Background and Objectives

This study was designed to identify and validate gene signatures that can predict disease free survival (DFS) in patients undergoing a radical resection for their colorectal liver metastases (CRLM).

Methods

Tumor gene expression profiles were collected from 119 patients undergoing surgery for their CRLM in the Paul Brousse Hospital (France) and the University Medical Center Utrecht (The Netherlands). Patients were divided into high and low risk groups. A randomly selected training set was used to find predictive gene signatures. The ability of these gene signatures to predict DFS was tested in an independent validation set comprising the remaining patients. Furthermore, 5 known clinical risk scores were tested in our complete patient cohort.

Result

No gene signature was found that significantly predicted DFS in the validation set. In contrast, three out of five clinical risk scores were able to predict DFS in our patient cohort.

Conclusions

No gene signature was found that could predict DFS in patients undergoing CRLM resection. Three out of five clinical risk scores were able to predict DFS in our patient cohort. These results emphasize the need for validating risk scores in independent patient groups and suggest improved designs for future studies.

Background

European nutritional guidelines recommend routine use of enteral feeding after pancreaticoduodenectomy (PD) whereas American guidelines do not. Data on the efficacy and, especially, complications of the various feeding strategies after PD are scarce.

Methods

Retrospective monocenter cohort study in 144 consecutive patients who underwent PD during a period wherein the routine post-PD feeding strategy changed twice. Patients not receiving nutritional support (n=15) were excluded. Complications were graded according to the Clavien-Dindo classification and the International Study Group of Pancreatic Surgery (ISGPS) definitions. Analysis was by intention-to-treat. Primary endpoint was the time to resumption of normal oral intake.

Results

129 patients undergoing PD (111 pylorus preserving) were included. 44 patients (34%) received enteral nutrition via nasojejunal tube (NJT), 48 patients (37%) via jejunostomy tube (JT) and 37 patients (29%) received total parenteral nutrition (TPN). Groups were comparable with respect to baseline characteristics, Clavien ≥II complications (P=0.99), in-hospital stay (P=0.83) and mortality (P=0.21). There were no differences in time to resumption of normal oral intake (primary endpoint; NJT/JT/TPN: median 13, 16 and 14 days, P=0.15) and incidence of delayed gastric emptying (P=0.30). Duration of enteral nutrition was shorter in the NJT- compared to the JT- group (median 8 vs. 12 days, P=0.02). Tube related complications occurred mainly in the NJT-group (34% dislodgement). In the JT-group, relaparotomy was performed in three patients (6%) because of JT-leakage or strangulation leading to death in one patient (2%). Wound infections were most common in the TPN group (NJT/JT/TPN: 16%, 6% and 30%, P=0.02).

Conclusion

None of the analysed feeding strategies was found superior with respect to time to resumption of normal oral intake, morbidity and mortality. Each strategy was associated with specific complications. Nasojejunal tubes dislodged in a third of patients, jejunostomy tubes caused few but potentially life-threatening bowel strangulation and TPN doubled the risk of infections.

Background

Chemotherapy treatment induces parenchymal changes that potentially affect imaging of CRLM. The purpose of this meta-analysis was to provide values of diagnostic performance of magnetic resonance imaging (MRI), computed tomography (CT), fluorodeoxyglucose positron emission tomography (FDG-PET), and FDG-PET/CT for preoperative detection of colorectal liver metastases (CRLM) in patients treated with neoadjuvant chemotherapy.

Methods

A comprehensive search was performed for original articles published from inception to 2011 assessing diagnostic performance of MRI, CT, FDG-PET, or FDG-PET/CT for preoperative evaluation of CRLM following chemotherapy. Intraoperative findings and/or histology were used as reference standard. For each imaging modality we calculated pooled sensitivities for patients who received neoadjuvant chemotherapy as well as for chemonaive patients, defined as number of malignant lesions detected divided by number of malignant lesions as confirmed by the reference standard.

Results

A total of 11 papers, comprising 223 patients with 906 lesions, were included. Substantial variation in study design, patient characteristics, imaging features, and reference tests was observed. Pooled sensitivity estimates of MRI, CT, FDG-PET, and FDG-PET/CT were 85.7% (69.7–94.0%), 69.9% (65.6–73.9%), 54.5% (46.7–62.1%), and 51.7% (37.8–65.4%), respectively. In chemonaive patients, sensitivity rates were 80.5% (67.0–89.4%) for CT, 81.3% (64.1–91.4%) for FDG-PET, and 71.0% (64.3–76.9%) for FDG-PET/CT. Specificity could not be calculated because of non-reporting of “true negative lesions.”

Conclusion

In the neoadjuvant setting, MRI appears to be the most appropriate imaging modality for preoperative assessment of patients with CRLM. CT is the second-best diagnostic modality and should be used in the absence of MRI. Diagnostic accuracy of FDG-PET and PET-CT is strongly affected by chemotherapy.

A 59-year-old woman presented with the clinical symptoms and radiologic investigations of a liver lesion suspect of metastasis. However, postoperative histopathology revealed a primary hepatic lymphoma (PHL). The case of a patient with a solitary PHL, which was treated by resection and subsequent chemotherapy, will be discussed with a short overview of the literature.

Background

Major oncologic surgery is associated with a high incidence of thromboembolic events (TEE). Addition of perioperative chemotherapy in esophageal cancer surgery may increase the risk of TEE.

Methods

The thromboembolic toxicity profile was analyzed in patients with esophageal adenocarcinoma (EAC). Two groups were identified: patients who underwent esophagectomy and received perioperative chemotherapy with epirubicin, cisplatin, and capecitabine (ECC; n = 52), and patients who were treated with surgery alone (n = 35).

Results

A total of 22 TEEs was observed in 17 patients (32.7%) in the chemotherapy group and 3 patients (7.5%) in the surgery-alone group (P < .01). The relative risk of developing a TEE for patients receiving perioperative chemotherapy during the whole treatment period was 3.8 (95% confidence interval 1.2–12.0). A preoperatively occurring TEE did not increase the risk of postoperative TEE, nor did it increase postoperative hospital stay (P = .325). Median postoperative hospital stay was 23 days (range 14–78) for patients with a postoperative TEE and 15 days (range 10–105) for patients without TEE (P = .126). Perioperative chemotherapy with the epirubicin, cisplatin, and capecitabine regimen was independently associated with the development of TEE in the combined preoperative and postoperative period (P = .034).

Conclusions

Perioperative chemotherapy improves survival for operable esophageal cancer but comes at the price of toxicity. Perioperative chemotherapy for EAC increases the risk of TEE. However, chemotherapy-related preoperative TEE did not increase the risk of postoperative TEE, nor did it increase postoperative hospital stay, justifying its use in clinical practice.

Background

Local tumor progression (LTP) is a serious complication after local ablation of malignant liver tumors, negatively influencing patient survival. LTP may be the result of incomplete ablation of the treated tumor. In this study, we determined whether viable tumor cells attached to the needle applicator after ablation was associated with LTP and disease-free survival.

Methods

In this prospective study, tissue was collected of 96 consecutive patients who underwent local liver ablations for 130 liver malignancies. Cells and tissue attached to the needle applicators were analyzed for viability using glucose-6-phosphate-dehydrogenase staining and autofluorescence intensity levels of H&E stained sections. Patients were followed-up until disease progression.

Results

Viable tumor cells were found on the needle applicators after local ablation in 26.7% of patients. The type of needle applicator used, an open approach, and the omission of track ablation were significantly correlated with viable tumor tissue adherent to the needle applicator. The presence of viable cells was an independent predictor of LTP. The attachment of viable cells to the needle applicators was associated with a shorter time to LTP.

Conclusions

Viable tumor cells adherent to the needle applicators were found after ablation of 26.7% of patients. An independent risk factor for viable cells adherent to the needle applicators is the omission of track ablation. We recommend using only RFA devices that have track ablation functionality. Adherence of viable tumor cells to the needle applicator after local ablation was an independent risk factor for LTP.

Background

The aim of this study was to evaluate the need of axillary staging in breast cancer patients showing exclusive lymphatic drainage to the internal mammary chain (IMC).

Methods

A total of 2203 patients treated for breast carcinoma in three participating hospitals between July 2001 and July 2008 were analyzed. Only patients showing drainage to the IMC on preoperative lymphoscintigraphy were included. The number of harvested IMC sentinel lymph nodes (SLNs), axillary SLNs, and metastases were recorded. Finally, the follow-up of this group of patients was analyzed.

Results

In 25/426 patients, drainage was exclusively to the IMC. Exploration of the axilla resulted in the harvesting of blue SLNs in 9 patients (36%) and the retrieval of an enlarged lymph node in 1 patient. In 4 of the remaining 15 patients, an axillary lymph node dissection (ALND) was done. Lymph node metastases were found in 3 patients who had blue axillary SLNs and in 1 patient who underwent ALND. In the 11 patients who had no blue SLNs and no ALND, no axillary recurrences were observed during follow-up (median = 26 months).

Conclusions

Proper staging of the axilla remains crucial in patients showing exclusive drainage to the IMC. When no axillary node can be retrieved, ALND remains subject to discussion.

Hepatocellular carcinoma (HCC) is a primary malignant tumor of the liver that accounts for an important health problem worldwide. Only 10–15% of HCC patients are suitable candidates for hepatic resection and liver transplantation due to the advanced stage of the disease at time of diagnosis and shortage of donors. Therefore, several minimally invasive image-guided therapies for locoregional treatment have been developed. Tumor ablative techniques are either based on thermal tumor destruction, as in radiofrequency ablation, cryoablation, microwave ablation, laser ablation and high-intensity focused ultrasound, or chemical tumor destruction, as in percutaneous ethanol injection. Image-guided catheter-based techniques rely on intra-arterial delivery of embolic, chemoembolic or radioembolic agents. These minimally invasive image-guided therapies have revolutionized the management of inoperable HCC. This review provides a description of all minimally invasive image-guided therapies currently available, an up-to-date overview of the scientific evidence for their clinical use, and thoughts for future directions.

The feasibility of large-core-needle magnetic resonance imaging (MRI)-guided breast biopsy at 3 T was assessed. Thirty-one suspicious breast lesions shown only by MRI were detected in 30 patients. Biopsy procedures were performed in a closed-bore 3-T clinical MR system on a dedicated phased-array breast coil with a commercially available add-on stereotactic biopsy device. Tissue sampling was technically successful in 29/31 (94%) lesions. Median lesion size (n = 29) was 9 mm. Histopathological analysis showed 19 benign lesions (66%) and one inconclusive biopsy result (3%). At follow-up of these lesions, 15 lesions showed no malignancy, no information was available in three patients and two lesions turned out to be malignant (one lesion at surgical excision 1 month after biopsy and one lesion at a second biopsy because of a more malignant enhancement curve at 12-months follow-up MRI). Nine biopsy results showed a malignant lesion (31%) which were all surgically removed. No complications occurred. MRI-guided biopsy at 3 T is a safe and effective method for breast biopsy in lesions that are occult on mammography and ultrasound. Follow-up MRI at 6 months after the biopsy should be performed in case of a benign biopsy result.

Tissue microarray (TMA) technology has been developed to facilitate high-throughput immunohistochemical and in situ hybridization analysis of tissues by inserting small tissue biopsy cores into a single paraffin block. Several studies have revealed novel prognostic biomarkers in esophageal squamous cell carcinoma (ESCC) by means of TMA technology, although this technique has not yet been validated for these tumors. Because representativeness of the donor tissue cores may be a disadvantage compared to full sections, the aim of this study was to assess if TMA technology provides representative immunohistochemical results in ESCC. A TMA was constructed containing triplicate cores of 108 formalin-fixed, paraffin-embedded squamous cell carcinomas of the esophagus. The agreement in the differentiation grade and immunohistochemical staining scores of CK5/6, CK14, E-cadherin, Ki-67, and p53 between TMA cores and a subset of 64 randomly selected donor paraffin blocks was determined using kappa statistics. The concurrence between TMA cores and donor blocks was moderate for Ki-67 (κ = 0.42) and E-cadherin (κ = 0.47), substantial for differentiation grade (κ = 0.65) and CK14 (κ = 0.71), and almost perfect for p53 (κ = 0.86) and CK5/6 (κ = 0.93). TMA technology appears to be a valid method for immunohistochemical analysis of molecular markers in ESCC provided that the staining pattern in the tumor is homogeneous.

Background

The majority of sentinel node (SN) positive breast cancer patients do not have additional non-SN involvement and may not benefit from axillary lymph node dissection (ALND). Previous studies in melanoma have suggested that microanatomic localization of SN metastases may predict non-SN involvement. The present study was designed to assess whether these criteria might also be used to be more restrictive in selecting breast cancer patients who would benefit from an ALND.

Methods

A consecutive series of 357 patients with invasive breast cancer and a tumor-positive axillary SN, followed by an ALND, was reviewed. Microanatomic SN tumor features (subcapsular, combined subcapsular and parenchymal, parenchymal, extensive localization, multifocality, and the penetrative depth from the SN capsule) were evaluated for their predictive value for non-SN involvement.

Results

Non-SN metastases were found in 136/357 cases (38%). Microanatomic location and penetrative depth of SN metastases were significant predictors for non-SN involvement (<0.001); limited penetrative depth was associated with a low frequency of non-SN involvement with a minimal of 10%.

Conclusions

Microanatomic location and penetrative depth of breast cancer SN metastases predict non-SN involvement. However, based on these features no subgroup of patients could be selected with less than 10% non-SN involvement.

Background

The combination of partial liver resection and radiofrequency ablation (RFA) is a novel concept in the treatment of unresectable liver malignancies. The aim of this study is to evaluate the results of this combined strategy in the Netherlands.

Methods

Thirty-five patients treated with a combination of partial liver resection and RFA were identified from a prospectively registered pooled multicentre database. All patients were operated between June 1999 and November 2003 in 8 medical centres in the Netherlands. Main outcome parameters were morbidity, mortality, local success rate, and survival.

Results

Thirty-seven operations were performed in 35 patients. The group consisted of 20 male and 15 female patients with a median age of 59 years (range 41–76). Seventy-six lesions were resected and RFA was performed to ablate 82 unresectable liver tumours. Twelve patients developed a total of 24 complications, resulting in an overall perioperative morbidity rate of 32%. In two patients major complications resulted in postoperative death (postoperative mortality rate 5.4%). Local success rate after RFA was 88% and the estimated 1-, 2- and 3-year overall survival rates were 84%, 70% and 43%, respectively.

Conclusion

This strategy should only be performed following strict patient selection and within the context of prospective clinical trials.

Background

Neuroendocrine tumours frequently metastasize to the liver. Although generally slowly progressing, hepatic metastases are the major cause of carcinoid syndrome and ultimately lead to liver dysfunction, cardiac insufficiency and finally death.

Methods

A literature review was performed to define the optimal treatment strategy and work-up in patients with neuroendocrine hepatic metastases. Based on this, an algorithm for the management of these patients was established.

Results

Platelet serotonin and chromogranin A are useful biomarkers for detection and follow-up of neuroendocrine tumour. Helical computed tomography and somatostatin receptor scintigraphy are the most sensitive diagnostic modalities. Surgical debulking is an accepted approach for reducing hormonal symptoms and to establish better conditions for medical treatment, but is frequently impossible due to the extent of disease. A novel approach is the local ablation of tumour by thermal coagulation using therapies such as radiofrequency ablation (RFA) or laser induced thermotherapy (LITT). These techniques preserve normal liver tissue. There is a tendency to destroy metastases early in the course of disease, thereby postponing or eliminating the surgically untreatable stage. This can be combined with postoperative radioactive octreotide to eliminate small multiple metastases. In patients with extensive metastases who are not suitable for local destruction, systemic therapy by octreotide, 131I-MIBG treatment or targeted chemo- and radiotherapy should be attempted. A final option for selective patients is orthotopic liver transplantation.

Conclusion

Treatment for patients with neuroendocrine hepatic metastases must be tailored for each individual patient. When local ablative therapies are used early in the course of the disease, the occurrence of carcinoid syndrome with end stage hepatic disease can be postponed or prevented.

Background

Hepatic metastases of carcinoid tumors cause incapacitating symptoms, but are usually diffuse and therefore unresectable. In this article we evaluate our experiences with local treatment techniques in the management of carcinoid patients with hepatic metastases and failing systemic treatment.

Methods

Fifteen consecutive carcinoid patients (11 men and 4 women; median age 60 years; range 45–71 years) were treated with either hepatic artery embolization (HAE) with Ivalon particles or radiofrequency ablation (RFA) (percutaneously or intra-operatively). Follow-up evaluation was performed by CT scan and 24-hours urinary 5-HIAA excretions.

Results

A total of 18 HAE's was performed in 13 patients, while 10 lesions in 3 patients were treated with RFA. Median follow-up was 12.5 months (2 – 25 months). Median duration of symptoms was 22 months (8 – 193 months). Median overall decrease of 5-HIAA excretion 2 months after HAE was 32% with tumor regression on CT-scan in 4 patients (30%) and improvement of symptoms with a median duration of 15 months in 3 of them (23%). Embolization led to fatal hepatic failure in one patient. The 3 patients treated with RFA showed a decrease of urinary 5-HIAA values of 34, 81 and 93% respectively, with tumor regression in all of them. Improvement of symptoms was reported in 2 patients up to 25 months.

Conclusion

Liver embolization performed late in the clinical course had limited effect on symptoms and biochemical and radiological parameters. First experiences with RFA are favorable and might encourage to apply RFA more widely in metastatic carcinoid.

Background

The purpose of this study was to evaluate the long-term results of partial liver resection for benign liver lesions.

Methods

All patients operated on for benign liver lesions from 1991 to 2002 were included. Information was retrieved from medical records, the hospital registration system and by a telephonic questionnaire.

Results

Twenty-eight patients with a median age of 41 years (17–71) were operated on (M/F ratio 5/23). The diagnosis was haemangioma in 8 patients, FNH in 6, HCA in 13 and angiomyolipoma in 1. Eight patients were known to have relevant co-morbidity. Median operating time was 207 minutes (45–360). The morbidity rate was 25% and no postoperative mortality was observed. Twenty-two patients (79%) had symptoms (mainly abdominal pain) prior to surgery. Twenty-five patients were reached for a questionnaire. The median follow up was 55 months (4–150). In 89% of patients preoperative symptoms had decreased or disappeared after surgery. Four patients developed late complications.

Conclusion

Long-term follow up after liver surgery for benign liver lesions shows considerable symptom relief and patient satisfaction. In addition to a correct indication these results justify major surgery with associated morbidity and mortality.

Background

Balloon injury (BI) of the rat carotid artery (CCA) is widely used to study intimal hyperplasia (IH) and decrease in lumen diameter (LD), but CCA's small diameter impedes the evaluation of endovascular therapies. Therefore, we validated BI in the aorta (AA) and iliac artery (CIA) to compare it with CCA.

Methods

Rats underwent BI or a sham procedure (control). Light microscopic evaluation was performed either directly or at 1, 2, 3, 4 and 16 weeks follow-up. The area of IH and the change in LD (LD at 16 weeks minus LD post BI) were compared.

Results

In the BI-groups the area of IH increased to 0.14 ± 0.08 mm2 (CCA), 0.14 ± 0.03 mm2 (CIA) and 0.12 ± 0.04 mm2 (AA) at 16 weeks (NS). The LD decreased with 0.49 ± 0.07 mm (CCA), compared to 0.22 ± 0.07 mm (CIA) and 0.07 ± 0.10 mm (AA) at 16 weeks (p < 0.05). The constrictive vascular remodelling (CVR = wall circumference loss combined with a decrease in LD) was -0.17 ± 0.05 mm in CIA but absent in CCA and AA. No IH, no decrease in LD and no CVR was seen in the control groups.

Conclusions

BI resulted in: (1.) a decrease in LD in CCA due to IH, (2.) a decrease in LD in CIA due to IH and CVR, (3.) no change in LD in AA, (4.) Comparable IH development in all arteries, (5.) CCA has no vasa vasorum compared to CIA and AA, (6.) The CIA model combines good access for 2 F endovascular catheters with a decrease in LD due to IH and CVR after BI.

Background

For esophageal cancer patients, radical esophagolymphadenectomy is the cornerstone of multimodality treatment with curative intent. Transthoracic esophagectomy is the preferred surgical approach worldwide allowing for en-bloc resection of the tumor with the surrounding lymph nodes. However, the percentage of cardiopulmonary complications associated with the transthoracic approach is high (50 to 70%).

Recent studies have shown that robot-assisted minimally invasive thoraco-laparoscopic esophagectomy (RATE) is at least equivalent to the open transthoracic approach for esophageal cancer in terms of short-term oncological outcomes. RATE was accompanied with reduced blood loss, shorter ICU stay and improved lymph node retrieval compared with open esophagectomy, and the pulmonary complication rate, hospital stay and perioperative mortality were comparable. The objective is to evaluate the efficacy, risks, quality of life and cost-effectiveness of RATE as an alternative to open transthoracic esophagectomy for treatment of esophageal cancer.

Methods/design

This is an investigator-initiated and investigator-driven monocenter randomized controlled parallel-group, superiority trial. All adult patients (age ≥18 and ≤80 years) with histologically proven, surgically resectable (cT1-4a, N0-3, M0) esophageal carcinoma of the intrathoracic esophagus and with European Clinical Oncology Group performance status 0, 1 or 2 will be assessed for eligibility and included after obtaining informed consent. Patients (n = 112) with resectable esophageal cancer are randomized in the outpatient department to either RATE (n = 56) or open three-stage transthoracic esophageal resection (n = 56). The primary outcome of this study is the percentage of overall complications (grade 2 and higher) as stated by the modified Clavien–Dindo classification of surgical complications.

Discussion

This is the first randomized controlled trial designed to compare RATE with open transthoracic esophagectomy as surgical treatment for resectable esophageal cancer. If our hypothesis is proven correct, RATE will result in a lower percentage of postoperative complications, lower blood loss, and shorter hospital stay, but with at least similar oncologic outcomes and better postoperative quality of life compared with open transthoracic esophagectomy. The study started in January 2012. Follow-up will be 5 years. Short-term results will be analyzed and published after discharge of the last randomized patient.

Trial registration

Dutch trial register: NTR3291 ClinicalTrial.gov: NCT01544790

Background

It has been estimated that between 5% and 10% of women diagnosed with breast cancer have a hereditary form of the disease, primarily caused by a BRCA1 or BRCA2 gene mutation. Such women have an increased risk of developing a new primary breast and/or ovarian tumor, and may therefore opt for preventive surgery (e.g., bilateral mastectomy, oophorectomy). It is common practice to offer high-risk patients genetic counseling and DNA testing after their primary treatment, with genetic test results being available within 4-6 months. However, some non-commercial laboratories can currently generate test results within 3 to 6 weeks, and thus make it possible to provide rapid genetic counseling and testing (RGCT) prior to primary treatment. The aim of this study is to determine the effect of RGCT on treatment decisions and on psychosocial health.

Methods/Design

In this randomized controlled trial, 255 newly diagnosed breast cancer patients with at least a 10% risk of carrying a BRCA gene mutation are being recruited from 12 hospitals in the Netherlands. Participants are randomized in a 2:1 ratio to either a RGCT intervention group (the offer of RGCT directly following diagnosis with tests results available before surgical treatment) or to a usual care control group. The primary behavioral outcome is the uptake of direct bilateral mastectomy or delayed prophylactic contralateral mastectomy. Psychosocial outcomes include cancer risk perception, cancer-related worry and distress, health-related quality of life, decisional satisfaction and the perceived need for and use of additional decisional counseling and psychosocial support. Data are collected via medical chart audits and self-report questionnaires administered prior to randomization, and at 6 month and at 12 month follow-up.

Discussion

This trial will provide essential information on the impact of RGCT on the choice of primary surgical treatment among women with breast cancer with an increased risk of hereditary cancer. This study will also provide data on the psychosocial consequences of RGCT and of risk-reducing behavior.

Trial registration

The study is registered at the Netherlands Trial Register (NTR1493) and ClinicalTrials.gov (NCT00783822).

Background

With the increasing number of non palpable breast carcinomas, the need of a good and reliable localization method increases. Currently the wire guided localization (WGL) is the standard of care in most countries. Radio guided occult lesion localization (ROLL) is a new technique that may improve the oncological outcome, cost effectiveness, patient comfort and cosmetic outcome. However, the studies published hitherto are of poor quality providing less than convincing evidence to change the current standard of care.

The aim of this study is to compare the ROLL technique with the standard of care (WGL) regarding the percentage of tumour free margins, cost effectiveness, patient comfort and cosmetic outcome.

Methods/design

The ROLL trial is a multi center randomized clinical trial. Over a period of 2–3 years 316 patients will be randomized between the ROLL and the WGL technique. With this number, the expected 15% difference in tumour free margins can be detected with a power of 80%. Other endpoints include cosmetic outcome, cost effectiveness, patient (dis)comfort, degree of difficulty of the procedures and the success rate of the sentinel node procedure.

The rationale, study design and planned analyses are described.

Trial Registration

(, study protocol number NCT00539474)