Primary Open Versus Closed Implantation Strategy for Totally Implantable Venous Access Ports: The Multicentre Randomized Controlled PORTAS-3 Trial (DRKS 00004900).

OBJECTIVES: PORTAS-3 was designed to compare the frequency of pneumothorax or haemothorax in a primary open versus closed strategy for port implantation. BACKGROUND DATA: The implantation strategy for totally implantable venous access ports with the optimal benefit/risk ratio remains unclear. METHODS: PORTAS-3 was a multicentre, randomized, controlled, parallel-group superiority trial. Adult patients with oncological disease scheduled for elective port implantation were randomized to a primary open or closed strategy. Primary endpoint was the rate of pneumothorax or haemothorax. Assuming a difference of 2.5% between the 2 groups, a sample size of 1154 patients was needed to prove superiority of the open group. A logistic regression model after the intention-to-treat principle was applied for analysis of the primary endpoint. RESULTS: Between November 9, 2014 and September 5, 2016, 1205 patients were randomized. Of these, 1159 (open n = 583; closed n = 576) were finally analyzed. The rate of pneumothorax or haemothorax was significantly reduced with the open strategy [odds ratio 0.27, 95% confidence interval (CI) 0.09-0.88; P = 0.029]. Operation time was shorter for the closed strategy. Primary success rates, tolerability, morbidity, dose rate of radiation, and 30-day mortality did not differ significantly between the groups. CONCLUSION: A primary open strategy by cut-down of the cephalic vein, if necessary enhanced by a modified Seldinger technique, reduces the frequency of pneumothorax or haemothorax after central venous port implantation significantly compared with a closed strategy by primary puncture of the subclavian vein without routine sonographic guidance. Therefore, open surgical cut-down should be the reference standard for port implantation in comparable cohorts. TRIAL REGISTRATION: German Clinical Trials Register DRKS 00004900.

Detection of lymph node involvement by cytokeratin immunohistochemistry is an independent prognostic factor after curative resection of esophageal cancer.

BACKGROUND: Involved lymph nodes (LN) are a negative prognostic factor in esophageal cancers. To assess the role of nodal micrometastases, we performed immunohistochemical analyses of LN after resection of node-negative esophageal cancers and correlated the results with survival. METHODS: Seventy patients with esophageal cancer after curative resection and conventionally negative nodes were included. The LN were examined with six consecutive sections (three hematoxylin and eosin (HE) stained and three stained immunohistochemically with the cytokeratin (CK) antibodies AE1/AE3). Survival was evaluated uni- and multivariately. Median follow-up was 4.1 years. RESULTS: Immunohistochemical analysis showed CK-positive LN in 16 (23%) patients. Of those 16 cases with CK-positive LN, nine had aviable macrometastases, ten had CK-positive scars/fibrosis and five had viable micrometastases. All patients with aviable macrometastases or CK-positive scars/fibrosis had undergone neoadjuvant chemoradiation. Five-year survival was 48% in all patients. In univariate analysis, survival was worse in patients with CK-positive LN (5-year survival of 30% vs. 54% in CK-negative LN; p < 0.02) and in patients with squamous cell carcinoma (5-year survival of 38% vs. 75% in adenocarcinoma; p = 0.05). Multivariate analysis revealed CK-positive LN (p = 0.02) and (borderline) squamous cell carcinoma (p = 0.06) as negative prognostic factors. CONCLUSIONS: The immunohistochemical analysis of LN may detect (viable or non-viable) tumor cells in lymph nodes after resection of conventionally node-negative esophageal cancers. Conventional pathological analysis by HE, therefore, understages esophageal cancer in these cases. The detection of CK-positive cells in resected LN is an independent prognostic factor in otherwise LN-negative esophageal cancer.

Outcome after resection of hepatic and pulmonary metastases of colorectal cancer.

INTRODUCTION: Multimodal therapies (especially surgery of metastases and "aggressive" chemotherapy) in patients with metastases of colorectal cancers (CRC) are increasingly performed and may provide long-term survival in selected patients with more than one location of metastases. In the current literature, there are only few studies with relatively low patient numbers reporting on the outcome after resection of both hepatic and pulmonary metastases of CRC. We therefore evaluated survival of patients who underwent sequential resection of hepatic and pulmonary metastases under potentially curative intention. MATERIAL AND METHODS: From 1987 until 2006, 44 patients (32% female; median age, 58 years) with hepatic and pulmonary CRC metastases underwent resections at both metastatic sites. The primary CRCs were in 50% rectal and in 50% colonic carcinomas (61% node positive, all with free resection margins). Metastases occurred synchronously (regarding primary CRC) in 32% of the patients. In 86%, liver resection was performed prior to pulmonary resection. The first resection of metastases was performed a median of 16 months after resection of the primary CRC; the median interval between the first and the second resection of metastases was 7 months. Forty-seven percent of the patients also underwent at least a third metastasectomy. During resection of the first and second site of metastases, free margins were achieved in 98% and 95%, respectively. Survival analysis was performed using Kaplan-Meier and Cox regression methods. RESULTS: The 5-year survival rates (SV) were 64% after initial surgery of CRC, 42% after the first resection of metastases, and 27% after the last metastasectomy. Patients with synchronous metastases had a 5-year SV after first metastasectomy of 43% and in patients with metachronous metastases of 41% (n.s.). The location of the primary tumor (20% 5-year SV in rectal vs. 57% in colonic cancer; p < 0.02) and the lung as primary site of metastatic disease (5-year SV 0% vs. 60% in patients with primarily hepatic metastases only; p < 0.001) significantly influenced survival in univariate analysis. Patients with rectal cancer had a significantly higher frequency of the lung as first metastatic site (46%) compared to patients with colonic cancer (14%; p < 0.03). Multivariate survival analysis revealed the lung as first metastatic site and as the sole significant independent factor for the outcome (p < 0.001; relative risk vs. liver first metastases 4.7). CONCLUSION: In selected patients with metastasized CRC resection of both hepatic and pulmonary metastases may improve survival rates or even provide long-term survival. Patients with lung as the first site of metastatic disease (either lung only or in combination with hepatic metastases) have a significantly worse outcome than patients with metastases primarily confined to the liver.

[Prognostic role of vascularisation and proliferation in rectal cancer with liver metastasis]. / A vascularisatio és a proliferatio prognosztikai szerepe májmetastasist adó rectumcarcinomákban.

BACKGROUND: The present study was designed to provide an analysis of factors for angiogenesis and proliferation. MATERIAL AND METHOD: We analyzed tumor tissues from 37 rectal cancer patients with concurrent or subsequent liver metastasis underwent preoperative radiotherapy, surgery and adjuvant chemotherapy. Immunohistochemistry was used for expression of proliferation (staining with anti-Ki67: MIB-1) and for detection of microvessel density (MVD, expressed by CD34). Clinicopathological findings were compared with outcome with emphasis to IHC. RESULTS: A vascular enumeration and pN status and the time of presence of the metastases has shown prognostic role along with the factors above. Increased proliferative activity of the tumor as expressed by MIB-1 staining has no prognostic value, similarly to the localization of tumor, gender, age or grading. SUMMARY: Different prognostic and predictive factors in colorectal cancer have been reported. Higher pN status and tumor vascularisation has been linked to poor prognosis in overall survival and tumor recurrence.

Possible role of human papilloma virus infection in response to neoadjuvant therapy in patients with esophageal cancer.

BACKGROUND/AIMS: Human papilloma virus (HPV) infection in esophageal cancer cases has been found in 0-70%, depending on different methods and geographical variances. Complete pathological response has been found in 30% of cases after neoadjuvant chemo-radiation (CRX). The aim of this study was to discover a possible relation between HPV-infection and response. METHODOLOGY: DNA was obtained from 26 esophageal cancer patients undergoing CRX and surgery. Polymerase chain reaction (PCR) and Southern Blot hybridization was used to detect HPV-infection (HPV-16 and -18). Clinicopathological parameters, disease-free survival and overall survival were also analyzed. RESULTS: Complete response (26.9%) and partial response (38.5%) after CRX was correlated significantly with better prognosis. Six patients had HPV-infection (3 from the CR- and 3 from PR-group). CONCLUSIONS: There was correlation between HPV-infection and response, but further analyses are necessary. Both responder-groups had a significantly better prognosis than non-responders.

Sentinel lymph node biopsy in colon cancer: a prospective multicenter trial.

INTRODUCTION: The clinical impact of sentinel lymph node biopsy (SLNB) in colon cancer is still controversial. The purpose of this prospective multicenter trial was to evaluate its clinical value to predict the nodal status and identify factors that influence these results. METHODS: Colon cancer patients without prior colorectal surgery or irradiation were eligible. The sentinel lymph node (SLN) was identified intraoperatively by subserosal blue dye injection around the tumor. The SLN underwent step sections and immunohistochemistry (IHC), if classified free of metastases after routine hematoxylin and eosin examination. RESULTS: At least one SLN (median, n = 2) was identified in 268 of 315 enrolled patients (detection rate, 85%). Center experience, lymphovascular invasion, body mass index (BMI), and learning curve were positively associated with the detection rate. The false-negative rate to identify pN+ patients by SLNB was 46% (38 of 82). BMI showed a significant association to the false-negative rate (P < 0.0001), the number of tumor-involved lymph nodes was inversely associated. If only slim patients (BMI < or =24) were investigated in experienced centers (>22 patients enrolled), the sensitivity increased to 88% (14 of 16). Moreover, 21% (30 of 141) of the patients, classified as pN0 by routine histopathology, revealed micrometastases or isolated tumor cells (MM/ITC) in the SLN. CONCLUSIONS: The contribution of SLNB to conventional nodal staging of colon cancer patients is still unspecified. Technical problems have to be resolved before a definite conclusion can be drawn in this regard. However, SLNB identifies about one fourth of stage II patients to reveal MM/ITC in lymph nodes. Further studies must clarify the clinical impact of these findings in terms of prognosis and the indication of adjuvant therapy.