Gastric cancer: Current status of lymph node dissection

D2 procedure has been accepted in Far East as the standard treatment for both early(EGC) and advanced gastric cancer(AGC) for many decades. Recently EGC has been successfully treated with endoscopy by endoscopic mucosal resection or endoscopic submucosal dissection, when restricted or extended Gotoda's criteria can be applied and D1+ surgery is offered only to patients not fitted for less invasive treatment. Furthermore, two randomised controlled trials(RCTs) have been demonstrating the non inferiority of minimally invasive technique as compared to standard open surgery for the treatment of early cases and recently the feasibility of adequate D1+ dissection has been demonstrated also for the robot assisted technique. In case of AGC the debate on the extent of nodal dissection has been open for many decades. While D2 gastrectomy was performed as the standard procedure in eastern countries, mostly based on observational and retrospective studies, in the west the Medical Research Council(MRC), Dutch and Italian RCTs have been conducted to show a survival benefit of D2 over D1 with evidence based medicine. Unfortunately both the MRC and the Dutch trials failed to show a survival benefit after the D2 procedure, mostly due to the significant increase of postoperative morbidity and mortality, which was referred to splenopancreatectomy. Only 15 years after the conclusion of its accrual, the Dutch trial could report a significant decrease of recur-rence after D2 procedure. Recently the long term survival analysis of the Italian RCT could demonstrate a benefit for patients with positive nodes treated with D2 gastrectomy without splenopancreatectomy. As nowadays also in western countries D2 procedure can be done safely with pancreas preserving technique and without preventive splenectomy, it has been suggested in several national guidelines as the recommended procedure for patients with AGC.

Problems faced by evidence-based medicine in evaluating lymphadenectomy for gastric cancer

Gastric cancer surgical management differs between Eastern Asia and Western countries. Extended lymphadenectomy(D2) is the standard of care in Japan and South Korea since decades, while the majority of United States patients receive at most a limited lymphadenectomy(D1). United States and Northern Europe are considered the scientific leaders in medicine and evidencebased procedures are the cornerstone of their clinical practice. However, surgeons in Eastern Asia are more experienced, as there are more new cases of gastric cancer in Japan(107898 in 2012) than in the entire European Union(81592), or in South Korea(31269) than in the entire United States(21155). For quite a long time evidence-based medicine(EBM) did not solve the question whether D2 improves long-term prognosis with respect to D1. Indeed, eastern surgeons were reluctant to perform D1 even in the frame of a clinical trial, as their patients had a very good prognosis after D2. Evidence-based surgical indications provided by Western trials were questioned, as surgical procedures could not be properly standardized. In the present study we analyzed indications about the optimal extension of lymphadenectomy in gastric cancer according to current scientific literature(2008-2012) and surgical guidelines. We searched PubMed for papers using the key words "lymphadenectomy or D1 or D2" AND "gastric cancer" from 2008 to 2012. Moreover, we reviewed national guidelines for gastric cancer management. The support to D2 lymphadenectomy increased progressively from 2008 to 2012: since 2010 papers supporting D2 have achieved a higher overall impact factor than the other papers. Till 2011, D2 was the procedure of choice according to experts' opinion, while three meta-analyses found no survival advantage after D2 with respect to D1. In 2012-2013, however, two meta-analyses reported that D2 improves prognosis with respect to D1. D2 lymphadenectomy was proposed as the standard of care for advanced gastric cancer by Japanese National Guidelines since 1981 and was adopted as the standard procedure by the Italian Research Group for Gastric Cancer since the Nineties. D2 is now indicated as the standard of surgical treatment with curative intent by the German, British and ESMO-ESSO-ESTRO guidelines. At variance American NCCN guidelines recommend a D1+ or a modified D2 lymph node dissection. In conclusion, D2 lymphadenectomy, originally developed by Eastern surgeons, is now becoming the procedure of choice also in the West. In gastric cancer surgery EBM is lagging behind national guidelines, rather than preceding and orienting them. To eliminate this lag, EBM should value to a larger extent Eastern Asian literature and should evaluate not only the quality of the study design but also the quality of surgical procedures.

Recurrence in node-negative advanced gastric cancer:Novel findings from an in-depth pathological analysis of prognostic factors from a multicentric series

AIM To analyze the clinicopathological characteristics of patients with both node-negative gastric carcinoma and diagnosis of recurrence during follow-up. METHODS We enrolled 41 patients treated with curative gastrectomy for p T2-4 a N0 gastric carcinoma between 1992 and 2010,who developed recurrence(Group 1). We retrospectively selected this group from the prospectively collected database of 4 centers belonging to the Italian Research Group for Gastric Cancer,and compared them with 437 p T2-4 a N0 patients without recurrence(Group 2). We analyzed lymphatic embolization,microvascular infiltration,perineural infiltration,and immunohistochemical determination of p53,Ki67,and HER2 in Group 1 and in a subgroup of Group 2(Group 2 bis) of 41 cases matched with Group 1 according to demographic and pathological characteristics. RESULTS T4 a stage and diffuse histotype were associated with recurrence in the group of p N0 patients. In-depth pathological analysis of two homogenous groups of p N0 patients,with and without recurrence during longterm follow-up(groups 1 and 2 bis),revealed two striking patterns: lymphatic embolization and perineural infiltration(two parameters that pathologists can easily report),and p53 and Ki67,represent significant factors for recurrence.CONCLUSION The reported pathological features should be considered predictive factors for recurrence and could be useful to stratify node-negative gastric cancer patients for adjuvant treatment and tailored follow-up.

Incidence and treatment of mediastinal leakage after esophagectomy:Insights from the multicenter study on mediastinal leaks

BACKGROUND Mediastinal leakage(ML) is one of the most feared complications of esophagectomy. A standard strategy for its diagnosis and treatment has beendifficult to establish because of the great variability in their incidence and mortality rates reported in the existing series.AIM To assess the incidence, predictive factors, treatment, and associated mortality rate of mediastinal leakage using the standardized definition of mediastinal leaks recently proposed by the Esophagectomy Complications Consensus Group(ECCG).METHODS Seven Italian surgical centers(five high-volume, two low-volume) affiliated with the Italian Society for the Study of Esophageal Diseases designed and implemented a retrospective study including all esophagectomies(n = 501) with intrathoracic esophagogastric anastomosis performed from 2014 to 2017.Anastomotic MLs were defined according to the classification recently proposed by the ECCG.RESULTS Fifty-nine cases of ML were recorded, yielding an overall incidence of 11.8%(95%CI: 9.1%-14.9%). The surgical approach significantly influenced the occurrence of ML: the proportion of leakage was 10.5% and 9% after open and hybrid esophagectomy(HE), respectively, and doubled(20%) after totally minimally invasive esophagectomy(TMIE)(P = 0.016). No other predictive factors were found. The 30-and 90-d overall mortality rates were 1.4% and 3.2%,respectively; the 30-and 90-d leak-related mortality rates were 5.1% and 10.2%,respectively; the 90-d mortality rates for TMIE and HE were 5.9% and 1.8%,respectively. Endoscopy was the first-line treatment in 49% of ML cases, with the need for retreatment in 17.2% of cases. Surgery was needed in 44.1% of ML cases.Endoscopic treatment had the lowest mortality rate(6.9%). Removal of the gastric tube with stoma formation was necessary in 8(13.6%) cases.CONCLUSION The incidence of ML after esophagectomy was high mainly in the TMIE group.However, the general and specific(leak-related) mortality rates were low. Early treatment(surgical or endoscopic) of severe leaks is mandatory to limit related mortality.

On the road to standardization of D2 lymph node dissection in a European population of patients with gastric cancer

The amount of lymph node dissection(LD) required during surgical treatment of gastric cancer surgery has been quite controversial.In the 1970 s and 1980 s,Japanese surgeons developed a doctrine of aggressive preventive gastric cancer surgery that was based on extended(D2) LD volumes.The West has relatively lower incidence rates of gastric cancer,and in Europe and the United States the most common LD volume was D0-1.This eventually caused a scientific conflict between the Eastern and Western schools of surgical thought.:Japanese surgeons determinedly used D2 LD in surgical practice,whereas European surgeons insisted on repetitive clinical trials in the European patient population.Today,however,one can observe the results of this complex evolution of views.The D2 LD is regarded as an unambiguous standard of gastric cancer surgical treatment in specialized European centers.Such a consensus of the Eastern and Western surgical schools became possible due to the longstanding scientific and practical search for methods that would help improve the results of gastric cancer surgeries using evidence-based medicine.Today,we can claim that D2 LD could improve the prognosis in European populations of patients with gastric cancer,but only when the surgical quality of LD execution is adequate.

Multimodal treatment of gastric cancer in the west: Where are we going?

The incidence of gastric cancer(GC) is decreasing worldwide,especially for intestinal histotype of the distal third of the stomach.On the contrary,proximal location and diffuse Lauren histotype have been reported to be generally stable over time.In the west,no clear improvement in long-term results was observed in clinical and population-based studies.Results of treatment in these neoplasms are strictly dependent on tumor stage.Adequate surgery and extended lymphadenectomy are associated with good long-term outcome in early-stage cancer; however,results are still unsatisfactory for advanced stages(Ⅲ and Ⅳ),for which additional treatments could provide a survival benefit.This implies a tailored approach to GC.The aim of this review was to summarize the main multimodal treatment options in advanced resectable GC.Perioperative or postoperative treatments,including chemotherapy,chemoradiotherapy,targeted therapies,and hyperthermic intraperitoneal chemotherapy have been reviewed,and the main ongoing and completed trials have been analyzed.An original tailored multimodal approach to non-cardia GC has been also proposed.

Endoscopic ablation of Barrett's esophagus using high power setting argon plasma coagulation: A prospective study

AIM: This prospective study evaluated the effectiveness of 90 W argon plasma coagulation (APC) for the ablation of Barrett's esophagus (BE) that is considered to be the main risk factor for the development of esophageal adenocarcinoma.METHODS: The results from 25 patients, observed at the First Department of General Surgery, University of Verona, Italy, from October 2000 to October 2003, who underwent APC for histologically proven BE were prospectively analyzed.RESULTS: The ablation treatment was completed in all the patients but one (96%). The mean number of APC sessions needed to complete ablation was 1.6 (total number: 40). The eradication was obtained in the majority of cases by one session only (60%), two sessions were required in 24% of the cases and three or more in 16%.About 43% of the sessions were complicated. Retrosternal pain (22.5%) and fever (17.5%) were the most frequent symptoms. Only one major complication occurred, it was an hemorrhage due to ulcer formation on the treated esophagus that required urgent endoscopic sclerosis and admission. The follow-up was accomplished in all the patients with a mean period of 26.3 mo and 20 patients (84%) with a follow-up period longer than 24 mo. Only one patient showed a relapse of metaplastic mucosa 12 mo after the completion of ablation. The patient was hence re-treated and now is free from recurrence 33 mo later.CONCLUSION: High power setting (90 W) APC showed to be safe and effective. The effects persist at a mean follow-up period of two years with a comparable cost in term of complications with respect to standard power settings. Further studies with greater number of patients are required to confirm these results and to assess if ablation reduces the incidence of malignant progression.

Follow-up after gastrectomy for cancer:results of an international web round table

Oncological follow-up after radical gastrectomy for cancer still represents a discrepancy in the field,with many retrospective series demonstrating that early diagnosis of recurrence does not result in an improvement in patient survival;yet,many centers with high quality of care still provide routine patient follow-up after surgery by clinical and instrumental controls.This was the topic for a web round table entitled"Rationale and limits of oncological follow-up after gastrectomy for cancer"that was launched one year before the 10th International Gastric Cancer Congress.Authors having specific expertise were invited to comment on their previous publications to provide the subject for an open debate.During a three-month-long discussion,32 authors from 12 countries participated,and 2299people visited the dedicated web page.Substantial differences emerged between the participants:authors from Japan,South Korea,Italy,Brazil,Germany and France currently engage in instrumental follow-up,whereas authors from Eastern Europe,Peru and India do not,and British and American surgeons practice it in a rather limited manner or in the context of experimental studies.Although endoscopy is still considered useful by most authors,all the authors recognized that computed tomography scanning is the method of choice to detect recurrence;however,many limit follow-up to clinical and biochemical examinations,and acknowledge the lack of improved survival with early detection.

Hepatic metastases from gastric cancer:A surgical perspective

Management of patients with hepatic metastases as the sole metastatic site at diagnosis of gastric cancer(synchronous setting) or detected during follow-up(metachronous) is controversial. The prevailing attitude in these cases is passive, leading to surgical palliation and, possibly, to chemotherapy. Authors focused this editorial in order to promote a more pragmatic attitude. They stress the importance of recognizing the good candidates to curative surgery of both gastric cancer and hepatic metastases(synchronous setting) or hepatic disease alone(metachronous disease) from those who will not benefit from surgical therapy. In fact, in adequately selected subgroup of patients surgery, especially if integrated in multimodal therapeutic strategies, may achieve unexpected 5-year survival rates, ranging from 10% to 40%. The critical revision of the literature suggests that some simple clinical criteria exist that may be effectively employed in patients selection. These are mainly related to the gastric cancer(factors T, N, G) and to the extent of hepatic involvement(factor H). Upon these criteria it is possible to adequately select about 50% of cases. In the remaining 50% of cases a critical discussion on a case-by-case basis is recommended, considering that among these patients some potential long-survivors exist, that survival is strictly influenced by the ablation of the tumor bulk and by multimodality treatments including chemotherapy and that in expert institutions this kind of surgery is performed with very low mortality and morbidity rates.