Open D2 Gastrectomy Research Articles

The long-term efficacy of laparoscopic surgery in early and advanced gastric cancer

Laparoscopic surgery for the treatment of gastrointestinal cancer has rapidly evolved over the last decade. Although critical analysis of the short-term outcomes of laparoscopic gastrectomy has provided evidence for the safety of this minimally invasive approach, little long-term survival data, particularly for patients with advanced stage II and III gastric cancer, are available [1]. This lack of evidence increases the skepticism about the ability of laparoscopic gastrectomy for advanced gastric cancer to control cancer cell dissemination and prevent recurrence. This gap between expectations of and concerns about the long-term impact of laparoscopic gastrectomy on gastric cancer patients has been bridged by the study of Pak et al. [2] reported in the January issue of Surgical Endoscopy. The authors have analyzed the results of 714 consecutive patients with gastric cancer who underwent laparoscopic gastrectomy in their institution between May 2003 and December 2009. After a median follow-up of 46 months, recurrence was observed in 26 patients (3.7 %), with the secondary tumor located in the peritoneum in seven patients), locoregional in six patients, in distant organs with hematogenous spread in five patients, and other less frequent failures. The 5-year recurrence-free survival rates according to the TNM staging system categories were 95.8 % in stage I patients, 83.4 % in stage II patients, and 46.4 % in stage III patients. This study provides excellent results, similar to those reported by the randomized controlled trials (RCTs) with open D2 gastrectomy for stage II–III disease by Sasako et al. [3]. However, what is the reality from a Western point of view? In contrast to the excellent expertise in laparoscopic gastrectomy of Korean surgeons, a sample size as large as 714 patients treated within 7 years is unrealistic in Western countries, even in specialized hospitals. This lack of high-volume surgeons, which is a predictive factor for safe and effective laparoscopic surgery, raises attention. Indeed, although laparoscopic resection tends to be routinely performed for colorectal cancer, laparoscopic D2 gastrectomy for advanced tumors still remains a grand challenge for Western surgeons [4–11]. Such an approach is less familiar to Western surgeons and can be associated with the reports of increased postoperative complications and mortality. While awaiting the results of confirmatory RCTs for laparoscopic D2 gastrectomy for advanced resectable gastric cancer, biomedical research is focused on novel drugs developed based on the concept of signaling transduction interaction networks. In the era of systems science and biological circuits, there is emerging research based on the latest genome sequencing technology and living-cells networks-based imaging technologies. These advances together with substantial progress in computational systems biology, synthetic biology engineered-based reconstruction of signaling circuits, and mathematical models now shape new horizons in the discovery of innovative biomarkertargeted drug complexes for personalized treatment of cancer patients [12–32].

Open versus laparoscopic versus robotic gastrectomy for cancer: need for comparative-effectiveness quality

New technologies and medical devices may improve both health care and research toward the development of new drugs. But they are a major driver of increases in U.S. health care expenditures, which have grown by an estimated 71% since 2000 [1]. In an economic crisis, cost effectiveness for new therapies (e.g., robotic surgery) should be considered. The U.S. market for drugs and devices is regulated by the Food and Drug Administration (FDA), which scrutinizes clinical trial data for evidence of safety and efficacy. Although the FDA has been criticized for missteps and inefficiencies in its approval process, more relevant is FDA oversight of the labeling and promotion of medical products. Indeed, the FDA does not require the inclusion of statements regarding a product’s comparative effectiveness. Clinicians, patients, and payers would be less willing to pay more for a new treatment such as robotic surgery without proof that it improves health outcomes. Comparative-effectiveness research is the current standard strategy for drawing robust conclusions about new drugs, medical devices, and surgical techniques [2]. Randomized phase 3 trials are the best tools for ultimate decisions in medicine. The current standard of care in the treatment of resectable gastric cancer includes gastrectomy and adjuvant chemotherapy with or without radiotherapy [3–5]. It is thought that the quality of surgery [6] including a standardized D2 lymphadenectomy can improve the survival of patients with stage 2 or 3 disease [7–12]. New techniques for improving patient outcomes include endoscopic submucosal resection for early gastric cancer, laparoscopic gastrectomy, and robotic surgery. All these new treatments should provide evidence of their superiority over open D2 gastrectomy before they are widely used. Oncologic outcomes are the principal priority in the treatment of cancer patients. Although minimally invasive surgery improves quality of life (QOL), it should be ensured that these techniques do not increase recurrence risk and mortality. In a recent issue of Surgical Endoscopy, Kim et al. [13] provided comparison-effectiveness information regarding robotic surgery versus laparoscopic or open gastrectomy for the treatment of gastric cancer. The authors compared the results of robotic gastrectomy using the da Vinci surgical system with those for 11 laparoscopic and 12 open gastrectomies performed during the same period (31 December 2007 to 30 June 2008). At baseline, no significant difference in clinicopathologic characteristics or tumor stage was observed between the three groups. The total number of lymph nodes retrieved (TNODS) and used as a quality control measure in gastric, colorectal, and other cancers, did not differ significantly among the groups. Robotic surgery was associated with significantly less blood loss and a shorter postoperative hospital stay. The postoperative morbidity was similar in the three groups. No open or laparoscopic conversion was performed in the robotic group. Kim and colleagues concluded that experienced laparoscopic surgeons can safely perform robotic surgery for gastric cancer, improving the short-term outcomes. This study provides encouraging data on the use of robotic surgery for gastric cancer. But it is a small retrospective with no information on long-term survival or G. Glantzounis D. Ziogas (&) G. Baltogiannis University of Ioannina, Ioannina, Greece e-mail: deziogas@hotmail.com

Impact of laparoscopic D2 gastrectomy on long-term survival for early gastric cancer

There has been a dramatic increase in the clinical use of laparoscopic gastrectomy for the treatment of early gastric cancer within a decade after its introduction in East Asia, particularly Korea [1]. There are several reasons that explain the rapid progress of laparoscopic D2 gastrectomy in Korea. These include the overall, high incidence of gastric cancer, the high rate of diagnosis at early stage, and the increasing number of high-volume hospitals and highvolume surgeons in laparoscopic gastrectomy in Korea. However, in an absence of both randomized, controlled trials and long-term, follow-up data, there is skepticism on a potential negative effect of laparoscopic gastrectomy on oncological outcomes. Lee et al. [2], in a recent issue of Surgical Endoscopy, reported on long-term results after laparoscopy-assisted distal gastrectomy (LADG) for early gastric cancer. This study comes to bridge the gap in the absence of long-term outcomes data. The authors analyzed the clinicopathologic data of 106 patients who underwent LADG and compared these results with those of 105 patients who underwent open distal gastrectomy (ODG) for early gastric cancer. The results on early postoperative outcomes are consisted with the literature and confirm the superiority of LADG vs. ODG regarding postoperative recovery, passing flatus, starting a liquid diet, and postoperative hospital stay and postoperative complications [3, 4]. The interest of this study is focused on long-term results. There was no significant difference in overall 5-year survival rate (5-YSR) between patients who underwent LADG (95.9%) and patients who had an ODG (94.9%). These survival results can be considered as excellent given that in the LADG group 6.6% of patients had lymph node metastasis and 37.7% of patients had a submucosal cancer, which both associated its less favorable survival than patients with mucosal and node-negative disease did. In Japan and Korea, two countries with high gastric cancer incidence and large experience with extended lymphadenectomy, open D2 gastrectomy has been the standard of care for localized gastric cancer. Compared with the treatment of gastric cancer in the west, results for early detection and survival are much better in Japan and Korea: 50% vs. \20% early-stage gastric cancer, and [60% vs. \40% overall survival after potential curative gastrectomy respectively in these two countries and western world [5, 6]. Two pivotal studies for advanced stage II/III gastric cancer from Japan have been published recently in the New England Journal of Medicine [7, 8]. The first phase III, adjuvant, randomized, controlled trial, compared D2 lymphadenectomy alone or D2 plus paraaortic nodal dissection (PAND). No patient received adjuvant treatment; Sasako et al. [7] reported the best global 5-year survival results of approximately 70% in both groups. Given that no survival benefit derived from D2 plus PAND, D2 surgery has been the standard approach. The second, a phase III adjuvant randomized trial compared D2 surgery alone vs. D2 surgery plus postoperative S-1 adjuvant chemotherapy. The study stopped due to a significant difference at 3-year survival rate in favor of S-1 chemotherapy in the planned interim analysis. D2 plus S-1 postoperative chemotherapy is the standard treatment for stage II/III gastric cancer in Japan. However, similar results, with exception survival of early gastric cancer [9, 10], have not yet been achieved in Europe or the United States. Indeed, in the west, although quality of surgery plays a predominant role for favorable D. Kanellos I. Kanellos (&) 4th Department of Surgery, Aristotle University of Thessaloniki, Thessaloniki, Greece e-mail: ik@hol.gr