Long-term Outcomes of Neoadjuvant Chemotherapy With Docetaxel, Cisplatin and S-1 for Stage III Gastric Cancer.

BACKGROUND/AIM: In the previous phase I/II study, we established neoadjuvant chemotherapy (NAC) using bi-weekly docetaxel, cisplatin, and S-1 (DCS) for clinical stage III gastric cancer. This study aimed to clarify long-term outcomes of this treatment. PATIENTS AND METHODS: Relapse-free survival (RFS) and overall survival (OS) were calculated by the Kaplan-Meier method and prognostic factors for RFS and OS were identified by univariate analysis. RESULTS: A total of 47 patients with clinical stage III gastric cancer were enrolled in this study. The 5-year RFS and OS rates were 69.8% and 74.3%, respectively, in all registered patients. Moreover, the 5-year OS and RFS rates in patients receiving R0 gastrectomy were 68.0% and 79.4%, respectively. Neutrophil-lymphocyte ratio (NLR) before NAC ≥2.41, prognostic nutritional index (PNI) before NAC ≤50.4, Glasgow prognostic score before NAC classification 2, NLR after NAC ≥1.43, PNI after NAC <48.0, and Grade 1a/1b pathological response significantly worsened RFS. NLR after NAC ≥1.43, PNI before NAC ≤50.4, NLR after NAC ≥1.43, and body weight loss >5 kg after NAC significantly worsened OS. CONCLUSION: Although bi-weekly DCS therapy as neoadjuvant setting showed acceptable long-term outcomes, poor immune-nutritional status before and after NAC caused worse long-term survival in stage III gastric cancer patients. It is warranted to conduct a well-designed prospective randomized control study to compare long-term outcomes using the bi-weekly DCS regimen between patients with and without immune-nutritional support during peri-NAC.

Is Prophylactic Splenectomy Necessary for Proximal Advanced Gastric Cancer Invading the Greater Curvature with Clinically Negative Splenic Hilar Lymph Node Metastasis? A Multi-Institutional Cohort Study (YCOG2003).

BACKGROUND: Prophylactic splenectomy for hilar lymph node (#10) dissection has shown no survival benefit for patients with proximal advanced gastric cancer that does not invade the greater curvature. However, the survival benefit of prophylactic splenectomy for proximal advanced gastric cancer invading the greater curvature side, particularly for clinically negative #10 lymph node metastasis (#10[-]) cases remains controversial. METHODS: This multi-institutional retrospective study enrolled 146 consecutive patients with proximal advanced gastric cancers invading the greater curvature side with clinical #10(-) who underwent R0 total gastrectomy. For 33 of these patients, splenectomy was performed, and the remaining 113 underwent spleen-preservation gastrectomy. Short- and long-term results were compared between the splenectomy and spleen-preservation groups, with the incidence of #10 metastasis in the splenectomy group and recurrence in the spleen-preservation group compared. RESULTS: In the splenectomy group, longer operative time, greater blood loss, more frequent postoperative abdominal infection, and longer hospital stay were observed than in the spleen-preservation group. The two groups exhibited no differences in median relapse-free survival time (31.1 vs 59.8 months; P = 0.684) or median overall survival time (64.9 vs 65.1 months; P = 0.765). The pathologic #10 lymph node metastasis rate was 3% in the splenectomy group, and the #10 lymph node recurrence rate was 2.7% in the spleen-preservation group. CONCLUSIONS: Prophylactic splenectomy showed more frequent postoperative morbidities and a longer hospital stay than spleen preservation, without any long-term survival benefits.

A Phase I/II Study of NAC with Docetaxel, Cisplatin, and S-1 for Stage III Gastric Cancer.

BACKGROUND/AIM: The aim of this phase I/II study was to determine the safety, and efficacy of combination of neoadjuvant chemotherapy (NAC) with biweekly docetaxel, cisplatin, and S-1 (DCS) in stage III gastric cancer patients. PATIENTS AND METHODS: In the phase I study, S1 was administered at doses of 80 mg/day to 120 mg/day depending on the body surface area and docetaxel was administered at 20 mg/m2, whereas cisplatin was initially administered at 25 mg/m2 and was escalated by 5 mg/m2 up to 50 mg/m2 In the phase II study, safety and therapeutic efficacy of DCS were evaluated using the recommended dose of cisplatin. RESULTS: In phase I, 21 patients were enrolled. In level II, perforation of gastric cancer occurred in one case although no dose limiting toxicities (DLTs) were noted in level III-VI. Recommended dose for cisplatin was 50 mg/m2/day. In phase II, among 47 patients, 14 experienced grade 3/4 adverse events. Clinically, response rate was 66.7% and disease control rate was 97.9%. The curative (R0) resection rate was 95.7%. Pathological response rate was 53.3%. Three-year overall survival and relapse-free survival rates were 78.5% and 65.3%, respectively. CONCLUSION: Biweekly DCS as NAC was efficient, safe, and acceptable; however, long-term survival should be evaluated to confirm the efficacy of biweekly DCS for stage III gastric cancer patients.

Feasibility of Laparoscopy-assisted Gastrectomy for Gastric Cancer in Elderly Patients: A Case-Control Study.

PURPOSE: The present study evaluated the safety and effectiveness of laparoscopic gastrectomy (LG) in elderly gastric cancer patients. PATIENTS AND METHODS: This study included 78 gastric cancer patients aged 80 years or above [39 in the LG group and 39 in the open gastrectomy group (matched)]. Patient characteristics, surgical outcomes, survival time, and immunonutritional status were compared. RESULTS: Mean blood loss was significantly lower in the LG group, although the operation time did not differ. There were no significant differences in the number of dissected lymph nodes, postoperative morbidity, mortality, total hospital stay, and the causes of death. The prognostic nutritional index and skeletal muscle index at 1 year were better maintained in the LG group than in the open gastrectomy group. The overall and relapse-free survivals did not differ. CONCLUSIONS: LG may be feasible in elderly patients with gastric cancer. A prospective randomized controlled trial should be conducted to confirm its efficacy.

Multicenter phase II study of capecitabine plus cisplatin as first-line therapy for human epidermal growth factor receptor 2-negative advanced gastric cancer: Yokohama Clinical Oncology Group Study YCOG1107.

PURPOSE: S-1 plus cisplatin therapy is the recommended standard first-line regimen for human epidermal growth factor receptor 2 (HER-2)-negative advanced unresectable or recurrent gastric cancer (AGC) in the Japanese Gastric Cancer Treatment Guidelines. By contrast, capecitabine plus cisplatin (XP) therapy has been second-line therapy for these patients. This prospective study aimed to evaluate the efficacy and safety of XP as a first-line regimen for HER2-negative patients with AGC. METHODS: In this multicenter, open-label, phase II study, patients received cisplatin (80 mg/m2 i.v. day 1) plus capecitabine (1000 mg/m2 orally, twice daily, days 1-14) at 3 week intervals until disease progression or non-continuation for various reasons. The primary endpoint was overall response rate; secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity profiles. RESULTS: Thirty-six patients with HER2-negative AGC were enrolled in this study. Of these, 16 patients with evaluable lesions were assessable for efficacy and 36 were assessable for toxicity. One patient achieved a complete response and five partial responses. The overall response rate was 37.5% [95% confidence interval (CI) 13.7-61.2%] calculated on an intention-to-treat basis. The median PFS and median OS were 5.2 months (95% CI 4.2-6.2 months) and 16.9 months (95% CI 5.8-27.9 months), respectively. Treatment-related adverse events were generally mild; the most common grade 3/4 adverse event was neutropenia (27.8%), followed by anorexia (19.4%), leucopenia (16.7%), anemia (16.7%), and nausea (13.9%). CONCLUSION: XP as first-line therapy is effective and well tolerated by patients with HER2-negative AGC.

Is Routine Prophylactic Cholecystectomy Necessary During Gastrectomy for Gastric Cancer?

BACKGROUND: Performing routine prophylactic cholecystectomy during gastrectomy in gastric cancer patients has been controversial. The frequency of cholelithiasis, cholecystitis, and cholangitis after gastrectomy has not been reported for large patient populations, so we carried out this retrospective study to aid the assessment of the necessity for prophylactic cholecystectomy. METHODS: This retrospective study reviewed 969 patients with gastric cancer who underwent distal gastrectomies with Billroth I reconstructions (DG) or total gastrectomies with Roux-en-Y reconstructions (TG), preserving the gallbladder, between January 2000 and May 2012. Risk factors for cholelithiasis, cholecystitis, and cholangitis after gastrectomy were evaluated using logistic regression analysis. RESULTS: The median follow-up period after gastrectomy was 48 months (range 12-159 months). After gastrectomy, cholelithiasis occurred in 6.1% (59/969) patients and cholecystitis and/or cholangitis occurred in 1.2% (12/969) patients. The method used for gastrectomy was an independent risk factor for both cholelithiasis (TG/DG: OR (95%CI): 1.900 (1.114-3.240), p = 0.018) and cholecystitis and/or cholangitis (TG/DG: OR (95%CI): 8.325 (1.814-38.197), p = 0.006). In patients who developed cholelithiasis, the incidence of cholecystitis and/or cholangitis was 31.3% (10/32) after TG, but only 7.4% after DG. CONCLUSIONS: Prophylactic cholecystectomy may be unnecessary in distal gastrectomy with Billroth I reconstruction.

Surgical advantages of reduced-port laparoscopic gastrectomy in gastric cancer.

BACKGROUND: Although a few studies have reported the use of reduced-port laparoscopic gastrectomy (RPG) in gastric cancer patients, the feasibility of routinely using this technique remains unclear. It is therefore important to evaluate the surgical advantages of this technique in this patient group. METHODS: Between August 2010 and July 2015, 165 patients underwent RPGs at our hospital, performed by a single surgeon. Of these patients, 88 underwent reduced-port laparoscopic distal gastrectomy (RPLDG) and 77 underwent reduced-port laparoscopic total gastrectomy (RPLTG). In addition to short-term surgical outcomes after RPG, survival times and the surgical learning curve were also evaluated. RESULTS: Blood losses during lymph node dissection in the RPLDG and RPLTG groups were not significantly different (p = 0.160). Conversion to open surgery was necessary in only two patients. Postoperative morbidities were observed in 14.8 % of the RPLDG group and 14.3 % of the RPLTG group, but there were no deaths. Most patients expressed high cosmetic satisfaction in both groups. In the RPLDG group, operation time during reconstruction decreased over the first 50 cases and then plateaued, as the surgeon's experience of the technique increased. In contrast, in the RPLTG group, operation times dropped with surgical experience for both lymph node dissection, plateauing after 40 cases, and for reconstruction, plateauing after 30 cases. Only three patients died of gastric cancer in the follow-up period and three patients died of other diseases. Five-year overall survival and 5-year disease-specific survival were 95.6 and 98.0 %, respectively. CONCLUSIONS: We have shown that reduced-port gastrectomy (RPG) could be an acceptable and satisfactory procedure for treating gastric cancer for an experienced laparoscopic gastric surgeon who has sufficient previous experience of conventional laparoscopic gastrectomies.

Impact of Neoadjuvant Chemotherapy Among Patients with Pancreatic Fistula After Gastrectomy for Advanced Gastric Cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has been widely adopted for patients with advanced gastric cancer; however, the safety of gastrectomy with D2 lymphadenectomy followed by NAC has not yet been evaluated. We retrospectively analyzed the influence of NAC on morbidity and mortality after gastrectomy in patients with advanced gastric cancer. PATIENTS AND METHODS: A series of 364 patients with advanced gastric cancer who underwent gastrectomy without pancreatectomy between January 2008 and December 2010 at eight hospitals registered to the Yokohama Clinical Oncology Group were studied retrospectively. There were 330 patients who underwent surgical treatment immediately after diagnosis (surgery alone group) and 34 patients (NAC group) who first received NAC and then underwent surgical resection. RESULTS: Although there were no significant differences in the morbidity rate between the two groups, postoperative pancreatic fistula was more often observed in NAC patients than in patients of the group treated with surgery alone [5 cases (14.7%) vs. 11 cases (3.3%); p=0.011]. In the univariate analysis, NAC (p=0.029), bursectomy (p<0.001) and operative bleeding (≥300 ml, p=0.002), were significantly correlated with postoperative pancreatic fistula, and NAC [odds ratio (OR)=4.901, 95% confidence interval (CI)=1.455-16.67; p=0.010] and bursectomy (OR=11.2, 95% CI=3.460-37.04; p<0.001) were independent risk factors for postoperative pancreatic fistula by multivariate analysis. The incidence of postoperative pancreatic fistula was 40.0% among patients who underwent gastrectomy with bursectomy followed by NAC. CONCLUSION: The incidence of pancreatic fistula in patients treated with NAC and bursectomy was significantly higher than that in other patients. Bursectomy may be discouraged for the prevention of pancreatic fistula from gastrectomy following NAC.

Implications of BMI for the Prognosis of Gastric Cancer among the Japanese Population.

BACKGROUND: The clinical significance of body mass index (BMI) on the surgical outcomes in gastric cancer patients still remains controversial. METHODS: The subjects included 427 patients who underwent gastrectomy between January 2001 and December 2005. The patients were principally divided into 3 groups on the basis of BMI: low (<18.5 kg/m2), normal (≥18.5-<25.0 kg/m2) and high (≥25.0 kg/m2). RESULTS: The low-BMI patients had more advanced disease than the other patients. There were no statistically significant differences in the characteristics of the normal- and high-BMI patients. The operation time was longer in the high-BMI group, but there were no differences in terms of lymph node dissection and postoperative complications among these 3 groups. The overall survival and disease-specific survival of the low-BMI group were worse than the other 2 groups. These survival rates of high-BMI group tended to be better than those of the normal BMI group; however, it was not statistically different. A multivariate analysis of these survival rate showed that a low BMI was an independent predictor of a poor prognosis. CONCLUSIONS: A low-BMI was an independent factor of poor prognosis for overall and disease-specific survivals after surgery in Japanese patients with gastric cancer. A high-BMI was not a risk factor.

[Clinical Experience of Nutritional Support in Patients Treated with Chemoradiotherapy for Locally Advanced Esophageal Cancer].

BACKGROUND: We investigated the efficacy of nutritional support in patients treated with chemoradiotherapy (CRT) for locally advanced esophageal cancer (LAEC). METHODS: Eleven patients treated with CRT for locally advanced esophageal squamous cell carcinoma were included. Oral intake energy expenditure (OIE) and total energy expenditure (TEE) of all patients were calculated. Oral nutrition supplementations (ONSs) were utilized as nutritional therapy for the patients with malnutrition (OIE/TEE<0.6). Enteral nutrition (EN) was used in the patients with tumor obstruction. RESULT: Two patients (18.9%) received ONS and 2 other patients received EN. Seven patients were able to take enough energy in the meal. The mean energy charge was increased from 67.9%to 84.9%. Nine patients (81.8%) completed the treatment regimen. During the CRT period, the prognostic nutritional index (PNI) and C-reactive protein level (mg/dL) were not significantly different. The body mass index decreased to 0.39 kg/m2 (p=0.039) and the mean weight loss was 1.57%. The overall response rate was 81.8%. CONCLUSION: The nutritional support in the patients treated with CRT for LAEC is effective for maintaining nutritional status. Moreover, the response rate is satisfactory.

[A Case of Resected Gastric Cancer Invading the Esophagus with Esophageal Recurrence That Responded to Weekly Docetaxel／Cisplatin Chemotherapy].

A 77-year-old man underwent total gastrectomy with D1+ lymph node dissection after being diagnosed with cT4aN2M0, cStage ⅢB gastric cancer. Peritoneal dissemination was detected in the bursa omentalis. The pathological diagnosis after surgery was pT4aN3b (21/41) M1 (P1). He was treated with 6 courses of S-1 chemotherapy. Two years after surgery, upper gastrointestinal endoscopy revealed the presence of a tumor in the mid-thoracic esophagus. It was diagnosed to as metastatic esophageal cancer and treated with combination chemotherapy consisting of docetaxel (25 mg/m2, days 1, 8, 15) and cisplatin (25 mg/m2, days 1, 8, 15) in a 28-day cycle. A clinically complete response was observed after 5 courses of chemotherapy. Currently, the patient is alive with no signs of recurrence 12 months after the initial recurrence.

Exosomal miRNAs from Peritoneum Lavage Fluid as Potential Prognostic Biomarkers of Peritoneal Metastasis in Gastric Cancer.

Peritoneal metastasis is the most frequent type of recurrence in patients with gastric cancer (GC) and is associated with poor prognosis. Peritoneal lavage cytology, used to evaluate the risk of peritoneal metastasis, has low sensitivity. Here, we assessed the diagnostic potential of exosomal miRNA profiles in peritoneal fluid for the prediction of peritoneal dissemination in GC. Total RNA was extracted from exosomes isolated from six gastric malignant ascites (MA) samples, 24 peritoneal lavage fluid (PLF) samples, and culture supernatants (CM) of two human gastric carcinoma cell lines that differ in their potential for peritoneal metastasis. Expression of exosomal miRNAs was evaluated with Agilent Human miRNA microarrays and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The microarray analysis indicated a low variability in the number and signal intensity of miRNAs detected among the samples. In the six MA fluids, miR-21 showed the highest signal intensity. We identified five miRNAs (miR-1225-5p, miR-320c, miR-1202, miR-1207-5p, and miR-4270) with high expression in MA samples, the PLF of serosa-invasive GC, and the CM of a highly metastatic GC cell line; these candidate miRNA species appear to be related to peritoneal dissemination. Differential expression of miR-21, miR-320c, and miR-1225-5p was validated in the PLF of serosa-invasive and non-invasive GC by qRT-PCR and miR-21 and miR-1225-5p were confirmed to be associated with serosal invasion in GC. PLF can be used to profile the expression of exosomal miRNAs. Our findings suggest that miR-21 and miR-1225-5p may serve as biomarkers of peritoneal recurrence after curative GC resection, thus providing a novel approach to early diagnosis of peritoneal dissemination of GC.

A systematic review of laparoscopic total gastrectomy for gastric cancer.

BACKGROUND: Laparoscopic total gastrectomy (LTG) has been performed since 1999. Although surgical outcomes have been reported from Japan, Korea, China, and many Western countries, the effectiveness of this technique has not been conclusively established. This study therefore aimed to review the literature systematically. METHODS: Our search of the research literature identified 150 studies, which were mostly retrospective and from single institutions. RESULTS: There has recently been a remarkable increase in the number of studies from Korea, and the number of patients included in studies has increased since 2009. In most studies, the surgical procedures were longer, blood loss was reduced, and the number of retrieved lymph nodes was the same in the LTG group as in the open total gastrectomy group. The incidence of postoperative complications and that of inflammation during postoperative recovery were the same in these two groups. CONCLUSIONS: During LTG, the method used for esophagojejunostomy is important for surgical reliability and to reduce postoperative complications. There has been rapid development of new techniques from the level of esophagojejunostomy through a small skin incision to the high level of intracorporeal esophagojejunostomy using various techniques. A nationwide prospective phase II study is urgently needed to establish the value of LTG.

Impact of S-1 plus Cisplatin Neoadjuvant Chemotherapy on Scirrhous Gastric Cancer.

OBJECTIVE: This retrospective study aimed to address the therapeutic outcome for scirrhous gastric cancer patients by evaluating the effect of neoadjuvant chemotherapy prior to gastrectomy. METHODS: Two cycles of a 3-week regimen of fluoropyrimidine S-1 (40 mg/m(2), orally, twice daily), together with cisplatin (60 mg/m(2), intravenously, day 8), were administered to patients, separated by a 2-week rest period. Surgery was performed 3 weeks later in the neoadjuvant group (n = 27). We retrospectively evaluated overall survival and prognostic factors in these patients. RESULTS: Univariate analysis showed that positive lavage cytology indicated significantly worse prognoses. In the 15 patients who also underwent curative gastrectomies after S-1 plus cisplatin chemotherapy, the pathological response grade was a significant prognostic factor for 5-year survival. Additionally, lymph node metastasis tended to be an adverse prognostic factor. CONCLUSION: After S-1 plus cisplatin neoadjuvant chemotherapy, a grade 2-3 pathological response may predict favorable outcomes in scirrhous gastric cancer patients receiving curative gastrectomy, but further studies are needed to confirm these results.

Serum Type IV Collagen Concentration Correlates with Indocyanine Green Retention Rate.

BACKGROUND/AIMS: Assessment of oxaliplatin-associated hepatotoxicity in patients receiving oxaliplatin, fluorouracil and leucovorin chemotherapy (FOLFOX) for colorectal cancer remains controversial. The aims of this study were to clarify which variables are indicators of such hepatotoxicity. METHODOLOGY: Twenty-seven patients who were to receive FOLFOX for colorectal cancer were included in this study. A range of liver function tests, including serum hyaluronic acid (HA) and type IV collagen concentrations, indocyanine green (ICG) retention rate at 15 min (ICGR15) and splenic volume were assessed before commencement of chemotherapy and after four cycles of FOLFOX. RESULTS: No significant changes were found in conventional liver function tests or splenic volume. Significant changes pre- and post-FOLFOX were found in type IV collagen concentrations and ICGR15. Correlation analyses showed that the following two factors were associated with significant changes in ICGR15 after four cycles of FOLFOX: platelet count (p = 0.028, correlation coefficient 0.423), and type IV collagen concentration (p < 0.001, correlation coefficient 0.830). The regression line between type IV collagen concentration and ICGR15 was Y = 2.70 + 0.84 x X. CONCLUSION: Serum type IV collagen concentration is an indicator of oxaliplatin-associated hepatotoxicity and correlates with significant changes in ICGR15 in patients receiving FOLFOX.

Serum Type IV Collagen Concentration Correlates with Indocyanine Green Retention Rate and is an Indicator Of Hepatotoxicity In Patients Receiving FOLFOX for Colorectal Cancer.

BACKGROUND: Assessment of oxaliplatin-associated hepatotoxicity in patients receiving oxaliplatin, fluorouracil and leucovorin chemotherapy (FOLFOX) for colorectal cancer remains controversial. The aims of this study were to clarify which variables are indicators of such hepatotoxicity. METHODOLOGY: Twenty-seven patients who were to receive FOLFOX for colorectal cancer were included in this study. A range of liver function tests, including serum hyaluronic acid (HA) and type IV collagen concentrations, indocyanine green (ICG) retention rate at 15 min (ICGR15) and splenic volume were assessed before commencement of chemotherapy and after four cycles of FOLFOX. RESULTS: No significant changes were found in conventional liver function tests or splenic volume. Significant changes pre- and post-FOLFOX were found in type IV collagen concentrations and ICGR15. Correlation analyses showed that the following two factors were associated with significant changes in ICGR15 after four cycles of FOLFOX: platelet count (p = 0.028, correlation coefficient 0.423), and type IV collagen concentration (p < 0.001, correlation coefficient 0.830). The regression line between type IV collagen concentration and ICGR15 was Y = 2.70 + 0.84 x X. CONCLUSION: Serum type IV collagen concentration is an indicator of oxaliplatin-associated hepatotoxicity and correlates with significant changes in ICGR15 in patients receiving FOLFOX.

[A Case of Advanced Gastric Cancer Responding to Neoadjuvant Docetaxel/CDDP/S-1 Therapy with Metallic Stent Placement, Leading to Curative Surgery].

A 59-year-old man presented with epigastralgia. A diagnosis of advanced gastric cancer MLU, Circ, Type 3, 160 mm, tub2, cT4b (SI: panc), cN1, cM0, cH0, cP0, cCY0, cStage ⅢB was made. Because of difficulty with oral intake due to malignant outlet obstruction and tumor bleeding, endoscopic self-expanding metallic stent placement was performed. We administered chemotherapy involving docetaxel, cisplatin, and S-1(DCS). After 2 courses of chemotherapy, the primary lesion and regional lymph nodes had reduced in size. His response was judged as SD according to the RECIST criteria. The patient elected to undergo explorative laparotomy for assessment of the gastric cancer. The intraoperative findings showed that there was no pancreatic invasion, peritoneal dissemination, or distal metastasis, so a total gastrectomy and D2 lymph node dissection was performed. The pathological findings showed that there were very few cancer cells in the primary lesion, and a lymph node metastasis was found. The final stage was gastric cancer MLU, Circ, Type 3, 100 mm, muc, ypT4a(SE), ypN3a (13/51), ypM0, ypH0, ypP0, ypCY0, ypStage ⅢC. The therapy evaluation was Grade 1b. In summary, we encountered a patient with gastric cancer in whom curative surgery was made possible by undergoing chemotherapy and metallic stent placement.

Application of reduced-port laparoscopic total gastrectomy in gastric cancer preserving the pancreas and spleen.

BACKGROUND: The feasibility of using reduced-port laparoscopic total gastrectomy (RPLTG) for the treatment of gastric cancer remains unclear. This study aimed to address the potentially important advantages of this surgical technique. METHODS: Between April 2002 and February 2014, 90 patients underwent laparoscopy-assisted total gastrectomies, performed by a single surgeon. Of these, 45 patients underwent RPLTG and 45 patients underwent conventional laparoscopy-assisted total gastrectomy (CLATG). Short-term outcomes were compared to evaluate the feasibility of RPLTG for gastric cancer. RESULTS: There were several significant differences between the RPLTG and CLATG groups in short-term outcomes: the mean total operation durations were significantly longer in the RPLTG group (319.0 min) than in the CLATG group (259.0 min). However, the mean volume of blood loss, the degree of lymph node dissection, and the number of dissected lymph nodes did not differ between the two groups. CONCLUSIONS: We have shown that RPLTG could be an acceptable and satisfactory procedure for the treatment of gastric cancer requiring total gastrectomy for surgeons sufficiently experienced in CLATG.

Thrombomodulin improves rat survival after extensive hepatectomy.

BACKGROUND: Recombinant human soluble thrombomodulin (rTM) protects against disseminated intravascular coagulopathy by inhibiting coagulation, inflammation, and apoptosis. This study tests the hypothesis that rTM is hepatoprotective after extensive hepatectomy (Hx) and investigates the mechanisms underlying this effect. MATERIALS AND METHODS: Experiment 1: rats (15 per group) were injected with rTM (1.0 or 2.0 mg/kg) or saline just before 95% Hx and their 7-d survival assessed. Experiment 2: rats were assigned to either a treated (2.0 mg/kg rTM just before Hx) or control group (n = 5 per group). Five rats per group were euthanized immediately after surgery, and at 1, 3, 6, 12, and 24 h postoperatively; serum and liver remnant samples were collected for biochemical and histologic analysis, as well as reverse-transcription polymerase chain reaction and Western blotting. RESULTS: All saline-injected rats died within 52 h of Hx, whereas injection of 2.0 mg/kg rTM prolonged survival (P = 0.003). rTM increased the number of Ki67-positive cells and reduced the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells. The number of myeloperoxidase-positive cells and the expression of high-mobility group box 1 protein did not differ. Reverse-transcription polymerase chain reaction revealed that rTM significantly enhanced protease-activated receptor-1 and sphingosine kinase 1 messenger RNA expression and significantly reduced plasminogen activator inhibitor-1 and Bax messenger RNA expression. Immunohistochemistry and Western blotting demonstrated that protease-activated receptor-1 expression 24 h after Hx was significantly higher in rTM-treated than in control rats. CONCLUSIONS: rTM may improve survival after extensive Hx by inhibiting apoptosis and promoting liver regeneration.