Retrospective analysis of the incidence of appendiceal neoplasm and malignancy in patients treated for suspected acute appendicitis.

BACKGROUND: Nonoperative management of uncomplicated appendicitis is currently being promoted as treatment option, albeit 0.7-2.5% of appendectomies performed due to suspected acute appendicitis show histologically malignant findings. The purpose of this study was to investigate the incidence of neoplasm and malignancy of the appendix in patients presenting with suspected acute appendicitis in real world setting. METHODS: This is a retrospective single-centre investigation of 457 patients undergoing appendectomy between the years 2017-2020. The patients' demographics, symptoms and diagnosis, intraoperative findings, and histopathological results were analysed. RESULTS: In 3.7% (n = 17) histological analysis revealed neoplasms or malignancies. Median age was 48 years (20-90 years), without sex predominance. Leukocytes (11.3 ± 3.7 G/l) and C-reactive protein (54.2 ± 69.0 mg/l) were elevated. Histological analysis revealed low-grade mucinous appendiceal neoplasia (n = 3), sessile serrated adenoma of the appendix (n = 3), neuroendocrine tumours (n = 7), appendiceal adenocarcinoma of intestinal type (n = 3), and goblet cell carcinoma (n = 1). Additional treatment varied between no treatment or follow-up due to early tumour stage (n = 4), follow-up care (n = 3), additional surgical treatment (n = 8), or best supportive care (n = 2). CONCLUSIONS: Preoperative diagnosis of appendiceal tumours is difficult. Nonoperative management of patients with acute, uncomplicated appendicitis potentially prevents the correct diagnosis of malignant appendiceal pathologies. Therefore, close follow-up or surgical removal of the appendix is mandatory.

The Simultaneous Presence of Isolated Tumour Cells and Bone Marrow Micrometastases in Stage I and II Colon Cancer-Challenging the Theory of a Chronological Pathway of Tumour Cell Dissemination.

BACKGROUND: According to the common tenet, tumour progression is a chronological process starting with lymphatic invasion. In this respect, the meaning of bone marrow micrometastases (BMM) in patients with lymph node negative colon cancer (CC) is unclear. This study examines the relationship of isolated tumour cells (ITC) in sentinel lymph nodes (SLN) and BMM in patients in early CC. METHODS: BM aspirates were taken from both pelvic crests and in vivo SLN mapping was done during open oncologic colon resection in patients with stage I and II CC. Stainings were performed with the pancytokeratin markers A45-B/B3 and AE1/AE3 as well as H&E. The correlation between the occurrence of ITC+ and BMM+ and their effects on survival was examined using Cox regression analysis. RESULTS: In a total of 78 patients with stage I and II CC, 11 patients (14%) were ITC+, 29 patients (37%) BMM+. Of these patients, only two demonstrated simultaneous ITC+ /BMM+. The occurrence of BMM+ was neither associated with ITC+ in standard correlation (kappa = - 0.13 [95% confidence interval [CI] = - 0.4-0.14], p = 0.342) nor univariate (odds ratio [OR] = 0.39, 95%CI:0.07-1.50, p = 0.180) or multivariate (OR = 0.58, 95%CI: 0.09-2.95, p = 0.519) analyses. Combined detection of ITC+ /BMM+ demonstrated the poorest overall (HR = 61.60, 95%CI:17.69-214.52, p = 0.032) and recurrence free survival (HR = 61.60, 95%CI: 17.69-214.5, p = 0.032). CONCLUSIONS: These results indicate that simultaneous and not interdependent presence of very early lymphatic and haematologic tumour spread may be considered as a relevant prognostic risk factor for patients with stage I and II CC, thereby suggesting the possible need to reconsider the common assumptions on tumour spread proposed by the prevalent theory of sequential tumour progression.

Evaluation of the prognostic relevance of the recommended minimum number of lymph nodes in colorectal cancer-a propensity score analysis.

PURPOSE: Nodal status in colorectal cancer (CRC) is an important prognostic factor, and adequate lymph node (LN) staging is crucial. Whether the number of resected and analysed LN has a direct impact on overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) is much discussed. Guidelines request a minimum number of 12 LN to be analysed. Whether that threshold marks a prognostic relevant cut-off remains unknown. METHODS: Patients operated for stage I-III CRC were identified from a prospectively maintained database. The impact of the number of analysed LN on OS, CSS and DFS was assessed using Cox regression and propensity score analysis. RESULTS: Of the 687 patients, 81.8% had ≥ 12 LN resected and analysed. Median LN yield was 17.0 (IQR 13.0-23.0). Resection and analysis of ≥ 12 LN was associated with improved OS (HR = 0.73, 95% CI: 0.56-0.95, p = 0.033), CSS (HR 0.52, 95% CI: 0.31-0.85, p = 0.030) and DFS (HR = 0.73, 95% CI: 0.57-0.95, p = 0.030) in multivariate Cox analysis. After adjusting for biasing factors with propensity score matching, resection of ≥ 12 LN was significantly associated with improved OS (HR = 0.59; 95% CI: 0.43-0.81; p = 0.002), CSS (HR = 0.34; 95% CI: 0.20-0.60; p < 0.001) and DFS (HR = 0.55; 95% CI: 0.41-0.74; p < 0.001) compared to patients with < 12 LN. CONCLUSION: Eliminating biasing factors by a propensity score matching analysis underlines the prognostic importance of the number of analysed LN. The set threshold marks the minimum number of required LN but nevertheless represents a cut-off regarding outcome in stage I-III CRC. This analysis therefore highlights the significance and importance of adherence to surgical oncological standards.

Molecular Lymph Node Staging with One-Step Nucleic Acid Amplification and its Prognostic Value for Patients with Colon Cancer: The First Follow-up Study.

BACKGROUND: Molecular lymph node workup with one-step nucleic acid amplification (OSNA) is a validated diagnostic adjunct in breast cancer and also appealing for colon cancer (CC) staging. This study, for the first time, evaluates the prognostic value of OSNA in CC. PATIENTS AND METHODS: The retrospective study includes patients with stage I-III CC from three centres. Lymph nodes were investigated with haematoxylin and eosin (H&E) and with OSNA, applying a 250 copies/µL threshold of CK19 mRNA. Diagnostic value of H&E and OSNA was assessed by survival analysis, sensitivity, specificity and time-dependent receiver operating characteristic curves. RESULTS: Eighty-seven patients were included [mean follow-up 53.4 months (± 24.9)]. Disease recurrence occurred in 16.1% after 19.8 months (± 12.3). Staging with H&E independently predicted worse cancer-specific survival in multivariate analysis (HR = 10.77, 95% CI 1.07-108.7, p = 0.019) but not OSNA (HR = 3.08, 95% CI 0.26-36.07, p = 0.197). With cancer-specific death or recurrence as gold standard, H&E sensitivity was 46.7% (95% CI 21.3-73.4%) and specificity 84.7% (95% CI 74.3-92.1%). OSNA sensitivity and specificity were 60.0% (95% CI 32.3-83.7%) and 75.0% (95% CI 63.4-84.5%), respectively. CONCLUSIONS: In patients with CC, OSNA does not add relevant prognostic value to conventional H&E contrasting findings in other cancers. Further studies should assess lower thresholds for OSNA (< 250 copies/µL).

Improved quality of colon cancer surveillance after implementation of a personalized surveillance schedule.

BACKGROUND: Early detection of recurrence through surveillance after curative surgery for primary colon cancer is recommended. We previously reported inadequate quality of surveillance among patients operated for colon cancer. These poor results led to the introduction of a personalized surveillance schedule. This study reassesses the quality of surveillance after the introduction of the personalized schedule. PATIENTS AND METHODS: A total of 93 patients undergoing curative surgery for colon cancer between January 2009 and December 2014 (prospective data registration) were included in this retrospective single-center cohort study. Written informed consent was given by all patients. Compliance with surveillance was compared with national guidelines, as well as with the previous results and analyzed depending on where surveillance was conducted (general practitioner or outpatient clinic). RESULTS: Adherence to surveillance was higher when performed by oncologists compared to general practitioners with an odds ratio (OR), 6.03 (95%CI: 3.41-10.67, P = .001). Compared with the previous study, adherence to surveillance was significantly higher in the later cohort with an OR = 4.55 (95%CI: 2.50-8.33, P < 0.001). CONCLUSION: This study demonstrates that the implementation of a personalized surveillance schedule improves adherence to recommendations and that awareness can be increased with this simple measure.

Clinical Outcome After Rectal Replacement With Side-to-End, Colon-J-Pouch, or Straight Colorectal Anastomosis Following Total Mesorectal Excision: A Swiss Prospective, Randomized, Multicenter Trial (SAKK 40/04).

OBJECTIVE: To compare, in a phase 3, prospective, randomized, multi-center clinical trial functional outcome of reconstruction procedures following total mesorectal excision (TME). SUMMARY BACKGROUND DATA: Intestinal continuity reconstruction following TME is accompanied by postoperative defecation dysfunctions known as "anterior resection syndrome." Commonly used reconstruction techniques are straight colorectal anastomosis (SCA), colon J -pouch (CJP), and side-to-end anastomosis (SEA). Comparison of their functional outcomes in prospective, randomized, multi-center studies, including long-term assessments, is lacking. METHODS: Patients requiring TME for histologically proven rectal tumor, with or without neoadjuvant treatment, age ≥ 18 years, normal sphincter function without history of incontinence, any pretreatment staging or adenoma, expected R0-resection, were randomized for standardized SCA, CJP, or SEA procedures. Primary endpoint was comparison of composite evacuation scores 12 months after TME. Comparison of composite evacuation and incontinence scores at 6, 18 and 24 months after surgery, morbidity, and overall survival represented secondary endpoints. Analysis was based on "per protocol" (PP) population, fully complying with trial requirements, and intention-to treat (ITT) population. RESULTS: Three hundred thirty-six patients from 15 hospitals were randomized. PP population included 257 patients (JCP = 63; SEA = 95; SCA = 99). Composite evacuation scores of PP and ITT populations did not show statistically significant differences among the 3 groups at any time point. Similarly, composite incontinence scores for PP and ITT populations showed no statistically significant difference among the 3 trial arms at any time point. CONCLUSIONS: Within boundaries of investigated procedures, surgeons in charge may continue to perform reconstruction of intestinal continuity following TME at their technical preference.

Quality of Life After Total Mesorectal Excision and Rectal Replacement: Comparing Side-to-End, Colon J-Pouch and Straight Colorectal Reconstruction in a Randomized, Phase III Trial (SAKK 40/04).

BACKGROUND: Functional outcomes of different reconstruction techniques have an impact on patients' quality of life (QoL), but information on long-term QoL is lacking. We compared QoL among three reconstruction techniques after total mesorectal excision (TME). METHODS: Quality of life was assessed within a randomized, multicenter trial comparing rectal surgery using side-to-end anastomosis (SEA), colon J-pouch (CJP), and straight colorectal anastomosis (SCA) by the Functional Assessment of Cancer Therapy-Colorectal scale (FACT-C) before randomization and every 6 months up to 2 years post-TME. The primary QoL endpoint was the change in the Trial Outcome Index (TOI), including the FACT-C subscales of physical and functional well-being and colorectal cancer symptoms (CSS), from baseline to month 12. Pair-wise comparisons of changes from baseline (presurgery) to each timepoint between the three arms were analyzed by Mann-Whitney tests. RESULTS: For the QoL analysis, 257 of 336 randomized patients were in the per protocol evaluation (SEA = 95; CJP = 63; SCA = 99). Significant differences between the reconstruction techniques were found for selected QoL scales up to 12 months, all in favor of CJP. Patients with SEA or SCA reported a clinically relevant deterioration for TOI and CSS at 6 months, those with SCA for CSS also at 12 months after TME. Patients with CJP remained stable. CONCLUSIONS: Although the three reconstruction techniques differ in their effects on QoL at months 6 and 12, these differences did not persist over the whole observation period of 24 months. Patients with a colon J-pouch may benefit with respect to QoL in the short-term.

Lymph node ratio is inferior to pN-stage in predicting outcome in colon cancer patients with high numbers of analyzed lymph nodes.

BACKGROUND: The lymph node ratio (LNR), i.e. the number of positive lymph nodes (LN) divided by the total number of analyzed LN, has been described as a strong outcome predictor in node-positive colon cancer patients. However, most published analyses are constrained by relatively low numbers of analyzed LN. Therefore, the objective of the present study was to evaluate the prognostic impact of LNR in colon cancer patients with high numbers of analyzed LN. METHODS: One hundred sixty-six colon cancer patients underwent open colon resection. All node-positive patients were analyzed for this study. The number of analyzed LN, of positive LN, the disease-free (DFS) and overall survival (OS) time were prospectively recorded. Patients were dichotomously allocated to a high or a low LNR-group, respectively, with the median LNR (0.125) as a cut-off value. Median follow-up was 34.3 months. RESULTS: Fifty-eight patients (34.9%) were node-positive. The median number of analyzed LN was 23 (range 8-54). DFS and OS were significantly shorter in pN2 vs pN1 patients (p < 0.001, and p = 0.001, respectively), and in LNR high vs low patients (p = 0.032, and p = 0.034, respectively). pN2 (vs pN1) disease showed hazard ratios (HR) of 6.2 (p < 0.001), and 6.8 (p < 0.005; for DFS and OS, respectively), while LNR high (vs low) showed HR of 3.0 (p =0.041), and 4.5 (p = 0.054). CONCLUSIONS: LNR is a reasonable outcome predictor in node-positive colon cancer patients. However, LNR is inferior to pN-stage in predicting survival in patients with high number of harvested lymph nodes.

Sentinel Lymph Node Mapping with Isosulfan Blue or Indocyanine Green in Colon Cancer Shows Comparable Results and Identifies Patients with Decreased Survival: A Prospective Single-Center Trial.

BACKGROUND: Sentinel lymph node (SLN) mapping was reported to improve lymph node staging in colon cancer. This study compares isosulfan blue (IB) with indocyanine green (ICG)-based SLN-mapping and assesses the prognostic value of isolated tumor cells (ITC) and micro-metastases in upstaged patients. METHODS: A total of 220 stage I-III colon cancer patients were included in this prospective single-center study. In 170 patients, SLN-mapping was performed in vivo with IB and in 50 patients ex vivo with ICG. Three levels of each SLN were stained with H&E. If negative for tumor infiltration, immunostaining for cytokeratin (AE1/3; cytokeratin-19) was performed. RESULTS: SLN detection rate for IB and ICG was 100 and 98%, respectively. Accuracy and sensitivity was 88 and 75% for IB, 82 and 64% for ICG, respectively (p = 0.244). Overall, 149 (68%) patients were node negative. In these patients, ITC and micro-metastases were detected in 26% (31/129) with IB and 17% (5/29) with ICG (p = 0.469). Patients with ITC and micro-metastases did show decreased overall survival (hazard ratio = 1.96, p = 0.09) compared to node negative disease. CONCLUSIONS: This study demonstrates a high diagnostic accuracy for both the IB and the ICG SLN-mapping. SLN-mapping upstaged a quarter of patients with node negative colon cancer, and the detected ITC and micro-metastases were an independent negative prognostic marker in multivariate analysis.

Intranodal Mapping Using Carbon Dye Results in More Accurate Lymph Node Staging in Colon Cancer Patients.

INTRODUCTION: Small nodal tumor infiltrates (SNTI)-defined as isolated tumor cells and micrometastases-are associated with worse disease-free and overall survival in stage I and II colon cancer patients. Their detection, however, remains challenging. The objective of the present study was to evaluate whether there is a correlation between the location of SNTI and phagocytosed carbon dye particles in sentinel lymph nodes (SLN) of colon cancer patients. MATERIALS AND METHODS: Isosulfan blue and carbon dye were injected intraoperatively near the tumor to mark the SLN. Serial sections of SLN were stained with hematoxylin-eosin and immunohistochemistry. Intranodal distribution of phagocytosed carbon particles was compared to the presence of SNTI. RESULTS: Of a cohort of 159 patients, 24 patients had SNTI in their lymph nodes (LN). SNTI were found in a total of 116 LN of which 66 were SLN and 50 were non-SLN. In 59, these 116 LN with SNTI phagocytosed carbon dye were found (50.9 %). Phagocytosed carbon dye was identified significantly more often in SLN (49 of 66 SNTI positive SLN) compared to 10 of 50 SNTI positive non-SLN (p < 0.001). In 52 out of 59 LN (88.1 %), phagocytosed carbon dye was in close proximity to SNTI. CONCLUSIONS: In the majority of patients, SNTI are located in the same SLN compartment as phagocytosed carbon dye particles. Our investigation provides evidence that the use of carbon dye facilitates SNTI detection and improves LN staging in colon cancer. Therefore, the concept of intranodal mapping-which has been previously described for melanoma-can be extended to colon cancer patients.

Long-term follow-up of a randomized controlled trial of Lichtenstein's operation versus mesh plug repair for inguinal hernia.

OBJECTIVE: To compare long-term results of Lichtenstein's operation versus mesh plug repair for open inguinal hernia repair. BACKGROUND: The technique of best choice in open prosthetic inguinal hernia repair remains a subject of ongoing debate. METHODS: In this prospective, randomized controlled multicenter trial, patients with primary or recurrent inguinal hernias were randomized to undergo either Lichtenstein's operation or mesh plug repair. The primary endpoint was the long-term recurrence rate. Secondary endpoints included chronic pain, sensibility disorders, and reoperation rate. RESULTS: In total, 697 hernias in 594 patients were randomized (297 patients per group). At a median follow-up of 6.5 years, 528 (76%) operated hernias in 444 (75%) patients were clinically evaluated. The recurrence rate was similar in both groups [mesh plug: 21/268 hernias = 7.8%; Lichtenstein: 21/260 hernias = 8.1%; adjusted odds ratio (OR): 0.92; 95% confidence interval (CI): 0.51, 1.68; P = 0.795]. We did not find a significant difference for chronic pain (Visual Analog Scale score >3) (OR: 0.58; 95% CI: 0.31, 1.09; P = 0.088) and sensory testing (17% vs 20% of patients; OR: 0.53; 95% CI: 0.21, 1.37; P = 0.190) between the 2 groups. There were less reoperations in the mesh plug than in the Lichtenstein's operation group (OR: 0.43; 95% CI: 0.22, 0.85; P = 0.016). CONCLUSIONS: The long-term results of this trial indicate not enough evidence for differences in recurrence, chronic pain, and sensibility disorders between mesh plug repair and Lichtenstein's operation but a lower likelihood for reoperation for mesh plug repair. Estimates for all endpoints were statistically not significant or based on large CIs. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov Identifier: NCT01637818.

Bone marrow micrometastases do not impact disease-free and overall survival in early stage sentinel lymph node-negative breast cancer patients.

BACKGROUND: The presence of lymph node metastases is the most important prognostic factor in early stage breast cancer. Whether bone marrow micrometastases (BMM) impact the prognosis in sentinel lymph node (SLN)-negative breast cancer patients remains a matter of debate. Therefore, the objective of this study was to assess the impact of BMM on 5-year disease-free and overall survival among those patients. METHODS: We analyzed 410 patients with early stage breast cancer (pT1 and pT2 ≤ 3 cm, cN0) who were prospectively enrolled into the Swiss Multicenter Sentinel Lymph Node Study in Breast Cancer between January 2000 and December 2003. All patients underwent bone marrow aspiration followed by SLN biopsy. All SLN were stained with hematoxylin and eosin and immunohistochemistry (Lu-5, CK-22). Cancer cells in the bone marrow were identified after staining with monoclonal antibodies A45-B/B3 against CK-8, -18, and -19. RESULTS: Negative SLN were found in 67.6% (277 of 410) of the enrolled patients. Of those, BMM status was negative in 75.8% (210 of 277) and positive in 24.2% (67 of 277) patients. Median follow-up was 61 (range 11-96) months. Five-year disease-free survival was 93.6% (95% confidence interval [CI] 89.1-96.0) in BMM-negative and 92.2% (95% CI 82.5-96.2) in BMM-positive patients (p = 0.50). Five-year overall survival was 92.7% (95% CI 87.9-95.8) for the BMM-negative and 92.5% (95% CI 83.4-96.2) for the BMM-positive group (p = 0.85). CONCLUSIONS: This is one of the first prospective studies to examine 5-year disease-free and overall survivals in SLN-negative patients in correlation to their BMM status. Although BMM are identified in one of four SLN-negative patients, they do not impact disease-free and overall survival.

Blue dye injection does not induce dissemination of epithelial cells during SLN procedure in colon cancer patients.

INTRODUCTION: The sentinel lymph node (SLN) procedure for colon cancer patients has been increasingly performed over the past decade and has shown advantages regarding lymph node staging. However, there are concerns that the manipulation of the colon, particularly the blue dye injection, results in isolated tumor cell dissemination to lymph nodes. Therefore, the objective of the present study was to evaluate whether the blue dye injection during the SLN procedure for colon cancer induces epithelial cell dissemination to the regional lymph nodes using a fake SLN procedure as a model. METHODS: One hundred seventy-four colon cancer patients underwent open oncologic colon resection and SLN procedure according to a standardized protocol. For the fake SLN procedure, blue dye was injected ex vivo, into the subserosa of a nontumor-bearing segment of the resected colon in 37 unselected patients. Three levels of each SLN were stained with H&E and with the pancytokeratin marker AE1/AE3 and were analyzed for the presence of cytokeratin positive cells. RESULTS: Identification of fake SLN was successful in 32 of the 37 patients (86 %). Seventy fake SLN were histologically confirmed. The median number of fake SLN was 2 per patient (range 1-8). None of the fake SLN showed any disseminated epithelial cells. CONCLUSIONS: The present prospective study provides compelling evidence that blue dye injection during sentinel lymph node procedure for colon cancer does not induce epithelial cell dissemination to the sentinel lymph nodes. Therefore, isolated tumor cells in sentinel lymph nodes result from a true metastatic process.

Factors influencing the success of in vivo sentinel lymph node procedure in colon cancer patients: Swiss prospective, multicenter study sentinel lymph node procedure in colon cancer.

BACKGROUND: The sentinel lymph node (SLN) procedure has the potential to provide relevant improvement in nodal staging in colon cancer patients. However, there remains room for improvement for SLN identification and sensitivity. Therefore, the objective of the present investigation was to analyze factors influencing the success of the SLN procedure in colon cancer patients. METHODS: One hundred seventy-four consecutive colon cancer patients were prospectively enrolled in this multicenter study and underwent in vivo SLN procedure with isosulfan blue 1 % followed by open standard oncologic colon resection. Several patient-, tumor-, and procedure-related factors possibly influencing the SLN identification and sensitivity were analyzed. RESULTS: Sentinel lymph node identification rate and accuracy were 89.1 and 83.9 %, respectively. Successful identification of SLN was significantly associated with the intraoperative visualization of blue lymphatic vessels (p < 0.001) and with female gender (p = 0.024). True positive SLN results were significantly associated with higher numbers of SLN (p = 0.026) and with pN2 stage (p = 0.004). There was a trend toward better sensitivity in patients with lower body mass index (BMI) (p = 0.050). CONCLUSIONS: The success of the SLN procedure in colon cancer patients depends on both procedure-related factors (intraoperative visualization of blue lymphatic vessels, high number of SLN identified) and patient factors (gender, BMI). While patient factors can not be influenced, intraoperative visualization of blue lymphatics and identification of high numbers of SLN are key for a successful SLN procedure.

Sentinel lymph node biopsy in early-stage breast cancer patients: improved survival through better staging?

PURPOSE: The objective of this review is to summarize the evidence demonstrating that the sentinel lymph node (SLN) procedure is not only associated with significantly less morbidity compared to the axillary dissection, but may also result in better staging and improved patient outcomes. METHODS: A search of MedLine and PubMed articles using the terms "sentinel lymph node biopsy", "breast cancer", "staging", "morbidity", "survival", and "outcomes" was conducted. RESULTS: Breast cancer staging includes axillary evaluation as an integral component. Over the past two decades, sentinel lymph node biopsy has evolved as a technique that has an improved morbidity over traditional axillary dissection. The sentinel node(s) undergo a more intensive pathologic examination than traditional axillary contents. In the node-negative group of patients, this may have led to stage migration and potentially improved disease-free and overall survival. CONCLUSION: The SLN procedure is not only associated with significantly less morbidity compared to the axillary lymph node dissection, it may also result in more accurate staging, better axillary tumor control and improved survival.

The Value of Indocyanine Green Image-Guided Surgery in Patients with Primary Liver Tumors and Liver Metastases.

INTRODUCTION: Successful R0 resection is crucial for the survival of patients with primary liver cancer (PLC) or liver metastases. Up to date, surgical resection lacks a sensitive, real-time intraoperative imaging modality to determine R0 resection. Real-time intraoperative visualization with near-infrared light fluorescence (NIRF) using indocyanine green (ICG) may have the potential to meet this demand. This study evaluates the value of ICG visualization in PLC and liver metastases surgery regarding R0 resection rates. MATERIALS AND METHODS: Patients with PLC or liver metastases were included in this prospective cohort study. ICG 10 mg was administered intravenously 24 h before surgery. Real-time intraoperative NIRF visualization was created with the SpectrumTM fluorescence imaging camera system. First, all liver segments were inspected with the fluorescence imaging system and intraoperative ultrasound for identification of the known tumor, as well as additional lesions, and were compared to preoperative MRI images. PLC, liver metastases, and additional lesions were then resected according to oncological principles. In all resected specimens, the resection margins were analyzed with the fluorescence imaging system for ICG-positive spots immediately after resection. Histology of additional detected lesions, as well as ICG fluorescence compared to histological resection margins, were assessed. RESULTS: Of the 66 included patients, median age was 65.5 years (IQR 58.7-73.9), 27 (40.9%) were female, and 18 (27.3%) were operated on laparoscopically. Additional ICG-positive lesions were detected in 23 (35.4%) patients, of which 9 (29%) were malignant. In patients with no fluorescent signal at the resection margin, R0 rate was 93.9%, R1 rate was 6.1%, and R2 rate was 0% compared to an ICG-positive resection margin with an R0 rate of 64.3%, R1 rate of 21.4%, and R2 rate of 14.3% (p = 0.005). One- and two-year overall survival rates were 95.2% and 88.4%, respectively. CONCLUSION: The presented study provides significant evidence that ICG NIRF guidance helps to identify R0 resection intraoperatively. This offers true potential to verify radical resection and improve patient outcomes. Furthermore, implementation of NIRF-guided imaging in liver tumor surgery allows us to detect a considerable amount of additional malignant lesions.

Molecular investigation of lymph nodes in colon cancer patients using one-step nucleic acid amplification (OSNA): a new road to better staging?

BACKGROUND: A new diagnostic system, called one-step nucleic acid amplification (OSNA), has recently been designed to detect cytokeratin 19 mRNA as a surrogate for lymph node metastases. The objective of this prospective investigation was to compare the performance of OSNA with both standard hematoxylin and eosin (H&E) analysis and intensive histopathology in the detection of colon cancer lymph node metastases. METHODS: In total, 313 lymph nodes from 22 consecutive patients with stage I, II, and III colon cancer were assessed. Half of each lymph node was analyzed initially by H&E followed by an intensive histologic workup (5 levels of H&E and immunohistochemistry analyses, the gold standard for the assessment of sensitivity/specificity of OSNA), and the other half was analyzed using OSNA. RESULTS: OSNA was more sensitive in detecting small lymph node tumor infiltrates compared with H&E (11 results were OSNA positive/H&E negative). Compared with intensive histopathology, OSNA had 94.5% sensitivity, 97.6% specificity, and a concordance rate of 97.1%. OSNA resulted in an upstaging of 2 of 13 patients (15.3%) with lymph node-negative colon cancer after standard H&E examination. CONCLUSIONS: OSNA appeared to be a powerful and promising molecular tool for the detection of lymph node metastases in patients with colon cancer. OSNA had similar performance in the detection of lymph node metastases compared with intensive histopathologic investigations and appeared to be superior to standard histology with H&E. Most important, the authors concluded that OSNA may lead to a potential upstaging of >15% of patients with colon cancer.

Sentinel lymph node procedure leads to upstaging of patients with resectable colon cancer: results of the Swiss prospective, multicenter study sentinel lymph node procedure in colon cancer.

BACKGROUND: The value of the sentinel lymph node (SLN) procedure in colon cancer patients remains a matter of debate. The objective of this prospective, multicenter trial was 3-fold: to determine the identification rate and accuracy of the SLN procedure in patients with resectable colon cancer; to evaluate the learning curve of the SLN procedure; and to assess the extent of upstaging due to the SLN procedure. METHODS: One hundred seventy-four consecutive colon cancer patients were enrolled onto this prospective trial. They underwent an intraoperative SLN procedure with isosulfan blue 1% injected peritumorally followed by open standard colon resection with oncologic lymphadenectomy. Three levels of each SLN were stained with hematoxylin and eosin (H&E) and immunostained with the pancytokeratin marker AE1/AE3 if H&E was negative. RESULTS: SLN identification rate and accuracy were 89.1% and 83.9%, respectively. SLN were significantly more likely to contain tumor infiltrates than non-SLN (P < 0.001). Both SLN identification rate (P = 0.021) and the sensitivity of the procedure (P = 0.043) significantly improved with experience. The use of immunohistochemistry in SLN resulted in an upstaging of 15.4% (16 of 104) stage I and II patients considered node-negative in initial H&E analysis. CONCLUSIONS: The SLN procedure for colon cancer has good identification and accuracy rates, which further improve with increasing experience. Most importantly, the SLN procedure results in upstaging of >15% of node-negative patients. The potential advantage of performing the SLN procedure appears to be particularly important in these patients because they may potentially benefit from adjuvant therapy.

Tissue banking in a regional hospital: a promising future concept? First report on fresh frozen tissue banking in a hospital without an integrated institute of pathology.

BACKGROUND: Vital tissue provided by fresh frozen tissue banking is often required for genetic tumor profiling and tailored therapies. However, the potential patient benefits of fresh frozen tissue banking are currently limited to university hospitals. The objective of the present pilot study--the first one in the literature--was to evaluate whether fresh frozen tissue banking is feasible in a regional hospital without an integrated institute of pathology. METHODS: Patients with resectable breast and colon cancer were included in this prospective study. Both malignant and healthy tissue were sampled using isopentan-based snap-freezing 1 h after tumor resection and stored at -80 °C before transfer to the main tissue bank of a University institute of pathology. RESULTS: The initial costs to set up tissue banking were 35,662 US$. Furthermore, the running costs are 1,250 US$ yearly. During the first 13 months, 43 samples (nine samples of breast cancer and 34 samples of colon cancer) were collected from 41 patients. Based on the pathology reports, there was no interference with standard histopathologic analyses due to the sample collection. CONCLUSIONS: This is the first report in the literature providing evidence that tissue banking in a regional hospital without an integrated institute of pathology is feasible. The interesting findings of the present pilot study must be confirmed by larger investigations.

[Surveillance after curative surgery for colorectal and breast cancer]. / Tumornachsorge nach potentiell kurativerResektion eines Karzinoms.

Surveillance programs have been recommended for colorectal and breast cancer patients in several countries, and appropriate surveillance guidelines have been issued by various societies. The Swiss Society of Gastroenterology consensus paper recommends a surveillance program for patients after curative resection of colorectal cancer (CRC), and the respective guidelines are updated regularly. Early detection of recurrent disease from CRC allows treatment with intention to cure. Five year survival rates after treatment for recurrent CRC can reach up to 50 % or more. Therefore tumor surveillance in CRC is important, and there is compelling evidence that patients benefit from intensive surveillance. In addition to clinical controls, measurements of carcinoembryonal antigen, colonoscopies and thoraco-abdominal CT scans should be performed on a regular basis. For surveillance of breast cancer (BC) patients, a regular schedule is recommended as well. However, this surveillance program is more focussing on the detection of possible loco-regional tumor relapse, as curative therapy of BC metastases is much less frequently possible than in CRC patients. Irrespective of the underlying tumor entity, surveillance is an important and challenging process that should be coordinated by one single physician. It is crucial that all involved physicians are aware of their responsibility and that they are informed about the respective surveillance program and its benefit to the patient.