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.

Preoperative pain measurements in correlation to deep endometriosis classification with Enzian

Background: Deep Endometriosis (DE) classification studies with Enzian never compared solitary compartments (A, B, C, F), and combinations of anatomical locations (A&B, A&C, B&C, A&B&C), in correlation to pain. Therefore, the results of these studies are challenging to translate to the clinical situation. Objectives: We studied pain symptoms and their correlation with the solitary and combinations of anatomical locations of deep endometriosis lesion(s) classified by the Enzian score. Materials and Methods: A prospective multi-centre study was conducted with data from university and non-university hospitals. A total of 419 surgical DE cases were collected with the web-based application called EQUSUM (www.equsum.org). Main Outcome Measures: Preoperative reported numeric rating scale (NRS) were collected along with the Enzian classification. Baseline characteristics, pain scores, surgical procedure and extent of the disease were also collected. Results: In general, more extensive involvement of DE does not lead to an increase in the numerical rating scale for pain measures. However, dysuria and bladder involvement do show a clear correlation AUC 0.62 (SE 0.04, CI 0.54-0.71, p< 0.01). Regarding the predictive value of dyschezia, we found a weak, but significant correlation with ureteric involvement; AUC 0.60 (SE 0.04, CI 0.53-0.67, p< 0.01). Conclusions: Pain symptoms poorly correlate with anatomical locations of deep endometriosis in almost all pain scores, with the exception of bladder involvement and dysuria which did show a correlation. Also, dyschezia seems to have predictive value for DE ureteric involvement and therefore MRI or ultrasound imaging (ureter and kidney) could be recommended in the preoperative workup of these patients. What's new?: Dyschezia might have a predictive value in detecting ureteric involvement.

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.

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.

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.

A history of loss of consciousness or post-traumatic amnesia in minor head injury: "conditio sine qua non" or one of the risk factors?

OBJECTIVE: A history of loss of consciousness (LOC) or post-traumatic amnesia (PTA) is commonly considered a prerequisite for minor head injury (MHI), although neurocranial complications also occur when LOC/PTA are absent, particularly in the presence of other risk factors. The purpose of this study was to evaluate whether known risk factors for complications after MHI in the absence of LOC/PTA have the same predictive value as when LOC/PTA are present. METHODS: A prospective multicentre study was performed in four university hospitals between February 2002 and August 2004 of consecutive blunt head injury patients (> or = 16 years) presenting with a normal level of consciousness and a risk factor. Outcome measures were any neurocranial traumatic CT finding and neurosurgical intervention. Common odds ratios (OR) were estimated for each of the risk factors and tested for homogeneity. RESULTS: 2462 patients were included: 1708 with and 754 without LOC/PTA. Neurocranial traumatic findings on CT were present in 7.5% and were more common when LOC/PTA was present (8.7%). Neurosurgical intervention was required in 0.4%, irrespective of the presence of LOC/PTA. ORs were comparable across the two subgroups (p>0.05), except for clinical evidence of a skull fracture, with high ORs both when LOC/PTA was present (OR = 37, 95% CI 17 to 80) or absent (OR = 6.9, 95% CI 1.8 to 27). LOC and PTA had significant ORs of 1.9 (95% CI 1.0 to 2.7) and 1.7 (95% CI 1.3 to 2.3), respectively. CONCLUSION: Known risk factors have comparable ORs in MHI patients with or without LOC or PTA. MHI patients without LOC or PTA need to be explicitly considered in clinical guidelines.

[Optimising postoperative recovery at home; individualised discharge policy and task division between GP and medical specialist]. / Optimaliseren van postoperatief herstel thuis.

In the last decennia, the length of hospital stay of admitted patients has significantly decreased in all medical fields. As a result, postoperative recovery mainly takes place at home, inherently leading to new challenges. Here, two patients are being discussed for whom the postoperative period was substandard. To guarantee optimal quality of care in the home situation, the medical specialist and the general practitioner need to make the necessary arrangements. We would first of all recommend providing each discharged patient with specific, structured and individualised advices regarding postoperative recovery but also regarding alarm symptoms and logistics (e.g. who to call in case of emergency). Finally, we believe that, as (serious) complications are rare, it should be agreed on the fact that the responsible medical specialist is the coordinator of the postoperative period and the first contact point for postoperative patients.

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.

Detection of malignant cells in cerebrospinal fluid using fluorescence in situ hybridization.

Cytologic examination of cerebrospinal fluid (CSF) is the diagnostic gold standard for leptomeningeal metastasis (LMM). However, this technique is only moderately sensitive when routine staining procedures are applied. The use of fluorescence in situ hybridization (FISH) to identify malignant cells may have an additional value in diagnosing LMM, since numerical chromosomal aberrations (NCA) can be detected at the single cell level. We tested the feasibility of FISH to detect tumor cells in CSF by analyzing 22 samples with proven LMM with a probe for chromosome 1 (1q12) to detect NCA in the cells. A control group consisted of samples from 10 patients with inflammatory neurologic disease. In 7 LMM samples no cells or only lysed cells were found, due to time delay before fixation. Of the other 15 LMM samples analyzed, 13 showed NCA (87%), while no NCA were found in the control group. Our results indicate that FISH may be a useful additional diagnostic tool to the cytodiagnosis of CSF in cases of LMM. We expect that FISH can become an additional marker for malignancy at the single cell level in patients with LMM, which may also be of use to determine the effect of therapy for LMM.

Cerebrospinal fluid carcinoembryonic antigen in patients with metastatic and nonmetastatic neurological diseases.

Cerebrospinal fluid (CSF) carcinoembryonic antigen (CEA) values were determined in 200 patients suffering from various neurological diseases. We found no relationship between CEA levels and age or sex. A positive test was defined as an upper limit of at least 4.0 ng/mL of CEA. We found raised CSF CEA levels in patients with leptomeningeal spread from carcinoma, but not in patients with leptomeningeal metastases from lymphoma. We also found high values of CSF CEA in three of 21 patients with epidural metastases and in two of 28 patients with cerebral metastases from solid tumors. Comparison was made with the CSF levels of total protein, glucose, and lactate dehydrogenase. The sensitivity of the CSF CEA determination in patients for the presence of leptomeningeal involvement of cancer is 31% and the specificity is 90%.

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.

A controlled trial with vasopressin analogue (DGAVP) on cognitive recovery immediately after head trauma.

Recent evidence suggests that the vasopressin analogue desglycinamide-arginine8-vasopressin (DGAVP) might specifically benefit mild brain trauma patients. We investigated the effect of intranasal DGAVP treatment in 32 patients who had sustained a mild head injury for 3 months in a double-blind, placebo-controlled, matched-pairs study. DGAVP did not have a positive effect on cognitive recovery in this group of mildly affected patients.

The value of interphase cytogenetics in cytology for the diagnosis of leptomeningeal metastases.

We studied the use of fluorescence in situ hybridization (FISH) in CSF to enhance the diagnostic yield for the detection of malignancy on the first lumbar puncture in patients clinically suspected of having leptomeningeal metastases (LMM). Although repeated lumbar punctures were still needed in some patients, the use of FISH did speed up the diagnosis in approximately one-third of the patients clinically suspected of having LMM with atypical cells at first cytology. This eliminates the need for repeated lumbar punctures in these patients and enables an earlier start of treatment.

Initial bolus of conventional versus high-dose dexamethasone in metastatic spinal cord compression.

We randomly assigned dexamethasone in an initial bolus of 10 mg IV or 100 mg IV followed by 16 mg daily orally to 37 patients with metastatic spinal cord compression. The average pain score before the start of treatment was 5.2 (SD = 2.8) and decreased significantly (p less than 0.001) to 3.8 at 3 hrs, 2.8 at 24 hrs, and 1.4 after 1 week. There were no differences between the conventional and high-dose group on pain, ambulation, or bladder function.

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.

Response rate and prognostic factors of recurrent oligodendroglioma treated with procarbazine, CCNU, and vincristine chemotherapy. Dutch Neuro-oncology Group.

OBJECTIVES: To determine the response rate and factors correlated with response of oligodendroglial tumors to procarbazine, lomustine (CCNU), and vincristine (PCV) chemotherapy. DESIGN: Retrospective, observational multicenter study. METHODS: Patients treated with PCV or intensified PCV chemotherapy for a recurrent oligodendroglial tumor after surgery and radiation therapy with measurable disease were retrospectively evaluated for response. A 50% reduction in cross-sectional enhancing tumor area was considered a partial response. Stabilized or responding patients received six cycles of PCV unless unacceptable toxicity occurred. RESULTS: Fifty-two patients were included; median time to progression (MTP) for the entire group was 10 months. In 17% of patients a complete response (MTP, 25 months) was obtained, and in 46% a partial response (MTP, 12 months) was obtained. Median overall survival was 20 months. Although treatment was discontinued for toxicity in seven patients, it was generally well tolerated. The intensified PCV regimen was more toxic. Patients initially presenting with seizures and patients with tumor necrosis in histologic specimens had a better response rate in contrast to patients who had their first relapse within 1 year of first treatment (surgery and radiation therapy). CONCLUSIONS: Oligodendroglial tumors are chemosensitive, but most patients will have relapsed after 12 to 16 months. New studies must aim at improving initial treatment and second-line chemotherapy.

An unusual cause of diplopia in a cancer patient.

A 47-year-old woman with metastatic infiltrating lobular carcinoma of the breast developed diplopia. Computed tomography of the orbits showed enlargement and irregularity of the right inferior rectus and inferior obliques muscles. Biopsies of these muscles contained breast carcinoma cells. This case report discusses the causes of diplopia in cancer patients, with special attention to the diagnostic problems of metastasis in extraocular muscles. The possible combined occurrence of metastasis in the leptomeninges and extraocular muscles is also to be borne in mind if the latter diagnosis is not to be missed.

Neuron-specific enolase in cerebrospinal fluid of patients with metastatic and non-metastatic neurological disease.

Neuron-specific enolase (NSE) activities were measured in cerebrospinal fluid (CSF) in 361 patients with various neurological diseases. CSF was collected as part of the diagnostic procedure both in the control group, which consisted of 189 subjects with low back pain, and in the patient group (172 patients). The mean CSF NSE level in 189 control subjects was 7.14 +/- 1.94 micrograms/l. Slight elevations of CSF NSE (> or = 11.0 micrograms/l) were observed in 9 patients with non-malignant diseases and in 2 patients with malignant diseases. The findings of this study indicate that measurement of NSE in CSF cannot be used as an adjunctive diagnostic test for CNS metastases.

Follow-up of cognitive functioning in patients with small cell lung cancer.

PURPOSE: Study of the course of possible treatment-related cognitive impairment in patients with small cell lung cancer. METHODS AND MATERIALS: Thirty-two consecutive patients with small cell lung cancer underwent successive neurologic and neuropsychologic examinations until 5 months after prophylactic cranial irradiation, and in their pretherapeutic condition were compared to matched controls. Patients with brain metastases were excluded from this study. RESULTS: Neurologic examination revealed central nervous system (CNS) abnormalities only in the 14 patients with brain metastases. In the remaining patients, neuropsychologic tests showed clear differences between the pretherapeutic performance of patients and that of matched controls (p < 0.001), but no significant deterioration either during or after therapy (0.1 < p < 0.8). CONCLUSION: The difference between the pretherapeutic performance of patients and that of matched controls may indicate disease-related cognitive impairment. Within the observation period, no adverse effects of the used therapy were found. Our observations underline the importance of a pretherapeutic assessment in neurotoxicity research.

Sequelae in long-term survivors of small cell lung cancer.

PURPOSE: Central nervous system (CNS) effects of chemotherapy and prophylactic cranial irradiation (PCI) are studied in long-term small cell lung cancer (SCLC) survivors. The exact significance and pathogenesis of the neurotoxicity is still unknown, as studies on this subject lack sufficient patient numbers and are performed in an extremely varied manner. METHODS AND MATERIALS: Fifty-nine survivors (> 2 years from diagnosis) were examined neurologically and neuropsychologically, and underwent a cranial computer tomography (CT) scan or magnetic resonance (MR). Eight patients were excluded from further analysis for various reasons (not SCLC-related CNS disease, n = 6; no chemotherapy nor PCI treatment, n = 2). The remaining 51 patients were divided into three groups; group 1 = chemotherapy alone (n = 21), group 2 = sequential PCI (n = 19), and group 3 = concurrent or sandwiched PCI (n = 11). Groups were neuropsychologically compared in matched controls. RESULTS: Performance status did not differ significantly between various treatment groups; all patients remained ambulatory and capable of self-care. Mental impairment (n = 20), motor abnormalities (n = 9), and visual complaints (n = 1), were found in five patients in group 1 (24%), eight patients in group 2 (42%), and eight patients in group 3 (73%). Analysis of brain atrophy revealed no significant results; however, white matter abnormalities were found more frequently in group 3. Neuropsychologically no significant group differences existed, although interference sensitivity and difficulties with divided attention tended to occur more frequently in patients treated with PCI. Mean neuropsychometric results of treatment groups were significantly worse than those of matched controls. CONCLUSIONS: Although more intensively treated patients showed more neurologic impairment and patients in group 3 had more white matter abnormalities, there was no statistic evidence for additional neurotoxicity of PCI. Marked neuropsychometric differences between patients and matched controls may indicate that cognitive impairment is partly disease related, probably due to emotional distress and deteriorated physical condition.