Andrea Mabilia

Treatment of gastric cancer

The authors focused on the current surgical treatment of resectable gastric cancer, and significance of peri- and post-operative chemo or chemoradiation. Gastric cancer is the 4(th) most commonly diagnosed cancer and the second leading cause of cancer death worldwide. Surgery remains the only curative therapy, while perioperative and adjuvant chemotherapy, as well as chemoradiation, can improve outcome of resectable gastric cancer with extended lymph node dissection. More than half of radically resected gastric cancer patients relapse locally or with distant metastases, or receive the diagnosis of gastric cancer when tumor is disseminated; therefore, median survival rarely exceeds 12 mo, and 5-years survival is less than 10%. Cisplatin and fluoropyrimidine-based chemotherapy, with addition of trastuzumab in human epidermal growth factor receptor 2 positive patients, is the widely used treatment in stage IV patients fit for chemotherapy. Recent evidence supports the use of second-line chemotherapy after progression in patients with good performance status.

Is complete mesocolic excision with central vascular ligation safe and effective in the surgical treatment of right-sided colon cancers? A prospective study

PurposeComplete mesocolic excision (CME) with central vascular ligation (CVL) has been proposed for treatment of colon cancers based on the same principles as total mesorectal excision. Impressive outcomes have been reported, however, direct comparisons with the classic procedure are lacking.MethodsForty-five consecutive patients operated on in the last 5xa0years with CME and CVL right hemicolectomy entered the study. Fifty-eight right-sided colon cancer patients operated in the previous 5xa0years with classic approach constituted the control group. Intra- and postoperative course assessed the safety of the procedure. Primary end-points for oncological adequacy were recurrence and survival rate.ResultsAll operations were successful with no increase in postoperative complications (pu2009=u20090.85). Number of harvested nodes and length of vascular ligation were shown to be significantly better in the CME group (pu2009<u20090.01). A higher number of tumor deposits were harvested thus allowing chemotherapy in newly upstaged patients. Locoregional recurrences were never experienced in CME patients (pu2009=u20090.03). The risk of cancer-related death was reduced by over one half in all CME patients, and even by three quarters in node-positive tumors. The classic operation was significantly associated with poor outcome (pu2009<u20090.01).ConclusionThis study shows that CME with CVL is a safe and effective surgical approach for right colon cancer, thus confirming the previously reported oncological adequacy. The procedure was shown to significantly decrease local recurrences and to improve the survival rate, particularly in node-positive patients. Urgent diffusion of this technique is warranted.

Postoperative Detection of Circulating Tumor Cells Predicts Tumor Recurrence in Colorectal Cancer Patients

IntroductionCirculating tumor cells are thought to play a crucial role in the development of distant metastases. Their detection in the blood of colorectal cancer patients may be linked to poor outcome, but current evidence is controversial.Materials and MethodsPre- and postoperative flow cytometric analysis of blood samples was carried out in 76 colorectal cancer patients undergoing surgical resection. The EpCAM/CD326 epithelial surface antigen was used to identify circulating tumor cells.ResultsFifty-four (71xa0%) patients showed circulating tumor cells preoperatively, and all metastatic patients showed high levels of circulating tumor cells. Surgical resection resulted in a significant decrease in the levels of circulating tumor cells. Among 69 patients undergoing radical surgery, 16 had high postoperative levels of circulating tumor cells, and 12 (75xa0%) experienced tumor recurrence. High postoperative level of circulating tumor cells was the only independent variable related to cancer relapse. In patients without circulating tumor cells, the progression-free survival rate increased from 16 to 86xa0%, with a reduction in the risk of tumor relapse greater than 90xa0%.ConclusionsHigh postoperative levels of circulating tumor cells accurately predicted tumor recurrence, suggesting that assessment of circulating tumor cells could optimize tailored management of colorectal cancer patients.

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

BACKGROUNDnAlthough 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.nnnMETHODSnPatients 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.nnnRESULTSnSurgical 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.nnnCONCLUSIONnThese 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.

Preoperative Neutrophil to Lymphocyte Ratio and Lymphocyte to Monocyte Ratio are Prognostic Factors in Gastric Cancers Undergoing Surgery

BackgroundCancer outcome is considered to result from the interplay of several factors, among which host inflammatory and immune status are deemed to play a significant role. The neutrophil-to-lymphocyte ratio (NLR) and the lymphocyte-to-monocyte ratio (LMR) have been profitably used as surrogate markers of host immunoinflammatory status and have also been shown to correlate with outcome in several human tumors. However, only a few studies on these biomarkers have been performed in gastric cancer patients, yielding conflicting results.MethodsData were retrieved from a prospective institutional database. Overall survival (OS) of 401 patients undergoing surgery for gastric cancer between January 2000 and June 2015 as well as disease-free survival (DFS) rates in 297 radically resected patients were calculated. MaxStat analysis was used to select cutoff values for NLR and LMR.ResultsNLR and LMR did not significantly correlate with tumor stage. Patients with a high NLR and a low LMR experienced more tumor recurrences (pxa0<xa00.001) and had a higher hazard ratio (HR) for both OS (HRxa0=xa02.4 and HRxa0=xa02.10; pxa0<xa00.001) and DFS (HRxa0=xa02.99 and HRxa0=xa02.46; pxa0<xa00.001) than low NLR and high LMR subjects. Both biomarkers were shown to independently predict OS (HRxa0=xa01.65, pxa0=xa00.016; HRxa0=xa02.01, pxa0=xa00.002, respectively) and DFS (HRxa0=xa03.04, pxa0=xa00.019; HRxa0=xa04.76, pxa0=xa00.002, respectively). A score system combining both biomarkers was found to significantly correlate with long-term results.ConclusionsA simple prognostic score including preoperative NLR and LMR can be used to easily predict outcome in gastric cancer patients undergoing surgery.

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.