Renate van den Bos

The CHEK2 1100delC mutation identifies families with a hereditary breast and colorectal cancer phenotype.

Because of genetic heterogeneity, the identification of breast cancer-susceptibility genes has proven to be exceedingly difficult. Here, we define a new subset of families with breast cancer characterized by the presence of colorectal cancer cases. The 1100delC variant of the cell cycle checkpoint kinase CHEK2 gene was present in 18% of 55 families with hereditary breast and colorectal cancer (HBCC) as compared with 4% of 380 families with non-HBCC (P<.001), thus providing genetic evidence for the HBCC phenotype. The CHEK2 1100delC mutation was, however, not the major predisposing factor for the HBCC phenotype but appeared to act in synergy with another, as-yet-unknown susceptibility gene(s). The unequivocal definition of the HBCC phenotype opens new avenues to search for this putative HBCC-susceptibility gene.

Endovenous Laser Ablation–Induced Complications: Review of the Literature and New Cases

BACKGROUND In the last decade, minimally invasive techniques have been introduced in the treatment of lower extremity varicosities. Of these therapies, endovenous laser ablation is the most widely accepted and used treatment option for insufficient great and short saphenous veins. OBJECTIVE To present a review of reported common and rare and minor and major complications associated with endovenous laser ablation. METHODS A systematic review of studies and case reports on endovenous laser ablation–induced complications. The complications were classified as minor or major according to the Society of Interventional Radiology Standards of Practice Committee guidelines on reporting complications. A case‐series of complications after endovenous laser ablation is presented. RESULTS Ecchymoses and pain are frequently reported side effects of endovenous laser ablation. Nerve injury, skin burns, deep vein thrombosis and pulmonary embolism seldom occur. An exceptional complication is a material or device that by accident remains inside the body after the procedure. Ecchymosis, pain, induration, skin burns, dysesthesia, superficial thrombophlebitis, and hematoma were classified as minor complications. Deep vein thrombosis and nerve injury were classified as major complications. CONCLUSION Endovenous laser ablation may be considered a safe treatment of lower extremity varicosities. The incidence of common side effects may decrease with better laser parameters. The authors have indicated no significant interest with commercial supporters.

Proof-of-principle study of steam ablation as novel thermal therapy for saphenous varicose veins

INTRODUCTION During the last decade, thermal ablation techniques such as endovenous laser ablation have been challenging the position of traditional surgery for the treatment of saphenous varicose veins. The newest method of thermal ablation is pulsated steam, which works by heating the vein with steam at 120°C. This study assessed the effectiveness of steam ablation of varicose veins in sheep and in humans. METHODS The safety of the procedure in sheep was assessed by cardiovascular monitoring during treatment. We used ultrasound imaging to examine occlusion of the veins. Changes in treated veins were examined microscopically. In a pilot study, 20 veins in 19 patients with insufficiency of the great or the small saphenous vein were treated with pulsated steam ablation. Anatomic success, patient satisfaction, and complications were investigated for 6 months after the procedure. RESULTS All veins in the sheep were occluded. No cardiovascular changes occurred during treatment. Histologic examination of treated veins showed typical changes of the vein wall, such as disappearance of the endothelial layer, fibrotic thrombosis, and major alterations in collagen fibers in the media. Steam ablation was effective in the 19 patients: 13 of 20 veins were completely closed, and 7 showed a very small segment of recanalization after 6 months of follow-up that did not seem to be clinically relevant. Nine patients had some ecchymoses at the puncture site, and one patient had a transient superficial phlebitis. A median maximal pain score of 1 (range, 0-10) was reported. No serious side effects, such as deep vein thrombosis, nerve injury, skin burns, or infections, were reported. Patients were very satisfied with the treatment, with a median satisfaction score of 9.25 (range, 0-10). CONCLUSIONS In this proof-of-principle study, pulsated steam ablation was an effective treatment for saphenous varicose veins.

Endovascular laser-tissue interactions and biological responses in relation to endovenous laser therapy

Endovenous laser treatment (ELT) has evolved into a frequently employed modality for the treatment of leg varicose veins. Due to the very high complete response rates, minimal complications and side effects, and the possibility to monitor therapeutic outcome noninvasively by duplex ultrasound, a considerable amount of reports have been published on clinical and translational studies, whereas disproportionally few studies have been performed to elucidate the molecular and cellular basis for post-ELT vessel obliteration. Consequently, this review addresses the putative molecular and cellular mechanisms responsible for varicose vein obliteration following laser irradiation in the context of endovenous laser–tissue interactions. First, the histological profile of laser-treated varicose veins is summarized, and an account is given of the temporal and spatial dynamics of cells involved in inflammation and remodeling in the heat-affected vein segment. Inasmuch as thrombotic occlusion of the venous lumen blocks circulatory access to the affected vessel segment and thermal damage in the vascular wall causes most cells to die, the majority of cells involved in inflammation and remodeling have to be recruited. Second, the (possible) biochemical triggers for the chemotactic attraction of immune cells and fibroblasts are identified, comprising (1) thermal coagula, (2) thrombi, (3) dead and dying cells in the vein wall, and (4) thermally denatured extracellular matrix proteins in the vein wall. The molecular biology underlying the chemotactic signaling and subsequent obliterative remodeling is elucidated. Finally, the relative contribution of every biochemical trigger to obliterative remodeling is addressed.

Epidemiology of Lentigo Maligna and Lentigo Maligna Melanoma in the Netherlands, 1989–2013

Lentigo maligna (LM) is considered a precursor to LM melanoma (LMM). We assessed trends in LM and LMM incidence rates between 1989 and 2013 in the Netherlands, and estimated the risk of an LMM after LM. Data on newly diagnosed LM and LMM were obtained from the Netherlands Cancer Registry and PALGA: Dutch Pathology Registry. Age-standardized incidence rates (European standardized rate), estimated annual percentage changes, and the cumulative incidence of LMM after LM were calculated. Between 1989 and 2013, 10,545 patients were diagnosed with a primary LM and 2,898 with a primary LMM in the Netherlands. The age-standardized incidence rate for LM increased from 0.72 to 3.84 per 100,000 person-years, and for LMM from 0.24 to 1.19 between 1989 and 2013. LM incidence increased from 2002 to 2013 with 6.8% annually, before an even steeper rise in LMM incidence from 2007 to 2013 (estimated annual percentage change: 12.4%). The cumulative incidence of LMM after a primary LM after 25-year follow-up was 2.0% for males and 2.6% for females. The increased incidence of LM and LMM in the Netherlands seems, besides increased awareness and increased histological confirmation of LM, to reflect a true increase. The absolute risk of an LMM (at any location) after a histologically confirmed LM was low (2.0-2.6%).

Endovenous ablation of refluxing saphenous and perforating veins

Since the end of the nineties endovenous thermal ablation and more recently non-thermal, non-tumescent techniques have been developed and improved. Until now, because of their favourable side effect profile in conjunction to sustained efficacy, in many countries they already replaced high ligation and stripping in the treatment of refluxing saphenous veins as well as for treatment of perforators and selected tributaries. Now, studies and comparative trials are available with long-term follow-ups for most of the techniques, providing valid data on occlusion and reflux rates, side effect profiles, and health related quality of life.

Mohs micrographic surgery of rare cutaneous tumours

Recurrence rates after Mohs micrographic surgery (MMS) for rare cutaneous tumours are poorly defined.

How We Do It: Digital Photomapping in Mohs Micrographic Surgery

Mohs micrographic surgery is a preferred treatment for skin tumors because of the low recurrence rate and preservation of healthy tissue. Although MMS is highly effective, the recurrence rate is not zero. The success of MMS mainly depends on the correct interpretation of slides, but is also dependent on the quality of the slides and the preciseness of the interpretation and documentation by the Mohs surgeon (e.g., when tumor is drawn in the file at the wrong side, healthy tissue instead of tumor tissue may erroneously be removed).

Differences in Rate of Complete Excision of Basal Cell Carcinoma by Dermatologists, Plastic Surgeons and General Practitioners: A Large Cross-Sectional Study

Background: Due to the increasing incidence of basal cell carcinoma (BCC) and rising health care costs, health care insurance companies seek ways to shift skin surgery for BCC from secondary to primary care. Objectives: To study the differences in complete excision of BCC by general practitioners (GPs), dermatologists, and plastic surgeons. Methods: A retrospective cross-sectional study of pathology records of 2,986 standard excisions of primary BCCs performed by a GP, dermatologist, or plastic surgeon in the area of Southwest Netherlands between 2008 and 2014. To compare the risk of an incomplete BCC excision between the specialties, the odds ratio (OR) was used adjusted for patient age, sex, tumor site, size, and histological subtype. Results: BCCs were completely excised by GPs in 70%, which was lower than the 93% by dermatologists and 83% by plastic surgeons (p < 0.001). Compared to the dermatologist, BCCs which were excised by a GP were 6 times higher at risk of an incomplete excision (adjusted OR 6, 95% CI 5–8) and 2 times higher at risk when excised by a plastic surgeon (adjusted OR 2, 95% CI 2–3). Conclusion: BCCs were more often completely excised by dermatologists than by GPs and plastic surgeons. Dermatologists probably perform better because of their extensive training and high experience in BCC care. To minimize incomplete BCC excision, GPs should receive specific training before the shift of BCC care from secondary to primary care is justifiable.