Showing papers in "Ejso in 2011"

Systematic review of radioguided surgery for non-palpable breast cancer

Abstract: Background This systematic review examines whether radioguided localization surgery (RGL) (radioguided occult lesion localization – ROLL and radioguided seed localization – RSL) for non-palpable breast cancer lesions produces lower positive margin rates than standard wire-guided localization surgery. Methods We performed a comprehensive literature review to identify clinical studies using either ROLL or RSL. Included studies examined invasive or in situ BC and reported pathologically assessed margin status or specimen volume/weight. Two reviewers independently assessed study eligibility and quality and abstracted relevant data on patient and surgical outcomes. Quantitative data analyses were performed. Results Fifty-two clinical studies on ROLL ( n = 46) and RSL ( n = 6) were identified. Twenty-seven met our inclusion criteria: 12 studies compared RGL to WGL and 15 studies were single cohorts using RGL. Ten studies were included in the quantitative analyses. Data for margin status and re-operation rates from 4 randomized controlled trials (RCT; n = 238) and 6 cohort studies were combined giving a combined odds ratio (OR) of 0.367 and 95% confidence interval (CI): 0.277 to 0.487 ( p p Conclusions The results of this systematic review of RGL versus WGL demonstrate that RGL technique produces lower positive margins rates and fewer re-operations. While this review is limited by the small size and quality of RCTs, the odds ratios suggest that RGL may be a superior technique to guide surgical resection of non-palpable breast cancers. These results should be confirmed by larger, multi-centered RCTs.

Validation of the Joensuu risk criteria for primary resectable gastrointestinal stromal tumour – The impact of tumour rupture on patient outcomes

Abstract: Background Approval of imatinib for adjuvant treatment of gastrointestinal stromal tumours (GIST) raised discussion about accuracy of prognostic factors in GIST and the clinical significance of the available risk stratification criteria. Methods We studied the influence of a new modification of the NIH Consensus Criteria (the Joensuu risk criteria), NCCN-AFIP criteria, and several clinicopathological factors, including tumour rupture, on relapse-free survival (RFS) in a prospectively collected tumour registry series consisting of 640 consecutive patients with primary, resectable, CD117-immunopositive GIST. The median follow-up time after tumour resection was 39 months. None of the patients received adjuvant imatinib. Results The median RFS time after surgery was 50 months. In univariable analyses, high Joensuu risk group, tumour mitotic count >5/50 HPF, size >5 cm, non-gastric location, tumour rupture (7% of cases; P = 0.0014) and male gender had adverse influence on RFS. In a multivariable analysis mitotic count >5/50HPF, tumour size >5 cm and non-gastric location were independent adverse prognostic factors. Forty, 151, 86 and 348 patients were assigned according to the Joensuu criteria to very low, low, intermediate and high risk groups and had 5-year RFS of 94%, 94%, 86% and 29%, respectively. Conclusion The Joensuu criteria, which include 4 prognostic factors (tumour size, site, mitotic count and rupture) and 3 categories for the mitotic count, were found to be a reliable tool for assessing prognosis of operable GIST. The Joensuu criteria identified particularly well high risk patients, who are likely the proper candidates for adjuvant therapy.

Prevention of seroma formation after axillary dissection in breast cancer: A systematic review

Abstract: Background The most common complication after breast cancer surgery is seroma formation. It is a source of significant morbidity and discomfort. Many articles have been published describing risk factors and preventive measures. The aim of this paper is to provide a systematic review of studies and reports on risk factors and preventive measures. Surgery lies at the core of seroma formation; therefore focus will be placed on surgical ways of reducing seroma. Methods A computer assisted medline search was carried out, followed by manual retrieval of relevant articles found in the reference listings of original articles. Results 136 relevant articles were reviewed. Though the level of evidence remain varied several factors, type of dissection, tools with which dissection is carried out, reduction of dead space, suction drainage, use of fibrin glue and octreotide usage, have been found to correlate with seroma formation and have been shown to significantly reduce seroma rates. Conclusion Seroma formation after breast cancer surgery cannot be avoided at present. There are however several methods to minimize seroma and associated morbidity. Future research should be directed towards the best ways of reducing seroma by combining proven methods.

Prognostic factors and oncologic outcome in 146 patients with colorectal peritoneal carcinomatosis treated with cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy: Italian multicenter study S.I.T.I.L.O.

Abstract: Aim The present study was specifically designed to assess the major clinical and pathological variables of patients with colorectal peritoneal carcinomatosis in order to investigate whether currently used criteria appropriately select candidates for peritonectomy procedures (cytoreductive surgery) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Patients and methods Preoperative, operative and follow-up data on 146 consecutive patients presenting with peritoneal carcinomatosis of colorectal origin and treated by surgical cytoreduction combined with HIPEC in 5 Italian Hospital and University Centers were prospectively entered in a common database. Univariate and multivariate analyses were used to assess the prognostic value of clinical and pathologic factors. Results Over a minimum 24-month follow-up, the overall morbidity rate was 27.4% (mortality rate: 2.7%) and was directly related to the extent of surgery. Peritoneal cancer index (PCI), unfavorable peritoneal sites, synchronous or previously resected liver metastasis and the completeness of cytoreduction, all emerged as independent prognostic factors correlated with survival. Conclusions Until research provides more effective criteria for selecting patients based upon the biomolecular features of carcinomatosis, patients should be selected according to the existing independent prognostic variables.

Positron emission tomography (PET) for assessment of axillary lymph node status in early breast cancer: A systematic review and meta-analysis

Abstract: Purpose Sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) are used to assess axillary nodal status in breast cancer, but are invasive procedures associated with morbidity, including lymphoedema. This systematic review evaluates the diagnostic accuracy of positron emission tomography (PET), with or without computed tomography (CT), for assessment of axillary nodes in early breast cancer. Methods Eleven databases including MEDLINE, EMBASE and the Cochrane Library, plus research registers and conference proceedings, were searched in April 2009. Study quality was assessed using the QUality Assessment of Diagnostic Accuracy Studies (QUADAS) checklist. Sensitivity and specificity were meta-analysed using a bivariate random effects approach. Results Across 26 studies evaluating PET or PET/CT ( n = 2591 patients), mean sensitivity was 63% (95% CI: 52–74%; range 20–100%) and mean specificity 94% (95% CI: 91–96%; range 75–100%). Across 7 studies of PET/CT ( n = 862), mean sensitivity was 56% (95% CI: 44–67%) and mean specificity 96% (90–99%). Across 19 studies of PET-only ( n = 1729), mean sensitivity was 66% (50–79%) and mean specificity 93% (89–96%). Mean sensitivity was 11% (5–22%) for micrometastases (≤2 mm; five studies; n = 63), and 57% (47–66%) for macrometastases (>2 mm; four studies; n = 111). Conclusions PET had lower sensitivity and specificity than SLNB. Therefore, replacing SLNB with PET would avoid the adverse effects of SLNB, but lead to more false negative patients at risk of recurrence and more false positive patients undergoing unnecessary ALND. The present evidence does not support the routine use of PET or PET-CT for the assessment of the clinically negative axilla.

A comparison of three methods for nonpalpable breast cancer excision

Abstract: Aims To evaluate the efficacy of three methods of breast-conserving surgery (BCS) for nonpalpable invasive breast cancer in obtaining adequate resection margins and volumes of resection. Materials and methods A total of 201 consecutive patients undergoing BCS for nonpalpable invasive breast cancer between January 2006 and 2009 in four affiliated institutions was retrospectively analysed. Patients with pre-operatively diagnosed primary or associated ductal carcinoma in situ (DCIS), multifocal disease, or a history of breast surgery or neo-adjuvant treatment were excluded from the study. The resections were guided by wire localisation (WL), ultrasound (US), or radio-guided occult lesion localisation (ROLL). The pathology reports were reviewed to determine oncological margin status, as well as tumour and surgical specimen sizes. The optimal resection volume (ORV), defined as the spherical tumour volume with an added 1.0-cm margin, and the total resection volume (TRV), defined as the corresponding ellipsoid, were calculated. By dividing the TRV by the ORV, a calculated resection ratio (CRR) was determined to indicate the excess tissue resection. Results Of all 201 excisions, 117 (58%) were guided by WL, 52 (26%) by US, and 32 (16%) by ROLL. The rate of focally positive and positive margins for invasive carcinoma was significantly lower in the US group (N = 2 (3.7%)) compared to the WL (N = 25 (21.3%)) and ROLL (N = 8 (25%)) groups (p = 0.023). The median CRRs were 3.2 (US), 2.8 (WL) and 3.8 (ROLL) (WL versus ROLL, p < 0.05), representing a median excess tissue resection of 3.1 times the optimal resection volume. Conclusion US-guided BCS for nonpalpable invasive breast cancer was more accurate than WL- and ROLL-guided surgery because it optimised the surgeon’s ability to obtain adequate margins. The excision volumes were large in all excision groups, especially in the ROLL group.

Management of follicular thyroid carcinoma should be individualised based on degree of capsular and vascular invasion

Abstract: Introduction Follicular thyroid carcinoma (FTC) includes a spectrum of neoplasms with varying propensity for metastasis. The aim of this study is to describe outcomes for FTC following multimodality treatment, with particular reference to the degree of capsular and vascular invasion and to recommend a rational management approach based on these characteristics. Methods Patients with histologically confirmed FTC were identified from a prospectively maintained database. Details of intervention and long-term outcomes were obtained. Outcomes were compared between patients with minimally invasive follicular carcinoma (MI FTC) without vascular invasion (Group 1); angioinvasive MI FTC (Group 2); and those with widely invasive FTC (Group 3). Results Between May 1983 and December 2008, 124 patients with FTC were identified. The overall disease-free survival rate was 85% at a median of 40 months follow-up. Disease-free survival was 97%, 81% and 46%, respectively, in Groups 1, 2 and 3, and significantly different between groups ( p p =0.03) and the presence of vascular invasion ( p =0.03) were the most powerful predictors of distant metastasis. Conclusions Survival is improved in those with minimally invasive compared with widely invasive FTC. In patients

Colon carcinoma – Classification into right and left sided cancer or according to colonic subsite? – Analysis of 29 568 patients

Abstract: Background It is common to distinguish between right and left colon cancer (RCC and LCC). But, little is known about the influence of its exact location on the tumor stage and characteristics when considering the colonic subsite within the right or left colon. Methods During a five-year period, 29 568 consecutive patients were evaluated by data from the German multi-centered observational study “Colon/Rectal Carcinoma”. Patients were split into 7 groups, each group representing a colonic subsite. They were compared regarding demographic factors, tumor stage, metastatic spread and histopathological characteristics. Results Analysis of tumor differentiation and histological subtype revealed a linear correlation to the ileocecal valve, supporting the right and left side classification model. However, cancers arising from the RCC’s cecum (52.3%) and LCC’s splenic flexure (51.0%) showed the highest proportion of UICC stage III/IV tumors and lymphatic invasion, whereas the RCC’s ascending colon (46.5%) and LCC’s descending (44.7%) showed the lowest, which supports a more complex classification system, breaking down the right and left sides into colonic subsites. Conclusions Age, tumor grade and histological subtype support the right and left side classification model. However, gender, UICC stage, metastatic spread, T and N status, and lymphatic invasion correlated with a specific colonic subsite, irrespective of the side. The classification of RCC or LCC provides a general understanding of the tumor, but identification of the colonic subsite provides additional prognostic information. This study shows that the standard right and left side classification model may be insufficient.

Natural orifice total mesorectal excision using transanal port and laparoscopic assistance

Abstract: Natural Orifice Transluminal Endoscopic Surgery (NOTES) is an emerging concept which has been recently applied to the field of rectal excision. The authors describe a case of total mesorectal excision using a transanal port and laparoscopic assistance. We described a procedure performed in a 45-year-old for a rectal adenocarcinoma (1 cm wide, T1sm3) 3 cm above the dentate line. The procedure is described in the text and in a didactic video.

Totally implantable venous access port systems and risk factors for complications: A one-year prospective study in a cancer centre

Abstract: Background: Totally Implantable Venous Access Port Systems (TIVAPS) are widely used in oncology, but complications are frequent, sometimes necessitating device removal and consequently delays in chemotherapy. The aim of this study was to investigate possible risk factors for morbidity. Methods: A total of 815 consecutive cancer patients (median age: 56.2 years [0.8e85.2]; 522 female) were enrolled in this observational, single-centre study between May 2nd 2006 and April 30th 2007. TIVAPS implantation involved principally cephalic or external jugular vein access. Patients were followed up for one year unless the device was removed earlier. Results: The overall morbidity rate was 16.1% (131/815). Complications necessitated device removal in 55 patients a mean of 3.7 months [0.2e12.0] after implantation. These comprised TIVAPS-related infection (19), port expulsion (14), catheter migration (6), venous thrombosis (5), mechanical problems (3), skin disorders (2), pain (2), drug extravasation (2) infection unrelated to TIVAPS (1) and inflammation (1). No patient died during the study. The factor most strongly predictive of complications was the interval between insertion and first use of the TIVAPS, ranging from 0 to 135 days (median: 8.0 days). The morbidity rate was 24.4% when this interval was 0e3 days, 17.1% when it was 4e7 days and 12.1% when it exceeded 7 days (p < 0.01; Chi 2 test). The median interval was 6 days (0e53) and 8 days (0e135), respectively, in patients with and without complications (p < 0.001). Conclusion: To reduce complications, an interval of at least 8 days between placement of the TIVAPS and its first use may be advisable. 2011 Elsevier Ltd. All rights reserved.

Management of lobular carcinoma in-situ and atypical lobular hyperplasia of the breast--a review.

Abstract: Objectives To determine the incidence of malignancy (invasive carcinoma or DCIS) in patients diagnosed with lobular neoplasia (B3) on core needle biopsy (CNB) of breast lesions by reviewing the published literature. Methods Medline, Embase, OVID-database and reference lists were searched to identify and review all English-language articles addressing the management of LN diagnosed on CNB. Studies on mixed breast pathologies were excluded. Results Of 1229 LN diagnosed on CNB, 789 (64%) underwent surgical excision. 211 (27%) of excisions contained either DCIS or invasive disease. 280 of the excision specimens were classified as ALH, 241 as LCIS, 22 as pleomorphic LCIS and 246 unspecified LN on the original CNB. After surgical excision, 19% of the ALH cases, 32% of the LCIS cases and 41% of the PLCIS cases, contained malignancy. 29% of the unspecified LNs were upgraded to malignancy. The higher incidence of malignancy within excision specimens for LCIS and PLCIS compared to ALH was significant (P Conclusion There is a significant underestimation of malignancy in patients diagnosed with breast LN on CNB. 27% cases of CNB-diagnosed LN were found to contain malignancy following surgical excision. All patients diagnosed with LN on CNB should be considered for surgical excision biopsy.

A population-based validation of the prognostic model PREDICT for early breast cancer.

Abstract: Introduction: Predict (www.predict.nhs.uk) is a prognostication and treatment benefit tool developed using UK cancer registry data. The aim of this study was to compare the 10-year survival estimates from Predict with observed 10-year outcome from a British Columbia dataset and to compare the estimates with those generated by Adjuvant! (www.adjuvantonline.com). Method: The analysis was based on data from 3140 patients with early invasive breast cancer diagnosed in British Columbia, Canada, from 1989e1993. Demographic, pathologic, staging and treatment data were used to predict 10-year overall survival (OS) and breast cancer specific survival (BCSS) using Adjuvant! and Predict models. Predicted outcomes from both models were then compared with observed outcomes. Results: Calibration of both models was excellent. The difference in total number of deaths estimated by Predict was 4.1 percent of observed compared to 0.7 percent for Adjuvant!. The total number of breast cancer specific deaths estimated by Predict was 3.4 percent of observed compared to 6.7 percent for Adjuvant! Both models also discriminate well with similar AUC for Predict and Adjuvant! respectively for both OS (0.709 vs 0.712) and BCSS (0.723 vs 0.727). Neither model performed well in women aged 20e35. Conclusion: In summary Predict provided accurate overall and breast cancer specific survival estimates in the British Columbia dataset that are comparable with outcome estimates from Adjuvant! Both models appear well calibrated with similar model discrimination. This study provides further validation of Predict as an effective predictive tool following surgery for invasive breast cancer. 2011 Elsevier Ltd. All rights reserved.

Lymph node metastases and prognosis in oesophageal carcinoma--a systematic review.

Abstract: Oesophageal cancer is the 7th most common cause of cancer-related death in the developed world and the incidence of oesophageal adenocarcinoma is now the fastest growing of any gastrointestinal cancer. Lymph node involvement is the single most important prognostic factor in oesophageal cancer. Imaging to determine the extent of lymph node involvement and plan treatment often requires a combination of modalities to avoid under-staging. The 7th edition of the staging system released by the International Union Against Cancer (IUCC) has stratified lymph node involvement according to the number of lymph nodes involved and redefined its groupings for location of metastatic lymph node involvement. This review discusses the prognostic and treatment implications of these modifications and explores micrometastatic lymph node involvement, capsular infiltration and lymph node ratio as possible additions to the staging system.

Quality of life after immediate breast reconstruction and skin-sparing mastectomy - a comparison with patients undergoing breast conserving surgery.

Abstract: Background Historically breast cancer surgery was associated with significant psychosocial morbidity and suboptimal cosmetic outcome. Recent emphasis on women’s quality of life following breast cancer treatment has drawn attention to the importance of aesthetic outcome and potential benefits of immediate breast reconstruction (IBR). Our primary aim was to assess patient’s quality of life after IBR, compared to a matched group undergoing breast conservation. We also investigated the oncological safety and morbidity associated with immediate reconstruction. Methods A prospectively collected database of all breast cancer patients who underwent IBR at a tertiary referral breast unit was reviewed. Patients were reviewed clinically, and administered two validated quality of life questionnaires, at least one year after completing their treatment. Results 255 patients underwent IBR following mastectomy over a 55 month period. Reconstruction with ipsilateral latissimus dorsi flap was most commonly performed (88%). After mean follow-up of 36 months, IBR patients’ quality of life was comparable to a group of age-matched women ( n = 160) who underwent breast conserving surgery ( p = 0.89). No patient experienced local recurrence (0%), distant metastases developed in 4.8% and disease related mortality was 2.2%. Post-operative morbidities included wound infection (11.8%), chronic pain (2.0%), capsular contracture (11%; 36% of whom had radiotherapy) and fat necrosis (14.1%). No patient experienced flap loss. Conclusions IBR is a highly acceptable form of treatment for women requiring mastectomy. With high rates of patient satisfaction, low associated morbidity, and proven oncological safety, it is an appropriate recommendation for all women requiring mastectomy.

Magnetic resonance for assessment of axillary lymph node status in early breast cancer: a systematic review and meta-analysis.

Abstract: Introduction Current methods of identifying axillary node metastases in breast cancer patients are highly accurate, but are associated with several adverse events. This review evaluates the diagnostic accuracy of magnetic resonance imaging (MRI) techniques for identification of axillary metastases in early stage newly diagnosed breast cancer patients. Methods Comprehensive searches were conducted in April 2009. Study quality was assessed. Sensitivity and specificity were meta-analysed using a bivariate random effects approach, utilising pathological diagnosis via node biopsy as the comparative gold standard. Results Based on the highest sensitivity and specificity reported in each of the nine studies evaluating MRI (n = 307 patients), mean sensitivity was 90% (95% CI: 78–96%; range 65–100%) and mean specificity 90% (95% CI: 75–96%; range 54–100%). Across five studies evaluating ultrasmall super-paramagnetic iron oxide (USPIO)-enhanced MRI (n = 93), mean sensitivity was 98% (95% CI: 61–100%) and mean specificity 96% (95% CI: 72–100%). Across three studies of gadolinium-enhanced MRI (n = 187), mean sensitivity was 88% (95% CI: 78–94%) and mean specificity 73% (95% CI: 63–81%). In the single study of in-vivo proton MR spectroscopy (n = 27), sensitivity was 65% (95% CI: 38–86%) and specificity 100% (95% CI: 69–100%). Conclusions USPIO-enhanced MRI showed a trend towards higher sensitivity and specificity and may make a useful addition to the current diagnostic pathway. Additional larger studies with standardised methods and standardised criteria for classifying a node as positive are needed. Current estimates of sensitivity and specificity do not support replacement of SLNB with any current MRI technology in this patient group.

Meta-analysis of predictive factors for non-sentinel lymph node metastases in breast cancer patients with a positive SLN.

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 >2 mm in size, extracapsular extension in the SLN, >1 positive SLN, ≤1 negative SLN, tumour size >2 cm, 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.

The clinical significance of circulating tumor cells in non-metastatic colorectal cancer--a review.

Abstract: Background Finding a clinical tool to improve the risk stratification and identifying those colorectal cancer patients with an increased risk of recurrence is of great importance. The presence of circulating tumor cells (CTC) in peripheral blood can be a strong marker of poor prognosis in patients with metastatic disease, but the prognostic role of CTC in non-metastatic colorectal cancer is less clear. The aim of this review is to examine the possible clinical significance of circulating tumor cells in non-metastatic colorectal cancer (TNM-stage I–III) with the primary focus on detection methods and prognosis. Methods The PubMed and Cochrane database and reference lists of relevant articles were searched for scientific literature published in English from January 2000 to June 2010. We included studies with non-metastatic colorectal cancer (TNM-stage I–III) and CTC detected pre- and/or post-operatively in peripheral blood. Results Nine studies qualified for further analyses. Detection rates of CTC in peripheral blood of patients with non-metastatic colorectal cancer varied from 4% to 57%. Seven studies applied RT-PCR and two studies used immunocytochemical methods. Seven studies found the presence of CTC to be a prognostic marker of poor disease-free survival. Conclusion The presence of CTC in peripheral blood is a potential marker of poor disease-free survival in patients with non-metastastic colorectal cancer. The low abundance of CTC in non-metastatic colorectal cancer requires very sensitive and specific detection methods. An international consensus on choice of detection method and markers, is warranted before incorporating CTC into risk stratification in the clinical setting.

Near-infrared fluorescence (NIRF) imaging in breast-conserving surgery: assessing intraoperative techniques in tissue-simulating breast phantoms.

Abstract: Purpose: Breast-conserving surgery (BCS) results in tumour-positive surgical margins in up to 40% of the patients. Therefore, new imaging techniques are needed that support the surgeon with real-time feedback on tumour location and margin status. In this study, the potential of near-infrared fluorescence (NIRF) imaging in BCS for pre- and intraoperative tumour localization, margin status assessment and detection of residual disease was assessed in tissue-simulating breast phantoms. Methods: Breast-shaped phantoms were produced with optical properties that closely match those of normal breast tissue. Fluorescent tumour-like inclusions containing indocyanine green (ICG) were positioned at predefined locations in the phantoms to allow for simulation of (i) preoperative tumour localization, (ii) real-time NIRF-guided tumour resection, and (iii) intraoperative margin assessment. Optical imaging was performed using a custom-made clinical prototype NIRF intraoperative camera. Results: Tumour-like inclusions in breast phantoms could be detected up to a depth of 21 mm using a NIRF intraoperative camera system. Real-time NIRF-guided resection of tumour-like inclusions proved feasible. Moreover, intraoperative NIRF imaging reliably detected residual disease in case of inadequate resection. Conclusion: We evaluated the potential of NIRF imaging applications for BCS. The clinical setting was simulated by exploiting tissue-like breast phantoms with fluorescent tumour-like agarose inclusions. From this evaluation, we conclude that intraoperative NIRF imaging is feasible and may improve BCS by providing the surgeon with imaging information on tumour location, margin status, and presence of residual disease in real-time. Clinical studies are needed to further validate these results.

Multidisciplinary management of hilar cholangiocarcinoma (Klatskin tumor): extended resection is associated with improved survival

Abstract: Background Effective diagnosis and treatment of patients with hilar cholangiocarcinoma (HCCA) is based on the synergy of endoscopists, interventional radiologists, radiotherapists and surgeons. This report summarizes the multidisciplinary experience in management of HCCA over a period of two decades at the Academic Medical Center in Amsterdam, with emphasis on surgical outcome. Methods From 1988 until 2003, 117 consecutive patients underwent resection on the suspicion of HCCA. Preoperative work-up included staging laparoscopy, preoperative biliary drainage, assessment of volume/function of future remnant liver and radiation therapy to prevent seeding metastases. More aggressive surgical approach combining hilar resection with extended liver resection was applied as of 1998. Outcomes of resection including actuarial 5-year survival were assessed. Results Eighteen patients (15.3%) appeared to have a benign lesion on microscopical examination of the specimen, leaving 99 patients with histologically proven HCCA. These 99 patients were analysed according to three 5-year time periods of resection, i.e. period 1 (1988–1993, n = 45), 2 (1993–1998, n = 25) and 3 (1998–2003, n = 29). The rate of R0 resections increased and actuarial five-year survival significantly improved from 20 ± 5% for the periods 1 and 2, to 33 ± 9% in period 3 (p < 0.05). Postoperative morbidity and mortality in the last period were 68% and 10%, respectively. Conclusion Extended surgical resection resulted in increased rate of R0 resections and significantly improved survival. Candidates for resection should be considered by a specialized, multidisciplinary team.

Advanced cytoreduction as surgical standard of care and hyperthermic intraperitoneal chemotherapy as promising treatment in epithelial ovarian cancer.

Abstract: Favorable oncological outcomes have been reported in several trials with the introduction of Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in the treatment of Advanced Epithelial Ovarian Cancer (EOC). However most of the studies testing the combined approach are observational and have been conducted in inhomogeneous series so that the evidence supporting the performance of this combined treatment is still poor. Median Overall and Disease Free Survivals of up to 64 months and 57 months, respectively have been reported. Although a rate of morbidity of up to 40% has been observed in some series the CRS + HIPEC continues to gain an increased popularity. Several prospective randomized trials are ongoing using the procedure in various time points of the disease. In this review several issues such as the impact of cytoreduction and residual disease (RD) on outcomes as well as the role of HIPEC will be updated from the literature evidence. Some controversial points HIPEC related will also be discussed. Recent experiences regarding the introduction of a more aggressive surgical approach to upper abdomen to resect peritoneal carcinomatosis (PC) allowed increased rates of optimal cytoreduction and has demonstrated an apparent better outcome. This evidence associated with the positive results phase III trial testing normothermic intraperitoneal as first-line chemotherapy is guiding some investigators to propose the CRS + HIPEC in the primary setting. Several prospective phase II and III trials have recently been launched to validate the role of the combined treatment in various time points of disease natural evolution.

Mastectomy with immediate breast reconstruction after neoadjuvant chemotherapy and radiation therapy. A new option for patients with operable invasive breast cancer. Results of a 20 years single institution study.

Abstract: Purpose To evaluate the feasability of immediate breast reconstruction (IBR) following mastectomy after neoadjuvant chemotherapy (NACT) and radiation therapy (RT) for operable invasive breast cancer (OIBC), in terms of incidence of local complications, locoregional control and survival. Patients and methods From 1990 to 2008, 210 patients were treated by NACT, RT and mastectomy with IBR for OIBC. One hundred and seven patients underwent a latissimus dorsi flap with implant (LDI), 56 patients a transverse rectus abdominis musculocutaneous (TRAM) flap, 25 an autologous latissimus dorsi flap (ALD) and 22, a retropectoral implant (RI) reconstruction. Results Forty-six (21.9%) early events were recorded: 20 necrosis, 9 surgical site infections and 6 haematomas, requiring further surgery in 23 patients. More necrosis were observed with TRAM flap reconstructions (p = 0.000004), requiring more surgical revision than LD reconstructions. Seromas represented 42% of early complications in LD reconstructions. Fifty-five patients presented with late complications (26.2%) with mainly implant complications (capsular contracture, infection, dislocation, deflation) (23.6%), requiring reintervention in 14 cases. There were more delayed surgical revisions in RI reconstructions (p = 0.0005). The 5 years overall and disease-free survival rates were respectively 86.7% and 75.6%. Sixty-four patients presented at least one recurrence (30.5%) with 5 local, 9 locoregional and 54 distant relapses. Conclusion This therapeutic sequence does not seem to increase the IBR morbidity nor alter disease-free and overall survival.

MicroRNAs in colorectal cancer: function, dysregulation and potential as novel biomarkers

Abstract: Background MicroRNAs (miRNAs) are short non-coding segments of RNA which are involved in normal cellular development and proliferation. Recent studies have identified altered miRNA expression in both tumour tissues and circulation in the presence of colorectal cancer. These altered expression patterns may serve as novel biomarkers for colorectal cancer. This review explores recent developments in this rapidly evolving field. Methods A thorough literature search was performed to identify studies describing miRNA expression in colorectal cancer. Specific areas of interest included miRNA expression patterns in relation to development, diagnosis, progression and recurrence of disease, and potential future therapeutic applications. Results MiRNAs are associated with the development and progression of colorectal cancer. These may be either overexpressed or underexpressed (depending on the specific miRNA). Although there are fewer published studies regarding circulating miRNAs, these appear to be reflective of alterations in tissue expression and may have a potential role as minimally invasive biomarkers. Conclusion MiRNAs have immense potential for refinement of the current processes for diagnosis, staging and prognostic prediction. They may also provide potential future therapeutic targets in the management of colorectal cancer.

MicroRNA-21 and PDCD4 expression in colorectal cancer

Abstract: Introduction MiRNAs regulate gene expression by binding to target sites and initiating translational repression and/or mRNA degradation. Studies have shown that miR-21 exerts its oncogenic activity by targeting the PDCD4 tumour suppressor 3′-UTR. However, the mechanism of this regulation is poorly understood. In colorectal cancer, loss of PDCD4 has been reported in association with increased tumour aggressiveness and poor prognosis. The purpose of this study was to delineate the interaction between PDCD4 and its oncogenic modulator miR-21 in colorectal cancer. Methods A cohort of 48 colorectal tumours, 61 normal tissues and 7 polyps were profiled for miR-21 and PDCD4 gene expression. A subset of 48 specimens (31 tumours and 17 normal tissues) were analysed for PDCD4 protein expression by immunohistochemistry. Results A significant inverse relationship between miR-21 and PDCD4 gene expression (p < 0.001) was identified by RT-qPCR. In addition, significant reduction of PDCD4 (p < 0.001) expression and reciprocal upregulation of miR-21 (p = 0.005) in a progressive manner from tumour-polyp-normal mucosae was identified. Analysis of protein expression by IHC revealed loss of PDCD4 staining in tumour tissue. Patients with disease recurrence had higher levels of miR-21. Conclusion This study demonstrates the inverse relationship between miR-21 and PDCD4, thus suggesting that miR-21 post-transcriptionally modulates PDCD4 via mRNA degradation. Pharmacological manipulation of the miR-21/PDCD4 axis could represent a novel therapeutic strategy in the treatment of colorectal cancer.

Survival after lung metastasectomy for colorectal cancer: importance of previous liver metastasis as a prognostic factor.

Abstract: Aims To analyse patient survival after the resection of lung metastases from colorectal carcinoma and specifically to verify whether presence of liver metastasis prior to lung metastasectomy affects survival. Methods All patients who, between 1998 and 2008, underwent lung metastasectomy due to colorectal cancer were included in the study. Kaplan–Meier survival analysis was performed with the log-rank test and Cox regression multivariate analysis. Results During this period, 101 metastasectomies were performed on 84 patients. The median age of patients was 65.4 years, and 60% of patients were male. The 30-day mortality rate was 2%, and incidence of complications was 7%. The overall survival was 72 months, with 3-and 5-year survival rates of 70% and 54%, respectively. A total of 17 patients (20%) had previously undergone resection of liver metastasis. No significant differences were found in the distribution of what were supposed to be the main variables between patients with and without previous hepatic metastases. Multivariate analysis identified the following statistically significant factors affecting survival: previous liver metastasectomy (p = 0.03), tumour-infiltrated pulmonary lymph nodes (p = 0.04), disease-free interval ≥ 48 months (p = 0.03), and presence of more than one lung metastasis (p Conclusions A previous history of liver metastasis shortens survival after lung metastasectomy. The time between hepatic resection and lung metastasectomy does not affect survival; however, patients with synchronous liver metastasis and colorectal neoplasia have poorer survival rates than those with metachronous disease.

Prognostic significance of Ki67 index after neoadjuvant chemotherapy in breast cancer

Abstract: Purpose Recently, Ki67 index (cell proliferation marker) has been attracting a considerable attention as a prognostic factor in breast cancer but the prognostic significance of Ki67 after neoadjuvant chemotherapy (NAC) has rarely been examined. Experimental design Primary breast cancer patients ( n = 102) treated with NAC (sequential paclitaxel 12 cycles (q1w) and 5-FU/epirubicin/cyclophosphamide 4 cycles (q3w)) were recruited in the study. Ki67, estrogen receptor (ER) and progesterone receptor (PR) and breast cancer resistant protein (BCRP) and P-glycoprotein were determined by immunohistochemistry and HER2 was determined by FISH in tumor tissues obtained before and after NAC, and their association with patient prognosis (relapse-free survival) was examined. Results Of the 102 patients, pCR was achieved in 30 (29.4%). In the 72 non-pCR patients, Ki67 index significantly ( P P = 0.022). Multivariate analysis has shown that Ki67 index after NAC is a marginally significant ( P = 0.05) prognostic factor and that other biomarkers including ER, PR, BCRP, and P-glycoprotein before and after NAC are not significant. Conclusions Ki67 after NAC, but not before NAC, is prognostic in breast cancer patients, and might be clinically useful in the prognosis prediction of patients who do not achieve pCR after NAC. On the other hand, BCRP and P-glycoprotein before and after NAC are unlikely to be useful as prognostic factors in these patients.

Post-operative imatinib in patients with intermediate or high risk gastrointestinal stromal tumor.

Abstract: Aims This study aims to determine whether adjuvant treatment with imatinib improves recurrence-free survival (RFS) in Chinese patients undergoing complete resection of localized primary gastrointestinal stromal tumor (GIST) compared with those not receiving adjuvant therapy. We also sought a correlation between c-KIT mutations and RFS. Methods Patients who had undergone complete tumor resection with intermediate or high risk of recurrence were enrolled in a single-center, non-randomized, prospective study. Patients either received adjuvant imatinib therapy (400 mg once-daily) for 3 years or did not. Mutation analyses of c-KIT were performed on available archival tumor samples. Results 105 patients were enrolled: 56 in the treatment group and 49 in the control group. Median follow-up was 45(43.1–46.9) months. RFS at 1, 2 and 3 years were higher in the treatment group than in the control group (100% vs. 90% at 1 year; 96% vs. 57% at 2 years; 89% versus 48% at 3 years, P P P = 0.039, HR = 0.254). Conclusions Adjuvant imatinib can improve 1-, 2- and 3-year RFS rates in patients at intermediate or high risk of recurrence after complete tumor resection. Clinical Trials Registration Number: ChiCTR-TCC-00000582

Single nucleotide polymorphisms and mRNA expression of VEGF-A in papillary thyroid carcinoma: Potential markers for aggressive phenotypes

Abstract: BACKGROUND AND OBJECTIVES: Polymorphisms of the VEGF gene are known to affect the biological behaviour of cancers but have seldom been studied in thyroid cancer. The aim of the current study is to evaluate the prevalence and relevance of VEGF-A polymorphisms and mRNA expression in papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: Genomic DNA and total RNA were isolated from paraffin-embedded tissue from 91 PTC (51 conventional PTC and 40 follicular variant) and 78 control thyroid tissues. Three DNA polymorphisms (+936C > T, +405C > G and -141A > C) in the 3' and 5' untranslated region (3'-UTR, 5'-UTR) of VEGF-A were studied using PCR and RFLP. Also, the mRNA expression of VEGF-A in these tissues was studied by real-time PCR. RESULTS: Distribution of polymorphisms in the 5'-UTR (VEGF-VEGF -141A > C and +405C > G) and 3'-UTR (VEGF +936C > T) were all significantly different in PTC and benign thyroid tissue (p = 0.0001, 0.001 and 0.028 respectively). The VEGF -141 C allele was more common in PTC with lymph node metastases (p = 0.026). VEGF + 405 Galleles andVEGF +936 CC genotype were more common in PTC of advanced pathological staging (p = 0.018 and 0.017 respectively). Also, increased expression of VEGF-A mRNA was noted in PTC compared to control (p = 0.009). Within the group of patients with conventional PTC, those with lymph nodal metastases had a higher level of VEGF-A mRNA expression than other patients (p = 0.0003). CONCLUSION: These findings suggest that VEGF polymorphisms and mRNA expression may predict the aggressiveness behaviour of thyroid cancer.

Variation in case-mix between hospitals treating colorectal cancer patients in the Netherlands.

Abstract: AIMS The purpose of this study was to determine how expected mortality based on case-mix varies between colorectal cancer patients treated in non-teaching, teaching and university hospitals, or high, intermediate and low-volume hospitals in the Netherlands. MATERIAL AND METHODS We used the database of the Dutch Surgical Colorectal Audit 2010. Factors predicting mortality after colon and rectum carcinoma resections were identified using logistic regression models. Using these models, expected mortality was calculated for each patient. RESULTS 8580 patients treated in 90 hospitals were included in the analysis. For colon carcinoma, hospitals' expected mortality ranged from 1.5 to 14%. Average expected mortality was lower in patients treated in high-volume hospitals than in low-volume hospitals (5.0 vs. 4.3%, p < 0.05). For rectum carcinoma, hospitals expected mortality varied from 0.5 to 7.5%. Average expected mortality was higher in patients treated in non-teaching and teaching hospitals than in university hospitals (2.7 and 2.3 vs. 1.3%, p < 0.01). Furthermore, rectum carcinoma patients treated in high-volume hospitals had a higher expected mortality than patients treated in low-volume hospitals (2.6 vs. 2.2% p < 0.05). We found no differences in risk-adjusted mortality. CONCLUSIONS High-risk patients are not evenly distributed between hospitals. Using the expected mortality as an integrated measure for case-mix can help to gain insight in where high-risk patients go. The large variation in expected mortality between individual hospitals, hospital types and volume groups underlines the need for risk-adjustment when comparing hospital performances.

Clinical significance of tumor suppressor PTEN in colorectal carcinoma.

Abstract: Background It has been demonstrated that the deletion, mutation, hypermethylation and subcellular location of the tumor suppressor phosphatase and tensin homologue (PTEN) are closely correlated with carcinogenesis, progression and prognosis of malignancy. Both mutation and the microsatellite instability of the PTEN gene influence regulation of the PI3K/Akt signaling pathway. This study investigated whether loss of nuclear PTEN is correlated with chemosensitivity, clinicopathological parameters and survival. Methods Intracellular levels of PTEN of multiple cell lines of colorectal carcinoma (CRC) were evaluated by Western blotting and immunocytochemistry. The chemosensitivity of cell lines with various expression levels of PTEN was evaluated using 5-flurouracil (5-FU), oxaliplatin and irinotecan (CPT), and clinical significance was evaluated by immunohistochemical analysis of 133 CRC specimens. Results Colon cancer cell lines HT-29, LoVo and SW480 differed in expression of PTEN, with high, moderate and low levels, respectively. HT-29 and LoVo PTEN expression was suppressed by a low concentration of 5-FU and oxaliplatin; however, SW480 was insensitive to these chemotherapeutic agents. Nuclear PTEN was overexpressed in most (>80%) normal colon mucosa samples, but the incidence significantly decreased (89.2% → 53.4%) in the CRC group. PTEN in the nucleus was negatively correlated with tumor size and vascular invasion in CRC, and CRC patients with negative PTEN expression in the nucleus exhibited poor survival. Conclusion Cell lines with a high expression of PTEN are sensitive to chemotherapy with 5-FU and oxaliplatin. Nuclear PTEN expression gradually decreases after malignant transformation, and loss of PTEN expression in the nucleus is associated with tumor progression and poor clinical outcome in CRC.

Impact on survival of the number of lymph nodes removed in patients with node-negative gastric cancer submitted to extended lymph node dissection

Abstract: Purpose This study was designed to establish whether the number of lymph nodes removed has an effect on prognosis in patients with node-negative gastric cancer. Patients and Methods We retrospectively analysed data of 114 consecutive patients who underwent gastrectomy and extended lymph node dissection for node-negative adenocarcinoma of the stomach between 2000 and 2005. Standard survival methods and restricted cubic spline multivariable Cox regression models were applied. Results Median age was 63 years and 67 patients out of 114 (59%) were males. Median number of dissected LNs was 22 (range 2–73). Median follow-up was 76 months. Patients who had ≤15 nodes removed had significantly worse distant disease-free survival, disease-free survival and overall survival at multivariable analysis than other patients. The results did not change when pT1 and pT2-3 cancer patients were analysed separately. The risk of distant metastases decreased as the number of dissected lymph nodes increased (>15). Conclusions More extended lymph node resection offered survival benefit even in the subgroup of patients with early stage disease. Lymphadenectomy involving more than 15 lymph nodes should be performed for the treatment of node-negative gastric cancer. Synopsis The impact on survival of the number of lymph nodes removed in patients with node-negative gastric cancer has not been established. This study suggests that more extended lymph node resection offers protection, as patients who had ≤15 nodes removed had significantly worse disease-free survival and overall survival at multivariate analysis than patients in whom >15 nodes were removed.