Efficacy of continuous hyperthermic peritoneal perfusion for the prophylaxis and treatment of peritoneal metastasis of advanced gastric cancer: evaluation by multivariate regression analysis.

Thirty-two patients with advanced gastric cancer underwent continuous hyperthermic peritoneal perfusion (CHPP) combined with surgery: to prevent peritoneal recurrence in 15 patients without peritoneal metastasis (prophylactic CHPP) and to treat 17 patients with peritoneal metastases (therapeutic CHPP). The postoperative outcome was compared with that of control patients treated with surgery alone. Peritoneal recurrence was less frequent (26%) and the 5-year survival rate was significantly higher (39%) in the patients with prophylactic CHPP than in 40 control patients (42 and 17%, respectively). The patients with therapeutic CHPP showed significantly better median survival than did 20 control patients (11 vs. 6 months). Cox multivariate regression analysis revealed that CHPP was an independent prognostic factor in the prophylactic study (hazard ratio = 0.3965), and that the independent prognostic factor in the therapeutic study was not CHPP but complete resection of the peritoneal metastasis. Thus, CHPP has no marked benefit for established peritoneal metastasis. CHPP for the prevention of peritoneal recurrence may have a beneficial effect on long-term survival, but a prospective randomized trial is needed to clarify its prognostic value.     

Continuous hyperthermic peritoneal perfusion with cisplatin and mitomycin C for peritoneal dissemination in gastric cancer

Thirty-four patients with advanced gastric cancers had received continuous hyperthermic peritoneal perfusion (CHPP) for prevention or treatment of peritoneal dissemination (PD). These patients received intra-abdominal perfusion 30-40 minutes by about 10-liter saline heated to 50-52 degrees C dissolving 200-300 mg cisplatin (CDDP) and 20-30 mg mitomycin C (MMC). The perfusate was infused in the peritoneal cavity through the peritoneal cavity expander (PCE Nihon Kayaku Co. Ltd.) newly developed for sufficient irrigation in our clinic. Eleven patients with macroscopic serosal invasion without PD (P0) or with mild PD (P1) underwent prophylactic CHPP for prevention of peritoneal recurrence. (Pn means degree of PD according to The General Rules for the Gastric Cancer Study.) Twenty-three patients with moderate PD (P2) or severe PD (P3) underwent therapeutic CHPP. The prognosis of patients having undergone prophylactic or therapeutic CHPP (CHPP (+) group) was compared with those not having done CHPP (CHPP (-) group) in the historical control study. In the prophylactic study two-year-survival rates of CHPP (+) group was 90% significantly higher than 63% in CHPP (-) group. There was no significant difference between two-year-survival rates of CHPP (+) (11%) and CHPP (-) (0%) in the therapeutic CHPP. But ascites was observed to disappear in five of twelve (41.7%). Surprisingly second look operation disclosed macroscopic and microscopic disappearance of PD in three of nine (33.3%). The side-effects in those patients had consisted of leakage, bone marrow suppression, perforation of small bowel and so on. But there was no mortality after introduction of PCE. About laboratory data, rises in WBC, BUN, creatinine and LDH and drops in total lymphocytes counts and platelets were all normalized within four weeks. The maximal concentrations of total and free, which emerged at five minutes after CHPP, were 2.19 and 1.29 micrograms/ml. These results suggested that CHPP with CDDP and MMC was well tolerated and effective for prevention of peritoneal recurrence and treatment of peritoneal dissemination in the gastric cancer.     

Intraperitoneal chemotherapy in gastric cancer patients with peritoneal dissemination

Peritoneal dissemination is one of the non-curative factors in gastric cancer and colon cancer. Although many treatments have been conducted for peritoneal dissemination, no standard chemotherapy has yet been established. For sometime we had used continuous hyperthermic peritoneal perfusion (CHPP)for peritoneal dissemination in gastric cancer and colon cancer. CHPP has a marked survival benefit for scirrhous type gastric cancer patients without liver metastasis. Patients with prophylactic CHPP have significantly better prognoses than those without prophylactic CHPP, and therapeutic CHPP has a survival benefit for gastric cancer patients with slight to moderate peritoneal dissemination (P 1-2). But CHPP has no significant prognostic benefit for gastric cancer patients with severe peritoneal dissemination (P 3). Therefore, a new cancer treatment is needed for those patients. On the other hand, many kinds of anticancer agents, including cisplatin, via intraperitoneal (ip) administration have been tried thus far for peritoneal dissemination therapy. Especially, intraperitoneal taxane anticancer agent is very effective for the treatment and local control of severe peritoneal dissemination in gastric cancer. A phase I/II study of taxane anticancer agents via ip administration should be tried in gastric cancer patients with peritoneal dissemination.     

Treatment of gastric cancer patients with peritoneal metastasis by continuous hyperthermic peritoneal infusion with mitomycin C and cisplatin

Following the resection of its primary lesion, continuous hyperthermic peritoneal perfusion (CHPP) with anticancer drug (mitomycin C, cisplatin) containing warmed physiological saline was performed on gastric cancer having peritoneal dissemination, and the effect of CHPP was examined by second look operation (SLO). The subjects were 41 cases of gastric cancer with peritoneal dissemination but without hepatic metastasis, which we have experienced in the past 7 years. The prognosis of these CHPP-treated cases was such that 50% survival period, 3 year survival rate and 5 year survival rate were 398 days, 28.5 and 12%, respectively. Comparison of the effects of CHPP by SLO revealed remarkable diminution of the peritoneal dissemination in 7 (44%) of 16 cases and disappearance of the ascites with a single course of CHPP in 7 of ascitic cases. Long-term survival (greater than 3 years) was noted in 4 of the CHPP-treated cases. Side effects were renal insufficiency, leukopenia and small intestinal perforation in 2(5), 2(5) and 1 cases (2%), respectively. The above results suggested the effectiveness of CHPP for the treatment of gastric cancer having peritoneal dissemination.     

Treatment results of peritoneal dissemination from gastric cancer by neoadjuvant intraperitoneal-systemic chemotherapy

No standard treatment exists for peritoneal dissemination from gastric cancer. We reviewed our experience using a novel treatment consisting of peritonectomy and intraoperative chemo-hyperthermic peritoneal perfusion (CHPP). Records of all patients who underwent CHPP and cytoreductive surgery from 1992 to 2001 were reviewed. RESULTS: Data from 107 patients (average age, 52 years) were available. P3 dissemination was found in 72 patients, and 8 and 27 patients showed P1 or P2 dissemination, respectively. Peritoneal metastasis was synchronous in 75 and metachronous in 32 patients. All patients received CHPP after cytoreductive surgery. Peritonectomy was performed in 42 patients. Complete cytoreduction (CC-0) was achieved in 47 patients (44%). Peritonectomy, resulted in CC-0 in 69% (29/42), but CC-0 was achieved in 18 of 65 (28%) patients by ordinary surgical techniques. There were 23 postoperative complications (21%) after operation. The overall operative mortality was 2.8% (3/107). Median follow-up for the entire study group was 46 months. Seventeen patients (15%) were disease-free, and 90 patients were dead at the time of analysis. Eighty-seven deaths were related to progression of disease. The median survival of all patients was 16.2 months, with an actual 5-year survival of 6%. Median survival of CHPP plus ordinary cyoreduction was 12.0 months and that after CHPP and peritonectomy was 22.8 months. Completeness of cytoreduction and peritonectomy were significant prognostic factors on univariate analysis and 5-year survival rate was 27%. Lymph node status, grade of peritoneal dissemination (P1-2 vs P3), age (>60 years vs <60 years), tumor volume of dissemination (>2.5 cm vs <2.5 cm in diameter), and histologic type (differentiated vs. poorly differentiated type) did not affect survival. The cox proportional model demonstrated that completeness of cytoreduction was the strongest prognostic factor. Patients who had an incomplete resection had 2.8-fold higher risk of dying from disease than patients who underwent complete cytoreduction. The 5-year survival after complete cytoreduction was 12%, compared with 2% for incomplete resection. Four patients lived more than 5 years. Cytoreduction was incomplete in one 5-year survivor who showed complete response to CHPP. CONCLUSION: Complete cytoreduction using peritonectomy and CHPP may improve survival of patients with peritoneal dissemination from gastric cancer. This procedure is most appropriate for highly motivated patients who are committed to survive as long as possible.     

C反应蛋白与胃癌腹腔转移及预后的相关性研究

目的 探讨C反应蛋白（CRP）与胃癌腹腔转移及预后的相关性。方法 回顾性分析2008年6月至2014年8月于本院接受一线化疗的晚期胃癌患者150例,根据腹腔转移情况分为腹腔转移组（112例）和非腹腔转移组（38例）,单因素和多因素分析年龄、性别、腹腔转移、CRP、白蛋白、ECOG评分对预后的影响,并比较腹腔转移组与非腹腔转移组的CRP、白蛋白和ECOG评分。结果 单因素生存分析发现CRP、ECOG评分、白蛋白和腹腔转移与患者预后有关,而性别和年龄与预后无关。多因素生存分析发现腹腔转移是影响胃癌预后的独立因素（P＜0.001）。与非腹腔转移组比较,腹腔转移组CRP、ECOG评分升高,而血浆白蛋白降低,差异均有统计学意义（P＜0.05）。结论 与非腹腔转移患者比较,胃癌腹腔转移患者预后较差,系统性炎症明显增强,应从炎症角度为胃癌腹腔转移患者提供治疗策略。     

Effectiveness of intraperitoneal chemotherapy using new-aged drugs for the peritoneal dissemination of gastric cancer

We evaluated the effectiveness of intraperitoneal chemotherapy for peritoneal dissemination of gastric cancer. A total of 104 patients with primary gastric cancer with peritoneal dissemination were enrolled in this study. In 72 of the 104 patients with gastrectomy performed, 5 patients underwent CDDP-ip (50-100 mg/100-200 ml), 16 patients underwent CHPP (CDDP 300 mg, MMC 30 mg, ETP 150 mg/8 l/42-43 degrees C/60 min), and 17 patients underwent CMV-ip (CDDP 150 mg, MMC 20 mg, ETP 100 mg/1 l/60 min). The prognosis of patients who underwent CMV-ip was significantly better than those who received other therapies. In 26 patients with severe peritoneal dissemination who were treated with TS-1 (60 mg/m2) and taxane-ip (docetaxel 40-60 mg/body or paclitaxel 120-180 mg/body), 9 of 18 responders performed complete cytoreduction. The median survival time (MST) in these 9 patients was 944 days and a 2-year survival rate was 63%. A multimodal therapy consisting of systemic chemotherapy, intraperitoneal chemotherapy and complete cytoreductive surgery may provide good prognosis to the gastric cancer patients with peritoneal dissemination.     

Continuous hyperthermic peritoneal perfusion for the treatment of peritoneal dissemination in gastric cancers and subsequent second-look operation

A total of 31 patients with gastric cancer showing peritoneal dissemination received continuous hyperthermic peritoneal perfusion (CHPP) in combination with the administration of cisplatin (CDDP) and mitomycin C (MMC). The authors developed a new special device named the peritoneal cavity expander (PCE) for sufficient perfusion and direct temperature measurement in the peritoneal cavity. As complications of CHPP three patients presented with bone marrow suppressions (leukocytes less than or equal to 3000/mm3 and/or platelets less than or equal to 30,000/mm3): one, leakage of intestinal anastomosis; one, intestinal perforation; and one, acute renal failure. But none of them was lethal. Twelve of 31 patients who had received CHPP during the initial operation underwent second-look operation (SLO) for the assessing the effects of CHPP and for resecting residual or recurrent tumors. Among 12 patients who received SLO complete response (CR) was observed in four patients, partial response (PR) in one, no change (NC) in three, and progressive disease (PD) in four, with the overall response rates (%CR + %PR) standing at 41%. Two-year survival rate of the complete and partial responders was 50%, which was significantly higher than 0% of the other responders (NC + PD). The survival curves of the two groups were significantly different (P less than 0.05, generalized Wilcoxon test). These results supported that CHPP was well tolerated and effective for the treatment of patients with peritoneal dissemination in gastric cancer when combined with anti-cancer drugs having synergism with hyperthermia. Since the outcome of SLO was one of prognostic factors it was important to follow up these patients by SLO.     

胃癌腹膜转移的临床病理特性及预后分析

目的 探讨胃癌腹膜转移(P2)的临床病理特性及不同术式对预后的影响。方法 对91例P2患者的临床病理资料及不同术式术后生存情况进行回顾性分析。结果 单因素分析发现,肿瘤大小、肿瘤部位、分化程度、Borrmann分型、脏器侵犯、淋巴结转移、浸润深度、肝转移与P2相关(P＜0.05)。Logistic回归分析显示,浸润深度和脏器侵犯是P2独立的影响因素(P＜0.05)。非根治切除术组和姑息手术组在年龄、腹水及脏器侵犯上差别有统计学意义(P＜0.05)。姑息手术组中造瘘术、胃肠吻合术与剖腹探查术间的生存时间差别无统计学意义(P＞0.05)。非根治切除术组的中位生存时间为13.4月,姑息手术组的中位生存时间为4.2月,差别有统计学意义(P＜0.01),Cox分析显示手术方式和肿瘤大小是影响P2患者预后的独立危险因素。结论 胃癌患者的临床病理特征与腹膜转移的发生密切相关,非根治切除术可改善胃癌腹膜转移(P2)患者的预后。     

Cytoreductive surgery and sandwich therapy with chemohyperthermic peritoneal perfusion and intra-aortic chemotherapy for peritoneal dissemination in gastric cancer

Cytoreductive resection (RST), chemohyperthermic peritoneal perfusion (CHPP) and/or intra-aortic chemotherapy (IA-chemo) were performed for peritoneal dissemination in gastric cancer. Ninety-six patients with peritoneal dissemination were grouped into tubercular (TB), 40; nodular (ND), 31; diffuse (DF) type, 19; and others, 6, respectively, by the gross findings. Sixty-three patients underwent RST. Fifty-nine patients received CHPP by 10-liter heated saline. Thirty patients underwent intra-aortic catheterization for the IA-chemo. The 1-year and 2-year survival rate (1-ysr and 2-ysr) of the RST(+) group were 47% and 10% significantly greater than the 9% and 0% of the RST(-) group (p<0.001). The 1-ysr and 2-ysr of the CHPP(+) group were 37% and 11% significantly greater than the 27% and 0% of the CHPP(-) group (p=0.04). In the TB type the 1-ysr and 2-ysr of the former was 43% and 8% significantly greater than the 15% and 0% of the latter (p=0.04). But there was no significant difference in survival time between the CHPP(+) and the CHPP(-) group in the ND type (p=0.22) or in the DF type (p=0.42). The 1-ysr and 2-ysr of the IA-chemo(+) group were 49% and 19% significantly greater than the 27% and 2% of the IA-chemo(-) group (p<0.01). In the DF type the 1-ysr and 2-ysr of the former was 50% and 33% significantly greater than the 8% and 0% of the latter (p=0.02). However, there was no significant difference in survival time between the IA-chemo(+) and the IA-chemo(-) group in the TB type (p=0.06) or in the ND type (p=0.50). Moreover, the effect of the combination therapy of CHPP and IA-chemo (the sandwich therapy, SDW) were examined. The 1-ysr and 2-ysr of the SDW(+) group were 49% and 22% significantly greater than the 24% and 0% of the SDW(-) group (p=0.002). The sandwich therapy should be performed in addition to cytoreductive surgery for improvement of prognosis in the patient with intractable peritoneal dissemination.     

Therapeutic strategy for patients with pN0 gastric carcinoma

BACKGROUND AND OBJECTIVES: The prognosis for patients with pN0 gastric cancer is moderately hopeful (expected 5-year survival: 80%). However, the relevant prognostic factors and most appropriate surveillance protocol have not been identified. METHODS: We investigated 733 gastric cancer patients without lymph node metastasis for prognostic factors by uni- and multi-variate analysis and by documenting causes of death and recurrence patterns. RESULTS: Univariate analysis revealed that age, tumor location, macroscopic appearance, tumor diameter, invasion depth, lymphatic invasion, and venous invasion affected prognosis. Multivariate analysis showed that age (> or = 60 years), ill-defined macroscopic appearance, and undifferentiated histological type independently reduced survival rates. Age (> or = 60 years) and undifferentiated histological type adversely influenced prognosis in 507 early gastric cancer patients whereas ill-defined macroscopic appearance adversely affected prognosis in 226 advanced cancer patients. Recurrence patterns in these patients were similar to those produced by lymph node metastasis. The predominant recurrence pattern was peritoneal dissemination, observed 2-3 years post-resection. CONCLUSIONS: This study identified adverse prognostic factors in pN0 gastric cancer patients. Randomized controlled studies of adjuvant chemotherapy are necessary to assess whether such therapy is beneficial for patients with adverse prognostic factors.     

Subtotal peritonectomy with chemohyperthermic peritoneal perfusion for peritonitis carcinomatosa in gastrointestinal cancer

Treatment for peritonitis carcinomatosa in gastrointestinal cancer remains to be established though it is one of the commonest causes of cancer death. Subtotal peritonectomy (SP) with chemohyperthermic peritoneal perfusion (CHPP) was developed for the new therapeutic strategy for peritoneal dissemination in gastrointestinal cancer in our department. SP includes resection of stomach, colon, small bowel, spleen, gall bladder, and parietal peritoneum. CHPP was carried out by heated saline containing 25 mg/l cisplatin, 10 mg/l mitomycin C, and 20 mg/l etoposide. Intraperitoneal temperature was maintained at 42 degrees C for 60 min. Fifteen gastric cancer and three colon cancer patients with severe peritoneal dissemination underwent these procedures. The averages of operating time, intraoperative bleeding volume, and total perioperative transfused blood volume were 9 h, 4400 ml, and 5600 ml, respectively. The patients estimated as complete resection and residual disease by histopathological study numbered 11 and 7. There was no treatment-related deaths though bleeding occurred in 5 patients; perforation in 2 patients; and abscesses in 2 patients. The 1-year survival rate (1ysr) and the 2-year survival rate (2-ysr) of all the patients were 57% and 21%, respectively. The 1-ysr and the 2-ysr of the patients who underwent complete resection were 67% and 40% significantly greater than the 43% and 0% of the patients who had residual tumors (p=0.02). The combination therapy of SP and CHPP is feasible in spite of its morbidity and has great possibilities in complete resection of peritoneal dissemination and prolongation of patient's survival.     

Carcinoembryonic antigen levels in peritoneal washings can predict peritoneal recurrence after curative resection of gastric cancer

Carcinoembryonic antigen (CEA) levels were determined in the peritoneal washings from 120 patients with gastric cancer and 9 patients with benign diseases. Elevated values (greater than 100 ng/g of protein) were observed in 20 of 25 patients with gastric cancer with visible dissemination and 16 of 25 patients with serosal invasion but no dissemination. The same elevation was found in only 9 of 70 patients with no serosal invasion and none of the patients with benign disease. The 2-year survival rates after curative operation for the patients with and without elevation of CEA levels were 21% (19 patients) and 100% (66 patients), respectively (P less than 0.001). A negative correlation was found between CEA levels and survival times after noncurative operation. These results indicate that the CEA level in peritoneal washings could be a sensitive detector of invisible peritoneal dissemination and a new predictor for the postoperative prognosis of gastric cancer.     

VEGF significance in peritoneal recurrence from gastric cancer

Background In gastric cancer, the management of peritoneal dissemination in the Peritoneal cavity is extremely important; however, peritoneal dissemination in the final stage of gastric cancer remains untreatable. Peritoneal dissemination involves several steps, including tumor-cell attachment, invasion, and growth in the peritoneum. Many cytokines, growth factors, matrix metalloproteinases (MMPs), and angiogenic factors play important roles in these steps. So far, few studies have investigated the correlation, if any, between peritoneal dissemination and the angiogenic factor, vascular endothelial growth factor (VEGF).Methods Immunohistochemical staining, using the avidin-biotin peroxidase complex method, was performed on slides of surgical specimens from 40 patients with stage II gastric cancer with serosal invasion, who underwent surgery at our hospital between 1990 and 2000. Anti-human VEGF rabbit polyclonal IgG was used as the primary antibody. VEGF expression was classified in one of four categories depending on the percentage of tumor-cell staining (P). VEGF expression was also classified in one of three categories depending on the staining intensity (I). The VEGF expression score was calculated as P × I.Results There were ten patients with peritoneal recurrence. Of these, seven had macroscopic type-4 scirrhous-type gastric carcinoma. In the immunohistochemical study, the VEGF score of patients with peritoneal recurrence was 9.40 ± 2.46; on the other hand, that of patients without peritoneal recurrence was 3.47 ± 2.36. The VEGF score of patients with peritoneal recurrence was significantly higher than that of patients without peritoneal recurrence. In patients with macroscopic type 4, the VEGF score of those with peritoneal recurrence was 9.14 ± 2.19, while on the other hand, that of the patients without peritoneal recurrence was 3.80 ± 3.03. The VEGF score of these patients with peritoneal recurrence was significantly higher than that of those without peritoneal recurrence. The survival rate in the VEGF low-expression group was significantly higher than that in the VEGF high-expression group. Multivariate analysis showed that the VEGF score was a significant parameter of peritoneal recurrence.Conclusion These results suggested that VEGF was correlated with peritoneal metastasis from gastric cancer, and that VEGF was a useful indicator of peritoneal recurrence.     

Correlation of peritoneal dissemination and integrin alpha 3 expression in gastric cancer

To clarify the interrelationship between alpha 3 integrin, subunit/E-cadherin expression and peritoneal dissemination in gastric cancer, alpha 3 integrin subunit and E-cadherin expression gas were immunohistochemically examined and were correlated with clinicopathologic parameters. Among 150 primary gastric cancers, alpha 3 integrin subunit and E-cadherin were strongly expressed in 96 (65%) and 88 (59%) tumors, respectively. Integrin alpha 3 expression was closely associated with peritoneal dissemiantion, but there was no relationship between integrin alpha 3 expression and histologic type, nodal status, macroscopic type or wall invasion. Furthermore, 22 (84%) of 26 tumors which recurred in peritoneum overexpressed integrin alpha 3 expression in primary tumors. All seven peritoneal foci obtained from peritoneal dissemination expressed integrin alpha 3 expression despite no integrin alpha 3 expression in two of these 7 primary tumors. Reduced E-cadherin expression in primary tumors was intimately associated with large tumor size (>6 cm), nodal involvement, peritoneal dissemination and positive serosal invasion. Peritoneal dissemination was most frequently found in the tumors with positive integrin alpha 3 expression and reduced E-cadherin expression. Patients with these type of tumor [E-cadherin expression (-), and integrin alpha 3 subunit (+)] showed the poorest prognosis as compared with the other groups of patients. These results indicate that upregulation of integrin alpha 3 expression and down regulation of E-cadherin might have an important role in the formation of peritoneal dissemination. These tumors have characteristics of easy detachment from the serosal surface via downregulation of E-cadherin and strong adhesion capacity to the peritoneum via up-regulation of integrin alpha 3 expression. The immunohisto-chemical combination analysis of E-cadherin and integrin alpha 3 expression on the primary gastric cancer may be a good screening method to predict peritoneal recurrence.     

Serum levels of mitomycin C following a high-dose continuous hyperthermic peritoneal perfusion

Valid therapeutic means have not been established for treatment of disseminated peritoneal metastasis of carcinoma. Continuous hyperthermic peritoneal perfusion (CHPP) with high-dose of mitomycin-C (MMC) was applied to 26 patients with peritoneal metastasis from gastric, rectal or ovarian cancers. Levels of MMC in the sera and in the perfusate were measured. The results obtained were: 1. Approximately a half of the dose of MMC added into the perfusion fluid was recovered. 2. When perfused with 100 mg of MMC, the maximum serum concentration of MMC was equivalent to 1/3 of the maximum serum level when injected with 10 mg of MMC intravenously. Therefore, MMC which could not be detected in CHPP seemed to be retained in the abdominal cavity. 3. Bone marrow inhibition caused by CHPP was observed in only 2 of 26 patients. 4. The total dose of 300 mg of MMC, consisting of the maximum dose of 100 mg each, is acceptable in CHPP without any severe side effect. 5. CHPP exerts antitumor effects when utilizing hyperthermia and a high-dose of MMC on the disseminated peritoneal foci of carcinoma.     

Type IV collagen levels are elevated in the serum of patients with peritoneal dissemination of gastric cancer

Type III procollagen (amino-terminal propeptide of procollagen type III) and type IV collagen are considered to be reliable serum markers for monitoring the progression of liver fibrosis. The peritoneal dissemination of gastric cancer is also characterised by abundant collagen deposition in the peritoneum. The present study was performed to investigate the potential of serum type III procollagen and IV collagen as biomarkers for peritoneal dissemination in gastric cancer. The study population consisted of 117 patients with gastric cancer: 32 patients had peritoneal dissemination which was pathologically diagnosed by laparotomy or laparoscopic examination, while 85 patients (45/40, early/advanced gastric cancer) had no peritoneal dissemination. We measured the serum levels of type III procollagen and type IV collagen in comparison to the commonly accepted tumor markers carcinoembryonic (CEA), carbohydrate antigen (CA)19-9 and CA125. The median type III procollagen levels showed no significant differences between the two groups, whereas the median type IV collagen levels were significantly (201 ng/ml) higher in patients with than in those without peritoneal dissemination (early/advanced gastric cancer, 124/136 ng/ml) (P<0.05). In receiver operating characteristic (ROC) curve analysis, type IV collagen had the largest area under the curve (0.83), followed by CA125 (0.72), CA19-9 (0.64), CEA (0.59) and type III procollagen (0.48). Type IV collagen was an independent marker (P<0.0001, odds ratio 15.7) for predicting peritoneal dissemination along with CA125 (P=0.0086, odds ratio 9.4) based on multivariate logistic regression. In conclusion, serum type IV collagen levels may be significant in the early detection and management of patients with peritoneal dissemination of gastric cancer.     

Survival outcomes and prognostic indicators for gastric cancer patients with positive peritoneal wash cytology but no peritoneal metastasis after radical gastrectomy

BACKGROUNDPositive peritoneal wash cytology with no peritoneal metastasis (CY1P0) is a special type of distant gastric cancer metastasis, which describes a patient with positive peritoneal lavage cytology, but no definitive peritoneal metastasis, and there are no widely accepted treatment guidelines. We enrolled 48 primary CY1P0 gastric cancer patients treated by radical gastrectomy in this study. Our study illustrated the efficacy of radical gastrectomy for CY1P0 gastric cancer patients, and suggested that the pathological N factor and vascular invasion were significant independent risk factors for overall survival (OS). AIMTo assess the survival of CY1P0 gastric cancer patient post-radical gastrectomy, and to identify factors associated with long-term prognosis.METHODSOur study included 48 patients with primary CY1P0 gastric cancer who had radical gastrectomies at the Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China between 2013 and 2018. R0 resection was achieved in all 48 patients. Twelve patients received neoadjuvant chemotherapy. Thirty patients received adjuvant chemotherapy and four received adjuvant chemoradiotherapy. OS statistics were available for 48 patients. Follow-up continued through March 2020. Univariate and multivariate analyses were performed using a Cox proportional hazards model to identify prognostic factors. RESULTSMedian OS was 22.0 mo (95% confidence interval: 13.366-30.634 mo) post-surgery. Univariate analyses demonstrated that tumor site (P = 0.021), pathological N factor (P = 0.001), pathological T factor (P = 0.028), vascular invasion (P = 0.046), and the level of CA199 prior to initiating therapy (P = 0.002) were significant risk factors for OS. Multivariate analyses demonstrated that pathological N factor (P = 0.001) and vascular invasion (P = 0.031) were significant independent risk factors for OS.CONCLUSIONThis study suggested that radical gastrectomy may be efficient for CY1P0 gastric cancer patient post-radical gastrectomy and the pathological N factor and vascular invasion are significant independent risk factors for OS.     

Closed continuous hyperthermic peritoneal perfusion model in mice with peritoneal dissemination of colon 26.

An original model of closed continuous hyperthermic peritoneal perfusion (CHPP) in mice is presented and was found to support the efficacy of intraperitoneal hyperthermia. Closed CHPP was performed after intraperitoneal inoculation of transplantable colon 26 cells into a mouse. Colon 26 cells (5 x 10(4)) were injected into 18 mice. The mice were then allocated to six groups of three each and subjected to peritoneal perfusion over time. Peritoneal washings from each mouse were sampled and counted by the cytosmear method. On day 10 after inoculation, colonies of the disseminated tumour were seen on the mesentery by staining with 0.1% methylene blue for 5 min. The number of tumour nodules on the mesentery was counted. The number of washed-out tumour cells decreased the most at 24 h after inoculation, and 76% of the inoculated cells did not wash out during the peritoneal perfusion procedure. CHPP was performed after 24 h when colon 26 cells were injected into the peritoneal cavity because this status may represent micrometastasis. The total number of nodules on the mesentery in the CHPP group was significantly smaller than that in the control (p < 0.02). In conclusion, because this treatment model is similar to the clinical CHPP, the biostaining model might be useful for the evaluation of peritoneal dissemination and it was unique and valuable in demonstrating an effective treatment for the prevention of peritoneal dissemination.