The crossroad between autoimmune disorder, tissue remodeling and cancer of the thyroid: The long pentraxin 3 (PTX3).

Thyroid is at the crossroads of immune dysregulation, tissue remodeling and oncogenesis. Autoimmune disorders, nodular disease and cancer of the thyroid affect a large amount of general population, mainly women. We wondered if there could be a common factor behind three processes (immune dysregulation, tissue remodeling and oncogenesis) that frequently affect, sometimes coexisting, the thyroid gland. The long pentraxin 3 (PTX3) is an essential component of the humoral arm of the innate immune system acting as soluble pattern recognition molecule. The protein is found expressed in a variety of cell types during tissue injury and stress. In addition, PTX3 is produced by neutrophils during maturation in the bone-marrow and is stored in lactoferrin-granules. PTX3 is a regulator of the complement cascade and orchestrates tissue remodeling and repair. Preclinical data and studies in human tumors indicate that PTX3 can act both as an extrinsic oncosuppressor by modulating complement-dependent tumor-promoting inflammation, or as a tumor-promoter molecule, regulating cell invasion and proliferation and epithelial to mesenchymal transition, thus suggesting that this molecule may have different functions on carcinogenesis. The involvement of PTX3 in the regulation of immune responses, tissue remodeling and oncosuppressive processes led us to explore its potential role in the development of thyroid disorders. In this review, we aimed to highlight what is known, at the state of the art, regarding the connection between the long pentraxin 3 and the main thyroid diseases i.e., nodular thyroid disease, thyroid cancer and autoimmune thyroid disorders.

Risk factors for recurrence and complications after laparoscopic repair of incisional hernia using a double-layered ePTFE/PP mesh: results of a retrospective study.

BACKGROUND: The objective was to analyse, risk factors for recurrence (primary outcome) and complications (secondary outome) after the implantation of a double layer ePTFE (expanded PolytTetraFluoroEthylene) / PP (PolyPropylene) mesh to treat incisional hernias (IH) using the Intraperitoneal Onlay Mesh (IPOM) technique. METHODS: We included all elective laparoscopic IH repairs with intraperitoneal placement of a ePTFE / PP mesh (Relimesh® - Herniamesh S.r.l.) from January 1, 2010 to December 31, 2017 at Humanitas Mater Domini Clinical Institute in Castellanza (Italy) and at the Centre for Minimally Invasive Surgery of Nis (Serbia). Performance was defined as long-term recurrence rate. RESULTS: A total of 284 patients were enrolled. According to the European Hernia Society (EHS) hernias were classified as: W1 (<4 cm) 60.29%, W2 (≥4-10 cm) 35.02% and W3 (≥10 cm) 4.69%; medial 90.85%, lateral 6.69%, both medial and lateral 2.11%. Average follow-up was 48 (11-110) months. The 30-days complication rate was 4.23%. Hernia recurrence rate was 3.36%. Long-term complication rate was 6.34%. At multivariable analysis, an increased risk of short-term complications was associated to chronic obstructive pulmonary disease (COPD) (OR 7.59 [2.23-25.83], P=0.001); an increased risk of long-term complications was associated to diabetes (OR 6.21 [1.80-21.42], P=0.004), an increased risk of recurrence was correlated to COPD (OR 13.40 [1.36-131.9], P=0.026) and hernia defects larger than 6 cm (OR 19.2 [1.12-329.9], P=0.042). CONCLUSIONS: Elective laparoscopic IH repair with a double-layered ePTFE/PP mesh is safe and effective. Compliance with indications and preoperative patients evaluation are essential to improve outcomes.

Rivaroxaban vs placebo for extended antithrombotic prophylaxis after laparoscopic surgery for colorectal cancer.

The clinical benefit of extended prophylaxis for venous thromboembolism (VTE) after laparoscopic surgery for cancer is unclear. The efficacy and safety of direct oral anticoagulants for this indication are unexplored. PROphylaxis of venous thromboembolism after LAParoscopic Surgery for colorectal cancer Study II (PROLAPS II) was a randomized, double-blind, placebo-controlled, investigator-initiated, superiority study aimed at assessing the efficacy and safety of extended prophylaxis with rivaroxaban after laparoscopic surgery for colorectal cancer. Consecutive patients who had laparoscopic surgery for colorectal cancer were randomized to receive rivaroxaban (10 mg once daily) or a placebo to be started at 7 ± 2 days after surgery and given for the subsequent 3 weeks. All patients received antithrombotic prophylaxis with low-molecular-weight heparin from surgery to randomization. The primary study outcome was the composite of symptomatic objectively confirmed VTE, asymptomatic ultrasonography-detected deep vein thrombosis (DVT), or VTE-related death at 28 ± 2 days after surgery. The primary safety outcome was major bleeding. Patient recruitment was prematurely closed due to study drug expiry after the inclusion of 582 of the 646 planned patients. A primary study outcome event occurred in 11 of 282 patients in the placebo group compared with 3 of 287 in the rivaroxaban group (3.9 vs 1.0%; odds ratio, 0.26; 95% confidence interval [CI], 0.07-0.94; log-rank P = .032). Major bleeding occurred in none of the patients in the placebo group and 2 patients in the rivaroxaban group (incidence rate 0.7%; 95% CI, 0-1.0). Oral rivaroxaban was more effective than placebo for extended prevention of VTE after laparoscopic surgery for colorectal cancer without an increase in major bleeding. This trial was registered at www.clinicaltrials.gov as #NCT03055026.

Blended practical learning in compliance with COVID-19 social distancing.

COVID-19 pandemic has imposed great changes in everyday life. Starting from January 2020, Humanitas University proposed to students digital instruction for continuing medical education, in particular, concerning practical activities. The latter, defined as Professionalizing activities, were transformed into complete online learning. From September 2020, in accordance to the imposed rules of social distancing, we modified the approach to Professionalizing activities. Despite following the new constrains, we came up with a blend online and face-to-face education program. The Kirkpatrick's evaluation model has been followed for validation of the project. Two ad hoc satisfaction questionnaires have been proposed to evaluate the project. Different approaches to blended learning have been described in literature; however, we propose a new method application, which fits to the post-pandemic era, with the purpose of sharing our experience in the field. Advantages and limitations are described. According to students, the overall satisfaction was rated 6.8, while tutors evaluated it with 7.4. The qualitative analysis of data confirms the advantage of the blended learning activities in order to guarantee a continuation of the clinical curriculum. Although it highlighted the necessity for, an increased technical support and an improvement in organization of the meetings. Blended learning is becoming more accepted among academic communities because it combines "the best of both worlds." However, its effectiveness depends on several factors. With our approach, we propose a method, specifically designed to make effective this kind of teaching, which can be considered essential in the pandemic era we are facing.

Multimodal treatment of colorectal postsurgical leaks: long-term results of the over-the-scope clip (OTSC) application.

BACKGROUND: Postsurgical anastomotic colorectal leaks often require a surgical second look with a definite morbidity and the risk of delaying adjuvant treatment. The aim of this study was to analyse the long-term results of the endoscopic closure of colorectal leak following low anterior resection (LAR) using the over-the-scope (Ovesco™; Ovesco Endoscopy AG, Tübingen, Germany) clip. METHODS: Patients who were submitted to endoscopic closure of a colorectal leak of maximum 2 cm with an Ovesco™ clip following LAR from 2016 to 2018 were enrolled in this retrospective single-center study (Humanitas Mater Domini Clinical Institute, Italy). The follow-up was obtained through radiologic and clinic assessments. RESULTS: In the analyzed study period, 48 patients were submitted to LAR. Six patients were enrolled in the study. The median diameter of the leak was 7 mm. 14/6t or 12/6t OTSC® clip was applied. Three patients were managed exclusively endoscopically, 2 of them had a protective ileostomy; 3 patients underwent urgent laparotomy with ostomy and then underwent endoscopic procedure. Complete healing was reached in all patients in a median of 23 days. Adjuvant chemotherapy was indicated and performed in 4 patients after a median of 64 days from the surgery. Among the 5 carriers of an ostomy, 4 patients underwent recanalization. The median follow-up was 21.5 months. During the follow-up no leak reoccurrence or complications were reported. CONCLUSIONS: In the multimodal management of anastomotic leaks following LAR, Ovesco™ clipping system appears a safe and effective technique in the closure of small leaks (<2 cm), allowing an early recanalization of the bowel and not delaying adjuvant chemotherapy when indicated.

Changes in body composition during neoadjuvant therapy can affect prognosis in rectal cancer patients: An exploratory study.

AIM: To establish the correlation between changes in body composition after neoadjuvant chemoradiotherapy (nCRT) and postoperative outcomes, in patients with advanced low rectal cancer. METHODS: Patients with clinical stage T≥3 or N+ rectal cancer who underwent nCRT and surgical resection were studied. Skeletal muscle, visceral, and subcutaneous fat cross-sectional area were measured by computed tomography before and after nCRT. Postoperative morbidity, pathologic response to nCRT, overall and disease-free survival was assessed. RESULTS: Fifty-two patients, median age 62 (range 32-79) were studied. A skeletal muscle loss >2% significantly correlated with a shorter disease-free survival both in the overall population (P = 0.048) and in the subgroup of N0 patients (P = 0.048). A subcutaneous fat loss >5% was also associated with a shorter disease-free survival (P = 0.012) in the whole population. CONCLUSIONS: Skeletal muscle loss, after neoadjuvant chemoradiotherapy, negatively impacts on disease-free survival in surgically treated rectal cancer patients.

Rivaroxaban for extended antithrombotic prophylaxis after laparoscopic surgery for colorectal cancer. Design of the PRO-LAPS II STUDY.

BACKGROUND: The clinical benefit of extending prophylaxis for venous thromboembolism (VTE) beyond hospital discharge after laparoscopic surgery for cancer is undefined. Extended prophylaxis with rivaroxaban is effective in reducing post-operative VTE after major orthopedic surgery without safety concern. METHODS: PROLAPS II is an investigator-initiated, randomized, double-blind study aimed at assessing the efficacy and safety of extended antithrombotic prophylaxis with rivaroxaban compared with placebo after laparoscopic surgery for colorectal cancer in patients who had received antithrombotic prophylaxis with low molecular-weight heparin for 7 ± 2 days (NCT03055026). Patients are randomized to receive rivaroxaban (10 mg once daily) or placebo for 3 weeks (up to day 28 ± 2 from surgery). The primary study outcome is a composite of symptomatic objectively confirmed VTE, asymptomatic ultrasonography-detected DVT or VTE-related death at 28 ± 2 days from laparoscopic surgery. The primary safety outcome is major bleeding defined according to the International Society of Thrombosis and Haemostasis. Symptomatic objectively confirmed VTE, asymptomatic ultrasonography-detected DVT, major bleeding or death by day 28 ± 2 and by day 90 from surgery are secondary outcomes. Assuming an 8% event rate with placebo and 60% reduction in the primary study outcome with rivaroxaban, 323 patients per group are necessary to show a statistically significant difference between the study groups. DISCUSSION: The PROLAPS II is the first study with an oral anti-Xa agent in cancer surgery. The study has the potential to improve clinical practice by answering the question on the clinical benefit of extending prophylaxis after laparoscopic surgery for colorectal cancer.

Total vs proximal gastrectomy for adenocarcinoma of the upper third of the stomach: a propensity-score-matched analysis of a multicenter western experience (On behalf of the Italian Research Group for Gastric Cancer-GIRCG).

BACKGROUND: The aim of this study is to compare surgical outcomes including postoperative complications and prognosis between total gastrectomy (TG) and proximal gastrectomy (PG) for proximal gastric cancer (GC). Propensity-score-matching analysis was performed to overcome patient selection bias between the two surgical techniques. METHODS: Among 457 patients who were diagnosed with GC between January 1990 and December 2010 from four Italian institutions, 91 underwent PG and 366 underwent TG. Clinicopathologic features, postoperative complications, and survivals were reviewed and compared between these two groups retrospectively. RESULTS: After propensity-score matching had been done, 150 patients (75 TG patients, 75 PG patients) were included in the analysis. The PG group had smaller tumors, shorter resection margins, and smaller numbers of retrieved lymph nodes than the TG group. N stages and 5-year survival rates were similar after TG and PG. Postoperative complication rates after PG and TG were 25.3 and 28%, respectively, (P = 0.084). Rates of reflux esophagitis and anastomotic stricture were 12 and 6.6% after PG and 2.6 and 1.3% after TG, respectively (P < 0.001 and P = 0.002). 5-year overall survival for PG and TG group was 56.7 and 46.5%, respectively (P = 0.07). Survival rates according to the tumor stage were not different between the groups. Multivariate analysis showed that type of resection was not an independent prognostic factor. CONCLUSION: Although PG for upper third GC showed good results in terms of survival, it is associated with an increased mortality rate and a higher risk of reflux esophagitis and anastomotic stricture.

Pre-treatment MDCT-based texture analysis for therapy response prediction in gastric cancer: Comparison with tumour regression grade at final histology.

PURPOSE: An accurate prediction of tumour response to therapy is fundamental in oncology, so as to prompt personalised treatment options if needed. The aim of this study was to investigate the ability of preoperative texture analysis from multi-detector computed tomography (MDCT) in the prediction of the response rate to neo-adjuvant therapy in patients with gastric cancer. MATERIAL AND METHODS: Thirty-four patients with biopsy-proven gastric cancer were examined by MDCT before neo-adjuvant therapy, and treated with radical surgery after treatment completion. Tumour regression grade (TRG) at final histology was also assessed. Image features from texture analysis were quantified, with and without filters for fine to coarse textures. Patients with TRG 1-3 were considered responders while TRG 4-5 as non- responders. The response rate to neo-adjuvant therapy was assessed both at univariate and multivariate analysis. RESULTS: Fourteen parameters were significantly different between the two subgroups at univariate analysis; in particular, entropy and compactness (higher in responders) and uniformity (lower in responders). According to our model, the following parameters could identify non-responders at multivariate analysis: entropy (≤6.86 with a logarithm of Odds Ratio - Log OR -: 4.11; p=0.003); range (>158.72; Log OR: 3.67; p=0.010) and root mean square (≤3.71; Log OR: 4.57; p=0.005). Entropy and three-dimensional volume were not significantly correlated (r=0.06; p=0.735). CONCLUSION: Pre-treatment texture analysis can potentially provide important information regarding the response rate to neo-adjuvant therapy for gastric cancer, improving risk stratification.

Apparent diffusion coefficient by diffusion-weighted magnetic resonance imaging as a sole biomarker for staging and prognosis of gastric cancer.

OBJECTIVE: To investigate the role of apparent diffusion coefficient (ADC) from diffusion-weighted magnetic resonance imaging (DW-MRI) when applied to the 7th TNM classification in the staging and prognosis of gastric cancer (GC). METHODS: Between October 2009 and May 2014, a total of 89 patients with non-metastatic, biopsy proven GC underwent 1.5T DW-MRI, and then treated with radical surgery. Tumor ADC was measured retrospectively and compared with final histology following the 7th TNM staging (local invasion, nodal involvement and according to the different groups - stage I, II and III). Kaplan-Meier curves were also generated. The follow-up period is updated to May 2016. RESULTS: Median follow-up period was 33 months and 45/89 (51%) deaths from GC were observed. ADC was significantly different both for local invasion and nodal involvement (P<0.001). Considering final histology as the reference standard, a preoperative ADC cut-off of 1.80×10-3 mm2/s could distinguish between stages I and II and an ADC value of ≤1.36×10-3 mm2/s was associated with stage III (P<0.001). Kaplan-Meier curves demonstrated that the survival rates for the three prognostic groups were significantly different according to final histology and ADC cut-offs (P<0.001). CONCLUSIONS: ADC is different according to local invasion, nodal involvement and the 7th TNM stage groups for GC, representing a potential, additional prognostic biomarker. The addition of DW-MRI could aid in the staging and risk stratification of GC.

Effect of neoadjuvant chemotherapy on HER-2 expression in surgically treated gastric and oesophagogastric junction carcinoma: a multicentre Italian study.

Predictors of response to neoadjuvant chemotherapy are not available for gastric and oesophago-gastric junction carcinoma. HER-2 over-expression in breast cancer correlates with poor prognosis and high incidence of recurrence. First aim of this study was to evaluate if the HER-2 expression/amplification is predictive of response to neoadjuvant chemotherapy in terms of pathologic regression. Secondary aim was to evaluate if HER-2 expression varies after neoadjuvant treatment. Thirty-five patients with locally advanced gastric or oesophago-gastric junction carcinoma underwent preoperative chemotherapy and surgical resection at San Raffaele Scientific Institute and Spedali Civili of Brescia. HER-2 expression/amplification was evaluated on every biopsy at diagnosis time and on every surgical sample after neoadjuvant chemotherapy. Pathologic response to chemotherapy was evaluated according to TNM classification (ypT status and ypN status) and Mandard's tumour regression grade classification. In our series 10 patients (28.6%) showed a reduction in HER-2 overexpression and in 6 of them (17.1%) HER-2 expression completely disappeared. Only three of the six patients with HER-2 disappearance had a complete pathological response to neoadjuvant chemotherapy. There was a strong correlation between HER-2 negativity on biopsy and absence of lymph node metastasis in surgical samples after neoadjuvant chemotherapy, irrespective of nodal status before chemotherapy. A direct correlation between HER-2 reduction after neoadjuvant chemotherapy and pathologic regression (primary tumour and lymph nodes) in surgical samples was found. HER-2 negativity may represent a predictor of pathologic response to neoadjuvant chemotherapy for gastric and oesophago-gastric junction adenocarcinoma. Neoadjuvant treatment can reduce HER-2 overexpression.

Gastric cancer: texture analysis from multidetector computed tomography as a potential preoperative prognostic biomarker.

OBJECTIVES: To investigate the association between preoperative texture analysis from multidetector computed tomography (MDCT) and overall survival in patients with gastric cancer. METHODS: Institutional review board approval and informed consent were obtained. Fifty-six patients with biopsy-proved gastric cancer were examined by MDCT and treated with surgery. Image features from texture analysis were quantified, with and without filters for fine to coarse textures. The association with survival time was assessed using Kaplan-Meier and Cox analysis. RESULTS: The following parameters were significantly associated with a negative prognosis, according to different thresholds: energy [no filter] - Logarithm of relative risk (Log RR): 3.25; p = 0.046; entropy [no filter] (Log RR: 5.96; p = 0.002); entropy [filter 1.5] (Log RR: 3.54; p = 0.027); maximum Hounsfield unit value [filter 1.5] (Log RR: 3.44; p = 0.027); skewness [filter 2] (Log RR: 5.83; p = 0.004); root mean square [filter 1] (Log RR: - 2.66; p = 0.024) and mean absolute deviation [filter 2] (Log RR: - 4.22; p = 0.007). CONCLUSIONS: Texture analysis could increase the performance of a multivariate prognostic model for risk stratification in gastric cancer. Further evaluations are warranted to clarify the clinical role of texture analysis from MDCT. KEY POINTS: • Textural analysis from computed tomography can be applied in gastric cancer. • Preoperative non-invasive texture features are related to prognosis in gastric cancer. • Texture analysis could help to evaluate the aggressiveness of this tumour.

Risk factor analysis for involvement of resection margins in gastric and esophagogastric junction cancer: an Italian multicenter study.

BACKGROUND: Resection margin (RM) involvement is associated with negative prognosis after gastrectomy. Intraoperative frozen section (IFS) analysis allows radical resection to be achieved in a single operation but is time-consuming and resource-consuming. The aim of this study was to assess risk factors associated with RM involvement to identify patients who would benefit from IFS analysis. METHODS: We retrospectively analyzed patients who underwent gastrectomy with curative intent for gastric or esophagogastric junction (EGJ) cancer from 2000 to 2014 in six Italian hospitals. RM status was assessed by IFS analysis and/or definitive histopathology examination. A set of 21 potential risk factors were compared in a multivariate analysis between patients with positive RMs on IFS analysis or definitive histopathology examination and a control cohort of similar patients with negative RMs, with the samples stratified into three subgroups (T1, T2-T4 Lauren intestinal pattern, T2-T4 Lauren diffuse/mixed pattern). RESULTS: One hundred forty-five patients had positive RMs. Survival was significantly worse in positive RM patients than in negative RM patients (89.5 months vs 28.9 months). Multivariate analysis showed that in T1 cancers a margin distance of less than 2 cm is a risk factor for RM involvement (odds ratio 15.7), in T2-T4 intestinal pattern cancers, serosa invasion (odds ratio 6.0), EGJ location (odds ratio 4.1), and a margin distance of less than 3 cm (odds ratio 4.0) are independent risk factors, and in T2-T4 diffuse/mixed pattern cancers, lymphatic infiltration (odds ratio 4.2), tumor diameter greater than 4 cm (odds ratio 3.5), EGJ location (odds ratio 2.8), and serosa invasion (odds ratio 2.2) are independent risk factors. CONCLUSIONS: Survival after gastrectomy is negatively affected by positive RMs. IFS analysis should be routinely used in patients with a high risk of positive RMs, especially in diffuse pattern cancers.

Prospective comparison of MR with diffusion-weighted imaging, endoscopic ultrasound, MDCT and positron emission tomography-CT in the pre-operative staging of oesophageal cancer: results from a pilot study.

OBJECTIVE: To compare the diagnostic performance of MR and diffusion-weighted imaging (DWI), multidetector CT, endoscopic ultrasonography (EUS) and 18F-FDG (fluorine-18 fludeoxyglucose) positron emission tomography CT (PET-CT) in the pre-operative locoregional staging of oesophageal cancer. METHODS: 18 patients with oesophageal or Siewert I tumour (9 directly treated with surgery and 9 addressed to chemo-/radiotherapy before) underwent 1.5-T MR and DWI, 64-channel multidetector CT, EUS and PET-CT before (n = 18) and also after neoadjuvant treatment (n = 9). All images were analysed and staged blindly by dedicated operators (seventh TNM edition). Two radiologists calculated independently the apparent diffusion coefficient from the first scan. Results were compared with histopathological findings. After the population had been divided according to local invasion (T1-T2 vs T3-T4) and nodal involvement (N0 vs N+), sensitivity, specificity, accuracy, positive- and negative-predictive values were calculated and compared. Quantitative measurements from DWI and PET-CT were also analysed. RESULTS: For T staging, EUS showed the best sensitivity (100%), whereas MR showed the highest specificity (92%) and accuracy (83%). For N staging, MR and EUS showed the highest sensitivity (100%), but none of the techniques showed adequate results for specificity. Overall, MR showed the highest accuracy (66%) for N stage, although this was not significantly different to the other modalities. The apparent diffusion coefficient was different between surgery-only and chemo-/radiotherapy groups (1.90 vs 1.30 × 10-3 mm2 s-1, respectively; p = 0.005)-optimal cut off for local invasion: 1.33 × 10-3 mm2 s-1 (p = 0.05). Difference in standardized uptake value was also very close to conventional levels of statistical significance (8.81 vs 13.97 g cm-3, respectively; p = 0.05)-optimal cut off: 7.97 g cm-3 (p = 0.44). CONCLUSION: In this pilot study, we have shown that MR with DWI could enrich the current pre-operative work-up for oesophageal cancer and could be used for T and N staging. However, larger studies will need to be carried out before introducing this technique in the standard diagnostic pathway, in order to understand if MR with DWI could change its management and replace more costly or invasive tests such as PET-CT or EUS. Advances in knowledge: This pilot study represents the first effort where the four techniques have been prospectively compared together for oesophageal cancer staging. The combination of MR and DWI could provide important, additional information for staging and initial treatment decision-making.

Prognostic utility of diffusion-weighted MRI in oesophageal cancer: is apparent diffusion coefficient a potential marker of tumour aggressiveness?

PURPOSE: To investigate the role of the apparent diffusion coefficient (ADC) as a potential prognostic biomarker in the evaluation of the aggressiveness of oesophageal cancer. MATERIALS AND METHODS: Between November 2009 and December 2013, 43 patients with evidence of oesophageal or oesophago-gastric junction cancer were referred to our institution and prospectively entered in our database. The final study population consisted of 23 patients (18 men; 5 women; mean age, 64.62 ± 10.91 years) who underwent diffusion-weighted Magnetic Resonance before surgical intervention. Specifically, 14 were directly treated with surgery and 9 were addressed to chemo/radiotherapy beforehand. Two radiologists independently measured mean tumour ADC and inter-observer agreement (Spearman's and intraclass correlation coefficient [ICC]) was assessed. In the univariate analysis, overall survival curves related to pathological ADC, pT, pN, tumour location and histotype were fitted using the Kaplan-Meier method. Survival curves were then compared using the log-rank test. RESULTS: Inter-observer reproducibility was very good (Spearman's rho = 0.95; ICC = 0.94). At a total median follow-up of 19 months (2-49 months), 4 patients had died. The median follow-up was 18.50 months (5-49 months) for the surgery-only group (1/4 events, 25 %) and 24 months (2-34 months) for the chemo/radiotherapy group (3/4 events, 75 %). Survival time at 48 months for the overall population was 59 % (±0.11), while for the surgery-only group and the chemo/radiotherapy group was 90 % (±0.09) and 61 % (±0.34), respectively. In the univariate analysis, ADC values below or equal to 1.4 × 10(-3) mm(2)/s were associated with a negative prognosis both in the total population (P = 0.016) and in the surgery-only group (P < 0.001). CONCLUSION: Despite the biggest limitation of our study (i.e. the small study population), we were able to show that pathological ADC could be considered a prognostic factor for oesophageal cancer. DWI might be introduced into clinical practice as a promising and reliable technique in the diagnostic pathway of this tumour.

Preoperative locoregional staging of gastric cancer: is there a place for magnetic resonance imaging? Prospective comparison with EUS and multidetector computed tomography.

BACKGROUND: The aim of this study was to prospectively compare the diagnostic performance of magnetic resonance imaging (MRI), multidetector computed tomography (MDCT) and endoscopic ultrasonography (EUS) in the preoperative locoregional staging of gastric cancer. METHODS: This study had Institutional Review Board approval, and informed consent was obtained from all patients. Fifty-two patients with biopsy-proven gastric cancer underwent preoperative 1.5-T MRI, 64-channel MDCT and EUS. All images were analysed blind, and the results were compared with histopathological findings according to the seventh edition of the TNM classification. After the population had been divided on the basis of the local invasion (T1-3 vs T4a-b) and nodal involvement (N0 vs N+), sensitivity, specificity, positive and negative predictive value, and accuracy were calculated and diagnostic performance measures were assessed using the McNemar test. RESULTS: For T staging, EUS showed higher sensitivity (94%) than MDCT and MRI (65 and 76%; p = 0.02 and p = 0.08). MDCT and MRI had significantly higher specificity (91 and 89%) than EUS (60%) (p = 0.0009 and p = 0.003). Adding MRI to MDCT or EUS did not result in significant differences for sensitivity. For N staging, EUS showed higher sensitivity (92%) than MRI and MDCT (69 and 73%; p = 0.01 and p = 0.02). MDCT showed better specificity (81%) than EUS and MRI (58 and 73%; p = 0.03 and p = 0.15). CONCLUSIONS: Our prospective study confirmed the leading role of EUS and MDCT in the staging of gastric cancer and did not prove, at present, the value of the clinical use of MRI.

Prognostic Role of Diffusion-weighted MR Imaging for Resectable Gastric Cancer.

PURPOSE: To prospectively investigate the role of apparent diffusion coefficient (ADC) calculated from diffusion-weighted magnetic resonance (MR) imaging as a potential prognostic biomarker in the evaluation of the aggressiveness of gastric cancer. MATERIALS AND METHODS: This prospective study had institutional review board approval. Informed consent was obtained from all patients. Between October 2009 and December 2013, a total of 99 patients (65 men, 34 women; mean age, 62.02 years; age range, 32.33-85.15 years) with biopsy-proved cancer (28 esophagogastric junction and 71 gastric cancers) were examined with a 1.5-T MR imaging system, including T1-, T2-, and diffusion-weighted sequences. ADC measurements were obtained. Seventy-one patients were directly treated with surgery, while 28 underwent neoadjuvant chemotherapy beforehand. Pathologic ADC, pathologic T and N stages, tumor location, surgical approach, and histologic subtype were investigated with univariate and multivariate analyses by using the Cox regression model. RESULTS: At a total median follow-up period of 21 months, 31 patients had died. The median follow-up was 25 months for the surgery-only group (19 of 31 events [61%]) and 28 months for the chemotherapy group (12 of 31 events [39%]). In the multivariate analysis, ADC values of 1.5 × 10(-3) mm(2)/sec or lower were associated with a negative prognosis, both in the total population (log-relative risk, 1.73; standard error, 0.56; P = .002) and in the surgery-only (log-relative risk, 1.97; standard error, 0.66; P = .003) and chemotherapy (log-relative risk, 2.93; standard error, 1.41; P = .03) groups, along with other significant prognostic factors (in particular, pathologic T and N stages). CONCLUSION: Pathologic ADC represents a strong independent prognostic factor in the evaluation of the aggressiveness of gastric cancer, in addition to clinical and surgical variables.

Duodenal stump fistula after gastric surgery for malignancies: a retrospective analysis of risk factors in a single centre experience.

BACKGROUND: Duodenal stump fistula (DSF) is the most severe surgical complication after gastrectomy. This study was designed to assess the incidence, to observe the consequences, and to identify the risk factors associated with DSF after gastrectomy. METHODS: All procedures involving total or sub-total gastrectomy for cancer, performed between January 1987 and June 2012 in a single institution, were prospectively entered into a computerized database. Risk factors analysis was performed between DSF patients, patients with complete uneventful postoperative course and patients with other major surgical complications. RESULTS: Over this 25 years period, 1287 gastrectomies were performed. DSF was present in 32 cases (2.5 %). Mean post-operative onset was 6.6 days. 19 patients were treated conservatively and 13 surgically. Mean DSF healing time was 31.2 and 45.2 days in the two groups, respectively. Mortality was registered in 3 cases (9.37 %), due to septic shock (2 cases) and bleeding (1 case). In monovariate analysis, heart disease (p < 0.001), pre-operative lymphocytes number (p = 0.003) and absence of manual reinforcement over duodenal stump (p < 0.001) were found to be DSF-specific risk factors, whereas liver cirrhosis (p = 0.002), pre-operative albumin levels (p < 0.001) and blood losses (p = 0.002) were found to be non-DSF-specific risk factors. In multivariate analysis heart disease (OR 5.18; p < 0.001), liver cirrhosis (OR 13.2; p < 0.001), bio-humoral nutritional status impairment (OR 2.29; p = 0.05), blood losses >300 mL (OR 4.47; p = 0.001) and absence of manual reinforcement over duodenal stump (OR 30.47; p < 0.001) were found to be independent risk factors for DSF development. CONCLUSIONS: Duodenal stump fistula still remains a life-threatening complication after gastric surgery. Co-morbidity factors, nutritional status impairment and surgical technical difficulties should be considered as important risk factors in developing this awful complication.