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Introduction: We retrospectively evaluated the blood coagulation activity using the D-dimer level in the early period after gastrectomy and investigated whether postoperative hypercoagulation affects tumor recurrence and long-term survival in gastric cancer patients., Methods: The study involved 650 patients who underwent curative resection for gastric cancer at Kanagawa Cancer Center between July 2009 and July 2013. They were divided into a low-D-dimer group (LD group) and high-D-dimer group (HD group) according to the median D-dimer level on postoperative day (POD) 7. The risk factors for overall survival (OS) and relapse-free survival (RFS) were identified., Results: Of the 448 enrolled patients, 218 were classified into the LD group and 230 into the HD group. The 5-year OS rates after surgery were 90.8% and 81.3% in the LD and HD groups, respectively (p < 0.001). The 5-year RFS rates after surgery were 89.9% and 76.1% in the LD and HD groups, respectively (p < 0.001). A high D-dimer level on POD 7 (≥ 4.9 μg/ml) was identified as an independent predictive factor for both the OS (hazard ratio [HR] 1.955, 95% confidence interval [CI] 1.158-3.303, p = 0.012) and RFS (HR 2.182, 95% CI 1.327-3.589, p = 0.002). Furthermore, hematological recurrence was significantly more frequent in the HD group than in the LD group (p = 0.014)., Conclusion: A high D-dimer level on POD 7 may predict tumor recurrence and the long-term survival in patients who undergo gastrectomy for locally advanced gastric cancer. Patients with an elevated postoperative D-dimer level need careful observation and diagnostic imaging to timely detect tumor recurrence.

Background: Several retrospective studies have shown that bone disorders occur after gastric cancer surgery. This study was designed to prospectively evaluate the changes in bone metabolism after gastrectomy for gastric cancer., Methods: We prospectively enrolled 39 men with early gastric cancer who underwent gastrectomy. We excluded women to avoid the effects of menopause. We employed dual energy X-ray absorptiometry (DEXA) to measure bone mineral density (BMD) of the lumbar spine. DEXA was performed before and 1 and 2 years after surgery. The serum levels of alkaline phosphatase (ALP), 1,25-dihydroxy vitamin D [1,25(OH) 2 VD], 25-hydroxy vitamin D [25(OH)VD], and estradiol were measured before surgery and every 3 months until 2 years after surgery., Results: DEXA revealed that BMD significantly decreased by 0.036 ± 0.033 g/cm 2 12 months after gastrectomy (P < 0.001) and by 0.046 ± 0.040 g/cm 2 24 months after gastrectomy (P < 0.001). The serum ALP level significantly increased by 38.31 ± 103.8 IU/L 24 months after surgery (P = 0.013). The serum 25(OH)VD level significantly decreased by 4.88 ± 6.42 ng/ml 24 months after surgery (P < 0.001), whereas the serum 1,25(OH) 2 VD levels were consistently in the normal range. The serum estradiol level significantly increased by 2.94 ± 7.49 pg/ml 12 months after gastrectomy (P = 0.035). A lower preoperative body mass index (BMI) significantly correlated with the reduction in BMD 12 months after surgery; the correlation coefficient was 0.37 (P = 0.025)., Conclusions: This study showed that a significant decrease in BMD was observed for up to 24 months after gastrectomy, not only 12 months.

Backgrounds: In Japan, standard regimens for advanced gastric cancer (AGC) include S-1 chemotherapy. The standard treatment for early relapse after adjuvant chemotherapy with fluoropyrimidine alone is platinum-based chemotherapy, while the standard treatment for early relapse after adjuvant chemotherapy with fluoropyrimidine plus platinum is second-line chemotherapy. To evaluate the efficacy and safety of capecitabine plus cisplatin (XP) treatment for AGC patients who relapse within 6 months after S-1-based therapy, we conducted a multicenter phase II trial (NCT01412294)., Methods: HER2-negative gastric cancer patients treated with adjuvant chemotherapy including S-1 for more than 12 weeks and relapsed within 6 months were treated with capecitabine 1000 mg/m 2 bid for 14 days plus cisplatin 80 mg/m 2 on day 1 of a 3-week cycle. The primary endpoint was PFS; secondary endpoints were OS, time to treatment failure, overall response rate (ORR) and safety., Results: Forty patients (median age 64) were enrolled; of those, 37 (92.5%) received adjuvant S-1 monotherapy. Median PFS was 4.4 months (95% CI 3.6-5.1), which was longer than the 2-month protocol-specified threshold (p < 0.001). Median OS was 13.7 months (95% CI 9.0-17.7) and ORR was 8/30 (26.7%) (95% CI 14.2-44.4). Most common grade ≥ 3 adverse events were neutropenia (23%), anemia (18%), elevated serum creatinine (18%), fatigue (13%), diarrhea (7.5%), and anorexia (7.5%)., Conclusions: XP was safe and effective in patients with early relapse after S-1 adjuvant chemotherapy for curatively resected gastric cancers. XP may be a good option for the treatment of patients after early failure after adjuvant S-1., Trial Registration: NCT01412294.

Background: The therapeutic efficacy of dissection of the splenic hilar lymph nodes (#10) has not been fully evaluated in locally advanced proximal gastric cancer (LAGC) invading the greater curvature of the stomach., Methods: Patients with LAGC invading the greater curvature who underwent D2 total gastrectomy with splenectomy between January 2000 and May 2015 were retrospectively examined. The therapeutic value index was calculated by multiplying the metastatic rate of a station and the 5-year survival of patients with metastasis to that station; the metastatic rate and the index of each lymph node station were then compared., Results: In total, 82 patients were eligible for the present study. The most frequent metastatic node was #3, followed by #1, #4d and #7, #2, #4sa and #10, and #4sb and #9. These lymph nodes had a metastatic rate of more than 10%. The node station with the highest index was #3, followed by #7, #4d, #1, #4sb, #4sa, #2, and #9. The index of #10 was lower, but exceeded those of #8a and #11p., Conclusions: The metastatic rate of #10 was relatively high at 13%, and the therapeutic value index was as high as those of other suprapancreatic nodes. D2 dissection for proximal cancer located in the greater curvature should include removal of node #10.

Background: Upfront surgery and subsequent S-1 chemotherapy is frequently selected for peritoneal cytology-positive (CY1) gastric cancer patients without other distant metastases (CY1-only). The objective of this study was to confirm the efficacy of this strategy in clinical practice and to identify the risk factors associated with survival., Methods: Overall survival (OS) and recurrence-free survival (RFS) were examined in 36 CY1-only patients who underwent macroscopic curative resection followed by postoperative S-1 chemotherapy between January 2000 and June 2015. Univariate and multivariate analyses were performed using a Cox proportional hazards model to identify risk factors., Results: The median OS was 22.3 months (95% confidence interval 18.7-31.0). When the OS was compared by a log-rank test, significant differences were observed in the status of lymph node metastasis of pathological N3b (pN3b). Moreover, the univariate and multivariate analyses demonstrated that the status of pN3b was a significant independent risk factor for OS and RFS. The median OS in patients with pathological N0-N3a (pN0-N3a) was 31.0 months, while that in patients with pN3b was 18.2 months (P = 0.002). The median RFS in patients with pN0-N3a was 16.4 months, while that in patients with pN3b was 7.9 months (P = 0.007)., Conclusions: The present study confirmed the efficacy of postoperative S-1 chemotherapy for CY1-only gastric cancer patients who received upfront surgery. This strategy might be recommended as clinical practice for patients with CY1 disease but a more effective treatment should be established for CY1-positive patients, especially for those who are diagnosed with CY1 and pN3b disease.

Aims: We previously demonstrated that body weight loss (BWL) at one month after gastrectomy, a common finding after surgery for gastric cancer, was an independent risk factor for the continuation of adjuvant chemotherapy with S-1. However, it is unclear whether BWL after gastrectomy leads to poor survival through poor compliance to adjuvant chemotherapy with S-1., Methods: We conducted this follow-up study in the same cohort as our previous study. Overall survival (OS) and recurrence-free survival (RFS) were examined in 103 patients who underwent curative D2 surgery and were pathologically diagnosed with stage II or III gastric cancer, and who received postoperative adjuvant chemotherapy with S-1 between June 2002 and December 2011., Results: The median follow-up period was 64.3 months. The 5-year OS rate in the patients with a BWL of <15% was 59.9%, while that in the patients with a BWL of ≥15% was 36.4% (p = 0.004). Univariate and multivariate analyses for OS demonstrated that pathological T factor and BWL were significant risk factors. On the other hand, the 5-year RFS rate was 56.4% in the BWL <15% group and 36.4% in the BWL ≥15% group (p = 0.016), while univariate and multivariate analyses for RFS demonstrated that BWL was a marginally significant risk factor., Conclusions: Severe postoperative BWL, which is closely related with poor S-1 compliance, is an important risk factor for survival. It merits testing if preventing BWL improves survival of gastric cancer patients who receive S-1 adjuvant chemotherapy.

Background: Sarcopenia is a decrease in both muscle mass and strength. It remains unclear whether sarcopenia is associated with morbidity after gastric cancer surgery. This study evaluated the impact of sarcopenia on the morbidity of gastric cancer surgery., Methods: A total of 293 gastric cancer patients who underwent curative surgery between May 2011 and June 2013 were retrospectively examined. Patients with performance status 3 or 4 were excluded. Preoperative lean body mass (LBM) was evaluated by bioelectrical impedance analysis and expressed as LBM index. Preoperative muscle function was measured by hand grip strength (HGS). The cutoff values were the gender-specific lowest 20 %. Grade 2 or higher morbidities, as retrospectively evaluated by the Clavien-Dindo classification, were obtained from the patient record. The risk factors for morbidity were examined by univariate and multivariate analyses., Results: Morbidity was observed in 39 patients (13.3 %), including 7 with pancreatic leakage, 12 with anastomotic leakage, and 4 with intraabdominal abscesses, but no mortality was observed. The univariate analysis showed that male gender, total gastrectomy, splenectomy, and a low HGS were significant risk factors for morbidity. A low LBM was not a significant risk factor. A low HGS, male gender, and total gastrectomy remained significant in the multivariate analysis., Conclusions: A low hand grip strength was a significant risk factor for morbidity after gastric cancer surgery. The importance of the hand grip strength as a risk factor should be examined in future prospective studies.

Background: A significant body weight loss (BWL) is observed during 1 month after gastrectomy for gastric cancer. However, it remains unclear which body component mainly accounts for the weight loss., Methods: Two-hundred forty-four patients who underwent gastrectomy for gastric cancer between May 2010 and October 2013 were examined. Body weight and composition were evaluated by a bioelectrical impedance analyzer within 1 week before surgery (first measurement), at 1 week after surgery (second measurement), and at 1 month after surgery (third measurement). The changes in the early period were defined as the differences until the second measurement, and those in the late period were defined as the differences from the second to the third measurement., Results: Total BWL within 1 month was -3.4 kg, and the rate of body weight at 1 month to the preoperative body weight was 94.1 %. BWL was significantly greater in the early period than in the late period (-2.1 kg vs -1.2 kg, p < 0.001). In the early period, loss of lean body mass was significantly greater than loss of fat mass (-1.5 kg vs -0.6 kg, p < 0.001). The same trend was observed when the subset of patients who had surgical morbidities was excluded., Conclusion: BWL during the first week after surgery was significantly greater than that during the subsequent 3 weeks. Furthermore, loss of lean body mass accounted for a significant part of the BWL during the first week.

Background: Postoperative infectious complications increase disease recurrence in colorectal cancer patients. We herein investigated the impact of infectious complications on gastric cancer recurrence after curative surgery., Methods: In total, 502 patients who underwent R0 resection for gastric cancer were reviewed. Patients were classified into those with infectious complications (IC group) and those without infectious complications (NO group). The risk factors for recurrence-free survival (RFS) were identified., Results: Infectious complications, which occurred in 52 patients (10.4%), included pneumonia, ileus with a systemic inflammatory reaction, anastomotic leakage, and intraperitoneal abscess. The overall 5-year RFS rate was 83% in the NO group and 58% in the IC group (p = 0.000). Multivariate analysis demonstrated that age, ASA score, stage, and infectious complications were significant predictors of RFS., Conclusions: Infectious complications were a risk factor for gastric cancer recurrence. To avoid causing infectious complications, the surgical procedure, surgical strategy, and perioperative care should be carefully planned.

Background: The management of T1 colorectal cancer after local resection is controversial. Regional lymph node metastasis often occurs, requiring subsequent colonic resection. The aim of this study was to reevaluate the risk factors of nodal metastasis of T1 colorectal cancer, especially to examine lymphatic vessel invasion in serially prepared hematoxylin and eosin sections and D2-40 immunostained sections to determine which is a better indicator of lymph node metastasis of T1 colorectal cancer., Methods: The study investigated 120 patients who underwent bowel resection and were histologically diagnosed to have T1 colorectal cancer in Kanagawa Cancer Center Hospital from 1995 to 2005. Serially prepared paraffin sections were stained with hematoxylin and eosin, or immunostained with D2-40 antibody or von Willebrand factor, and reevaluated for lymphatic vessel invasion and other risk factors, including venous invasion, histological grade, depth of submucosal invasion, and budding., Results: Lymphatic invasion diagnosed with either hematoxylin and eosin staining (p = 0.022), or D2-40 immunostaining (p = 0.001), and budding (p = 0.013) were significant risk factors for lymph node metastasis in the univariate analysis. Venous involvement, histological grade, or depth of submucosal invasion was not significant. The multivariate logistic regression analysis for the three risk factors found lymphatic invasion diagnosed with D2-40 as an independent risk factor (odds ratio 6.048, p = 0.018, CI 1.360-26.89). The sensitivity, specificity, positive predictive value, and negative predictive value were 58 %, 88 %, 35 %, and 95 %, respectively., Conclusions: Lymphatic vessel invasion diagnosed with D2-40 was a better indicator to evaluate the risk for lymph node metastasis by T1 colorectal cancer.

Laparoscopic esophagojejunostomy using a circular stapler is associated with technical difficulties in the purse-string sutures used to insert the anvil head and in obtaining an adequate visual field to prevent rolling the mesentery and the wall of the jejunum on the mesenteric side into the anastomosis. To overcome these difficulties, we used the EndoStitch to create the purse-string suture and the ENDOCAMELEON to create the visual field to stretch the jejunum. After resecting the esophagus, purse-string sutures were placed using the EndoStitch. A total of five to six needle deliveries were performed. Next, the anvil head was inserted into the esophagus. The main unit of the EEA was inserted from the end of the resected jejunum. Then, the scope was changed to the ENDOCAMELEON. The main unit was slowly moved toward the anvil head. After making sure that the mesentery and the wall of the jejunum on the mesenteric side were not rolled into the anastomosis under the visual field created by the ENDOCAMELEON, the main unit was then fired. Thereafter, esophagojejunostomy was successfully completed. This technique was applied in 20 patients between April 2010 and May 2012. Laparoscopic esophagojejunostomy after total gastrectomy for gastric cancer was completed in all 20 patients. No case required conversion to open surgery. Neither anastomotic leakage nor stenosis was observed. This method is simple and useful for laparoscopic esophagojejunostomy after total gastrectomy for gastric cancer.

Background and Objectives: We clarified the impact of omentectomy for advanced gastric cancer on patient survival from the surgical results of a high-volume center in Japan., Methods: Patients who received curative gastrectomy were divided into two groups based on whether they underwent omentectomy. The propensity score-matching method was used to assemble a well-balanced cohort, and relapse-free survival and the pattern of recurrence were compared., Results: For this study, 330 patients who fulfilled the inclusion criteria participated and were divided into two groups: group R, patients who received omentectomy, and group P, patients who received omentum-preserving gastrectomy. After performing score-matching, 196 patients were selected. The 3- and 5-year relapse-free survival rates were 72.9% (95% confidence interval, 64.1-81.7) and 66.2% (56.6-75.8%) in group R, and 76.7% (67.9-81.2) and 67.3% (55.1-79.5) in group P, which were not significantly different (P = 0.750). Regarding sites of relapses, no differences were observed between the groups (P = 0.863)., Conclusions: In this series, omentum-preserving gastrectomy for advanced gastric cancer did not increase the peritoneal relapse rate or affect patient survival compared to conventional gastrectomy. The non-inferiority of the omission of omentectomy should be evaluated by a randomized controlled trial.

Background: The aim of this prospective study was to evaluate the feasibility and safety of laparoscopy-assisted distal gastrectomy (LADG) initiated by surgeons with much experience of open gastrectomy and laparoscopic surgery., Methods: Three surgeons who each had experience with more than 300 cases of open gastrectomy, more than 100 cases of laparoscopic cholecystectomy, more than 5 cases of laparoscopic colectomy, and more than 5 cases of laparoscopic partial gastrectomy were nominated as LADG operators. All three operators received training for LADG with study materials including videotapes, a box simulator, and an animal laboratory, with lectures and assistance from LADG instructors who each had experience of more than 50 LADG operations. Then the nominated LADG operators performed LADG with the instructors, in which their skills were evaluated and certified. Thereafter, they performed LADG without assistance from the instructors. The target of this study was clinical stage I gastric cancer that was resectable by distal gastrectomy. D1 + alpha, D1 + beta, or D2 dissection was performed laparoscopically. Basically reconstruction was done extracorporeally with a Billroth-I gastroduodenostomy. An extramural review board checked the surgical quality of the operations performed by the three surgeons. The primary endpoint was morbidity and mortality., Results: A total of 193 patients were enrolled in this study between August 2004 and July 2009. The median blood loss was 35 ml and the median operation time was 250 min. Conversion to open surgery was seen in 6 patients; 4 due to bleeding and 2 due to advanced disease. Overall morbidity was 1.6 %, including grade 2 anastomotic leakage in 0.5 % and grade 2 pancreatic fistula in 0.5 %. No mortality was observed. The number of cases required until the LADG operators acted as LADG surgeons without an instructor was 3 for each of the three surgeons. When comparing the data between that in the training period (n = 9) and the operators' data (n = 174), the median operation time was significantly longer in the training period (355 min) than in the latter period (247.5 min) (p = 0.015). Median blood loss was also greater in the training period (150 ml) than the latter period (32.5 ml), but the difference did not reach statistical significance (p = 0.084). During the training period, no patient developed any complications of ≥ grade 2., Conclusion: These results suggested that LADG could be initiated and performed feasibly and safely if surgeons with much experience of open gastrectomy and laparoscopic surgery received adequate training for LADG.

Paraneoplastic neurological syndromes (PNSs) are a heterogeneous group of neurological disorders caused by immune-mediated mechanisms. The incidence of PNS is much less than 1% for solid tumors, except for small-cell lung cancer and thymoma. We report a rare case of gastric cancer that presented with primary clinical findings of PNS. The patient was a 63-year-old woman who was admitted for worsening neuropathy. Laboratory and neurological tests excluded a nutritional deficit, diabetes mellitus, and connective tissue disease as causes of her neuropathy. Computed tomography (CT) of the abdomen, positron emission tomography (PET)-CT, and endoscopy of the stomach revealed gastric cancer with lymph node swelling. Distal gastrectomy was performed and pathological and immunohistochemical examinations indicated endocrine cell carcinoma. The gastrectomy stopped the exacerbation of her symptoms and recurrence was not observed, but the neurological disorders were irreversible. This case suggests that early diagnosis of the primary tumor is required to improve the outcome in patients with PNS.

Background: We previously reported that the administration of 1alpha hydroxy vitamin D3 was effective for treating post-gastrectomy bone disorders. Accordingly, we performed the present study to obtain evidence supporting the effectiveness of 1alpha hydroxy vitamin D3 in post-gastrectomy patients., Methods: The study involved 22 outpatients who had undergone gastrectomy for gastric cancer and had not been treated with 1alpha hydroxy vitamin D3 or calcium. They comprised 17 men and 5 women, with a mean age of 61.9 years. Laboratory tests were performed to examine the following parameters: 1,25(OH)(2) vitamin D3; 25(OH) vitamin D3; 24,25(OH)(2) vitamin D3; ionized calcium; calcium; phosphorus; alkaline phosphatase; N-parathyroid hormone; and osteocalcin., Results: The level of 1,25(OH)(2) vitamin D3, the most active of the vitamin D metabolites, was found to be normal in all of the patients. In contrast, the level of 25(OH) vitamin D3, which shows weak activity, was below the normal range in 7 of the 22 patients (31.8%). The mean serum level of 25(OH) vitamin D3 was significantly lower in patients at 1 year or more postoperatively than the level in those at less than 1 year postoperatively (P = 0.041), as well as being significantly lower in patients who had received total gastrectomy than in patients who underwent other gastrectomy procedures. The level of 24,25(OH)(2) vitamin D3, a metabolite of 25(OH) vitamin D3 that shows weak activity, was below the normal range in 19 of the 22 patients (86.4%). On multivariate analyses, factors associated with the change in vitamin D metabolites did not remain., Conclusion: The patients showed a decrease of 25(OH) vitamin D3 and 24,25(OH)(2) vitamin D3, which are metabolites that show weak activity. This suggests that a homeostatic response maintains the normal level of 1,25(OH)(2) vitamin D3, which is important for calcium regulation. Thus, it was suggested that gastrectomy had a moderate influence on the metabolism of vitamin D. However we could not detect any factor associated with the decrease of 25(OH) vitamin D3 and 24,25(OH)(2) vitamin D3.

Lung metastasis from gastric or colonic cancer, without liver metastasis, is seldom seen. However, its metastatic pathway has not been delineated on imaging. We present and discuss such a lymphatic route in a patient with gastric cancer. The appearance of the mediastinum on a lymphangiogram is discussed. To the best of our knowledge, the lymphangiographic demonstration of the route from the paraaortic lymphatics to the tracheobronchial lymph nodes has been not reported. Lymphatics running from the paraaortic to the tracheobronchial lymph nodes through the diaphragm may play an important part in direct metastasizing to lung or tracheobronchial lymph nodes in certain patients.

A rare case of osteoclast-like giant cell tumor of the pancreas is reported. A 45-year-old woman presented with upper abdominal pain and weight loss. Examination revealed a tumor in the tail of pancreas, and distal pancreatectomy with splenectomy was performed. Pathological findings showed the tumor was composed of two cell types: atypical mononuclear round cells and abundant osteoclast-like multinucleated giant cells with central nucleoli. Immunohistochemical study showed that the atypical cells were strongly reactive for vimentin and negative for CD68, while the giant cells were immunoreactive for CD68, but negative for vimentin. The tumor was diagnosed as osteoclast-like giant cell tumor of the pancreas. We report this case and review 31 cases previously described in the literature.

Background: To date, we have few effective chemotherapeutic agents against advanced and recurrent gastric cancer. 5-Fluorouracil (5-FU) and cisplatin (CDDP) are the most widely used drugs, and their combination has demonstrated favorable outcomes. However, the method (especially the timing) of CDDP administration is not well established., Methods: We examined the in-vitro effect of a combination of 5-FU and CDDP on four human gastric cancer cell lines: MKN-1, MKN-28, MKN-45, and MKN-74. The cell lines were exposed to 50% of the inhibitory concentrations of 5-FU and CDDP for 72 h and 8 h, respectively. CDDP was applied before, simultaneously with, and after the start of treatment with 5-FU., Results: When CDDP was applied after 5-FU, the cytotoxic activity against MKN-28, MKN-45, and MKN-74 was significantly potentiated. Against MKN-1, the earlier the initiation of CDDP treatment, the stronger was the cytotoxic effect., Conclusion: Our results suggest that the cytotoxicity of a combination of 5-FU and CDDP against human gastric cancer cells is both cell-line- and schedule-dependent and is especially affected by the timing of the CDDP treatment.