The sacral chordoma margin.

OBJECTIVE: Aim of the manuscript is to discuss how to improve margins in sacral chordoma. BACKGROUND: Chordoma is a rare neoplasm, arising in half cases from the sacrum, with reported local failure in >50% after surgery. METHODS: A multidisciplinary meeting of the "Chordoma Global Consensus Group" was held in Milan in 2017, focusing on challenges in defining and achieving optimal margins in chordoma with respect to surgery, definitive particle radiation therapy (RT) and medical therapies. This review aims to report on the outcome of the consensus meeting and to provide a summary of the most recent evidence in this field. Possible new ways forward, including on-going international clinical studies, are discussed. RESULTS: En-bloc tumor-sacrum resection is the cornerstone of treatment of primary sacral chordoma, aiming to achieve negative microscopic margins. Radical definitive particle therapy seems to offer a similar outcome compared to surgery, although confirmation in comparative trials is lacking; besides there is still a certain degree of technical variability across institutions, corresponding to different fields of treatment and different tumor coverage. To address some of these questions, a prospective, randomized international study comparing surgery versus definitive high-dose RT is ongoing. Available data do not support the routine use of any medical therapy as (neo)adjuvant/cytoreductive treatment. CONCLUSION: Given the significant influence of margins status on local control in patients with primary localized sacral chordoma, the clear definition of adequate margins and a standard local approach across institutions for both surgery and particle RT is vital for improving the management of these patients.

Extended lymphadenectomy in elderly and/or highly co-morbid gastric cancer patients: A retrospective multicenter study.

BACKGROUND: Gastrectomy with extended lymphadenectomy is considered the gold standard treatment for advanced gastric cancer, with no age- or comorbidity-related limitations. We evaluated the safety and efficacy of curative gastrectomy with extended nodal dissection, verifying survival in elderly and highly co-morbid patients. METHODS: In a retrospective multicenter study, we examined 1322 non-metastatic gastric-cancer patients that underwent curative gastrectomy with D2 versus D1 lymphadenectomy from January 2000 to December 2009. Postoperative complications, overall survival (OS), and disease-specific survival (DSS) according to age and the Charlson Comorbidity Score were analyzed in relation to the extent of lymphadenectomy. RESULTS: Postoperative morbidity was 30.4%. Complications were more frequent in highly co-morbid elderly patients, and, although general morbidity rates after D2 and D1 lymphadenectomy were similar (29.9% and 33.2%, respectively), they increased following D2 in highly co-morbid elderly patients (39.6%). D2-lymphadenectomy significantly improved 5-year OS and DSS (48.0% vs. 37.6% in D1, p < 0.001 and 72.6% vs. 58.1% in D1, p < 0.001, respectively) in all patients. In elderly patients, this benefit was present only in 5-year DSS. D2 nodal dissection induced better 5-year OS and DSS rates in elderly patients with positive nodes (29.7% vs. 21.2% in D1, p = 0.008 and 47.5% vs. 30.6% in D1, p = 0.001, respectively), although it was present only in DSS when highly co-morbid elderly patients were considered. CONCLUSION: Extended lymphadenectomy confirmed better survival rates in gastric cancer patients. Due to high postoperative complication rate and no significant improvement of the OS, D1 lymphadenectomy should be considered in elderly and/or highly co-morbid gastric cancer patients.

Does a minimum number of 16 retrieved nodes affect survival in curatively resected gastric cancer?

BACKGROUND: According to the TNM classification, the analysis of 16 or more lymph nodes is required for the appropriate staging of gastric cancer. The aim of this study was to evaluate whether this number of resected lymph nodes also affects survival. METHODS: This was a multicenter retrospective study based on an analysis of 992 patients with gastric adenocarcinoma who underwent curative resection between January 1980 and December 2009. Patients were classified according to the number of resected lymph nodes (<16 and ≥16 lymph nodes), the anatomical extent of lymph node dissection (D2 vs. D1), and the staging criteria of the seventh edition of the UICC/AJCC TNM staging system. Survival estimates were determined by univariate and multivariate analyses. RESULTS: Based on the univariate and multivariate analyses, the resection of 16 or more lymph nodes was associated with significantly better survival [p = 0.002; hazard ratio (HR) (95% confidence interval [CI]): 0.519 (0.345-0.780)]. Patients with a lymph node count <16 had a significantly worse survival rate than patients with a lymph node count ≥16 in the pN0 (p = 0.001), pN1 (p = 0.007) and pN2 (p = 0.001) stages. In the majority of cases, ≥16 lymph nodes were retrieved when D2 dissection was performed. CONCLUSIONS: In gastric cancer the retrieval of less than 16 lymph nodes may cause inaccurate staging and/or inadequate treatment, thus affecting survival rates. These patients should be considered a high-risk group for stage migration and worse survival compared with those who have a retrieval of more than 16 lymph nodes.

Peritonectomy and hyperthermic intraperitoneal chemotherapy: cost analysis and sustainability.

BACKGROUND: Malignancies of the peritoneum remain a challenge in any hospital that accepts to manage them, due not only to difficulties associated with the complexity of the procedures involved but also the costs, which - in Italy and other countries that use a diagnosis-related group (DRG) system - are not adequately reimbursed. MATERIAL AND METHODS: We analyzed data relative to 24 patients operated on between September 2010 and May 2013 with special regard to operating room expenditure, ICU stay, duration of hospitalization, and DRG reimbursement. The total costs per patient included clinical, operating room, procedure, pathology, imaging, ward care, allied healthcare, pharmaceutical, and ICU costs. RESULTS: Postoperative hospital stay, drugs and materials, and operating room occupancy were the main factors affecting the expenditure for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. We had a median hospitalization of 14 days, median ICU stay of 2.4 days, and median operating room occupancy of 585 min. The median expenditure for each case was € 21,744; the median reimbursement by the national health system € 8,375. CONCLUSIONS: In a DRG reimbursement system, the economic effort in the management of patients undergoing peritonectomy procedures may not be counterbalanced by adequate reimbursement. Joint efforts between medical and administration parties are mandatory to develop appropriate treatment protocols and keep down the costs.

cDNA-microarray analysis as a new tool to predict lymph node metastasis in gastric cancer.

BACKGROUND: The aim of the present study was to investigate whether microarray gene expression analysis can be used to predict lymph node status in gastric cancer. METHODS: Twenty-nine patients undergoing gastrectomy for cancer were enrolled and subdivided according to the pathologic nodal involvement of their disease (N+ vs. N0). Molecular profiling was performed by cDNA microarray on tumor tissue and healthy mucosa. Data were processed to identify differently expressed genes. Selected genes were categorized with gene ontology. RESULTS: Compared to healthy gastric mucosa, 52 genes were differently expressed in N+ patients, and 50 genes in N0 patients. Forty-five genes were similarly regulated in N+ and N0 patients, whereas 12 genes were differently expressed between N+ and N0 patients. Seven genes were exclusively expressed in N+ patients: Egr-1 was upregulated; Claudin-18, AKR1C2, Cathepsin E, CA II, TFF 1, and progastricsin were downregulated. Five genes were exclusively expressed in N0 patients: Complement C5 receptor 1, PLA2/VII, and MMP- 9 were upregulated; MAO-A and ID-4 were downregulated. CONCLUSIONS: Microarray analysis could be a valuable tool to identify genes associated with lymph node metastasis in gastric cancer. This technique could improve the selection of patients with locally advanced disease who are candidates for extended lymph node dissection, multimodal treatment options, or alternative therapeutic strategies.

Multidisciplinary care of gastrointestinal stromal tumour: a review and a proposal for a pre-treatment classification.

The introduction of receptor tyrosine kinase inhibitors (TKIs) has revolutionized the management of gastrointestinal stromal tumour (GIST). Strong evidence supports the use of imatinib as first-line treatment in metastatic or unresectable tumours and its efficacy in the post-operative adjuvant setting has been confirmed by phase III trials. There are a number of reports concerning the administration of imatinib in the pre-operative setting, however, the heterogeneity of the terminology used and the indications for pre-operative treatment make it difficult to determine the true value of pre-operative imatinib. Larger studies, or a phase III trial could be helpful but patient accrual and standardization of care could be difficult. We propose a pre-treatment classification of GIST in order to facilitate the comparison and collection of data from different institutions, and overcome the difficulties related to accrual. Moreover, in the current era of multidisciplinary treatment of GIST, an appropriate classification is mandatory to properly design clinical trials and plan stage-adapted treatment.

Surgical issues after neoadjuvant treatment for gastric cancer.

Gastric carcinoma is one of the most frequent malignancies in the world and its clinical behavior depends on the metastatic potential of the tumour. Particularly, lymphatic metastasis is one of the main predictor of tumour recurrence and survival and current pathologic staging systems reflect the concept that lymphatic spread is the most relevant prognostic factor in patients resected with curative intent. This is deducted by the observation that two thirds of gastric cancers in the western world present at an advanced stage, with nearly 85% of tumors accompanied by lymph node metastasis at diagnosis. To date most therapeutic efforts are directed toward individualization of therapeutic protocols, tailoring the extent of resection integrated by the administration of preoperative and postoperative treatment. The goal of such strategies is to improve prognosis towards the achievement of a curative resection (R0-resection) with minimal morbidity and mortality, with better postoperative quality of life. A brief review of literature about preoperative therapy for gastric carcinoma will be herein illustrated. The rationale and the general drawbacks of preoperative treatments will be both discussed in order to demonstrate its value in terms of safety and efficacy.

Ratio of metastatic lymph nodes: impact on staging and survival of gastric cancer.

AIMS: No consensus exists on the level and number of lymph nodes to be dissected and examined for accurate staging of patients with resectable gastric cancer. The aim of this study was to examine the prognostic value and staging accuracy of the metastatic lymph nodes ratio (NR). METHODS: The postoperative survival of 247 patients with gastric cancer who underwent gastrectomy was analyzed. Lymph nodes status was assigned according to three different classifications: 6th UICC/AJCC TNM; JGCA; NR (NR0: 0%; NR1: < or =20%; NR2: >20%). Staging accuracy of the three classifications was compared according to patients survival. RESULTS: A significant difference in survival was observed in patients with NR1 versus NR2. At multivariate analysis only NR along with pT and grading were found to be independent prognostic factors. Stage migration was present in 84 cases (51%) with JGCA classification, in 30 (19%) with 6th UICC/AJCC TNM classification and in only 18 cases (11%) when NR was applied. CONCLUSIONS: Our data showed that NR is a simply reproducible and highly reliable staging system with a strong ability to predict patients' outcome. Compared to other nodal staging classifications, NR is less influenced from the number of the lymph nodes dissected and examined, reducing the stage migration phenomenon.

A case-control study comparing methylene blue directed biopsies and random biopsies for detecting pre-cancerous lesions in the follow-up of gastric cancer patients.

OBJECTIVES: To compare the accuracy of Methylene Blue (MB) targeted biopsies with random biopsies in detecting intestinal metaplasia and dysplasia in the follow-up of patients after gastrectomy for gastric cancer. METHODS: Thirty patients (21 Billroth II, 9 Billroth 1) for cancer, referred to the Gastroenterology Unit for an elective esophagogastroduodenoscopy (EGD), were enrolled. All endoscopies were performed with a high-resolution videoendoscope with an adjustable image magnification: EG-485ZH (Fujinon, Omiya, Japan). During EGD three random biopsies were taken in the stomach and, after staining with MB, three targeted biopsies were taken from every stained area. RESULTS: In 28 patients traditional endoscopy showed hyperemia of the anastomosis, in 2 patients a lesion. After MB in 6/30 there were stained area (2 lesions seen with traditional endoscopy and 4 blue areas in other patients). As regards histology: 24 patients showed inflammation, while 2 patients with alterations in traditional endoscopy and with MB showed metaplasia and high grade dysplasia. In 4/30 (13.3%) patients MB guided biopsies showed significant lesions (3 intestinal metaplasia, 1 low grade dysplasia) while random biopsies showed only inflammation. CONCLUSIONS: After partial gastrectomy, the mucosa of the residual stomach usually undergoes severe changes, and these lesions are known to be pre-cancerous. The diagnostic accuracy of the MB technique seems to be superior to random biopsies for identification of intestinal metaplasia, dysplasia, and may be helpful in targeting biopsies and early endoscopic treatment.

[Clinical significance and prognostic value of tumor maximum diameter in gastric carcinoma]. / Significatività clinica e valore prognostico del diametro massimo del tumore nel carcinoma gastrico.

Maximum tumor diameter (MTD) is considered by many authors as an important prognostic factor in gastric cancer and, in some series, is reported to be strongly correlated with depth of infiltration. Aim of this study was to evaluate the prognostic value of tumor diameter in a monoistitutional series of 153 gastric cancer patients. The Spearman correlation coefficient was also calculated between MTD and other known prognostic factors. For statistical analysis, patients were grouped as follows: MTD 1, < or = 40 mm, and MTD2, > 40 mm. In our series, MTD resulted significantly linked to survival at univariate analysis (p = 0.0001), but multivariate analysis did not evidence MTD as an independent prognostic indicator. The Spearman correlation test documented that MTD2 is strongly correlated with tumor depth (pT), nodal status (pN) and p-stage (p < 0.01) and is a good predictor of locally advanced stage. This retrospective study showed that patients with larger tumor are at an increased risk for tumor advancement and, therefore, MTD could represent a useful parameter for choosing the most appropriate therapeutic strategy.