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Background: Results in breast cancer research are reported using study endpoints. Most are composite endpoints (such as locoregional recurrence), consisting of several components (for example local recurrence) that are in turn composed of specific events (such as skin recurrence). Inconsistent endpoint selection and definition might lead to unjustified conclusions when comparing study outcomes. This study aimed to determine which locoregional endpoints are used in breast cancer studies, and how these endpoints and their components are defined., Methods: PubMed was searched for breast cancer studies published in nine leading journals in 2011. Articles using endpoints with a local or regional component were included and definitions were compared., Results: Twenty-three different endpoints with a local or regional component were extracted from 44 articles. Most frequently used were disease-free survival (25 articles), recurrence-free survival (7), local control (4), locoregional recurrence-free survival (3) and event-free survival (3). Different endpoints were used for similar outcomes. Of 23 endpoints, five were not defined and 18 were defined only partially. Of these, 16 contained a local and 13 a regional component. Included events were not specified in 33 of 57 (local) and 27 of 50 (regional) cases. Definitions of local components inconsistently included carcinoma in situ and skin and chest wall recurrences. Regional components inconsistently included specific nodal sites and skin and chest wall recurrences., Conclusion: Breast cancer studies use many different endpoints with a locoregional component. Definitions of endpoints and events are either not provided or vary between trials. To improve transparency, facilitate trial comparison and avoid unjustified conclusions, authors should report detailed definitions of all endpoints., (© 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.)

Abstract Correct histological classification of malignant lymphomas is important but has always been a difficult challenge. Since 2001 the World Health Organization (WHO) classification has been used, which should make it easier to define distinct disease entities. The purpose of this study was to evaluate the usefulness of a panel of expert hematopathologists in reviewing the diagnosis of malignant lymphomas and to examine whether the discordance between primary and panel diagnoses has declined throughout the years. All patients with a primary malignant lymphoma diagnosed between 2000-2001 and 2005-2006 were identified through the population based cancer registry. All diagnoses were reviewed by a panel of three expert pathologists. In 2000-2001, 344 patients were included, and in 2005-2006, 370 patients. The overall discordance rate decreased from 14% in 2000-2001 to 9% in 2005-2006 (p = 0.06). We were able to identify lymphoma subgroups with the highest discordance rates and lowest discordance rates (mantle cell lymphoma and classical Hodgkin lymphoma), which remained unchanged throughout the years. Based on these results we would propose to review all cases of malignant lymphoma with the exception of mantle cell lymphoma and classical Hodgkin lymphoma, when the initial pathologist has no doubt about the diagnosis.

The introduction of autologous stem cell transplantation (SCT) and novel drugs has improved overall survival in multiple myeloma (MM) patients. However, minimal residual disease (MRD) remains and most patients eventually relapse. Myeloma plasma cells express tumor-associated antigens (TAA), which are interesting targets for immunotherapy. In this phase 1 study, we investigated the safety and immunological effects of TAA-mRNA-loaded dendritic cell (DC) vaccination for treatment for MRD in MM after SCT. Mature monocyte-derived DCs were pulsed with keyhole limpet hemocyanin (KLH) and electroporated with MAGE3, Survivin or B-cell maturation antigen (BCMA) mRNA. Twelve patients were vaccinated three times with intravenous (5-22 × 10(6) DCs) and intradermal vaccines (4-11 × 10(6) DCs), at biweekly intervals. Immunological responses were monitored in blood and delayed-type hypersensitivity (DTH) biopsies. All patients developed strong anti-KLH T-cell responses, but not KLH antibodies. In 2 patients, vaccine-specific T cells were detected in DTH biopsies. In one patient, we found MAGE3-specific CD4(+) and CD8(+) T cells, and CD3(+) T cells reactive against BCMA and Survivin. In the other patient, we detected low numbers of MAGE3 and BCMA-reactive CD8(+) T cells. Vaccination was well tolerated with limited toxicity. These findings illustrate that TAA-mRNA-electroporated mature DCs are capable of inducing TAA-T-cell responses in MM patients after SCT.

As axillary recurrence (AR) after a negative sentinel lymph node biopsy (SLNB) is rare, the prognosis of these patients is unknown. Since treatment paradigms for patients with breast cancer are shifting toward less axillary surgery, the number of ARs might increase. In this study, we evaluated primary and salvage treatment as well as long-term survival of patients diagnosed with an AR. A retrospective analysis of the cancer registry of 16 breast cancer units in the Netherlands was used to identify patients who developed an AR after a negative SLNB performed between 2002 and 2004. Using local hospital records we recorded primary patient-, tumor-, and treatment-characteristics, as well as salvage treatment. We identified 54 patients with an AR, median 30 months (range 3-79) after SLNB. Eighteen patients (33 %) were initially treated with breast conserving therapy, 15 of whom received external beam radiation therapy (EBRT). Thirty-three patients (61 %) did not receive adjuvant systemic treatment. In 45 of the 54 (83 %) patients, a salvage axillary lymph node dissection was performed showing a median of three positive nodes (range 1-24). Nine patients (17 %) were not treated surgically: three were treated with salvage EBRT and six with salvage systemic therapy only. At time of detection of the AR, a total of 7 patients (13 %) had proven distant metastases. After a median follow-up of 47 months (range 3-118), the 5-year "post-recurrence" distant metastasis free survival was 50 % and overall survival was 58 %. Significant negative predictors of survival were negative estrogen receptor (ER) status and receiving adjuvant chemotherapy at initial treatment. AR following a negative SLNB is associated with a 58 % 5-year OS. Prognostic factors are ER- primary tumor and receiving adjuvant chemotherapy as a part of initial treatment, reflecting an aggressive phenotype. Adequate regional and systemic salvage therapy constitute a chance for long-term survival after AR.

The aim of this study was to evaluate the value of Ultrasonography (US) guided fine-needle aspiration (FNA) of the axilla to identify breast cancer patients with extensive nodal involvement. A prospective database of breast cancer patients who underwent US-guided FNA of suspicious nodes, diagnosed between 2000 and 2007 was analyzed. Patients with a negative axillary US or C2 (benign) FNA result underwent SLNB. Patients with C5 (malignant) FNA result underwent axillary lymph node dissection (ALND). All SLNB positive patients underwent completion ALND. The number of positive nodes after ALND was documented and analyzed. A total of 1,448 patients were included. US sensitivity was 34.2 %, specificity was 96.2 % and the accuracy was 71.7 %. For US-guided FNA this was 89, 100 and 90.4 %, respectively. In 234/1,448 patients (16.2 %) US-guided FNA was performed. A total of 19/41 C2 patients (46.3 %) had a positive SLNB. A median of 1 (range 1-6) positive node was found. A median of 4 (range 1-30) positive nodes were found in 158 C5 patients. In 376/1,214 patients with a negative US, SLNB was positive. A median of 2 (range 1-38) positive nodes were found. There was a significant difference in nodal involvement between C5 and SLNB positive patients (p = 0.043 and p < 0.0001, respectively). Ultrasound-guided FNA is a highly specific technique for detecting axillary metastases in breast cancer patients. Patients with US-guided FNA-diagnosed axillary metastases have significantly more involved nodes compared to SLNB positive patients.

Background: Internationally, there is no consensus on the pathology protocol to be used to examine the sentinel lymph node (SN) in breast cancer patients. Previously, we reported that ultra-staging led to more axillary lymph node dissections (ALND). The question was, whether ultra-staging is effective in reducing the risk of regional relapse., Methods: From January 2002 to July 2003, 541 patients from 4 hospitals were prospectively registered when they underwent a SN biopsy. In hospitals A, B, and C, 3 levels of the SN were examined pathologically, whereas in hospital D at least 7 additional levels were examined. Patients with a positive SN, including isolated tumor cells, underwent an ALND. This analysis focuses on the 341 patients with a negative SN. Primary endpoint was 5-year regional recurrence rate., Results: In hospital D 34% of the patients had a negative SN as compared to 71% in hospitals A, B, and C combined (p < 0.001). At 5 years follow-up, 9 (2.6%) patients had developed a regional lymph node relapse. In hospital D none of the patients had a regional recurrence, as compared to 9 (2.9%) cases of recurrence in hospitals A, B, and C., Conclusion: The less intensified SN pathology protocol appeared to be associated with a slightly increased risk of regional recurrence. The absolute risk was still less than 3%, and does not seem to justify the intensified SN pathology protocol of hospital D., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Aims: Patients with breast cancer metastasized to the liver have a median survival of 4-33 months and treatment options are usually restricted to palliative systemic therapy. The aim of this observational study was to evaluate the effectiveness and safety of resection of liver metastases from breast cancer and to identify prognostic factors for overall survival., Methods: Patients were identified using the national registry of histo- and cytopathology in the Netherlands (PALGA). Included were all patients who underwent resection of liver metastases from breast cancer in 11 hospitals in The Netherlands of the last 20 years. Study data were retrospectively collected from patient files., Results: A total of 32 female patients were identified. Intraoperative and postoperative complications occurred in 3 and 11 patients, respectively. There was no postoperative mortality. After a median follow up period of 26 months (range, 0-188), 5-year and median overall survival after partial liver resection was 37% and 55 months, respectively. The 5-year disease-free survival was 19% with a median time to recurrence of 11 months. Solitary metastases were the only independent significant prognostic factor at multivariate analysis., Conclusion: Resection of liver metastases from breast cancer is safe and might provide a survival benefit in a selected group of patients. Especially in patients with solitary liver metastasis, the option of surgery in the multimodality management of patients with disseminated breast cancer should be considered., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Introduction: The objective of this study was to conduct a multicentre data analysis to identify prognostic factors for developing an axillary recurrence (AR) after negative sentinel lymph node biopsy (SLNB) in a large cohort of breast cancer patients with long follow-up., Patients and Methods: The prospective databases from different hospitals of clinically node negative breast cancer patients operated on between, 2000 and 2002 were analyzed. SLNB was performed and pathological analysis done by local pathologists according to national guidelines. Adjuvant treatment was given according to contemporary guidelines. Multivariate analysis was performed using all available variables, a p-value of <0,05 was considered to be significant., Results: A total of 929 patients who did not undergo axillary lymph node dissection were identified. After a median follow up of 77 (range 1-106) months, fifteen patients developed an isolated AR (AR rate 1,6%). Multivariate analysis showed that young age (p = 0.007) and the absence of radiotherapy (p = 0.010) significantly increased the risk of developing an AR. Distant metastasis free survival (DMFS) was significantly worse for patients with an AR compared to all other breast cancer patients (p < 0,0001)., Conclusion: Even after long-term follow up, the risk of developing an AR after a negative SLN in breast cancer is low. Young age and absence of radiation therapy are highly significant factors for developing an axillary recurrence. DMFS is worse for AR patients compared to patients initially diagnosed with N0 or N1 disease., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

We aimed to retrospectively assess (1) the conclusiveness of breast fine needle aspiration (FNA) in a histologically confirmed population and (2) the clinical and radiologic determinants of a conclusive diagnosis. Aspirates were diagnosed as inadequate, benign, atypical, suspicious or malignant. We defined a conclusive FNA diagnosis as 'benign' in histologically benign lesions and as 'malignant' in histologically malignant lesions. In 2419 breast lesions, the proportion of conclusive diagnoses was 46.1% (95% confidence interval, 42.0-50.2%) in histologically benign lesions (n = 571) and 81.6% (95% confidence interval, 79.8%-83.4%) in histologically malignant lesions (n = 1848). On multivariate analysis, factors associated with a conclusive preoperative diagnosis included tumour diameter of 2-2.9 cm (P < 0.001), malignant histology (P < 0.001) and the pathologist examining the aspirate (P = 0.02). Breast FNA has to be utilised selectively in the routine work-up of breast lesions. In suspicious lesions of large size, FNA may still be used to obtain a quick confirmation of malignancy., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Aim: A quick and reliable preliminary diagnosis is essential in the management of a same-day breast clinic. In a preclinical study we developed an alternative method of core wash cytology (CWC). This study is an evaluation of this new CWC method introduced into the clinical setting., Methods: From April 2008 to April 2009, biopsies were taken from lesions in the breast. CWC was obtained from core needle biopsy (CNB) with a modified technique and classified into the categories: malignant, suspicious for malignancy, atypical, benign and inadequate. CWC and CNB diagnoses were correlated with the histopathology of subsequently obtained resection specimens. The sensitivity and specificity were calculated., Results: CWC was obtained from 226 breast lesions. In 167 of these cases subsequent resection of the lesion was performed revealing 149 carcinomas and 18 benign lesions. Of the 149 malignant cases, 136 were considered as either malignant or suspicious for malignancy by CWC, 7 as atypical, 4 as benign and 2 as inadequate. None of the 18 benign lesions were classified as suspicious or malignant on CWC. Eight out of 149 resected carcinomas were not recognized as malignant by histological analysis of the CNB, while 7 of these cases the CWC was considered malignant. The sensitivity and specificity were 97% and 100%, respectively., Conclusions: In the vast majority of patients the modified CWC technique can provide a quick and reliable diagnosis of malignant breast lesions. Furthermore, combining CWC with CNB histology can improve adequate, preoperative recognition of the malignant character of breast lesions., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: Non-operative pathology diagnoses constitute an essential part of the work-up of breast lesions. With fine needle aspiration (FNA) and core needle biopsy (CNB) both having unique advantages, there is an increasing acceptance of CNB. This paper aims to outline the scientific basis of this trend. Additionally, we provide an update on novel techniques that derive cytological specimens from CNB (i.e., touch imprint (TI) and core wash (CW) cytology) in an attempt to get the best of both worlds., Methods: In addition to using the authors' experience, we performed a search of the Medline database combining the search terms "breast cancer diagnosis", "core needle biopsy", "fine needle aspiration", "touch imprint cytology", "core wash cytology" and "complications". We defined a conclusive non-operative diagnosis as "malignant" in lesions that were malignant on follow-up and "benign" in lesions that were benign on follow-up., Results: CNB was more often conclusive than FNA in benign and malignant lesions in 4 prospective studies. Although the more rapid diagnoses by FNA result in less patient anxiety during diagnostic work-up, CNB allows for fairly reliable estimation of invasion, histological type, grade, and receptor expression. CW and TI cytology seem promising techniques with conclusiveness rates that are roughly comparable to that of FNA., Conclusions: All new suspicious breast lesions require careful non-operative investigation by CNB. However, additional cytological assessment by FNA can still be useful as a same-day diagnosis decreases patient anxiety and facilitates surgical treatment planning. TI and CW cytology techniques are promising same-day diagnosis modalities., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Aim: Preoperative stratification of patients presenting with nipple discharge (ND) according to malignancy risk has proven difficult. Nevertheless, cytological examination is considered to be a diagnostic aid. The aim of this study was to determine its complementary value in clinical decision-making in patients presenting with ND., Methods: We retrospectively collected data on macroscopic ND colour, ND cytology, physical examination, mammography, ultrasound and fine-needle aspiration cytology results. On ND cytology, benign diagnoses were considered negative, whereas suspicious and malignant diagnoses were considered positive for malignancy., Results: From 1992 to 2006, 618 patients had an ND smear, of those 163 patients had a biopsy. Sensitivity and specificity were 16.7% and 66.1%, respectively. These values were lower when ND was bloody than when ND was non-bloody (p=0.66 and p<0.05 for sensitivity and specificity, respectively). When macroscopically defining bloody ND as positive and non-bloody ND as negative, macroscopic ND colour examination had a remarkably higher sensitivity (60.6 vs. 18.2%, p<0.001) and only a slightly lower specificity (53.6 vs. 65.0%, p=0.07) when compared to cytological ND examination. Only 1 malignant lesion was designated positive solely by ND cytology (unique sensitivity (95% CI), 2.8% (0.0-8.4%)) and 3 lesions were correctly classified as negative by ND cytology (unique specificity (95% CI), 1.6%, 0.0-3.7%))., Conclusion: Nipple discharge cytology has little complementary diagnostic value. Therefore, its routine use for detection of ND-related breast pathology should be reconsidered carefully. Nipple discharge cytology may redirect patient management well in some cases, but it may confuse work-up in the majority.

Fine-needle aspiration (FNA) of breast lesions provides indeterminate (C1, C3, and C4) diagnoses in a high proportion of cases. The aim of the present study was to retrospectively determine whether repeat FNA or core needle biopsy (CNB) most frequently provides a correct and more conclusive diagnosis. All patients who had an indeterminate primary FNA followed by repeat FNA or CNB within 1 month from 1992 to 2007 were included. FNA was diagnosed as C1-C5; CNB was diagnosed as B1-B5. Improvement in preoperative diagnosis by repeat FNA or CNB was defined as C2/B2 in benign lesions, C3/B3 in premalignant lesions, C4/B4 or C5/B5 in malignant lesions where primary FNA was C1, and C5/B5 in malignant lesions where primary FNA was C3 or C4. Among 255 eligible cases, CNB improved the preoperative diagnosis more often than did repeat FNA (78.0% vs. 54.8%, odds ratio = 2.9, P < .001). When corrected for patient age, appearance on mammogram (mass or not), clinical findings (palpable or not), tumor size, and aspiration mode (freehand vs. image guided), this difference slightly increased (odds ratio = 3.0, P = .001). CNB should be performed after an indeterminate FNA of a breast lesion to obtain a reliable and clear preoperative diagnosis.

Objective: To establish the frequency of re-excision or mastectomy in women who had breast-conserving treatment for invasive lobular mammary carcinoma., Design: Retrospective., Method: Data on the number of patients with invasive carcinoma from 1998-2006 were obtained from the national pathology database (PALGA) and the Dutch Comprehensive Cancer Centre East. The following data on patients who had undergone breast-conserving treatment for invasive lobular carcinoma were collected from the electronic patient records: age, localization procedure with wire-localisation and tumour size., Results: The frequency of re-excision or mastectomy following initial breast-conserving surgery in 123 patients with invasive lobular carcinoma was 46.3 % versus 31.5 % in 877 patients with other types of invasive carcinoma. The number of re-excisions was higher in the group with invasive non-lobular carcinoma (4.9% versus 9.2%), and the number of conversions to mastectomy was higher in the group with invasive lobular carcinoma (41.5% versus 20.1%). The age of the patient, the localisation procedure and tumour size were not significant predictors of a tumour-free surgical margin or for the necessity of re-excision., Conclusion: The frequency of re-excision in patients with invasive lobular carcinoma was higher than in patients with other types of breast cancer. There was no statistically significant predictor for obtaining a tumour-free surgical margin.

Unlabelled: Chronic pain after breast cancer surgery is a major problem and is expected to increase in the coming years because of an increased prevalence of breast cancer coupled with better survival. Axillary lymph node dissection (ALND) in patients with breast cancer is associated with nerve damage. The present study investigated the effect of ALND on the prevalence and intensity of chronic pain after breast cancer surgery. Furthermore, we studied the effect of chemotherapy and radiotherapy on chronic pain and the quality of life after breast cancer surgery. We analyzed 317 questionnaires of patients who underwent surgery for breast cancer between 2002 and 2004. In the first part, questions were asked concerning the prevalence of chronic pain, its intensity (visual analog scale), and phantom breast pain. The second part covered quality of life and included the EORTC QLQ-C30/BR-23. The prevalence of chronic pain after breast cancer surgery with ALND is double that without ALND (51% vs 23%). Chronic pain intensity and prevalence of phantom breast pain were not influenced by ALND. Chemotherapy and radiotherapy in interaction with ALND were associated with increased prevalence of chronic pain. The quality of life in patients was mainly affected by chronic pain and to a lesser extent by type of surgery., Perspective: Nerve injury is particularly efficient at producing central sensitization. ALND in conjunction with breast cancer surgery is associated with a doubled prevalence of chronic pain, which has not been described to date. ALND and nerve injury may play a major role in pain chronification after breast cancer surgery.

Pain is a prominent issue in inguinal hernia repair research as its persisting appearance is a severe complication. The interest is also urged by the combination of a high number of repairs with an estimated risk for chronic postoperative pain of 11%. Almost every healthcare provider could encounter this complication. Pain is a complex study subject, mostly defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Various explanatory factors for pain following hernia repair have been reported. Most investigators, however, discuss only a few aspects. In the present review, these factors are collected to provide a more holistic synopsis of pain following hernia repair. It may be a resource for understanding this and other postsurgical pain.

A palpable abnormality of the breast was found in three women, one aged 57 and two aged 41. The first two patients predominantly showed the characteristics of a purulent inflammation, and on mammogram the third patient appeared to have mastitis carcinomatosa. Histopathological investigation revealed a lobular, non-caseating granulomatous inflammation. They were treated with prednisone and the first and third patients also received azathioprine. After some time, the condition recurred in the contralateral breast in the second and third patients. Once again, medicinal treatment was given. When a palpable tumour of the breast is found the primary goal is to exclude malignancy. Granulomatous lobular mastitis is a rare and benign tumour of the breast that clinically mimics carcinoma. Often, conventional imaging does not lead to the diagnosis. A histological needle biopsy is the best way to reach a diagnosis. Immunosuppressive therapy is effective and is preferred over surgery.

Recently, an activating somatic mutation of Janus kinase 2 (JAK2V617F) was identified in the myeloproliferative disorders (MPDs). In this study, we investigated the occurrence of JAK2V617F in patients with slightly elevated platelets or hemoglobin without a secondary cause, who did not meet the criteria of polycythemia vera or essential thrombocythemia. Six out of 18 patients (33%) were positive for the JAK2 mutation, and five of these six patients had a history of thrombosis. These findings suggest that apart from thrombocytosis/erythrocytosis, other mechanisms exist that cause thrombosis, and more patients with a latent form of MPD are likely to exist. Future studies will have to elucidate how to treat these patients.

Background: Chronic pain is a severe complication of mesh-based inguinal hernia repair. Its perceived risk varies widely in the literature. The current objectives are to review the incidence, severity, and consequences of chronic pain and its etiologies., Data Sources: A multi-database systematic search was conducted for prospective trials on mesh-based inguinal hernia repair reporting the measurement and outcome of pain at least 3 months postoperatively with a minimum follow-up of 80%., Conclusions: After mesh-based inguinal hernia repair, 11% of patients suffer chronic pain. More than a quarter of these patients have moderate to severe pain, mostly with a neuropathic origin. As a consequence of chronic pain, almost one third of patients have limitations in daily leisure activities. Chronic pain is less frequent after endoscopic repair and with the use of a light-weighted mesh.

Background: The open preperitoneal approach in inguinal hernia repair might have the benefit of a mesh in the preferred space without the disadvantages of an endoscopic procedure., Methods: A total of 172 patients with primary inguinal hernia were randomized to undergo the open preperitoneal Kugel or the standard open anterior Lichtenstein procedure in a teaching hospital. The main outcome measures were operating variables, visual analog scale (VAS) pain scores, and consumed analgesics during the first 2 weeks postoperatively and at 3 months, neurological examination, and complications., Results: In the Lichtenstein group the operation took longer (54 min versus 41 min; p < .001). There were no clinically important differences in VAS pain score or number of analgesics during the first 2 weeks postoperatively. In the Kugel group the mean VAS pain score at 3 months was less (0.3 versus 0.9; p = .002), as was the proportion of patients reporting pain (21 versus 40%; p = .007). Pain was merely described as neuropathic, especially in the Lichtenstein group. With the anterior repair significantly more nerves were encountered, numbness reported, and cutaneous sensory changes found with neurological examination (all p < .001)., Conclusions: For those surgeons preferring an open approach, the Kugel procedure is a feasible alternative for the standard Lichtenstein procedure and is associated with less chronic pain at three months. Most likely the neuropathic pain and numbness with the Lichtenstein technique are results of more nerves at risk with the anterior approach.

A 22-year-old man was admitted to the hospital with an ecstasy (MDMA) intoxication which was accompanied by hyperthermia. The patient developed rhabdomyolysis with hyperkalaemia, hypoglycaemia and acidosis, followed by multiple organ failure with disseminated intravascular coagulation and cerebral oedema. Despite maximal symptomatic treatment, the patient died after 4 days. MDMA is a serotonin agonist but also has noradrenergic and dopaminergic effects. It is a popular drug in the Netherlands among young people and is often wrongly considered to be safe. The occurrence of serious side effects is unpredictable and can have fatal consequences. Especially hyperthermia as a side effect of MDMA is a potentially life-threatening complication. The treatment is mainly symptomatic and consists of cooling, fluids, treatment of electrolyte disturbances, and support for respiration and circulation. The usefulness of dantrolene in the treatment of MDMA-induced hyperthermia is controversial, but for now it is still recommended.

Hypothesis: Surgeons' preferences for any of 3 methods of inguinal hernia repair are comparable in terms of operating time, incision length, perceived difficulty, and surgeon's satisfaction., Design: Randomized patient-blinded study., Setting: Teaching hospital., Patients: A total of 334 patients randomized to receive 1 of the 3 repairs., Interventions: Patients underwent hernia repair with the Prolene Hernia System, mesh plug repair, or Lichtenstein technique., Main Outcome Measures: Operating variables, surgeon's rating of satisfaction and difficulty, grade and experience of the operating team, and complications., Results: The Lichtenstein technique took significantly the longest operating time (52 minutes vs 41 or 42 minutes; P<.001). The mesh plug repair scored the best results in difficulty and satisfaction. Overall, surgeons having performed more than 5 procedures rated the repairs less difficult and with significantly more satisfaction (P<.001 and P = .001, respectively). The complication rate did not differ between the treatment groups. None of the operative findings was correlated to the outcome, except for adverse correlation with the body mass index., Conclusion: From a surgeon's point of view, the mesh plug repair is superior to the Lichtenstein technique and the Prolene Hernia System in terms of operating time, incision length, perceived difficulty, and surgeon's satisfaction.

A 60-year-old woman presented a year after breast-conserving surgery with severe erysipelas caused by a group-B Streptococcus agalactiae. She recovered after treatment with intravenous penicillin.

Aims: The aim of this study is to report initial experience with radiofrequency thermoablation (RFA) of malignant hepatic tumours., Methods: From June 1999 to November 2001, a seven centre study of 50 patients who had undergone RFA, included 102 primary or metastatic tumours. Multimodality therapy, complications, disease free survival and location of recurrence were recorded. Histopathologic examination was performed in a number of tumours treated with RFA and subsequently resected to determine the effect of RFA on the tissue level., Results: 11 tumours (seven patients) were resected after prior treatment with RFA; NADH-diaphorase staining in all these tumours demonstrated non-viable tumour. Postoperative morbidity and mortality occurred in 14 patients and one patient, respectively, in three cases related to the RFA procedure. Median follow-up of 41 patients with non-resected RF ablated tumours was 11 months (range 1-24 months). 26 patients developed a recurrence of which three at the RFA site after 6-12 months., Conclusions: RFA provides a simple method for local treatment of liver tumours. The introduction of this technique nevertheless involves morbidity and mortality.

Objective: To describe policy and prognosis of patients with a cystic mammary lesion caused by an intracystic mammary carcinoma (ICMC)., Design: Retrospective, descriptive., Method: The study concerned retrospective analysis of 17 patients presenting with intracystic carcinoma of the breast in an educational clinic in the period 1988-2000, who were selected by searching the national pathology database (PALGA). None of the patients was on hormone replacement therapy. In addition a literature search was carried out in the Medline system., Results: The patients with an intracystic carcinoma of the breast were 10 years older compared to the other breast cancer patients and presented themselves with a palpable mass. Mammography showed a single, well-defined and lobulated mass. Microcalcifications were uncommon. Ultrasound investigation showed a well-defined, inhomogenous and hypoechoic mass. 6 patients had encysted lesions and in 3 a solid, hypoechoic component within the cystic mass was found. Cytology of the cystic fluid is false negative in 36% (5/14). All patients were treated surgically, varying from excisional biopsy to modified radical mastectomy. In 15 patients an intracystic papillary carcinoma (ICPC) was found. 5 patients show a 'pure' ICPC. In the other 10 patients, 5 had an ICPC with a component of DCIS and 5 patients an ICPC with an invasive component. The median follow-up was 84 months (range: 28-165). In 15 patients no evidence of disease was found at follow-up; 2 patients developed local recurrence. The survival was 100%., Conclusion: Based on the investigation and on the available literature it is concluded that cysts in breasts of postmenopausal women, who do not use hormone replacement therapy, are malignant until proved otherwise. Ultrasound is invaluable in the diagnostic pathway of intracystic carcinoma of the breast. When ICPC is suspected excisional biopsy with sentinel node biopsy is the treatment of choice. The prognosis is good.

The aim of the study was to clarify the factors causing and/or influence morbidity following axillary dissection in patients treated for breast cancer by either lumpectomy or mastectomy. The records of 106 women with invasive breast cancer treated between 1996 and 1997 were retrospectively reviewed. Objective assessment included measurement of lymphoedema, shoulder mobility and axillary sensation. A questionnaire was used for subjective assessment of arm morbidity and pain. Lymphoedema was present in 13% of patients, a restriction in shoulder function in 24%, while 93% of patients had an impaired sensation in the axillary region. Lymphoedema and restriction in shoulder function were common in patients after adjuvant axillary radiation. Morbidity following axillary lymph node dissection is high and confirms the potentially severe effects of a staging procedure on a relatively young population. Adjuvant radiotherapy increases morbidity significantly and therefore indications for adjuvant axillary radiotherapy should be revised with scrutiny for each patient individually, bearing in mind the disastrous consequences of the combination of radiotherapy and surgery on the axilla.

Background: The need for deep groin dissection when superficial nodes contain metastatic melanoma is controversial., Methods: A review of 362 therapeutic groin dissections performed at our tertiary referral center between 1961 and 1995 revealed 71 patients (20%) with positive iliac and/or obturator nodes. This group was analyzed for survival rates, prognostic factors for survival, regional tumor control, and morbidity., Results: Patients with involved deep nodes exhibited overall 5-year and 10-year survival rates of 24% (SE, 5%) and 20% (SE, 5%), respectively. Independent prognostic factors for survival were the number of positive iliac nodes (P = .0011), the Breslow thickness (P = .0069), and the site of the primary tumor (P = .0075). Patients with an unknown primary tumor seemed to have better prognoses. Seven patients (10%) experienced recurrence in the surgically treated groin. The short- and long-term morbidity rates (infection, 17%; skin flap necrosis, 15%; seroma, 17%; mild/ moderate lymphedema, 19%; severe lymphedema, 6%) compared well with those of other series studying inguinal as well as ilioinguinal dissections., Conclusions: From the present study it can be concluded that removal of deep lymph node metastases is worthwhile, because one of every five such patients survives for 10 years. Prognostic factors for survival are the number of involved iliac nodes, the Breslow thickness, and the site of the primary tumor. Long-term regional tumor control can be obtained for 90% of the patients. The morbidity of an additional deep lymph node dissection is acceptable.

Aims: To identify prognostic factors determining overall survival in patients with surgically treated neck node metastases of cutaneous melanoma., Methods: A retrospective study was carried out in 70 patients who were surgically treated with curative intent for cervical lymph-node metastasis from cutaneous head and neck melanoma at our institution between 1960 and 1986., Results: Median follow-up of the 14 patients still alive was 10 years. Of the 70 patients, 64 underwent a radical neck dissection, four a modified radical neck dissection and two a postero-lateral neck dissection. In 63 patients, the node dissection was for palpable involved nodes and in seven for microscopic disease. Survivals after 5 and 10 years were 23% (SE 5%) and 20% (SE 5%), respectively. Five-year survival was 62% (SE 17%) for patients with a melanoma less than 1.5 mm thick and 16% for lesions thicker than 1.5 mm. A regional recurrence in the neck occurred in 16 (23%) patients, of whom 14 were found also to have distant metastases. All patients with regional recurrence died from disease., Conclusions: Of the 15 patient-, tumour- and treatment-related factors tested, only the Breslow thickness of the primary lesion carried prognostic significance for survival (Bonferroni corrected P-value: 0.026).

Purpose: In the past 15 years breast conserving therapy (BCT) has become an important treatment option for primary breast cancer. Thirty three angiosarcomas (AS) after BCT have been described in a total of 20 published reports. Limited follow-up data and the lack of information on incidence of AS prompted the authors to review the comprehensive experience in the Netherlands., Methods: Between 1987 and 1995 twenty-one patients with BCT-associated AS were diagnosed in the Netherlands. Follow-up after diagnosis of AS ranged from 6 to 82 months with a median of 24 months. Information on the total number of patients treated with BCT and on the numbers of angiosarcoma in the breast was obtained., Results: The median interval between BCT and AS was 74 months (range: 29-106) and appeared to decrease with higher age. Detection of skin changes followed by incisional biopsy provided the diagnosis. Two year overall (OS) and disease free survivals were 72% (s.e. 10.9) and 35% (s.e. 10.7), respectively. Two year OS after initial complete surgical resection was 86% (s.e. 9.3) compared to 0% after incomplete resection of the AS (P = 0.04). The estimated incidence of AS after BCT is 0.16%., Conclusions: BCT-associated AS arises after a relatively short interval. Although the incidence of AS is low, the absolute number of patients at risk is increasing. This calls for vigilance concerning skin changes occurring after BCT. An incisional biopsy provides the only reliable diagnosis. The prognosis appears to be related to the completeness of surgical resection.

A total of 469 in-transit or satellite lesions were treated by carbon dioxide (CO2) laser vaporization in 15 patients. The treatment was performed mostly on an outpatient basis, under local anaesthesia. The technique was easily mastered and quickly performed. Wound healing and patient acceptance were good. A major drawback, however, proved to be the unexpected high incidence of recurrences at the lasered sites. In our opinion CO2 laser treatment may be considered as a palliative option in patients with a moderate to extensive amount of cutaneous metastases, whose lesions preferably are < 10 mm and in whom local excision is not feasible anymore. For extremity lesions this treatment may have a place after failure of isolated limb perfusion. CO2 laser treatment cannot be considered a first-line option unless the issue of local recurrences is solved.

Three patients with carcinoid tumors of the ileum are presented; two had severe intestinal ischemia, one with infarction of the small intestine. In all three cases, histopathological examination revealed elastic vascular sclerosis (EVS) in the mesenteric blood vessels. Intestinal ischemia in the presence of a carcinoid tumor is probably due to a combination of tumoral secretion products, vascular changes, mesenterial retraction and nodal involvement. Selective superior mesenteric artery arteriography is diagnostic. All the reported carcinoid tumors with ischemic manifestations are ileal and invaded the mesentery or had positive nodes or metastases; two-thirds had EVS, and one-third mesenterial vascular luminal narrowing. Intestinal ischemia may be the underlying cause of vague symptoms in patients with a carcinoid tumor. This tumor may be small and must be looked for during laparotomy, mild intestinal ischemia or mesenterial thickening are important signs. Early resection can prevent intestinal complications. An aggressive attitude, including debulking of metastases, is justifiable.