Complications, secondary interventions and long term morbidity after en bloc sacrectomy.

PURPOSE: En bloc sacrectomy is a demanding surgical procedure to remove tumors from the sacrum. Comprehensive data on readmissions for complications endured months to years after initial discharge are scant. The purpose of this study is to present the long-term complications, readmissions and secondary interventions for patients having undergone en bloc sacrectomy. METHODS: Patients were included if en bloc sacrectomy and follow-up were conducted in the authors institution. Correspondence from all specialties involved in the treatment of patients was retrieved. Predefined parameters were scored and assigned to five distinct phases: diagnostic phase; surgery; postoperative period to 1 year after surgery; second year after surgery until follow-up and last follow-up. RESULTS: Sixteen patients underwent anterior-posterior en bloc sacrectomy for a locally aggressive tumor (n=2); malignant tumor (n=13) or solitary metastasis (n=1). The type of resection was low (n=1); middle (n=3); high (n=4); total (n=3) and hemisacrectomy (n=5). The median surgical duration was 12.7 h and median blood lost was 12 l. A total of 73 major complications (average per patient 5; median 4; range 0-12) were recorded and 73 secondary interventions (average per patient 5; median 5; range 0-11) were performed in the first year postsurgery. From the second year until follow-up complications and secondary interventions markedly decreased. At final follow-up (65-266 months), considerable morbidity was found for the eleven patients still alive. CONCLUSIONS: En bloc sacrectomy is a procedure with a high rate of major complications, regardless of tumor histology, often necessitating readmissions and secondary interventions. Long-term survival is associated with considerable morbidity and extensive preoperative counseling should be conducted to discuss the risks and outcome of the procedure.

Current pathology work-up of extremity soft tissue sarcomas, evaluation of the validity of different techniques.

OBJECTIVE: In patients with extremity soft tissue sarcomas (STSs) a correct histopathological diagnosis is considered important before surgical treatment. We evaluated the preoperative use and sensitivity of the various pathology techniques. METHODS: In a population-based study in patients operated for a newly diagnosed extremity STS between January 2000 and December 2003 the preoperative pathology work-up was evaluated. Data were retrieved from a national pathology database (PALGA). The sensitivity of the three techniques was assessed considering an examination affirmative when the conclusion of the pathology report stated the presence of mesenchymal malignancy. RESULTS: The pathology reports of 573 patients were identified in the database. In 177 patients (31%) no pathology examination was done before resection of the tumour. In the remaining 396 patients the pathology procedure of first choice had been an incisional biopsy (IB) in 195 patients (49%), a core-needle biopsy (CNB) in 90 patients (23%) and a fine needle aspiration (FNA) in 111 patients (28%). An affirmative diagnosis was established in 95% of the patients following an IB, in 78% after a CNB and in 38% following FNA. After an initial CNB an additional IB was performed in 18 of the 90 patients improving the yield to 89%. After an initial FNA a subsequent histological biopsy was done in 53 of the 111 patients, increasing the sensitivity to 71%. CONCLUSIONS: In this population-based study in patients treated for extremity STS, the proportion of patients operated without preoperative pathology evaluation was high. In the remaining patients an incisional biopsy was still the most commonly performed technique with the highest yield.

Axillary recurrence rate after tumour negative and micrometastatic positive sentinel node procedures in breast cancer patients, a population based multicenter study.

BACKGROUND: The sentinel lymph node procedure is a widely accepted method for staging of patients with early breast cancer. This study evaluates the incidence of axillary relapse after negative sentinel node biopsy in the seven hospitals in the central part of the Netherlands. METHODS: This study concerns all patients with a T1-2 breast carcinoma who were staged with a sentinel lymph node biopsy in one of the hospitals in the region. Patients with a tumour-free sentinel node without additional axillary lymph node dissection and patients with a sentinel node containing micrometastases were prospectively included and data concerning tumour and primary treatment were recorded. After a median follow-up period of 46 months supplementary data were collected of all patients. RESULTS: Between January 2002 and December 2003, 541 patients underwent a sentinel node biopsy of which the sentinel node was negative for metastatic disease. During the follow-up period three patients were diagnosed with an axillary recurrence. The incidence of axillary relapse after tumour negative sentinel node biopsy in this study is 0.6% (3/541). In 23 patients a distant metastasis developed. An event occurred in 11% of the patients with a micrometastasis in the sentinel node. This was not significantly different from the patients with a tumour-free sentinel node. CONCLUSION: The results suggest that the sentinel lymph node procedure as performed in the region Middle Netherlands is a reliable and accurate instrument for staging of patients with early breast cancer. In our study we observed a non-significant different risk of distant disease in case of micrometastases compared to a tumour negative sentinel node.

The role of APC and beta-catenin in the aetiology of aggressive fibromatosis (desmoid tumors).

BACKGROUND: Aggressive fibromatosis (syn. desmoid tumor) is a sporadically occurring neoplastic proliferation of fibroblasts originating from musculoaponeurotic planes, forming invasively growing masses without the capability to metastasize. The choice of treatment remains surgical resection with or without radiotherapy, and is characterized by high recurrence rates. Better understanding of the aetiology of aggressive fibromatosis is needed to be able to develop new treatment strategies to cope with the high recurrence rates. METHODS: Relevant studies were identified through a search of the electronic databases PubMed/ Medline. The following search terms were used: 'aggressive fibromatosis', 'desmoid tumor', 'adenomatous polyposis coli', 'APC', 'beta-catenin', 'Wnt', 'Wingless' and 'Wnt/Wingless'. Studies were selected for review on the basis of abstract reading. A hand search was performed by checking reference lists in selected articles. RESULTS: The neoplastic nature of aggressive fibromatosis and the role of the adenomatous polyposis coli (APC) and beta-catenin signaling cascade in driving the onset and progression of this disease are discussed. CONCLUSION: Mutations in either the APC or beta-catenin genes are likely to be a major driving force in the formation of these desmoid tumors. More research is needed to develop new treatment strategies.

Long-term prognosis of primary retroperitoneal soft tissue sarcoma.

AIMS: To evaluate the result of treatment and long-term outcome of a population-based cohort of patients with retroperitoneal soft tissue sarcoma (RSTS). METHODS: Between 1 January 1989 and 1 January 1994, 143 patients diagnosed as having primary RSTS were selected from a national pathology database (PALGA) in the Netherlands. In this population-based group of patients, the result of surgery, overall survival (OS) and disease-free survival (DFS) were analysed as well as factors affecting OS and DFS. Median follow-up was 10.2 years. RESULTS: Operative treatment resulted in a complete tumour resection in 55% of the patients (n=78), low- and intermediate-grade tumours were more often completely resected than high-grade tumours (P=0.016). Five- and 10-year cumulative OS was 39% and 21%, respectively, while DFS was 22% and 17%, respectively. In a multivariate analysis low malignancy grade (P=0.017) and a complete tumour resection (P<0.001) were associated with better OS. CONCLUSIONS: Complete tumour resection and low malignancy grade were independent favourable prognosticators. However, these factors were related too, since surgical success was influenced by malignancy grade.

Introduction of sentinel node biopsy and stage migration of breast cancer.

AIM: The purpose of this study was to examine in a large population based group of breast cancer patients treated in a regular care setting whether the introduction of the Sentinel Node Biopsy (SNB) led to detection of a higher percentage of patients with positive regional lymph nodes. METHODS: The study includes 3665 early breast cancer patients, aged 30-85 years, diagnosed in the period 1997-2002 and registered at the Regional Cancer Registry of the Comprehensive Cancer Centre Middle Netherlands. During this period the SNB was introduced. The outcome of staging was compared for groups staged with or without SNB. A logistic regression model was used to adjust for age, calendar period and tumour size. RESULTS: Overall a quarter of all patients over the period 1997-2002 underwent a SNB as method of lymphatic staging. The use of SNB clearly increased over time: from 2% in 1998 to 65% in 2002. The percentage node positive patients also rose significantly; before introduction of the SNB 30% of all patients were diagnosed with positive lymph nodes, and after SNB introduction this percentage was 40%. The increase is largely explained by the increase of patients diagnosed with only micrometastases. Adjustment did not change the results. CONCLUSION: In conclusion, introduction of the SNB in early breast cancer led to significant upstaging of breast cancer patients treated in a regular care setting, due to the detection of more micrometastases. Since the relevance of micrometastases for long term survival is not yet known, this upstaging potentially led to over treatment of patients. On the other side, for some patients axillary lymph node dissection was prevented by the SNB procedure, preventing comorbidity.

[Partial liver resections: mortality, morbidity and risk factors for postoperative complications in 133 patients/137 operations; Utrecht University Medical Center 1991/2000]. / Partiële leverresecties: sterfte, morbiditeit en risicofactoren voor postoperatieve complicaties bij 133 patiënten/137 operaties; Universitair Medisch Centrum Utrecht, 1991/'00.

OBJECTIVE: Evaluation of the results of partial liver resections for both benign and malignant abnormalities and the identification of risk factors for the development of complications. DESIGN: Descriptive, retrospective. METHOD: All consecutive partial liver resections performed between January 1991 and October 2000 at the University Medical Centre Utrecht, the Netherlands, were reviewed for preoperative, peroperative and postoperative parameters. Risk factors were determined by means of a univariate analysis and a multiple logistic regression analysis. The 5-year survival rates were calculated using the Kaplan-Meier method. RESULTS: A total of 133 patients (71 men and 62 women; median age: 58 years (range: 17-79)) underwent 137 hepatic resections for benign (n = 29) and malignant (n = 108) liver abnormalities. In total, 74 procedures (54%) were considered to be major hepatic resections and blood transfusion was required in 97 patients (71%). A total of 43 complications was observed in 32 patients (32/137; 23%). Eight patients died as a result of postoperative complications (8/137; 5.8%). Independent risk factors associated with the development of major complications were a major resection (OR: 3.6) and more than 2 peroperative units of packed cells (OR: 5.0). The principal indication for liver resection were colorectal metastases (n = 69). The 5-year survival rate after liver resection for colorectal metastases was 38% (95% CI: range 21-54) with a 5-year disease-free survival rate of 25% (range 10-41). The postoperative mortality in this group was 2.9%. CONCLUSION: After partial liver resection for benign and malignant lesions the mortality was 5.8% and the morbidity 23%. The risk of postoperative morbidity was related to the number of peroperative units of packed cells and the extent of the resection.

Locoregional recurrence of retroperitoneal soft tissue sarcoma: second chance of cure for selected patients.

BACKGROUND: Locoregional recurrence of a retroperitoneal soft tissue sarcoma (RSTS) may offer a second chance of curative surgical treatment. In a population-based study the proportion of patients developing isolated locoregional recurrences (LR) was determined and the outcome of these patients was analysed. METHOD: In a retrospective nationwide study, data were collected on 142 patients treated between 1 January 1989 and 1 January 1994 for primary RSTS. In patients who had been treated radically for their primary sarcoma (77/142, 54%), the pattern of recurrence was evaluated. Factors predictive of survival for patients with LR were studied. RESULTS: After a median follow-up of 86 (range 60-101) months, 32 patients (42%) had developed LR, and distant metastasis (DM) had been diagnosed in 17 patients (22%). Median disease-free interval between the initial operation and the establishment of LR or DM was 22 and 19 months, respectively. Five-year cumulative survival of patients with established LR was 37% in comparison with 11% for patients with DM (P=0.062). Factors predictive of favourable outcome in patients with LR were the absence of multifocal recurrence (n=13 P=0.01), lipomatous histomorphology (n=20 P=0.02), and a complete resection of recurrent sarcoma (n=17 P=0.04). CONCLUSION: After a median follow-up of 7 years following radical treatment of a primary RSTS, 42% of the patients had developed isolated locoregional recurrences. A complete resection of recurrent disease, lipomatous histomorphology and the absence of multifocal growth influenced prognosis favourably.

Soft tissue carcinoma in the retroperitoneum: an often neglected diagnosis.

AIMS: Successful surgical treatment of patients with retroperitoneal soft tissue sarcoma (RSTS) is based on pre-operative planning that starts with a correct pre-operative diagnosis. In a population-based study, we determined which patients were initially treated for assumed other conditions. The effect of an erroneous diagnosis on the installed treatment was analysed. METHOD: With the help of the Dutch Network and National Database for Pathology (PALGA), data were collected on 143 patients in the Netherlands in whom a primary RSTS was found and confirmed histologically between 1 January 1989 and 1 January 1994. Satisfactory clinical information was obtained on 138 patients, 64 males and 74 females (54%). The median age was 60 (range 18-88) years. RESULTS: At the time of actual treatment 37% of the patients with RSTS were assumed to have another disorder (group 1 n=51), whereas 87 patients were diagnosed as having RSTS (group 2). In group 1, an acute presentation was more common (18 vs 2% P=0.002), and the tumour was less often palpable at physical examination (43 vs 69% P=0.004), while clinical work-up less frequently included CT-imaging (57 vs 89% P<0.001) and a biopsy (29 vs 77% P<0.001). Although tumours in group 1 were smaller (median diameter 13 vs 19 cm P<0.05), this was not reflected in a better operative result: less patients underwent complete tumour resection (51 vs 57%) and more patients underwent surgery for tumours that proved to be irresectable (14 vs 1% P=0.004). CONCLUSIONS: (1) More than one-third of patients with RSTS are misdiagnosed and inappropriately treated; and (2) biopsies and cross-sectional imaging improve diagnosis.

Soft tissue sarcoma: the predominant primary malignancy in the retroperitoneum.

Purpose. In the clinical work-up of a retroperitoneal mass, the diagnosis of soft tissue sarcoma is often not considered. Incidence rates of various malignant and benign retroperitoneal tumours were studied to determine the incidence of soft tissue sarcoma in comparison with other neoplasms in the retroperitoneal space.Method. Nation-wide data on retroperitoneal tumours, collected prospectively over a 5-year period (1 January 1989- 1 January 1994), were supplied by the Netherlands Cancer Registry and The Dutch Network and National Database for Pathology.Results. Seven hundred and six patients with a primary retroperitoneal neoplasm were identified; 566 patients had a malignant tumour (80%). A soft tissue sarcoma (STS) was the most frequently diagnosed malignant tumour (n = 192), The agestandardised incidence of retroperitoneal STS was 2.5 per million person-years. The male/female ratio for STS was 0.73. In females, STS comprised 41%of all malignant retroperitoneal tumours, carcinoma of unknown primary tumour site (CUP) comprised 31%, and malignant lymphomas (ML) comprised 22%, whereas in males these values were 28% (STS), 30% (CUP), and 32% (ML), respectively.Discussion. Soft tissue sarcomas, albeit rare, are relatively common primary tumours in the retroperitoneum, especially in women.

Sentinel node biopsies in melanoma patients: a protocol for accurate, efficient, and cost-effective analysis by preselection for immunohistochemistry on the basis of Tyr-PCR.

BACKGROUND: Immunohistochemistry (IHC) of serial sectioning is considered the gold standard for detection of melanoma activity in sentinel node (SN) biopsies. However, this is cost and labor intensive. In contrast, tyrosinase reverse transcription-polymerase chain reaction (RT-PCR) is simple and quick, but it is hampered by its extreme sensitivity. This study was performed to test whether a strategy that combines the two methods, using tyrosinase RT-PCR to preselect nodes for IHC, could be accurate and cost effective. METHODS: In 36 patients, SNs were identified by scintigraphy and patent blue uptake. Of each SN, one cross section was analyzed first by hematoxylin and eosin staining. Next, all nodes were examined by serial sectioning and IHC of one-half and tyrosinase RT-PCR of the other. Before comparison, all results were documented in a blinded manner. Material costs and workload estimates were noted per SN. RESULTS: Fifty-five SNs were retrieved from the 36 patients. Hematoxylin and eosin staining of the first cross section revealed tumor positivity in 3 patients (6 SN). Tyrosinase RT-PCR was positive in 11 of the remaining 33 patients (19 of 49 SN). Of these same 11 patients, only 5 were shown to have tumor-positive SNs by using IHC on serial sections (7 SN). All these nodes had been positive for tyrosinase on PCR. For IHC, an average of 40 sections were prepared and examined per SN at a cost of $200(U.S.)/SN. In contrast, routine tyrosinase RT-PCR costs $37(U.S.)/SN, and takes 5% of the time necessary for IHC. A strategy including hematoxylin and eosin staining on the first cross section, followed by tyrosinase RT-PCR on half of each negative (half) node, could preselect nodes to be taken through serial sectioning. In these series, such a strategy would have prevented serial sectioning and IHC of 30 SN from 22 patients. Apart from a considerable gain in efficiency, this would have reduced material costs by a minimum of $6000 (U.S.). This discrepancy would be even higher if work intensity of analysts and pathologists were considered. CONCLUSIONS: In routine analysis of SN biopsies in melanoma patients, tyrosinase RT-PCR can be used effectively to preselect nodes for further IHC of serial sections. This method seems both time and cost effective.

Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group.

OBJECTIVE: The survival benefit of adjuvant radiotherapy and 5-fluorouracil versus observation alone after surgery was investigated in patients with pancreatic head and periampullary cancers. SUMMARY BACKGROUND DATA: A previous study of adjuvant radiotherapy and chemotherapy in these cancers by the Gastrointestinal Tract Cancer Cooperative Group of EORTC has been followed by other studies with conflicting results. METHODS: Eligible patients with T1-2N0-1aM0 pancreatic head or T1-3N0-1aM0 periampullary cancer and histologically proven adenocarcinoma were randomized after resection. RESULTS: Between 1987 and 1995, 218 patients were randomized (108 patients in the observation group, 110 patients in the treatment group). Eleven patients were ineligible (five in the observation group and six in the treatment group). Baseline characteristics were comparable between the two groups. One hundred fourteen patients (55%) had pancreatic cancer (54 in the observation group and 60 in the treatment group). In the treatment arm, 21 patients (20%) received no treatment because of postoperative complications or patient refusal. In the treatment group, only minor toxicity was observed. The median duration of survival was 19.0 months for the observation group and 24.5 months in the treatment group (log-rank, p = 0.208). The 2-year survival estimates were 41% and 51 %, respectively. The results when stratifying for tumor location showed a 2-year survival rate of 26% in the observation group and 34% in the treatment group (log-rank, p = 0.099) in pancreatic head cancer; in periampullary cancer, the 2-year survival rate was 63% in the observation group and 67% in the treatment group (log-rank, p = 0.737). No reduction of locoregional recurrence rates was apparent in the groups. CONCLUSIONS: Adjuvant radiotherapy in combination with 5-fluorouracil is safe and well tolerated. However, the benefit in this study was small; routine use of adjuvant chemoradiotherapy is not warranted as standard treatment in cancer of the head of the pancreas or periampullary region.

Fulminant acute pancreatitis and infected necrosis: results of open management of the abdomen and "planned" reoperations.

BACKGROUND: Controversy still surrounds the management of fulminant acute necrotizing pancreatitis. Because mortality rates continue to be high, especially in patients with fulminant acute pancreatitis and infected necrosis, aggressive surgical techniques, such as open management of the abdomen and "planned" reoperations, seem to be justified. STUDY DESIGN: From 1988 through 1995, 28 patients with fulminant acute pancreatitis and infected necrosis were treated with open management of the abdomen followed by planned reoperations at our surgical intensive care unit. RESULTS: All patients had infected necrosis with severe clinical deterioration: 12 patients had an Acute Physiology and Chronic Health Evaluation (APACHE) II score > or = 20 and 16 patients had a Simplified Acute Physiology Score (SAPS) > or = 15. Nineteen patients suffered from severe multiorgan failure; the remaining 9 patients needed only ventilatory and inotropic support. The mean number of reoperations was 17. In 14 patients, major bleeding occurred; fistula developed in 7. Later, 9 abscesses were drained percutaneously. The hospital mortality rate was 39%. Longterm morbidity in survivors was substantial, especially concerning abdominal-wall defects. CONCLUSIONS: Open management of the abdomen followed by planned reoperations is an aggressive but reasonably successful surgical treatment strategy for patients with fulminant acute pancreatitis and infected necrosis. Morbidity and mortality rates were high, but in these critically ill patients, such high rates could be expected. Because management and clinical surveillance require specific expertise, management of these patients is best undertaken in specialized centers.

[Towards safer and parenchyma-conserving liver resections: experience with three-dimensional reconstructions of spiral CT scan]. / Naar veiliger en parenchymsparende leverresecties; ervaringen met driedimensionale reconstructies van de spiraal-CT-scan.

New techniques are available for the diagnosis and treatment of liver metastases. Three patients, a male aged 52 and two females aged 70 and 47, developed liver metastases after resection of a colorectal carcinoma. Spiral CT scanning made possible detailed three dimensional imaging of the liver to determine the extension of the metastases and the site of the metastasis in relation to blood vessels and bile ducts. This enabled the surgeon preoperatively to arrive at a balanced operation strategy, with the objectives of radical resection of the metastasis and conservation of sufficient residual liver tissue with minimal morbidity and mortality. In addition, use was made of peroperative clamping of blood vessels to determine the possibility of resecting along anatomical borders. This offers the advantages that less blood is lost and a smaller resection often suffices. In the 3 patients followed respectively a wedge excision of the tumour, a wedge excision combined with a hemihepatectomy and a resection of two segments.

c-Src protein expression is increased in human breast cancer. An immunohistochemical and biochemical analysis.

In human breast cancer, c-Src activity is elevated compared to normal breast tissue. It is not yet known whether this increase in c-Src activity is accompanied by an increase in c-Src protein expression. In this study, c-Src activity and protein expression were determined in a series of human breast cancers and in normal breast tissue, using immune complex kinase assays and immunoblotting. As the heterogeneity of breast cancer is not taken into account in these biochemical experiments, immunohistochemistry was also used to distinguish between normal and malignant cells. In human breast cancers, the c-Src activity is increased 4- to 30-fold, compared with normal breast tissue. This enhanced activity is accompanied by an increase in c-Src protein expression, as shown by both immunoblotting and immunohistochemistry. Immunohistochemistry indicates that the majority of c-Src appears to be concentrated around the nucleus in malignant cells, whereas in normal cells, it is distributed more evenly in the cytoplasm. These data confirm that c-Src activity is increased in human breast cancer. In addition, this study provides strong immunohistochemical evidence that the c-Src protein is also overexpressed, enabling a distinction to be made between normal and malignant cells.

Focal liver lesions: characterization with triphasic spiral CT.

PURPOSE: To assess whether triphasic spiral CT enables characterization of a wide range of focal liver lesions. MATERIALS AND METHODS: One hundred five patients with suspected focal liver disease underwent triphasic liver CT. After injection of contrast material, the liver was scanned in arterial (scanning delay, 22-27 seconds), portal (scanning delay, 49-73 seconds), and equilibrium (scanning delay, 8-10 minutes) phases. Enhancement of each lesion in each phase was evaluated, and the lesions were tabulated according to one of 11 enhancement patterns. RESULTS: In 94 patients, 375 liver lesions were detected. The nature of the lesion was confirmed in 326 lesions (87%). Six of 11 enhancement patterns were always due to benign disease and caused by areas with hyper- or hypoperfusion, hemangiomas, cysts, focal nodular hyperplasias, or benign but nonspecified lesions. Two of 11 patterns were always due to malignant disease, and one pattern was due to malignant disease in 38 (97%) of 39 patients with known malignancy elsewhere or with chronic liver disease. The other two patterns were seen in metastases and partly fibrosed hemangiomas. CONCLUSION: Triphasic liver CT enables characterization of a wide range of focal liver lesions, including the benign liver lesions that occur most frequently.

[Digital roentgen-guided large-needle biopsy as an alternative to surgical biopsy in patients with nonpalpable mammographic abnormalities]. / Digitale röntgengestuurde dikkenaaldbiopsie als alternatief voor chirurgische biopsie bij patiënten met niet-palpabele mammografische afwijkingen.

OBJECTIVE: To compare histopathological findings from stereotaxic needle core biopsies and from excision biopsies performed on patients with impalpable breast lesions suggestive of carcinoma. DESIGN: Prospective and descriptive, with a description of the stereotaxic needle core biopsy procedure. SETTING: Academic Hospital Utrecht, the Netherlands. METHODS: In 36 patients core biopsies were done with 14-gauge biopsy needles, followed by a localisation procedure with surgical biopsy. The pathological features of the core and excision specimens were compared. RESULTS: Results of 35 (97%) core biopsies corresponded to those of excision biopsies. Stereotaxic core biopsy was not possible due to technical problems in 2 cases. CONCLUSION: Stereotaxic core biopsy appears to be an acceptable alternative to excision biopsy.

Mammary Paget's disease confined to the areola and associated with multifocal Toker cell hyperplasia.

A hitherto unreported variant of mammary Paget's disease (MPD) limited to the areola, leaving the nipple unaffected, has been analyzed by serial sectioning of the whole areola and nipple. This otherwise characteristic MPD proved to be confined to the epidermis. There was no underlying carcinoma. This MPD was associated with a multifocal presence of monomorphic but otherwise similar cells in small collections surrounding the ostia of areolar mammary glands in the clinically unaffected area. This condition was interpreted as hyperplasia of mammary gland-related cells also found in normal nipples (so-called Toker cells). The observations hint at a possible derivation of some cases of mammary and extramammary Paget's disease from such Toker cells.

Planning of liver surgery using three dimensional imaging techniques.

In the simplified Couinaud classification, in which the liver is divided into eight segments, each supplied by a central vasculo-biliary sheath, little attention is given to the high prevalence of anatomical variations which occur, especially in the right hemiliver. Using volumetric acquisition techniques, such as magnetic resonance imaging or spiral computed tomography scanning, detailed insight into the individual segmental anatomy can now be obtained in a non-invasive manner. The significance of this anatomical insight lies in the planning of anatomical resections, whereby the relationship between tumour and individual segmental anatomy can be depicted in a three-dimensional format. As such, three dimensional (3D) liver imaging helps to design an individualised resection, tailored to the topographical relationship between individual segmental anatomy and tumour tissue present. Three dimensional liver imaging is of most practical value if a resection of one or more segments or sectors is considered, especially in the right hemiliver. In these cases, 3D liver imaging can demonstrate the precise location of the scissuras to the surgeon pre-operatively.