Rie Makuuchi

Robotic surgery for gastric cancer

Laparoscopic gastrectomy is a widely used minimally invasive surgery for gastric cancer. However, skillful techniques are required to perform lymph node dissection using straight shaped forceps, particularly for D2 dissection. Robotic surgery using the da Vinci surgical system is anticipated to be a powerful tool for performing difficult techniques using high-resolution three-dimensional (3D) images and the EndoWrist equipped with seven degrees of freedom. Attempts are being made to apply robotic surgery in gastrectomy procedures mainly in Japan, South Korea, and Europe. Although definite superiority to laparoscopic gastrectomy is yet to be proven, robotic surgery has been reported to have a shorter learning curve and offer more precise dissection for total gastrectomy. Hence, its oncological efficacy needs to be verified in a clinical trial.

Comprehensive analysis of gene mutation and expression profiles in neuroendocrine carcinomas of the stomach

The gene mutation and expression profiles of gastric neuroendocrine carcinoma (NEC) have not been comprehensively determined. Here, we examined the gene mutation and expression profiles of NEC using whole exome sequencing (WES) and microarray analysis. Six patients with gastric NEC and 13 with gastric adenocarcinoma (GAD) were included in this study. Single nucleotide variants were compared and multivariate statistical investigation with orthogonal partial least squares discriminant analysis (OPLS-DA) was performed to compare the difference in expression profiles between NEC and GAD. NEC showed a significantly higher mutation rate than GAD and the percentage difference in the mutation pattern of NEC compared with GAD was 92.8%. OPLSDA clearly discriminated between NEC and GAD. We identified 35 genes, including CPLX2 (Complexin 2), which were expressed more strongly in NEC than in GAD, of which 14 were neural-related. Immunohistochemical analysis showed the strong expression of CPLX2 in all NECs, versus expression in only 2 of 13 GADs. Gastric NEC had a specific mutation pattern with a significantly higher gene mutation rate than GAD, and completely differed from GAD on the basis of gene expression profile. CPLX2 might be a potential novel biomarker for the diagnosis of NEC.

Reply to comment on “Are body mass index and performance status enough to assess the nutritional and functional status of elderly patients undergoing gastric cancer surgery?”

We thank Lidoriki et al. for their interest in our paper [1], which investigated the feasibility of gastrectomy for very elderly patients (≥ 85 years of age). The results of our study suggest that chronological age alone is not a valid reason for avoiding gastrectomy, and a comprehensive assessment is necessary to determine the optimum treatment strategy for elderly patients with gastric cancer. The results of a multivariate analysis, which did not identify chronological age as an independent prognostic factor, also support our view that gastrectomy should be considered regardless of chronological age as long as the physical capacity is maintained [1]. We partially agree with Lidoriki et al. that sarcopenia and frailty have recently emerged as significant prognostic factors for the postoperative outcomes of geriatric patients. Indeed, previous studies have clearly demonstrated a significant relationship between sarcopenia and postoperative complications [2]; however, whether or not this relationship holds true in terms of the long-term post-surgical survival remains controversial. A recent meta-analysis included only two studies with a long-term survival assessment, and the results were inconsistent [2]. We also investigated the impact of sarcopenia on the long-term outcomes in elderly gastric cancer patients and reported adverse effects on the survival outcomes [3], which is consistent with the findings of a study conducted by Zhuang et al. [4]. In addition, Kudou et al. reported a strong relationship between the postoperative development of sarcopenia and poor long-term survival outcome [5]. Conversely, Tegels et al. [6] reported no association of sarcopenia with the postoperative morbidity and survival outcomes. Such inconsistency among studies most likely reflects the different definitions of sarcopenia and elderly in each study. Consequently, sarcopenia cannot be considered a robust prognosticator for elderly patients undergoing gastrectomy, although this issue remains to be fully investigated. Therefore, it is not necessary to include sarcopenia as a covariate for multivariable analyses of the long-term survival outcomes. In conclusion, while sarcopenia should definitely be integrated into the preoperative assessment tool for elderly patients, robust evidence needs to be gathered concerning both the early postoperative outcomes and the long-term survival.

Esophagojejunal anastomotic leakage following gastrectomy for gastric cancer

Esophagojejunal anastomotic leakage (EJAL) is a serious complication of total or proximal gastrectomy for gastric cancer, with a reported incidence of 2.1–14.6% and mortality of up to 50%. EJAL is an independent prognostic factor for the poor survival of gastric cancer patients. Meticulous surgical techniques, experience with anastomotic devices, and a thorough understanding of various risk factors and preventive measures are essential and early diagnosis is critical for preventing EJAL-related death. Patients with suspected EJAL must be evaluated promptly, but contrast swallow is not recommended. There is no standard treatment strategy for EJAL, although conservative treatment with drainage and nutritional support is the most common approach. Effective endoscopic treatments have been reported but need further validation. Surgical treatment is associated with high mortality but should be considered to prevent death from suboptimal EJAL management, for patients with severe sepsis or when conservative treatment has failed.

Feasibility of Laparoscopic Distal Gastrectomy for Stage I Gastric Cancer in Patients Outside of Clinical Trials

BackgroundRandomized controlled trials, including the Japan Clinical Oncology Group (JCOG) 0912 trial, have shown the safety of laparoscopy-assisted distal gastrectomy (LADG) for select healthy patients. It is unclear whether LADG is feasible in patients who do not meet trial eligibility criteria.MethodsThe present study retrospectively reviewed 547 patients with clinical stage I gastric cancer who underwent distal or pylorus-preserving gastrectomy. Of these, 185 were identified as not fulfilling the eligibility criteria of JCOG 0912; the short-term surgical outcomes between LADG and open distal gastrectomy (ODG) were compared in this group before and after propensity score matching.ResultsPatients who were not eligible for inclusion in the trial comprised 33.8% of the total. After matching, there were 59 patients each in the LADG and ODG groups, with an improved balance of confounding factors between the two groups. LADG was associated with significantly longer operation time, less blood loss, and shorter postoperative hospital stay than ODG. The rate of overall postoperative complications of Clavien–Dindo Grade II or higher did not differ significantly between the LADG and ODG groups (23.7 vs. 18.6%, respectively; p = 0.653). The incidence of pneumonia (6.8 vs. 5.1%), intra-abdominal infectious complications (5.1 vs. 3.4%), and stasis syndrome (5.1 vs. 3.4%) was also comparable between the two groups.ConclusionLADG was as safe as ODG in patients who did not meet the eligibility criteria of JCOG 0912. LADG could be a standard treatment option for patients with stage I gastric cancer, regardless of their general condition.

Pancreaticoduodenectomy for gastric cancer

Pancreaticoduodenectomy (PD) is performed to achieve an R0 resection for gastric cancer with pancreatic and/or duodenal invasion. Several retrospective case series have been published, but the sample cohorts in each study were heterogeneous and small. Moreover, the absence of prospective studies results in a lack of solid evidence that will help determine who can benefit from this procedure. Although the morbidity and mortality of PD have been reported by most studies to be acceptable and that the procedure is feasible, these remained to be much higher than those of standard gastrectomy. Therefore, careful selection of patients should be considered. Based on a review of previous case series and our own experience, PD appears to be beneficial to patients with gastric cancer with pancreatic invasion when R0 resection is possible. In addition, multidisciplinary treatment such as neoadjuvant chemotherapy, is anticipated to improve survival. Nevertheless, considering that prospective randomized studies are difficult to perform, a large-scale multicenter retrospective cohort study is required to evaluate this highly invasive procedure.

Metabolomic profling in gastric cancer tissues using time-of-flight mass spectrometry.

66Background: To explore carcinogenic and prognostic biomarkers for gastric cancer, genomics, transcriptomics and proteomics approaches have been extensively applied;however, little has been invest...

Impact of extra-nodal metastasis on survival in gastric cancer patients with lymph node involvement.

57Background: Extra-nodal metastasis (ENM) is defined as a tumor nodule without lymph node structure, and distinguished from lymph node metastasis by histological findings. Despite the possible difference in metastatic mechanism, both are counted as metastasized lymph nodes according to the 3rd English edition of Japanese Classification of Gastric Carcinoma, and thus the prognostic value of ENM remains unclear. The aim of this study was to clarify the clinicopathogical characteristics and prognostic impact of ENM in gastric cancer patients with lymph node involvement. Methods: This study included 388 patients who underwent curative gastrectomy for primary gastric cancer between January 2009 and August 2013. A total of 2093 pathologically positive tumor nodules, including both metastatic lymph nodes and ENM, were examined. Clinicopathological characteristics and survival outcomes were compared between an ENM positive (ENMP) group (95 patients) and an ENM negative (ENMN) group (293 patients). In addition, m...

Molecular classification of Japanese gastric adenocarcinoma.

e15565Background: Gastric cancer is well known as having heterogeneous features. Recently, TGCA project had successfully established a molecular classification of gastric adenocarcinoma. In additio...

Impact of sarcopenia on short- and long-term outcomes in patients with gastric cancer.

19 Background: Depletion of skeletal muscle in aged people (sarcopenia) regarded as a poor prognostic factor in various cancers. The aim of this study was to assess the impact of preoperative sarcopenia on postoperative short- and long-term outcomes in patients with gastric cancer underwent curative resection. Methods: A total of 881 patients who underwent R0 resection for gastric cancer aged 65 or older between June 2003 and March 2011 were included in this study. Muscle mass was assessed by measuring percentage of arm muscle area (%AMA). Preoperative sarcopenia was defined as aged 65 or older, %AMA <80%, and decline in grip strength ( <25kg in men, <20kg in women), according to algorithm suggested by European Working Group on Sarcopenia in Older People (EWGSOP) with slight modification. Relationship between sarcopenia and short- and long-term outcomes were evaluated using uni- and multi-variate analysis. Results: Of 881 patients, sarcopenia was diagnosed in 62 patients (7.0%). Incidence of sarcopenia wa...