Annamaria Auricchio

Neutrophil to lymphocyte ratio is a strong predictor of tumor recurrence in early colon cancers: A propensity score-matched analysis.

BACKGROUND Systemic inflammation and immune response play a crucial role in tumor growth, and the neutrophil to lymphocyte ratio (NLR) may be a simple way to assess the host inflammatory response. The NLR has been shown to be a prognostic indicator in many human tumors; in early colon cancers, it has been evaluated only in a few studies and its role remains controversial. METHODS We analyzed data from 503 colon cancer patients. The best cutoff value for NLR was defined by receiver operating characteristic curve analysis. We grouped 276 Dukes A/B colon cancers, not receiving adjuvant chemotherapy, into low (<2.36) and high (>2.36) NLR and subjected to further analyses related to disease-free survival (DFS). A propensity score-matched analysis and the inverse probability of treatment weighting (IPTW) were performed to avoid confounding bias. RESULTS The NLR correlated with tumor stage and oncologic outcome. The best NLR cutoff value was identical in the whole cohort and in Dukes A/B patients. Low NLR patients had a significantly better DFS rate than high NLR patients (hazard ratio [HR], 0.27; P = .0001); along with elevated carcinoembryonic antigen levels and Dukes B stage, high NLR was an independent prognostic factor of worse prognosis (HR, 2.86; P = .0033). Even in Dukes A patients, NLR discriminated between relapsing and nonrelapsing patients. Propensity score and IPTW analyses confirmed such results, thus excluding possible misinterpretation. CONCLUSION Preoperative NLR, an inexpensive and readily available biomarker, can predict tumor relapse and should be assessed for implementation of tailored therapy in early stage colon cancer.

The Over-The-Scope-Clip (OTSC) System is Effective in the Treatment of Chronic Esophagojejunal Anastomotic Leakage

IntroductionManagement of postoperative esophagojejunal anastomotic leakage after total gastrectomy represents a very challenging event. Surgical repair is difficult, and conservative treatment can predispose to more severe complications. Endoclips and self-expanding stents are useful endoscopic therapeutic options but present some drawbacks. The Over-The-Scope-Clip (OTSC) system has been shown to be appropriate to close acute small gastrointestinal perforations, but its use in the treatment of chronic leakage remains controversial.Case SeriesThe present series reports three consecutive chronic esophagojejunal anastomotic leaks successfully treated with OTSC. In all cases, clip application was simple, safe and effective, without early and late complications.DiscussionThe OTSC system may represent a new therapeutic option in the management of postoperative esophagojejunal anastomotic leakage.

Modified versus standard D2 lymphadenectomy in total gastrectomy for nonjunctional gastric carcinoma with lymph node metastasis

BACKGROUND Although D2 lymphadenectomy has been shown to improve outcomes in gastric cancer, it may increase postoperative morbidity, mainly owing to splenopancreatic complications. In addition, the effects of nodal dissection along the proper hepatic artery have not been extensively elucidated. We hypothesized that modified D2 (ie, D1+) lymphadenectomy may decrease surgical risks without impairing oncologic adequacy. METHODS Patients with node-positive gastric cancer undergoing curative total gastrectomy were intraoperatively randomized to D1+ (group 1, 36 patients) or standard D2 lymphadenectomy (group 2, 37 patients), the latter including splenectomy and nodal group 12a. The index of estimated benefit was used to assess the efficacy of dissection of each nodal station. The primary endpoint for oncologic adequacy was the disease-free survival (DFS) rate. RESULTS Surgical complications were significantly more common in group 2, which also included 2 postoperative deaths. Overall, 35 patients (49%) experienced tumor recurrence. The primary site of tumor relapse and the 5-year DFS rate were not different between the 2 groups. Involvement of the second nodal level was associated with a worse DFS rate; however, patients undergoing more extensive lymphadenectomy did not show a better DFS rate. The incidence of involvement of nodal stations 10, 11d, and 12a was 5%, and the 5-year DFS rate was zero. Consequently, the benefit to dissect such lymph nodes was null. CONCLUSION These findings suggest that modified D2 lymphadenectomy confers the same oncologic adequacy as standard D2 lymphadenectomy, with a significant reduction of postoperative morbidity.

Conversion chemotherapy followed by hepatic resection in colorectal cancer with initially unresectable liver-limited metastases

The best management choice in colorectal cancer patients with unresectable liver-only metastases should be represented by conversion chemotherapy aiming to reduce liver cancer deposits, thereby permitting curative surgery. Forty-eight consecutive stage IV colorectal cancer patients were treated with different chemotherapeutic regimens including biological drugs. Objective responses to chemotherapy were seen in 27 patients (56.2%; 95% CI 42.1-70.2%). Four patients (8.3%) showed complete response, 23 patients (47.9%) partial and 13 patients (27.1%) stable response. Eight patients (16.7%) progressed. The conversion rate was 35.4% (95% CI 21.8-48.9%) with 17 patients suitable for liver resection. Four complete responder patients refused surgery. The remaining 13 patients underwent curative hepatic resection (resection rate 27.1%; 95% CI 14.5-39.6%). The likelihood of a successful conversion chemotherapy appeared significantly related to the best response and to the K-Ras status. Wild-type K-Ras patients undergoing cetuximab therapy showed the best conversion rate. The four-year survival rate was significantly enhanced in converted compared to non-converted patients (57.1 and 0%, respectively), and in resected compared to non-resected patients (53.3 and 10.1%, respectively). Synchronous metastases and no conversion were shown to be the only covariates independently associated with a poorer long-term outcome. The possibility of curative liver surgery significantly prolongs outcome for colorectal cancer patients with unresectable liver-limited metastases. Prospective randomized trials are required to define the conversion rates with biological drugs.

Comparison of the current AJCC-TNM numeric-based with a new anatomical location-based lymph node staging system for gastric cancer: A western experience.

Background In gastric cancer, the current AJCC numeric-based lymph node staging does not provide information on the anatomical extent of the disease and lymphadenectomy. A new anatomical location-based node staging, proposed by Choi, has shown better prognostic performance, thus soliciting Western world validation. Study design Data from 284 gastric cancers undergoing radical surgery at the Second University of Naples from 2000 to 2014 were reviewed. The lymph nodes were reclassified into three groups (lesser and greater curvature, and extraperigastric nodes); presence of any metastatic lymph node in a given group was considered positive, prompting a new N and TNM stage classification. Receiver-operating-characteristic (ROC) curves for censored survival data and bootstrap methods were used to compare the capability of the two models to predict tumor recurrence. Results More than one third of node positive patients were reclassified into different N and TNM stages by the new system. Compared to the current staging system, the new classification significantly correlated with tumor recurrence rates and displayed improved indices of prognostic performance, such as the Bayesian information criterion and the Harrell C-index. Higher values at survival ROC analysis demonstrated a significantly better stratification of patients by the new system, mostly in the early phase of the follow-up, with a worse prognosis in more advanced new N stages, despite the same current N stage. Conclusions This study suggests that the anatomical location-based classification of lymph node metastasis may be an important tool for gastric cancer prognosis and should be considered for future revision of the TNM staging system.

CD26-positive/CD326-negative circulating cancer cells as prognostic markers for colorectal cancer recurrence.

The present study evaluated the presence and clinical relevance of a cluster of differentiation (CD)26+/CD326− subset of circulating tumor cells (CTCs) in pre- and post-operative blood samples of colorectal cancer patients, who had undergone curative or palliative intervention, in order to find a novel prognostic factor for patient management and follow-up. In total, 80 colorectal cancer patients, along with 25 healthy volunteers were included. The easily transferable methodology of flow cytometry, along with multiparametric antibody staining were used to selectively evaluate CD26+/CD326− CTCs in the peripheral blood samples of colorectal cancer patients. The multiparametric selection allowed any enrichment methods to be avoided thus rendering the whole procedure suitable for clinical routine. The presence of CD26+/CD326− cells was higher in advanced Dukes’ stages and was significantly associated with poor survival and high recurrence rates. Relapsing and non-surviving patients showed the highest number of CD26+/CD326− CTCs. High pre-operative levels of CD26+/CD326− CTCs correctly predicted tumor relapse in 44.4% of the cases, while 69% of post-operative CD26+/CD326− CTC-positive patients experienced cancer recurrence, with a test accuracy of 88.8%. By contrast, post-operative CD26+/CD326− CTC-negative patients showed an increase in the three-year progression-free survival rate of 86%, along with a reduced risk of tumor relapse of >90%. In conclusion, CD26+/CD326− CTCs are an independent prognostic factor for tumor recurrence rate in multivariate analysis, suggesting that their evaluation could be an additional factor for colorectal cancer recurrence risk evaluation in patient management.

Indocyanine Green Fluorescence Imaging-Guided Surgery in Primary and Metastatic Liver Tumors

Background. After surgery for liver tumors, recurrence rates remain high because of residual positive margins or undiagnosed lesions. It has been suggested that detection of hepatic tumors can be obtained with near-infrared fluorescence imaging (FI). Indocyanine green (ICG) has been used with contrasting results. The aims of this study were to explore ICG-FI-guided surgery methodology and to assess its potential applications. Materials and Methods. Out of 14 patients with liver tumors, 5 were not operated on, and 9 patients (3 primary and 6 metastatic tumors) underwent surgery. ICG (0.5 mg/kg) was injected intravenously 24 hours before surgery. Fluorescence was investigated prior to resection to detect liver lesions, during hepatic transection to guide surgery, on both cross-section and benchtop to assess surgical margins, and for pathological evaluation. Results. All operations were successful and had a short duration. ICG-FI detected all already known lesions (n = 10), and identified 2 additional small tumors (1 hepatocarcinoma and 1 metastasis, diagnostic improvement = 20%). Two hepatocarcinomas were hyperfluorescent; the remaining one, with a central hypofluorescent area and a hyperfluorescent ring, was indeed a mixed cholangiohepatocarcinoma. All metastatic nodules were hypofluorescent with a hyperfluorescent rim. In all cases, in vivo and ex vivo fluorescence revealed clear liver margins. Postoperative pathological examination greatly benefited of liver fluorescence to assess radicality. Conclusion. ICG-FI-guided surgery was shown to be an effective tool to improve both intraoperative staging and radicality in the surgical treatment of primary and metastatic liver tumors.

Naples Prognostic Score, Based on Nutritional and Inflammatory Status, is an Independent Predictor of Long-term Outcome in Patients Undergoing Surgery for Colorectal Cancer

BACKGROUND: The existing scores reflecting the patient’s nutritional and inflammatory status do not include all biomarkers and have been poorly studied in colorectal cancers. OBJECTIVE: The purpose of this study was to assess a new prognostic tool, the Naples prognostic score, comparing it with the prognostic nutritional index, controlling nutritional status score, and systemic inflammation score. DESIGN: This was an analysis of patients undergoing surgery for colorectal cancer. SETTINGS: The study was conducted at a university hospital. PATIENTS: A total of 562 patients who underwent surgery for colorectal cancer in July 2004 through June 2014 and 468 patients undergoing potentially curative surgery were included. MaxStat analysis dichotomized neutrophil:lymphocyte ratio, lymphocyte:monocyte ratio, prognostic nutritional index, and the controlling nutritional status score. The Naples prognostic scores were divided into 3 groups (group 0, 1, and 2). The receiver operating characteristic curve for censored survival data compared the prognostic performance of the scoring systems. MAIN OUTCOME MEASURES: Overall survival and complication rates in all patients, as well as recurrence and disease-free survival rates in radically resected patients, were measured. RESULTS: The Naples prognostic score correlated positively with the other scoring systems (p < 0.001) and worsened with advanced tumor stages (p < 0.001). Patients with the worst Naples prognostic score experienced more postoperative complications (all patients, p = 0.010; radically resected patients, p = 0.026). Compared with group 0, patients in groups 1 and 2 had worse overall (group 1, HR = 2.90; group 2, HR = 8.01; p < 0.001) and disease-free survival rates (group 1, HR = 2.57; group 2, HR = 6.95; p < 0.001). Only the Naples prognostic score was an independent significant predictor of overall (HR = 2.0; p = 0.03) and disease-free survival rates (HR = 2.6; p = 0.01). The receiver operating characteristic curve analysis showed that the Naples prognostic score had the best prognostic performance and discriminatory power for overall (p = 0.02) and disease-free survival (p = 0.04). LIMITATIONS: This is a single-center study, and its validity needs additional external validation. CONCLUSIONS: The Naples prognostic score is a simple tool strongly associated with long-term outcome in patients undergoing surgery for colorectal cancer. See Video Abstract at http://links.lww.com/DCR/A469.

Different Biomarkers Address Different Colorectal Cancer Stem Cell Populations: Who's the Killer?

Recent findings suggested the presence in several cancers, comprising colorectal malignancies, of a small subset of tumor-initiating cells, or cancer stem cells. So the isolation and characterization of tumorigenic colorectal cancer cells was extremely important for the development of new diagnostic and therapeutic procedures. Even if a defined and universally approved phenotype of colorectal cancer stem cells has not been defined yet, several markers have been reported able to isolate cancer stem-like cells. For the majority of these markers, it has not been associated a clear function but more of them seem to be involved in colon cancer stem cell maintenance, survival and proliferation through well known pathways such as the Wnt-β-catenin pathway whose activity has been demonstrated to define colorectal cancer stem cells. Even if the knowledge on colorectal cancer stem cell “functioning” is still little detailed and elusive, the importance to develop new therapeutic strategies that precisely target colorectal cancer stem cells prompted researchers to test different approaches to this aim. We summarize here the phenotypic and functional characteristics associated with colon cancer stem cells along with the approaches experimented to selectively target and kill these cancer cells. We also reviewed innovative approaches targeting colorectal cancer stem cells based on new delivery systems to precisely kill them or also on the combination of conventional therapies with functional dietary elements.