Search

The stomach exhibits abundant lymphatic flow, and metastasis to lymph nodes is common. In the case of gastric cancer, there is a regularity to the spread of lymph node metastasis, and it does not easily metastasize outside the regional nodes. Furthermore, when its extent is limited, nodal metastasis of gastric cancer can be cured by appropriate lymph node dissection. Therefore, identifying and determining the extent of lymph node metastasis is important for ensuring accurate diagnosis and appropriate surgical treatment in patients with gastric cancer. However, precise detection of lymph node metastasis remains difficult. Most nodal metastases in gastric cancer are microscopic metastases, which often occur in small-sized lymph nodes, and are thus difficult to diagnose both preoperatively and intraoperatively. Preoperative nodal diagnoses are mainly made using computed tomography, although the specificity of this method is low because it is mainly based on the size of the lymph node. Furthermore, peripheral nodal metastases cannot be palpated intraoperatively, nodal harvesting of resected specimens remains difficult, and the number of lymph nodes detected vary greatly depending on the skill of the technician. Based on these findings, gastrectomy with prophylactic lymph node dissection is considered the standard surgical procedure for gastric cancer. In contrast, several groups have examined the value of sentinel node biopsy for accurately evaluating nodal metastasis in patients with early gastric cancer, reporting high sensitivity and accuracy. Sentinel node biopsy is also important for individualizing and optimizing the extent of uniform prophylactic lymph node dissection and determining whether patients are indicated for function-preserving curative gastrectomy, which is superior in preventing post-gastrectomy symptoms and maintaining dietary habits. Notably, advancements in surgical treatment for early gastric cancer are expected to result in individualized surgical strategies with sentinel node biopsy. Chemotherapy for advanced gastric cancer has also progressed, and conversion gastrectomy can now be performed after downstaging, even in cases previously regarded as inoperable. In this review, we discuss the importance of determining lymph node metastasis in the treatment of gastric cancer, the associated difficulties, and the need to investigate strategies that can improve the diagnosis of lymph node metastasis. [ABSTRACT FROM AUTHOR]

Background: The correlation between tumor location and lymphatic flow distribution in gastric cancer has been previously reported, and PTD (Proximal - Transitional - Distal) classification was proposed. Our group updated and developed the nPTD classification.Method: We retrospectively studied gastric cancer patients who underwent the dye method sentinel node biopsy from 1993 to 2020. The inclusion criteria were a single lesion type 0 cancer of ≤5 cm in the long axis, clinically node-negative, and invasion within the proper muscle layer pathologically. In this study, the distribution of dyed lymphatic flow was evaluated for each occupied area of the tumor.Results: We included 416 patients in this study. The tumors located in the watershed of the right and left gastroepiploic arteries near greater curvature had extensive lymphatic flow; therefore, a newly circular region with a diameter of 5 cm is set on the watershed of the greater curvature between P and T zone as the 'n' zone. In addition, for cancers located in the lesser P curvature, lymphatic flow to the greater curvature was not observed. Therefore, the P zone was divided into two: the lesser curvature side (PL) and the greater curvature side (PG).Conclusions: The advantage of the nPTD classification is that it provides not only proper nodal dissection but also adequate function-preserving gastrectomy. If the tumor is localized within the PL, the proximal gastrectomy resection area can be further reduced. In contrast, for cancers located in the 'n' zone, near-total gastrectomy is required because of the extensive lymphatic flow. [ABSTRACT FROM AUTHOR]

Background: The relationship between chronological nutritional changes and development of fatty liver after total gastrectomy (TG) in gastric cancer (GC) patients is still unclear. This study aimed to evaluate relationship between development of fatty liver and chronological changes of nutritional parameters during 12 months after TG.Methods: We retrospectively analyzed medical records of 59 patients with GC who underwent TG at the Kanazawa Medical University Hospital between January 2009 and December 2017. We defined fatty liver change as a mean liver-to-spleen attenuation ratio (L/S ratio) of less than 1.2 in the computed tomography images at 12 months after TG and divided the patients into fatty liver (FL) and non-FL groups from the L/S ratio. We analyzed serum levels of total protein and albumin, and psoas muscle index (PMI) before TG and at 6 and 12 months after TG in the non-FL and FL groups.Results: Six patients showed an L/S ratio of less than 1.2 at 12 months after TG and were included into FL group. There was no significant difference between the groups in serum parameters, L/S ratio, and PMI before TG. In the FL group, the mean levels of total protein and albumin decreased after TG and were significant lower at 6 months, compared with the non-FL group. And then, these levels in the FL group recovered at 12 months. In contrast, the mean levels of total protein and albumin in the non-FL group did not decrease below the preoperative levels throughout the year after surgery. As with laboratory parameters, all patients in the FL group showed decrease of PMI at 6 months after TG. This proportion was significantly higher than that in the non-FL group (100% vs. 40.8%, P = 0.006).Conclusions: We evaluated that the patients with fatty liver occurring after TG had significantly lower levels of serum nutritional parameters and skeletal muscle index at 6 months, not but 12 months, after TG. [ABSTRACT FROM AUTHOR]

Introduction: In patients with gastric cancer, 6-27% of patients are diagnosed with T4b disease that invades adjacent organs, and curative resection can improve the prognosis of these patients.Case Presentation: A 70-year-old Japanese man presented with an abdominal tumor and was diagnosed with advanced gastric cancer (L-Circ type 3 T4b N2 M0 H0 stage IVA, based on the 15th edition of the Japanese Classification of Gastric Carcinoma) with extensive abdominal wall invasion. We performed open gastrojejunal bypass for gastric obstruction and initiated a chemotherapeutic regimen comprising S-1 (120 mg/day) and oxaliplatin (100 mg/m2). Upper gastrointestinal endoscopy performed after the administration of six courses of the S-1 and oxaliplatin regimen revealed a persistent primary lower gastric wall lesion; however, the diameter of the abdominal wall invasion and metastatic lymph nodes was significantly reduced, in addition to decreased serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels. Subsequently, the patient underwent distal gastrectomy with D2 lymphadenectomy combined with transverse colon and abdominal wall resection. We performed radical en bloc resection and achieved a tumor-free resection margin. Simple abdominal wall closure was performed without mesh or musculocutaneous flap placement. Histopathological examination of the resected tumor specimen showed direct invasion of the mesocolon and rectus abdominis muscle. The patient was postoperatively diagnosed with L Gre-Ant type5 T4b (SI: rectus abdominis muscle) N2 PM0 DM0 Stage IIIA R0 Grade 2a gastric cancer based on histopathological findings and received S-1 as adjuvant chemotherapy, 2 months postoperatively. No recurrence was detected 6 months postoperatively.Conclusions: We report a case of advanced gastric cancer with extensive abdominal wall invasion that was successfully treated with gastrectomy combined with resection of adjacent organs showing tumor invasion after effective systemic chemotherapy. A therapeutic approach comprising curative surgery combined with perioperative chemotherapy is useful in patients with T4b gastric cancer. [ABSTRACT FROM AUTHOR]

Extravasated platelet aggregation (EPA) serves an important role in the cancer microenvironment during cancer progression, and has been demonstrated to interact with tumor cells in several types of cancer. EPA induces epithelial-mesenchymal transition (EMT) via transforming growth factor-β, and also recruits immunosuppressive cells, including regulatory T (Treg) cells and myeloid-derived suppressor cells (MDSCs). However, the role of EPA in gastric cancer with peritoneal metastasis remains unknown. The present study analyzed the association between EPA and prognosis in patients with gastric cancer with peritoneal metastasis. The present study evaluated 62 patients diagnosed with advanced gastric cancer with peritoneal metastasis between 2001 and 2016. EPA, EMT, Treg cells and MDSCs in peritoneal metastatic lesions were detected by immunohistochemical evaluation of CD42b, SNAIL, FOXP3 and CD33, respectively. CD42b expression was observed in 56.5% (35/62) of peritoneal metastatic lesions. CD42b expression in peritoneal metastatic lesions was associated with poor overall survival compared with lower frequencies (hazard ratio, 2.03; 95% confidence interval, 1.12–3.69; P=0.018). SNAIL, FOXP3 and CD33 expression were not associated with overall survival, but CD33 expression was markedly higher in CD42b-positive patients (P=0.022). These results indicated that EPA affects immunosuppression by recruiting MDSCs in the tumor microenvironment via the secretion of soluble factors, resulting in tumor progression. EPA may be a novel therapeutic target for gastric cancer with peritoneal metastasis. [ABSTRACT FROM AUTHOR]

It has previously been suggested that postgastrectomy syndrome (PGS) is more severe in patients after surgery for advanced gastric cancer than in patients with early gastric cancer. Using the postgastrectomy syndrome assessment scale-45 (PGSAS-45), the present study aimed to determine whether PGS for postgastrectomy patients, in Kanazawa Medical University Hospital, with advanced gastric cancer was more severe than for patients with early gastric cancer. A questionnaire survey was conducted using PGSAS-45 for curative gastric cancer gastrectomy cases at Kanazawa Medical University Hospital. The questionnaire data were combined with patient background data, anonymized and moved to an unlinked file for patient privacy. Using this dataset, non-recurrent cases of distal partial gastrectomy were extracted and divided into two groups, stage IA or IB patients (group E), and stage IIA or higher (group A). The main outcome measures (MOMs) of PGSAS-45 were compared between the two groups. The participants in the present study included 35 cases in group E and 22 cases in group A. The results of a univariate analysis to compare the MOMs between the two groups showed that only the dumping subscale was significantly different in group A and was judged to be caused by the underlying bias of the background factor. There were no MOMs with significant differences in the pathological stage based on multiple regression analyses. In cases of distal partial gastrectomy, the PGS and quality of life (QoL) of patients following advanced gastric cancer surgery were similar to those of patients with early gastric cancer. The standardized treatment for advanced gastric cancer did not induce notable postoperative failures, and QoL was not impaired. In contrast, for early-stage gastric cancer cases, the present study suggests that it is necessary to distinguish metastasis-negative cases to indicate an appropriate, function-preserving curative gastrectomy. [ABSTRACT FROM AUTHOR]

Background: Conversion surgery (CS) following a response to chemotherapy occasionally leads to prolonged survival in patients with stage IV gastric cancer (GC). This study aimed to evaluate the predictive value of the neutrophil/lymphocyte ratio (NLR) for the success of CS in patients with stage IV GC.Methods: We retrospectively analyzed data of 50 patients with stage IV GC who received systemic chemotherapy between January 2009 and December 2017 at the Kanazawa Medical University Hospital. The successful CS group included the patients who underwent R0 or R1 resection with CS, and the failed CS group included the patients who did not undergo CS after chemotherapy or those who, despite undergoing CS, had to additionally undergo R2 resection. Clinicopathological characteristics were examined in both groups. Univariate and multivariate analyses were performed to identify pretherapeutic parameters that were independently associated with the achievement of successful CS.Results: The number of patients in the successful and failed CS groups were 12 and 38, respectively. On univariate analysis, gender (P = 0.01), NLR (P = 0.003), albumin levels (P = 0.004), and absence of peritoneal metastasis (P = 0.004) were found to be significantly correlated with a successful CS. On multivariate analysis, NLR < 4 and absence of peritoneal metastasis were independently correlated with a successful CS (P = 0.02 and P = 0.002, respectively). In patients without peritoneal metastasis, successful CS rates in patients with NLR < 4 were significantly higher than those in patients with NLR ≥ 4 (61.1% vs. 10.0%, P = 0.005).Conclusions: The NLR was a significant independent predictor of the achievement of successful CS in stage IV GC patients, especially among the patients without peritoneal metastasis. Patients with a low NLR could have higher possibility of achieving successful CS. [ABSTRACT FROM AUTHOR]

Totally implantable vascular access devices (TIVADs) are often used to administer chemotherapy by prolonged intravenous infusion. The objective of the present study was to investigate the incidence of long-term complications and identify risk factors associated with TIVAD placement in patients with gastric cancer. A total of 121 patients with gastric cancer who had undergone 150 TIVAD placement procedures for chemotherapy or supportive care were enrolled in the present retrospective cohort study. A number of risk factors were analyzed, including age, sex, hypertension, diabetes mellitus, history of thrombosis, body mass index, disease stage, and site and purpose of TIVAD. In total, 40 TIVADs (26.7%) developed long-term complications, of which 27 (18.0%) were infections, seven (4.7%) were catheter-related deep vein thrombosis (CR-DVT), and six (4.0%) were obstructions. Chemotherapy was associated with an increased rate of infectious adverse events (odds ratio 2.925; 95% CI, 1.104–7.750; P=0.031) according to the multivariate analysis. CR-DVT occurred more frequently in upper arm ports than in chest wall ports; however, this difference was not statistically significant (7.5 vs. 0.0%; P=0.084) according to the univariable analysis. All CR-DVTs developed in the upper arm sites. Chemotherapy and the upper arm site were associated with long-term complications in patients with TIVAD. However, further studies are needed to confirm the findings of the present study and to determine the reasons for the high incidence of long-term complications in these patients. [ABSTRACT FROM AUTHOR]

Segmental gastrectomy, mini-distal gastrectomy and local resection of the stomach are function-preserving curative gastrectomies (FPGs), which are used to treat gastric cancer in specialized centers. These surgical options are less invasive and can alleviate postgastrectomy symptoms more than standard gastrectomy; however, their association with prognosis remains to be fully elucidated. The present study aimed to compare the survival prognosis of patients diagnosed as node-negative by sentinel node biopsy (SNB) treated via FPG with reduced lymph node dissection with that of patients who underwent guideline gastrectomy (GL). This retrospective study was conducted between April 1999 and March 2016. The inclusion criteria were a diagnosis of gastric cancer type 0, of ≤5 cm, located in L or M areas, and pT1N0. Patients who underwent distal gastrectomy and pylorus-preserving gastrectomy were included as controls in the GL group. Among the 146 and 300 patients in the FPG and GL groups, respectively, only 1 patient in the GL group experienced recurrence. The overall survival (OS) of the FPG group was 96.6% at 5 years and 92.5% at 10 years, which was significantly higher than that of the GL group (P<0.05). In addition, the cumulative incidence of non-cancer-related deaths, especially pulmonary diseases, was lower in the FPG group than that in the GL group (P<0.05). Notably, the OS and non-cancer death rate in the FPG group remained significantly better after propensity score-matching analysis. In conclusion, for early gastric cancer located in M or L areas, patients treated via FPG guided by SNB have a better prognosis and fewer deaths caused by respiratory disease than those treated via GL. The present clinical trial was registered under the following trial registration numbers: UMIN000010154 (2013/3/4), UMIN000023828 (2016/8/29), jRCTs041180006 (2018/10/9). [ABSTRACT FROM AUTHOR]

Cytokeratin 18 (CK18) fragments are released into circulation during epithelial cell death. M30 (reflects caspase-cleaved CK18 fragment) and M65 (reflects total CK18 fragment) enzyme-linked immunosorbent assay (ELISA) detect circulating CK18 fragments released during caspase-dependent or total cell death, respectively; thus, CK18 has the potential of being a biomarker for epithelial cancers. In the present study, we investigated the serum levels of M30 and M65 in patients with gastric cancer, determined correlation of these levels with clinical features, and evaluated the usefulness of these enzymes as diagnostic and prognostic markers. We enrolled 54 gastric cancer patients and 12 healthy volunteers in this study. We measured the serum levels of M30 and M65 by quantitative ELISA. The levels of M30 and M65 in gastric cancer patients were significantly higher than those in healthy volunteers ( P = 0.001, P < 0.001). The enzyme levels were elevated with the progress of gastric cancer. The sensitivity and specificity of M30 as a diagnostic marker were 67.5 and 90.9 %, respectively, and those of M65 were 70.1 and 90.9 %, respectively. The serum levels of M30 and M65 in patient with early gastric cancer were elevated in 38.1 and 66.7 %, respectively. Further, increased serum level of M65 is an independent indicator of poor prognosis ( P = 0.036). The serum levels of M30 and M65 may be useful biomarkers for gastric cancer as diagnostic markers that can reflect the extent of cancer. Moreover, M65 levels can be used as a prognostic indicator. [ABSTRACT FROM AUTHOR]

Background: Management of peritoneal dissemination is the most critical problem in gastric cancer. This study was performed to investigate the inhibitory effects of valproic acid (VPA) on a highly peritoneal-seeding cell line of human scirrhous gastric cancer, OCUM-2MD3, and to explore the mechanism and the potential of VPA. Methods: The effects of VPA on the growth of OCUM-2MD3 cells were assessed by MTT assay. In addition, paclitaxel (PTX) was combined with VPA to evaluate their synergistic effects. HDAC1 and HDAC2 expression were evaluated by western blotting in OCUM-2MD3 cells and other gastric cancer cell lines (TMK-1, MKN-28). The acetylation status of histone H3 and α-tubulin after exposure to VPA were analyzed by western blotting. The activities of cell cycle regulatory proteins and apoptosis-modulating proteins were also examined by western blotting. The effects of VPA in vivo were evaluated in a xenograft model, and apoptotic activity was assessed by TUNEL assay. Results: OCUM-2MD3 cells showed high levels of HDAC1 and HDAC2 expression compared with TMK-1 and MKN-28. The concentration of VPA required for significant inhibition of cell viability (P < 0.05) was 5 mM at 24 h and 0.5 mM at 48 h and 72 h. The inhibition of VPA with PTX showed dose-dependent and combinatorial effects. VPA increased acetyl-histone H3, acetyl-a-tubulin, and p21WAF1 levels accompanied by upregulation of p27, caspase 3, and caspase 9, and downregulation of bcl-2, cyclin D1, and survivin. In the xenograft model experiment, the mean tumor volume of the VPA-treated group was significantly reduced by 36.4%, compared with that of the control group at 4 weeks after treatment (P < 0.01). The apoptotic index was significantly higher in the VPA-treated group (42.3% ± 3.5%) than in the control group (7.7% ± 2.5%) (P < 0.001). Conclusions: VPA induced dynamic modulation of histone H3 and α-tubulin acetylation in relation with the anticancer effect and the enhancement of PTX in the OCUM-2MD3 cell line. Therefore, VPA in combination with PTX is expected to be a promising therapy for peritoneal dissemination of scirrhous gastric cancer. [ABSTRACT FROM AUTHOR]