Peritoneal dissemination represents a devastating form of gastric cancer(GC) progression with a dismal prognosis. There is no effective therapy for this condition. The 5-year survival rate of ...patients with peritoneal dissemination is 2%, even including patients with only microscopic free cancer cells without macroscopic peritoneal nodules. The mechanism of peritoneal dissemination of GC involves several steps: detachment of cancer cells from the primary tumor, survival in the free abdominal cavity, attachment to the distant peritoneum, invasion into the subperitoneal space and proliferation with angiogenesis. These steps are not mutually exclusive, and combinations of different molecular mechanisms can occur in each process of peritoneal dissemination. A comprehensive understanding of the molecular events involved in peritoneal dissemination is important and should be systematically pursued. It is crucial to identify novel strategies for the prevention of this condition and for identification of markers of prognosis and the development of molecular-targeted therapies. In this review, we provide an overview of recently published articles addressing the molecular mechanisms of peritoneal dissemination of GC to provide an update on what is currently known in this field and to propose novel promising candidates for use in diagnosis and as therapeutic targets.
Surgery had been and remains a mainstay in the treatment of gastric cancer. The Japanese surgical oncologists employed surgery-first approach to treat gastric cancer because of the widespread use of ...D2 lymph node dissection and the high incidence of oncologically resectable cancer, and early attempts at the multimodality treatment strategy featured surgery followed by postoperative chemotherapy. Although evidence to treat Stage II/III gastric cancer with this strategy is now abundant in the Far East, poor compliance of the post-gastrectomy patients to intense combination chemotherapies has been a limitation associated with this strategy. Evidence in support of neoadjuvant chemotherapy in the West and in various other types of cancer prompted the Japan Clinical Oncology Group (JCOG) researchers to explore this strategy, primarily for a selected population of locally advanced cancer that could either be unresectable by the surgery-first approach or is known to suffer from a poor prognosis; cancers with bulky lymph node metastases or those with a scirrhous phenotype. Encouraged by some promising results from these neoadjuvant trials and taking into account the aforementioned limitations associated with postoperative chemotherapy, the JCOG researchers decided to embark on a phase III trial to explore neoadjuvant chemotherapy among patients with clinically Stage III cancer. This review describes the development of the neoadjuvant strategy for gastric cancer in Japan, mainly by going through a series of clinical trials conducted by the JCOG.
Gastric cancer(GC) is the third most common cause of cancer-related death in the world,representing a major global health issue. Although the incidence of GC is declining,the outcomes for GC patients ...remain dismal because of the lack of effective biomarkers to detect early GC and predict both recurrence and chemosensitivity. Current tumor markers for GC,including serum carcinoembryonic antigen and carbohydrate antigen 19-9,are not ideal due to their relatively low sensitivity and specificity. Recent improvements in molecular techniques are better able to identify aberrant expression of GC-related molecules,including oncogenes,tumor suppressor genes,micro RNAs and long non-coding RNAs,and DNA methylation,as novel molecular markers,although the molecular pathogenesis of GC is complicated by tumor heterogeneity. Detection of genetic and epigenetic alterations from gastric tissue or blood samples has diagnostic value in the management of GC. There are high expectations for molecular markers that can be used as new screening tools for early detection of GC as well as for patient stratification towards personalized treatment of GC through prediction of prognosis and drug-sensitivity. In this review,the studies of potential molecular biomarkers for GC that have been reported in the publicly available literature between 2012 and 2015 are reviewed and summarized,and certain highlighted papers are examined.
Conversion therapy for gastric cancer (GC) has been the subject of much recent attention. It is defined as a surgical treatment aiming at an R0 resection after chemotherapy for tumors that were ...originally unresectable or marginally resectable for technical and/or oncological reasons. However, the indications for resection remain to be clarified. In the present review, we focus on the biology and heterogeneous characteristics of stage IV GC and propose new categories of classification. Stage IV GC patients can be divided based on the absence (categories 1 and 2) or presence (categories 3 and 4) of macroscopically detectable peritoneal dissemination, which has a different biological outcome compared to hematological metastasis. Category 1 is defined oncologically as stage IV but the metastasis is technically resectable. Category 2 includes a marginally resectable metastasis or patients for whom the operation would not necessarily be the best choice. Category 3 includes a potentially unresectable metastasis of peritoneal dissemination that is only macroscopically detectable. Category 4 includes noncurable metastasis with peritoneal and other organ metastasis. The indications for conversion therapy might include the patients from category 2, some patients from category 3 and a very small number of patients from category 4. The longer survival can be expected for patients corresponding to categories 1, 2 and, to a lesser extent, 3, while the treatment of other patients focuses on “care.” The provision of conversion therapy for stage IV GC patients might be one of the main roles of surgical oncologists in the near future.
The incidence of gastric cancer and the number of gastric cancer patients that a surgeon treats annually are so vastly different between countries and regions that it is not easy to define which type ...of gastric cancer surgery should be considered the global standard. Nevertheless, a consensus that D2 dissection is the most appropriate way to treat resectable advanced gastric cancer has arguably been reached after long-term follow-up and flexible interpretation of the Dutch D1 versus D2 trial and evidence from the Japan Clinical Oncology Group 9501 study which denied survival benefit of more extensive lymphadenectomy. After the Japan Clinical Oncology Group 9501 trial, surgeons gradually lost interest in attempting to improve survival through extended resection and instead began to expend greater resources on establishing and standardizing the technique of minimally invasive surgery and proving its oncological non-inferiority compared with the conventional approach. Laparoscopic distal gastrectomy has become an option in daily clinical practice in the Far East, and more demanding procedures such as laparoscopic total gastrectomy and laparoscopic surgery for advanced gastric cancer are currently being explored in clinical trials from the viewpoint of both safety and oncological feasibility. In addition, the high proportion of early-stage cancer in the Far East prompted surgeons to develop limited surgery such as proximal gastrectomy and pylorus-preserving gastrectomy, which warrant further evaluation regarding benefits in terms of postoperative nutritional state and/or quality of life measurements to convince the rest of the world.
Gastric cancer with metastases outside of the regional lymph nodes is deemed oncologically unresectable. Nevertheless, some metastatic lesions are technically resectable by applying established ...surgical techniques such as para‐aortic lymphadenectomy and hepatectomy. At the time of compilation of the Japanese gastric cancer treatment guidelines version 4, systematic reviews were conducted to see whether it is feasible to make any recommendation to dissect both the primary and metastatic lesions with intent to cure, possibly as part of multimodality treatment. Long‐term survivors were found among carefully selected groups of patients both in prospective and retrospective studies. In addition, there is a growing list of publications reporting encouraging outcomes of gastrectomy conducted after exceptionally good response to chemotherapy, usually among patients who underwent R0 resection. This type of surgery is often referred to as conversion surgery. It is sometimes difficult to define a clear borderline between curative surgery scheduled after neoadjuvant chemotherapy and the conversion surgery. This review summarizes what we knew after the literature reviews conducted at the time of compiling the Japanese guidelines and in addition reflects some new findings obtained thereafter through clinical trials and retrospective studies. Metastases were divided into three categories based on the major metastatic pathways: lymphatic, hematogenous, and peritoneal. In each of these categories, there were findings that could provide hope for patients with metastatic disease. These findings implied that the surgical technique that we already use could become more useful upon further developments in antineoplastic agents and drug delivery.
Resection by surgery with intent to cure can be considered for a limited population of stage IV gastric cancer.
Background
The Japanese Gastric Cancer Association (JGCA) started a new nationwide gastric cancer registration in 2008.
Methods
From 208 participating hospitals, 53 items including surgical ...procedures, pathological diagnosis, and survival outcomes of 13,626 patients with primary gastric cancer treated in 2002 were collected retrospectively. Data were entered into the JGCA database according to the JGCA classification (13th edition) and UICC TNM classification (5th edition) using an electronic data collecting system. Finally, data of 13,002 patients who underwent laparotomy were analyzed.
Results
The 5-year follow-up rate was 83.3 %. The direct death rate was 0.48 %. UICC 5-year survival rates (5YEARSs)/JGCA 5YEARSs were 92.2 %/92.3 % for stage IA, 85.3 %/84.7 % for stage IB, 72.1 %/70.0 % for stage II, 52.8 %/46.8 % for stage IIIA, 31.0 %/28.8 % for stage IIIB, and 14.9 %/15.3 % for stage IV, respectively. The proportion of patients more than 80 years old was 7.8 %, and their 5YEARS was 51.6 %. Postoperative outcome of the patients with primary gastric carcinoma in Japan have apparently improved in advanced cases and among the aged population when compared with the archival data. Further efforts to improve the follow-up rate are needed.
Conclusions
Postoperative outcome of the patients with primary gastric carcinoma in Japan have apparently improved in advanced cases and among the aged population when compared with the archival data. Further efforts to improve the follow-up rate are needed.
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