Significant variation in histopathological assessment of endoscopic resections for Barrett's neoplasia suggests need for consensus reporting: propositions for improvement.

Endoscopic resection (ER) is an important diagnostic step in management of patients with early Barrett's esophagus (BE) neoplasia. Based on ER specimens, an accurate histological diagnosis can be made, which guides further treatment. Based on depth of tumor invasion, differentiation grade, lymphovascular invasion, and margin status, the risk of lymph node metastases and local recurrence is judged to be low enough to justify endoscopic management, or high enough to warrant invasive surgical esophagectomy. Adequate assessment of these histological risk factors is therefore of the utmost importance. Aim of this study was to assess pathologist concordance on these histological features on ER specimens and evaluate causes of discrepancy. Of 62 challenging ER cases, one representative H&E slide and matching desmin and endothelial marker were digitalized and independently assessed by 13 dedicated GI pathologists from 8 Dutch BE expert centers, using an online assessment module. For each histological feature, concordance and discordance were calculated. Clinically relevant discordances were observed for all criteria. Grouping depth of invasion categories according to expanded endoscopic treatment criteria (T1a and T1sm1 vs. T1sm2/3), ≥1 pathologist was discrepant in 21% of cases, increasing to 45% when grouping diagnoses according to the traditional T1a versus T1b classification. For differentiation grade, lymphovascular invasion, and margin status, discordances were substantial with 27%, 42%, and 32% of cases having ≥1 discrepant pathologist, respectively. In conclusion, histological assessment of ER specimens of early BE cancer by dedicated GI pathologists shows significant discordances for all relevant histological features. We present propositions to improve definitions of diagnostic criteria.

The SpaTemp cohort: 168 nondysplastic Barrett's esophagus surveillance patients with and without progression to early neoplasia to evaluate the distribution of biomarkers over space and time.

The ReBus cohort is a matched nested case-control cohort of patients with nondysplastic (ND) Barrett's esophagus (BE) at baseline who progressed (progressors) or did not progress (nonprogressors) to high-grade dysplasia (HGD) or cancer. This cohort is constructed using the most stringent inclusion criteria to optimize explorative studies on biomarkers predicting malignant progression in NDBE. These explorative studies may benefit from expanding the number of cases and by incorporating samples that allow assessment of the biomarker over space (spatial variability) and over time (temporal variability). To (i) update the ReBus cohort by identifying new progressors and (ii) identify progressors and nonprogressors within the updated ReBus cohort containing spatial and temporal information. The ReBus cohort was updated by identifying Barrett's patients referred for endoscopic work-up of neoplasia at 4 tertiary referral centers. Progressors and nonprogressors with a multilevel (spatial) endoscopy and additional prior (temporal) endoscopies were identified to evaluate biomarkers over space and over time. The original ReBus cohort consisted of 165 progressors and 723 nonprogressors. We identified 65 new progressors meeting the same strict selection criteria, resulting in a total number of 230 progressors and 723 matched nonprogressors in the updated ReBus cohort. Within the updated cohort, 61 progressors and 107 nonprogressors (mean age 61 ± 10 years) with a spatial endoscopy (median level 3 [2-4]) were identified. 33/61 progressors and 50/107 nonprogressors had a median of 3 (2-4) additional temporal endoscopies. Our updated ReBus cohort consists of 230 progressors and 723 matched nonprogressors using the most strict selection criteria. In a subgroup of 168 Barrett's patients (the SpaTemp cohort), multiple levels have been sampled at baseline and during follow-up providing a unique platform to study spatial and temporal distribution of biomarkers in BE.

Adherence to pre-set benchmark quality criteria to qualify as expert assessor of dysplasia in Barrett's esophagus biopsies - towards digital review of Barrett's esophagus.

Background: Dysplasia assessment of Barrett's esophagus biopsies is associated with low observer agreement; guidelines advise expert review. We have developed a web-based review panel for dysplastic Barrett's esophagus biopsies. Objective: The purpose of this study was to test if 10 gastrointestinal pathologists working at Dutch Barrett's esophagus expert centres met pre-set benchmark scores for quality criteria. Methods: Ten gastrointestinal pathologists twice assessed 60 digitalized Barrett's esophagus cases, enriched for dysplasia; then randomised (7520 assessments). We tested predefined benchmark quality criteria: (a) percentage of 'indefinite for dysplasia' diagnoses, benchmark score ≤14% for all cases, ≤16% for dysplastic subset, (b) intra-observer agreement; benchmark score ≥0.66/≥0.39, (c) percentage agreement with 'gold standard diagnosis'; benchmark score ≥82%/≥73%, (d) proportion of cases with high-grade dysplasia underdiagnosed as non-dysplastic Barrett's esophagus; benchmark score ≤1/78 (≤1.28%) assessments for dysplastic subset. Results: Gastrointestinal pathologists had seven years' Barrett's esophagus-experience, handling seven Barrett's esophagus-cases weekly. Three met stringent benchmark scores; all cases and dysplastic subset, three met extended benchmark scores. Four pathologists lacked one quality criterion to meet benchmark scores. Conclusion: Predefined benchmark scores for expert assessment of Barrett's esophagus dysplasia biopsies are stringent and met by some gastrointestinal pathologists. The majority of assessors however, only showed limited deviation from benchmark scores. We expect further training with group discussions will lead to adherence of all participating gastrointestinal pathologists to quality criteria, and therefore eligible to join the review panel.

The Amsterdam ReBus progressor cohort: identification of 165 Barrett's surveillance patients who progressed to early neoplasia and 723 nonprogressor patients.

Patient selection is suboptimal in most studies focused on identifying biological markers for neoplastic progression in Barrett's esophagus (BE). This study aims to describe a stringently selected community-based case-control cohort of non-dysplastic BE (NDBE) patients who progressed to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) and BE patients who never progressed to be used for future biomarker studies. We identified all patients referred for endoscopic work-up of BE neoplasia at three tertiary referral centers for treatment of BE neoplasia between 2000 and 2013. We performed a detailed registration of any endoscopic surveillance history before neoplastic progression. Controls were selected from a retrospective BE surveillance registration in 10 community hospitals. A total of 887 patients were referred for endoscopic work-up of BE neoplasia. Based on predefined selection criteria, we identified 165 progressor patients (82% men; mean age 55 years ± 10.4) with a baseline endoscopy demonstrating NDBE > 2 years before neoplastic progression. Using the same predefined selection criteria, 723 nonprogressor patients (67% men; mean age 57 years ± 11.3) with >2 years of endoscopic surveillance were identified. Median length of the BE segment was 5 cm (IQR 4-7) in progressors and 4 cm (IQR 2-6) in controls. Median duration of surveillance was 89 months (IQR 54-139) in progressors and 76 months (IQR 47-116) in nonprogressors. Paraffin embedded biopsies are available for biomarker research in all patients. Ethical approval was obtained and material transfer agreements were signed with all 58 contributing pathology labs. This is the largest community-based case-control cohort of BE patients with and without progression to early neoplasia. The stringent selection criteria and the availability of paraffin embedded biopsy specimens make this a unique cohort for biomarker studies.

Endoscopic management and follow-up of patients with a submucosal esophageal adenocarcinoma.

INTRODUCTION: The risk of lymph node metastases (LNM) in submucosal esophageal adenocarcinoma (EAC) patients is subject to debate. These patients might be treated endoscopically if the risk of LNM appears to be low. OBJECTIVE: The objective of this article is to evaluate the outcome of patients who underwent an endoscopic resection (ER) and subsequent endoscopic follow-up for a submucosal EAC. METHODS: All patients who underwent ER for submucosal EAC between January 2012 and August 2016 and were subsequently managed with endoscopic follow-up were retrospectively identified. Primary outcome was the number of patients diagnosed with LNM; secondary outcomes included intraluminal recurrences. RESULTS: Thirty-five patients (median age 68 years) were included: 17 low-risk (submucosal invasion <500 microns, G1-G2, no lymphovascular invasion (LVI)), and 18 high-risk (submucosal invasion >500 microns, and/or G3-G4, and/or LVI, and/or a tumor-positive deep resection margin (R1)) EACs. After a median follow-up of 23 (IQR 15-43) months, in which patients underwent a median of six (IQR 4-8) endoscopies and a median of four (IQR 2-8) endoscopic ultrasound procedures, none of the included patients were diagnosed with LNM. Five (14%) patients developed a local intraluminal recurrence a median of 18 (IQR 11-21) months after baseline ER that were treated endoscopically. CONCLUSIONS: In 35 patients with a submucosal EAC, no LNM were found during a median follow-up of 23 months. Endoscopic therapy may be an alternative for surgery in selected patients with a submucosal EAC.

Development of benchmark quality criteria for assessing whole-endoscopy Barrett's esophagus biopsy cases.

BACKGROUND: Dysplasia in Barrett's esophagus (BE) biopsies is associated with low observer agreement among general pathologists. Therefore, expert review is advised. We are developing a web-based, national expert review panel for histological review of BE biopsies. OBJECTIVE: The aim of this study was to create benchmark quality criteria for future members. METHODS: Five expert BE pathologists, with 10-30 years of BE experience, weekly handling 5-10 cases (25% dysplastic), assessed a case set of 60 digitalized cases, enriched for dysplasia. Each case contained all slides from one endoscopy (non-dysplastic BE (NDBE), n = 21; low-grade dysplasia (LGD), n = 20; high-grade dysplasia (HGD), n = 19). All cases were randomized and assessed twice followed by group discussions to create a consensus diagnosis. Outcome measures: percentage of 'indefinite for dysplasia' (IND) diagnoses, intra-observer agreement, and agreement with the consensus 'gold standard' diagnosis. RESULTS: Mean percentage of IND diagnoses was 8% (3-14%) and mean intra-observer agreement was 0.84 (0.66-1.02). Mean agreement with the consensus diagnosis was 90% (95% prediction interval (PI) 82-98%). CONCLUSION: Expert pathology review of BE requires the scoring of a limited number of IND cases, consistency of assessment and a high agreement with a consensus gold standard diagnosis. These benchmark quality criteria will be used to assess the performance of other pathologists joining our panel.

Digital microscopy as valid alternative to conventional microscopy for histological evaluation of Barrett's esophagus biopsies.

Management of Barrett's esophagus (BE) relies heavily on histopathological assessment of biopsies, associated with significant intra- and interobserver variability. Guidelines recommend biopsy review by an expert in case of dysplasia. Conventional review of biopsies, however, is impractical and does not allow for teleconferencing or annotations. An expert digital review platform might overcome these limitations. We compared diagnostic agreement of digital and conventional microscopy for diagnosing BE ± dysplasia. Sixty BE biopsy glass slides (non-dysplastic BE (NDBE); n = 25, low-grade dysplasia (LGD); n = 20; high-grade dysplasia (HGD); n = 15) were scanned at ×20 magnification. The slides were assessed four times by five expert BE pathologists, all practicing histopathologists (range: 5-30 years), in 2 alternating rounds of digital and conventional microscopy, each in randomized order and sequence of slides. Intraobserver and pairwise interobserver agreement were calculated, using custom weighted Cohen's kappa, adjusted for the maximum possible kappa scores. Split into three categories (NDBE, IND, LGD+HGD), the mean intraobserver agreement was 0.75 and 0.84 for digital and conventional assessment, respectively (p = 0.35). Mean pairwise interobserver agreement was 0.80 for digital and 0.85 for conventional microscopy (p = 0.17). In 47/60 (78%) of digital microscopy reviews a majority vote of ≥3 pathologists was reached before consensus meeting. After group discussion, a majority vote was achieved in all cases (60/60). Diagnostic agreement of digital microscopy is comparable to that of conventional microscopy. These outcomes justify the use of digital slides in a nationwide, web-based BE revision platform in the Netherlands. This will overcome the practical issues associated with conventional histologic review by multiple pathologists.

Pilot-study on the feasibility of sentinel node navigation surgery in combination with thoracolaparoscopic lymphadenectomy without esophagectomy in early esophageal adenocarcinoma patients.

High-risk submucosal esophageal adenocarcinoma's might be treated curatively by means of radical endoscopic resection, followed by thoracolaparoscopic lymphadenectomy without concomitant esophagectomy. A preclinical study has shown the feasibility and safety of this approach; however, no studies are performed in a clinical setting. In addition, sentinel node navigation surgery could be valuable in tailoring the extent of the lymphadenectomy. This study aimed to evaluate the feasibility and safety of thoracolaparoscopic lymphadenectomy without esophagectomy (phase I) and sentinel node navigation surgery (phase II) in patients with early esophageal adenocarcinoma. Patients with T1N0M0 early esophageal adenocarcinoma scheduled for esophagectomy without neoadjuvant therapy were included. Phase I: Two-field, esophagus preserving, thoracolaparoscopic lymphadenectomy was performed, followed by esophagectomy in the same session. Primary outcome parameters were the number of lymph nodes resected, and number of retained lymph nodes in the esophagectomy specimen. Phase II: A radioactive tracer was injected endoscopically the day before surgery. Static imaging was performed 15 and 120 minutes after injection. The day of surgery, sentinel node navigation surgery followed by esophagectomy was performed. Primary outcome parameters were the percentage of patients with a detectable sentinel node, and the concordance between static imaging and probe-based detection of sentinel node. Phase I: Five patients were included, and a median of 30 (IQR: 25-46) lymph nodes was resected. A median of 6 (IQR: 2-9) retained lymph nodes was found in the esophagectomy specimen. No acute adverse events occurred, but near the end of lymphadenectomy esophageal discoloration was observed, possibly indicating ischemia. Phase II: In all five included patients sentinel nodes could be visualized and resected, at a median of 3 (IQR: 2-5) locations. There was a high concordance between imaging and probe-based detection of sentinel nodes. In conclusion, sentinel node navigation surgery followed by lymphadenectomy without concomitant esophagectomy seems feasible in patients with high-risk submucosal early esophageal adenocarcinoma. More evidence is however needed before applying this technique in clinical practice.

Multimodality endoscopic eradication for neoplastic Barrett oesophagus: results of an European multicentre study (EURO-II).

OBJECTIVE: Focal endoscopic resection (ER) followed by radiofrequency ablation (RFA) safely and effectively eradicates Barrett's oesophagus (BO) containing high-grade dysplasia (HGD) and/or early cancer (EC) in smaller studies with limited follow-up. Herein, we report long-term outcomes of combined ER and RFA for BO (HGD and/or EC) from a single-arm multicentre interventional study. DESIGN: In 13 European centres, patients with BO ≤ 12 cm with HGD and/or EC on 2 separate endoscopies were eligible for inclusion. Visible lesions (<2 cm length; <50% circumference) were removed with ER, followed by serial RFA every 3 months (max 5 sessions). Follow-up endoscopy was scheduled at 6 months after the first negative post-treatment endoscopic control and annually thereafter. OUTCOMES: complete eradication of neoplasia (CE-neo) and intestinal metaplasia (CE-IM); durability of CE-neo and CE-IM (once achieved) during follow-up. Biopsy and resection specimens underwent centralised pathology review. RESULTS: 132 patients with median BO length C3M6 were included. After entry-ER in 119 patients (90%) and a median of 3 RFA (IQR 3-4) treatments, CE-neo was achieved in 121/132 (92%) and CE-IM in 115/132 patients (87%), per intention-to-treat analysis. Per-protocol analysis, CE-neo and CE-IM were achieved in 98% and 93%, respectively. After a median of 27 months following the first negative post-treatment endoscopic control, neoplasia and IM recurred in 4% and 8%, respectively. Mild-to-moderate adverse events occurred in 25 patients (19%); all managed conservatively or endoscopically. CONCLUSIONS: In patients with early Barrett's neoplasia, intensive multimodality endotherapy consisting of ER combined with RFA is safe and highly effective, and the treatment effect appears to be durable during mid-term follow-up. TRIAL REGISTRATION NUMBER: NTR 1211, http://www.trialregister.nl.

Thoracolaparoscopic dissection of esophageal lymph nodes without esophagectomy is feasible in human cadavers and safe in a porcine survival study.

High-risk early esophageal adenocarcinoma (i.e. submucosal invasion >500 nm, poor differentiation, and/or presence of lymphovascular invasion) is currently treated with esophagectomy with lymph node (LN) dissection given the high rates of LN metastases. However, esophagectomy is associated with substantial morbidity and mortality. Endoscopic radical resection followed by thoracolaparoscopic LN dissection without concomitant esophagectomy could be an alternative. The study aim was to evaluate the feasibility and safety of thoracolaparoscopic dissection of esophageal LNs in a preclinical setting. (i) In human cadavers, thoracolaparoscopic dissection of LNs involved in drainage of the esophagus was performed. Subsequently, esophagectomy was performed to be able to detect retained LNs. Outcome parameters included the number of dissected LNs, the number of retained LNs in the esophagectomy specimen (ES), and technical success. (ii) In swine, thoracolaparoscopic LN dissection was also performed. After the procedure, the swine survived for 28 days. Thereafter, the swine were sacrificed and esophagectomy was performed. Outcome parameters included the presence of ischemia and/or stenosis in the ES and other complications. (i) In five human cadavers, a median of 26 LNs (interquartile range 22-46) were dissected. In two ES, one retained LN was found: one high paraesophageal, one low paraesophageal. Technical success rate was 100%. (ii) None of the seven porcine ES showed signs of ischemia or stenosis. One swine died because of ventricular fibrillation during surgery; during follow up no complications were observed. Thoracolaparoscopic dissection of LNs involved in the drainage of the esophagus is feasible in human cadavers and swine. The porcine survival study suggests that the esophageal vascularity is not severely compromised by the procedure. As anatomy differs between swine and humans, safety of the procedure will have to be investigated thoroughly before applying this new technique as the treatment of choice.

Radiofrequency ablation for the endoscopic eradication of esophageal squamous high grade intraepithelial neoplasia and mucosal squamous cell carcinoma.

BACKGROUND AND STUDY AIMS: Radiofrequency ablation (RFA) with or without prior endoscopic resection safely and effectively removes early neoplasia in Barrett's esophagus. We speculated that this approach might also be suited for early squamous neoplasia of the esophagus. The aim of the study was to assess our initial experiences with RFA for high grade intraepithelial neoplasia (HGIN) and esophageal squamous cell cancer (ESCC) limited to the mucosa. PATIENTS AND METHODS: This was a prospective case series study in two tertiary centers. Patients with at least one unstained lesion (USL) of the esophagus using Lugol's chromoendoscopy and squamous HGIN/ESCC upon biopsy were included. In the case of nonflat USLs, endoscopic resection was performed for staging and to render the mucosa flat. After endoscopic resection and subsequent circumferential RFA, chromoendoscopy was repeated every 3 months with focal RFA of residual USLs. Follow-up chromoendoscopy was repeated at 6 months and annually thereafter. The main outcome measure was complete histological response for any squamous intraepithelial neoplasia or ESCC. RESULTS: A total of 13 patients (10 HGIN, three ESCC) were included. Following endoscopic resection in nine patients, the median extent of USLs was 4 cm and 50 % of circumference. All 13 patients achieved a complete response after a median of 2 RFA sessions (IQR 1 - 3 sessions). RFA-related complications included two mucosal lacerations (at the endoscopic resection scar) and one intramural hematoma, none requiring therapy. Endoscopic resection-/RFA-related complications were three stenoses. Dilation resulted in perforation in one patient (managed with a covered stent). There were no recurrences (median follow-up 17 months [IQR 11 - 22 months]). CONCLUSIONS: This study suggests that RFA with or without prior endoscopic resection for esophageal squamous HGIN and mucosal ESCC is feasible and effective.

Safety and efficacy of multiband mucosectomy in 1060 resections in Barrett's esophagus.

INTRODUCTION: Multiband mucosectomy (MBM) is a relatively new technique for endoscopic resection in Barrett's esophagus. This ligate-cut technique uses a modified variceal band ligator allowing for six consecutive resections without prior submucosal lifting. The aim was to evaluate the safety of MBM and its efficacy for complete endoscopic removal of delineated target areas in Barrett's esophagus. METHODS: Prospective registration of all MBM procedures in Barrett's esophagus was carried out between November 2004 and October 2009 in two hospitals. Prior to MBM, the target area was delineated with coagulation markings, followed by endoscopic resection until the delineated area was completely resected. Primary end points were acute (during procedure) plus early complications (<30 days) and the rate of complete endoscopic resection of the delineated target area. RESULTS: A total of 243 MBM procedures, with 1060 resections, were performed in 170 patients. MBM was performed for focal lesions (n=113), for Barrett's esophagus removal as part of a (stepwise) radical endoscopic resection protocol (n=117), and as escape treatment after radiofrequency ablation (n=13). The only acute complication was bleeding (in 3%, endoscopically managed); no perforations occurred despite absence of submucosal lifting. Early complications consisted of delayed bleeding (in 2%, endoscopically managed) and stenosis, which occurred in 48% of patients treated in a (stepwise) radical resection protocol; patients treated for focal lesions or in escape treatment showed no stenosis. Complete endoscopic resection was achieved in 91% of the focal lesions, in 86% of cases treated under the (stepwise) radical endoscopic resection protocol, and 100% for escape treatment after radiofrequency ablation. CONCLUSION: MBM is a safe and effective technique for the removal of delineated target areas in Barrett's esophagus.

Risk of thrombosis and infections of central venous catheters and totally implanted access ports in patients treated for cancer.

INTRODUCTION: Thrombosis and infections are well known complications of central venous catheters and totally implanted access ports. These complications lead to increased costs due to prolonged hospitalisation, increased antibiotics use and need for replacement. The objectives of the study were to document the occurrence of catheter related thrombosis and infections in patients with central venous catheters and totally implanted chest ports in cancer patients and to investigate whether factor V Leiden is a risk factor for catheter related thrombosis. MATERIALS AND METHODS: Between February 2002 and November 2004, 43 patients with central venous catheter or totally implanted access port were followed up to document the occurrence of catheter related thrombosis and infections. Patients received chemotherapy either for haematological malignancy or for solid tumours. Factor V Leiden (R506Q) was determined by restriction fragment length polymorphism analysis. Follow-up period ended in April 2007. RESULTS: Catheter related thrombosis occurred in 4 patients (4/43; 9.3%) with a totally implanted access port. None of the 3 patients with factor V Leiden had catheter related infection or thrombosis. Catheter related infections occurred in 15 patients: 10 patients (23.3%; 10/43) with central venous catheter and 5 patients (11.6%; 5/43) with totally implanted access ports. Time to infection was 32.5 days in the central venous catheter group compared to 88 days in the totally implanted access port group. CONCLUSION: A higher incidence of catheter related infections was observed in patients with central venous catheters in contrast to patients with totally implanted access ports were venous thrombosis was more frequent.

[Differences between men and women in the composition of atherosclerotic plaque, as an explanation for the lower success rate of carotid endarterectomy in women]. / Verschillen in samenstelling van de atherosclerotische plaque tussen mannen en vrouwen als verklaring voor het geringere succes van carotisendarteriëctomie bij vrouwen.

OBJECTIVE: To determine whether men and women differ in the histological characteristics of plaque material removed at carotid endarterectomy. DESIGN: Observational and descriptive. METHODS: Carotid endarterectomy plaque specimens obtained from 45 degrees consecutive patients (135 women, 315 men) were assessed for the presence of macrophages, smooth muscle cells, collagen, calcifications, and luminal thrombus by means ofimmunohistochemical staining. The plaques were categorised in 3 phenotypes according to the overall presentation of histological characteristics and the lipid level. Protein was isolated from the plaques to determine the interleukin-6 (IL-6) and IL-8 concentrations and the activity of matrix metalloproteinase-8 (MMP-8) and MMP-9. RESULTS: Atheromatous plaques (> 40% fat) were less frequently observed in women than in men (22 versus 40%; p < 0.001). In addition, more women than men had a low macrophage staining (18 versus 11%; p = 0.05) and strong smooth muscle cell staining (38 versus 24%; p = 0.001). Compared with men, women had a lower plaque concentration of IL-8 and lower MMP-8 activity. The observed differences were most pronounced in the asymptomatic group. An atheromatous plaque occurred in 9% of asymptomatic women compared to 39% ofasymptomatic men (p = 0.02). Moreover, a large proportion of plaques obtained from asymptomatic women showed high smooth muscle cell content (53 versus 30%; p = 0.03) and high collagen content (55 versus 24%; p = 0.003). All relations between gender and plaque characteristics, except for MMP-8, remained the same in a multivariate analysis that was adjusted for clinical presentation and other cardiovascular risk factors. CONCLUSION: Women with a carotid stenosis had more stable plaques than men, independent of clinical presentation and cardiovascular risk profile. Asymptomatic women demonstrated the highest prevalence of stable plaques. These findings may explain why women benefit less from carotid endarterectomy than men.

Monoarthritis of the elbow due to metastatic colon carcinoma: diagnosis based on the presence of adenocarcinoma cells in synovial fluid.

There are many diseases that can cause monoarthritis, malignancy being one of the more rare causes. We present such a case and discuss the relationship between malignancy and arthritis. Typically a large joint is involved, most frequently the knee and very rarely the elbow. The value of cytological examination of synovial fluid is stressed. Synovial fluid in malignant joint disease is usually sanguineous and not consistent with an inflammatory process. Synovial fluid analysis can avoid a biopsy of bone or synovium and lead to an early diagnosis and palliative treatment.

Predictive value of tumor load in breast cancer sentinel lymph nodes for second echelon lymph node metastases.

BACKGROUND: The need for routine axillary lymph node dissection (ALND) in patients with invasive breast cancer and low-volume sentinel node (SN) involvement is questionable. Accurate prediction of second echelon lymph node involvement could identify those patients most likely to benefit from ALND. METHODS: A consecutive series of 317 patients with invasive breast cancer and a tumor positive axillary SN followed by ALND was reviewed. Clinicopathologic features of the primary tumor and the SN were assessed as possible predictors of second echelon lymph node involvement. RESULTS: Second echelon metastases were found in 116/317 cases (36.6%). Frequency of second echelon lymph node involvement in patients with isolated tumor cells (ITC, N=23), micro- (N=101) and macrometastases (N=193) was 13%, 20% and 48%, respectively (p<0.001). Based on the area % of SN occupied by tumor no subgroup of patients could be selected with less than 20% second echelon lymph node involvement. However, none of the patients with SN ITC or micrometastases and a primary tumor size

Paraneoplastic hypertrichosis lanuginosa acquisita: uncommon or overlooked?

Acquired hypertrichosis lanugo-type or hypertrichosis lanuginosa acquisita (HLA) is often associated with metabolic and endocrine disorders and use of certain drugs. The occurrence of HLA with malignancy was first noted in 1865, and it has since been described in 56 patients as a paraneoplastic syndrome both in women and in men. Sometimes HLA occurs concurrent with acanthosis nigricans, papillary hypertrophy of the tongue, and glossitis. The predominance of female cases is striking. Malignancy-associated HLA seems to occur especially in the age group 40-70 years. In women with HLA the most frequent malignancy is colorectal cancer, followed in order by lung cancer and breast cancer; in men lung cancer is the malignancy most frequently associated with HLA, followed by colorectal cancer. In 3 years we saw 10 patients with HLA, in whom the malignancy was usually metastasized. Only one patient had local disease; after removal of the primary tumour it took 2 years before the lanugo hair recurred. The aetiology of the syndrome is not clear: no specific hormonal or biochemical abnormalities have been identified as yet. The difference between hirsutism and lanugo-type hypertrichosis is discussed. It is stressed that the appearance of lanugo-type hypertrichosis in body areas previously perceived by patients as 'hairless' is highly indicative of internal malignancy.

Relationship between histological subtypes and clinical characteristics at presentation and outcome in biopsy-proven temporal arteritis. Identification of a relatively benign subgroup.

Temporal arteritis (TA) may offer major complications, whilst high dosage of prednisone may result in serious side effects. We tried to identify a subgroup of TA, which can be treated with a lower dosage of prednisone. Retrospectively, clinical and laboratory data were studied at presentation, as well as the outcome in 44 consecutive patients with biopsy-proven temporal arteritis. These data were related to three particular histological subgroups, (a) classical giant cell arteritis, (b) atypical arteritis, and (c) 'healed arteritis', defined according to Allsop and Gallagher (The American Journal of Surgical Pathology 5:317-332, 1981). At presentation in subgroup c, erythrocyte sedimentation rate was lower and the level of haemoglobin was higher than in the other two subgroups. During follow-up in the healed arteritis group, reactivation, recurrence, or early death were not observed, whilst prednisone dosage after 2 and 3 years was lower compared to subgroup b. Major complications (permanent blindness and cerebrovascular accident) were only observed in subgroups a and b. We believe that the healed arteritis subgroup represents a relatively benign subgroup with a mild clinical presentation and a good prognosis. Therefore, a much lower initial prednisone dosage (15 mg/day) is suggested for patients in subgroup c than in the other two subgroups (40-60 mg/day).