extensive neurological examination by a neurologist was performed as part of initial staging evaluation of 91 neurologic asymptomatic patients with large cell carcinoma or adenocarcinoma of the lung. Patients were followed up for at least 6 months. Evidence of metastatic brain disease was documented in 13 (14%) patients. Two of these patients were found suspective of brain metastases (BM) by the neurologist. The detection of BM resulted in upstaging of 1 (3%) patient in stage I/II, 4 (21%) patients in stage IIIA and 2 (11%) patients in IIIB. Especially for patients in stage III this upstaging is of importance as aggressive locoregional treatment can be abandoned. Evaluation of the brain with MRI is a sensitive method of detecting BM in neurologic asymptomatic patients and is recommended as part of the initial staging of patients with large cell carcinoma or adenocarcinoma of the lung in stage III. Additional examination by the neurologist is of little value to provide information of the neurologic status.

Proliferation and aneusomy predict survival of young patients with astrocytoma grade II.

The clinical course of astrocytoma grade II (AII) is highly variable and not reflected by histological characteristics. As one of the best prognostic factors, higher age identifies rapid progressive A II. For patients over 35 years of age, an aggressive treatment is normally propagated. For patients under 35 years, there is no clear guidance for treatment choices, and therefore also the necessity of histopathological diagnosis is often questioned. We studied the additional prognostic value of the proliferation index and the detection of genetic aberrations for patients with A II. The tumour samples were obtained by stereotactic biopsy or tumour resection and divided into two age groups, that is 18-34 years (n=19) and > or =35 years (n=28). Factors tested included the proliferation (Ki-67) index, and numerical aberrations for chromosomes 1, 7, and 10, as detected by in situ hybridisation (ISH). The results show that age is a prognostic indicator when studied in the total patient group, with patients above 35 years showing a relatively poor prognosis. Increased proliferation index in the presence of aneusomy appears to identify a subgroup of patients with poor prognosis more accurately than predicted by proliferation index alone. We conclude that histologically classified cases of A II comprise a heterogeneous group of tumours with different biological and genetic constitution, which exhibit a highly variable clinical course. Immunostaining for Ki-67 in combination with the detection of aneusomy by ISH allows the identification of a subgroup of patients with rapidly progressive A II. This is an extra argument not to defer stereotactic biopsy in young patients with radiological suspicion of A II.

Difference in distribution of muscle weakness between myasthenia gravis and the Lambert-Eaton myasthenic syndrome.

BACKGROUND: Myasthenia gravis and the Lambert-Eaton myasthenic syndrome (LEMS) may have a similar distribution of muscle weakness. Deciding on a diagnosis of myasthenia gravis or LEMS on clinical grounds may therefore be difficult. OBJECTIVE: To compare the localisation of initial muscle weakness and the distribution of weakness at the time of maximum severity in patients with myasthenia gravis and LEMS. SUBJECTS: 101 patients with myasthenia gravis and 38 patients with LEMS. RESULTS: In myasthenia gravis, initial weakness involved extraocular muscles in 59%, bulbar muscles in 29%, and limb muscles in 12% of the patients. In LEMS no patient had ocular weakness, 5% had bulbar weakness, and 95% had weakness of the limbs as the first symptom (p < 0.001). At the point of maximum severity, weakness in myasthenia gravis was purely ocular in 25%, oculobulbar in 5%, restricted to the limbs in 2%, and present in both oculobulbar muscles and limbs in 68%. At this point, none of the LEMS patients had weakness restricted to extraocular or bulbar muscles (p = 0.002). The legs were affected in all LEMS patients, whereas in 12 patients with generalised myasthenia gravis limb weakness was restricted to the arms (p = 0.024). CONCLUSIONS: In a patient suspected to have a myasthenic syndrome whose first symptom is ocular weakness, LEMS is virtually excluded. Limb weakness confined to the arms is only found in generalised myasthenia gravis and not in LEMS. Muscle weakness in myasthenia gravis tends to develop in a craniocaudal direction, and in the opposite direction in LEMS.

HLA class I and II in Lambert-Eaton myasthenic syndrome without associated tumor.

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder, in which antibodies against voltage-gated calcium channels located at nerve terminals cause muscle weakness and autonomic dysfunction. In approximately half of the patients the autoimmune process is initiated by a tumor. In the other half of patients no tumor is found and the etiology is unknown. The aims of this study were to investigate the strength of HLA-associations with nontumor LEMS (NT-LEMS) and to study the relation of HLA-haplotypes with age at onset of LEMS and other clinical features. Therefore, typing of HLA class I and II was performed in 19 patients with NT-LEMS, who were clinically evaluated. NT-LEMS was significantly associated with alleles of both HLA-class I (i.e. HLA-B8) as well as -class II (i.e. HLA-DR3 and -DQ2). HLA-B8+ patients had significantly younger age at onset of LEMS and tended to be female. This study shows that HLA-class I haplotype is associated with a distinct phenotype in NT-LEMS.

Differentiation between reactive gliosis and diffuse astrocytoma by in situ hybridization.

The authors examined the use of chromosomal analysis by in situ hybridization to differentiate between nonneoplastic reactive gliosis and astrocytomas in cases in which routine histology was inconclusive. Numerical chromosomal aberrations were found in 80% of low-grade astrocytoma specimens and in none of the reactive gliosis specimens. Aneusomic tumor cells were detected in four of 13 stereotactic samples with an initially inconclusive tissue diagnosis, three of which were later diagnosed as astrocytoma. The in situ hybridization procedure may have additional value in the differential diagnosis of reactive gliosis versus low-grade astrocytoma.

Asymptomatic brain metastases (BM) in small cell lung cancer (SCLC): MR-imaging is useful at initial diagnosis.

PURPOSE: In this study we evaluated the usefulness of MR-imaging in the detection of asymptomatic brain metastases (BM) at the initial diagnosis in patients with small cell lung cancer (SCLC) and studied the follow-up of these patients. PATIENTS AND METHODS: One-hundred and twenty-five patients with SCLC were investigated with MR-imaging. RESULTS: In 112 patients with normal neurological findings, MR-imaging of the brain demonstrated BM in 17 patients (15%). Six of these 17 patients were therefore upgraded to extensive disease (ED). Two of these 17 patients died during chemotherapy because of progressive disease and 3 patients became neurologic symptomatic with progressive disease on MR-imaging of the brain. After completion of chemotherapy a repeated MR-imaging of the brain in the remaining 12 patients showed 1 complete remission, 4 partial remission and 7 progressive disease of the BM. CONCLUSION: This study showed that at presentation an unexpectedly high percentage of SCLC patients had asymptomatic BM on MR-imaging. We propose that MR-imaging of the brain should be included in the staging of SCLC patients as well for staging, prognosis and therapy.

Treatment of leptomeningeal metastases evaluated by interphase cytogenetics.

PURPOSE: Although cytologic examination of CSF is the primary method for the evaluation of response to therapy for leptomeningeal metastases (LMMs), the procedure's sensitivity decreases throughout the course of protracted therapy. We studied whether this response could be monitored more accurately through the detection of numerical chromosomal aberrations by interphase cytogenetics, using fluorescence in situ hybridization (FISH). PATIENTS AND METHODS: Seven patients treated for LMMs and with a known numerical aberration for chromosome 1 in their pretreatment CSF were included in this study. Up to 16 consecutive CSF samples were analyzed by means of the fluorescence in situ hybridization (FISH) technique for cells with aberrant chromosome 1 content. The results of routine cytology and FISH analyses were compared and were correlated with each patient's neurologic status. RESULTS: Routine cytology detected malignancies in only 24 of the 76 samples, all of which were classified as chromosomally abnormal by FISH (except for two samples that could not be evaluated). Moreover, FISH demonstrated aneusomic cells in 32 additional samples, which could therefore be classified as malignant. The FISH results correlated better with patient neurologic status in that more malignant cells were detected in the CSF of neurologically deteriorating patients. CONCLUSION: Using FISH in addition to performing routine cytologic examination of CSF led to a more accurate evaluation of response to treatment in patients treated for LMMs.

The role of chemotherapy in intracranial germinoma: a case report.

BACKGROUND: The case of a 29-year-old man with histologically proven simultaneous germinoma (seminoma) of the pineal gland and a stage I embryonal carcinoma of the testis is reported. An intradural metastatic lesion from the pineal germinoma was diagnosed at the level of the first thoracic vertebra. Treatment, after inguinal orchiectomy, was chemotherapy only, rather than conventional radiotherapy for the pineal germinoma. METHODS: Therapy consisted of bleomycin (B), etoposide (E) and cisplatin (P). MRI was used to assess the effectiveness of BEP chemotherapy. RESULTS: A complete remission of the pineal gland germinoma and the epidural metastasis was documented after two cycles of BEP chemotherapy and after 15 months of follow-up the patient remains free of relapse. DISCUSSION: The pathogenesis of simultaneously occurring germinoma of the pineal gland and embryonal cell carcinoma of the testis is discussed. The choice of therapy in these circumstances is a matter of debate and the good result of chemotherapy alone in this patient suggest that primary chemotherapy may be the therapy of choice in patients with pineal germinomas.

Presenting features and value of diagnostic procedures in leptomeningeal metastases.

OBJECTIVE: To study the presenting features and value of routine diagnostic procedures in patients with leptomeningeal metastases (LMM) related to the primary malignancy to improve diagnostic assessment. METHODS: The authors studied the presenting features and value of routine diagnostic procedures in relation to the histology of primary malignant disease in 45 patients with LMM of solid (n = 30) or hematologic (n = 15) malignancies. RESULTS: Patients with solid LMM present mostly with spinal or radicular symptoms (53%), whereas patients with hematologic LMM more often show cranial nerve dysfunction at presentation (53%). Multifocal neurologic symptoms were seen in 67% of patients. The first CSF cytology demonstrated malignant cells more frequently in solid LMM compared with hematologic LMM (73% versus 53%). Extralumbar punctures increased the sensitivity of cytology to a greater extent in hematologic LMM than in solid LMM (34% versus 10%). Abnormal neuroimaging findings were found more often in solid LMM than in hematologic LMM (67% versus 40%). Increased total CSF protein in combination with either multifocal neurologic symptoms or abnormal neuroimaging findings was found in 73% of patients with a negative first CSF cytology. CONCLUSIONS: Patients with LMM presented differently depending on the histology of the primary tumor. In patients with a negative first CSF cytologic examination, multiple lumbar punctures increased the diagnostic accuracy, especially in hematologic LMM. LMM could also be diagnosed in patients with known cancer if total CSF protein was increased in combination with either multifocal neurologic symptoms or abnormal neuroimaging findings, preferably MRI.

Anti-Hu antibody titre and brain metastases before and after treatment for small cell lung cancer.

OBJECTIVES: To follow up the level of anti-Hu antibody titres during chemotherapy and to compare the pattern of metastases and other neurological complications before and after chemotherapy in patients with small cell lung cancer (SCLC) with and without low titre anti-Hu antibodies. Seventeen per cent of patients with SCLC without paraneoplastic syndromes have a low titre of anti-Hu antibodies in their serum. Previous studies suggested that these antibodies correlate with a more indolent tumour growth. METHODS: The serum of 52 consecutive patients with SCLC were studied before and during chemotherapy, and the correlation with stage of disease and pattern of metastases was examined. All serum samples were investigated using western blot and enzyme linked immunosorbent assay (ELISA) with HuD recombinant protein. All patients with SCLC were investigated using MRI of the brain, CSF, bone marrow aspiration, ultrasound of the abdomen, and radionuclide bone scan. RESULTS: Nine (17%) of 52 SCLC serum samples were positive by western blot. At the time of diagnosis none of the anti-Hu positive patients had either CNS (brain or leptomeningeal), epidural, adrenal, or bone marrow metastases and 56% had limited disease. In eight of 43 anti-Hu negative patients CNS metastases were found at the time of diagnosis, and only 30% had limited disease. The prevalence of bone and liver metastases was similar in both groups. Survival was 11 (SD ) months for the 43 anti-Hu negative and 10 (SD 6) months for the nine anti-Hu positive patients. Male:female ratio in the anti-Hu negative group was 4.4:1, and in the anti-Hu positive group 2:1. CONCLUSIONS: No anti-Hu antibody positive serum, as tested by western blot, became negative during chemotherapy. Anti-Hu positive and anti-Hu negative patients had similar survival, but anti-Hu positive patients tended to be women, had limited disease at the time of tumour diagnosis, and initially metastases seemed to spare the nervous system.