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First, this study aimed to assess the prognostic value of different definitions for resection margin status on disease-free survival (DFS) and overall survival (OS) in pancreatic ductal adenocarcinoma (PDAC). Second, preoperative predictors of direct margin involvement were identified. This nationwide observational cohort study included all patients who underwent upfront PDAC resection (2014–2016), as registered in the prospective Dutch Pancreatic Cancer Audit. Patients were subdivided into three groups: R0 (≥1 mm margin clearance), R1 (<1 mm margin clearance) or R1 (direct margin involvement). Survival was compared using multivariable Cox regression analysis. Logistic regression with baseline variables was performed to identify preoperative predictors of R1 (direct). 595 patients with a median OS of 18 months (IQR 10-32 months) months were analysed. R0 (≥1 mm) was achieved in 277 patients (47%), R1 (<1 mm) in 146 patients (24%) and R1 (direct) in 172 patients (29%). R1 (direct) was associated with a worse OS, as compared with both R0 (≥1 mm) (hazard ratio (HR) 1.35 [95% and confidence interval (CI) 1.08–1.70); P < 0.01) and R1 (<1 mm) (HR 1.29 [95%CI 1.01–1.67]; P < 0.05). No OS difference was found between R0 (≥1 mm) and R1 (<1 mm) (HR 1.05 [95% CI 0.82–1.34]; P = 0.71). Preoperative predictors associated with an increased risk of R1 (direct) included age, male sex, performance score 2–4, and venous or arterial tumour involvement. Resection margin clearance of <1 mm, but without direct margin involvement, does not affect survival, as compared with a margin clearance of ≥1 mm. Given that any vascular tumour involvement on preoperative imaging was associated with an increased risk of R1 (direct) resection with upfront surgery, neoadjuvant therapy might be considered in these patients. [ABSTRACT FROM AUTHOR]

Introduction Occult nodal tumour cells should be categorised as micrometastasis (MMs) and isolated tumour cells (ITCs). A recent meta-analysis demonstrated that MMs, but not ITCs, are prognostic for disease recurrence in patients with stage I/II colon cancer. Aims & methods The objective of this retrospective multicenter study was to correlate MMs and ITCs to characteristics of the primary tumour, and to determine their prognostic value in patients with stage I/II colon cancer. Results One hundred ninety two patients were included in the study with a median follow up of 46 month (IQR 33–81 months). MMs were found in eight patients (4.2%), ITCs in 37 (19.3%) and occult tumour cells were absent in 147 patients (76.6%). Between these groups, tumour differentiation and venous or lymphatic invasion was equally distributed. Advanced stage (pT3/pT4) was found in 66.0% of patients without occult tumour cells (97/147), 72.9% of patients with ITCs (27/37), and 100% in patients with MMs (8/8), although this was a non-significant trend. Patients with MMs showed a significantly reduced 3 year-disease free survival compared to patients with ITCs or patients without occult tumour cells (75.0% versus 88.0% and 94.8%, respectively, p = 0.005). When adjusted for T-stage, MMs independently predicted recurrence of cancer (OR 7.6 95% CI 1.5–37.4, p = 0.012). Conclusion In this study, the incidence of MMs and ITCs in patients with stage I/II colon cancer was 4.2% and 19.3%, respectively. MMs were associated with an reduced 3 year disease free survival rate, but ITCs were not. [ABSTRACT FROM AUTHOR]

Aim The value of frequent Carcino-Embryonic Antigen (CEA) measurements and CEA-triggered imaging for detecting recurrent disease in colorectal cancer (CRC) patients was investigated in search for an evidence-based follow-up protocol. Methods This is a randomized-controlled multicenter prospective study using a stepped-wedge cluster design. From October 2010 to October 2012, surgically treated non-metastasized CRC patients in follow-up were followed in eleven hospitals. Clusters of hospitals sequentially changed their usual follow-up care into an intensified follow-up schedule consisting of CEA measurements every two months, with imaging in case of two CEA rises. The primary outcome measures were the proportion of recurrences that could be treated with curative intent, recurrences with definitive curative treatment outcome, and the time to detection of recurrent disease. Results 3223 patients were included; 243 recurrences were detected (7.5%). A higher proportion of recurrences was detected in the intervention protocol compared to the control protocol (OR = 1.80; 95%-CI: 1.33–2.50; p = 0.0004). The proportion of recurrences that could be treated with curative intent was higher in the intervention protocol (OR = 2.84; 95%-CI: 1.38–5.86; p = 0.0048) and the proportion of recurrences with definitive curative treatment outcome was also higher (OR = 3.12, 95%-CI: 1.25–6.02, p-value: 0.0145). The time to detection of recurrent disease was significantly shorter in the intensified follow-up protocol (HR = 1.45; 95%-CI: 1.08–1.95; p = 0.013). Conclusion The CEAwatch protocol detects recurrent disease after colorectal cancer earlier, in a phase that a significantly higher proportion of recurrences can be treated with curative intent. [ABSTRACT FROM AUTHOR]

Background Multicentric breast cancer is often considered a contra-indication for sentinel lymph node (SLN) biopsy due to concerns with sensitivity and false negative rate. To assess SLN feasibility and accuracy in multicentric breast cancer, the multi-institutional SMMaC trial was conducted. Methods In this study 30 patients with multicentric breast cancer and a clinically negative axilla were prospectively included. Periareolar injection of radioisotope and blue dye was administered. In all patients SLN biopsy was validated by back-up completion axillary lymph node dissection. Results the SLN was successfully identified in 30 of 30 patients (identification rate 100%). The incidence of axillary metastases was 66.7% (20/30). The false negative rate was 0% (0/20) and the sensitivity was 100% (20/20). The negative predictive value was 100% (10/10). Conclusion SLN biopsy in multicentric breast cancer seems feasible and accurate and should therefore be considered in patients with multicentric breast cancer and clinically negative axilla. [ABSTRACT FROM AUTHOR]

Abstract: Background: In breast cancer, sentinel node biopsy is considered the standard method to assess the lymph node status of the axilla. Preoperative identification of sentinel lymph nodes (SLN) is performed by injecting a radioactive tracer, followed by lymphoscintigraphy. In some patients there is a discrepancy between the number of lymphoscintigraphically identified sentinel nodes and the number of nodes found during surgery. We hypothesized that the inability to find peroperatively all the lymphoscintigraphically identified sentinel nodes, might lead to an increase in axillary recurrence because of positive SLNs not being removed. Methods: Patients who underwent sentinel node biopsy between January 2000 and July 2010 were identified from a prospectively collected database. The number of lymphoscintigraphically and peroperatively identified sentinel nodes were reviewed and compared. Axillary recurrences were scored. Results: 1368 patients underwent a SLN biopsy. Median follow up was 58.5 months (range 12–157). Patient and tumour characteristics showed no significant differences. In 139 patients (10.2%) the number of radioactive nodes found during surgery was less than preoperative scanning (group 1) and in 89.8% (N = 1229) there were equal or more peroperative nodes identified than seen lymphoscintigraphically (group 2). In group 1, 0/139 patients (0%) developed an axillary recurrence and in the second group this was 25/1229 (2.0%) respectively. No significant difference between groups regarding axillary recurrence, sentinel node status and distant metastasis was found. Conclusion: Axillary recurrence rate is not influenced by the inability to remove all sentinel nodes during surgery that have been identified preoperatively by scintigraphy. [Copyright &y& Elsevier]

Abstract: Purpose: To assess the feasibility and effectiveness of radiofrequency ablation (RFA) in breast cancer, using different histopathologic staining methods to evaluate tissue viability. Materials and methods: In twenty patients with unifocal small (≤1, 5 cm) invasive ductal carcinoma, ultrasound-guided RFA was performed immediately after surgery. Cell viability was assessed using cytokeratin 8 (CK 8) and nicotinamide adenine dinucleotide diaphorase (NADHD) in addition to hematoxylin–eosin (HE). Results: At histopathological examination, ex vivo RFA resulted in complete cell death of the target lesion in 17/20 patients. In two cases viable ductal carcinoma in situ (DCIS) was found just outside the completely ablated lesion. Conclusion: RFA of small invasive breast cancer seems to be a feasible treatment option. Both NADHD and CK 8 demonstrate a clear and comparable demarcation between viable and non-viable tissue. A high level of accuracy is required in proper positioning of the needle electrode and a “hot retraction” is mandatory. [Copyright &y& Elsevier]

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

Abstract: Background: A subgroup of stage II colonic cancer patients are considered to be at high-risk for recurrent/metastatic disease based on 1) tumour obstruction/perforation 2) <10 lymph nodes 3) T4 lesions and 4) lymphangio-invasion. Their prognosis is regarded as comparable to stage III (T1-4N+M0) colonic cancer and it is therefore strongly advised to treat them with adjuvant chemotherapy. The purpose of this study was i) to determine the magnitude of prognostic significance of the conventional high-risk factors and ii) to determine whether the number of high-risk factors influences outcome. Methods: We retrospectively analyzed 212 stage II colonic cancer patients undergoing surgery between January 2002 and December 2008. No adjuvant chemotherapy was given. Survival analyses were performed. Results: 154/212 (73%) patients were considered to be high-risk patients based on conventional high-risk factors. 58 patients did not meet any high-risk factor, 125 patients met 1 high-risk factor and 29 patients met ≥2 high-risk factors. Median follow up was 40 months. Multivariate analysis identified four independent risk factors for recurrent/metastatic disease: age, obstruction, perforation and lymphangio-invasion. The three-year-DFS-rates for the low-risk group, the high-risk group with 1 high-risk factor and the high-risk group with ≥2 high-risk criteria are 90.4%, 87.6% and 75.9% respectively. Patients meeting ≥2 conventional high-risk criteria had a significantly worse three-year disease free survival (p < 0.002). Conclusions: Four independent high-risk factors were identified. The number of high-risk factors does influence outcome. More attention should be given to the definition and treatment of high-risk stage II colonic cancer patients. [Copyright &y& Elsevier]

Abstract: Aims: Though most studies on surgical resection of the breast tumor in patients with primary distant metastatic breast cancer (MBC) indicated that surgery is associated with prolonged overall survival, some state that this effect has been confounded by indication and timing of surgery. In this study we analyzed these possible confounders and their relation to overall survival. Methods: To determine the impact of potential confounders, individual charts of 279 patients with primary MBC were reviewed. Results: The median survival in patients treated with surgery of the breast tumor was 39 months, compared to 15 months for those without surgery (p < 0.0001). The median survival of patients with symptomatic metastatic disease (n = 112) was 19 months, compared to 22 months for those without symptomatic disease (n = 167) (p = 0.15). Patients who received surgery and whose metastases were detected before surgery of the breast tumor had taken place (n = 40) had a median survival of 38 months, compared to 40 months for patients in whom the metastatic disease was diagnosed after surgery (n = 43) (p = 0.81). Conclusion: Presence of symptomatic metastatic disease was no significant prognostic factor for patients with distant metastasis at diagnosis, neither was the timing of surgery. It is unlikely that the prolonged survival after surgery is explained by these potentials confounders. [Copyright &y& Elsevier]

Abstract: Gastric cancer is one of the main causes of cancer-related deaths around the world. The prevalence of early gastric cancer (EGC) among all gastric cancers of 45–51% in Japan, but only 7–28% in Western countries. The prevalence of EGC is growing partly because of better diagnostics and screening programmes. Possible treatment options for EGC treatment are expanded by the introduction of endoscopic mucosal resection and endoscopic submucosal dissection Therefore, detailed knowledge about nodal metastatic risk is warranted. We performed a systematic review of the literature concerning studies investigating the role of sentinel lymph node biopsy in EGCr and whether there is enough proof to introduce SLN as a part of treatment for EGC in the Netherlands. Several detection substances (dye or radiocolloid) and injection methods (submucosal or subserosal) are investigated. An overall sensitivity percentage of 85.4% was found. In comparison, high and clinically sufficient percentages were observed for specificity (98.2%), negative predictive value (90.7%) and accuracy (94%). Subgroup analyses showed that the combination of dye and radiocolloid detection substances is the best method for sentinel lymph node detection in early gastric cancer. However, the precise method of sentinel lymph node biopsy in EGC has to be determined further. Large, randomized series should be initiated in Europe to address this issue. [Copyright &y& Elsevier]

Abstract: Introduction: At least 15 lymph nodes should be retrieved for proper TNM-staging in gastric cancer. We evaluated nodal harvest and examined its relation to stage distribution and survival at a population-based level, including the value of N-ratio (metastatic/evaluated) as a staging modality. Methods: All patients resected for primary M0 gastric cancer diagnosed in 1999–2007 in the Dutch Eindhoven Cancer Registry area were included (N = 880). Determinants of lymph node evaluation and their relationship with stage and survival were assessed in multivariable regression analyses. N-ratio categories were determined (N-ratio 0, 0%; N-ratio 1, 0.1%–19%; N-ratio 2, 20%–29%; N-ratio 3, ≥30%) Results: The median number of lymph nodes examined was 7, dependent on N-category (N0: 7; N+: 8). It varied between departments of pathology from 5 to 9. This variation remained after adjustment for relevant patient- and tumour factors. Stage distribution differed between pathology departments (proportion N0 ranging from 14% to 21%, p = 0.003). Among resected patients with N0M0 disease and <7 nodes examined, 5-year survival was 56%, compared to 69% among patients with ≥7 nodes examined (p = 0.012). Five-year survival for N-ratio 0 was 58%, N-ratio 1 50%, N-ratio 2 18% and N-ratio 3 11% (p < 0.0001), while 5-year survival ranged from 58% for N0, 17% for N1, and 11% for N2/3 (p < 0.0001). Conclusion: In this series of patients with a relatively low number of evaluated lymph nodes, a high prognostic accuracy of N-ratio was found. However, improvement in nodal assessment is mandatory. [Copyright &y& Elsevier]

Abstract: Aims: A meta-analysis was performed to identify the clinicopathological variables most predictive of non-sentinel node (NSN) metastases when the sentinel node is positive. Methods: A Medline search was conducted that ultimately identified 56 candidate studies. Original data were abstracted from each study and used to calculate odds ratios. The random-effects model was used to combine odds ratios to determine the strength of the associations. Findings: The 8 individual characteristics found to be significantly associated with the highest likelihood (odds ratio >2) of NSN metastases are SLN metastases >2mm in size, extracapsular extension in the SLN, >1 positive SLN, ≤1 negative SLN, tumour size >2cm, ratio of positive sentinel nodes >50% and lymphovascular invasion in the primary tumour. The histological method of detection, which is associated with the size of metastases, had a correspondingly high odds ratio. Conclusions: We identified 8 factors predictive of NSN metastases that should be recorded and evaluated routinely in SLN databases. These factors should be included in a predictive model that is generally applicable among different populations. [Copyright &y& Elsevier]

Abstract: Objective: Recent studies indicate that removal of the primary tumour may have a beneficial effect on mortality risk of patients with primary distant metastatic breast cancer (stage IV), although most of them did not rule out confounding by the presence of co-morbidity. In this retrospective study the impact of surgical resection of the primary tumour on the survival of patients with primary distant metastatic disease is investigated, taking into account the presence of co-morbidity and other potential confounders. Methods: Between 1993 and 2004, 15 769 patients with breast cancer were diagnosed in the south of the Netherlands. This study included the 728 patients with distant metastatic disease at initial presentation, which was 5% of all patients. Of them, 40% had surgery of the primary tumour. Follow-up was carried out until 1 July 2006. Results: Median survival of the patients who had surgery of their primary tumour was significantly longer than for the patients who did not have surgery (31 vs. 14 months). The 5-year survival rates were 24.5% and 13.1%, respectively (p <0.0001). In a multivariable Cox regression analysis, adjusting for age, period of diagnosis, T-classification, number of metastatic sites, co-morbidity, use of loco-regional radiotherapy and use of systemic therapy, surgery appeared to be an independent prognostic factor for overall survival (HR=0.62; 95% CI 0.51–0.76). Conclusion: Removal of the primary tumour in patients with primary distant metastatic disease was associated with a reduction of the mortality risk of around 40%. The association was independent of age, presence of co-morbidity and other potential confounders, but a randomized controlled trial will be needed to rule out residual confounding. [Copyright &y& Elsevier]

Abstract: Approximately 30% of the patients with Dukes A/B colon carcinoma will develop loco-regional recurrence or distant metastases. The aim of this study was to evaluate if patients with micro-metastases are at higher risk for developing distant metastases and therefore a worse disease-free survival and overall survival. In the period January 2000–January 2002, 137 patients underwent curative surgery for colon cancer. When patients had a Dukes A/B colon carcinoma, additional staining and sectioning on the harvested lymph nodes were performed retrospectively. Lymph nodes were examined using 4 multilevel sections at 250-μm intervals and stained with Pan-Cytokeratin. There were 11 patients with a Dukes A and 61 patients with a Dukes B colon carcinoma. Twenty-two patients developed metastases in time (group I) whereas 50 patients did not (group II). After additional staining and sectioning 41% of the patients of group I and 16% of the patients of group II showed micro-metastases (p <0.05). The 5-year overall survival rate in the group with micro-metastases was 62% against 79% in the group without micro-metastases. The disease-free survival (DFS) was 51% and 72% (p <0.05), respectively. Patients with micro-metastases develop significant more distant metastases in time and have a significant worse DFS. [Copyright &y& Elsevier]

Abstract: Background: Gastric cancer is fourth on the incidence list of cancers worldwide with a high disease-related mortality rate. Curation can only be achieved by a radical resection including an adequate lymphadenectomy. However, prognosis remains poor and cancer recurrence rates are high, also due to lymph node metastases. To improve outcome, (neo)adjuvant treatment strategies with chemo- and/or radiotherapy regimes are employed. Aims: Accurate staging of gastric cancer at primary diagnosis is essential for adequate treatment. In this non-systematic review the role 18-F-Fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) in preoperative staging is investigated. Furthermore, the results of neoadjuvant chemotherapy-induced tumour response monitoring by FDG-PET are discussed. Results and conclusion: It is concluded that currently FDG-PET has no role in the primary detection of gastric cancer due to its low sensitivity. FDG-PET shows, however, slightly better results in the evaluation of lymph node metastases in gastric cancer compared to CT and could have therefore a role in the preoperative staging. Improvement in accuracy could be achieved by using PET/CT or other PET tracers than FDG, but these modalities need further investigation. FDG-PET, however, adequately detects therapy responders at an early stage following neoadjuvant chemotherapy. [Copyright &y& Elsevier]

Abstract: Aim: Ductal carcinoma in situ (DCIS) refers to the preinvasive stage of breast carcinoma and should not give axillary metastases. Its diagnosis, however, is subject to sampling errors. The role of sentinel lymph node biopsy (SLNB) in management of DCIS or DCISM (with microinvasion) remains unclear. The purpose of this study was to review our experience with SLNB in DCIS and DCISM. Methods: A review of 51 patients with a diagnosis of DCIS (n =45) or DCISM (n =6), who underwent SLNB and a definitive breast operation between January 1999 and December 2006, was performed. Results: In 10 patients (19.6%) definitive histology revealed an invasive carcinoma. SLN (micro)metastases were detected in 5 out of 51 patients, of whom 2 had a preoperative diagnosis of grade III DCIS and 3 of DCISM. Three patients (75%) had micrometastases (<2mm) only. In 2 patients, histopathology demonstrated a macrometastasis (>2mm). All 5 patients underwent axillary dissection. No additional positive axillary lymph nodes were found. Conclusions: In case of a preoperative diagnosis of grade III DCIS or a grade II DCIS with comedo necrosis and DCIS with microinvasion, an SLNB procedure has to be considered because in almost 20% of the patients an invasive carcinoma is found after surgery. In this case the SLNB procedure becomes less reliable after a lumpectomy or ablation has been performed. SLN (micro)metastases were detected in nearly 10% of the patients. The prognostic significance of individual tumour cells remains unclear. [Copyright &y& Elsevier]

Abstract: Background: The purpose of this study was to evaluate the feasibility and reliability of ex vivo sentinel lymph node mapping in patients with colorectal cancer. Methods: In the period January–June 2006, 44 consecutive patients underwent curative surgery for colorectal cancer. In patients with colon and rectal cancer, 0.5–2ml of Patent Blue Dye was injected submucosally. The injection sites where then gently massaged for 5min. Results: In 96% of the patients with colon cancer and 94% of the patients with rectal cancer, at least one sentinel lymph node was found. There were no patients with a false negative sentinel node. The sensitivity was 100% with a negative predictive value of 100%. In 19% of the patients with colon cancer and 18% of the patients with rectal cancer the sentinel node was the exclusive site of lymph node metastases. After additional sectioning and staining, 7 of the 23 patients (30%) with a Dukes B colorectal cancer were upstaged. Conclusion: The technique of ex vivo sentinel lymph node mapping is technically feasible with high sensitivity, high negative predictive value and a high rate of upstaging. The next step is to investigate, if detection of micro-metastases is associated with decreased survival and/or increased local recurrence rates. [Copyright &y& Elsevier]