[Show abstract][Hide abstract] ABSTRACT: 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.
Gut 03/2015; DOI:10.1136/gutjnl-2015-309298 · 14.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pelvic serous carcinoma is usually advanced stage at diagnosis, indicating that abdominal spread occurs early in carcinogenesis. Recent discovery of a precursor sequence in the fallopian tube, culminating in serous tubal intraepithelial carcinoma (STIC), provides an opportunity to study early disease events. This study aims to explore novel metastatic routes in STICs. A BRCA1 mutation carrier (patient A) who presented with a STIC and tubal intraluminal shedding of tumor cells upon prophylactic bilateral salpingo-oophorectomy (PBSO) instigated scrutiny of an additional 23 women who underwent a PBSO and 40 patients with pelvic serous carcinoma involving the tubes. Complete serial sectioning of tubes and ovaries of patient A did not reveal invasive carcinoma, but subsequent staging surgery showed disseminated abdominal disease. STIC, intraluminal tumor cells, and abdominal metastases displayed an identical immunohistochemical profile (p53/WT1/PAX8/PAX2) and TP53 mutation. In 16 serous carcinoma patients (40%) tubal intraluminal tumor cells were found, compared with none in the PBSO group. This is the first description of a STIC, which plausibly metastasized without the presence of invasion through intraluminal shedding of malignant surface epithelial cells in the tube and subsequently spread throughout the peritoneal cavity. These findings warrant a reconsideration of the malignant potential of STICs and indicate that intraluminal shedding could be a risk factor for early intraperitoneal metastasis. Although rare in the absence of invasive cancer, we show that intraluminal shedding of tumor cells in the fallopian tubes from serous carcinoma cases are common and a likely route of abdominal spread.
The American journal of surgical pathology 05/2013; 37(8). DOI:10.1097/PAS.0b013e318282da7f · 5.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND & AIMS: The current procedure for circumferential balloon-based radiofrequency ablation (c-RFA) for the removal of dysplastic Barrett's esophagus (BE) is labor-intensive, comprising 2 ablation passes with a cleaning step to remove debris from the ablation zone and electrode. We compared the safety and efficacy of 3 different c-RFA ablation regimens. METHODS: We performed a prospective trial of consecutive patients with flat-type BE with high-grade dysplasia. Fifty-seven patients (45 men, 64±15 y old, 28 with prior endoscopic resection) were randomly assigned to groups that underwent c-RFA with a double application of RFA (12 J/cm(2)). The standard group received c-RFA, with device removal and cleaning, followed by c-RFA; the simple-with-cleaning group underwent c-RFA, with device cleaning without removal, followed by c-RFA; and the simple-no-cleaning group received 2 applications of c-RFA, and the device was not removed or cleaned. The primary outcome was surface regression of BE 3 months later, graded by 2 blinded, expert endoscopists. Calculated sample size was 57 patients, based on a non-inferiority design. RESULTS: Median BE surface regression at 3 months was 83% in the standard group, 78% in the simple-with-cleaning group, and 88% in the simple-no-cleaning group (P =.14). RF ablation time was 20 min (inter-quartile range [IQR], 18-25 min) for the standard group, 13 min (IQR, 11-15 min) for the simple-with- cleaning group, and 5 min (IQR, 5-9 min) for the simple-no-cleaning group (P <.01). The median number of introductions (RFA devices/endoscope) for the standard group was 7, vs 4 for the simple groups ( P <.01). CONCLUSIONS: This randomized, prospective study suggests that c-RFA is easier and faster, but equally safe and effective, when the cleaning phase between ablations is omitted or simplified. Trialregister.nl, NTR 2495.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 12/2012; 11(5). DOI:10.1016/j.cgh.2012.12.005 · 7.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Carcinoids are slow-growing neuroendocrine tumors that, in the lung, can be subclassified as typical (TC) or atypical (AC). To identify genetic alterations that improve the prediction of prognosis, we investigated 34 carcinoid tumors of the lung (18 TCs, 15 ACs, and 1 unclassified) by using array comparative genomic hybridization (array CGH) on 3700 genomic bacterial artificial chromosome arrays (resolution ≤1 Mb). When comparing ACs with TCs, the data revealed: i) a significant difference in the average number of chromosome arms altered (9.6 versus 4.2, respectively; P = 0.036), with one subgroup of five ACs having more than 15 chromosome arms altered; ii) chromosomal changes in 30% of ACs or more with additions at 9q (≥1 Mb) and losses at 1p, 2q, 10q, and 11q; and iii) 11q deletions in 8 of 15 ACs versus 1 of 18 TCs (P = 0.004), which was confirmed via fluorescence in situ hybridization. The four critical regions of interest in 45% ACs or more comprised 11q14.1, 11q22.1-q22.3, 11q22.3-q23.2, and 11q24.2-q25, all telomeric of MEN1 at 11q13. Results were correlated with patient clinical data and long-term follow-up. Thus, there is a strong association of 11q22.3-q25 loss with poorer prognosis, alone or in combination with absence of 9q34.11 alterations (P = 0.0022 and P = 0.00026, respectively).
American Journal Of Pathology 09/2011; 179(3):1129-37. DOI:10.1016/j.ajpath.2011.05.028 · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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]).
This study suggests that RFA with or without prior endoscopic resection for esophageal squamous HGIN and mucosal ESCC is feasible and effective.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
MBM is a safe and effective technique for the removal of delineated target areas in Barrett's esophagus.
[Show abstract][Hide abstract] ABSTRACT: Radiofrequency ablation (RFA) is safe and effective for eradicating Barrett's esophagus (BE) and BE-associated early neoplasia. Most RFA studies have limited the baseline length of BE (<10 cm), and therefore little is known about RFA for longer BE.
To assess the safety and efficacy of RFA with or without prior endoscopic resection (ER) for BE ≥ 10 cm containing neoplasia.
Two tertiary-care centers.
This study involved consecutive patients with BE ≥ 10 cm with early neoplasia.
Focal ER for visible abnormalities, followed by a maximum of 2 circumferential and 3 focal RFA procedures every 2 to 3 months until complete remission.
Complete remission, defined as endoscopic resolution of BE and no intestinal metaplasia (CR-IM) or neoplasia (CR-neoplasia) in biopsy specimens.
Of the 26 patients included, 18 underwent ER for visible abnormalities before RFA. The ER specimens showed early cancer in 11, high-grade intraepithelial neoplasia (HGIN) in 6, and low-grade intraepithelial neoplasia (LGIN) in 1. The worst residual histology, before RFA and after any ER, was HGIN in 16 patients and LGIN in 10 patients. CR-neoplasia and CR-IM were achieved in 83% (95% confidence interval [CI], 63%-95%) and 79% (95% CI, 58%-93%), respectively. None of the patients had fatal or severe complications and 15% (95% CI, 4%-35%) had moderate complications. During a mean (± standard deviation) follow-up of 29 (± 9.1) months, no neoplasia recurred.
Tertiary-care center, short follow-up.
ER for visible abnormalities, followed by RFA of residual BE is a safe and effective treatment for BE ≥ 10 cm containing neoplasia, with a low chance of recurrence of neoplasia or BE during follow-up.
[Show abstract][Hide abstract] ABSTRACT: When breast cancer patients develop distant metastases, the choice of systemic treatment is usually based on tissue characteristics of the primary tumor as determined by immunohistochemistry (IHC) and/or molecular analysis. Several previous studies have shown that the immunophenotype of distant breast cancer metastases may be different from that of the primary tumor ("receptor conversion"), leading to inappropriate choice of systemic treatment. The studies published so far are however small and/or methodologically suboptimal. Therefore, definite conclusions that may change clinical practice could not yet be drawn. We therefore aimed to study receptor conversion for estrogen receptor alpha (ERα), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in a large group of distant (non-bone) breast cancer metastases by re-staining all primary tumors and metastases with current optimal immunohistochemical and in situ hybridization methods on full sections.
233 distant breast cancer metastases from different sites (76 skin, 63 liver, 43 lung, 44 brain and 7 gastro-intestinal) were IHC stained for ERα, PR and HER2, and expression was compared to that of the primary tumor. HER2 in situ hybridization (ISH) was done in cases of IHC conversion or when primary tumors or metastases showed an IHC 2+ result.
Using a 10% threshold, receptor conversion by IHC for ERα, PR occurred in 10.3%, 30.0% of patients, respectively. In 10.7% of patients, conversion from "ER+ or PR+" to ER-/PR- and in 3.4% from ER-/PR- to "ER+ or PR+" was found. Using a 1% threshold, ERα and PR conversion rates were 15.1% and 32.6%. In 12.4% of patients conversion from "ER+ or PR+" to ER-/PR-, and 8.2% from ER-/PR- to "ER+ or PR+" occurred. HER2 conversion occurred in 5.2%. Of the 12 cases that showed HER2 conversion by IHC, 5 showed also conversion by ISH. One further case showed conversion by ISH, but not by IHC. Conversion was mainly from positive in the primary tumor to negative in the metastases for ERα and PR, while HER2 conversion occurred equally both ways. PR conversion occurred significantly more often in liver, brain and gastro-intestinal metastases.
Receptor conversion by immunohistochemistry in (non-bone) distant breast cancer metastases does occur, is relatively uncommon for ERα and HER2, and more frequent for PR, especially in brain, liver and gastro-intestinal metastases.
Breast cancer research: BCR 09/2010; 12(5):R75. DOI:10.1186/bcr2645 · 5.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PURPOSE Application of current nodal status classification is complicated in lobular breast carcinoma metastases. The aim of this study was to define the optimal interpretation of the pTNM classification in sentinel node (SN) -positive patients to select patients with limited or with a high risk of non-SN involvement. PATIENTS AND METHODS SN metastases of 392 patients with lobular breast carcinoma were reclassified according to interpretations of the European Working Group for Breast Screening Pathology (EWGBSP) and guidelines by Turner et al, and the predictive power for non-SN involvement was assessed. Results Reclassification according to definitions of EWGBSP and Turner et al resulted in different pN classification in 73 patients (19%). The rate of non-SN involvement in the 40 patients with isolated tumor cells according to Turner et al and with micrometastases according to EWGBSP was 20%, which is comparable to the established rate for micrometastases. The rate of non-SN involvement in the 29 patients with micrometastases according to Turner et al and with macrometastases according to EWGBSP was 48%, which is comparable to the established rate for macrometastases. Therefore, the EWGBSP method to classify SN tumor load better reflected the risk of non-SN involvement than the Turner et al system. CONCLUSION Compared with the guidelines by Turner et al, the EWGBSP definitions better reflect SN metastatic tumor load and allow better differentiation between patients with lobular breast carcinoma who have a limited or a high risk of non-SN metastases. Therefore, we suggest using the EWGBSP definitions in these patients to select high-risk patients who may benefit from additional local and/or systemic therapy.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
Thrombosis Research 08/2009; 125(4):318-21. DOI:10.1016/j.thromres.2009.06.008 · 2.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mucinous cystadenocarcinoma of the appendix is a rare malignancy. This is a report of a 74-year-old man who presented with recurrent pneumonia which turned out to be a postobstructive pneumonia complicating a large mucinous cystadenocarcinoma of the appendix with massive retroperitoneal and intrathoracic extension. Mucinous cystadenocarcinoma of the appendix is a low-grade malignancy characterized by expansive growth due to progressive accumulation of mucinous fluid produced by the cancer cells. The tendency of this tumor to expand massively is well demonstrated by this case. The unusual retroperitoneal location of appendix in this patient probably allowed the tumor to expand massively in the retroperitoneal space and the thoracic cavity. In addition to computed tomography, [(18)F]fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) was used as an ancillary method for staging in this patient. The value of (18)F-FDG PET in the diagnosis of mucinous cystadenocarcinoma of the appendix has not been determined yet, but it might be promising. The most common presentation of this tumor is abdominal pain or a palpable ileocoecal mass. To the knowledge of the authors, this is the first report of an appendiceal mucinous cystadenocarcinoma with expansion into the thoracic cavity presenting with recurrent pneumonia.
[Show abstract][Hide abstract] ABSTRACT: Left atrial myxomas are benign, slow-growing primary cardiac tumors. They present with gradual onset of one or more of a triad of obstructive, embolic, or constitutional symptoms. Transesophageal echocardiography aids in the detailed preoperative and intraoperative evaluation of the myxoma for surgical strategy planning. We describe a previously unreported case of interstitial hemorrhage in a left atrial myxoma leading to rapid expansion of the tumor with features of acute, mitral valve obstruction. Transesophageal echocardiography showed a cystic area in the left atrial tumor that corresponded to an area of recent hemorrhage confirmed on surgical removal.
The Annals of thoracic surgery 03/2009; 87(2):636-8. DOI:10.1016/j.athoracsur.2008.06.019 · 3.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Rheumatology International 05/2008; 28(11):1177-8. DOI:10.1007/s00296-008-0588-6 · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
British Journal of Dermatology 01/2008; 157(6):1087-92. DOI:10.1111/j.1365-2133.2007.08253.x · 4.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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).
[Show abstract][Hide abstract] ABSTRACT: A 37-year-old patient presented with severe aortic valve insufficiency due to massive dilatation of the neo-aortic root (77 mm diameter) 14 years after a Ross procedure. Intraoperatively, the dilatation appeared to be caused by a localized chronic dissection of the pulmonary autograft. Surgery consisted of a modified Bentall procedure with a mechanical composite valve, with an uncomplicated postoperative course.
The Journal of heart valve disease 04/2007; 16(2):162-4. · 0.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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 </=1 cm (N=12, 3.8%) had second echelon lymph node involvement.
Accurately measured SN tumor load predicts second echelon lymph node involvement. However, even in patients with ITC, the second echelon lymph nodes are involved in 13% justifying ALND.
Cellular oncology: the official journal of the International Society for Cellular Oncology 01/2007; 29(6):497-505. · 4.17 Impact Factor