Extension of lymphadenectomy for gastric cancer:Audit at European specialist centres.

Gastric cancer is still one of the leading causes of cancer-related deaths worldwide, and its treatment management differs between Eastern Asia and Western countries. Screening program, early diagnosis, and surgical treatment was primarily established in Japan and was rapidly disseminated to other countries. In other parts of the world, such as the USA and Western Europe, the incidence of gastric cancer has declined, and efforts for screening and early detection have not been an issue of higher priority over the management of other diseases. Thus, gastric cancer in the West is often more advanced and is either inoperable or needs more radical surgery for resection. The only treatment method that can potentially cure gastric cancer is the surgical approach. Depending on the extension of the tumor, surgeons may execute an operation that involves removing all or part of the stomach with some nearby lymph nodes (lymphadenectomy). Lymphadenectomy is a crucial step during surgical operation that involves the removal of one or more lymph nodes located in the drainage area of a tumor, in which there is a high possibility of lymph node metastasis. The Japanese guidelines define the criteria of lymphadenectomy procedure into D1 D1+ or D2 according to the type of gastrectomy executed. The extent of lymphadenectomy has long been a subject of debate. Indeed, Japanese surgeons introduced extended lymphadenectomy (D2), which has also been progressively adopted in Europe and included in almost all international guidelines. However, the procedure requires a long learning curve, which involves a high volume of interventions; therefore, US guidelines do not recommend the D2, and many Italian and European centres do not yet perform this procedure. Indeed, the current European Consensus guidelines recommend D2 dissection in regional specialist centres for patients with moderate comorbidity. However, compliance with guidelines is unclear, and in some recent RCTs, the standard approach of surgical treatment is at the "surgeon's discretion." This study aims to evaluate the current practice of D2 lymphadenectomy in Europe to determine any variation in practice and compare it with the Japanese guidelines. The study consists of two parts: first, a questionnaire based on hypothetical clinical scenarios was administered to expert surgeons belonging to European Chapter of the International Gastric Cancer Association from high-volume European centers. They were asked to select the appropriate lymphadenectomy extension for each hypothetical case and the associated lymph node stations to remove. In the second part of the study, the same surgeons were asked to collect their data about gastric cancer gastrectomies performed in 2015 for comparative analysis. The study results show that the expert surgeons of high-volume centres are quite in agreement with the choice of D2 lymphadenectomy in the different clinical scenarios. The surgical choice seems to have been influenced by the tumor stage, site, and histology of the tumor. More specifically, the D2 procedure is recommended for cases with diffuse histology compared to tumors with intestinal histology. However, the selection of the D2 dissection procedure rarely conformed to Japanese guidelines: the choice of lymph node stations revealed the presence of a wide variation in execution. In the review of the gastrectomy experience, it was observed that a high surgical standard was achieved: in fact, in 97% of gastric cancer gastrectomies after D2, an adequate number of lymph nodes (≥15 nodes) were removed. In conclusion, even if an adequate lymphadenectomy was obtained in almost all cases in dedicated centers, there is still significant variability in the number of recovered lymph nodes. The histology of the tumor largely influences the surgeon's choice regarding the extent of the lymphadenectomy; however, the role of histology in the planning of surgical procedures is not considered in the current guidelines and must be verified in prospective studies

Is fall prevention by vitamin D mediated by a change in postural or dynamic balance?

Introduction: The objectives were:(1) to validate a quantitative balance assessment method for fall risk prediction; (2) to investigate whether the effect of vitamin D and calcium on the risk of falling is mediated through postural or dynamic balance, as assessed by this method. Materials and methods: A secondary analysis of a double blind randomized controlled trial was employed, which included 64 institutionalized elderly women with complete balance assessment (age range: 65-97; mean 25-hydroxyvitamin D levels: 16.4ng/ml (SD ±9.9). Participants received 1,200mg calcium plus 800IU cholecalciferol (n=33) or 1,200mg calcium (n=31) per day over a 3-month treatment period. Using an electronic device attached to the lower back of the participant, balance was assessed as the degree of trunk angular displacement and angular velocity during a postural task (standing on two legs, eyes open, for 20 s) and a dynamic task (get up from a standard height chair with arm rests, sit down and then stand up again and remain standing). Results: It was found that both postural and dynamic balance independently and significantly predicted the rate of falling within the 3-month follow-up. Vitamin D plus calcium reduced the rate of falls by 60% [relative risk (RR)=0.40; 95% CI: 0.17, 0.94] if compared with calcium alone. Once postural and dynamic balance were added to the regression analysis, they both attenuated the effect of vitamin D plus calcium on the rate of falls. For postural balance, the RR changed by 22% from 0.40 to 0.62 if angular displacement was added to the model, and by 9% from 0.40 to 0.49 if angular velocity was added. For dynamic balance, it changed by 1% from 0.40 to 0.41 if angular displacement was added, and by 14% from 0.40 to 0.54 if angular velocity was added. Discussion: Thus, balance assessment using trunk angular displacement is a valid method for the prediction of falls in older women. Of the observed 60% reduction in the rate of falls by vitamin D plus calcium supplementation compared with calcium alone, up to 22% of the treatment effect was explained by a change in postural balance and up to 14% by dynamic balanc

Pathological prognostic factors in the second British Stomach Cancer Group trial of adjuvant therapy in resectable gastric cancer.

The second British Stomach Cancer Group trial was a prospective randomised controlled trial of adjuvant radiotherapy or cytotoxic chemotherapy after gastrectomy for adenocarcinoma. It recruited between 1981 and 1986. No survival advantage has been demonstrated for the patients receiving either type of adjuvant therapy compared with those undergoing surgery alone. We report on 436 patients randomised into the trial together with 203 patients, who did not fulfil the trial criteria, referred to the trial. A univariate (log-rank) analysis of pathological factors obtained from the local referring centres showed that tumour size, macroscopic type, number os sites involved, depth of invasion, involvement of resection lines and lymph nodes and histological grade were significant determinants of survival. Histological review by two experienced histopathologists found that the Lauren classification and histological grade, but not the Ming classification, were significant prognostic factors. The degree of lymphocytic and eosinophilic infiltration and presence of dysplasia assessed by one of the pathologists showed a significant correlation with survival. However, inter-observer correlation for these histological parameters and grade was poor. Multivariate analysis identified only depth of invasion, resection line and nodal involvement as significant independent pathological variables influencing survival. This study confirms the need for expert preparation of the resected specimen to obtain the important information on depth of invasion and nodal status and also reveals some variation in histological assessment, particularly grading, in gastric carcinoma

Loss of Ep-CAM (CO17-1A) expression predicts survival in patients with gastric cancer

Preoperative staging of gastric cancer is difficult and not optimal. The TNM stage is an important prognostic factor, but it can only be assessed reliably after surgery. Therefore, there is need for additional, reliable prognostic factors that can be determined preoperatively in order to select patients who might benefit from (neo) adjuvant treatment. Expression of immunohistochemical markers was demonstrated to be associated with tumour progression and metastasis. The expression of p53, CD44 (splice variants v5, v6 and v9), E-cadherin, Ep-CAM (CO17-1A antigen) and c-erB2/neu were investigated in tumour tissues of 300 patients from the Dutch Gastric Cancer Trial, investigating the value of extended lymphadenectomy compared to that of limited lymphadenectomy). The expression of tumour markers was analysed with respect to patient survival. Patients without loss of Ep-CAM-expression of tumour cells (19%) had a significantly better 10-year survival (P<0.0001) compared to patients with any loss: 42% (s.e.=7%) vs 22% (s.e.=3%). Patients with CD44v6 (VFF18) expression in more than 25% of the tumour cells (69% of the patients) also had a significantly better survival (P=0.01) compared to patients with expression in less than 25% of the tumour cells: 10 year survival rate of 29% (s.e.=3%) vs 19% (s.e.=4%). The prognostic value of both markers was stronger in stages I and II, and independent of the TNM stage. Ep-CAM and CD44v6-expression provides prognostic information additional to the TNM stage. Loss of Ep-CAM-expression identifies aggressive tumours especially in patients with stage I and II disease. This information may be helpful in selecting patients suitable for surgery or for additional treatment pre- or postoperatively