[A decade of sentinel lymph node biopsy for breast cancer: time for adaptations]. / Een decennium schildwachtklierbiopsie voor borstkanker; tijd voor aanpassingen.

A decade of sentinel lymph node biopsy for breast cancer has taught us that old assumptions on contraindications (prior surgery, clinical positive axilla, multicentricity/multifocality, and neoadjuvant chemotherapy) should be discarded. Many clinical evaluation studies have shown that a new sentinel lymph node procedure after previous surgery of the breast and the axilla is feasible. It allows specialists to determine more precisely the biological activity of local recurrences and to re-conserve the axilla. In order to save as many axillas as possible, clinically suspect axillary lymph nodes should only be considered tumour positive if this is proven by biopsy. Also, in cases of multicentricity or multifocality a sentinel lymph node procedure should be performed. With the objective of conserving the axilla in as many patients as possible, a sentinel lymph node biopsy should be performed after neoadjuvant chemotherapy.

[Secondary breast operations are often necessary and are no indication of poor oncological quality]. / Een tweede borstoperatie: vaak een noodzakelijke ingreep en geen teken van onvoldoende oncologische zorg.

The most important factor for tumour recurrence after breast-saving surgery is the margin status. In the Netherlands a 1-mm free margin has been formulated as sufficient, and totally free margins are not necessary in all cases. The current Dutch Health Inspectorate performance indicator, i.e. 10% reexcisions allowed to achieve free margins, is a performance indicator of questionable validity. As long as there is worldwide discussion about the ideal margin in breast-saving surgery a specific norm cannot not be dictated. The aim of the discussion should be how to prevent local recurrence. This percentage is the real performance indicator.

Variations in treatment of ductal carcinoma in situ of the breast: a population-based study in the East Netherlands.

AIMS: Differences in treatment of ductal carcinoma in situ (DCIS) of the breast were analysed for a geographically defined population in the East Netherlands. METHODS: Data from the Cancer Registry of the Comprehensive Cancer Centre East Netherlands were analysed for treatment of DCIS in the period between January 1989 and December 2003. The study population consisted of 800 female patients with a first diagnosis of DCIS of whom 798 underwent surgical treatment. The distribution of tumour characteristics and treatment were compared for several time periods. RESULTS: Surgical treatment was specified for 648 patients: 51% underwent breast-conserving surgery. The proportion of patients treated with breast-conserving surgery increased: 43% in the period 1994-1998 and 55 after 1999 (p<0.01). An axillary staging procedure was performed in 149 patients (19%), of whom 2 (1%) had tumour-involved lymph nodes. Of patients treated with breast-conserving surgery, 133 (40%) received radiation therapy: 7% in the period 1994-1998 compared to 62% after 1999 (p<0.01). Patients (60%) of 50 years or younger were treated with mastectomy compared to 44% in patients aged 50-69 years and 50% in patients of 70 years and older (p<0.01). The rate in use of radiation therapy after breast-conserving surgery was comparable to both age groups. CONCLUSION: This study shows variability in the treatment of DCIS in a geographically defined region. Approximately half of all patients were treated with mastectomy and 19% underwent an axillary staging procedure; this may represent aggressive, unwarranted treatment. In contrast, 38% of patients treated with breast-conserving surgery were not treated with radiation therapy after 1999, which may represent under-treatment.

[Diagnostic image (318). A man with a non-healing preauricular wound]. / Diagnose in beeld (318). Een man met een niet-genezend wondje vóór het oor.

A 23-year-old man presented with a left-sided non-healing small preauricular wound, which existed for several months after an operation for an infected suspected 'epidermal cyst'. At operation a preauricular sinus with fistula was excised.

Circulating gelatinases and tissue inhibitor of metalloproteinase-1 in colorectal cancer metastatic liver disease.

AIMS: The degradation of the extracellular matrix is intrinsic to the invasion and progression of cancer. Matrix metalloproteinase (MMP)-2 and -9 and their natural inhibitors are involved in this process. The study aims to investigate if plasma MMP-2, -9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) can be useful markers in the diagnosis and prognosis of colorectal cancer (CRC) metastatic liver disease. METHODS: Fifty-seven patients undergoing liver metastasis operation were followed prospectively. ProMMP-2, -9 and TIMP-1 plasma levels were determined by zymography and ELISA, before and after the resection of liver metastases. Data were compared with those of healthy controls (n=51) and primary CRC patients (n=94). The diagnostic and prognostic potential was investigated with ROC-curves and Kaplan-Meier survival analysis. RESULTS: Plasma proMMP-2 levels were lower (P<0.001), and TIMP-1 levels higher (P<0.001) in CRC metastatic liver disease than in healthy controls. If compared to those in primary CRC patients, no differences were found. In ROC-curves, the area under the curve was 0.48 and 0.61 for proMMP-2 and -9, respectively. Plasma proMMP-2, -9 and TIMP-1 levels were unsuitable to predict survival. In both diagnostic and prognostic examinations, CEA proved to be a better marker. In the postoperative follow-up, protracted low levels of proMMP-2 seemed related to disease recurrence. CONCLUSION: The preoperative plasma proMMP-2, -9 and TIMP-1 levels have no potential value as diagnostic or prognostic markers in CRC liver metastatic disease.

[MRI-guided biopsy of the breast: new possibilities but also new problems]. / MRI-geleide biopsie van de borst: nieuwe mogelijkheden, maar ook nieuwe problemen.

The use of MRI in the detection and management of breast cancer is increasing. Because of its relatively low specificity, many patients turn out in retrospect to have a false-positive biopsy. Conversely, due to the shortcomings of available biopsy techniques, breast cancer can also be missed and left behind in the breast. The introduction of MRI of the breast in daily practice may therefore have a great psychological impact on the group of mostly young patients who are offered this diagnostic modality because of their familial risk. In order to prevent learning curves in every clinic where MRI screening is implemented, the management of this special group should be concentrated in centres with broad experience in the treatment of patients with a genetic predisposition for breast cancer.

[MRI breast-cancer screening: particularly important in women at increased risk]. / Borstkankerscreening met MRI: vooral voor vrouwen met verhoogd risico.

In some women, the density of breast tissue is a limiting factor in the detection of early-stage breast cancer by palpation and mammography. This is the case in young women, for example. MRI sensitivity is not influenced by tissue density. For this reason, it would appear that young women with a genetic or familial predisposition to breast cancer would benefit from MRI screening. A series of prospective studies has shown that the sensitivity of MRI is almost twice that of mammography in these women. As a result, the disease stage in those patients screened by MRI is lower than in the patients screened by a different method. In well-defined groups MRI of the breasts may be an important additional screening tool in women at increased risk of breast cancer.

Efficacy of fluorine-18-deoxyglucose positron emission tomography in detecting tumor recurrence after local ablative therapy for liver metastases: a prospective study.

PURPOSE: The aims of this prospective study were to investigate the potential role of fluorine-18-deoxyglucose (FDG) positron emission tomography (PET) in determining the efficacy of the local tumor ablative process and to determine the added value of FDG-PET in the detection of tumor recurrence during follow-up. PATIENTS AND METHODS: Twenty-three patients with unresectable colorectal liver metastases were followed up after local ablative therapy consisting of a standard protocol including FDG-PET scanning, computed tomography (CT) scanning, and carcinoembryonic antigen measurements. The mean follow-up period was 16 months (range, 10 to 21 months). RESULTS: Ninety-six lesions was treated, 56 by local ablative treatment. Within 3 weeks after local ablative treatment, 51 lesions became photopenic on FDG-PET, while five lesions (in five patients) showed persistent activity on FDG-PET. In four of five FDG-PET-positive lesions, a local recurrence developed during follow-up; one FDG-PET-positive lesion turned out to be an abscess. None of the FDG-PET-negative lesions developed a local recurrence during a mean follow-up period of 16 months. During follow-up, 11 patients showed recurrence in the liver outside of the treated area. In all cases, previously negative FDG-PET scans became positive. Extrahepatic recurrence was encountered in nine patients during follow-up; FDG-PET showed all nine cases of tumor recurrence. There was one false-positive FDG-PET caused by an intra-abdominal abscess. In all patients, the time point of detection of recurrence by FDG-PET was considerably earlier than the detection by CT. CONCLUSION: FDG-PET seems to have a significant impact in measuring treatment efficacy directly after local ablative therapy. Furthermore, FDG-PET has an added value in patient follow-up because it reveals recurrences earlier than conventional diagnostic modalities.

Value of positron emission tomography with [F-18]fluorodeoxyglucose in patients with colorectal liver metastases: a prospective study.

PURPOSE: To assess prospectively the value of fluor-18-deoxyglucose (FDG) positron emission tomography (PET), in addition to conventional diagnostic methods (CDM), as a staging modality in candidates for resection of colorectal liver metastases. PATIENTS AND METHODS: In 51 patients analyzed for resection of colorectal liver metastases, clinical management decisions were recorded after a complete work-up with CDM. Afterward, FDG-PET scans were performed and any change of clinical management according to FDG-PET results was carefully documented. Discordances between FDG-PET and CDM results were identified and related to the final diagnosis by histopathology, intraoperative findings, and follow-up. RESULTS: In 10 (20%) out of 51 patients, clinical management decisions based on CDM were changed after FDG-PET findings were known. FDG-PET detected unresectable pulmonary (n = 5) and hepatic metastases (n = 1) and ruled out extrahepatic (n = 2) and hepatic disease (n = 2). Due to FDG-PET, eight patients were spared unwarranted liver resection or laparotomy and two other patients were identified as candidates for liver resection. When the results of FDG-PET were regarded as decisive in a retrospective analysis, potential change of management was 29% (15 patients). FDG-PET and CDM showed discordant extrahepatic results in 11 patients (22%) and discordant hepatic results in eight patients (16%). Compared with CDM, FDG-PET resulted in true upstaging (n = 11), true downstaging (n = 5), false upstaging (n = 1), and false downstaging (n = 2). The detection rate of liver metastases on a lesion basis was generally better for computed tomography than for FDG-PET (80% v 65%); this was related to tumor size. CONCLUSION: FDG-PET as a complementary staging method improves the therapeutic management of patients with colorectal liver metastases, especially by detecting unsuspected extrahepatic disease.

Cryosurgery and radiofrequency ablation for unresectable colorectal liver metastases.

AIMS: To report immediate local treatment efficacy and long-term results of cryosurgical ablation (CSA) and radiofrequency ablation (RFA) in patients with colorectal liver metastases not eligible for resection. METHODS: Fifty-eight patients with unresectable colorectal liver metastases were included. Under ultrasound guidance, CSA or RFA were performed with or without concomitant resection. CT scanning and FDG-PET were used to determine local efficacy of the ablative procedure. RESULTS: Median follow-up was 26 and 25 months for CSA and RFA, respectively. One and 2-year survival rates were 76 and 61% for CSA and 93 and 75% for RFA, respectively. In a lesion based analysis, the local recurrence rate was 9% after CSA and 6% after RFA. Complication rates were 30 and 11% after CSA and RFA, respectively, (p=0.052). In a subgroup analysis on 43 patients with 104 ablated lesions, CT scan immediate after treatment was not able to predict local treatment failure, whereas FDG-PET scan within 3 weeks after local ablative treatment predicted six of the seven local recurrences. CONCLUSIONS: In patients with unresectable colorectal liver metastases, CSA and RFA can be used either alone or as an effective adjunct to resection in achieving complete tumour clearance of the liver. More widespread use of these techniques seems promising but requires further investigation in randomized trials comparing local ablative treatment with chemotherapy.

[MRI for breast disease diagnosis; an asset, but the proper place has to be determined first]. / MRI in de mammadiagnostiek: een aanwinst, maar plaats nog niet zeker.

MRI of the breast is a technique of increasing clinical importance. As a screening modality it is superior to mammography in young females with a familial or genetic predisposition. Still, the ultimate effect, particularly the benefit for the individual patient, requires further study. Because of the relatively low specificity, the number of false positive findings is high, while the need for histological confirmation may cause unnecessary delays in treatment. Both lead to high costs for the patient as well as for the community. For the time being, MRI of the breast should not be introduced as a routine examination in patients with a suspicion of breast cancer and should be confined to centres with special experience in the management of MRI-detected lesions.

[Diagnostic image (243). A woman with an epigastric mass and vomiting]. / Diagnose in beeld (243). Een vrouw met een zwelling in de bovenbuik en klachten van braken.

An 87-year-old woman presented with epigastric pain and vomiting. Abdominal examination revealed an epigastric mass of 10 by 15 cm. Computed tomography of the abdomen demonstrated protrusion of peritoneal contents through a large defect in the linea alba.

Breast cancer screening: using familiality for earlier detection.

It is the purpose of this study to investigate whether breast cancer in patients with a positive family history is detected at an earlier stage with better prognostic markers than breast cancer in patients without a positive family history. In 481 patients, tumour size, tumour type, lymph vessel invasion, blood vessel invasion, receptor state, lymphatic spread, mitotic activity index (MAI) and survival were measured and compared, according to their family history. No difference was found between patients without a family history, patients with first-degree relatives or patients with second-degree relatives with breast cancer. Tumours were detected in the same stages and prognostic factors, MAI and survival were similar in all groups. A positive family history of breast cancer does not lead to earlier detection of breast cancer or a better survival.

The oncological implications of immediate breast reconstruction.

AIMS: The timing of breast reconstruction following mastectomy has been an area of contention. The purpose of this study was to report the oncologic safety of mastectomy and immediate breast reconstruction, primarily with a tissue expander. METHODS: We offered 54 patients (58 reconstructions) an immediate breast reconstruction after a modified radical mastectomy was done for invasive breast cancer. RESULTS: Fifty-eight mastectomies were done for an invasive cancer. Thirteen out of 54 women suffered relapse of their cancer and nine patients died of their disease during the follow-up period. Only in one patient a local recurrence was detected at an early stage and treated without removal of the prosthesis. Disease free survival for all patients was 93% at 5 years. CONCLUSION: Immediate breast reconstruction after mastectomy is an oncologically safe approach and represents a clear improvement in the quality of life for patients with breast cancer. Thus this procedure can safely be offered to appropriately selected women.

The management of clear cell sarcoma.

Clear cell sarcoma is a rare soft tissue tumour, constituting approximately 1% of all soft tissue sarcomas. Prognosis is reported to be poor due to the great propensity to metastasise regionally and distantly. In this paper, we report the surgical experience of two university hospitals. Both disease-free and overall survival after resection of clear cell sarcoma in this limited study were excellent, which may be explained by relatively small tumour size in seven out of eight patients and adjuvant radiation treatment. The current treatment for clear cell sarcoma is wide local tumour excision, with adjuvant radiation therapy for resection margins of less than 1 mm.

New diagnostic techniques in staging in the surgical treatment of cutaneous malignant melanoma.

The emphasis of the research on the surgical treatment of melanoma has been on the resection margins, the role of elective lymph node dissection in high risk patients and the value of adjuvant regional treatment with hyperthermic isolated lymph perfusion with melphalan. Parallel to this research, new diagnostic techniques, such as Positron Emission Tomography and the introduction of the sentinel lymph node biopsy with advanced laboratory methods such as immuno-histochemical markers, and reverse transcriptase polymerase chain reaction, have been developed to facilitate early detection of metastatic melanoma. The role of these new techniques on the staging and surgical treatment of melanoma is discussed in this paper.

Small but significant survival benefit in patients who undergo routine follow-up after colorectal cancer surgery.

BACKGROUND: The benefit of follow-up for patients after resection of primary colorectal cancer is unproven. The aim of this study was to evaluate the value of a standardised follow-up program considering detection of recurrent disease, eligibility for surgical treatment and survival. METHODS: Five hundred and sixty-four patients' records were evaluated. Detection of recurrent disease was distinguished in routine follow up (RF), interval visit (IV) or accidental finding (AF). RESULTS: One hundred and forty-nine patients (26%) had recurrent disease of which 68 were detected by routine follow-up. In 42 patients a resection was performed with curative intent (RF 18, IV 14, AF 10). In 26 patients radical resection (R(0)) was possible (RF 13, IV 5, AF 8), seven of them were long-term survivors. Routine follow-up itself had no significant influence on overall survival (P=0.08), although increased survival was observed if recurrent disease was detected by routine follow-up and resection was performed with curative intent (P=0.006). Median survival after resection was 4.2 years if recurrent disease was detected during routine follow-up and 0.5 years if detected during interval visits. CONCLUSIONS: Patients undergoing resection with curative intent for recurrent disease survive significantly longer if the disease is detected by routine follow-up. Routine follow-up itself did not improve overall survival.

Relevance of disseminated tumour cells in blood and bone marrow of patients with solid epithelial tumours in perspective.

Currently-used systems to predict prognosis in patients with solid epithelial tumours after surgical resection of the tumour do not give any guarantees for the individual patient. In this respect the clinical relevance of the presence of disseminated tumour cells in blood and bone marrow has been frequently studied. Because of growing awareness that information on merely the presence of disseminated tumour cells is not sufficient for prognostic and therapeutic purposes, attention for characterization of disseminated tumour cells has increased. Numerous reviews have already been published on the detection and clinical relevance of disseminated tumour cells. Therefore, this paper will mainly focus on the biological significance of these cells and discusses the (in)efficiency of the metastatic process, the genotypic and phenotypic characteristics of disseminated tumour cells, and their structure of appearance. Despite the fact that information gained on the several individual aspects is substantial, it did not render any solid solutions for individual patient management yet. Hence, a combined approach of several aspects of disseminated tumour cells together with characteristics and behaviour of the primary tumour is needed to substantially improve our knowledge on the role of disseminated tumour cells in the complex process of tumour metastasis.

Fluorodeoxyglucose-positron emission tomography and sentinel lymph node biopsy in staging primary cutaneous melanoma.

AIM: We report the value of sentinel lymph node (SLN) biopsy and fluorodeoxyglucose-positron emission tomography (FDG-PET) in relation to SLN biopsy in staging primary cutaneous melanoma. METHODS: Fifty-five patients with primary cutaneous melanoma >1.0 mm. Breslow thickness and no palpable regional lymph nodes underwent a FDG-PET scan before SLN biopsy. RESULTS: SLN's were retrieved in 53 patients. Melanoma metastases were found in the SLN of 13 patients. FDG-PET detected the lymph node metastases in two of the 13 patients with SLN metastases. In five patients FDG accumulation was recorded in a regional lymph node basin, while no tumour positive SLN was found. In eight patients FDG-PET showed increased activity at a site of possible distant metastasis. Metastatic disease was confirmed in one patient. No explanation for the positive FDG-PET result could be found in five cases. CONCLUSION: FDG-PET should not be considered in this group. SLN biopsy reveals regional metastases that are too small to be detected by FDG-PET. The prevalence of distant metastases is too small to justify routine use of FDG-PET.

Residual disease after excision of non-palpable breast tumours: analysis of tumour characteristics.

INTRODUCTION: A tumour-positive resection margin is a well-known prognostic factor for local recurrence. The aim of this study was to evaluate tumour characteristics that might be predictive for the presence of residual disease after excisional surgery. PATIENTS AND METHODS: Data of 295 patients, subjected to a wire-guided excisional breast biopsy were studied. Type and size of the primary tumour, the presence of DCIS and an extensive in situ component (EIC), multifocality of the tumour and nodal status were recorded. RESULTS: Residual disease was found in 51% of the patients undergoing a re-operation. 80% of the patients with positive margins were treated by mastectomy. Nodal status and the presence of an extensive in situ component were the only two variables that were statistically significant. CONCLUSION: In case of tumour positive margins axillary involvement and an extensive in situ component in the primary tumour were predictive for residual disease. No subgroups could be defined in whom additional surgery could be omitted. More 'aggressive' surgical therapy is justified in patients belonging to these risk groups.