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Introduction The simultaneous assessment of multiple indicators for quality of care is essential for comparisons of performance between hospitals and health care systems. The aim of this study was to assess the rates of in-hospital mortality and 30-day readmission and length of hospital stay (LOS) in patients who underwent surgical procedures for colorectal cancer between 2005 and 2014 in Italy. Methods All patients in the National Italian Hospital Discharge Dataset who underwent a surgical procedure for colorectal cancer during the study period were included. The adjusted odd ratios for risk factors for in-hospital mortality, 30-day readmission, and LOS were calculated using multilevel multivariable logistic regression. Results Among the 353 941 patients, rates of in-hospital mortality and 30-day readmission were 2.5% and 6%, respectively, and the median LOS was 13 days. High comorbidity, emergent/urgent admission, male gender, creation of a stoma, and an open approach increased the risks of all the outcomes at multivariable analysis. Age, hospital volume, hospital geographic location, and discharge to home/non-home produced different effects depending on the outcome considered. The most frequent causes of readmission were infection (19%) and bowel obstruction (14.6%). Conclusions We assessed national averages for mortality, LOS and readmission and related trends over a 10-year time. Laparoscopic surgery was the only one that could be modified by improving surgical education. Higher hospital volume was associated with a LOS reduction, but our findings only partially support a policy of centralization for colorectal cancer procedures. Surgical site infection was identified as the most preventable cause of readmission. [ABSTRACT FROM AUTHOR]

Background Owing to its rarity, the published evidence on gastrointestinal (GI) carcinoid is often based on small series of patients or population-based studies regarding all neuroendocrine tumors. Here, we present a comprehensive epidemiological and survival analysis of the largest cohort of patients with GI carcinoid ever reported. Patients and methods Patients with histological diagnosis of GI carcinoid (n = 25 531) were identified from the Surveillance Epidemiology End Results (SEER) database (including 18 USA cancer registries and spanning the 1973–2009 time frame). Demographic and disease data were used for epidemiological and survival analyses. Results The incidence of GI carcinoid is steadily increasing over the past three decades at a rate higher than any other cancer [annual percentage change (APC) = 4.4, 95% confidence interval (CI) 4.0–4.8]. These patients have a higher risk of further primary tumor (standardized incidence ratio, SIR = 1.15, 95% CI 1.10–1.21), but also a reduced risk of skin melanoma (SIR = 0.64, 95% CI 0.41–0.95). Despite the overall favorable prognosis (5-year disease-specific and relative survival rate: 91.3% and 87.4%, respectively), the mortality rate is increasing over time (APC = 3.5, 95% CI 3.0–4.0) and the 5-year survival rate of patients dying of GI carcinoid (28.5%), though better than that reported for GI cancers in general (8.4%), cannot be considered satisfactory. Finally, a nomogram is provided to predict patient survival on the basis of clinico-pathological factors independently associated with prognosis at multivariate analysis. Conclusions These findings can be clinically useful for the management of patients with GI carcinoid and eagerly prompt the continuous effort to develop more effective therapeutic strategies against this slow-growing but chemoresistant tumor. [ABSTRACT FROM PUBLISHER]

Abstract: Background: The prognostic value of T subclassification in patients with gastric carcinoma has been just implemented in the new AJCC TNM staging system, which has reclassified T2a and T2b into T2 and T3 tumors, respectively. The aim of the present study was to validate the prognostic significance of the new T categorization within the frame of the latest TNM staging system. Methods: We retrospectively reviewed the records of 686 T2/T3 patients among 2155 subjects who underwent radical resection for gastric carcinoma at six Italian centers from 1988 through 2006. Results: Upon multivariate analysis, the new T categories, extent of lymph node dissection (D) and patient’s age were retained by the survival model as independent prognostic factors. In particular, the death risk for patients with T3 tumors was higher than that of patients with T2 tumors (HR: 1.42, P = 0.005). Among the 686 patients previously classified as having T2 tumors, patients with T2 and T3 disease were 270 (39.4%) and 416 (60.6%), respectively. After a median follow-up of 55 months, the 5-year overall survival rates were 67.3% and 52.3% for patients with T2 and T3 tumors, respectively (P < 0.001). The survival advantage for the T2 as compared to T3 category was maintained even when N0 and N+ patients were separately considered (P = 0.0154 and P < 0.001, respectively). Conclusions: Our data confirm the prognostic difference between the newly proposed T2 and T3 categories, which should be implemented in the routine clinical practice to improve risk stratification of patients with gastric cancer. [Copyright &y& Elsevier]

Abstract: Aims: Investigators from the Memorial Sloan Kettering Cancer Centre (MSKCC) have proposed a nomogram for predicting the sentinel node (SN) status in patients with cutaneous melanoma. The negative predictive value (NPV) of this test, which might help identify low-risk patients who might be safely spared SN biopsy (SNB), has not been yet investigated. Methods: We tested the discrimination (area under the curve [AUC]), the calibration (linear regression) and the NPV of MSKCC nomogram in 543 patients treated at our institution. Different cut-off values were tested to assess the NPV, the reduction of SNB performed and the overall error rate obtained with the MSKCC nomogram. Results: SN was positive in 147 patients (27%). Mean predicted probability was 17.8% (95%CI: 16.8–18.8%). Nomogram discrimination was significant (area under the curve = 0.68; P < 0.0001) and mean predicted probabilities of SN positivity well correlated with the observed risk (R 2 = 0.99). Cut-off values between 4% and 9% led to a NPV, SNB reduction and overall error rates ranging between 100 and 91.2%, 2.2 and 27.2%, and 0 and 2.3%, respectively. Conclusion: In our series, the nomogram showed a significant predictive accuracy, although the incidence of SN metastasis was higher than that observed in the MSKCC series (27% vs 16%). Using the nomogram, a NPV greater than 90% could be obtained, which would be associated with a clinically meaningful reduction of the SNB rate and an acceptable error rate. If validated in large prospective series, this tool might be implemented in the clinical setting for SNB patient selection. [Copyright &y& Elsevier]

Abstract: Background: Positive lumpectomy margins (LM) usually mandate re-excision. However, approximately half of these patients have no residual tumour in the re-excision specimen. The aim of this study was to investigate if separate cavity margin (CM) excision can safely reduce the need of re-operation. Methods: Rate of re-operation for margin involvement and incidence of residual tumour in the re-excision specimen were retrospectively evaluated in 237 patients (group A) who underwent lumpectomy alone, and in 271 patients (group B) treated by lumpectomy and CM excision. Patients with positive LM (group A) or CM (group B) underwent re-excision. Results: In the group A, 50/237 patients (21.1%) had LM+ and underwent re-excision. In the group B, 74/271 patients (27.3%) had LM+, but tumour was found within the CM specimen in 46 patients (17.0%), 24 LM+ and 22 LM−, and reached the CM cut edge in only 15 (5.5%), who finally underwent re-excision. Residual tumour was found in the re-excision specimen in 28/50 patients (56.0%) of the group A and in 7/15 patients (46.7%) of the group B. Conclusions: Separate CM excision strongly decreases the rate of re-operation for involved margin. However, the finding of various combinations of LM and CM status and the evidence that CM excision does not improve the positive predictive value of margin involvement suggest prudent conclusions. Only long term follow up of patients treated according to the CM status can exclude that the reduced rate of re-operations allowed by this procedure would expose to an increased risk of local recurrence. [Copyright &y& Elsevier]

Abstract: Background: The treatment of hepatic metastases from gastric cancer is controversial, due to biologic aggressiveness of the disease. Objective: To survey the clinical approach to the subset of patients presenting with metachronous hepatic metastases as sole site of recurrence after curative resection of gastric cancer, focusing on the results achieved by different therapies and to investigate the prognostic factors of major clinical relevance. Methods: Retrospective multi-center chart review evaluating 73 patients, previously submitted to D ≥2 gastrectomy for gastric cancer, who developed exclusive hepatic recurrence. Prognostic factors related to the patient, to the gastric malignancy and its treatment, and to the metastatic disease and its therapy were evaluated. Results: Forty-five patients received supportive care, 17 were submitted to chemotherapy, and 11 to hepatic resection. Survival was independently influenced by the variables T (p =0.019), N (p =0.05) and G (p =0.018) of the gastric primary and by the therapeutic approach to the metastases (p <0.005). In particular, T4 gastric cancer, presence of lymph-node metastases and G3 tumor displayed a negative prognostic value. Therapeutic approach to the metastases was the principal prognostic variable: 1, 2, and 3 years survival rates were 22.2%, 4.4% and 2.2%, respectively, for patients without specific treatment; 44.9%, 12.8% and 6.4% after chemotherapy (p =0.08) and 80.8%, 30.3% and 20.2% after surgical resection (p <0.001). Conclusions: Our data suggest some clinical criteria that may facilitate selection of therapy for patients with hepatic recurrence after primary gastric cancer resection. The best survival rates are associated with surgical treatment, which should be chosen whenever possible. [Copyright &y& Elsevier]

Abstract: Objectives: p53 Gene variants BstUI RFLP at codon 72 in exon 4, 16bp tandem repeat in intron 3 and MspI RFLP in intron 6, which code for two functionally different protein isoforms, have been shown to modulate susceptibility to different types of human neoplasms. Methods: p53 genotype was assessed in 90 CRC patients, 321 age-matched controls and 322 centenarians. Results: The p53 codon 72 arginine, the p53 16bp deletion, and the MspI RFLP were significantly more frequent in CRC patients in comparison to the controls and to the centenarians (odd ratio 1.44 and 1.93). In the CRC group, the BstUI RFLP polymorphism was the more frequent combination (62.2%), and it was significantly associated with highly infiltrating (p <0.01), poorly differentiated (p <0.01), and metastatic (p <0.05) tumours. Our findings indicate that the p53 codon 72 polymorphisms are associated with a higher risk of CRC and are associated with more advanced and undifferentiated tumours. [Copyright &y& Elsevier]

Abstract: Aim: Rectal cancer staging represents a crucial step to select the best treatment for this tumour. Particularly after neo-adjuvant chemoradiotherapy (CRT), it may influence the surgical procedure (e.g. radical resection vs. local excision). The aim of this study was to determine the best lymph node size cut-off at computed tomography (CT) to predict nodal metastasis in rectal cancer patients with and without preoperative CRT. Methods: A consecutive series of patients operated on for primary mid–low rectal adenocarcinoma, all staged with pelvic CT scan, were subdivided as follows: those who underwent surgery alone treatment without CRT (Group A) and those who underwent preoperative CRT (Group B). All CT scans were re-viewed by a single radiologist and, based on the lymph node size, findings were compared with pathologic lymph node status (pN). At each lymph node size cut-off value, the following were calculated: accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). The best cut-off value was defined as having an accuracy ≥70% with the highest NPV. Results: The study population consisted of 162 patients: Group A (n =52) and Group B (n =110). Patients classified as pN-positive (n =45) had a higher number of and larger sized lymph nodes by CT scan than patients classified as pN-negative (n =117). The cut-off values with an accuracy ≥70% ranged between 7 and 11mm in Group A and between 9 and 14mm in Group B. The cut-off with the best NPV was 7mm for Group A and 10mm for Group B. Conclusions: Acknowledging the limitations of the dimensional criterion, lymph node size cut-off values found in our study may be useful for planning rectal cancer treatment using CT scan. [Copyright &y& Elsevier]

Abstract: Aims: To evaluate the incidence of false-negative (FN) sentinel lymph node (SLN) cases, their correlation with a series of clinico-pathologic parameters and their impact on adjuvant treatment indications and on clinical axillary relapse in the setting of a multicentric clinical trial comparing SLN biopsy with axillary lymph node dissection (ALND). Methods: A series of 697 patients with primary breast cancer≤3cm were randomized to SLN biopsy associated with ALND (ALND arm) or to SLN biopsy followed by ALND only if the SLN was metastatic (SLN arm). The FN SLN rate was assessed in the ALND arm. A series of 11 clinico-pathological parameters were tested for a possible association with FN results. The indications for adjuvant treatments were evaluated by considering both the FN nodal stages, as indicated by the SLN, and the true positive axillary status, as indicated by completion ALND. The occurrence of clinically evident axillary recurrences was evaluated in the two arms. Results: The FN rate was 16.7%. Of the clinico-pathologic parameters tested, only a tumour size≤2cm and the presence of a single metastatic axillary node was significantly associated with a risk of FN (p =0.033 and p =0.018, respectively). The FN SLN would have led to different adjuvant therapy indications in 12/18 cases. At 56 months, no clinically evident axillary nodal recurrences were present in the ALND arm patients, whereas one case of axillary recurrence was detected in the SLN arm patients. Conclusions: FN SLN biopsy is not uncommon, especially in the presence of a small primary tumour with a single nodal metastasis. An FN finding can lead to less than optimal adjuvant treatment. However, the clinical impact of FN in terms of axillary recurrence at 56 months was minimal. [Copyright &y& Elsevier]

Abstract: Aims: The proportion between metastatic and examined lymph nodes (N-ratio) has been proposed as an independent prognostic factor in patients with gastric cancer. In the present work we validated the reliability of N-ratio in a large, multicenter series. Patients and methods: We retrospectively reviewed the data of 1853 patients who underwent radical resection for gastric carcinoma. Survival of patients with >15 (Group-1, n =1421) and those with ≤15 (Group-2, n =432) lymph nodes examined was separately analyzed in order to evaluate the influence of lymph node dissection on disease staging. N-ratio categories (N-ratio 0, 0%; N-ratio 1, 1–9%; N-ratio 2, 10–25%; N-ratio 3, >25%) were determined by the best cut-off approach. Results: At multivariate analysis, N-ratio (but not TNM N-category) was retained as an independent prognostic factor both in Group-1 and Group-2 (HR for N-ratio 1, N-ratio 2 and N-ratio 3=1.67, 2.96 and 6.59, and 1.56, 2.68 and 4.28, respectively). After a median follow-up of 45.5months, the 5-year overall survival rates of TNM N0, N1 and N2 patients were significantly different in Group-1 vs Group-2. This was not the case when adopting the N-ratio classification, suggesting that a low number of excised lymph nodes can lead to patients being understaged using the N-category, but not N-ratio. Moreover, N-ratio identified subsets of patients with significantly different survival rates within TNM N1 and N2 categories in both groups. Conclusions: N-ratio is a simple and reproducible prognostic tool that can stratify patients with gastric cancer, including those cases with limited lymph node dissection. These data support the rationale to propose the implementation of N-ratio into the current TNM staging system. [Copyright &y& Elsevier]

Abstract: Aims: To investigate early and late complications in 44 patients with locally advanced mid-low rectal cancer enrolled in a phase I–II study, who had received an aggressive chemoradiation treatment (50.4Gy/28F; 5-FU continuous infusion and weekly Oxaliplatin) followed by total mesorectal excision and 5-FU based postoperative chemotherapy. The aim of the present study is also to evaluate functional outcome and quality of life (QoL) in a sub-group of 22 patients. Methods: Standardized forms for early and late surgical complications were completed for all patients. Anorectal function and QoL were also investigated in 22 patients who underwent surgery in the same surgical unit, using the fecal incontinence scoring system (FIS) and EORTC-QLQ-CR38 questionnaires, compiled before and after radiotherapy and at least 8 months after surgery. The differences over time in scores were analyzed using repeated measure ANOVA. Results: The median age of patients (25 males and 19 females) was 58 (range: 34–73) years. A low anterior resection was performed in 39 cases, radical resection in 41, and 12 patients had a pathological complete response. There were no operative deaths; 4 and 9 patients required re-operation for early and late complications, respectively. FIS score did not present a significant worsening over time. According to data in the EORTC-QLQ-CR38 questionnaire, a significant improvement over time was found only for “future perspective”. Conclusion: Our findings seem to indicate that this aggressive 5-FU–Oxalipaltin-based treatment implies no impairment of QoL and anorectal function, even if a high rate of late major complications was observed. Studies on larger series are required to confirm these results. [Copyright &y& Elsevier]

Abstract: Aims: To investigate the survival benefit of extended lymphadenectomy (D2) in EGC patients in one European Institution. Methods: A review was made of our prospective gastric database from January 1980 to December 2001. Of 527 patients with primary gastric adenocarcinoma, 119 with EGC underwent potentially curative resection (R0) with D2 lymphadenectomy. Results: There were two post-operative deaths. Of the 117 evaluable cases, 96 were classified as N0 and 21 as N+, with metastases in the perigastric lymph nodes (level 1) in 13, and beyond this site (level 2) in eight. Five-year survival was 85.9 and 83.0% in N0 and N+ patients, respectively. During a median follow-up of 90 months, five of the eight patients with level 2 metastases died of recurrent disease and three were alive. The estimated survival benefit for 119 patients with EGC was 2.5% (3/119 cases). Conclusions: In patients with EGC, metastases to level 2 are rare. Our results indicate that D2 lymphadenectomy has a limited survival benefit and that in these cases a less extensive lymphadenectomy (D1) could be performed. [Copyright &y& Elsevier]

Abstract: Aims: To determine the axillary recurrence rate in breast cancer patients with negative sentinel lymph nodes (SLN) who did not undergo further axillary lymph node dissection (ALND), and to establish whether this conservative axillary approach leads to an increased recourse to diagnostic axillary biopsy during the follow-up period because of the clinical suspicion of nodal recurrence. Methods: In 479 patients, operated on for early breast cancer between 1998 and 2002 in five institutions, SLN biopsy was negative and no further axillary surgery was performed. SLN was localized using subdermal injection with 30–50MBq of 99m-Tc-colloidal albumin. Follow-up controls were performed at 6-monthly intervals. Results: The mean number of SLNs removed was 1.4 per patient. Most patients (90.6%) were given adjuvant systemic therapy, based on the primary tumour characteristics. At a median follow-up of 35.8 months, no clinical axillary recurrence was found. No patient underwent surgical axillary biopsy for suspicious clinical or ultrasonographic findings. Conclusions: Our results confirm that SLN biopsy without ALND in SLN-negative patients with early breast cancer is not followed by clinically evident axillary recurrence in the short-term. [Copyright &y& Elsevier]

Abstract: Aim: To report the pattern of lymphatic mapping following intrasubdermal injections of radiocolloid and of blue dye in different sites of the breast. Methods: Prior to surgery 137 breast cancer patients underwent intrasubdermal injection of 30–50MBq 99mTc-colloidal albumin over the tumour site (ISI group). Ten minutes before surgery, 2ml patent blue was injected in the subareolar area (SAI group) in 117/137 patients, while 20 patients received intrasubdermal blue-dye in the quadrant opposite the tumour site (OQI group). The different injection routes were considered concordant when the hottest sLN was also blue. Results: In 134/137 patients radiocolloid drained to one or more axillary nodes, while blue nodes were found in 98/117 SAI patients and in 17/20 OQI patients. Multiple hot nodes were found in 63/134 cases and multiple blue nodes in 35/115. In patients in whom both tracers reached the axilla, the hottest node was also blue in 108/115 cases (93/98 SAI and 15/17 OQI patients). In the seven discordant cases, the hottest node was not blue, but in two cases the blue node was also radioactive. Conclusions: Superficial lymphatic drainage from the breast most frequently merges to a single axillary lymph node, irrespective of the site of tracer injection. In a few cases different injection sites identify different, often closely interconnected sLNs. [Copyright &y& Elsevier]

This paper show the results of a clinical study conducted in Italy on the efficacy of the adjuvant chemotherapy in operable gastric cancer. The study shows conclusively that an intensive polychemotherapy given as postoperative treatment achieves the same results, in terms of disease-free and overall survival, of a monotherapy with fluorouracil. The strength of the study is in the large number of patients included over a limited period, making it one of the most significant in the western world.Background Some trial have demonstrated a benefit of adjuvant fluoropirimidine with or without platinum compounds compared with surgery alone. ITACA-S study was designed to evaluate whether a sequential treatment of FOLFIRI [irinotecan plus 5-fluorouracil/folinic acid (5-FU/LV)] followed by docetaxel plus cisplatin improves disease-free survival in comparison with 5-FU/LV in patients with radically resected gastric cancer. Patients and methods Patients with resectable adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to either FOLFIRI (irinotecan 180 mg/m2 day 1, LV 100 mg/m2 as 2 h infusion and 5-FU 400 mg/m2 as bolus, days 1 and 2 followed by 600 mg/m2/day as 22 h continuous infusion, q14 for four cycles) followed by docetaxel 75 mg/m2 day 1, cisplatin 75 mg/m2 day 1, q21 for three cycles (sequential arm) or De Gramont regimen (5-FU/LV arm). Results From February 2005 to August 2009, 1106 patients were enrolled, and 1100 included in the analysis: 562 in the sequential arm and 538 in the 5-FU/LV arm. With a median follow-up of 57.4 months, 581 patients recurred or died (297 sequential arm and 284 5-FU/LV arm), and 483 died (243 and 240, respectively). No statistically significant difference was detected for both disease-free [hazard ratio (HR) 1.00; 95% confidence interval (CI): 0.85–1.17; P = 0.974] and overall survival (OS) (HR 0.98; 95% CI: 0.82–1.18; P = 0.865). Five-year disease-free and OS rates were 44.6% and 44.6%, 51.0% and 50.6% in the sequential and 5-FU/LV arm, respectively. Conclusions A more intensive regimen failed to show any benefit in disease-free and OS versus monotherapy. Clinical trial registration ClinicalTrials.gov Identifier: NCT01640782. [ABSTRACT FROM AUTHOR]

Background The impact of adherence to clinical practice guidelines (CPGs) for loco-regional treatment (i.e. surgery and radiotherapy) and chemotherapy on local disease control and survival in sarcoma patients was investigated in a European study conducted in an Italian region (Veneto). Patients and methods The completeness of the adherence to the Italian CPGs for sarcomas treatment was assessed by comparing the patient's charts and the CPGs. Propensity score-adjusted multivariate survival analysis was used to assess the impact of CPGs adherence on patient clinical outcomes. Results A total of 151 patients were included. Adherence to CPGs for loco-regional therapy and chemotherapy was observed in 106 out of 147 (70.2%) and 129 out of 139 (85.4%) patients, respectively. Non-adherence to CPGs for loco-regional treatment was independently associated with AJCC stage III disease [odds ratio (OR) 1.77, P = 0.011] and tumor-positive excision margin (OR 3.55, P = 0.003). Patients not treated according to the CPGs were at a higher risk of local recurrence [hazard ratio (HR) 5.4, P < 0.001] and had a shorter sarcoma-specific survival (HR 4.05, P < 0.001), independently of tumor stage. Conclusions Incomplete adherence to CPGs for loco-regional treatment of sarcomas was associated with worse prognosis in patients with non-metastatic tumors. [ABSTRACT FROM AUTHOR]

Active specific immunotherapy holds great potential in the search for new therapeutic approaches for patients with cancer. Much preclinical and clinical evidence has shown that the immune system can be polarised against malignant cells by several vaccination strategies. Although no anticancer vaccine can be recommended outside clinical trials at present, tumour response and immunological findings in animals and humans should prompt researchers to investigate further the potential of this biotherapy. We summarise strategies for cancer vaccines so far implemented in the clinical setting, report the results of more than 200 clinical trials published over the past two decades, and discuss insights into preclinical tumour immunology that might aid the design of the next generation of cancer vaccines. [ABSTRACT FROM AUTHOR]